bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental Stress in Chickens and the Potential Effectiveness of Dietary Vitamin Supplementation
Authors: Akinyemi Fisayo , Adewole Deborah
Published: November 2021

Environmental stressors can promote the vulnerability of animals to infections; it is therefore, essential to understand how stressors affect the immune system, the adaptive capacity of animals to respond, and effective techniques in managing stress. This review highlights scientific evidence regarding environmental stress challenge models and the potential effectiveness of vitamin supplementation. The major environmental stressors discussed are heat and cold stress, feed restriction, stocking density, and pollutants. Much work has been done to identify the effects of environmental stress in broilers and layers, while few involved other types of poultry. Studies indicated that chickens' performance, health, and welfare are compromised when challenged with environmental stress. These stressors result in physiological alterations, behavioral changes, decreased egg and meat quality, tissue and intestinal damage, and high mortalities. The application of vitamins with other nutritional approaches can help in combating these environmental stressors in chickens. Poultry birds do not synthesize sufficient vitamins during stressful periods. It is therefore suggested that chicken diets are supplemented with vitamins when subjected to environmental stress. Combination of vitamins are considered more efficient than the use of individual vitamins in alleviating environmental stress in chickens.
Starvation to Glucose Reprograms Development of Neurovascular Unit in Embryonic Retinal Cells
Authors: Özgümüs Türküler , Sulaieva Oksana , Jain Ruchi , Artner Isabella , Lyssenko Valeriya
Published: November 2021

Perinatal exposure to starvation is a risk factor for development of severe retinopathy in adult patients with diabetes. However, the underlying mechanisms are not completely understood. In the present study, we shed light on molecular consequences of exposure to short-time glucose starvation on the transcriptome profile of mouse embryonic retinal cells. We found a profound downregulation of genes regulating development of retinal neurons, which was accompanied by reduced expression of genes encoding for glycolytic enzymes and glutamatergic signaling. At the same time, glial and vascular markers were upregulated, mimicking the diabetes-associated increase of angiogenesis—a hallmark of pathogenic features in diabetic retinopathy. Energy deprivation as a consequence of starvation to glucose seems to be compensated by upregulation of genes involved in fatty acid elongation. Results from the present study demonstrate that short-term glucose deprivation during early fetal life differentially alters expression of metabolism- and function-related genes and could have detrimental and lasting effects on gene expression in the retinal neurons, glial cells, and vascular elements and thus potentially disrupting gene regulatory networks essential for the formation of the retinal neurovascular unit. Abnormal developmental programming during retinogenesis may serve as a trigger of reactive gliosis, accelerated neurodegeneration, and increased vascularization, which may promote development of severe retinopathy in patients with diabetes later in life.
Identification of a Five Autophagy Subtype-Related Gene Expression Pattern for Improving the Prognosis of Lung Adenocarcinoma
Authors: Zhang Meng-Yu , Huo Chen , Liu Jian-Yu , Shi Zhuang-E. , Zhang Wen-Di , Qu Jia-Jia , Yue Yue-Liang , Qu Yi-Qing
Published: November 2021

Background: Autophagy plays an important role in lung adenocarcinoma (LUAD). In this study, we aimed to explore the autophagy-related gene (ARG) expression pattern and to identify promising autophagy-related biomarkers to improve the prognosis of LUAD.

Methods: The gene expression profiles and clinical information of LUAD patients were downloaded from the Cancer Genome Atlas (TCGA), and validation cohort information was extracted from the Gene Expression Omnibus database. The Human Autophagy Database (HADb) was used to extract ARGs. Gene expression data were analyzed using the limma package and visualized using the ggplot2 package as well as the pheatmap package in R software. Functional enrichment analysis was also performed for the differentially expressed ARGs (DEARGs). Then, consensus clustering revealed autophagy-related tumor subtypes, and differentially expressed genes (DEGs) were screened according to the subtypes. Next, the univariate Cox and multivariate Cox regression analyses were used to identify independent prognostic ARGs. After overlapping DEGs and the independent prognostic ARGs, the predictive risk model was established and validated. Correlation analyses between ARGs and clinicopathological variables were also explored. Finally, the TIMER and TISIDB databases were used to further explore the correlation analysis between immune cell infiltration levels and the risk score as well as clinicopathological variables in the predictive risk model.

Results: A total of 222 genes from the HADb were identified as ARGs, and 28 of the 222 genes were pooled as DEARGs. The most significant GO term was autophagy (p = 3.05E-07), and KEGG analysis results indicated that 28 DEARGs were significantly enriched in the ErbB signaling pathway (p < 0.001). Then, consensus clustering analysis divided the LUAD into two clusters, and a total of 168 DEGs were identified according to cluster subtypes. Then univariate and multivariate Cox regression analyses were used to identify 12 genes that could serve as independent prognostic indicators. After overlapping 168 DEGs and 12 genes, 10 genes (ATG4A, BAK1, CAPNS1, CCR2, CTSD, EIF2AK3, ITGB1, MBTPS2, SPHK1, ST13) were selected for the further exploration of the prognostic pattern. Survival analysis results indicated that this risk model identified the prognosis (p = 4.379E-10). Combined with the correlation analysis results between ARGs and clinicopathological variables, five ARGs were screened as prognostic genes. Among them, SPHK1 expression levels were positively correlated with CD4+ T cells and dendritic cell infiltration levels.

