Search results for: TLR4/NF-κB pathway

Authors: Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

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Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice; however, commercial substitutes, such as BeePro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism. Gene ontology enrichment revealed that, compared with poor diet (carbohydrates (C)), bees fed pollen (P > C), BeePro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions and superior proteolysis. The superiority of the pollen diet was also evident through the remarkable overexpression of vitellogenin in bees fed pollen instead of MegaBee or BeePro. Upregulation of bioprocesses under carbohydrates feeding compared to pollen (C > P) provided a clear poor nutritional status, uncovering stark expression changes that were slight or absent relatively to BeePro (C > B) or MegaBee (C > M). Poor diet feeding (C > P) induced starvation response genes and hippo signaling pathway, while it repressed growth through different mechanisms. Carbohydrate feeding (C > P) also elicited ‘adult behavior’, and developmental processes suggesting transition to foraging. Finally, it altered the ‘circadian rhythm’, reflecting the role of this mechanism in the adaptation to nutritional stress in mammals. Nosema-infected bees fed pollen compared to carbohydrates (PN > CN) upheld certain bioprocesses of uninfected bees (P > C). Poor nutritional status was more apparent against pollen (CN > PN) than BeePro (CN > BN) or MegaBee (CN > MN). Nosema accentuated the effects of malnutrition since more starvation-response genes and stress response mechanisms were upregulated in CN > PN compared to C > P. The bioprocess ‘Macromolecular complex assembly’ was also enriched in CN > PN, and involved genes associated with human HIV and/or influenza, thus providing potential candidates for bee-Nosema interactions. Finally, the enzyme Duox emerged as essential for guts defense in bees, similarly to Drosophila. These results provide evidence of the superior nutritional status of bees fed pollen instead of artificial substitutes in terms of overall health, even in the presence of a pathogen.

Keywords: honeybee, immunity, Nosema, nutrition, RNA-seq

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: Nada Mohamed, Abdel Aziz Mohamed

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Climate change in coastal areas is a global issue that can be felt on local scale and will be around for decades and centuries to come to an end; it also has critical risks on the city’s economy, communities, and the natural environment. One of these changes that cause a huge risk on coastal cities is the sea level rise (SLR). SLR is a result of scarcity and reduction in global environmental system. The main cause of climate change and global warming is the countries with high development index (HDI) as Japan and Germany while the medium and low HDI countries as Egypt does not have enough awareness and advanced tactics to adapt with this changes that destroy urban areas and cause loss in land and economy. This is why Climate Resilience is one of the UN sustainable development goals 2030, which is calling for actions to strengthen climate change resilience through mitigation and adaptation. For many reasons, adaptation has received less attention than mitigation and it is only recently that adaptation has become a focal global point of attention. This adaption can be achieved through some actions such as upgrading the use and the design of the land, adjusting business and activities of people, and increasing community understanding of climate risks. To reach the adaption goals, and we have to apply a strategic pathway to Climate Resilience, which is the Urban Bioregionalism Paradigm. Resiliency has been framed as persistence, adaptation, and transformation. Climate Resilience decision support system includes a visualization platform where ecological, social, and economic information can be viewed alongside with specific geographies that's why Urban Bioregionalism is a socio-ecological system which is defined as a paradigm that has potential to help move social attitudes toward environmental understanding and deepen human-environment connections within ecological development. The research aim is to achieve an adaptive integrated urban development model throughout the analyses of tactics and strategies that can be used to adapt urban areas and coastal communities to the challenges of climate changes especially SLR and also simulation model using advanced technological software for a coastal city corridor to elaborates the suitable strategy to apply.

Keywords: climate resilience, sea level rise, SLR, coastal resilience, adaptive development simulation

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

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Wayde Veldman, Ozlem T. Bishop, Igor Polikarpov

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In bacteria, mono and disaccharides are phosphorylated during uptake into the cell via the widely used phosphoenolpyruvate (PEP)-dependent phosphotransferase transport system. As an initial step in the phosphorylated disaccharide metabolism pathway, certain glycoside hydrolase family 1 (GH1) enzymes play a crucial role in releasing phosphorylated and non-phosphorylated monosaccharides. However, structural determinants for the specificity of these enzymes still need to be clarified. GH1 enzymes are known to have a wide array of functions. According to the CAZy database, there are twenty-one different enzymatic activities in the GH1 family. Here, the structure and substrate specificity of a GH1 enzyme from Bacillus licheniformis, hereafter known as BlBglH, was investigated. The sequence of the enzyme BlBglH was compared to the sequences of other characterized GH1 enzymes using sequence alignment, sequence identity calculations, phylogenetic analysis, and motif discovery. Through these various analyses, BlBglH was found to have sequence features characteristic of the 6-phospho-β-glucosidase activity enzymes. Additionally, motif and structure comparisons of the three most commonly studied GH1 enzyme-activities revealed a shared loop amongst the different structures that consist of different sequence motifs – this loop is thought to guide specific substrates (depending on activity) towards the active-site. To further affirm BlBglH enzyme activity, molecular docking and molecular dynamics simulations were performed. Docking was carried out using 6-phospho-β-glucosidase enzyme-activity positive (p-Nitrophenyl-beta-D-glucoside-6-phosphate) and negative (p-Nitrophenyl-beta-D-galactoside-6-phosphate) control ligands, followed by 400 ns molecular dynamics simulations. The positive-control ligand maintained favourable interactions within the active site until the end of the simulation. The negative-control ligand was observed exiting the enzyme at 287 ns. Binding free energy calculations showed that the positive-control complex had a substantially more favourable binding energy compared to the negative-control complex. Jointly, the findings of this study suggest that the BlBglH enzyme possesses 6-phospho-β-glucosidase enzymatic activity.

