bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopaminergic Stimulation Leads B-cell Infiltration into the Central Nervous System upon Autoimmunity
Authors: Prado Carolina , Osorio-Barrios Francisco , Espinoza Alexandra , Saez Juan J , Yuseff María I , Pacheco Rodrigo
Published: May 2021

Background. Recent evidence has shown dopamine as a major regulator of inflammation. Accordingly, dopaminergic regulation of adaptive and innate immune cells plays an important role in the physiopathology of inflammatory disorders. Multiple sclerosis (MS) is an inflammatory disease involving a CD4+ T-cell-driven autoimmune response to central nervous system (CNS) derived antigens. Evidence from animal models has suggested that B-cells play a fundamental role as antigen-presenting cells (APC) re-stimulating CD4+ T-cells in the CNS as well as regulating T-cell response by mean of inflammatory or anti-inflammatory cytokines. Here we addressed the role of the dopamine receptor D3 (DRD3), which display the highest affinity for dopamine, in B-cells in animal models of MS. Methods. Mice harbouring Drd3-deficient or Drd3-suficient B-cells were generated by bone marrow transplantation into recipient mice devoid of B-cells. In these mice we compare the development of experimental autoimmune encephalomyelitis (EAE) induced by immunization with a myelin oligodendrocyte glycoprotein (MOG)-derived peptide (pMOG), a model that leads to CNS-autoimmunity irrespective of the APC function of B-cells, or by immunization with full-length human MOG protein (huMOG), a model in which antigen-specific activated B-cells display a fundamental APCs function in the CNS.Results. Our data shows that, by promoting the expression of the chemokine receptor CXCR3 in autoreactive B-cells, DRD3-stimulation favours the CNS-tropism in a subset of B-cells that act as APC in the CNS, which is fundamental for disease development. Furthermore, we found that DRD3- stimulation induced the expression of the CNS-homing molecule CD49d in a B-cell subset with anti-inflammatory features, thus attenuating EAE manifestation in a CNS-autoimmunity model independent of the APC function of B-cells.Conclusions. Our findings demonstrate that DRD3-stimulation in B-cells exerts a dual role in CNS-autoimmunity, favouring CNS-tropism of pro-inflammatory B-cells with APC function, and also promoting CNS-homing of B-cells with anti-inflammatory features. Thus, these results show DRD3-signalling in B-cells as a key regulator of CNS-autoimmunity.
An Extensive Operational Law for Monotone Functions of LR Fuzzy Intervals with Applications to Fuzzy Optimization
Authors: Zhao Mingxuan , Han Yulin , Zhou Jian
Published: May 2021

The operational law put forward by Zhou et al. on strictly monotone functions with regard to regular LR fuzzy numbers makes a valuable push to the development of fuzzy set theory. However, its applicable conditions are confined to strictly monotone functions and regular LR fuzzy numbers, which restricts its application in practice to a certain degree. In this paper, we propose an extensive operational law that generalizes the one proposed by Zhou et al. to apply to monotone (but not necessarily strictly monotone) functions with regard to regular LR fuzzy intervals (LR-FIs), of which regular fuzzy numbers can be regarded as particular cases. By means of the extensive operational law, the inverse credibility distributions (ICDs) of monotone functions regarding regular LR-FIs can be calculated efficiently and effectively. Moreover, the extensive operational law has a wider range of applications, which can deal with the situations hard to be handled by the original operational law. Subsequently, based on the extensive operational law, the computational formulae for expected values (EVs) of LR-FIs and monotone functions with regard to regular LR-FIs are presented. Furthermore, the proposed operational law is also applied to dispose fuzzy optimization problems with regular LR-FIs, for which a solution strategy is provided, where the fuzzy programming is converted to a deterministic equivalent first and then a newly-devised solution algorithm is utilized. Finally, the proposed solution strategy is applied to a purchasing planning problem, whose performances are evaluated by comparing with the traditional fuzzy simulation-based genetic algorithm. Experimental results indicate that our method is much more efficient, yielding high-quality solutions within a short time.
Complete Loss of CASK Causes Severe Ataxia Through Cerebellar Degeneration
Authors: Patel Paras , Hegert Julia , Cristian Ingrid , Kerr Alicia , LaConte Leslie , Fox Michael , Srivast Sarika , Mukherjee Konark
Published: May 2021

Heterozygous loss of X-linked genes like CASK and MeCP2 (Rett syndrome) causes neurodevelopmental disorders (NDD) in girls, while in boys loss of the only allele of these genes leads to profound encephalopathy. The cellular basis for these disorders remains unknown. CASK is presumed to work through the Tbr1-reelin pathway in neuronal migration. Here we report clinical and histopathological analysis of a deceased 2-month-old boy with a CASK-null mutation. Although smaller in size, the CASK-null human brain exhibits normal lamination without defective neuronal differentiation, migration, or axonal guidance, excluding the role of reelin. The hypoplastic cerebellum instead displayed astrogliosis, a marker for neuronal loss. We therefore hypothesized that cerebellar hypoplasia with CASK loss is a result of early neurodegeneration. We generated a mouse line where CASK is completely deleted (hemizygous and homozygous) from post-migratory neurons in the cerebellum. Data confirm that a small cerebellum in CASK-loss results from post-developmental degeneration of cerebellar granule neurons. We further demonstrate that at least in cerebellum the functional loss with CASK deletion results secondary to degeneration of granule cells rather that any acute molecular functional loss of CASK. Intriguingly, female mice with heterozygous deletion of CASK in the cerebellum did not display any neurodegeneration. We suggest that NDDs like CASK mutation and Rett syndrome are pathologically neurodegenerative; however, random X-chromosome inactivation in the heterozygous mutant girls results in 50% of cells expressing the functional gene, resulting in a non-progressive pathology, whereas complete loss of the only allele in boys leads to unconstrained degeneration and encephalopathy.
A Study for Consecutive Precipitation Pattern Based on Stochastic Ordering
Authors: Cai Wenxiang , Zhang Hao , Xu Yanyan
Published: May 2021