Conclusions: In this study, we constructed a predictive risk model and identified a five autophagy subtype-related gene expression pattern to improve the prognosis of LUAD. Understanding the subtypes of LUAD is helpful to accurately characterize the LUAD and develop personalized treatment.
Kinetically Stabilizing Mutations in Beta Tubulins Create Isotype-Specific Brain Malformations
Authors: Park Kristen , Hoff Katelyn J. , Wethekam Linnea , Stence Nicholas , Saenz Margarita , Moore Jeffrey K.
Published: November 2021

Mutations in the family of genes encoding the tubulin subunits of microtubules are associated with a spectrum of human brain malformations known as tubulinopathies. How these mutations impact tubulin activity to give rise to distinct developmental consequences is poorly understood. Here we report two patients exhibiting brain malformations characteristic of tubulinopathies and heterozygous T178M missense mutations in different β-tubulin genes, TUBB2A or TUBB3. RNAseq analysis indicates that both TUBB2A and TUBB3 are expressed in the brain during development, but only TUBB2A maintains high expression in neurons into adulthood. The T178 residue is highly conserved in β-tubulins and located in the exchangeable GTP-binding pocket of β-tubulin. To determine the impact of T178M on β-tubulin function we created an analogous mutation in the β-tubulin of budding yeast and show that the substitution acts dominantly to produce kinetically stabilized microtubules that assemble and disassemble slowly, with fewer transitions between these states. In vitro experiments with purified mutant tubulin demonstrate that T178M decreases the intrinsic assembly activity of β-tubulin and forms microtubules that rarely transition to disassembly. We provide evidence that the T178M substitution disrupts GTPase-dependent conformational changes in tubulin, providing a mechanistic explanation for kinetic stabilization. Our findings demonstrate the importance of tubulin’s GTPase activity during brain development, and indicate that tubulin isotypes play different, important roles during brain development.
Current State and Progress of Research on the Role of lncRNA in HBV-Related Liver Cancer
Authors: Wang Xueke , Kang Meisong , Liu Chun , Lin Ting , Han Xiao , Jiang Xiwen
Published: November 2021

Hepatocellular carcinoma (HCC) is a malignant tumor with the highest mortality rate in the world, and hepatitis B virus (HBV) plays an important role in its development. Long noncoding RNA (lncRNA) is highly related to the inactivation of tumor suppressor genes and the activation of oncogenes in HCC. Researchers have used high-throughput sequencing technology to identify many noncoding transcripts related to the development of HCC and have studied the interaction between these transcripts and DNA, RNA, or protein to determine the relevant mechanism in the development of HCC. In general, the research on lncRNA represents a new field of cancer research, and the imbalance in lncRNA plays an pivotal role in the occurrence of liver cancer. In this review, we summarize some of the dysfunctional lncRNAs in human HCC associated with HBV infection. Their regulatory pathways, functions, and potential molecular mechanisms in the occurrence and development of HCC are discussed.
Can the SARS-CoV-2 Spike Protein Bind Integrins Independent of the RGD Sequence?
Authors: Beaudoin Christopher A. , Hamaia Samir W. , Huang Christopher L.-H. , Blundell Tom L. , Jackson Antony P.
Published: November 2021

The RGD motif in the Severe Acute Syndrome Coronavirus 2 (SARS-CoV-2) spike protein has been predicted to bind RGD-recognizing integrins. Recent studies have shown that the spike protein does, indeed, interact with αVβ3 and α5β1 integrins, both of which bind to RGD-containing ligands. However, computational studies have suggested that binding between the spike RGD motif and integrins is not favourable, even when unfolding occurs after conformational changes induced by binding to the canonical host entry receptor, angiotensin-converting enzyme 2 (ACE2). Furthermore, non-RGD-binding integrins, such as αx, have been suggested to interact with the SARS-CoV-2 spike protein. Other viral pathogens, such as rotaviruses, have been recorded to bind integrins in an RGD-independent manner to initiate host cell entry. Thus, in order to consider the potential for the SARS-CoV-2 spike protein to bind integrins independent of the RGD sequence, we investigate several factors related to the involvement of integrins in SARS-CoV-2 infection. First, we review changes in integrin expression during SARS-CoV-2 infection to identify which integrins might be of interest. Then, all known non-RGD integrin-binding motifs are collected and mapped to the spike protein receptor-binding domain and analyzed for their 3D availability. Several integrin-binding motifs are shown to exhibit high sequence similarity with solvent accessible regions of the spike receptor-binding domain. Comparisons of these motifs with other betacoronavirus spike proteins, such as SARS-CoV and RaTG13, reveal that some have recently evolved while others are more conserved throughout phylogenetically similar betacoronaviruses. Interestingly, all of the potential integrin-binding motifs, including the RGD sequence, are conserved in one of the known pangolin coronavirus strains. Of note, the most recently recorded mutations in the spike protein receptor-binding domain were found outside of the putative integrin-binding sequences, although several mutations formed inside and close to one motif, in particular, may potentially enhance binding. These data suggest that the SARS-CoV-2 spike protein may interact with integrins independent of the RGD sequence and may help further explain how SARS-CoV-2 and other viruses can evolve to bind to integrins.
Discursive Institutionalism and Food Policy Research: The Case Study of Canada’s National Food Policy
Authors: Coulas Mary
Published: November 2021

