bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial Matrix Remodeling in Atrial Fibrillation Patients with Aortic Stenosis
Authors: Fragão-Marques Mariana , Miranda I , Martins D , Barroso Isaac , Mendes C , Pereira-Neves A , Falcão-Pires I , Leite-Moreira A 
Published: October 2020

Abstract
Background: This study aimed to evaluate atrium extracellular matrix remodeling in Atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets. Methods: A posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to Aortic valve replacement (AVR) surgery in a tertiary hospital were selected. Results: Fibrosis was significantly increased in the AF group when compared to Sinus Rhythm (SR) patients (p=0.024). Moreover, cardiomyocyte area was significantly higher in AF patients vs SR patients (p=0.008). Conversely, collagen III gene expression was increased in AF patients (p=0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/TIMP4 ratio was significantly decreased in AF patients (p=0.006). TIMP1 (p=0.004) and TIMP2 (p=0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p=0.0159) and mean (p=0.031) gradients demonstrated a negative association with serum TIMP1. Conclusion: Atrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.
Epidemiology of Sheep Lice and Efficacy Evaluation of 60% Diazinon and 1% Ivermectin against Bovicola ovis in Sayint District, South Wollo, Ethiopia
Authors: Legesse Simegn , Hailemelekot Mussie , Tamrat Habtamu , Ferede Yeshwas 
Published: October 2020

Abstract
Background

Sheep lice, caused by Bovicola ovis are very common in Ethiopia. It can result decreased production and reproduction, downgrading and rejection of skins in tannery industries. A cross-sectional and experimental study were conducted in Sayint District, South Wollo, Ethiopia which aims to determine the prevalence of sheep lice with the associated risk factors, identify the major sheep lice species and evaluate the efficacy of 60% Diazinon and 1% Ivermectin against Bovicola ovis. Study kebeles and animals were selected using purposive and multistage sampling techniques. Accordingly, a total of 232 sheep were sampled to estimate the prevalence of sheep lice. Fifteen sheep for in-vivo and 80 Bovicola ovis lice for in-vitro test were used for drug efficacy trial, by using completely randomized design.
Results

The overall prevalence of sheep lice in this study was 48%. Hair length (OR = 2, P = 0.00), body condition (OR = 1.9, P = 0.02), agro ecology (OR = 1.19, P = 0.00) and season (OR = 2, P = 0.01) were significantly (P < 0.05) associated with sheep lice infestation. The dominant sheep lice species in the study area were Bovicola ovis with prevalence of 83% and mixed infestation of 17% Bovicola ovis with Linognatus ovillus. In this study, the efficacy of 60% Diazinon and 1% Ivermectin against Bovicola ovis were 97% and 81%, respectively.
Conclusion

The overall prevalence of sheep lice infestation in the present study area was higher, in which Bovicola ovis was predominant and resistant against 1% Ivermectin. Therefore, tailor made intervention is required with a view to reducing the prevalence of sheep lice infestation and addressing drug resistance in the study area.
Structure and assembly of the S-layer determine virulence in C. difficile
Authors: Banerji Oishik , Lanzoni-Mangutchi Paola , Vaz Filipa , Barwinska-Sendra Anna , Wilson Jason , Kirk Joseph , O'Beirne Shauna , Basle Arnaud , Omari Kamel El , Wagner Armin , Fairweather Neil , Douce Gillian , Bullough Per , Fagan Robert P , Salgado Paula 
Published: October 2020

Abstract
Many bacteria and archaea possess a cell surface layer – S-layer – made of a 2D protein array that covers the entire cell. As the outermost component of the cell envelope, S-layers play crucial roles in many aspects of cell physiology. Importantly, many clinically relevant bacterial pathogens possess a distinct S-layer that forms an initial interface with the host, making it a potential target for development of species-specific antimicrobials. Targeted therapeutics are particularly important for antibiotic resistant pathogens such as Clostridioides difficile, the most frequent cause of hospital acquired diarrhea, which relies on disruption of normal microbiota through antibiotic usage.
Despite the ubiquity of S-layers, only partial structural information from a very limited number of species is available and their function and organization remains poorly understood.
Here we report the first complete atomic level structure and in situ assembly model of an S-layer from a bacterial pathogen and reveal its role in disease severity. SlpA, the main C. difficile S-layer protein, assembles through tiling of triangular prisms abutting the cell wall, interlocked by distinct ridges facing the environment. This forms a tightly packed array, unlike the more porous S-layer models previously described. We report that removing one of the SlpA ridge features dramatically reduces disease severity, despite being dispensable for overall SlpA structure and S-layer assembly. Remarkably, the effect on disease severity is independent of toxin production and bacterial colonization within the mouse model of disease.
Our work combines X-ray and electron crystallography to reveal a novel S-layer organization in atomic detail, highlighting the need for multiple technical approaches to obtain structural information on these paracrystalline arrays. These data also establish a direct link between specific structural elements of S-layer and virulence for the first time, in a crucial paradigm shift in our understanding of C. difficile disease, currently largely attributed to the action of potent toxins.
This work highlights the crucial role of S-layers in pathogenicity and the importance of detailed structural information for providing new therapeutic avenues, targeting the S-layer. Understanding the interplay between S-layer and other virulence factors will further enhance our ability to tackle pathogens carrying an S-layer. We anticipate that this work provides a solid basis for development of new, C. difficile-specific therapeutics, targeting SlpA structure and S-layer assembly to reduce the healthcare burden of these infections.
Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis
Authors: Cecere Germano , Singh Meetali , Cornes Eric , Li Blaise , Quarato Piergiuseppe , Bourdon Loan , Dingli Florent , Loew Damarys , Procaccia Simone 
Published: October 2020