Keywords: 6-P-β-glucosidase, glycoside hydrolase 1, molecular dynamics, sequence analysis, substrate specificity

Procedia PDF Downloads 107

Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Vikas Kumar

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Portable batteries are reliable source of mobile energy to power smart wearable electronics, medical devices, communications, and others internet of thing (IoT) devices. There is a continuous increase in demand for thinner, more flexible battery with high energy density and reliability to meet the requirement. For a flexible battery, factors that affect these properties are the stability of current collectors, electrode materials and their interfaces with the corrosive electrolytes. State-of-the-art conventional and flexible batteries utilise carbon as an electrode and current collectors which cause high internal resistance (~100 ohms) and limit the peak current to ~1mA. This makes them unsuitable for a wide range of applications. Replacing the carbon parts with metallic components would reduce the internal resistance (and hence reduce parasitic loss), but significantly increases the risk of corrosion due to galvanic interactions within the battery. To overcome these challenges, low cost electroplated nickel (Ni) on copper (Cu) was studied as a potential anode current collector for a zinc-manganese oxide primary battery with different concentration of NH4Cl/ZnCl2 electrolyte. Using electrical impedance spectroscopy (EIS), we monitored the open circuit potential (OCP) of electroplated nickel (different thicknesses) in different concentration of electrolytes to optimise the thickness of Ni coating. Our results show that electroless Ni coating suffer excessive corrosion in these electrolytes. Corrosion rates of Ni coatings for different concentrations of electrolytes have been calculated with Tafel analysis. These results suggest that for electroplated Ni, channelling and/or open porosity is a major issue, which was confirmed by morphological analysis. These channels are an easy pathway for electrolyte to penetrate thorough Ni to corrode the Ni/Cu interface completely. We further investigated the incorporation of a special printed graphene layer on Ni to provide corrosion protection in this corrosive electrolyte medium. We find that the incorporation of printed graphene layer provides the corrosion protection to the Ni and enhances the chemical bonding between the active materials and current collector and also decreases the overall internal resistance of the battery system.

Keywords: corrosion, electrical impedance spectroscopy, flexible battery, graphene, metal current collector

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Authors: Stefan Kurbatfinski, Aliyah Dosani, Andrew F. Hayes, Deborah Dewey, Nicole Letourneau

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Background: Maternal adverse childhood experiences (ACEs) have been associated with internalizing and externalizing behavioral problems in preschool children. However, little is known about the influence of maternal adult attachment patterns on this association. Further, potential moderation by maternal mental health, maternal social support, or child sex is poorly understood. Therefore, this study examined associations between 1) maternal ACEs and preschool children’s behavioural problems, with mediation through maternal attachment patterns and moderation by maternal mental health, maternal social support, and child sex; and 2) maternal attachment patterns and children’s behavioural problems, with mediation through maternal mental health and social support and moderation by child sex. Methods: This secondary analysis used data (n=625) from a high socioeconomic, longitudinally prospective cohort (Alberta Pregnancy Outcomes and Nutrition). Child behaviour (BASC-2) and maternal adult attachment (ECR-Q) were measured at five years of child age, maternal ACEs (ACEs Questionnaire) at around 12 months, and maternal mental health (CESD and SCL-90-R) and social support (SSQ) across various prenatal and postnatal time points. All moderation and mediation analyses occurred through RStudio using PROCESS, interpreting significant interactions through Johnson-Neyman plots. Findings: Maternal ACEs interacted with maternal anxiety symptoms to predict both behavioural problems (pexternalizing=0.007; pinternalizing=0.0159). An indirect pathway via dismissive attachment was moderated by maternal social support ([0.0058, 0.0596]). Attachment patterns predicted all behavioural problems (p<0.05) and interacted with maternal anxiety symptoms to predict internalizing behaviours among male children ([0.0321, 0.1307]; [0.0321, 0.1291]). Interpretation: Maternal attachment patterns may predict children’s behavioural problems more than ACEs. Social support interventions may not always be beneficial for highly dismissively attached mothers. Implications for policy and child health include mandatory sex and gender education for teachers; assessing attachment patterns prior to recommending social support as an intervention; and anxiety-focused interventions for mothers in higher socioeconomic populations.

Keywords: maternal adverse childhood experiences, internalizing behaviours, externalizing behaviours, mediators and moderators, attachment patterns, child health

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Authors: Sabri Sudirman, Yuan-Hua Hsu, Zwe-Ling Kong

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Male reproductive dysfunction is predominantly due to insulin resistance and hyperglycemia result in inflammation and oxidative stress. Furthermore, nanotechnology provides an alternative approach to improve the bioavailability of natural active food ingredients. Therefore, the aim of this study were to investigate nanoencapsulated triterpenoids from petri-dish cultured Antrodia cinnamomea (PAC) nanoparticles whether it could increase the bioavailability; in addition, the anti-inflammatory and anti-oxidative effects could more effectively ameliorate the reproductive function of diabetic male rats. First, PAC encapsulated in chitosan-silica nanoparticles (Nano-PAC) were prepared by biosilicification method. Scanning electron micrographs confirm the average particle size is about 30 nm, and the encapsulation efficiency is 83.7% by HPLC. Diabetic male Sprague-Dawley rats were induced by high fat diet (40% kcal from fat) and streptozotocin (35 mg/kg). Nano-PAC was administered by oral gavage in three doses (4, 8 and 20 mg/kg) for 6 weeks. Besides, metformin (300 mg/kg) and nanoparticles (Nano) were treated as the positive and negative control respectively. Results indicated that 4 mg/kg Nano-PAC administration for 6 weeks improved hyperglycemia, insulin resistance, and also reduced advanced glycation end products in plasma. In addition, 8 mg/kg Nano-PAC ameliorated morphological of testicular seminiferous tubules, sperm morphology and motility, reactive oxygen species production and mitochondrial membrane potential. Moreover, 20 mg/kg Nano-PAC restored reproductive endocrine system function and increased KiSS-1 level in plasma. In plasma or testis anti-oxidant superoxide dismutase, glutathione peroxidase and catalase were increased whereas malondialdehyde, as well as pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, and interferon-gamma, decreased. Most importantly, 8 mg/kg Nano-PAC down-regulated the oxidative stress induced c-Jun N-terminal kinase (JNK) signaling pathway. Our study successfully nanoencapsulated PAC to form nanoparticles and low-dose Nano-PAC improved diabetes-induced hyperglycemia, inflammation and oxidative stress to ameliorate the reproductive function of diabetic male rats.