Consecutive precipitation extremes may cause more catastrophes than occasional extreme 9 events. They may pose more serious threats to the safety of people's lives and property. They also 10 can cause great damage to the healthy development of social economy. It is of practical significance 11 to explore this issue. In this work, a nonparametric approach based on stochastic ordering combined 12 with EI Barmi-McKeague test was employed, which is more flexible if the trend is non-monotonic 13 or more complex to model. The average summer consecutive precipitation in 31 provinces of China 14 were compared in three periods, 960-1965, 1985-1990 and 2010-2015. Based on this approach, the 15 results showed that, in 17 out of the 31 provinces, the consecutive precipitation in summer increase 16 stochastically from period 1 to period 2 or period 3, or increase stochastically from period 2 to period 17 3. These 17 provinces mainly located in Northwest and Southeast China. Given the increases in the 18 average summer consecutive precipitation and the high single consecutive precipitation of prov- 19 inces which located in the Southeast China and socio-economic vulnerability to such extremes in 20 China, the local government and relevant national departments should adopt more strategies to 21 alleviate and adapt to the increasing trend of consecutive precipitation extremes.
Neutralizing activity of BBIBP-CorV vaccine-elicited sera against multiple SARS-CoV-2 variants of concern
Authors: Zhang Xinxin , Yu Xiaoqi , Wei Dong , Xu Wenxin , Guo Wentian , Li Xinxin , Tan Wei , Liu Leshan , Qu Jieming , Yang Zhi-Tao , Chen Erzhen
Published: May 2021

We assessed the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine BBIBP-CorV, especially measured the resistance of four global variants of concern: Lineage B.1.1.7, Lineage B.1.351, Lineage P.1, and Lineage B.1.526 to neutralizing activity of vaccine-elicited sera. Among 1006 enrolled participants, no serious adverse event was reported within 28 days post-vaccination. Seroconversion of neutralizing antibodies was seen in 698 (91.84%) of 760 healthcare workers, and the geometric mean titres (GMTs) of neutralizing antibody titre was 62.68 (57.02–68.91) after the second immunization. We found that 57 (12.13%), 99 (20.97%), and 114 (24.26%) vaccine-elicited sera showed complete or partial loss of neutralizing activity against lineage B.1.1.7, lineage B.1.526, and lineage P.1, respectively, while 199 (42.34%) vaccine-elicited sera preserved neutralizing activity against lineage B.1.351, albeit at relatively low dilutions. These data indicated that humoral responses against SARS-CoV-2 could be effectively induced in vaccine recipients, although diminished neutralization potency against multiple variants was observed.
Thyroid and Sex Hormones Ratios in Predicting Breast Cancer Risk
Authors: Akalanka Kasuni , Ekanayake Sagarika , Samarasinghe Kamani
Published: May 2021

Purpose: The study intended to analyze the incidence of thyroid related diseases and to assess thyroid to sex hormones ratios of breast cancer (BC) patients Methods: TSH, T3, T4, Estrogen, progesterone and testosterone levels of newly diagnosed BC patients (n=155) aged 30 to 75 years and age-matched normal controls (n=75) were analyzed. Data on history of thyroid related diseases were collected from an interviewer administered questionnaire. Thyroid/sex hormone ratios were analyzed and compared against healthy women. Results: History of thyroid related diseases was significantly higher (p<0.05) in BC patients compared to controls. Patients (10%) with history of thyroid related diseases were excluded from the study. Subclinical hyperthyroidism was identified among 14% of the remaining BC patients and was the only dysfunction (7%) among healthy women. Significantly higher (p<0.05) mean T3 and T4 values, lower TSH levels and non-significant levels of estrogen and progesterone were observed in patients with BC when compared to healthy. Serum Testosterone of BC patients were significantly low (p<0.05). Considering the thyroid to sex hormones ratios among postmenopausal women, T3/testosterone, T4/testosterone, T3/estrogen, T4/ estrogen, ratios were significantly different in the two groups and the highest significance was found with T3/testosterone. Cutoff values studied from receiver operative characteristic curves indicated that a woman having T3/testosterone above 7.47 showed 12.5 times odds (p=0.000) of being diagnosed with BC. Conclusion: Incidence of thyroid related diseases are higher among BC patients and elevation of T3/testosterone ratio indicated a significant risk of BC. However, a study involving a larger number of participants could confirm the above.
Modeling and Optimization of Weld Bead Profile with Varied Welding Stages for Weathering Steel A606
Authors: Zhao Dawei , Bezgans Yuriy , Vdonin Nikita , Radionova Liudmila , Bykov Vitaly
Published: May 2021