“Food” and “policy” are ambiguous concepts. In turn, the study of food policy has resulted in varying approaches by different disciplines. However, the power behind the discursive effects of these concepts in policymaking—how food policy is understood and shaped by different actors as well as how those ideas are shared in different settings—requires a rigorous yet flexible research approach. This paper will introduce the contours of discursive institutionalism and demonstrate methodological application using the case study example of Canada’s national food policy,Food Policy for Canada: Everyone at the Table!Selected examples of communicative and coordination efforts and the discursive power they carry in defining priorities and policy boundaries are used to demonstrate how discursive institutionalism is used for revealing the causal and material consequences of food policy discourses.
Drivers of Predator Killing by Rural Residents and Recommendations for Fostering Coexistence in Agricultural Landscapes
Authors: Gálvez Nicolás , St. John Freya A. V. , Davies Zoe G.
Published: November 2021

Predators inhabiting human-dominated landscapes are vulnerable to various anthropogenic actions, including people killing them. We assess potential drivers of predator killing in an agricultural landscape in southern Chile, and discuss the implications for policies and interventions to promote coexistence. We evaluate five different types of motivation: (i) sociodemographics and household economy; (ii) livestock loss; (iii) predator encounter rates; (iv) knowledge of legal protection (all native predators are currently protected); and, (v) tolerance to livestock predation. As the killing of native predators is illegal, the prevalence of this behavior by rural residents was estimated using a symmetrical forced-response randomized response technique (RRT), a method designed to ask sensitive questions. A total of 233 rural residents from randomly assigned sample units (4 km2) across the study region completed our questionnaire. More conspicuous species, such as hawks (Falconiformes sp), foxes (Lycalopex sp) and free-roaming domestic dogs (Canis lupus familiaris), were killed by a higher proportion of farmers than more cryptic species, like the felid güiña (Leopardus guigna), skunk (Conepatus chinga) and pumas (Puma concolor). The proportion of respondents admitting to killing predators was highest for hawks (mean = 0.46, SE = 0.08), foxes (mean = 0.29, SE = 0.08) and dogs (mean = 0.30, SE = 0.08) and lowest for güiña (mean = 0.10, SE = 0.09), which is the only species of conservation concern we examine (considered Vulnerable on the IUCN Red List). From our five motivation categories, past killing of predators was associated with higher reported predator encounter rates (guina, hawks), lower tolerance to livestock predation (hawks, dogs), higher reported livestock loss (dogs) and sociodemographics and household economy (foxes). Our results demonstrate that a one-size-fits-all approach to predator persecution is unlikely to reduce or eliminate illegal killings for the suite of species we examined. We identify and describe two main types of intervention that could foster coexistence, improvement of livestock management and domestic dog management in rural areas, as well as discussing the potential for social marketing.
Protecting Half the Planet and Transforming Human Systems Are Complementary Goals
Authors: Crist Eileen , Kopnina Helen , Cafaro Philip , Gray Joe , Ripple William J. , Safina Carl , Davis John , DellaSala Dominick A. , Noss Reed F. , Washington Haydn , Rolston Holmes , Taylor Bron , Orlikowska Ewa H. , Heister Anja , Lynn William S. , Piccolo John J.
Published: November 2021

The unfolding crises of mass extinction and climate change call for urgent action in response. To limit biodiversity losses and avert the worst effects of climate disruption, we must greatly expand nature protection while simultaneously downsizing and transforming human systems. The conservation initiative Nature Needs Half (or Half Earth), calling for the conservation of half the Earth's land and seas, is commensurate with the enormous challenges we face. Critics have objected to this initiative as harboring hardship for people near protected areas and for failing to confront the growth economy as the main engine of global ecological destruction. In response to the first criticism, we affirm that conservation policies must be designed and implemented in collaboration with Indigenous and local communities. In response to the second criticism, we argue that protecting half the Earth needs to be complemented by downscaling and reforming economic life, humanely and gradually reducing the global population, and changing food production and consumption. By protecting nature generously, and simultaneously contracting and transforming the human enterprise, we can create the conditions for achieving justice and well-being for both people and other species. If we fail to do so, we instead accept a chaotic and impoverished world that will be dangerous for us all.
Virtual Actuator Design for Uncertain Metzler Systems
Authors: Krokavec Dušan , Filasová Anna
Published: November 2021

