Search results for: live cells imaging

Authors: P.P. Rupasinghe, A.H. Farid

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The Aleutian mink disease virus (AMDV, Carnivore amdoparvovirus 1) causes persistent infection, plasmacytosis, and formation and deposition of immune complexes in various organs in adult mink, leading to glomerulonephritis, arteritis and sometimes death. The disease has no cure nor an effective vaccine, and identification and culling of mink positive for anti-AMDV antibodies have not been successful in controlling the infection in many countries. The failure to eradicate the virus from infected farms may be caused by keeping false-negative individuals on the farm, virus transmission from wild animals, or neighboring farms. The identification of sources of infection, which can be performed by comparing viral sequences, is important in the success of viral eradication programs. High mutation rates could cause inaccuracies when viral sequences are used to trace back an infection to its origin. There is no published information on the mutation rate of AMDV either in vivo or in vitro. The in vivo estimation is the most accurate method, but it is difficult to perform because of the inherent technical complexities, namely infecting live animals, the unknown numbers of viral generations (i.e., infection cycles), the removal of deleterious mutations over time and genetic drift. The objective of this study was to determine the mutation rate of AMDV on which no information was available. A homogenate was prepared from the spleen of one naturally infected American mink (Neovison vison) from Nova Scotia, Canada (parental template). The near full-length genome of this isolate (91.6%, 4,143 bp) was bidirectionally sequenced. A group of black mink was inoculated with this homogenate (descendant mink). Spleen sampled were collected from 10 descendant mink after 16 weeks post-inoculation (wpi) and from anther 10 mink after 176 wpi, and their near-full length genomes were bi-directionally sequenced. Sequences of these mink were compared with each other and with the sequence of the parental template. The number of nucleotide substitutions at 176 wpi was 3.1 times greater than that at 16 wpi (113 vs 36) whereas the estimates of mutation rate at 176 wpi was 3.1 times lower than that at 176 wpi (2.85×10-3 vs 9.13×10-4 substitutions/ site/ year), showing a decreasing trend in the mutation rate per unit of time. Although there is no report on in vivo estimate of the mutation rate of DNA viruses in animals using the same method which was used in the current study, these estimates are at the higher range of reported values for DNA viruses determined by various techniques. These high estimates are logical based on the wide range of diversity and pathogenicity of AMDV isolates. The results suggest that increases in the number of nucleotide substitutions over time and subsequent divergence make it difficult to accurately trace back AMDV isolates to their origin when several years elapsed between the two samplings.

Keywords: Aleutian mink disease virus, American mink, mutation rate, nucleotide substitution

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Authors: Khaled Alabduljabbar

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Background: Benign, isolated, recurrent sixth nerve palsy is very rare in children. Here we report a case of recurrent abducens nerve palsy with no obvious etiology. It is a diagnosis of exclusion. A recurrent benign form of 6th nerve palsy, a rarer still palsy, has been described in the literature, and it is of most likely secondary to inflammatory causes, e.g, following viral and bacterial infections. Purpose: To present a case of 14 months old girl with recurrent attacks of isolated left sixth cranial nerve palsy following upper respiratory tract infection. Observation: The patient presented to opthalmology clinic with sudden onset of inward deviation (esotropia) of the left eye with a compensatory left face turn one week following signs of upper respiratory tract infection. Ophthalmological examination revealed large angle esotropia of the left eye in primary position, with complete limitation of abduction of the left eye, no palpebral fissure changes, and abnormal position of the head (left face turn). Visual acuity was normal, and no significant refractive error on cycloplegic refraction for her age. Fundus examination was normal with no evidence of papilledema. There was no relative afferent pupillary defect (RAPD) and no anisocoria. Past medical history and family history were unremarkable, with no history of convulsion attacks or head trauma. Additional workout include CBC. Erythrocyte sedimentation rate, Urgent magnetic resonance imaging (MRI), and angiography of the brain were performed and demonstrated the absence of intracranial and orbital lesions. Referral to pediatric neurologist was also done and concluded no significant finding. The patient showed improvement of the left sixth cranial nerve palsy and left face turn over a period of two months. Seven months since the first attack, she experienced a recurrent attack of left eye esotropia with left face turn concurrent with URTI. The rest of eye examination was again unremarkable. CT scan and MRI scan of brain and orbit were performed and showed only signs of sinusitis with no intracranial pathology. The palsy resolved spontaneously within two months. A third episode of left 6th nerve palsy occurred 6 months later, whichrecovered over one month. Examination and neuroimagingwere unremarkable. A diagnosis of benign recurrent left 6th cranial nerve palsy was made. Conclusion: Benign sixth cranial nerve palsy is always a diagnosis of exclusion given the more serious and life-threatening alternative causes. It seems to have a good prognosis with only supportive measures. The likelihood of benign 6th cranial nerve palsy to resolve completely and spontaneously is high. Observation for at least 6 months without intervention is advisable.