Keywords: Antrodia cinnamomea, diabetes mellitus, male reproduction, nanoparticles

Procedia PDF Downloads 202

Authors: Keshav Prasad Kandel, Balaram Khadka, Karan Bhatta, Basu Dev Ghimire

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Earthquakes still exist as a threating disaster. Being able to predict earthquakes will certainly help prevent substantial loss of life and property. Perhaps, Very Low Frequency/Low Frequency (VLF/LF) signal band (3-30 kHz), which is effectively reflected from D-layer of ionosphere, can be established as a tool to predict earthquake. On May 20 and May 29, 2012, earthquakes of magnitude 6.1 and 5.8 respectively struck Emilia-Romagna of Italy. A year back, on August 24, 2016, an earthquake of magnitude 6.2 struck Central Italy (42.7060 N and 13.2230 E) at 1:36 UT. We present the results obtained from the US Navy VLF Transmitter’s NSY signal of 45.9 kHz transmitted from Niscemi, in the province of Sicily, Italy and received at the Kiel Longwave Monitor, Germany for 2012 and 2016. We analyzed the terminator times, their individual differences and nighttime fluctuation counts. We also analyzed trends, dispersion and nighttime fluctuation which gave us a possible precursors to these earthquakes. Since perturbations in VLF amplitude could also be due to various other factors like lightning, geomagnetic activities (storms, auroras etc.) and solar activities (flares, UV flux, etc.), we filtered the possible perturbations due to these agents to guarantee that the perturbations seen in VLF/LF amplitudes were as a precursor to Earthquakes. As our TRGCP path is North-south, the sunrise and sunset time in transmitter and receiver places matches making pathway for VLF/LF smoother and therefore hoping to obtain more natural data. To our surprise, we found many clear anomalies (as precursors) in terminator times 5 days to 16 days before the earthquakes. Moreover, using night time fluctuation method, we found clear anomalies 5 days to 13 days prior to main earthquakes. This exactly correlates with the findings of previous authors that ionospheric perturbations are seen few days to one month before the seismic activity. In addition to this, we were amazed to observe unexpected decrease of dispersion on certain anomalies where it was supposed to increase, thereby not supporting our finding to some extent. To resolve this problem, we devised a new parameter called dispersion nighttime (dispersion). On analyzing, this parameter decreases significantly on days of nighttime anomalies thereby supporting our precursors to much extent.

Keywords: D-layer, TRGCP (Transmitter Receiver Great Circle Path), terminator times, VLF/LF

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: Wei Wang, Yannick Liu, Lu Zhen, H. Wang

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Maritime transport plays an important role in global economic development but also inevitably faces increasing pressures from all sides, such as ship operating cost reduction and environmental protection. An ideal innovation to address these pressures is electric ships. The electric ship is in the early stage. Considering the special characteristics of electric ships, i.e., travel range limit, to guarantee the efficient operation of electric ships, the service network needs to be re-designed carefully. This research designs a cost-efficient and environmentally friendly service network for electric ships, including the location of charging stations, charging plan, route planning, ship scheduling, and ship deployment. The problem is formulated as a mixed-integer linear programming model with the objective of minimizing total cost comprised of charging cost, the construction cost of charging stations, and fixed cost of ships. A case study using data of the shipping network along the Yangtze River is conducted to evaluate the performance of the model. Two operating scenarios are used: an electric ship scenario where all the transportation tasks are fulfilled by electric ships and a conventional ship scenario where all the transportation tasks are fulfilled by fuel oil ships. Results unveil that the total cost of using electric ships is only 42.8% of using conventional ships. Using electric ships can reduce 80% SOx, 93.47% NOx, 89.47% PM, and 42.62% CO2, but will consume 2.78% more time to fulfill all the transportation tasks. Extensive sensitivity analyses are also conducted for key operating factors, including battery capacity, charging speed, volume capacity, and a service time limit of transportation task. Implications from the results are as follows: 1) it is necessary to equip the ship with a large capacity battery when the number of charging stations is low; 2) battery capacity will influence the number of ships deployed on each route; 3) increasing battery capacity will make the electric ship more cost-effective; 4) charging speed does not affect charging amount and location of charging station, but will influence the schedule of ships on each route; 5) there exists an optimal volume capacity, at which all costs and total delivery time are lowest; 6) service time limit will influence ship schedule and ship cost.

Keywords: cost reduction, electric ship, environmental protection, sustainable shipping

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Authors: C. Scurr, J. Jeans, S. Srivastava

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Introduction: Acute type two respiratory failure (T2RF) has become a common presentation over the last two decades primarily due to an increase in the prevalence of chronic lung disease. Acute exacerbations can be managed either medically or in combination with non-invasive ventilation (NIV) which should be monitored with regular arterial blood gas samples (ABG). Arterial lines allow more frequent arterial blood sampling with less patient discomfort. We present the experience from a teaching hospital emergency department (ED) and level 2 medical high-dependency unit (HDU) that together form the pathway for management of acute type 2 respiratory failure. Methods: Patients acutely presenting to Charing Cross Hospital, London, with T2RF requiring non-invasive ventilation (NIV) over 14 months (2011 to 2012) were identified from clinical coding. Retrospective data collection included: demographics, co-morbidities, blood gas numbers and timing, if arterial lines were used and who performed this. Analysis was undertaken using Microsoft Excel. Results: Coding identified 107 possible patients. 69 notes were available, of which 41 required NIV for type 2 respiratory failure. 53.6% of patients had an arterial line inserted. Patients with arterial lines had 22.4 ABG in total on average compared to 8.2 for those without. These patients had a similar average time to normalizing pH of (23.7 with arterial line vs 25.6 hours without), and no statistically significant difference in mortality. Arterial lines were inserted by Foundation year doctors, Core trainees, Medical registrars as well as the ICU registrar. 63% of these were performed by the medical registrar rather than ICU, ED or a junior doctor. This is reflected in that the average time until an arterial line was inserted was 462 minutes. The average number of ABGs taken before an arterial line was 2 with a range of 0 – 6. The average number of gases taken if no arterial line was ever used was 7.79 (range of 2-34) – on average 4 times as many arterial punctures for each patient. Discussion: Arterial line use was associated with more frequent arterial blood sampling during each inpatient admission. Additionally, patients with an arterial line have less individual arterial punctures in total and this is likely more comfortable for the patient. Arterial lines are normally sited by medical registrars, however this is normally after some delay. ED clinicians could improve patient comfort and monitoring thus allowing faster titration of NIV if arteral lines were regularly inserted in the ED. We recommend that ED doctors insert arterial lines when indicated in order improve the patient experience and facilitate medical management.