Abstract
In the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with ribosome translation in the cytoplasm, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting.
How to build a water-splitting machine: structural insights into photosystem II assembly
Authors: Zabret Jure , Bohn Stefan , Schuller Sandra , Arnolds Oliver , Möller Madeline , Meier-Credo Jakob , Liauw Pasqual , Chan Aaron , Tajkhorshid Emad , Langer Julian , Stoll Raphael , Krieger-Liszkay Anja , Engel Benjamin , Rudack Till , Schuller Jan , Nowaczyk Marc 
Published: October 2020

Abstract
Biogenesis of photosystem II (PSII), nature’s water splitting catalyst, is assisted by auxiliary proteins that form transient complexes with PSII components to facilitate stepwise assembly events. Using cryo-electron microscopy, we solved the structure of such a PSII assembly intermediate with 2.94 Å resolution. It contains three assembly factors (Psb27, Psb28, Psb34) and provides detailed insights into their molecular function. Binding of Psb28 induces large conformational changes at the PSII acceptor side, which distort the binding pocket of the mobile quinone (QB) and replace bicarbonate with glutamate as a ligand of the non-heme iron, a structural motif found in reaction centers of non-oxygenic photosynthetic bacteria. These results reveal novel mechanisms that protect PSII from damage during biogenesis until water splitting is activated. Our structure further demonstrates how the PSII active site is prepared for the incorporation of the Mn4CaO5 cluster, which performs the unique water splitting reaction.
Supply chain diversity buffers cities against food shocks
Authors: Mejia Alfonso , Gomez Michael , Ruddell Ben , Rushforth Richard 
Published: October 2020

Abstract
Food supply shocks are increasing worldwide, urging discovery of methods to manage the risk of food shock and boost food supply chain resilience. Ecological theory suggests that network structure is crucial for the resilience of the food supply chain. Here we show that boosting a city’s food supply chain diversity increases the resistance of a city to food shocks of mild to moderate severity up to 15%. We develop an intensity-duration-frequency model linking food shock risk to supply chain diversity. The empirical-statistical model is based on annual food inflow observations from all metropolitan areas in the United States during the years 2012-2015, years when most of the country experienced moderate to severe droughts. This model is simple, operationally useful, and hazard-agnostic. Using this method cities can improve their resistance to food supply shocks with policies that increase the food supply chain’s diversity.
The Loss of DLG2 Isoform 7/8, But Not Isoform 2, is Critical in Advanced Staged Neuroblastoma
Authors: Keane Simon , Martinsson Tommy , Kogner Per , Ejeskar Katarina 
Published: October 2020