Keywords: 6th nerve pasy, abducens nerve pasy, recurrent nerve palsy, cranial nerve palsy

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Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

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Authors: J. R. Büttler, T. Pham

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Basic understanding of interfacial mechanisms is of importance for the development of polymer composites. For this purpose, we need techniques to analyze the quality of interphases, their chemical and physical interactions and their strength and fracture resistance. In order to investigate the interfacial phenomena in detail, advanced characterization techniques are favorable. Dynamic mechanical thermal analysis (DMTA) using a rheological system is a sensitive tool. T-peel tests were performed with this system, to investigate the temperature-dependent peel behavior of woven textile composites. A model system was made of polyamide (PA) woven fabric laminated with films of polypropylene (PP) or PP modified by grafting with maleic anhydride (PP-g-MAH). Firstly, control measurements were performed with solely PP matrixes. Polymer melt investigations, as well as the extensional stress, extensional viscosity and extensional relaxation modulus at -10°C, 100 °C and 170 °C, demonstrate similar viscoelastic behavior for films made of PP-g-MAH and its non-modified PP-control. Frequency sweeps have shown that PP-g-MAH has a zero phase viscosity of around 1600 Pa·s and PP-control has a similar zero phase viscosity of 1345 Pa·s. Also, the gelation points are similar at 2.42*104 Pa (118 rad/s) and 2.81*104 Pa (161 rad/s) for PP-control and PP-g-MAH, respectively. Secondly, the textile composite was analyzed. The extensional stress of PA66 fabric laminated with either PP-control or PP-g-MAH at -10 °C, 25 °C and 170 °C for strain rates of 0.001 – 1 s^-1 was investigated. The laminates containing the modified PP need more stress for T-peeling. However, the strengthening effect due to the modification decreases by increasing temperature and at 170 °C, just above the melting temperature of the matrix, the difference disappears. Independent of the matrix used in the textile composite, there is a decrease of extensional stress by increasing temperature. It appears that the more viscous is the matrix, the weaker the laminar adhesion. Possibly, the measurement is influenced by the fact that the laminate becomes stiffer at lower temperatures. Adhesive lap-shear testing at room temperature supports the findings obtained with the T-peel test. Additional analysis of the textile composite at the microscopic level ensures that the fibers are well embedded in the matrix. Atomic force microscopy (AFM) imaging of a cross section of the composite shows no gaps between the fibers and matrix. Measurements of the water contact angle show that the MAH grafted PP is more polar than the virgin-PP, and that suggests a more favorable chemical interaction of PP-g-MAH with PA, compared to the non-modified PP. In fact, this study indicates that T-peel testing by DMTA is a technique to achieve more insights into polymeric textile composites.

Keywords: dynamic mechanical thermal analysis, interphase, polyamide, polypropylene, textile composite

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Authors: Mansouri Ouarda, Abdennour Cherif, Saidi Malika

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Since the industrial revolution, many anthropogenic activities have caused environmental, considerable and overall changes. The lead represents a very dangerous disruptive for the functioning of the body. In this context the current study aims at evaluating a natural therapy by the use of the plant grass in wheat (Triticum durum) against the toxicity of lead in rat wistar male. The rats were divided into three groups: the control group, the group treated with 600 mg /kg food of lead only (Pb) is the group treated with the combination of 600 mg/kg of food and 9g/rat /day of the plant grass in wheat (Pb-bl). The duration of the treatment is 6 weeks. The results of the biometrics of the organs (thyroid, kidney, testis and epididymis) show no significant difference between the three groups. The dosage of a few parameters and hormonal biochemical shows a decrease in the concentration of the hormone T3 and TSH levels among the group pb alone compared to the control and Pb-Bl. These results have been confirmed by the study of histological slices. A morphological changes represented by a shrinking volume of vesicles with the group treated with Pb alone. A return to the normal state of the structure of the follicles was observed. The concentration in serum testosterone, urea and creatinine was significantly increased among the group treated by Pb only in relation to the control and Pb-Bl. whereas the rate of glucose did not show any significant difference. The histology study of the kidney, testis and epididymal weights show no modification at the group Pb-bl comparing to the control. The parenchyma of the kidney shows a dilation of tubes distal and proximal causing a tubular nephropathy for the batch processed by Pb only. The testicles have marked a destruction or absence of germ cells and the light of some seminiferous are almost empty. Conclusion: The supplementation of the plant Triticum durum has caused a considerable improvement which ensures the return of parameters investigated in the normal state.