Keywords: non invasive ventilation, arterial blood gas, acute type, arterial line

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Hebah M. Musalem, Jeylan El-Mansoury, Lin M. Tuleimat, Selwa Alhazza, Abdul-Aziz A. Al Zoba

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Background: Amblyopia is a condition that affects the visual system triggering a decrease in visual acuity without a known underlying pathology. It is due to abnormal vision development in childhood or infancy. Most importantly, vision loss is preventable or reversible with the right kind of intervention in most of the cases. Strabismus, sensory defects, and anisometropia are all well-known causes of amblyopia. However, ocular misalignment in Strabismus is considered the most common form of amblyopia worldwide. The risk of developing amblyopia increases in premature children, developmentally delayed or children who had brain lesions affecting the visual pathway. The prevalence of amblyopia varies between 2 to 5 % in the world according to the literature. Objective: To determine the different causes of Amblyopia in pediatric patients seen in ophthalmology clinic of a tertiary care center, i.e. King Faisal Specialist Hospital and Research Center (KFSH&RC). Methods: This is a hospital based, random retrospective, based on reviewing patient’s files in the Ophthalmology Department of KFSH&RC in Riyadh city, Kingdom of Saudi Arabia. Inclusion criteria: amblyopic pediatric patients who attended the clinic from 2015 to 2016, who are between 6 months and 18 years old. Exclusion Criteria: patients above 18 years of age and any patient who is uncooperative to obtain an accurate vision or a proper refraction. Detailed ocular and medical history are recorded. The examination protocol includes a full ocular exam, full cycloplegic refraction, visual acuity measurement, ocular motility and strabismus evaluation. All data were organized in tables and graphs and analyzed by statistician. Results: Our preliminary results will be discussed on spot by our corresponding author. Conclusions: We focused on this study on utilizing various examination techniques which enhanced our results and highlighted a distinguished correlation between amblyopia and its’ causes. This paper recommendation emphasizes on critical testing protocols to be followed among amblyopic patient, especially in tertiary care centers.

Keywords: amblyopia, amblyopia causes, amblyopia diagnostic criterion, amblyopia prevalence, Saudi Arabia

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Authors: Pranav Gunhal., Krish Jhurani

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This study tackles the significant computational challenge of predicting excited state dynamics in organic photovoltaic (OPV) materials—a pivotal factor in the performance of solar energy solutions. Time-dependent density functional theory (TDDFT), though effective, is computationally prohibitive for larger and more complex molecules. As a solution, the research explores the application of transformer neural networks, a type of artificial intelligence (AI) model known for its superior performance in natural language processing, to predict excited state dynamics in OPV materials. The methodology involves a two-fold process. First, the transformer model is trained on an extensive dataset comprising over 10,000 TDDFT calculations of excited state dynamics from a diverse set of OPV materials. Each training example includes a molecular structure and the corresponding TDDFT-calculated excited state lifetimes and key electronic transitions. Second, the trained model is tested on a separate set of molecules, and its predictions are rigorously compared to independent TDDFT calculations. The results indicate a remarkable degree of predictive accuracy. Specifically, for a test set of 1,000 OPV materials, the transformer model predicted excited state lifetimes with a mean absolute error of 0.15 picoseconds, a negligible deviation from TDDFT-calculated values. The model also correctly identified key electronic transitions contributing to the excited state dynamics in 92% of the test cases, signifying a substantial concordance with the results obtained via conventional quantum chemistry calculations. The practical integration of the transformer model with existing quantum chemistry software was also realized, demonstrating its potential as a powerful tool in the arsenal of materials scientists and chemists. The implementation of this AI model is estimated to reduce the computational cost of predicting excited state dynamics by two orders of magnitude compared to conventional TDDFT calculations. The successful utilization of transformer neural networks to accurately predict excited state dynamics provides an efficient computational pathway for the accelerated discovery and design of new OPV materials, potentially catalyzing advancements in the realm of sustainable energy solutions.

Keywords: transformer neural networks, organic photovoltaic materials, excited state dynamics, time-dependent density functional theory, predictive modeling

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Authors: Philip Friedlander, John Rutledge, Jason Suh

Abstract:

Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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Authors: Tai Chen, Caihuan Tian, Xiuxia Ren, Jingqi Xue, Xiuxin Zhang

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The herbaceous peony has become increasingly popular worldwide in recent years, especially as a cut flower with great economic value. However, peony has a very short vase life, only 3-5 d usually, which seriously affects its commodity value. In this study, we used the cut peony (Paeonia lactiflora cv. Sarah) as a material and found that melatonin treatment significantly improved its postharvest performance. In the control group, its vase life was 4.8 d, accompanied by petal dropping at last; melatonin treatment (40 μM) increased this time to 6.9 d without petal dropping at the end. Further study showed that melatonin treatment significantly increased the activity of antioxidant enzymes as well as reduced sugar content in petals, whereas the starch content in petals decreased. These results indicated that melatonin treatment may delay the oxidation reaction caused by aging, which also provides extra energy for maintaining flowering. Through full-length transcriptome sequencing, a total of 2819 differentially expressed genes (DEGs) between control and melatonin treatment groups were identified. KEGG enrichment analysis showed that these DEGs were mainly involved in three pathways, including melatonin synthesis, starch and sucrose conversion, and plant disease resistance. After the RT-qPCR verification, we identified three DEGs, named PlBAM3, PlWRKY22 and PlTIP1, and they should play major roles in melatonin-improved postharvest performance. One possible reason is that PlBAM3 caused maltose production (by starch degradation), maintained the proline biosynthesis, and then alleviated oxidative stress. Another reason is that both PlBAM3 and PlWRKY22 are key drought resistance regulators, which have the ability to alleviate osmotic stress and improve water absorption, which may also help to improve the postharvest quality of cut peony. In addition, PlTIP1 is involved in the sugar signal pathway, indicating sugar may also as a signal substance during this process. Our work may give new ideas for developing new ways to prolong the vase life of cut peony and improve its commodity value eventually.

