Search results for: cellular targeting

Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Nastaran Khoshsabk

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The evolution of communication through the Internet has influenced shaping and reshaping the self-presentation of social media users. Online communities both connect people and give voice to the voiceless allowing them to present themselves nationally and globally. People all around the world are experiencing censorship in different aspects of their life. Censorship can be externally imposed because of the political situations, or it can be self-imposed. Social media users choose the content they want to share and decide about the online audiences with whom they want to share this content. Most social media networks, such as Facebook, enable their users to be selective about the shared content and its availability to other people. However, sometimes instead of targeting a specific audience, users self-censor themselves or decide not to share various forms of information. These decisions are of particular importance in countries such as Iran where Internet is not the arena of free self-presentation and people are encouraged to stay away from political participation in the country and acting against the Islamic values. Facebook and some other social media tools are blocked in countries such as Iran. This project investigates the importance of social media in the life of Iranians to explore how they present themselves and construct their digital selves. The notion of cultural identity is applied in this research to explore the educational and informative role of social media in the identity formation and cultural representation of Facebook users. This study explores the self-censorship of Iranian adult Facebook users through their online self-representation and communication on the Internet. The data in this qualitative multiple case study have been collected through individual synchronous online interviews with the researcher’s Facebook friends and through the analysis of the participants’ Facebook profiles and activities over a period of six months. The data is analysed with an emphasis on the identity formation of participants through the recognition of the underlying themes. The exploration of online interviews is on the basis of participants’ personal accounts of self-censorship and cultural understanding through using social media. The driven codes and themes have been categorised considering censorship and place of culture on representation of self. Participants were asked to explain their views about censorship and conservatism through using social media. They reported their thoughts about deciding which content to share on Facebook and which to self-censor and their reasons behind these decisions. The codes and themes have been categorised considering censorship and its role in representation of idealised self. The ‘actual self’ showed to be hidden by an individual for different reasons such as its influence on their social status, academic achievements and job opportunities. It is hoped that this research will have implications for education contexts in countries that are experiencing social media filtering by offering an increased understanding of the importance of online communities; which can provide an educational environment to talk and learn about social taboos and constructing adults’ identity in virtual environment and through cultural self-presentation.

Keywords: cultural identity, identity formation, online communities, self-censorship

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Authors: Ashima Sharma, Tapan K. Chaudhuri

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Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.

Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing

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Authors: N. B. Chandrakala

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Domestic violence is one of the most under-reported crimes. Problem with domestic violence is that it is not even considered as abuse in many parts of the world especially certain parts of Asia, Africa and Middle East. It is viewed as “doing the needful”. Domestic violence could be in form of emotional harassment, physical injury or psychological abuse perpetrated by one of the family members to another. It is a worldwide phenomenon mainly targeting women. The acts of violence have terrible negative impact on women. It is also an infringement of women’s rights and can be safely termed as human rights abuse. In cases pertaining to domestic violence, male adults often misuses his authority and power to control another using physical or psychological means. Violence and other forms of abuse are common in domestic violence. Sexual assaults, molestation and battering are common in these cases. Domestic violence is a human rights issue and a serious deterrent to development. Domestic violence could also take place in subtle forms like making the person feel worthless or not giving the victims any personal space or freedom. The problematic aspect is cases of domestic violence are very rarely reported. The majority of the victims are women but children are also made to suffer silently. They are abused and neglected. Their innocent minds are adversely affected with the incidents of domestic violence. According to a report by World Health Organization (WHO), sexual trafficking, female feticide, dowry death, public humiliation and physical torture are some of the most common forms of domestic violence against Indian women. Such acts belie our growth and claim as an economic superpower. It is ironic that we claim to be one of the most rapidly advancing countries in the world and yet we have done hardly anything of note against social hazards like domestic violence. Laws are not that stringent when it comes to reporting acts of domestic violence. Even if the report is filed it turns out to be a long drawn process and not every victim has that much resource to fight till the end. It is also a social taboo to make your family matters public. The big challenge in front now is to enforce it in true sense. Steps that are actually needed; tough laws against domestic violence, speedy execution and change in the mindset of society only then we can expect to have some improvement in such inhuman cases. An effective response to violence must be multi-sectoral; addressing the immediate practical needs of women experiencing abuse; providing long-term follow up and assistance; and focusing on changing those cultural norms, attitudes and legal provisions that promote the acceptance of and even encourage violence against women, and undermine women's enjoyment of their full human rights and freedoms. Hence the responses to the problem must be based on integrated approach. The effectiveness of measures and initiatives will depend on coherence and coordination associated with their design and implementation.

Keywords: domestic violence, human rights, sexual assaults, World Health Organization

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Authors: Gleb Fomin, Kairat Tabynov, Nurkeldy Turebekov, Dinara Turegeldiyeva, Rinat Islamov

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The level of major cytokines in the blood of patients with COVID-19 varies greatly depending on age, gender, duration and severity of infection, and comorbidity. There are two clinically significant cytokines, IL-6 and TNF-α, which increase in levels in patients with severe COVID-19. However, in a model of COVID-19 in hamsters, TNF-α levels are unchanged or reduced, while the expression of other cytokines reflects the profile of cytokines found in patients’ plasma. The aim of our study was to evaluate the relationship between the level of cytokines in the blood, lungs, and lung damage in the model of the Syrian hamster (Mesocricetus auratus) infected with the SARS-CoV-2 strain. The study used outbred female and male Syrian hamsters (n=36, 4 groups) weighing 80-110 g and 5 months old (protocol IACUC, #4, 09/22/2020). Animals were infected intranasally with the hCoV-19/Kazakhstan/KazNAU-NSCEDI-481/2020 strain and euthanized at 3 d.p.i. The level of cytokines IL-6, TNF-α, IFN-α, and IFN-γ was determined by ELISA MyBioSourse (USA) for hamsters. Lung samples were subjected to histological processing. The presence of pathological changes in histological preparations was assessed on a 3-point scale. The work was carried out in the ABSL-3 laboratory. The data were analyzed in GraphPad Prism 6.00 (GraphPad Software, La Jolla, California, USA). The work was supported by the MES RK grant (AP09259865). In the blood, the level of TNF-α increased in males (p=0.0012) and IFN-γ in males and females (p=0.0001). On the contrary, IFN-α production decreased (p=0.0006). Only TNF-α level increased in lung tissues (p=0.0011). Correlation analysis showed a negative relationship between the level of IL-6 in the blood and lung damage in males (r -0.71, p=0.0001) and females (r-0.57, p=0.025). On the contrary, in males, the level of IL-6 in the lungs and score is positively correlated (r 0.80, p=0.01). The level of IFN-γ in the blood (r -0.64, p=0.035) and lungs (r-0.72, p=0.017) in males has a negative correlation with lung damage. No links were found for TNF-α and IFN-α. The study showed a positive association between lung injury and tissue levels of IL-6 in male hamsters. It is known that in humans, high concentrations of IL-6 in the lungs are associated with suppression of cellular immunity and, as a result, with an increase in the severity of COVID-19. TNF-α and IFN-γ play a key role in the pathogenesis of COVID-19 in hamsters. However, the mechanisms of their activity require more detailed study. IFN-α plays a lesser role in direct lung injury in a Syrian hamster model. We have shown the significance of tissue IL-6 and IFN-γ as predictors of the severity of lung damage in COVID-19 in the Syrian hamster model. Changes in the level of cytokines in the blood may not always reflect pathological processes in the lungs with COVID-19.