The paper presents the design conditions adequate in design of virtual actuators and utilizable by nominal static output control structures in fault-tolerant control for strictly Metzler systems. The positive stabilization with H∞ norm performance is also addressed for virtual actuator design for strictly Metzler systems with interval uncertainty matrix representations of single actuator faults. Taking into account disturbance conditions and changes of values of variables after the virtual actuator activation, the design conditions are outlined in the terms of linear matrix inequalities. The approach provides a way to obtain acceptable dynamics of the closed loop system after virtual actuator activation.
Body Roundness Index Is a Superior Obesity Index in Predicting Diabetes Risk Among Hypertensive Patients: A Prospective Cohort Study in China
Authors: Liu Yingshan , Liu Xiaocong , Guan Haixia , Zhang Shuting , Zhu Qibo , Fu Xiaoying , Chen Hongmei , Tang Songtao , Feng Yingqing , Kuang Jian
Published: November 2021

Objective: Individuals with both hypertension and diabetes have been confirmed to significantly increase the risk of cardiovascular disease morbidity and mortality compared with those with only hypertension or diabetes. This study aimed to evaluate the potential of different anthropometric indices for predicting diabetes risk among hypertensive patients.

Methods: The study group consisted of 6,990 hypertensive adults without diabetes who were recruited in China. Demographic and clinical assessment, physical examinations, laboratory tests, and anthropometric measurements, including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and novel indices (ABSI, AVI, BAI, BRI, CI, WWI, and WHHR), were performed at baseline and during the (median) 3-year follow-up. Cox regression analyses were conducted to estimate effects from these indices for the onset of diabetes. Receiver operator characteristic (ROC) analyses were conducted to assess the predictive capacities of the anthropometric indices and determine the optimal cut-points.

Results: A total of 816 (11.7%) developed diabetes during our prospective study. Multivariate Cox regression analyses revealed weight, WC, WHR, WHtR, BAI, BRI, and WWI as the independent risk factor for diabetes among hypertensive patients, regardless of whether it was treated as a continuous or categorical variable (P < 0.05). Further Cox analyses combining BMI and different central obesity indices showed that elevated WC, WHR, WHtR, AVI, BRI, CI, regardless of the general obesity status, were found to be each independently associated with increased diabetes risk (P < 0.05). Dynamic increases of BRI < 5.24 to BRI ≥ 5.24 were associated with increased risk (HR = 1.29; 95% CI, 1.02, 1.64), and its reversal was associated with reduced risk (HR = 1.56; 95% CI, 1.23, 1.98) compared with the others (HR = 1.95; 95% CI, 1.63, 2.32). ROC analysis indicated that the areas under the ROC curves (AUC) of the anthropometric indices ranged from 0.531 to 0.63, with BRI (cut-off value = 4.62) and WHtR having the largest area.

Conclusions: Based on this novel study, BRI was the most superior predictor and independent determinant for diabetes onset among the hypertensive population. Hypertensive patients with BRI > 4.62, regardless of general obesity status, were at high risk of diabetes. Thus, the prompt screening and diagnosis of diabetes should be carried out among these patients for timely integrated intervention.
Big Steps, Little Change: A Case Study in French University Teachers’ Cognitions in the Context of Pedagogical Innovation
Authors: Lami Raphaël , Gastineau Sylvie , Flom Haley , Desdevises Yves
Published: November 2021

The rate of failure of French students during their first years at university is substantial, with only 42% graduating in the expected three or 4 years. As a result, French universities have called for a “pedagogical transformation” encouraging innovative teaching practices to improve undergraduate students’ academic success, notably the introduction of blended learning methods. In 2015, teachers from the three marine stations of Sorbonne Université created the online blended learning platform e-marin’lab for their marine science programs. In this paper, we investigated the participating teachers’ cognitions with regard to teaching and learning. Despite the success of the project that relied on their substantial voluntary commitment, the teachers demonstrated an adhesion to more traditional views (i.e., directive teacher-student transmission of knowledge is more efficient for students’ learning). Perhaps more paradoxically, our data reveal that the same teachers saw themselves as teaching in a student-oriented way, and that their students’ lack of engagement in class was due to their poor study skills and intrinsic motivation. Among other factors that will be discussed, we believe that these results are influenced by a context that does not provide many teacher training opportunities and that places little importance on teaching in university professors’ career recognition. Finally, the importance of the e-marin’lab platform in the context of the SARS-CoV-2 pandemic situation from 2020 and the massive use of distance teaching in marine sciences during national lockdown periods is discussed.
Drug Repositioning For Allosteric Modulation of VIP and PACAP Receptors
Authors: Langer Ingrid , Latek Dorota
Published: November 2021