Keywords: cut peony, melatonin, vase life, oxidation reaction, energy supply, differentially expressed genes

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Authors: Shailendra Kumar, Kamal Kumar Gupta

Abstract:

Dysdercus koenigii is an economically important pest of cotton worldwide. The pest damages the crop by sucking sap, staining lint, reducing the oil content of the seeds and deteriorating the quality of cotton. Plant possesses a plethora of secondary metabolites which are used as defense mechanism against herbivores. One of the important categories of such chemicals is insect growth regulators and the intermediates in their biosynthesis. Farnesol belongs to sesquiterpenoid. It is an intermediate in Juvenile hormone biosynthetic pathway in insects has been widely reported in the variety of plants. This chemical can disrupt the normal metabolic function and therefore, affects various life processes of the insects. Present study tested the efficacy of farnesol against Dysdercus koenigii. 2μl of 5% (100µg) and 10% (200µg) of the farnesol was applied topically on the dorsum of thoracic region of the newly emerged fifth instar nymphs of Dysdercus. The treated insects were observed daily for their survival, weight gain, and developmental anomalies for a period of ten days. The results indicated that treatment with 200µg farnesol decreased survival of the insects to 70% after 24h of exposure. At lower doses, no significant decrease in the survival was observed. However, the surviving nymphs showed alteration in growth, development, and metamorphosis. The weight gain in the treated nymphs showed deviation from control. The treated nymphs showed an increase in mortality during subsequent days and increase in the nymphal duration. The number of nymphs undergoing metamorphosis decreased to 46% and 88% in the treatments with the dose of 200µg and 100µg respectively. Severe developmental anomalies were also observed in the treated nymphs. The treated nymphs moulted into supernumerary nymphs, adultoids, adults with exuviae attached and adults with wing deformities. On treatment with 200µg; 26% adultoid, 4% adults with exuviae attached and 12% adults with wing deformed were produced. Treatment with 100µg resulted in production of 34% adultoid, 26% adults with deformed wing and 4% adults with exuviae attached. Many of the treated nymphs did not metamorphose into adults, remained in nymphal stage and died. Our results indicated potential application plant-derived secondary metabolites like farnesol in the management of Dysdercus population.

Keywords: development, Dysdercus koenigii, farnesol, survival

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Authors: Magdalena Smoktunowicz, Renata Wawrzyniak, Malgorzata Waleron, Krzysztof Waleron

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Pectobacterium spp. were previously classified into the Erwinia genus founded in 1917 to unite at that time all Gram-negative, fermentative, nonsporulating and peritrichous flagellated plant pathogenic bacteria. After work of Waldee (1945), on Approved Lists of Bacterial Names and bacteriology manuals in 1980, they were described either under the species named Erwinia or Pectobacterium. The Pectobacterium genus was formally described in 1998 of 265 Pectobacterium strains. Currently, there are 21 species of Pectobacterium bacteria, including Pectobacterium betavasculorum since 2003, which caused soft rot on sugar beet tubers. Based on the biochemical experiments carried out for this, it is known that these bacteria are gram-negative, catalase-positive, oxidase-negative, facultatively anaerobic, using gelatin and causing symptoms of soft rot on potato and sugar beet tubers. The mere fact of growing on sugar beet may indicate a metabolism characteristic only for this species. Metabolomics, broadly defined as the biology of the metabolic systems, which allows to make comprehensive measurements of metabolites. Metabolomics, in combination with genomics, are complementary tools for the identification of metabolites and their reactions, and thus for the reconstruction of metabolic networks. The aim of this study was to apply the GC-MS-based untargeted metabolomics to study the metabolism of P. betavasculorum in different growing conditions. The metabolomic profiles of biomass and biomass media were determined. For sample preparation the following protocol was used: extraction with 900 µl of methanol: chloroform: water mixture (10: 3: 1, v: v) were added to 900 µl of biomass from the bottom of the tube and up to 900 µl of nutrient medium from the bacterial biomass. After centrifugation (13,000 x g, 15 min, 4oC), 300µL of the obtained supernatants were concentrated by rotary vacuum and evaporated to dryness. Afterwards, two-step derivatization procedure was performed before GC-MS analyses. The obtained results were subjected to statistical calculations with the use of both uni- and multivariate tests. The obtained results were evaluated using KEGG database, to asses which metabolic pathways are activated and which genes are responsible for it, during the metabolism of given substrates contained in the growing environment. The observed metabolic changes, combined with biochemical and physiological tests, may enable pathway discovery, regulatory inference and understanding of the homeostatic abilities of P. betavasculorum.

Keywords: GC-MS chromatograpfy, metabolomics, metabolism, pectobacterium strains, pectobacterium betavasculorum

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Authors: Ali Hamza

Abstract:

Accurate segmentation of breast ultrasound images is of paramount importance in enhancing the diagnostic capabilities of breast cancer detection. This study presents an approach utilizing the U-Net architecture for segmenting breast ultrasound images aimed at improving the accuracy and reliability of mass identification within the breast tissue. The proposed method encompasses a multi-stage process. Initially, preprocessing techniques are employed to refine image quality and diminish noise interference. Subsequently, the U-Net architecture, a deep learning convolutional neural network (CNN), is employed for pixel-wise segmentation of regions of interest corresponding to potential breast masses. The U-Net's distinctive architecture, characterized by a contracting and expansive pathway, enables accurate boundary delineation and detailed feature extraction. To evaluate the effectiveness of the proposed approach, an extensive dataset of breast ultrasound images is employed, encompassing diverse cases. Quantitative performance metrics such as the Dice coefficient, Jaccard index, sensitivity, specificity, and Hausdorff distance are employed to comprehensively assess the segmentation accuracy. Comparative analyses against traditional segmentation methods showcase the superiority of the U-Net architecture in capturing intricate details and accurately segmenting breast masses. The outcomes of this study emphasize the potential of the U-Net-based segmentation approach in bolstering breast ultrasound image analysis. The method's ability to reliably pinpoint mass boundaries holds promise for aiding radiologists in precise diagnosis and treatment planning. However, further validation and integration within clinical workflows are necessary to ascertain their practical clinical utility and facilitate seamless adoption by healthcare professionals. In conclusion, leveraging the U-Net architecture for breast ultrasound image segmentation showcases a robust framework that can significantly enhance diagnostic accuracy and advance the field of breast cancer detection. This approach represents a pivotal step towards empowering medical professionals with a more potent tool for early and accurate breast cancer diagnosis.