Keywords: syrian hamster, COVID-19, cytokines, biological model

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Authors: Bela Lebedeva

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Characteristics of the Web as a channel of information dissemination - accessibility and openness, interactivity and multimedia news - become wider and cover the audience quickly, positively affecting the perception of content, but blur out the understanding of the journalistic work. As a result audience and advertisers continue migrating to the Internet. Moreover, online targeting allows monetizing not only the audience (as customarily given to traditional media) but also the content and traffic more accurately. While the users identify themselves with the qualitative characteristics of the new market, its actors are formed. Conflict of interests is laid in the base of the economy of their relations, the problem of traffic tax as an example. Meanwhile, content monetization actualizes fiscal interest of the state too. The balance of supply and demand is often violated due to the political risks, particularly in terms of state capitalism, populism and authoritarian methods of governance such social institutions as the media. A unique example of access to journalistic material, limited by monetization of content is a television channel Dozhd' (Rain) in Russian web space. Its liberal-minded audience has a better possibility for discussion. However, the channel could have been much more successful in terms of unlimited free speech. Avoiding state pressure and censorship its management has decided to save at least online performance and monetizing all of the content for the core audience. The study Methodology was primarily based on the analysis of journalistic content, on the qualitative and quantitative analysis of the audience. Reconstructing main events and relationships of actors on the market for the last six years researcher has reached some conclusions. First, under the condition of content monetization the capitalization of its quality will always strive to quality characteristics of user, thereby identifying him. Vice versa, the user's demand generates high-quality journalism. The second conclusion follows the previous one. The growth of technology, information noise, new political challenges, the economy volatility and the cultural paradigm change – all these factors form the content paying model for an individual user. This model defines him as a beneficiary of specific knowledge and indicates the constant balance of supply and demand other conditions being equal. As a result, a new economic quality of information is created. This feature is an indicator of the market as a self-regulated system. Monetized information quality is less popular than that of the Public Broadcasting Service, but this audience is able to make decisions. These very users keep the niche sectors which have more potential of technology development, including the content monetization ways. The third point of the study allows develop it in the discourse of media space liberalization. This cultural phenomenon may open opportunities for the development of social and economic relations architecture both locally and regionally.

Keywords: content monetization, state capitalism, media liberalization, media economy, information quality

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Authors: Yuliya Huseva

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To investigate the contents of tears to determine latent blood. Methods: Tear samples from 72 women were studied with the microscopy of tears aspirated with a capillary and stained by Nocht and with a chemical method of test strips with chromogen. Statistical data processing was carried out using statistical packages Statistica 10.0 for Windows, calculation of Pearson's chi-square test, Yule association coefficient, the method of determining sensitivity and specificity. Results:, In 30.6% (22) of tear samples erythrocytes were revealed microscopically. Correlations between the presence of erythrocytes in the tear and the phase of the menstrual cycle has been discovered. In the follicular phase of the cycle, erythrocytes were found in 59.1% (13) people, which is significantly more (x2=4.2, p=0.041) compared to the luteal phase - in 40.9% (9) women. In the first seven days of the follicular phase of the menstrual cycle the erythrocytes were predominanted of in the tears of women examined testifies in favour of the vicarious bleeding from the mucous membranes of extragenital organs in sync with menstruation. Of the other cellular elements in tear samples with latent haemolacria, neutrophils prevailed - in 45.5% (10), while lymphocytes were less common - in 27.3% (6), because neutrophil exudation is accompanied by vasodilatation of the conjunctiva and the release of erythrocytes into the conjunctival cavity. It was found that the prognostic significance of the chemical method was 0.53 of the microscopic method. In contrast to microscopy, which detected blood in tear samples from 30.6% (22) of women, blood was detected chemically in tears of 16.7% (12). An association between latent haemolacria and endometriosis was found (k=0.75, p≤0.05). Microscopically, in the tears of patients with endometriosis, erythrocytes were detected in 70% of cases, while in healthy women without endometriosis - in 25% of cases. The proportion of women with erythrocytes in tears, determined by a chemical method, was 41.7% among patients with endometriosis, which is significantly more (x2=6.5, p=0.011) than 11.7% among women without endometriosis. The data obtained can be explained by the etiopathogenesis of the extragenital endometriosis which is caused by hematogenous spread of endometrial tissue into the orbit. In endometriosis, erythrocytes are found against the background of accumulations of epithelial cells. In the tear samples of 4 women with endometriosis, glandular cuboidal epithelial cells, morphologically similar to endometrial cells, were found, which may indicate a generalization of the disease. Conclusions: Single erythrocytes can normally be found in the tears, their number depends on the phase of the menstrual cycle, increasing in the follicular phase. Erythrocytes found in tears against the background of accumulations of epitheliocytes and their glandular atypia may indicate a manifestation of extragenital endometriosis. Both used methods (microscopic and chemical) are informative in revealing latent haemolacria. The microscopic method is more sensitive, reveals intact erythrocytes, and besides, it provides information about other cells. At the same time, the chemical method is faster and technically simpler, it determines the presence of haemoglobin and its metabolic products, and can be used as a screening.