Abstract
BACKGROUND: Neuroblastoma is a childhood neural crest tumor showing large clinical and genetic heterogeneity, one form displaying 11q-deletion is very aggressive. It has been shown that 11q-deletion results in decreased expression of DLG2, a gene residing in the deleted region. DLG2 has a number of different isoforms with the main difference is the presence or absence of a L27 domain. The L27 domain containing DLG proteins can form complexes with CASK/MPP and LIN7 protein family members, which will control cell polarity and signaling. METHODS: We evaluated the DLG gene family and the LIN7 gene family for their expression in differently INSS staged neuroblastoma from publically available neuroblastoma data and primary tumors, we included two distinct DLG1 and DLG2 N-terminal transcript isoforms encoding L27 domains for their expression. Functionality of DLG2 isoforms and of LIN7A were evaluated in the 11q-deleted neuroblastoma cell line SKNAS.RESULTS: In neuroblastoma only two DLG2 isoforms were expressed: isoform 2 and isoform 7/8. Using the array data we could determine that higher expression of DLG members that contain L27 domains correlated to better survival and prognosis. Whilst DLG1 showed a decrease in both isoforms with increased INSS stage, only the full length L27 containing DLG2 transcripts DLG2-isoform 7/8 showed a decrease in expression in high stage neuroblastoma. We could show that the protein encoded by DLG2-isoform 7 could bind to LIN7A, and increased DLG2-isoform 7 gene expression increased the expression of LIN7A, this reduced neuroblastoma cell proliferation and viability.CONCLUSION: We have provided evidence that gene expression of the L27 domain containing DLG2-isoform 7/8 but not L27 domain lacking DLG2-isoform 2 is disrupted in neuroblastoma, in particular in the aggressive subsets of tumors. The presence of the complete L27 domain allows for the binding to LIN7A, which will control cell polarity and signaling, thus affecting cancer cell viability.
Hypoproliferative human NPC xenografts survived extendedly in the brain of immunocompetent rats
Authors: Liu Chunhua , Wang Xiaoyun , Huang Wenhao , Meng Wei , Su Zhenghui , Xing Qi , Shi Heng , Zhang Di , Zhou Min , Zhao Yifan , Wang Haitao , Pan Guangjin , Zhong Xiaofen , Pei Duanqing , Guo Yiping 
Published: October 2020

Abstract
Background: There is a huge controversy about whether xenograft or allograft in the “immune-privileged” brain needs immunosuppression. In animal studies, prevailing sophiscated immunosuppression or immunodeficiency is detrimental for the recipients, which results in short lifespan of animals, and confounds functional behavioral readout of the graft benefit, discouraging long-term follow-up. Methods: Neuron-restricted human neural progenitor cells (NPCs) were derived from human embryonic stem cells (ESCs, including H1, its gene-modified cell lines for better visualization, and HN4), propagated for different passages and then transplanted into the brain of immunocompetent rats without use of immunosuppressant. The graft survivals, their cell fates and HLA expression levels were examined over time (up to months after transplantation). We compared the survival capability of NPCs from different passages, and in different transplantation sites (brain parenchyma vs. para-and intra-ventricular sites). The host responses to the grafts were also investigated.Results: Our results show that human ESC-derived neuron-restricted NPCs survive extendedly in adult rat cerebro-parenchyma with no need of immunosuppression whereas a late-onset graft rejection seems inevitable. Both donor HLA expression level and host MHC-II expression level remain relatively low and little change over the long-term survival, and therefore can’t predict the late-onset rejection. Human grafts in or close to cerebroventricle are more vulnerable to the immune attack than the intra-striatum grafts. Prevention of graft hyperplasia by using hypoproliferative late-passaged human NPCs further significantly extends the graft survival time. Our new data also shows that a subpopulation of host microglia upregulate MHC-II expression in response to the human graft, but fail to present the human antigen to the host immune system, suggestive of the immune-isolation role of the blood–brain barrier (BBB). Conclusions: The present study confirms the “immune privilege” of the brain parenchyma, and more importantly, unveils that choosing hypoproliferative NPCs for transplantation can benefit graft outcome in terms of both lower tumor-genic risk and the prolonged survival time without immunosuppression.
The quorum sensing system luxS gene contributes to the environmental fitness of Streptococcus suis
Authors: Li Jinpeng , Wang Yuxin , Du Yanbin , Zhang Hui , Fan Qingyin , Sun Liyun , Yi Li , Wang Shaohui , Wang Yang 
Published: October 2020

Abstract
Background: Streptococcus suis type 2 (SS2) is an important zoonotic pathogen. We have previously reported the structure of LuxS protein and found that the luxS gene is closely related to biofilm, virulence gene expression and drug resistance of SS2. However, the mechanism of luxS mediated SS2 stress response is unclear. Therefore, this experiment performed stress response to luxS mutant (ΔluxS) and complement strain (CΔluxS), overexpression strain (luxS+) and wild-type SS2 strain HA9801, and analyzed the differential phenotypes in combination with transcriptome data.Results: The results indicate that the luxS gene causes a wide range of phenotypic changes, including chain length. RNA sequencing identified 278 luxS-regulated genes, of which 179 were up-regulated and 99 were down-regulated. Differential genes focus on bacterial growth, stress response, metabolic mechanisms and drug tolerance. Multiple mitotic genes were down-regulated; while the ABC transporter system genes, cobalamin /Fe3+-iron carrier ABC transporter ATPase and oxidative stress regulators were up-regulated. The inactivation of the luxS gene caused a significant reduction in the growth and survival in the acid and iron stress environments. However, the mutant strain ΔluxS showed increased antioxidant activity to H2O2. Conclusions: The luxS gene in SS2 appears to play roles in iron metabolism and protective responses to acidic and oxidative environmental conditions.
Impact involving the community in entomological surveillance of the Triatoma infestans vectorial control
Authors: Abrahan Luciana , Cavallo María José , Amelotti Ivana 
Published: October 2020

