bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of the HIV-1 accessory proteins Nef and Vpu by flow cytometry represents a new tool to study their functional interplay within a single infected CD4+ T cell
Authors: Prévost Jérémie , Richard Jonathan , Gasser Romain , Medjahed Halima , Kirchhoff Frank , Hahn Beatrice H. , Kappes John C. , Ochsenbauer Christina , Duerr Ralf , Finzi Andrés 
Published: November 2021

ABSTRACTThe HIV-1 Nef and Vpu accessory proteins are known to protect infected cells from antibody-dependent cellular cytotoxicity (ADCC) responses by limiting exposure of CD4-induced (CD4i) envelope (Env) epitopes at the cell surface. Although both proteins target the host receptor CD4 for degradation, the extent of their functional redundancy is unknown. Here, we developed an intracellular staining technique that permits the intracellular detection of both Nef and Vpu in primary CD4+ T cells by flow cytometry. Using this method, we show that the combined expression of Nef and Vpu predicts the susceptibility of HIV-1-infected primary CD4+ T cells to ADCC by HIV+ plasma. We also show that Vpu cannot compensate for the absence of Nef, thus providing an explanation for why some infectious molecular clones that carry a LucR reporter gene upstream of Nef render infected cells more susceptible to ADCC responses. Our method thus represents a new tool to dissect the biological activity of Nef and Vpu in the context of other host and viral proteins within single infected CD4+ T cells.IMPORTANCEHIV-1 Nef and Vpu exert several biological functions that are important for viral immune evasion, release and replication. Here, we developed a new method allowing simultaneous detection of these accessory proteins in their native form together with some of their cellular substrates. This allowed us to show that Vpu cannot compensate the lack of a functional Nef, which has implication for studies that use Nef-defective viruses to study ADCC responses.
Transcription Factor Acj6 Controls Dendrite Targeting via Combinatorial Cell-Surface Codes
Authors: Xie Qijing , Li Jiefu , Li Hongjie , Udeshi Namrata D , Svinkina Tanya , Orlin Daniel , Kohani Sayeh , Guajardo Ricardo , Mani DR , Xu Chuanyun , Li Tongchao , Han Shuo , Wei Wei , Andrew Shuster S , Luginbuhl David J , Quake Stephen R. , Murthy Swetha E. , Ting Alice Y , Carr Steven A , Luo Liqun 
Published: November 2021

SUMMARYTranscription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and proteins previously not associated with wiring, such as Piezo, whose mechanosensitive ion channel activity is dispensable for its function in PN dendrite targeting. Comprehensive genetic analyses revealed that Acj6 employs unique sets of cell-surface proteins in different PN types for dendrite targeting. Combinatorial expression of Acj6 wiring executors rescued acj6 mutant phenotypes with higher efficacy and breadth than expression of individual executors. Thus, Acj6 controls wiring specificity of different neuron types by specifying distinct combinatorial expression of cell- surface executors.
Evaluation of plasma N-terminal pro-B-type natriuretic peptide levels in healthy North American Salukis with normal echocardiographic measurements
Authors: Brennan Christopher , Gunasekaran Tamilselvam , Sanders Robert A 
Published: November 2021

AbstractMeasurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels has been shown to have clinical significance for diagnosis and management of heart disease in dogs. Evaluation of current reference limits for specific breeds is necessary to ensure the test can accurately distinguish between healthy and diseased animals. The objective of this study is to evaluate the adequacy of currently established NT-proBNP reference limits for clinical use in healthy Salukis. Cardiac health of 33 clinically healthy Salukis was evaluated via echocardiography using available breed standards. Plasma concentrations of NT-proBNP were measured using a commercially available assay. A one-sided 97.5 % upper reference limit for the NT-proBNP concentrations was calculated using non-parametric percentile method. The 97.5 % upper reference limit was 769 pmol/L (90% CI, 547-1214 pmol/L) for the study dogs. This upper reference limit was within the currently established non-breed specific NT-proBNP upper reference limit of 900 pmol/L. No relationship between sex, age, or body weight on plasma levels of NT-proBNP was noted. Results of this study supports the use of currently available non-breed specific NT-proBNP cut-off values for clinical evaluation of healthy Salukis.
Fine-mapping from summary data with the “Sum of Single Effects” model
Authors: Zou Yuxin , Carbonetto Peter , Wang Gao , Stephens Matthew 
Published: November 2021