Keywords: mage segmentation, U-Net, deep learning, breast cancer detection, diagnostic accuracy, mass identification, convolutional neural network

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Authors: Afifa Hafidh, Fathi Touati, Ahmed Hichem Hamzaoui, Sayda Somrani

Abstract:

The objective of the present study has been to synthesize and to characterize silica hybrid materials using sol-gel technic and to investigate their properties. Silica materials were successfully fabricated using various bi-functional 1,3,4-thiadiazoles and tetraethoxysilane (TEOS) as co-precursors via a facile one-pot sol-gel pathway. TEOS was introduced at room temperature with 1,3,4-thiadiazole 2,5-difunctiunal adducts, in ethanol as solvent and using HCl acid as catalyst. The sol-gel process lead to the formation of monolithic, coloured and transparent gels. TEOS was used as a principal network forming agent. The incorporation of 1,3,4-thiadiazole molecules was realized by attachment of these later onto a silica matrix. This allowed covalent linkage between organic and inorganic phases and lead to the formation of Si-N and Si-S bonds. The prepared hybrid materials were characterized by Fourier transform infrared, NMR ²⁹Si and ¹³C, scanning electron microscopy and nitrogen absorption-desorption measurements. The optic and magnetic properties of hybrids are studied respectively by ultra violet-visible spectroscopy and electron paramagnetic resonance. It was shown in this work, that heterocyclic moieties were successfully attached in the hybrid skeleton. The formation of the Si-network composed of cyclic units (Q3 structures) connected by oxygen bridges (Q4 structures) was proved by ²⁹Si NMR spectroscopy. The Brunauer-Elmet-Teller nitrogen adsorption-desorption method shows that all the prepared xerogels have isotherms type IV and are mesoporous solids. The specific surface area and pore volume of these materials are important. The obtained results show that all materials are paramagnetic semiconductors. The data obtained by Nuclear magnetic resonance ²⁹Si and Fourier transform infrared spectroscopy, show that Si-OH and Si-NH groups existing in silica hybrids can participate in adsorption interactions. The obtained materials containing reactive centers could exhibit adsorption properties of metal ions due to the presence of OH and NH functionality in the mesoporous frame work. Our design of a simple method to prepare hybrid materials may give interest of the development of mesoporous hybrid systems and their use within the domain of environment in the future.

Keywords: hybrid materials, sol-gel process, 1, 3, 4-thiadaizole, TEOS

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Authors: Regiane A. Oliveira, Carlos E. Vaz Rossell, Rubens Maciel Filho

Abstract:

Lactic acid, besides a valuable chemical may be considered a platform for other chemicals. In fact, the feasibility of hemicellulosic sugars as feedstock for lactic acid production process, may represent the drop of some of the barriers for the second generation bioproducts, especially bearing in mind the 5-carbon sugars from the pre-treatment of sugarcane bagasse. Bearing this in mind, the purpose of this study was to use the hemicellulosic liquor from sugarcane bagasse as a substrate to produce lactic acid by fermentation. To release of sugars from hemicellulose it was made a pre-treatment with a diluted sulfuric acid in order to obtain a xylose's rich liquor with low concentration of inhibiting compounds for fermentation (≈ 67% of xylose, ≈ 21% of glucose, ≈ 10% of cellobiose and arabinose, and around 1% of inhibiting compounds as furfural, hydroxymethilfurfural and acetic acid). The hemicellulosic sugars associated with 20 g/L of yeast extract were used in a fermentation process with Lactobacillus plantarum to produce lactic acid. The fermentation process pH was controlled with automatic injection of Ca(OH)2 to keep pH at 6.00. The lactic acid concentration remained stable from the time when the glucose was depleted (48 hours of fermentation), with no further production. While lactic acid is produced occurs the concomitant consumption of xylose and glucose. The yield of fermentation was 0.933 g lactic acid /g sugars. Besides, it was not detected the presence of by-products, what allows considering that the microorganism uses a homolactic fermentation to produce its own energy using pentose-phosphate pathway. Through facultative heterofermentative metabolism the bacteria consume pentose, as is the case of L. plantarum, but the energy efficiency for the cell is lower than during the hexose consumption. This implies both in a slower cell growth, as in a reduction in lactic acid productivity compared with the use of hexose. Also, L. plantarum had shown to have a capacity for lactic acid production from hemicellulosic hydrolysate without detoxification, which is very attractive in terms of robustness for an industrial process. Xylose from hydrolyzed bagasse and without detoxification is consumed, although the hydrolyzed bagasse inhibitors (especially aromatic inhibitors) affect productivity and yield of lactic acid. The use of sugars and the lack of need for detoxification of the C5 liquor from sugarcane bagasse hydrolyzed is a crucial factor for the economic viability of second generation processes. Taking this information into account, the production of second generation lactic acid using sugars from hemicellulose appears to be a good alternative to the complete utilization of sugarcane plant, directing molasses and cellulosic carbohydrates to produce 2G-ethanol, and hemicellulosic carbohydrates to produce 2G-lactic acid.

Keywords: fermentation, lactic acid, hemicellulosic sugars, sugarcane

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Authors: Aurea C. L. Lacerda, Paulo R. H. Moreno, Bruna M. P. Vianna, Cristina H. R. Serra, Airton Martin, André R. Baby, Vladi O. Consiglieri, Telma M. Kaneko

Abstract:

The modified Franz cell is the most widely used model for in vitro permeation studies, however it still presents some disadvantages. Thus, some alternative methods have been developed such as Skin PAMPA, which is a bio- artificial membrane that has been applied for skin penetration estimation of xenobiotics based on HT permeability model consisting. Skin PAMPA greatest advantage is to carry out more tests, in a fast and inexpensive way. The membrane system mimics the stratum corneum characteristics, which is the primary skin barrier. The barrier properties are given by corneocytes embedded in a multilamellar lipid matrix. This layer is the main penetration route through the paracellular permeation pathway and it consists of a mixture of cholesterol, ceramides, and fatty acids as the dominant components. However, there is no consensus on the membrane composition. The objective of this work was to compare the performance among different bio-artificial membranes for studying the permeation in skin PAMPA system. Material and methods: In order to mimetize the lipid composition`s present in the human stratum corneum six membranes were developed. The membrane composition was equimolar mixture of cholesterol, ceramides 1-O-C18:1, C22, and C20, plus fatty acids C20 and C24. The membrane integrity assay was based on the transport of Brilliant Cresyl Blue, which has a low permeability; and Lucifer Yellow with very poor permeability and should effectively be completely rejected. The membrane characterization was performed using Confocal Laser Raman Spectroscopy, using stabilized laser at 785 nm with 10 second integration time and 2 accumulations. The membrane behaviour results on the PAMPA system were statistically evaluated and all of the compositions have shown integrity and permeability. The confocal Raman spectra were obtained in the region of 800-1200 cm-1 that is associated with the C-C stretches of the carbon scaffold from the stratum corneum lipids showed similar pattern for all the membranes. The ceramides, long chain fatty acids and cholesterol in equimolar ratio permitted to obtain lipid mixtures with self-organization capability, similar to that occurring into the stratum corneum. Conclusion: The artificial biological membranes studied for Skin PAMPA showed to be similar and with comparable properties to the stratum corneum.