Keywords: tear, blood, microscopy, epitheliocytes

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: África Vicario, Fernando J. Álvarez, Felipe Parralejo, Fernando Aranda

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The irrigation systems of traditional agriculture, such as gravity-fed irrigation, produce a great waste of water because, generally, there is no control over the amount of water supplied in relation to the water needed. The AIRON Project tries to solve this problem by implementing an IoT-based system to sensor the irrigation plots so that the state of the crops and the amount of water used for irrigation can be known remotely. The IoT system consists of a sensor network that measures the humidity of the soil, the weather conditions (temperature, relative humidity, wind and solar radiation) and the irrigation water flow. The communication between this network and a central gateway is conducted by means of long-range wireless communication that depends on the characteristics of the irrigation plot. The main objective of the AIRON project is to deploy an IoT sensor network in two different plots of the irrigation community of Aranjuez in the Spanish region of Madrid. The first plot is 2 km away from the central gateway, so LoRa has been used as the base communication technology. The problem with this plot is the absence of mains electric power, so devices with energy-saving modes have had to be used to maximize the external batteries' use time. An ESP32 SOC board with a LoRa module is employed in this case to gather data from the sensor network and send them to a gateway consisting of a Raspberry Pi with a LoRa hat. The second plot is located 18 km away from the gateway, a range that hampers the use of LoRa technology. In order to establish reliable communication in this case, the long-term evolution (LTE) standard is used, which makes it possible to reach much greater distances by using the cellular network. As mains electric power is available in this plot, a Raspberry Pi has been used instead of the ESP32 board to collect sensor data. All data received from the two plots are stored on a proprietary server located at the irrigation management company's headquarters. The analysis of these data by means of machine learning algorithms that are currently under development should allow a short-term prediction of the irrigation water demand that would significantly reduce the waste of this increasingly valuable natural resource. The major finding of this work is the real possibility of deploying a remote sensing system for irrigated plots by using Commercial-Off-The-Shelf (COTS) devices, easily scalable and adaptable to design requirements such as the distance to the control center or the availability of mains electrical power at the site.

Keywords: internet of things, irrigation water control, LoRa, LTE, smart farming

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Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

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Authors: S. E. Mohmad-Saberi, W. Song, N. Oliver, M. Adrian, T.C. Hsu, A. Darbyshire

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Biodegradable polyurethane (PU) has emerged as a potential material to promote repair and regeneration of damaged/diseased tissues in heart valve regeneration due to its excellent biomechanical profile. Understanding the effects of sterilization on their properties is vital since they are more sensitive and more critical of porous structures compared to bulk ones. In this study, the effects of low concentration of hydrogen peroxide (H₂O₂) solution sterilization has been investigated to determine whether the procedure would be efficient and non-destructive to porous three-dimensional (3D) elastomeric nanocomposite, polyhedral oligomeric silsesquioxane-terminated poly (ethylene-diethylene glycol succinate-sebacate) urea-urethane (POSS-EDSS-PU) scaffold. All the samples were tested for sterility following sterilization using phosphate buffer saline (PBS) as control and 5 % v/v H₂O₂ solution. The samples were incubated in tryptic soy broth for the cultivation of microorganisms under agitation at 37˚C for 72 hours. The effects of the 5 % v/v H₂O₂ solution sterilization were evaluated in terms of morphology, chemical and mechanical properties using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) and tensile tester apparatus. Toxicity effects of the 5 % v/v H₂O₂ solution decontamination were studied by in vitro cytotoxicity test, where the cellular responses of human dermal fibroblast (HDF) were examined. A clear, uncontaminated broth using 5 % v/v H₂O₂ solution method indicated efficient sterilization after 3 days, while the non-sterilized control shows clouding broth indicated contamination. The morphology of 3D POSS-EDSS-PU scaffold appeared to have similar morphology after sterilization with 5 % v/v H₂O₂ solution regarding of pore size and surface. FTIR results show that the sterilized samples and non-sterilized control share the same spectra pattern, confirming no significant alterations over the surface chemistry. For the mechanical properties of the H₂O₂ solution-treated scaffolds, the tensile strain was not significantly decreased, however, become significantly stiffer after the sterilization. No cytotoxic effects were observed after the 5 % v/v H₂O₂ solution sterilization as confirmed by cell viability assessed by Alamar Blue assay. The results suggest that low concentration of 5 % v/v hydrogen peroxide solution can be used as an alternative method for sterilizing biodegradable 3D porous scaffold with micro/nano-architecture without structural deformation. This study provides the understanding of the sterilization effects on biomechanical profile and cell proliferation of 3D POSS-EDSS-PU scaffolds.

Keywords: biodegradable, hydrogen peroxide solution, POSS-EDSS-PU, sterilization

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Authors: Igor V. Grigoriev

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Understanding of biological processes encoded in fungi is instrumental in addressing future food, feed, and energy demands of the growing human population. Genomics is a powerful and quickly evolving tool to understand these processes. The Fungal Genomics Program of the US Department of Energy Joint Genome Institute (JGI) partners with researchers around the world to explore fungi in several large scale genomics projects, changing the fungal genomics landscape. The key trends of these changes include: (i) rapidly increasing scale of sequencing and analysis, (ii) developing approaches to go beyond culturable fungi and explore fungal ‘dark matter,’ or unculturables, and (iii) functional genomics and multi-omics data integration. Power of comparative genomics has been recently demonstrated in several JGI projects targeting mycorrhizae, plant pathogens, wood decay fungi, and sugar fermenting yeasts. The largest JGI project ‘1000 Fungal Genomes’ aims at exploring the diversity across the Fungal Tree of Life in order to better understand fungal evolution and to build a catalogue of genes, enzymes, and pathways for biotechnological applications. At this point, at least 65% of over 700 known families have one or more reference genomes sequenced, enabling metagenomics studies of microbial communities and their interactions with plants. For many of the remaining families no representative species are available from culture collections. To sequence genomes of unculturable fungi two approaches have been developed: (a) sequencing DNA from fruiting bodies of ‘macro’ and (b) single cell genomics using fungal spores. The latter has been tested using zoospores from the early diverging fungi and resulted in several near-complete genomes from underexplored branches of the Fungal Tree, including the first genomes of Zoopagomycotina. Genome sequence serves as a reference for transcriptomics studies, the first step towards functional genomics. In the JGI fungal mini-ENCODE project transcriptomes of the model fungus Neurospora crassa grown on a spectrum of carbon sources have been collected to build regulatory gene networks. Epigenomics is another tool to understand gene regulation and recently introduced single molecule sequencing platforms not only provide better genome assemblies but can also detect DNA modifications. For example, 6mC methylome was surveyed across many diverse fungi and the highest among Eukaryota levels of 6mC methylation has been reported. Finally, data production at such scale requires data integration to enable efficient data analysis. Over 700 fungal genomes and other -omes have been integrated in JGI MycoCosm portal and equipped with comparative genomics tools to enable researchers addressing a broad spectrum of biological questions and applications for bioenergy and biotechnology.