Keywords: creatinine, glucose, histological sections, T3, TSH, testosterone

Procedia PDF Downloads 372

Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

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Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

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Authors: K. O’Mara, T. Cresswell

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Nearly half of the world’s population live near the coast, and as a result, estuaries and coastal bays in populated or industrialized areas often receive metal pollution. Heavy metals have a chemical affinity for sediment particles and can be stored in estuarine sediments and become biologically available under changing conditions. Organisms inhabiting estuaries can be exposed to metals from a variety of sources including metals dissolved in water, bound to sediment or within contaminated prey. Metal uptake and assimilation responses can vary even between species that are biologically similar, making pollution effects difficult to predict. A multi-trophic level experiment representing a common Eastern Australian estuarine food chain was used to study the sources for Cd, Mn and Zn uptake and assimilation in organisms occupying several trophic levels. Sand cockles (Katelysia scalarina), school prawns (Metapenaeus macleayi) and sand whiting (Sillago ciliata) were exposed to radiolabelled seawater, suspended sediment and food. Three pulse-chase trials on filter-feeding sand cockles were performed using radiolabelled phytoplankton (Tetraselmis sp.), benthic microalgae (Entomoneis sp.) and suspended sediment. Benthic microalgae had lower metal uptake than phytoplankton during labelling but higher cockle assimilation efficiencies (Cd = 51%, Mn = 42%, Zn = 63 %) than both phytoplankton (Cd = 21%, Mn = 32%, Zn = 33%) and suspended sediment (except Mn; (Cd = 38%, Mn = 42%, Zn = 53%)). Sand cockles were also sensitive to uptake of Cd, Mn and Zn dissolved in seawater. Uptake of these metals from the dissolved phase was negligible in prawns and fish, with prawns only accumulating metals during moulting, which were then lost with subsequent moulting in the depuration phase. Diet appears to be the main source of metal assimilation in school prawns, with 65%, 54% and 58% assimilation efficiencies from Cd, Mn and Zn respectively. Whiting fed contaminated prawns were able to exclude the majority of the metal activity through egestion, with only 10%, 23% and 11% assimilation efficiencies from Cd, Mn and Zn respectively. The findings of this study support previous studies that find diet to be the dominant accumulation source for higher level trophic organisms. These results show that assimilation efficiencies can vary depending on the source of exposure; sand cockles assimilated more Cd, Mn, and Zn from the benthic diatom than phytoplankton and assimilation was higher in sand whiting fed prawns compared to artificial pellets. The sensitivity of sand cockles to metal uptake and assimilation from a variety of sources poses concerns for metal availability to predators ingesting the clam tissue, including humans. The high tolerance of sand whiting to these metals is reflected in their widespread presence in Eastern Australian estuaries, including contaminated estuaries such as Botany Bay and Port Jackson.

Keywords: cadmium, food chain, metal, manganese, trophic, zinc

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Authors: Kyoko Monden

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Tourism has moved to the forefront of national attention in Japan since September of 2013 when Tokyo won its bid to host the 2020 Summer Olympics. The number of foreign tourists has continued to break records, reaching 13.4 million in 2014, and is now expected to hit 20 million sooner than initially targeted 2020 due to government stimulus promotions; an increase in low cost carriers; the weakening of the Japanese yen, and strong economic growth in Asia. The tourism industry can be an effective trigger in Japan’s economic recovery as foreign tourists spent two trillion yen ($16.6 million) in Japan in 2014. In addition, 81% of them were all from Asian countries, and it is essential to know that 68.9% of the world’s Muslims, about a billion people, live in South and Southeast Asia. An important question is ‘Do Muslim tourists feel comfortable traveling in Japan?’ This research was initiated by an encounter with Muslim visitors in Hiroshima, a popular international tourist destination, who said they had found very few suitable restaurants in Hiroshima. The purpose of this research is to examine halal implementation in Hiroshima and suggest the next steps to be taken to improve current efforts. The goal will be to provide anyone, Muslims included, with first class hospitality in the near future in preparation for the massive influx of foreign tourists in 2020. The methods of this research were questionnaires, face-to-face interviews, phone interviews, and internet research. First, this research aims to address the significance of growing inbound tourism in Japan, especially the expected growth in Muslim tourists. Additionally, it should address the strong popularity of eating Japanese foods in Asian Muslim countries and as ranked no. 1 thing foreign tourists want to do in Japan. Secondly, the current incipient stage of Hiroshima’s halal implementation at hotels, restaurants, and major public places were exposed, and the existing action plans by Hiroshima Prefecture Government were presented. Furthermore, two surveys were conducted to clarify basic halal awareness of local residents in Hiroshima, and to gauge the inconveniences Muslims living in Hiroshima faced. Thirdly, the reasons for this lapse were observed and compared to the benchmarking data of other major tourist sites, Hiroshima’s halal implementation plans were proposed. The conclusion is, despite increasing demands and interests in halal-friendly businesses, overall halal actions have barely been applied in Hiroshima. 76% of Hiroshima residents had no idea what halal or halaal meant. It is essential to increase halal awareness and its importance to the economy and to launch further actions to make Muslim tourists feel welcome in Hiroshima and the entire country.

Keywords: halaal, halal implementation, Hiroshima, inbound tourists in Japan

Procedia PDF Downloads 218

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

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Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.

Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa

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Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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Authors: Howaida I. Abd-Alla, Omnia Kutkat, Yassmin Moatasim, Magda T. Ibrahim, Marwa A. Mostafa, Mohamed GabAllah, Mounir M. El-Safty

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Artemisia judaica (known shih-balady), Azadirachta indica and Sophora tomentosa (known yellow necklace pod) are members of available medicinal plants well-known for their traditional medical use in Egypt which suggests that they probably harbor broad-spectrum antiviral, immunostimulatory and anti-inflammatory functions. Their ethyl acetate-dichloromethane (1:1, v/v) extracts were evaluated for the potential anti-Middle East respiratory syndrome-related coronavirus (anti-MERS-CoV) activity. Their cytotoxic activity was tested in Vero-E6 cells using 3-(4,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method with minor modification. The plot of percentage cytotoxicity for each extract concentration has calculated the concentration which exhibited 50% cytotoxic concentration (TC50). A plaque reduction assay was employed using safe dose of extract to evaluate its effect on virus propagation. The highest inhibition percentage was recorded for the yellow necklace pod, followed by Shih-balady. The possible mode of action of virus inhibition was studied at three different levels viral replication, viral adsorption and virucidal activity. The necklace pod leaves have induced virucidal effects and direct effects on the replication of virus. Phytochemical investigation of the promising necklace pod led to the isolation and structure determination of nine compounds. The structure of each compound was determined by a variety of spectroscopic methods. Compounds 4-O-methyl sorbitol 1, 8-methoxy daidzin 6 and 6-methoxy apigenin-7-O-β-D-glucopyranoside 8 were isolated for the first time from the Sophora genus and the other six compounds were the first time that they were isolated from this species according to available works of literature. Generally, the highest anti-CoV 2 activity of S. tomentosa was associated with the crude ethanolic extract, indicating the possibility of synergy among the antiviral phytochemical constituents (1-9).

Keywords: coronavirus, MERS-CoV, mode of action, necklace pod, shih-balady

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species

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Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo

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Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.

Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine

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Authors: Hai L. Tran

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Previous research on agenda setting effects has often focused on the top-down influence of the media at the aggregate level, while overlooking the capacity of audience members to select media and content to fit their individual dispositions. The decentralized characteristics of online communication and digital news create more choices and greater user control, thereby enabling each audience member to seek out a unique blend of media sources, issues, and elements of messages and to mix them into a coherent individual picture of the world. This study examines how audiences use media differently depending on their prior dispositions, thereby making sense of the world in ways that are congruent with their preferences and cognitions. The current undertaking is informed by theoretical frameworks from two distinct lines of scholarship. According to the ideological migration hypothesis, individuals choose to live in communities with ideologies like their own to satisfy their need to belong. One tends to move away from Zip codes that are incongruent and toward those that are more aligned with one’s ideological orientation. This geographical division along ideological lines has been documented in social psychology research. As an extension of agenda setting, the agendamelding hypothesis argues that audiences seek out information in attractive media and blend them into a coherent narrative that fits with a common agenda shared by others, who think as they do and communicate with them about issues of public. In other words, individuals, through their media use, identify themselves with a group/community that they want to join. Accordingly, the present study hypothesizes that because ideology plays a role in pushing people toward a physical community that fits their need to belong, it also leads individuals to receive an idiosyncratic blend of media and be influenced by such selective exposure in deciding what issues are more relevant. Consequently, the individualized focus of media choices impacts how audiences perceive political news coverage and what they know about political issues. The research project utilizes recent data from The American Trends Panel survey conducted by Pew Research Center to explore the nuanced nature of agenda setting at the individual level and amid heightened polarization. Hypothesis testing is performed with both nonparametric and parametric procedures, including regression and path analysis. This research attempts to explore the media-public relationship from a bottom-up approach, considering the ability of active audience members to select among media in a larger process that entails agenda setting. It helps encourage agenda-setting scholars to further examine effects at the individual, rather than aggregate, level. In addition to theoretical contributions, the study’s findings are useful for media professionals in building and maintaining relationships with the audience considering changes in market share due to the spread of digital and social media.

Keywords: agenda setting, agendamelding, audience fragmentation, ideological migration, partisanship, polarization

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Adi Sharabi, Dafna Marom-Golan