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two neuropeptides that contribute to the regulation of intestinal motility and secretion, exocrine and endocrine secretions, and homeostasis of the immune system. Their biological effects are mediated by three receptors named VPAC1, VPAC2 and PAC1 that belong to class B GPCRs. VIP and PACAP receptors have been identified as potential therapeutic targets for the treatment of chronic inflammation, neurodegenerative diseases and cancer. However, pharmacological use of endogenous ligands for these receptors is limited by their lack of specificity (PACAP binds with high affinity to VPAC1, VPAC2 and PAC1 receptors while VIP recognizes both VPAC1 and VPAC2 receptors), their poor oral bioavailability (VIP and PACAP are 27- to 38-amino acid peptides) and their short half-life. Therefore, the development of non-peptidic small molecules or specific stabilized peptidic ligands is of high interest. Structural similarities between VIP and PACAP receptors are major causes of difficulties in the design of efficient and selective compounds that could be used as therapeutics. In this study we performed structure-based virtual screening against the subset of the ZINC15 drug library. This drug repositioning screen provided new applications for a known drug: ticagrelor, a P2Y12 purinergic receptor antagonist. Ticagrelor inhibits both VPAC1 and VPAC2 receptors which was confirmed in VIP-binding and calcium mobilization assays. A following analysis of detailed ticagrelor binding modes to all three VIP and PACAP receptors with molecular dynamics revealed its allosteric mechanism of action. Using a validated homology model of inactive VPAC1 and a recently released cryo-EM structure of active VPAC1 we described how ticagrelor could block conformational changes in the region of ‘tyrosine toggle switch’ required for the receptor activation. We also discuss possible modifications of ticagrelor comparing other P2Y12 antagonist – cangrelor, closely related to ticagrelor but not active for VPAC1/VPAC2. This comparison with inactive cangrelor could lead to further improvement of the ticagrelor activity and selectivity for VIP and PACAP receptor sub-types.
Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis
Authors: Peng Yajie , Zhu Hui , Han Bing , Xu Yue , Liu Xuemeng , Song Huaidong , Qiao Jie
Published: November 2021

Background

Androgen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46,XY disorder of sexual development. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes.

Methods

Peripheral blood mononuclear cells (PBMCs) of partial AIS (PAIS) patients and healthy controls were separated, and RNA-seq was performed to investigate transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein–protein interaction (PPI) network analyses were performed; and the key modules were identified. Finally, the RNA expression of differentially expressed genes (DEGs) of interest was validated by quantitative real-time PCR (qRT-PCR).

Results

In our dataset, a total of 725 DEGs were captured, with functionally enriched reproduction and immune-related pathways and Gene Ontology (GO) functions. The most highly specific systems centered on hematologic/immune and reproductive/endocrine systems. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the PPI network and manual screening of tissue-specific gene expression. These genes provide novel insight into the pathogenesis of AIS in the immune system or metabolism and bring forward possible molecular markers for clinical screening. The qRT-PCR results showed a consistent trend in the expression levels of related genes between PAIS patients and healthy controls.

Conclusion

The present study sheds light on the molecular mechanisms underlying the pathogenesis and progression of AIS, providing potential targets for diagnosis and future investigation.
Effects of Proton Pump Inhibitor Therapy, H. pylori Infection and Gastric Preneoplastic Pathology on Fasting Serum Gastrin Concentrations
Authors: Veysey-Smith Reuben , Moore Andrew R. , Murugesan Senthil V. , Tiszlavicz Laszlo , Dockray Graham J. , Varro Andrea , Pritchard D. Mark
Published: November 2021

Background

Hypergastrinaemia occasionally indicates the presence of a gastrinoma. However it is much more commonly associated with various benign causes including proton pump inhibitor (PPI) use, Helicobacter pylori infection and/or atrophic gastritis. The extent to which these factors interact to influence fasting serum gastrin concentrations remains incompletely understood.

Materials and Methods

Fasting serum gastrin concentrations were measured by radioimmunoassay in 1,400 patients attending for diagnostic oesophagogastro-duodenoscopy. After exclusions, 982 patients were divided into four groups and their results analysed. We compared gastrin concentrations in normal patients (no H. pylori infection, no PPI use and no histological evidence of gastric preneoplasia (n=233)), with those in patients who were taking regular PPIs (H. pylori negative with no gastric preneoplasia (n=301)), patients who had active H. pylori infection but no gastric preneoplasia (n=164) and patients with histologically confirmed gastric preneoplasia (n=284).

Results

Median fasting gastrin concentration in the normal group was 20pM and was significantly increased in PPI users (46pM, p<0.0001), patients with active H. pylori infection (27pM, p<0.0001), and patients with antral (25pM, p<0.01) or corpus (48pM, p<0.0001) gastric preneoplasia. PPI use resulted in further significant increases in fasting serum gastrin concentrations in patients who were infected with H. pylori (50pM, n=56) or who had antral gastric preneoplasia (53pM, n=87), but did not significantly alter serum gastrin concentrations in patients with corpus preneoplasia (90pM, n=66).