Keywords: fungal genomics, single cell genomics, DNA methylation, comparative genomics

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Authors: Ashir Ahmed

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Generally, radicalization happens when a person's thinking and behaviour become significantly different from how most of the members of their society and community view social issues and participate politically. Radicalization often leads to violent extremism that refers to the beliefs and actions of people who support or use violence to achieve ideological, religious or political goals. Studies on radicalization negate the common myths that someone must be in a group to be radicalised or anyone who experiences radical thoughts is a violent extremist. Moreover, it is erroneous to suggest that radicalisation is always linked to religion. Generally, the common motives of radicalization include ideological, issue-based, ethno-nationalist or separatist underpinning. Moreover, there are number of factors that further augments the chances of someone being radicalised and may choose the path of violent extremism and possibly terrorism. Since there are numbers of factors (and sometimes quite different) contributing in radicalization and violent extremism, it is highly unlikely to devise a single solution that could produce effective outcomes to deal with radicalization, violent extremism and terrorism. The pathway to deradicalization, like the pathway to radicalisation, is different for everyone. Considering the need of having customized deradicalization resolution, this study proposes a multi-tier framework, called ‘pyramid of deradicalization’ that first help identifying the stage at which an individual could be on the radicalization pathway and then propose a customize strategy to deal with the respective stage. The first tier (tier 1) addresses broader community and proposes a ‘universal approach’ aiming to offer community-based design and delivery of educational programs to raise awareness and provide general information on possible factors leading to radicalization and their remedies. The second tier focuses on the members of community who are more vulnerable and are disengaged from the rest of the community. This tier proposes a ‘targeted approach’ targeting the vulnerable members of the community through early intervention such as providing anonymous help lines where people feel confident and comfortable in seeking help without fearing the disclosure of their identity. The third tier aims to focus on people having clear evidence of moving toward extremism or getting radicalized. The people falls in this tier are believed to be supported through ‘interventionist approach’. The interventionist approach advocates the community engagement and community-policing, introducing deradicalization programmes to the targeted individuals and looking after their physical and mental health issues. The fourth and the last tier suggests the strategies to deal with people who are actively breaking the law. ‘Enforcement approach’ suggests various approaches such as strong law enforcement, fairness and accuracy in reporting radicalization events, unbiased treatment by law based on gender, race, nationality or religion and strengthen the family connections.It is anticipated that the operationalization of the proposed framework (‘pyramid of deradicalization’) would help in categorising people considering their tendency to become radicalized and then offer an appropriate strategy to make them valuable and peaceful members of the community.

Keywords: deradicalization, framework, terrorism, violent extremism

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Thais O. de Paula, Marjorie R. A. Sarmiento, Francis M. Borges, Alessandra B. Ferreira-Machado, Juliana A. Resende, Dioneia E. Cesar, Vania L. Silva, Claudio G. Diniz

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Obesity is currently a worldwide public health threat, being considered a pandemic multifactorial disease related to the human gut microbiota (GM). Add to that GM is considered an important reservoir of antimicrobial resistance genes (ARG) and little is known on GM and ARG in obesity, considering the altered physiology and xenobiotics intake. As regional and social behavior may play important roles in GM modulation, and most of the studies are based on small sample size and various methodological approaches resulting in difficulties for data comparisons, this study was focused on the investigation of GM bacterial diversity in obese (OB), overweight (OW) and eutrophic individuals (ET) considering their nutritional, clinical and social characteristics; and comparative screening of AGR related to their physiology and xenobiotics intake. Microbial community was accessed by FISH considering phyla as a taxonomic level, and PCR-DGGE followed by dendrograms evaluation (UPGMA method) from fecal metagenome of 72 volunteers classified according to their body mass index (BMI). Nutritional, clinical, social parameters and xenobiotics intake were recorded for correlation analysis. The fecal metagenome was also used as template for PCR targeting 59 different ARG. Overall, 62% of OB were hypertensive, and 12% or 4% were, regarding the OW and ET individuals. Most of the OB were rated as low income (80%). Lower relative bacterial densities were observed in the OB compared to ET for almost all studied taxa (p < 0.05) with Firmicutes/Bacteroidetes ratio increased in the OB group. OW individuals showed a bacterial density representative of GM more likely to the OB. All the participants were clustered in 3 different groups based on the PCR-DGGE fingerprint patterns (C1, C2, C3), being OB mostly grouped in C1 (83.3%) and ET mostly grouped in C3 (50%). The cluster C2 showed to be transitional. Among 27 ARG detected, a cluster of 17 was observed in all groups suggesting a common core. In general, ARG were observed mostly within OB individuals followed by OW and ET. The ratio between ARG and bacterial groups may suggest that AGR were more related to enterobacteria. Positive correlations were observed between ARG and BMI, calories and xenobiotics intake (especially use of sweeteners). As with nutritional and clinical characteristics, our data may suggest that GM of OW individuals behave in a heterogeneous pattern, occasionally more likely to the OB or to the ET. Regardless the regional and social behaviors of our population, the methodological approaches in this study were complementary and confirmatory. The imbalance of GM over the health-disease interface in obesity is a matter of fact, but its influence in host's physiology is still to be clearly elucidated to help understanding the multifactorial etiology of obesity. Although the results are in agreement with observations that GM is altered in obesity, the altered physiology in OB individuals seems to be also associated to the increased xenobiotics intake and may interfere with GM towards antimicrobial resistance, as observed by the fecal metagenome and ARG screening. Support: FAPEMIG, CNPQ, CAPES, PPGCBIO/UFJF.