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Parents’ involvement in the care of their children with Autism Spectrum Disorder (ASD) and its beneficial effect on the children’s developmental and educational outcomes is well documented. At the same time, parents of children with ASD tend to experience greater psychological distress than parents of children with other developmental disabilities or with typical development. Positive social support is an important resource used by parents to reduce their psychological distress. The goal of the current research was to examine the contribution of formal and informal social support in explaining mothers’ and fathers’ involvement with their young children with ASD. The sample consisted of 107 parents who live in Israel (61 mothers and 46 fathers) of children aged between 2 and 7, all diagnosed with ASD and attending special kindergartens or special day care for children with ASD. Parental involvement and social support perception were assessed. Initial analysis focused on the relations between involvement, support, and demographic variables. In addition, analysis of variance (ANOVA) was conducted to test differences between mothers and fathers. Two hierarchical multiple regression analyses were performed to examine the predicted factors in the involvement model while controlling for group (mothers/fathers). Results indicate that mothers reported significantly higher levels of parenting involvement than fathers. Mothers reported higher levels of general involvement and all sub-types of involvement. For example, mothers reported that they were more interested in and have higher levels of attendance in their child’s educational program. They were also more collaborative in their child’s educational therapeutic program, and socialized with other parents of children from their child’s kindergarten than fathers. Mothers’ involvement was found to be related to their informal support (non-formal relatives). Findings also reveal significant differences between mothers and fathers on the formal support subscale measure of specializes services. Fathers, more than mothers, reported more specializes services support such as social workers or professional therapists. Separate hierarchical multiple regression analyses revealed a unique gender difference in the factors that explained parental involvement. Specifically, informal support only had a unique positive contribution in explaining mothers’, but not fathers’ involvement. This study highlights the central role of mothers in maintaining constant contact with the educational system and the professionals who help care for their child with ASD. At the same time, this research emphasizes the crucial role of both mothers and fathers in their child's development and well-being at every development stage, particularly in early development. Further, different kinds of social support seem to relate to the different kinds of parental involvement. It is in the best interest of educators and family therapists who work with families with children with ASD to support the cohesiveness of the family and the collaboration of the parents by understanding and respecting the way each member addresses the responsibilities of parenting a child with ASD, and her or his need for different types of social support.

Keywords: parental differences, parental involvement, social support, specialized support services

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Authors: Jiangang Shen

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Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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Authors: A. R. Shokoohi, E. A. M. Bulder, C. Th. van Alphen, D. F. den Hertog, E. J. Hin

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The Northern region of the Netherlands has beautiful landscapes, a nice diversity of green and blue areas, and dispersed settlements. However, some recent population changes can become threats to health and wellbeing in these areas. The rural areas in the three northern provinces -Groningen, Friesland, and Drenthe, see youngsters leave the region for which reason they are aging faster than other regions in the Netherlands. As a result, some villages have faced major population decline that is leading to loss of facilities/amenities and a decrease in accessibility and social cohesion. Those who still live in these villages are relatively old, low educated and have low-income. To develop a deeper understanding of the health status of the people living in these areas, and help them to improve their living environment, the GO!-Method is being applied in this study. This method has been developed by the National Institute for Public Health and the Environment (RIVM) of the Netherlands and is inspired by the broad definition of health by Machteld Huber: the ability to adapt and direct control, in terms of the physical, emotional and social challenges of life, while paying extra attention to vulnerable groups. A healthy living environment is defined as an environment that residents find it pleasant and encourages and supports healthy behavior. The GO!-method integrates six domains that constitute a healthy living environment: health and lifestyle, facilities and development, safety and hygiene, social cohesion and active citizens, green areas, and air and noise pollution. First of all, this method will identify opportunities for a healthier living environment using existing information and perceptions of residents and other local stakeholders in order to strengthen social participation and quality of life in these rural areas. Second, this approach will connect identified opportunities with available and effective evidence-based interventions in order to develop an action plan from the residents and local authorities perspective which will help them to design their municipalities healthier and more resilient. This method is being used for the first time in rural areas to our best knowledge, in close collaboration with the residents and local authorities of the three provinces to create a sustainable process and stimulate social participation. Our paper will present the outcomes of the first phase of this project in collaboration with the municipality of Westerkwartier, located in the northwest of the province of Groningen. And will describe the current situation, and identify local assets, opportunities, and policies relating to healthier environment; as well as needs and challenges to achieve goals. The preliminary results show that rural demographic changes in the northern Netherlands have negative impacts on service provisions and social cohesion, and there is a need to understand this complicated situation and improve the quality of life in those areas.

Keywords: population decline, rural areas, healthy environment, Netherlands

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Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Radmila Maksimovic, Sonja Ketin, Rade Biocanin, Jelena Maksimovic

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The abnormal conditions of life and work genetic factors often play a major role in incidence of diabetes-diabetes, heart disease and vascular disease, jaundice, and post traumatic stress. Trauma and post traumatic stress are most common in the displaced persons,and the focus of this paper is to shed light on this issue in former Yugoslavia, Yugoslavia and now in our country. This is caused by increased beta-cell sensitivity to viruses, the development of autoimmune antibodies against its own pancreascells, degenerative changes in cells that r esult in change of structure and insulin. In this paper, we dealt with traumatic events and long-term psycho social consequences for internally displaced persons, several years after displacement, and found a high level of PTSD symptoms. This stress is present in almost 1/3 of internally displaced persons, and every sixth person is suffering from PTSD in the past. Respondents generally suffer from symptoms of intrusion, but there was a large number of symptoms, avoidance and increased arousal. We also found that gender, age andeducation related to the symptoms. Females, and older respondents and internally displaced persons with lower levels of education how a higher level of PTSD symptoms, especially symptoms of intrusion and increase darousal. It is a highly traumatized sample in which more than 1/2 of respondents experienced more than three traumatic events in life,although the number of traumas experienced before, during and after the conflict varies.We found that during the war, internally displaced persons haveexperienced more traumatic events compared with the periodbefore and after the conflict. Trauma are different in type. No significant correlation between the number of experienced trauma and PTSD, suggesting that it is necessary to further study the structure of past traumas and the intermediary effects of certain risk factors and protective factors.