Keywords: bio-artificial membranes, comparison, confocal Raman, skin PAMPA

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Authors: Lubaina Soni, Claire Farrell, Christopher Szota, Tim D. Fletcher

Abstract:

Green roofs are a promising engineered ecosystem for reducing stormwater runoff and restoring vegetation cover in cities. Plants can contribute to rainfall retention by rapidly depleting water in the substrate; however, this increases the risk of plant drought stress. Green roof configurations, therefore, need to provide plants the opportunity to efficiently deplete the substrate but also avoid severe drought stress. This study used green roof modules placed in a rainout shelter during a six-month rainfall regime simulated in Melbourne, Australia. Rainfall was applied equally with an overhead irrigation system on each module. Aside from rainfall, modules were under natural climatic conditions, including temperature, wind, and radiation. A single species, Ficinia nodosa, was planted with five different treatments and three replicates of each treatment. In this experiment, we tested the impact of three plant cover treatments (0%, 50% and 100%) on rainfall retention and plant drought stress. We also installed two runoff zone treatments covering 50% of the substrate surface for additional modules with 0% and 50% plant cover to determine whether directing rainfall resources towards plant roots would reduce drought stress without impacting rainfall retention. The retention performance for the simulated rainfall events was measured, quantifying all components for hydrological performance and survival on green roofs. We found that evapotranspiration and rainfall retention were similar for modules with 50% and 100% plant cover. However, modules with 100% plant cover showed significantly higher plant drought stress. Therefore, planting at a lower cover/density reduced plant drought stress without jeopardizing rainfall retention performance. Installing runoff zones marginally reduced evapotranspiration and rainfall retention, but by approximately the same amount for modules with 0% and 50% plant cover. This indicates that reduced evaporation due to the installation of the runoff zones likely contributed to reduced evapotranspiration and rainfall retention. Further, runoff occurred from modules with runoff zones faster than those without, indicating that we created a faster pathway for water to enter and leave the substrate, which also likely contributed to lower overall evapotranspiration and retention. However, despite some loss in retention performance, modules with 50% plant cover installed with runoff zones showed significantly lower drought stress in plants compared to those without runoff zones. Overall, we suggest that reducing plant cover represents a simple means of optimizing green roof performance but creating runoff zones may reduce plant drought stress at the cost of reduced rainfall retention.

Keywords: green roof, plant cover, plant drought stress, rainfall retention

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Authors: Hamza Javar Magnier, Robin Curtis

Abstract:

There have been rapid advances in the upstream processing of protein therapeutics, which has shifted the bottleneck to downstream purification and formulation. Finding liquid formulations with shelf lives of up to two years is increasingly difficult for some of the newer therapeutics, which have been engineered for activity, but their formulations are often viscous, can phase separate, and have a high propensity for irreversible aggregation1. We explore means to develop improved predictive ability from a better understanding of how protein-protein interactions on formulation conditions (pH, ionic strength, buffer type, presence of excipients) and how these impact upon the initial steps in protein self-association and aggregation. In this work, we study the initial steps in the aggregation pathways using a minimal protein model based on square-well potentials and discontinuous molecular dynamics. The effect of model parameters, including range of interaction, stiffness, chain length, and chain sequence, implies that protein models fold according to various pathways. By reducing the range of interactions, the folding- and collapse- transition come together, and follow a single-step folding pathway from the denatured to the native state2. After parameterizing the model interaction-parameters, we developed an understanding of low-temperature conformational properties and fluctuations, and the correlation to the folding transition of proteins in isolation. The model fluctuations increase with temperature. We observe a low-temperature point, below which large fluctuations are frozen out. This implies that fluctuations at low-temperature can be correlated to the folding transition at the melting temperature. Because proteins “breath” at low temperatures, defining a native-state as a single structure with conserved contacts and a fixed three-dimensional structure is misleading. Rather, we introduce a new definition of a native-state ensemble based on our understanding of the core conservation, which takes into account the native fluctuations at low temperatures. This approach permits the study of a large range of length and time scales needed to link the molecular interactions to the macroscopically observed behaviour. In addition, these models studied are parameterized by fitting to experimentally observed protein-protein interactions characterized in terms of osmotic second virial coefficients.

Keywords: protein folding, native-ensemble, conformational fluctuation, aggregation

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Authors: Pierre-Louis Lucas, Corinne Loutelier-Bourhis, Narimane Mati-Baouche, Philippe Chan Tchi-Song, Patrice Lerouge, Elodie Mathieu-Rivet, Muriel Bardor

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N-glycosylation is a post-translational modification taking place in the Endoplasmic Reticulum and the Golgi apparatus where defined glycan features are added on protein in a very specific sequence Asn-X-Thr/Ser/Cys were X can be any amino acid except proline. Because it is well-established that those N-glycans play a critical role in protein biological activity, protein half-life and that a different N-glycan structure may induce an immune response, they are very important in Biopharmaceuticals which are mainly glycoproteins bearing N-glycans. From now, most of the biopharmaceuticals are produced by mammalian cells like Chinese Hamster Ovary cells (CHO) for their N-glycosylation similar to the human, but due to the high production costs, several other species are investigated as the possible alternative system. In this purpose, the green microalgae Chlamydomonas reinhardtii was investigated as the potential production system for Biopharmaceuticals. This choice was influenced by the facts that C. reinhardtii is a well-study microalgae which is growing fast with a lot of molecular biology tools available. This organism is also producing N-glycan on its endogenous proteins. However, the analysis of the N-glycan structure of this microalgae has revealed some differences as compared to the human. Rather than in Human where the glycans are processed by key enzymes called N-acetylglucosaminyltransferase I and II (GnTI and GnTII) adding GlcNAc residue to form a GlcNAc₂Man₃GlcNAc₂ core N-glycan, C. reinhardtii lacks those two enzymes and possess a GnTI independent glycosylation pathway. Moreover, some enzymes like xylosyltransferases and methyltransferases not present in human are supposed to act on the glycans of C. reinhardtii. Furthermore, the recent structural study by mass spectrometry shows that the N-glycosylation precursor supposed to be conserved in almost all eukaryotic cells results in a linear Man₅GlcNAc₂ rather than a branched one in C. reinhardtii. In this work, we will discuss the new released MS information upon C. reinhardtii N-glycan structure and their impact on our attempt to modify the glycan in a Human manner. Two strategies will be discussed. The first one consisted in the study of Xylosyltransferase insertional mutants from the CLIP library in order to remove xyloses from the N-glycans. The second will go further in the humanization by transforming the microalgae with the exogenous gene from Toxoplasma gondii having an activity similar to GnTI and GnTII with the aim to synthesize GlcNAc₂Man₃GlcNAc₂ in C. reinhardtii.