The profile of the welding bead changes with the welding process parameters during the gas metal arc welding (GMAW) process, the reinforcement disappears and the penetration becomes sunken when the excessive welding heat input is applied. However, little research work is specially planned to cope with the studying of welding bead at these stages. A systematic studying of the relationships among the welding process variables and welding bead geometric features and optimization of the welding quality is presented. The influences of the welding technological parameters (voltage, welding speed, and wire feed speed) on the welding geometry were revealed and the models correlating them were established. The features of the weld bead geometry were composed of top reinforcement width, top reinforcement height, penetration depth, bottom reinforcement width, and bottom reinforcement height. By the desirability function approach, the recommendation of suitable welding parameters to meet the contradicting demands of multiple bead geometric features is fulfilled. The microstructure in different welding regions and mechanical performances of the welding joints produced by the verification test were also studied.
Strategies To Implement SARS-CoV-2 Point-of-Care Testing Into Primary Care Settings: A Qualitative Secondary Analysis Guided By The Behaviour Change Wheel
Authors: Kierkegaard Patrick , Hicks Timothy , Allen A. Joy , Yang Yaling , Hayward Gail , Glogowska Margaret , Nicholson Brian D. , Buckle Peter
Published: May 2021

Background: There is little empirical evidence to inform implementation strategies for introducing SARS-CoV-2 point of care (POC) testing into primary care settings. The purpose of this study is to develop a theory-driven understanding of the behavioural determinants underpinning the implementation of SARS-CoV-2 POC testing in primary care. This will allow identification of potential intervention strategies that could encourage successful implementation of testing into routine practice and facilitate face-to-face consultations.Methods: We used a secondary qualitative analysis approach to re-analyse data from a qualitative study that involved interviewing 22 primary care physicians from 21 primary care practices across three regions in England. We followed the three-step method based on the Behaviour Change Wheel to identify barriers/enablers to the implementation of SARS-CoV-2 POC testing and identified behaviour change techniques to inform intervention strategies that targeted the barriers/enablers.Results: We identified 10 barriers and enablers to POC implementation under eight Theoretical Domains Framework (TDF): (1) knowledge; (2) behavioural regulation; (3) reinforcement; (4) skills; (5) environmental context and resources; (6) social influence; (7) professional role and identity; and (8) belief about consequences. Linkages with the Behaviour Change Techniques (BCT) taxonomy enabled the identification of intervention strategies to address the social and contextual factors influencing primary care physician’s willingness and capacity to adopt POC testing.Conclusions: A theory-informed approach identified barriers to the adoption of POC tests in primary care as well as guiding implementation strategies to address these challenges.
GABRQ is Overexpressed and Correlated with Tumor Progression in Breast Cancer
Authors: Mei Ran , Cui Xichun , Zheng Lili , Jingyi Li
Published: May 2021

Background: Breast cancer (BRCA) is the most common type of women's cancer with a high incidence. The function of gamma-aminobutyric acid A receptor θ subunit (GABRQ) has been studied in other cancers. The results demonstrated that the expression levels of GABRQ were closely associated with tumor prognosis. However, the functions and mechanisms of GABRQ in BRCA remain unclear.Materials and methods: We used the public genome datasets and a tissue microarray (TMA) cohort to analyze the GABRQ expression levels. We performed Immunohistochemistry (IHC) and Western blot to determine GABRQ expression in BRCA cell lines and tissues. Cell proliferation was assessed by EDU assay and colony formation assay. Transwell assay was carried out to investigate the cell invasion ability in vitro and Xenograft nude mouse model was constructed to test the function of GABRQ on tumor growth in vivo. Moreover, we utilized bioinformatic analysis to identify the potential molecular mechanisms mediated by GABRQ modification in BRCA.Results: GABRQ was markedly up-regulated in BRCA tissues, and the expression levels of GABRQ were closely associated with BRCA prognosis. Functional analysis elucidated that knockdown of GABRQ could suppress BRCA cell growth and invasion in vitro, and inhibit tumor development in vivo. Moreover, we found that GABRQ overexpression activated the EMT signaling pathway.Conclusions: These results demonstrated that the function of GABRQ in BRCA progression provided potential prognostic predictors for BRCA patients.
CeO2/CdS Heterojunctions Decorated Cotton Fabrics as Facile Recyclable Photocatalysts for Highly Efficient Visible Light Driven Degradation of Methylene Blue
Authors: Zou Rui , Li Linhua , Yang Lin , lan jianwu , Liu Hongyu , Dou Baojie , Shang Jiaojiao , Lin Shaojian
Published: May 2021

In this work, visible light response CeO2/CdS decorated cotton fabrics as durable and facile recyclable composite photocatalysts were fabricated for photo-degradation of methylene blue (MB). First of all, amino-functionalized CeO2/CdS nanoparticles were synthesized through a fast, efficient and low-cost coprecipitation method. Subsequently, the as-prepared CeO2/CdS nanoparticles were immobilized on aldehyde-functionalized cotton fabric surfaces as composite photocatalysts via "amine-aldehyde" chemical reaction. The surface microstructure and chemical composition of the CeO2/CdS decorated cotton fabric (CeO2/CdS-CF) were characterized by SEM, FTIR and XPS, respectively. The results showed that CeO2/CdS nanoparticles were successfully anchored on the surface of cotton fabric, and distributed uniformly. As expected, the as-prepared CeO2/CdS-CF exhibited excellent photocatalytic activity, which can degrade MB within 90 min with a degradation efficiency of 93.8% under simulated sunlight irradiation, due to the CeO2/CdS heterostructure with the efficient photo-generated charge transfer and separation. In addition, the degradation efficiency remained above 90.3% after five successive degradation cycles, indicating that the obtained CeO2/CdS-CF possessed excellent stability and recyclability. This work opened up a facile preparation way for the fabrication of durable and recyclable composite photocatalysts, and has a promising application in treating dye contaminated wastewater.
Experimental and Numerical Investigation of Effect of Cadmium Sorption by River Sediments on Longitudinal Dispersion
Authors: Nasrabadi Mohsen , Mazdeh Ali Mahdavi , Omid Mohammad Hossein
Published: May 2021