AbstractIn recent work, Wang et al introduced the “Sum of Single Effects” (SuSiE) model, and showed that it provides a simple and efficient approach to fine-mapping genetic variants from individual-level data. Here we present new methods for fitting the SuSiE model to summary data, for example to single-SNP z-scores from an association study and linkage disequilibrium (LD) values estimated from a suitable reference panel. To develop these new methods, we first describe a simple, generic strategy for extending any individual-level data method to deal with summary data. The key idea is to replace the usual regression likelihood with an analogous likelihood based on summary data. We show that existing fine-mapping methods such as FINEMAP and CAVIAR also (implicitly) use this strategy, but in different ways, and so this provides a common framework for understanding different methods for fine-mapping. We investigate other common practical issues in fine-mapping with summary data, including problems caused by inconsistencies between the z-scores and LD estimates, and we develop diagnostics to identify these inconsistencies. We also present a new refinement procedure that improves model fits in some data sets, and hence improves overall reliability of the SuSiE fine-mapping results. Detailed evaluations of fine-mapping methods in a range of simulated data sets show that SuSiE applied to summary data is competitive, in both speed and accuracy, with the best available fine-mapping methods for summary data.Author summaryThe goal of fine-mapping is to identify the genetic variants that causally affect some trait of interest. Fine-mapping is challenging because the genetic variants can be highly correlated, due to a phenomenon called linkage disequilibrium (LD). The most successful current approaches to fine-mapping frame the problem as a variable selection problem, and here we focus on one such approach based on the “Sum of Single Effects” (SuSiE) model. The main contribution of this paper is to extend SuSiE to work with summary data, which is often accessible when the full genotype and phenotype data are not. In the process of extending SuSiE, we also developed a new mathematical framework that helps to explain existing fine-mapping methods for summary data, why they work well (or not), and under what circumstances. In simulations, we show that SuSiE applied to summary data is competitive with the best available fine-mapping methods for summary data. We also show how different factors such as accuracy of the LD estimates can affect the quality of the fine-mapping.
A microRNA cluster downstream of the selector gene Fezf2 coordinates fate specification with dendritic branching in cortical neurons
Authors: Iyer Asha , Siththanandan Verl B , Lu Victoria , Nair Ramesh , Vaasjo Lee O. , Galazo Maria J , Tharin Suzanne 
Published: November 2021

AbstractIn the cerebral cortex, cortical projection neurons comprise classes of neurons project to distant regions of the central nervous system. These neurons develop from the same progenitor pool, but they acquire strikingly different inputs and outputs to underpin strikingly different functions. The question of how corticospinal projection neurons - involved in motor function and implicated in paralysis - and callosal projection neurons - involved in cognitive function and implicated in autism - develop represents a fundamental and clinically important question in neurodevelopment. A network of transcription factors, including the selector gene Fezf2, is central to specifying cortical projection neuron fates. Gene regulation up- and down-stream of these transcription factors, however, is not well understood, particularly as it relates to the development of the major inputs to cortical projection neurons. Here we show that the miR-193b~365 microRNA cluster downstream of Fezf2 cooperatively represses the signaling molecule Mapk8, and impacts dendritic branching of cortical projection neurons.
Akaby - cell-free protein expression system for linear templates
Authors: Sato Wakana , Sharon Judee , Deich Christopher , Gaut Nathaniel , Cash Brock , Engelhart Aaron E , Adamala Katarzyna P 
Published: November 2021