Keywords: living environment, displaced persons, jaundice, diabetes, trauma, diabetic hypertension, post-traumatic stress (PTSD), treatment

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Authors: Boor Singh Lalia, Yarjan Abdul Samad, Raed Hashaikeh

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Three different kinds of solid polymer electrolytes were prepared using polyethylene oxide (PEO) as a base polymer, networked cellulose (NC) as a physical support and LiClO4 as a conductive salt for the electrolytes. Networked cellulose, a modified form of cellulose, is a biodegradable and environmentally friendly additive which provides a strong fibrous networked support for structural stability of the electrolytes. Although the PEO/NC/LiClO4 electrolyte retains its structural integrity and mechanical properties at 100oC as compared to pristine PEO-based polymer electrolytes, it suffers from poor ionic conductivity. To improve the room temperature conductivity of the electrolyte, PEO is replaced by the polyethylene glycol (PEG) which is a liquid phase that provides high mobility for Li+ ions transport in the electrolyte. PEG/NC/LiClO4 shows improvement in ionic conductivity compared to PEO/NC/LiClO4 at room temperature, but it is brittle and tends to form cracks during processing. An advanced solid polymer electrolyte with optimum ionic conductivity and mechanical properties is developed by using a ternary system: TEGDME/PEO/NC+LiClO4. At room temperature, this electrolyte exhibits an ionic conductivity to the order of 10-5 S/cm, which is very high compared to that of the PEO/LiClO4 electrolyte. Pristine PEO electrolytes start melting at 65 °C and completely lose its mechanical strength. Dynamic mechanical analysis of TEGDME: PEO: NC (70:20:10 wt%) showed an improvement of storage modulus as compared to the pristine PEO in the 60–120 °C temperature range. Also, with an addition of NC, the electrolyte retains its mechanical integrity at 100 oC which is beneficial for Li-ion battery operation at high temperatures. Differential scanning calorimetry (DSC) and thermal gravimetry analysis (TGA) studies revealed that the ternary polymer electrolyte is thermally stable in the lithium ion battery operational temperature range. As-prepared polymer electrolyte was used to assemble LiFePO4/ TEGDME/PEO/NC+LiClO4/Li half cells and their electrochemical performance was studied via cyclic voltammetry and charge-discharge cycling.

Keywords: solid polymer electrolyte, ionic conductivity, mechanical properties, lithium ion batteries, cyclic voltammetry

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Authors: Sercan Altundemir, Pinar Eribol, A. Kerem Uguz

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Microfluidics systems allow many-large scale laboratory applications to be miniaturized on a single device in order to reduce cost and advance fluid control. Moreover, such systems enable to generate and control droplets which have a significant role on improved analysis for many chemical and biological applications. For example, they can be employed as the model for cells in microfluidic systems. In this work, the interfacial instability of two immiscible Newtonian liquids flowing in a microchannel is investigated. When two immiscible liquids are in laminar regime, a flat interface is formed between them. If a direct current electric field is applied, the interface may deform, i.e. may become unstable and it may be ruptured and form micro-droplets. First, the effect of thickness ratio, total flow rate, viscosity ratio of the silicone oil and ethylene glycol liquid couple on the critical voltage at which the interface starts to destabilize is investigated. Then the droplet sizes are measured under the effect of these parameters at various voltages. Moreover, the effect of total flow rate on the time elapsed for the interface to be ruptured to form droplets by hitting the wall of the channel is analyzed. It is observed that an increase in the viscosity or the thickness ratio of the silicone oil to the ethylene glycol has a stabilizing effect, i.e. a higher voltage is needed while the total flow rate has no effect on it. However, it is observed that an increase in the total flow rate results in shortening of the elapsed time for the interface to hit the wall. Moreover, the droplet size decreases down to 0.1 μL with an increase in the applied voltage, the viscosity ratio or the total flow rate or a decrease in the thickness ratio. In addition to these observations, two empirical models for determining the critical electric number, i.e., the dimensionless voltage and the droplet size and another model which is a combination of both models, for determining the droplet size at the critical voltage are established.