This paper concerns the cadmium sorptive effects by river bed sediments on longitudinal coefficient in an open-channel flow via experimental and numerical study. For this purpose, a circular flume was used with mean diameter of 1.6 m and a width of 0.2 m. The adsorbing bed was considered as a thin layer of the sediment particles with mean diameter of 0.5 mm and three sediment concentrations of 3, 12, and 20 gr/lit. To determine the sorption parameters of the sediments, some experiments were conducted with three cadmium concentrations of 150, 460, and 770 ppb. Then, the dispersion experiments were carried out with and without the bed sediments. To solve the advection-dispersion equation with considering the sorption term by river bed sediments, a numerical model was then developed. The longitudinal dispersion coefficients were estimated by comparing the experimental and numerical breakthrough curves. The results showed that, with increasing the sediment concentrations, the sediment sorption rate increased and the longitudinal dispersion coefficient decreased by about 38, 36 and 33 percent, respectively, for cadmium concentrations of 150, 460 and 770 ppb. In addition, by increasing the cadmium concentrations, the changes in the longitudinal dispersion coefficient are decreased. Furthermore, a relationship was developed using non-dimensional longitudinal dispersion as a function of the new parameter of sorption ratio. From a practical point of view, the results of this study demonstrated that, at the presence of sediment, the cadmium is longitudinally dispersed with more delay in comparison with no sediment at the river bed.
Epigenetic Quantification of Circulating Immune Cells in Peripheral Blood of Triple-negative Breast Cancer Patients
Authors: Manoochehri Mehdi , Hielscher Thomas , Borhani Nasim , Gerhäuser Clarissa , Fletcher Olivia , Swerdlow Anthony J , Ko Yon-Dschun , Brauch Hiltrud , Brüning Thomas , Hamann Ute
Published: May 2021

Background: A shift in the proportions of blood immune cells is a hallmark of cancer development. Here, we investigated whether methylation-derived immune cell type ratios and methylation-derived neutrophil-to-lymphocyte ratios (mdNLRs) are associated with triple-negative breast cancer (TNBC). Methods: Leukocyte subtype-specific un/methylated CpG sites were selected and methylation levels at these sites used as proxies for immune cell type proportions and mdNLR estimation in 231 TNBC cases and 231 age-matched controls. Data were validated using the Houseman deconvolution method. Additionally, the natural killer (NK) cell ratio was measured in a prospective sample set of 146 TNBC cases and 146 age-matched controls. Results: The mdNLRs were higher in TNBC cases compared with controls and associated with TNBC (odds ratio (OR) range (2.66-4.29), all Padj.<1e-04). A higher neutrophil ratio and lower ratios of NK cells, CD4+ T cells, CD8+ T cells, monocytes, and B cells were associated with TNBC. The strongest association was observed with decreased NK cell ratio (OR range (1.28-1.42), all Padj.<1e-04). The NK cell ratio was also significantly lower in pre-diagnostic samples of TNBC cases compared with controls (P=0.019).Conclusion: This immunomethylomic study shows that a shift in the ratios/proportions of leukocyte subtypes is associated with TNBC, with decreased NK cell showing the strongest association. These findings improve our knowledge of the role of the immune system in TNBC and point to the possibility of using NK cell level as a non-invasive molecular marker for TNBC risk assessment, early detection, and prevention.
Association of EAAT1 and EAAT2 Genes Polymorphism With Schizophrenia in Chinese Han Population
Authors: Wang Lina , Ma Tantan , Qiao Dongdong , Cui Kaiyan , Bi Xiaojiao , Han Chao , Yang Limin , Sun Mengmeng , Liu Lanfen
Published: May 2021

Background: Previous studies have linked schizophrenia to EAAT1 and EAAT2 genes. The aim of this study was to investigate the relationship between polymorphism of these two genes and schizophrenia in Chinese Han population. Methods: A total of 233 schizophrenic patients and 342 healthy controls were enrolled. Six SNPs including rs2269272、rs2731880、rs12360706、rs3088168、rs12294045、rs10836387 were genotyped by SNaPshot. Clinical features were collected using a general demographic questionnaire. Symptoms were measured by the Positive and Negative Syndrome Scale (PANSS), and cognitive function was assessed by Matrics Consensus Cognitive Battery (MCCB). Results: The allele frequency of EAAT1 rs2731880 was significantly different between patients and controls (c2=4.205, R=0.040). The allele and genotype frequency of EAAT2 rs12294045 were significantly different between case and control group (allele:c2 = 8.144，R = 0.004; genotype: c2 = 8.054, R = 0.02). Patients with family history of psychosis were more likely to have the CT genotype of rs12294045 than patients without family history of psychosis，while patients with CT genotype of rs12294045 had significantly lower scores of verbal learning and working memory.Conclusions: The polymorphism of EAAT1 and EAAT2 genes in Chinese Han population may be associated with schizophrenia. The CT genotype of EAAT2 rs12294045 may be one of the risk factors for verbal learning memory and working operational memory dysfunction in patients.
Diversity of Culturable Gut Bacteria of Diamondback Moth, Plutella Xylostella (Linnaeus) (Lepidoptera: Yponomeutidae) Collected From Different Geographical Regions of India
Authors: Kaur Mandeep , Thakur Meena , Sagar Vinay , Sharma Ranjna
Published: May 2021