Conclusions

PPI use, H. pylori infection and atrophic gastritis all caused significant elevations of median fasting gastrin concentrations. However, several patients who had potential risk factors for hypergastrinaemia still demonstrated fasting serum gastrin concentrations within the normal range.
Practical Method for Data-Driven User Phase Identification in Low-Voltage Distribution Networks
Authors: Yu Huang , Wu Yufeng , Guan Weiling , Zhang Daolu , Yu Tao , Liu Qianjin
Published: November 2021

For low-voltage distribution networks (LVDNs), accurate models depicting network and phase connectivity are crucial to the analysis, planning, and operation of these networks. However, phase connectivity data in the LVDN are usually incorrect or missing. Wrong or incomplete phase information collected could lead to unbalanced operation of three-phase distribution systems and increased power loss. Based on the advanced measurement infrastructure (AMI) in the development of smart grids, in this study, a novel data-driven phase identification algorithm is proposed. Firstly, the method involves extracting features from voltage–time matrices using a non-linear dimension reduction algorithm. Secondly, the density-based spatial clustering of applications with noise (DBSCAN) algorithm is used to divide customers into clusters with arbitrary shape. Finally, the algorithms were tested with the IEEE European Low Voltage Test Feeder of the IEEE PES AMPS DSAS Test Feeder working group. The results showed an accuracy of over 90% for the method.
Cattle Grazing Effects on Vegetation and Wild Ungulates in the Forest Ecosystem of a National Park in Northeastern China
Authors: Roberts Nathan James , Zhang Yueheng , Convery Ian , Liang Xin , Smith Darrell , Jiang Guangshun
Published: November 2021

There is evidence that cattle grazing in forests limits big cat abundance. There is concern, too, about competition with wild ungulate prey through bottom-up effects on vegetation. Hence, there have been calls to remove or control forest livestock grazing in aid of restoring endangered large carnivores and their prey. To help inform scientific debate and decision making, we explored cattle-vegetation-prey dynamics in Northeast Tiger and Leopard National Park, northeast China and present a reappraisal of livestock grazing in the context of coexistence and an integrated approach to land use in China. Inside long-term forest grazing enclosures, wild boar (Sus scrofa) density increased with cattle density. Roe deer (Capreolus pygargus) density and occurrence probability of wild boar and roe deer were not influenced by cattle density. Wild ungulate densities were not related with the number of annual shoots, i.e., forage plant abundance. The presence/absence and abundance of annual shoots was not related with cattle density. Wild ungulate density had mixed associations with vegetation structure; arbor tree diameter at breast height (DBH) and habitat “openness” increased with cattle density. Finally, inside and outside enclosures had different vegetation characteristics and wild boar densities, while roe deer densities were equal. We conclude that cattle density and associated changes to vegetation have positive, negative, and neutral effects on two wild ungulate prey species. Each of these factors warrant consideration in evidence-based management decisions in regard to regulating ungulate community composition to support different large predators as preferred prey in core areas and corridors of habitats.
Whole-Genome Selective Scans Detect Genes Associated With Important Phenotypic Traits in Sheep (Ovis aries)
Authors: Xu Song-Song , Gao Lei , Shen Min , Lyu Fenghua
Published: November 2021

Sheep (Ovis aries) is one of the important livestock with diverse phenotypic traits. However, little is known about the molecular mechanism of diverse phenotypic traits in domestic sheep. Using the genome-wide high-density SNP data (600K) in 253 samples from 13 populations, we conducted the tests of selective sweeps (i.e., pairwise FST and XP-CLR) associated with several important phenotypic traits (e.g., tail types, horn morphology, prolificacy, coat pigmentation, ear size, milk production, meat production, body size and wool fineness). We identified strong selective signatures in previously reported (e.g., T, RXFP2, BMPR1B, TYRP1, MSRB3, TF, CEBPA, GPR21 and HOXC8) and novel genes associated with the traits, such as CERS6, BTG1, RYR3, SLC6A4, NNAT and OGT for fat deposition in the tails, FOXO4 for fertility, PTCH1 and EMX2 for ear size, and RMI1 and SCD5 for body size. Further gene annotation analysis showed that these genes were identified to be the most probable genes accounting for the diverse phenotypic traits. Our results provide novel insights into the genetic mechanisms underlying the traits and also new genetic markers for genetic improvement in sheep and other livestock.
Identification of Two Long Non-Coding RNAs AC010082.1 and AC011443.1 as Biomarkers of Coronary Heart Disease Based on Logistic Stepwise Regression Prediction Model
Authors: Liu Chao , Liu Lanchun , Gao Jialiang , Wang Jie , Liu Yongmei
Published: November 2021