Abstract
BackgroundVectorial transmission is the principal way of Trypanosoma cruzi infection, the parasite that cause Chagas disease. In Argentina, Triatoma infestans is the principal vector, for this reason, vector control is the main strategy for the prevention of this illness. Provincial Program of Chagas La Rioja (PPCHLR) carries out entomological evaluation of domiciliary units (DU) and spraying those where T. infestans are found. The lack of government funds generated low visit frequency of PPCHLR, especially in areas with a low infestation that they were not prioritized. For this reason, seeking possible alternatives to complement control activities are necessary. Involving householders in entomologic evaluation would be a control alternative. The major objective was to determine the cost of entomological evaluation with and without community participation.MethodsFor entomological evaluation without community participation, PPCHLR data collected in February 2017 over 359 DU of Castro Barros Department (CBD) were used. For entomological evaluation with community participation, 434 DU of the same department were selected in November 2017. Each householder was trained in the insect collection that were kept in labelled plastic bags and recovered after two weeks to analyse T. cruzi presence in laboratory. Entomological evaluation costs with and without community participation over DU visited number, over DU evaluated number, and over DU sprayed were calculated and compared between methodologies. In addition, DU evaluated number out DU visited number was compared. ResultsThe results showed that the triatomines did not show evidence of T. cruzi infection. Costs in relation to DU visited, to those evaluated and to those sprayed, were lowered with community participation (p< 0.05). In addition, a greater number of DU evaluated in relation to those visited as well as greater surface were covered with community participation. ConclusionThe participation of the community in the infestation survey is an efficient complement of vertical control, allowing the spraying to be focused on infested houses and thus reducing costs and intervention times by PPCHLR.
Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression
Authors: Sheehan Stephanie A. , Hamilton Kelly L. , Retzbach Edward P. , Balachandran Premalatha , Krishnan Harini , Leone Paola , Goldberg Gary S. 
Published: October 2020

Abstract
COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface “spike” protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
Glucose Transporter 1 and Hypoxia-Inducible Factor 1α is Indicators of Head and Neck Squamous Cell Carcinoma Aggressiveness and Poor Prognosis: A Case Control Study
Authors: Liu Jia , Xu Qiong , Luo Yun-Zhen , Yao Hong-Tian , Zhou Shui-Hong 
Published: October 2020

Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive malignancy with a high morbidity and mortality profile. Increased levels of expression of the tumor hypoxia markers, hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT-1), are indicators of poor prognosis in carcinoma.Materials and methods: This study involved detection of HIF-1α and GLUT-1 expression with a mean follow-up period of 10 years in 69 cases of HNSCC (23 cases of hypopharyngeal carcinoma and 46 of laryngeal carcinoma) and 30 controls (15 cases of vocal cord polyps and 15 of leukoplakia). The χ2 test, Fisher’s exact probability method, Pearson’s test, Kaplan–Meier method, Cox proportional hazards regression model of SPSS version 22.0 was used. In all analyses, P < 0.05 was taken to indicate statistical significance.Results: Compared with inflammatory and precancerous lesion tissues, the levels of GLUT-1 and HIF-1α expression were significantly increased in HNSCC (P < 0.001). There was a positive correlation between HIF-1α and GLUT-1 (r = 0.338, P = 0.004). GLUT-1 expression was significantly associated with primary tumor site (P = 0.032), clinical stage (P = 0.036), lymph node metastasis (P = 0.032), and distant metastasis (P = 0.002). HIF-1α expression was significantly related to recurrence (P = 0.013), distant metastasis (P = 0.044), second primary cancer (P = 0.040), and overall survival (OS) (P = 0.029). The OS of the 69 patients with HNSCC was significantly associated with the primary tumor site (P = 0.024), clinical stage (P = 0.041), and lymph node metastasis (P = 0.039). Conclusion: The increased levels of GLUT-1 and HIF-1α expression may serve as molecular markers for diagnosis of HNSCC. High GLUT-1 and HIF-1α expression, especially HIF-1α expression, may be indicators of HNSCC aggressiveness and poor prognosis.