Diamondback moth, Plutella xylostella is one of the important pests of cole crops, the larvae of which cause damage to leaves from seedling stage to the harvest thus reducing the quality and quantity of the yield. The insect gut posses a large variety of microbial communities among which, the association of bacteria is the most spread and common. Due to variations in various agro-climatic factors, the insect often assumes the status of major pest. These geographical variations in insects influence various biological parameters including insecticide resistance due to diversity of microbes/bacteria. The diverse role of gut bacteria in insect fitness traits has now gained perspectives for biotechnological exploration. The present study was aimed to determine the diversity of larval gut bacteria of diamondback moth collected from five different geographical regions of India. The gut bacteria of this pest were found to be influenced by different geographical regions. A total of 14 larval gut bacterial isolates were obtained. Majority of these bacteria belong to Enterobacteriaceae followed by Yersiniaceae, Morganellaceae and Enterococcaceae. Phylogeny analysis of all the bacterial isolates collected from five different geographical regions of India revealed that all the isolated strains are resolved in well-defined clades with their closest type species.
Dexmedetomidine Attenuates Hippocampal Damage and Improves Cognition by Up-Regulating Glyoxalase1 in APP/PS1 Mice
Authors: Guo Chunyan , Zhang Lei , Gao Yaoxing , Sun Junzhi , Fan Lingling , Bai Yuguang , Zhang Jing , Naren Gaowa , Yang Jiwen , Li Libiao
Published: May 2021

Background: Dexmedetomidine (DEX), an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against postoperative cognitive impairment. GLO-1 plays a key role in the pathogenesis of Alzheimer’s disease (AD). Here, the primary goal was to assess whether DEX affect GLO-1 and protect cognition impairment in APP/PS1 transgenic mice.Methods: After DEX was intraperitoneally injected in APP/PS1 mice, behavior was tested by Water Maze to illustrate whether DEX treatment has a significantly positive effect on ameliorating the cognition deficits in AD. We assessed the effect of DEX on the expression of GLO-1 and the production of other oxidative stress factors by ELISA and Western blot. To determine whether DEX play roles in the Aβ induced neuron apoptosis, flow cytometry was used.Results: DEX treatment significantly ameliorated cognition deficits in APP/PS1 mice. DEX increased GLO-1 expression and decreased MG activity in the hippocampus. In addition, DEX increased activity of SOD, GSH and reduced the activity of MDA. In vitro, DEX could protect the neuron apoptosis induced by Aβ. GLO-1 inhibitor could block the protective role of DEX.Conclusion: Taken together, our findings suggest that DEX prevents progression of AD-like pathology through upregulating GLO-1.
Childhood Disability in Rural Niger: A Population-based Assessment Using the Key Informant Method
Authors: Banks Lena Morgon , Liu Jing , Kielland Anne , Tahirou Ali Bako , Harouna Abdoul Karim Seydou , Mactaggart Islay , Dybdahl Ragnhild , Mounkaila Dan Firoun , Grønningsaeter Arne
Published: May 2021

Background: Data on childhood disability is essential for planning health, education and other services. However, information is lacking in many low- and middle-income countries, including Niger. This study uses the Key Informant Method, an innovative and cost-effective strategy for generation population-based estimates of childhood disability, to estimate the prevalence and causes of moderate/severe impairments and disabling health conditions in children of school-going age (7-16 years) in the Kollo department of western Niger. Methods: Community-based key informants were trained to identify children who were suspected of having the impairment types/health conditions included in this study. Children identified by key informants were visited by paediatricians and underwent an assessment for moderate/severe vision, hearing, physical and intellectual impairments, as well as epilepsy, albinism and emotional distress. Results: 2,561 children were identified by key informants, of whom 2191 were visited by paediatricians (response rate = 85.6%). Overall, 597 children were determined to have an impairment/health condition, giving a prevalence of disability of 11.4 per 1000 children (10.6- 12.2). Intellectual impairment was most common (4.9 per 1000), followed by physical (4.9 per 1000) and hearing impairments (4.7 per 1000). Many children had never sought medical attention for their impairment/health condition, with health seeking ranging from 40.0% of children with visual impairment to 67.2% for children with physical impairments. Conclusion: The Key Informant Method enabled the identification of a large number of children with disabling impairments and health conditions in rural Niger, many of whom have unmet needs for health and other services.
Gibberellic Acid Biosynthesis During Dehydration Phase of Priming Increases Seed Vigour of Tomato
Authors: S Seethalakshmi , R Umarani , Maduraimuthu Djanaguiraman
Published: May 2021