Keywords: Chlamydomonas reinhardtii, N-glycosylation, glycosyltransferase, mass spectrometry, humanization

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Authors: Scott Hollier, Ruchi Permvattana

Abstract:

The purpose of this abstract is to share the findings of a recently completed disability-related Internet of Things (IoT) project undertaken at Curtin University in Australia. The project focused on identifying how IoT could support people with disabilities with their educational outcomes. To achieve this, the research consisted of an analysis of current literature and interviews conducted with students with vision, hearing, mobility and print disabilities. While the research acknowledged the ability to collect data with IoT is now a fairly common occurrence, its benefits and applicability still need to be grounded back into real-world applications. Furthermore, it is important to consider if there are sections of our society that may benefit from these developments and if those benefits are being fully realised in a rush by large companies to achieve IoT dominance for their particular product or digital ecosystem. In this context, it is important to consider a group which, to our knowledge, has had little specific mainstream focus in the IoT area –people with disabilities. For people with disabilities, the ability for every device to interact with us and with each other has the potential to yield significant benefits. In terms of engagement, the arrival of smart appliances is already offering benefits such as the ability for a person in a wheelchair to give verbal commands to an IoT-enabled washing machine if the buttons are out of reach, or for a blind person to receive a notification on a smartphone when dinner has finished cooking in an IoT-enabled microwave. With clear benefits of IoT being identified for people with disabilities, it is important to also identify what implications there are for education. With higher education being a critical pathway for many people with disabilities in finding employment, the question as to whether such technologies can support the educational outcomes of people with disabilities was what ultimately led to this research project. This research will discuss several significant findings that have emerged from the research in relation to how consumer-based IoT can be used in the classroom to support the learning needs of students with disabilities, how industrial-based IoT sensors and actuators can be used to monitor and improve the real-time learning outcomes for the delivery of lectures and student engagement, and a proposed method for students to gain more control over their learning environment. The findings shared in this presentation are likely to have significant implications for the use of IoT in the classroom through the implementation of affordable and accessible IoT solutions and will provide guidance as to how policies can be developed as the implications of both benefits and risks continue to be considered by educators.

Keywords: disability, higher education, internet of things, students

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Authors: Nadia E. Christiana, Azzahra A. N. Ginting, Ardhito Nurcahya, Havisa P. Novira

Abstract:

One of the quickest ways to do a short trip in urban areas is by walking, either individually, in couple or groups. Walkability nowadays becomes one of the parameters to measure the quality of an urban neighborhood. As a Central Business District and public transport transit hub, Dukuh Atas area becomes one of the highest numbers of commuters that pass by the area and interchange between transportation modes daily. Thus, as a public transport hub, a lot of investment should be focused to speed up the development of the area that would support urban transit activity between transportation modes, one of them is revitalizing pedestrian walkways. The purpose of this research is to formulate the visual design concept of 'Walkable City' based on the results of the observation and a series of rankings. To achieve this objective, it is necessary to accomplish several stages of the research that consists of (1) Identifying the system of pedestrian paths in Dukuh Atas area using descriptive qualitative method (2) Analyzing the sidewalk walkability rate according to the perception and the walkability satisfaction rate using the characteristics of pedestrians and non-pedestrians in Dukuh Atas area by using Global Walkability Index analysis and Multicriteria Satisfaction Analysis (3) Analyzing the factors that determine the integration of pedestrian walkways in Dukuh Atas area using descriptive qualitative method. The results achieved in this study is that the walkability level of Dukuh Atas corridor area is 44.45 where the value is included in the classification of 25-49, which is a bit of facility that can be reached by foot. Furthermore, based on the questionnaire, satisfaction rate of pedestrian walkway in Dukuh Atas area reached a number of 64%. It is concluded that commuters have not been fully satisfied with the condition of the sidewalk. Besides, the factors that influence the integration in Dukuh Atas area have been reasonable as it is supported by the utilization of land and modes such as KRL, Busway, and MRT. From the results of all analyzes conducted, the visual design and the application of the concept of walkable city along the pathway pedestrian corridor of Dukuh Atas area are formulated. Achievement of the results of this study amounted to 80% which needs to be done further review of the results of the analysis. The work of this research is expected to be a recommendation or input for the government in the development of pedestrian paths in maximizing the use of public transportation modes.

Keywords: design, global walkability index, mass rapid transit, walkable city

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Authors: Samantha A. Cintron, Janet Pierce, Mihaela E. Sardiu, Diane Mahoney, Jill Peltzer, Bhanu Gupta, Qiuhua Shen

Abstract:

High output heart failure (HOHF) is characterized a high output state resulting from an underlying disease process and is commonly caused by obesity. As obesity levels increase, more individuals will be at risk for obesity-related HOHF. However, the underlying pathophysiologic mechanisms of obesity-related HOHF are not well understood and need further research. The aim of the study was to describe the differences in leukocyte transcriptomes of morbidly obese patients with HOHF and those with non-HOHF. In this cross-sectional study, the study team collected blood samples, demographics, and clinical data of six patients with morbid obesity and HOHF and six patients with morbid obesity and non-HOHF. The study team isolated the peripheral blood leukocyte RNA and applied stranded total RNA sequencing. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and mechanistic and causal networks that were associated with the significantly different leukocyte transcriptomes. The study team identified 116 differentially expressed genes; 114 were upregulated, and 2 were downregulated in the HOHF group (Benjamini-Hochberg adjusted p-value ≤ 0.05 and log2(fold-change) of ±1). The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. Upstream regulator GATA Binding Protein 1 (GATA1) and a network associated with nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) were also identified based on the different leukocyte transcriptomes of morbidly obese patients with HOHF and non-HOHF. To the author’s best knowledge, this is the first study that reported the differential gene expression in patients with obesity-related HOHF and demonstrated the unique pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Keywords: cardiac output, heart failure, obesity, transcriptomics

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