Keywords: antimicrobial resistance, bacterial diversity, gut microbiota, obesity

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Authors: Weiam Daear, Patrick Lai, Elmar Prenner

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The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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Authors: Ivana Knezevic, Kenneth D. Candido, N. Nick Knezevic

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Background: While pain intensity scales remain generally accepted assessment tool, and the numeric pain rating score is highly subjective, we nevertheless rely on them to make a judgment about treatment effects. Misinterpretation of pain can lead practitioners to underestimate or overestimate the patient’s medical condition. The purpose of this study was to analyze how the numeric rating pain scores given by patients with low back pain correlate with their functional activity levels. Methods: We included 100 consecutive patients with radicular low back pain (LBP) after the Institutional Review Board (IRB) approval. Pain scores, numeric rating scale (NRS) responses at rest and in the movement,Oswestry Disability Index (ODI) questionnaire answers were collected 10 times through 12 months. The ODI questionnaire is targeting a patient’s activities and physical limitations as well as a patient’s ability to manage stationary everyday duties. Statistical analysis was performed by using SPSS Software version 20. Results: The average duration of LBP was 14±22 months at the beginning of the study. All patients included in the study were between 24 and 78 years old (average 48.85±14); 56% women and 44% men. Differences between ODI and pain scores in the range from -10% to +10% were considered “normal”. Discrepancies in pain scores were graded as mild between -30% and -11% or +11% and +30%; moderate between -50% and -31% and +31% and +50% and severe if differences were more than -50% or +50%. Our data showed that pain scores at rest correlate well with ODI in 65% of patients. In 30% of patients mild discrepancies were present (negative in 21% and positive in 9%), 4% of patients had moderate and 1% severe discrepancies. “Negative discrepancy” means that patients graded their pain scores much higher than their functional ability, and most likely exaggerated their pain. “Positive discrepancy” means that patients graded their pain scores much lower than their functional ability, and most likely underrated their pain. Comparisons between ODI and pain scores during movement showed normal correlation in only 39% of patients. Mild discrepancies were present in 42% (negative in 39% and positive in 3%); moderate in 14% (all negative), and severe in 5% (all negative) of patients. A 58% unknowingly exaggerated their pain during movement. Inconsistencies were equal in male and female patients (p=0.606 and p=0.928).Our results showed that there was a negative correlation between patients’ satisfaction and the degree of reporting pain inconsistency. Furthermore, patients talking opioids showed more discrepancies in reporting pain intensity scores than did patients taking non-opioid analgesics or not taking medications for LBP (p=0.038). There was a highly statistically significant correlation between morphine equivalents doses and the level of discrepancy (p<0.0001). Conclusion: We have put emphasis on the patient education in pain evaluation as a vital step in accurate pain level reporting. We have showed a direct correlation with patients’ satisfaction. Furthermore, we must identify other parameters in defining our patients’ chronic pain conditions, such as functionality scales, quality of life questionnaires, etc., and should move away from an overly simplistic subjective rating scale.

Keywords: pain score, functionality scales, low back pain, lumbar

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Authors: Pedro Batista, André Vinha, Filipe Castelo, Bárbara Costa, Ricardo Sousa, Raquel Ricardo, André Pinto

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Background: Septic arthritis is a diagnosis that must be considered in any patient presenting with acute joint swelling and fever. Among the several risk factors for septic arthritis, such as age, rheumatoid arthritis, recent surgery, or skin infection, diabetes mellitus can sometimes be the main risk factor. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, it is uncommon in monomicrobial necrotizing fasciitis. Objectives: A case report of concomitant septic arthritis and necrotizing fasciitis in a patient with undiagnosed diabetes based on clinical history. Study Design & Methods: We report a case of a 58-year-old Portuguese previously healthy man who presented to the emergency department with fever and left knee swelling and pain for two days. The blood work revealed ketonemia of 6.7 mmol/L and glycemia of 496 mg/dL. The vital signs were significant for a temperature of 38.5 ºC and 123 bpm of heart rate. The left knee had edema and inflammatory signs. Computed tomography of the left knee showed diffuse edema of the subcutaneous cellular tissue and soft tissue air bubbles. A diagnosis of septic arthritis and necrotising fasciitis was made. He was taken to the operating room for surgical debridement. The samples collected intraoperatively were sent for microbiological analysis, revealing infection by multi-sensitive Staphylococcus aureus. Given this result, the empiric flucloxacillin (500 mg IV) and clindamycin (1000 mg IV) were maintained for 3 weeks. On the seventh day of hospitalization, there was a significant improvement in subcutaneous and musculoskeletal tissues. After two weeks of hospitalization, there was no purulent content and partial closure of the wounds was possible. After 3 weeks, he was switched to oral antibiotics (flucloxacillin 500 mg). A week later, a urinary infection by Pseudomonas aeruginosa was diagnosed and ciprofloxacin 500 mg was administered for 7 days without complications. After 30 days of hospital admission, the patient was discharged home and recovered. Results: The final diagnosis of concomitant septic arthritis and necrotizing fasciitis was made based on the imaging findings, surgical exploration and microbiological tests results. Conclusions: Early antibiotic administration and surgical debridement are key in the management of septic arthritis and necrotizing fasciitis. Furthermore, risk factors control (euglycemic blood glucose levels) must always be taken into account given the crucial role in the patient's recovery.