Priming of seed is intended to reduce the time to germination through activation of pre-germinative processes. Seed priming is controlled hydration and followed by a drying (dehydration) process. The physiological processes during hydration (imbibition) were studied in detail in tomato. In contrast, gibberellic acid (GA) changes during the dehydration phase were not studied in detail. We hypothesize that there would be a change in the GA concentration during the dehydration phase of the seed priming process, which may influence the vigour characteristics of the resultant seedling. The objective was to understand the influence dehydration phase of seed priming on GA biosynthesis and its subsequent effect on seed germination and seedling traits of tomato. First, the hydroprimed and unprimed seeds were re-imbibed for 3, 6, 9, and 12 h to initiate the germination process, and the GA concentration and seedling vigour associated parameters were recorded. In the second experiment, the imbibed seeds were dehydrated for 3, 6, 9, and 12 h, then re-imbibed for 3, 6, 9, and 12 h to understand the effect of dehydration on the GA concentration and its associated traits. Results revealed that hydroprimed seeds had a higher GA concentration and seedling vigour than unprimed seeds. The seeds that are completely dehydrated for 12 h had the highest GA and seed vigour parameters. Therefore, increased vigour of hydroprimed seeds is due to the higher levels of GA accumulated during the dehydration phase of seed priming, which can improve seed germination and seedling vigour of tomato.
Stepwise membrane binding of the C2 domains of the extended synaptotagmins revealed by optical tweezers
Authors: Ge Jinghua , Bian Xin , Ma Lu , Cai Yiying , Li Yanghui , Yang Jie , Karatekin Erdem , De Camilli Pietro , Zhang Yongli
Published: May 2021

Extended synaptotagmins (E-Syts) mediate lipid exchange between the endoplasmic reticulum (ER) and the plasma membrane (PM). Anchored on ER, E-Syts bind the PM via an array of C2 domains in a Ca2+- and lipid-dependent manner, drawing the two membranes close to facilitate lipid exchange. How these C2 domains bind the PM and regulate the ER-PM distance have not been well understood. Here, we applied optical tweezers to dissect PM membrane binding by E-Syt1 and E-Syt2. We detected Ca2+- and lipid-dependent membrane binding kinetics of both E-Syts and determined the binding energies and rates of individual C2 domains or pairs. We incorporated these parameters in a theoretical model to recapitulate various properties of E-Syt-mediated membrane contacts observed in vivo, including their equilibrium distances and probabilities. Our methods can be applied to study other proteins containing multiple membrane-binding domains linked by disordered polypeptides.
Fine Structure Constant derived from Principle Theory.
Authors: Geilhaupt Manfred
Published: May 2021

Derivation of mass (m), charge (e) and fine structure constant (FSC) from theory are unsolved problems in physics up to now. Neither the Standard Model (SM) nor the General theory of Relativity (GR) has provided a complete explanation for the existence of the rest mass, i.e. restmass of the electron. The question “of what is rest mass” is therefore still essentially unanswered. We will show that the combination of two Principle Theories, General Relativity and Thermodynamics (TD), is able to derive the restmass of an electron (m), which surprisingly depends on the (Sommerfeld) FSC (same for the charge (e)).
Iron Therapy-Induced Leukopenia in Arab Female Population, an experience in Qatar
Authors: Almasri Hussam , Soliman Ashraf , Desanctis Vincenzo , Alsaud Arwa , Alhashimy Roua , Babikr Mona , Ahmad Rita , Aldwairi Majd , Kloub Mohammad , Ahmed Shaima , Al-Tikrity Mustafa , Eisa Mahmoud , Yassin Mohamed
Published: May 2021

IntroductionIron deficiency anemia (IDA) is the most common cause of anemia in both developed and developing countries. Leukopenia is an infrequent side effect of iron therapy reported in the literature as sporadic cases. We conducted a study to clarify this issue and to check its consequences in a big cohort of patients with IDA.ObjectiveTo assess the relationship between iron therapy (intravenous) and leukopenia, neutropenia or lymphocytopenia, and its clinical impact, if any, on patients.Materials and Methodsthis is a retrospective study conducted in Hamad Medical Corporation, Doha/Qatar. the clinical and biochemical data of 1567 females with IDA who attended the hematology clinic and were treated with intravenous iron therapy were collected and analysed. Complete and differential blood counts and iron profile were studied before and after iron treatment. In addition, cases who developed infections during the time of leukopenia were noted and checked for possible complications.ResultsAfter iron therapy, out of 1567 case of iron deficiency anemia, 30 cases (1.914%) developed leukopenia,15 cases (0.957%) developed neutropenia and 12 cases (0.765%) developed lymphocytopenia. All had normal WBC counts before treatment. 2 patients (6.66%) had infection, 1 had upper respiratory tract infection and 1 urinary tract infection, the latter was treated with antibiotics. There were no reported infections during or after iron therapy.ConclusionsLeukopenia in form of neutropenia or lymphocytopenia may occur as a side effect of IV iron therapy, however, its clinical significance appeared to be limited.
A nationwide study of adolescent psychosocial well-being one year after the outbreak of the COVID-19 pandemic
Authors: von Soest Tilmann , Kozák Michal , Rodriguez-Cano Ruben , Fluit Sam , Cortés-García Laura , Ulseth Vidar , Haghish E. F. , Bakken Anders
Published: May 2021