Keywords: droplet formation, electrohydrodynamics, microfluidics, two-phase flow

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Authors: Kahina Amal Djiar, Mouna Gharbi, Maha Messaoudene, Oumelkheir Chareb

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Over the last decade, Algerian authorities have implemented an ambitious program of urban renewal, which includes important relocation operations. The objectives behind such strategic interventions are on the one hand, to carry out an incremental approach aiming at eradicating precarious housing and on the other hand, to diversify alternative housing options for families requiring better living spaces. It is precisely for these same purposes that the Djenan el-Hassan and Carrières Jaubert estates, which are both located in Algiers, have undergone major urban transformations. These dwelling sites were built as part of the famous "Battle of Housing", which was launched by French colonial administration in the 1950s just before the independence of Algeria in 1962. Today, the Djenan el-Hassan estate is almost entirely demolished following the relocation of 171 families. The Carrières Jaubert estate, for its part, has seen two kinds of operations. The first has been shaped by a process of urban requalification and redevelopment, which allowed some of the residents to stay on site after the transformation of most housing cells into larger apartments. The second operation has required the relocation of over 300 families to entirely newly built dwellings. Such projects of urban renewal are supposed to create new opportunities, not only in terms of local urban development, but also in terms of social perspectives for those families who are involved, either directly or indirectly, in the process of relocation. In fact, the percentage of urban violence in Algiers has increased instead. Recent events in the newly built estates show that residents are repeatedly experiencing and even instigating episodes of brutality, hostility and aggression. The objective of this paper is to examine the causes that have engendered such rise in urban violence in newly built housing estates in Algiers. This paper aims to present the findings of a recent qualitative research and highlight the way that poorly designed neighbourhood, combined with a relocation process that leaves little room for community participation, create inevitably severe social tensions.

Keywords: relocation, social housing, violence, Algiers

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Authors: Willian C. De Brito, Hernan D. C. Munoz, Erlan V. C. Carvalho, Helder L. C. De Oliveira

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In order to improve commute time for small distance trips and relieve large cities traffic, a new transport category has been the subject of research and new designs worldwide. The air taxi travel market promises to change the way people live and commute by using the concept of vehicles with the ability to take-off and land vertically and to provide passenger’s transport equivalent to a car, with mobility within large cities and between cities. Today’s civil air transport remains costly and accounts for 2% of the man-made CO₂ emissions. Taking advantage of this scenario, many companies have developed their own Vertical Take Off and Landing (VTOL) design, seeking to meet comfort, safety, low cost and flight time requirements in a sustainable way. Thus, the use of green power supplies, especially batteries, and fully electric power plants is the most common choice for these arising aircrafts. However, it is still a challenge finding a feasible way to handle with the use of batteries rather than conventional petroleum-based fuels. The batteries are heavy and have an energy density still below from those of gasoline, diesel or kerosene. Therefore, despite all the clear advantages, all electric aircrafts (AEA) still have low flight autonomy and high operational cost, since the batteries must be recharged or replaced. In this sense, this paper addresses a way to optimize the energy consumption in a typical mission of an aerial taxi aircraft. The approach and landing procedure was chosen to be the subject of an optimization genetic algorithm, while final programming can be adapted for take-off and flight level changes as well. A real tilt rotor aircraft with fully electric power plant data was used to fit the derived dynamic equations of motion. Although a tilt rotor design is used as a proof of concept, it is possible to change the optimization to be applied for other design concepts, even those with independent motors for hover and cruise flight phases. For a given trajectory, the best set of control variables are calculated to provide the time history response for aircraft´s attitude, rotors RPM and thrust direction (or vertical and horizontal thrust, for independent motors designs) that, if followed, results in the minimum electric power consumption through that landing path. Safety, comfort and design constraints are assumed to give representativeness to the solution. Results are highly dependent on these constraints. For the tested cases, performance improvement ranged from 5 to 10% changing initial airspeed, altitude, flight path angle, and attitude.

Keywords: air taxi travel, all electric aircraft, batteries, energy consumption, genetic algorithm, landing performance, optimization, performance improvement, tilt rotor, VTOL design

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Authors: Nishanthi N. S., Srikanth Vedantam

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Intracellular delivery of materials has always proved to be a challenge in research and therapeutic applications. Usually, vector-based methods, such as liposomes and polymeric materials, and physical methods, such as electroporation and sonoporation have been used for introducing nucleic acids or proteins. Reliance on exogenous materials, toxicity, off-target effects was the short-comings of these methods. Microinjection was an alternative process which addressed the above drawbacks. However, its low throughput had hindered its adoption widely. Mechanical deformation of cells by squeezing them through constriction channel can cause the temporary development of pores that would facilitate non-targeted diffusion of materials. Advantages of this method include high efficiency in intracellular delivery, a wide choice of materials, improved viability and high throughput. This cell squeezing process can be studied deeper by employing simple models and efficient computational procedures. In our current work, we present a finite sized dissipative particle dynamics (FDPD) model to simulate the dynamics of the cell flowing through a constricted channel. The cell is modeled as a capsule with FDPD particles connected through a spring network to represent the membrane. The total energy of the capsule is associated with linear and radial springs in addition to constraint of the fixed area. By performing detailed simulations, we studied the strain on the membrane of the capsule for channels with varying constriction heights. The strain on the capsule membrane was found to be similar though the constriction heights vary. When strain on the membrane was correlated to the development of pores, we found higher porosity in capsule flowing in wider channel. This is due to localization of strain to a smaller region in the narrow constriction channel. But the residence time of the capsule increased as the channel constriction narrowed indicating that strain for an increased time will cause less cell viability.