Keywords: septic arthritis, Necrotizing fasciitis, diabetes, Staphylococcus Aureus

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Authors: Andreas Hirseland, Lukas Kerschbaumer

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In Germany, during the past years there constantly are about one million long term unemployed who did not benefit from the prospering labor market while most short term unemployed did. Instead, they are continuously dependent on welfare and sometimes precarious short-term employment, experiencing work poverty. Long term unemployment thus turns into a main obstacle to regular employment, especially if accompanied by other impediments such as low level education (school/vocational), poor health (especially chronical illness), advanced age (older than fifty), immigrant status, motherhood or engagement in care for other relatives. Almost two thirds of all welfare recipients have multiple impediments which hinder a successful transition from welfare back to sustainable and sufficient employment. Hiring them is often considered as an investment too risky for employers. Therefore formal application schemes based on formal qualification certificates and vocational biographies might reduce employers’ risks but at the same time are not helpful for long-term unemployed and welfare recipients. The panel survey ‘Labor market and social security’ (PASS; ~15,000 respondents in ~10,000 households), carried out by the Institute of Employment Research (the research institute of the German Federal Labor Agency), shows that their chance to get back to work tends to fall to nil. Only 66 cases of such unlikely transitions could be observed. In a sequential explanatory mixed-method study, the very scarce ‘success stories’ of unlikely transitions from long term unemployment to work were explored by qualitative inquiry – in-depth interviews with a focus on biography accompanied by qualitative network techniques in order to get a more detailed insight of relevant actors involved in the processes which promote the transition from being a welfare recipient to work. There is strong evidence that sustainable transitions are influenced by biographical resources like habits of network use, a set of informal skills and particularly a resilient way of dealing with obstacles, combined with contextual factors rather than by job-placement procedures promoted by Job-Centers according to activation rules or by following formal paths of application. On the employer’s side small and medium-sized enterprises are often found to give job opportunities to a wider variety of applicants, often based on a slow but steadily increasing relationship leading to employment. According to these results it is possible to show and discuss some limitations of (German) activation policies targeting welfare dependency and long-term unemployment. Based on these findings, indications for more supportive small scale measures in the field of labor-market policies are suggested to help long-term unemployed with multiple impediments to overcome their situation.

Keywords: against-all-odds, economic sociology, long-term unemployment, mixed-methods

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Authors: T. S. Terence Ma, Irene T. Ho

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Conducting adequate assessment of the challenges students with ASD (Autism Spectrum Disorder) face and the support they need is imperative for promoting their school adjustment. Students with ASD often show deficits in communication, social interaction, emotional regulation, and self-management in learning. While targeting these areas in intervention is often helpful, we argue that not enough attention has been paid to weak self-regulation being a key factor underlying their manifest difficulty in all these areas. Self-regulation refers to one’s ability to moderate their behavioral or affective responses without assistance from others. Especially for students with high functioning autism, who often show problems not so much in acquiring the needed skills but rather in applying those skills appropriately in everyday problem-solving, self-regulation becomes a key to successful adjustment in daily life. Therefore, a greater understanding of the construct of self-regulation, its relationship with other daily skills, and its role in school functioning for students with ASD would generate insights on how students’ school adjustment could be promoted more effectively. There were two focuses in this study. Firstly, we examined the extent to which self-regulation is a distinct construct that is differentiable from other daily skills and the most salient indicators of this construct. Then we tested a model of relationships between self-regulation and other daily school skills as well as their relative and combined effects on school adjustment. A total of 1,345 Grade1 to Grade 6 students with ASD attending mainstream schools in Hong Kong participated in the research. In the first stage of the study, teachers filled out a questionnaire consisting of 136 items assessing a wide range of student skills in social, emotional and learning areas. Results from exploratory factor analysis (EFA) with 673 participants and subsequent confirmatory factor analysis (CFA) with another group of 672 participants showed that there were five distinct factors of school skills, namely (1) communication skills, (2) pro-social behavior, (3) emotional skills, (4) learning management, and (5) self-regulation. Five scales representing these skill dimensions were generated. In the second stage of the study, a model postulating the mediating role of self-regulation for the effects of the other four types of skills on school adjustment was tested with structural equation modeling (SEM). School adjustment was defined in terms of the extent to which the student is accepted well in school, with high engagement in school life and self-esteem as well as good interpersonal relationships. A 5-item scale was used to assess these aspects of school adjustment. Results showed that communication skills, pro-social behavior, emotional skills and learning management had significant effects on school adjustment only indirectly through self-regulation, and their total effects were found to be not high. The results indicate that support rendered to students with ASD focusing only on the training of well-defined skills is not adequate for promoting their inclusion in school. More attention should be paid to the training of self-management with an emphasis on the application of skills backed by self-regulation. Also, other non-skill factors are important in promoting inclusive education.

Keywords: autism, assessment, factor analysis, self-regulation, school adjustment

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Authors: Natalia Alvarado, Myldred Hernandez-Gonzalez, Mary Laird, Madeline Phillips, Elizabeth Miller, Luis Mendez, Teresa Satterfield Linares

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Objectives: Focusing on the reported levels of depressive symptoms from Hispanic individuals in the U.S. during the ongoing COVID-19 pandemic, we analyze the psychological effects of being labeled an ‘essential worker/trabajador(a) esencial.’ We situate this attribute within the complex context of how an individual’s mental health is linked to work status and his/her community’s attitude toward such a status. Method: 336 Spanish-speaking adults (Mage = 34.90; SD = 11.00; 46% female) living in the U.S. participated in a mixed-method study. Participants completed a self-report Spanish-language survey consisting of COVID-19 prompts (e.g., Soy un trabajador esencial durante la pandemia. I am an ‘essential worker’ during the pandemic), civic engagement scale (CES) attitudes (e.g., Me siento responsable de mi comunidad. I feel responsible for my community) and behaviors (e.g., Ayudo a los miembros de mi comunidad. I help members of my community), and the Center for Epidemiological Studies Depression Scale (e.g., Me sentía deprimido/a. I felt depressed). The survey was conducted several months into the pandemic and before the vaccine distribution. Results: Regression analyses show that being labeled an essential worker was correlated to CES attitudes (b= .28, p < .001) and higher CES behaviors (b= .32, p < .001). Essential worker status also reported higher levels of depressive symptoms (b= .17, p < .05). In addition, we found that CES attitudes and CES behaviors were related to higher levels of depressive symptoms (b= .11, p <.05, b = .22, p < .001, respectively). These findings suggest that those who are on the frontlines during the COVID-19 pandemic suffer higher levels of depressive symptoms, despite their affirming community attitudes and behaviors. Discussion: Hispanics/Latinxs make up 53% of the high-proximity employees who must work in person and in close contact with others; this is the highest rate of any racial or ethnic category. Moreover, 31% of Hispanics are classified as essential workers. Our outcomes show that those labeled as trabajadores esenciales convey attitudes of remaining strong and resilient for COVID-19 victims. They also express community attitudes and behaviors reflecting a sense of responsibility to continue working to help others during these unprecedented times. However, we also find that the pressure of maintaining basic needs for others exacerbates mental health challenges and stressors, as many essential workers are anxious and stressed about their physical and economic security. As a result, community attitudes do not protect from depressive symptoms as Hispanic essential workers are failing to balance everyone’s needs, including their own (e.g., physical exhaustion and psychological distress). We conclude with a discussion on alternatives to the phrase ‘essential worker’ and of incremental steps that can be taken to address pandemic-related mental health issues targeting US Hispanic workers.