]The COVID-19 pandemic has dramatically restricted adolescents’ lives. We used nationwide Norwegian survey data collected from 2014–2021 (N = 227,258; ages 13–18) to address three essential questions: What are the psychosocial consequences of the pandemic? Are disadvantaged adolescents disproportionally affected by the pandemic? Do pandemic effects vary with geographical variations in infection rates and restrictions? Multilevel models revealed higher depressive symptoms and lower optimism during the pandemic than before the pandemic, even when accounting for the measures’ time trends. Further, alcohol and cannabis use decreased, and screen time increased. Social relationships and conduct problems remained stable. Girls, younger adolescents, and adolescents from low socioeconomic backgrounds were disproportionally affected by the pandemic. The pandemic’s effects varied little with municipality infection rates and restrictions. These findings can inform means and interventions to reduce negative pandemic effects and identify groups that need particular attention during and after the pandemic.
RAISING: a high-performance method for identifying random transgene integration sites
Authors: Wada Yusaku , Sato Tomoo , Hasegawa Hiroo , Matsudaira Takahiro , Nao Naganori , Coler-Reilly Ariella , Tasaka Tomohiko , Yamauchi Shunsuke , Okagawa Tomohiro , Momose Haruka , Tanio Michikazu , Kuramitsu Madoka , Sasaki Daisuke , Yagishita Naoko , Yamauchi Junji , Araya Natsumi , Tanabe Kenichiro , Yamagishi Makoto , Nakashima Makoto , Nakahata Shingo , Iha Hidekatsu , Ogata Masao , Imaizumi Yoshitaka , Uchimaru Kaoru , Miyazaki Yasushi , Konnai Satoru , Yanagihara Katsunori , Morishita Kazuhiro , Watanabe Toshiki , Yamano Yoshihisa , Saito Masumichi
Published: May 2021

Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive next-generation sequencing. To model our method, we analyzed samples from 698 patients infected with the retrovirus HTLV-1, which causes adult T-cell leukemia/lymphoma (ATL). We defined a clonality value identifying ATL patients with 100% sensitivity and 95.3% specificity, and our preliminary longitudinal analysis suggests this may also be useful for ATL risk assessment. We anticipate future studies will confirm the broad applicability of our technology, especially in the emerging gene therapy sector.
Nonlinear Analysis of L-shaped Pipe Conveying Fluid with the Aid of Absolute Nodal Coordinate Formulation
Authors: Zhou K. , Yi H.R. , Dai Huliang , Yan H , Guo Z.L. , Xiong F.R. , Ni Q. , Hagedorn P. , Wang L.
Published: May 2021

By adopting the absolute nodal coordinate formulation, a novel and general nonlinear theoretical model, which can be applied to solve the dynamics of combined straight-curved fluid-conveying pipes with arbitrary initially configurations and any boundary conditions, is developed in the current study. Based on this established model, the nonlinear behaviors of the cantilevered L-shaped pipe conveying fluid with and without base excitations are systematically investigated. Before starting the research, the developed theoretical model is verified by performing three validation examples. Then, with the aid of this model, the static deformations, linear stability, and nonlinear self-excited vibrations of the L-shaped pipe without the base excitation are determined. It is found that the cantilevered L-shaped pipe suffers from the static deformations when the flow velocity is subcritical, and will undergo the limit-cycle motions as the flow velocity exceeds the critical value. Subsequently, the nonlinear forced vibrations of the pipe with a base excitation are explored. It is indicated that the period-n, quasi-periodic and chaotic responses can be detected for the L-shaped pipe, which has a strong relationship with the flow velocity, excitation amplitude and frequency.
Transcription Factors Linked to the Molecular Signatures in the Development of HCC on a Cirrhotic Background
Authors: Motalebzadeh Jamshid , Eskandari Elaheh
Published: May 2021

Mechanisms underlying the regulation of gene expression in cancer have been surveyed for decades to find novel prognostic factors and new targets for molecular targeted therapies in cancer. Because most cases of liver cancer are associated with liver cirrhosis, we aimed to analyze the gene expression signatures and the gene regulatory mechanism in hepatocellular carcinoma (HCC) on a cirrhotic background using high-throughput data analysis. In the present study, three valid array-based datasets containing HCC and liver cirrhosis samples were obtained to identify common differentially expressed genes (DEGs). Moreover, a comprehensive data analysis was conducted based on RNA-Seq data and using Kaplan-Meier curve analysis to find molecular signatures that reduce patients' overall survival rate. Furthermore, we proposed a gene regulatory network (GRN) to explore the possible regulatory mechanism of these molecular signatures by transcription factors in HCC progression from cirrhosis. Besides, we analyzed protein-protein interactions, gene ontology (GO), and pathway enrichment to elucidate the cellular and molecular function of the GRN elements in HCC. In this way, we found a list of 231 molecular signatures in HCC derived from cirrhosis. We also found the importance of TCF4, RUNX1, HINFP, KDM2B, MAF, JUN, NR5A2, NFYA, and AR as key differentially expressed transcription factors (DETFs) in the progression of HCC from cirrhosis. In conclusion, the identified molecular signatures and their transcription factors propose candidate prognostic markers and possible molecular targets in the progression of HCC.
Long-Term Dynamics of Bird Dispersal Network Structures Associated with the Functions in Bird Migration and Fruit Abundance
Authors: Ohkawara Kyohsuke , Kimura Kazuya , Satoh Fumio
Published: May 2021