Coronary heart disease (CHD) is a global health concern with high morbidity and mortality rates. This study aimed to identify the possible long non-coding RNA (lncRNA) biomarkers of CHD. The lncRNA- and mRNA-related data of patients with CHD were downloaded from the Gene Expression Omnibus database (GSE113079). The limma package was used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs, respectively). Then, miRcode, TargetScan, miRDB, and miRTarBase databases were used to form the competing endogenous RNA (ceRNA) network. Furthermore, SPSS Modeler 18.0 was used to construct a logistic stepwise regression prediction model for CHD diagnosis based on DElncRNAs. Of the microarray data, 70% was used as a training set and 30% as a test set. Moreover, a validation cohort including 30 patients with CHD and 30 healthy controls was used to verify the hub lncRNA expression through real-time reverse transcription-quantitative PCR (RT-qPCR). A total of 185 DElncRNAs (114 upregulated and 71 downregulated) and 382 DEmRNAs (162 upregulated and 220 downregulated) between CHD and healthy controls were identified from the microarray data. Furthermore, through bioinformatics prediction, a 38 lncRNA-21miRNA-40 mRNA ceRNA network was constructed. Next, by constructing a logistic stepwise regression prediction model for 38 DElncRNAs, we screened two hub lncRNAs AC010082.1 and AC011443.1 (p < 0.05). The sensitivity, specificity, and area under the curve were 98.41%, 100%, and 0.995, respectively, for the training set and 93.33%, 91.67%, and 0.983, respectively, for the test set. We further verified the significant upregulation of AC010082.1 (p < 0.01) and AC011443.1 (p < 0.05) in patients with CHD using RT-qPCR in the validation cohort. Our results suggest that lncRNA AC010082.1 and AC011443.1 are potential biomarkers of CHD. Their pathological mechanism in CHD requires further validation.
NILs of Cold Tolerant Japonica Cultivar Exhibited New QTLs for Mineral Elements in Rice
Authors: Ali Muhammad Kazim , Sun Zheng-Hai , Yang Xiao-Meng , Pu Xiao-Ying , Duan Cheng-Li , Li Xia , Wang Lu-Xiang , Yang Jia-Zhen , Zeng Ya-Wen
Published: November 2021

Chilling stress at booting stage can cause floret deterioration and sterility by limiting the supply of food chain and the accumulation of essential mineral elements resulting in reduction of yield and grain quality attributes in rice. Genomic selection of chilling tolerant rice with reference to the accumulation of mineral elements will have great potential to cope with malnutrition and food security in times of climate change. Therefore, a study was conducted to explore the genomic determinants of cold tolerance and mineral elements content in near-isogenic lines (NILs) of japonica rice subjected to chilling stress at flowering stage. Detailed morphological analysis followed by quantitative analysis of 17 mineral elements revealed that the content of phosphorus (P, 3,253 mg/kg) and potassium (K, 2,485 mg/kg) were highest while strontium (Sr, 0.26 mg/kg) and boron (B, 0.34 mg/kg) were lowest among the mineral elements. The correlation analysis revealed extremely positive correlation of phosphorus (P) and copper (Cu) with most of the cold tolerance traits. Among all the effective ear and the second leaf length correlation was significant with half of the mineral elements. As a result of comparative analysis, some QTLs (qBRCC-1, qBRCIC-2, qBRZC-6, qBRCHC-6, qBRMC-6, qBRCIC-6a, qBRCIC-6b, qBRCHC-6, and qBRMC-6) identified for calcium (Ca), zinc (Zn), chromium (Cr) and magnesium (Mg) on chromosome number 1, 2, and 6 while, a novel QTL (qBCPC-1) was identified on chromosome number 1 for P element only. These findings provided bases for the identification of candidate genes involved in mineral accumulation and cold tolerance in rice at booting stage.
Pattern-Recognition Receptor Agonist-Containing Immunopotentiator CVC1302 Boosts High-Affinity Long-Lasting Humoral Immunity
Authors: Du Luping , Hou Liting , Yu Xiaoming , Cheng Haiwei , Chen Jin , Zheng Qisheng , Hou Jibo
Published: November 2021

Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators.
Insights Into the Immune Response of the Black Soldier Fly Larvae to Bacteria
Authors: Bruno Daniele , Montali Aurora , Mastore Maristella , Brivio Maurizio Francesco , Mohamed Amr , Tian Ling , Grimaldi Annalisa , Casartelli Morena , Tettamanti Gianluca
Published: November 2021