Keywords: capsule, cell squeezing, dissipative particle dynamics, intracellular delivery, microfluidics, numerical simulations

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Authors: Daniela Proca, Yuan Rong, Salvatore Luceno, Jalil Nasibli

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Introduction: Solitary Fibrous Tumors (SFT) have many histologic mimickers and the only way to diagnose it, particularly in an unusual location, such as peripheral nerve trunks, is to use a comprehensive immunohistochemical staining panel. Monoclonal STAT6 immunostain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases. Methods: We describe a solitary fibrous tumor (SFT) involving the right branchial plexus in a 66 yo female with 4-year history of slowly growing chest wall mass with recent dysesthesias in fingers 4th and 5th. MRI showed a well-circumscribed heterogenous mass measuring 5.4 x 3.8 x 4.0 cm and encircling peripheral nerves of the branchial plexus; no involvement of the bone or muscle was noted. A biopsy showed a bland spindled and epithelioid proliferation with no significant mitotic activity, no necrosis, and no atypia; peripheral nerve fascicles were encircled by the lesion. The main clinical and pathologic differential diagnosis included peripheral nerve sheath tumor, particularly schwannoma; HE microscopy didn’t show the classic Antoni A and B areas but showed focal subtle nuclear palisading, as well as prominent vessels with hyalinization. Immunohistochemical stains showed focal, weak cytoplasmic S100 positivity in the lesion; CD 34 and Vimentin were strongly and diffusely positive; the neoplastic cells were negative with AE1/AE3, EMA, CD31, SMA, Desmin, Calretinin, HMB-45, Melan A, PAX-8, NSE. The immunohistochemical and histologic pattern was not typical of peripheral nerve sheath tumor. On additional stains, the tumor was positive with STAT-6 and bcl-2 and focally positive with CD99. Given this profile, the final diagnosis was that of a solitary fibrous tumor. Results: NA Conclusion: Very few SFTs involving peripheral nerves and mimicking a peripheral nerve sheath tumor are described in the literature. Although histologically benign on this biopsy, long-term follow-up is required because of the risk of recurrence of these tumors and their uncertain biological behavior.

Keywords: solitary fibrous tumor, pathology, diagnosis, immunohistochemistry

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Authors: Anurag Devkota

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Foreign employment serves to be the strongest pillar in engendering employment options for a large number of the young Nepali population. Nepali workers are forced to leave the comfort of their homes and are exposed to precarious conditions while on a journey to earn enough money to live better their lives. The exponential rise in foreign labour migration has produced a snowball effect on the economy of the nation. The dramatic variation in the economic development of the state has proved to establish the fact that migration is increasingly significant for livelihood, economic development, political stability, academic discourse and policy planning in Nepal. The foreign employment practice in Nepal largely incorporates the role of individual agents in the entire process of migration. With the fraudulent acts and false promises of these agents, the problems associated with every Nepali migrant worker starts at home. The workers encounter tremendous pre-departure malpractice and exploitation at home by different individual agents during different stages of processing. Although these epidemic and repetitive ill activities of intermediaries are dominant and deeply rooted, the agents have been allowed to walk free in the absence of proper laws to curb their wrongdoings and misconduct. It has been found that the existing regulatory mechanisms have not been utilised to their full efficacy and often fall short in addressing the actual concerns of the workers because of the complex legal and judicial procedures. Structural changes in the judicial setting will help bring perpetrators under the law and victims towards access to justice. Thus, a qualitative improvement of the overall situation of Nepali migrant workers calls for a proper 'regulatory' arrangement vis-à-vis these brokers. Hence, the author aims to carry out a doctrinal study using reports and scholarly articles as a major source of data collection. Various reports published by different non-governmental and governmental organizations working in the field of labour migration will be examined and the research will focus on the inductive and deductive data analysis. Hence, the real challenge of establishing a pro-migrant worker regime in recent times is to bring the agents under the jurisdiction of the court in Nepal. The Gulf Visit Study Report, 2017 prepared and launched by the International Relation and Labour Committee of Legislature-Parliament of Nepal finds that solving the problems at home solves 80 percent of the problems concerning migrant workers in Nepal. Against this backdrop, this research study is intended to determine the ways and measures to curb the role of agents in the foreign employment and labour migration process of Nepal. It will further dig deeper into the regulatory mechanisms of Nepal and map out essential determinant behind the impunity of agents.

Keywords: foreign employment, labour migration, human rights, migrant workers

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