In temperate zones, the complex network of seed dispersal by migrant birds is formed and the structure is dynamic on long time scale. Over 12 years, we examined interannual variability of structures of bird dispersal networks and factors affecting them by observing the characteristics of fruit abundance, bird migration and bird dispersal interactions in central Japan. The fruit abundance exhibited a remarkable fluctuation across years, with the number of fruiting trees and matured fruits fluctuating repeatedly every other year, leading to the periodic fluctuations. The abundance of migrants was also fluctuated. According to the abundance of fruits and migrants, the 12 years as study period was classified into three types. The seed transporting frequency and the dispersal networks were investigated by collecting faeces of migrants. Of the 6652 samples collected from 15 bird species, 1671 (25.1%) included seeds from 60 plant species. Main dispersers were composed of Turdus pallidus, T. obscurus and Zosterops japonicus. The structures of bird dispersal networks were highly nested over 12 years, suggesting the networks are stable. Specifically, the nested structure developed in years when fruit abundance was low. GLM analyses showed the abundance of migrants, particularly T. pallidus and T. obscurus, had strong positive effects on construction of nested structure. The development of nested structure may be caused by the fact the two Turdus species were more frequently functioning as generalist dispersers when fruit abundance was lower. Our study revealed one of the mechanisms determining the structure of bird dispersal network on long time scale.
Mutational signatures of complex genomic rearrangements in human cancer
Authors: Yang Lixing , Bao Lisui , Zhong Xiaoming , Yang Yang
Published: May 2021

Complex genomic rearrangements (CGRs) are common in cancer and are known to form via two aberrant cellular structures—micronuclei and chromatin bridge. However, which mechanism is more relevant to CGR formation in cancer cells and whether there are other undiscovered mechanisms remain open questions. Here, we analyze 2,014 CGRs from 2,428 whole-genome sequenced tumors and deconvolute six CGR signatures based on the topology of CGRs. Through rigorous benchmarking, we show that our CGR signatures are highly accurate and biologically meaningful. Three signatures can be attributed to known biological processes—micronuclei- and chromatin-bridge-induced chromothripsis and extrachromosomal DNA. More than half of the CGRs belong to the remaining three newly discovered signatures. A unique signature (we named “hourglass chromothripsis”) with highly localized breakpoints and small amount of DNA loss is abundant in prostate cancer. Through genetic association analysis, we find SPOP as a candidate gene causing hourglass chromothripsis and playing important role in maintaining genome integrity. Our study offers valuable insights into the formation of CGRs.
A Candidate Multi-epitope Vaccine Against Porcine Reproductive and Respiratory Syndrome Virus and Mycoplasma Hyopneumoniae
Authors: Gao Zhisong , Chen Lingxiao , Pan Xuan , Li Xiaojing , Lu Guangzong , Tang Yajie , Wu Xiang , Zhao Baohua , Zhang Ran
Published: May 2021

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) are two of the most common pathogens involved in the porcine respiratory disease complex (PRDC) which results in significant worldwide economic losses. Vaccination is reported to be the most effective approach to prevent the disease. Since PRRSV and Mhp co-infections are very common, an efficient dual vaccine against PRRSV and Mhp co-infections is required for the global swine industry. Compare with the traditional vaccine, the multi-epitope vaccines have several advantages, such as comparatively easy production and construction, chemical stability, and lack of infectious potential.Results: In this study, to develop a safe and effective vaccine, B cell epitopes and T cell epitopes of PRRSV-GP5, PRRSV-M, Mhp-P46 and Mhp-P65 protein had been screened to construct a recombinant epitope protein rEP-PM which has good hydrophilicity, strong antigenicity and high surface accessibility, and each epitope is independent and complete. After immunization in mice, rEP-PM could induce the production of high levels of antibodies and effective cellular immune response.Conclusions: Our results showed that the rEP-PM protein could be potential candidate to develop into a safe and effective multi-epitope peptide combined vaccine used in the control of PRRSV and Mhp infection.
New Insight into Regulation of αIIbβ3 Integrin Signaling by Filamin A
Authors: Lamrani Lamia , Adam Frédéric , Soukaseum Christelle , Denis Cécile V. , Raslova Hana , Rosa Jean-Philippe , Bryckaert Marijke
Published: May 2021

Filamin (FLN) regulates many cell functions through its scaffolding activity cross-linking cytoskeleton and integrins. FLN was shown to inhibit integrin activity, but the exact mechanism remains unclear. Here, we report on the regulation of platelet integrin αIIbβ3 signaling by the FLNa subtype. Three FLNa deletion mutants were overexpressed in the erythro-megakaryocytic leukemic cell line HEL: Del1 which lacks the N-terminal CH1-CH2 domains mediating the FLNa-actin interaction; Del2 lacking the immunoglobulin-like (Ig) repeat 21 which mediates the FLNa-β3 interaction; and Del3 lacking the C-terminal Ig repeat 24, responsible for FLNa dimerization and interaction with the small Rho GTPase involved in actin cytoskeleton reorganisation. Fibrinogen binding to HEL cells in suspension and talin-β3 interaction in cells adherent to immobilized fibrinogen were assessed using the PKC agonist (phorbol 12-myristate 13-acetate) also to activate αIIbβ3. Our results show that FLNa-actin and FLNa-β3 interactions negatively regulate αIIbβ3 activation. Moreover FLNa-actin interaction represses Rac activation, contributing to the negative regulation of αIIbβ3 activation. In contrast, the FLNa dimerization domain which maintains Rho inactive, was found to negatively regulate αIIbβ3 outside-in signaling. We conclude that FLNa negatively controls αIIbβ3 activation by regulating actin polymerization and restraining activation of Rac, as well as outside-in signaling by repressing Rho.