Keywords: COVID-19, essential worker, mental health, race and ethnicity

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Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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Authors: Susan Thurstans, Natalie Sessions, Carmel Dolan, Kate Sadler, Bernardette Cichon, Shelia Isanaka, Dominique Roberfroid, Heather Stobagh, Patrick Webb, Tanya Khara

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For many years, wasting and stunting have been viewed as separate conditions without clear evidence supporting this distinction. In 2014, the Emergency Nutrition Network (ENN) examined the relationship between wasting and stunting and published a report highlighting the evidence for linkages between the two forms of undernutrition. This systematic review aimed to update the evidence generated since this 2014 report to better understand the implications for improving child nutrition, health and survival. Following PRISMA guidelines, this review was conducted using search terms to describe the relationship between wasting and stunting. Studies related to children under five from low- and middle-income countries that assessed both ponderal growth/wasting and linear growth/stunting, as well as the association between the two, were included. Risk of bias was assessed in all included studies using SIGN checklists. 45 studies met the inclusion criteria- 39 peer reviewed studies, 1 manual chapter, 3 pre-print publications and 2 published reports. The review found that there is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Possible interconnected physiological processes and common risk factors drive an accumulation of vulnerabilities. Peak incidence of both wasting and stunting was found to be between birth and three months. A significant proportion of children experience concurrent wasting and stunting- Country level data suggests that up to 8% of children under 5 may be both wasted and stunted at the same time, global estimates translate to around 16 million children. Children with concurrent wasting and stunting have an elevated risk of mortality when compared to children with one deficit alone. These children should therefore be considered a high-risk group in the targeting of treatment. Wasting, stunting and concurrent wasting and stunting appear to be more prevalent in boys than girls and it appears that concurrent wasting and stunting peaks between 12- 30 months of age with younger children being the most affected. Seasonal patterns in prevalence of both wasting and stunting are seen in longitudinal and cross sectional data and in particular season of birth has been shown to have an impact on a child’s subsequent experience of wasting and stunting. Evidence suggests that the use of mid-upper-arm circumference combined with weight-for-age Z-score might effectively identify children most at risk of near-term mortality, including those concurrently wasted and stunted. Wasting and stunting frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence suggests there is a process of accumulation of nutritional deficits and therefore risk over the life course of a child demonstrates the need for a more integrated approach to prevention and treatment strategies to interrupt this process. To achieve this, undernutrition policies, programmes, financing and research must become more unified.

Keywords: Concurrent wasting and stunting, Review, Risk factors, Undernutrition

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Authors: M. Louise Humbert, Karen E. Chad, Natalie E. Houser, Marta E. Erlandson

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Physical literacy is the motivation, confidence, physical competence, knowledge, and understanding to value and takes responsibility for engagement in physical activities for life. In recent years, physical literacy has emerged as a determinant of health, promoting a positive lifelong physical activity trajectory. Physical literacy’s holistic approach and emphasis on the intrinsic valuation of movement provide an encouraging avenue for intervention among children to develop competent and confident movers. Although there is research on physical literacy interventions, no evidence exists on the outcomes of multi-sectoral interventions involving a combination of home, school, and community contexts. Since children interact with and in a wide range of contexts (home, school, community) daily, interventions designed to address a combination of these contexts are critical to the development of physical literacy. Working with school administrators and teachers, sports and recreation leaders, and community members, our team of university and community researchers conducted and evaluated one of the first multi-contextual and multi-sectoral physical literacy interventions in Canada. Schools played a critical role in this multi-sector intervention, and in this project, teachers and administrators focused their actions on developing physical literacy in students 10 to 14 years of age through the instruction of physical literacy-focused physical education lessons. Little is known about the experiences of educators when they work alongside an array of community representatives to develop physical literacy in school-aged children. Given the uniqueness of this intervention, we sought to answer the question, ‘What were the experiences of school-based educators involved in a multi-sectoral partnership focused on creating a physical literacy enriched community intervention?’ A thematic analysis approach was used to analyze data collected from interviews with educators and administrators, informal conversations, documents, and observations at workshops and meetings. Results indicated that schools and educators played the largest role in this multi-sector intervention. Educators initially reported a limited understanding of physical literacy and expressed a need for resources linked to the physical education curriculum. Some anxiety was expressed by the teachers as their students were measured, and educators noted they wanted to increase their understanding and become more involved in the assessment of physical literacy. Teachers reported that the intervention’s focus on physical literacy positively impacted the scheduling and their instruction of physical education. Administrators shared their desire for school and division-level actions targeting physical literacy development like the current focus on numeracy and literacy, treaty education, and safe schools. As this was one of the first multi-contextual and multi-sectoral physical literacy interventions, it was important to document creation and delivery experiences to encourage future growth in the area and develop suggested best practices.

Keywords: physical literacy, multi sector intervention, physical education, teachers

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Authors: Ali Abdul Kadhim, Fue Lien