In insects, a complex and effective immune system that can be rapidly activated by a plethora of stimuli has evolved. Although the main cellular and humoral mechanisms and their activation pathways are highly conserved across insects, the timing and the efficacy of triggered immune responses can differ among different species. In this scenario, an insect deserving particular attention is the black soldier fly (BSF), Hermetia illucens (Diptera: Stratiomyidae). Indeed, BSF larvae can be reared on a wide range of decaying organic substrates and, thanks to their high protein and lipid content, they represent a valuable source of macromolecules useful for different applications (e.g., production of feedstuff, bioplastics, and biodiesel), thus contributing to the development of circular economy supply chains for waste valorization. However, decaying substrates bring the larvae into contact with different potential pathogens that can challenge their health status and growth. Although these life strategies have presumably contributed to shape the evolution of a sophisticated and efficient immune system in this dipteran, knowledge about its functional features is still fragmentary. In the present study, we investigated the processes underpinning the immune response to bacteria in H. illucens larvae and characterized their reaction times. Our data demonstrate that the cellular and humoral responses in this insect show different kinetics: phagocytosis and encapsulation are rapidly triggered after the immune challenge, while the humoral components intervene later. Moreover, although both Gram-positive and Gram-negative bacteria are completely removed from the insect body within a few hours after injection, Gram-positive bacteria persist in the hemolymph longer than do Gram-negative bacteria. Finally, the activity of two key actors of the humoral response, i.e., lysozyme and phenoloxidase, show unusual dynamics as compared to other insects. This study represents the first detailed characterization of the immune response to bacteria of H. illucens larvae, expanding knowledge on the defense mechanisms of this insect among Diptera. This information is a prerequisite to manipulating the larval immune response by nutritional and environmental factors to increase resistance to pathogens and optimize health status during mass rearing.
Hyperoxia/Hypoxia Exposure Primes a Sustained Pro-Inflammatory Profile of Preterm Infant Macrophages Upon LPS Stimulation
Authors: Twisselmann Nele , Pagel Julia , Künstner Axel , Weckmann Markus , Hartz Annika , Glaser Kirsten , Hilgendorff Anne , Göpel Wolfgang , Busch Hauke , Herting Egbert , Weinberg Jason B. , Härtel Christoph
Published: November 2021

Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O2) and infections. We hypothesized that dysregulated macrophage (MФ) activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. Therefore, we aimed to determine age-dependent differences in immune responses of monocyte-derived MФ comparing cord blood samples derived from preterm (n=14) and term (n=19) infants as well as peripheral blood samples from healthy adults (n=17) after lipopolysaccharide (LPS) exposure. Compared to term and adult MФ, LPS-stimulated preterm MФ showed an enhanced and sustained pro-inflammatory immune response determined by transcriptome analysis, cytokine release inducing a RORC upregulation due to T cell polarization of neonatal T cells, and TLR4 surface expression. In addition, a double-hit model was developed to study pulmonary relevant exposure factors by priming MФ with hyperoxia (O2 = 65%) or hypoxia (O2 = 3%) followed by lipopolysaccharide (LPS, 100ng/ml). When primed by 65% O2, subsequent LPS stimulation in preterm MФ led to an exaggerated pro-inflammatory response (e.g. increased HLA-DR expression and cytokine release) compared to LPS stimulation alone. Both, exposure to 65% or 3% O2 together with subsequent LPS stimulation, resulted in an exaggerated pro-inflammatory response of preterm MФ determined by transcriptome analysis. Downregulation of two major transcriptional factors, early growth response gene (Egr)-2 and growth factor independence 1 (Gfi1), were identified to play a role in the exaggerated pro-inflammatory response of preterm MФ to LPS insult after priming with 65% or 3% O2. Preterm MФ responses to LPS and hyperoxia/hypoxia suggest their involvement in excessive inflammation due to age-dependent differences, potentially mediated by downregulation of Egr2 and Gfi1 in the developing lung.
Persistence of High Levels of Serum Complement C5a in Severe COVID-19 Cases After Hospital Discharge
Authors: Senent Yaiza , Inogés Susana , López-Díaz de Cerio Ascensión , Blanco Andres , Campo Arantxa , Carmona-Torre Francisco , Sunsundegui Patricia , González-Martín Antonio , Ajona Daniel , Okrój Marcin , Prósper Felipe , Pio Ruben , Yuste José Ramón , Tavira Beatriz
Published: November 2021

Evidence supports a role of complement anaphylatoxin C5a in the pathophysiology of COVID-19. However, information about the evolution and impact of C5a levels after hospital discharge is lacking. We analyzed the association between circulating C5a levels and the clinical evolution of hospitalized patients infected with SARS-CoV-2. Serum C5a levels were determined in 32 hospitalized and 17 non-hospitalized patients from Clinica Universidad de Navarra. One hundred and eighty eight serial samples were collected during the hospitalization stay and up to three months during the follow-up. Median C5a levels were 27.71 ng/ml (25th to 75th percentile: 19.35-34.96) for samples collected during hospitalization, versus 16.76 ng/ml (12.90-25.08) for samples collected during the follow-up (p<0.001). There was a negative correlation between serum C5a levels and the number of days from symptom onset (p<0.001). C5a levels also correlated with a previously validated clinical risk score (p<0.001), and was associated with the severity of the disease (p<0.001). An overall reduction of C5a levels was observed after hospital discharge. However, elevated C5a levels persisted in those patients with high COVID-19 severity (i.e. those with a longest stay in the hospital), even after months from hospital discharge (p=0.020). Moreover, high C5a levels appeared to be associated with the presence of long-term respiratory symptoms (p=0.004). In conclusion, serum C5a levels remain high in severe cases of COVID-19, and are associated with the presence of respiratory symptoms after hospital discharge. These results may suggest a role for C5a in the long-term effects of COVID-19 infection.