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Solid particle distribution on an impingement surface has been simulated utilizing a graphical processing unit (GPU). In-house computational fluid dynamics (CFD) code has been developed to investigate a 3D turbulent impinging jet using the lattice Boltzmann method (LBM) in conjunction with large eddy simulation (LES) and the multiple relaxation time (MRT) models. This paper proposed an improvement in the LBM-cellular automata (LBM-CA) probabilistic method. In the current model, the fluid flow utilizes the D3Q19 lattice, while the particle model employs the D3Q27 lattice. The particle numbers are defined at the same regular LBM nodes, and transport of particles from one node to its neighboring nodes are determined in accordance with the particle bulk density and velocity by considering all the external forces. The previous models distribute particles at each time step without considering the local velocity and the number of particles at each node. The present model overcomes the deficiencies of the previous LBM-CA models and, therefore, can better capture the dynamic interaction between particles and the surrounding turbulent flow field. Despite the increasing popularity of LBM-MRT-CA model in simulating complex multiphase fluid flows, this approach is still expensive in term of memory size and computational time required to perform 3D simulations. To improve the throughput of each simulation, a single GeForce GTX TITAN X GPU is used in the present work. The CUDA parallel programming platform and the CuRAND library are utilized to form an efficient LBM-CA algorithm. The methodology was first validated against a benchmark test case involving particle deposition on a square cylinder confined in a duct. The flow was unsteady and laminar at Re=200 (Re is the Reynolds number), and simulations were conducted for different Stokes numbers. The present LBM solutions agree well with other results available in the open literature. The GPU code was then used to simulate the particle transport and deposition in a turbulent impinging jet at Re=10,000. The simulations were conducted for L/D=2,4 and 6, where L is the nozzle-to-surface distance and D is the jet diameter. The effect of changing the Stokes number on the particle deposition profile was studied at different L/D ratios. For comparative studies, another in-house serial CPU code was also developed, coupling LBM with the classical Lagrangian particle dispersion model. Agreement between results obtained with LBM-CA and LBM-Lagrangian models and the experimental data is generally good. The present GPU approach achieves a speedup ratio of about 350 against the serial code running on a single CPU.

Keywords: CUDA, GPU parallel programming, LES, lattice Boltzmann method, MRT, multi-phase flow, probabilistic model

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Authors: Vlad Andrei Raducanu, Mariana Lucia Angelescu, Ion Cinca, Vasile Danut Cojocaru, Doina Raducanu

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By using smart digital tools, such as generative design (GD) and digital fabrication (DF), problems of high actuality concerning resources optimization (materials, energy, time) can be solved and applications or products of free-form type can be created. In the new digital technology materials are active, designed in response to a set of performance requirements, which impose a total rethinking of old material practices. The article presents the design procedure key steps of a free-form architectural object - a column type one with connections to get an adaptive 3D surface, by using the parametric design methodology and by exploiting the properties of conventional metallic materials. In parametric design the form of the created object or space is shaped by varying the parameters values and relationships between the forms are described by mathematical equations. Digital parametric design is based on specific procedures, as shape grammars, Lindenmayer - systems, cellular automata, genetic algorithms or swarm intelligence, each of these procedures having limitations which make them applicable only in certain cases. In the paper the design process stages and the shape grammar type algorithm are presented. The generative design process relies on two basic principles: the modeling principle and the generative principle. The generative method is based on a form finding process, by creating many 3D spatial forms, using an algorithm conceived in order to apply its generating logic onto different input geometry. Once the algorithm is realized, it can be applied repeatedly to generate the geometry for a number of different input surfaces. The generated configurations are then analyzed through a technical or aesthetic selection criterion and finally the optimal solution is selected. Endless range of generative capacity of codes and algorithms used in digital design offers various conceptual possibilities and optimal solutions for both technical and environmental increasing demands of building industry and architecture. Constructions or spaces generated by parametric design can be specifically tuned, in order to meet certain technical or aesthetical requirements. The proposed approach has direct applicability in sustainable architecture, offering important potential economic advantages, a flexible design (which can be changed until the end of the design process) and unique geometric models of high performance.

Keywords: parametric design, algorithmic procedures, free-form architectural object, sustainable architecture

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Authors: Carolina Schencke, Cristian Sandoval, Belgica Vasquez, Mariano Del Sol

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Introduction: In a burn injury, the successful repair requires not only the participation of various cells, such as granulocytes and fibroblasts, but also of collagen, which plays a crucial role as a structural and regulatory molecule of scar tissue. Since honey and ascorbic acid have presented a great therapeutic potential to cellular and structural level, experimental studies have proposed its combination in the treatment of wounds. Aim: To evaluate stereological and morphometric parameters of healing wounds, caused by burns, treated with honey Ulmo (Eucryphia cordifolia) unsupplemented, comparing its effect with Ulmo honey supplemented with ascorbic acid. Materials and Methods: Fifteen healthy adult guinea pigs (Cavia porcellus) were used, of both sexes, average weight 450 g from the Centro de Excelencia en Estudios Morfológicos y Quirúrgicos (CEMyQ) at the Universidad de La Frontera, Chile. The animals were divided at random into three groups: positive control (C+), honey only (H) and supplemented honey (SH) and were fed on pellets supplemented with ascorbic acid and water ad libitum, under ambient conditions controlled for temperature, ambient noise and a cycle of 12h light–darkness. The protocol for the experiment was approved by the Scientific Ethics Committee of the Universidad de La Frontera, Chile. The parameters measured were number density per area (NA), volume density (VV), and surface density (SV) of fibroblast; NA and VV of polymorphonuclear cells (PMN) and, evaluation of the content of collagen fibers in the scar dermis. One-way ANOVA was used for statistics analysis and its respective Post hoc tests. Results: The ANOVA analysis for NA, VV and SV of fibroblasts, NA and VV of PMN, and evaluation of collagen content, type I and III, showed that at least one group differs from other (P≤ 0.001). There were differences (P= 0.000) in NA of fibroblast between the groups [C+= 3599.560 mm-2 (SD= 764.461), H= 3355.336 mm-2 (SD= 699.443) and SH= 4253.025 mm-2 (SD= 1041.751)]. The VV and SV of fibroblast increased (P= 0.000) in the SH group [20.400% (SD= 5.897) and 100.876 mm2/mm3 (SD= 29.431), respectively], compared to the C+ [16.324% (SD= 7.719) and 81.676 mm2/mm3 (SD= 28.884), respectively). The mean values of NA and VV of PMN were higher (P= 0.000) in the H [756.875 mm-2 (SD= 516.489) and 2.686% (SD= 2.380), respectively) group. Regarding to the evaluation of the content of collagen fibers, type I and III, the one-way analysis of ANOVA showed a statistically significant difference (P< 0.05). The content of collagen fibers type I was higher in C+ (1988.292 μm2; SD= 1312.379), while the content of collagen fibers type III was higher in SH (1967.163 μm2; SD= 1047.944 μm2) group. Conclusions: The stereological results were correlated with the stage of healing observed for each group. These results suggest that the combination of honey with ascorbic acid potentiate the healing effect, where both participated synergistically.

Keywords: ascorbic acid, morphometry, stereology, Ulmo honey

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Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

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Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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