AbstractCell-free protein expression is increasingly becoming popular for biotechnology, biomedical and research applications. Among cell-free systems, the most popular one is based on Escherichia coli (E. coli). Endogenous nucleases in E. coli cell-free transcription-translation (TXTL) degrade the free ends of DNA, resulting in inefficient protein expression from linear DNA templates. RecBCD is a nuclease complex that plays a major role in nuclease activity in E. coli, with the RecB subunit possessing the actual nuclease activity. We created a RecB knockout of an E. coli strain optimized for cell-free expression. We named this new strain Akaby. We demonstrated that Akaby TXTL successfully reduced linear DNA degradations, rescuing the protein expression efficiency from the linear DNA templates. The practicality of Akaby for TXTL is an efficient, simple alternative for linear template expression in cell-free reactions. We also use this work as a model protocol for modifying the TXTL source E. coli strain, enabling the creation of TXTL systems with other custom modifications.
Isolation and characterization of a novel temperate Escherichia coli bacteriophage, Kapi1, which modifies the O-antigen and contributes to the competitiveness of its host during colonization of the murine gastrointestinal tract
Authors: Pick Kat , Ju Tingting , Willing Benjamin P. , Raivio Tracy 
Published: November 2021

AbstractIn this study, we describe the isolation and characterization of novel bacteriophage vB_EcoP_Kapi1 (Kapi1) isolated from a strain of commensal Escherichia coli inhabiting the gastrointestinal tract of healthy mice. We show that Kapi1 is a temperate phage integrated into tRNA argW of strain MP1 and describe its genome annotation and structure. Kapi1 shows limited homology to other characterized prophages but is most similar to the seroconverting phages of Shigella flexneri, and clusters taxonomically with P22-like phages. The receptor for Kapi1 is the lipopolysaccharide O-antigen, and we further show that Kapi1 alters the structure of its hosts O-antigen in multiple ways. Kapi1 displays unstable lysogeny, and we find that lysogeny is favored during growth in simulated intestinal fluid. Furthermore, Kapi1 lysogens have a competitive advantage over their non-lysogenic counterparts both in vitro and in vivo, suggesting a role for Kapi1 during colonization. We thus report the use of MP1 and Kapi1 as a model system to explore the molecular mechanisms of mammalian colonization by E. coli to ask what the role(s) of prophages in this context might be.ImportanceAlthough research exploring the microbiome has exploded in recent years, our understanding of the viral component of the microbiome is lagging far behind our understanding of the bacterial component. The vast majority of intestinal bacteria carry prophages integrated into their chromosomes, but most of these bacteriophages remain uncharacterized and unexplored. Here, we isolate and characterize a novel temperate bacteriophage infecting a commensal strain of Escherichia coli. We aim to explore the interactions between bacteriophages and their hosts in the context of the gastrointestinal tract, asking what role(s) temperate bacteriophage may play in growth and survival of bacteria in the gut. Understanding the fundamental biology of gut commensal bacteria can inform the development of novel antimicrobial or probiotic strategies for intestinal infections.
Strategies for communicating health evidence to health policymakers and the population. Scoping review protocol
Authors: Martimbianco Ana Luiza Cabrera , Pacheco Rafael Leite , Bagattini Ângela Maria , Moreira Roberta de Fátima Carreira , Riera Rachel 
Published: November 2021

AbstractEvidence-based health information is provided by evidence synthesis and health technology assessments. Nevertheless, this information is complex for public understanding, pointing to the need to disseminate clearly. This scoping review aims to identify different strategies for communicating health evidence to policymakers and the general population. A scoping review will be conducted following the Joanna Briggs Institute Manual for Scoping Reviews. This comprehensive mapping will contribute to identifying the literature on health evidence-based information, identify the most appropriate approaches for each audience, and the literature gaps to guide future studies.
Measuring College Students’ with Disabilities Attitudes Toward Taking COVID-19 Vaccines
Authors: Taylor Z.W. , Charran Chelseaia 
Published: November 2021

AbstractThis survey explores attitudes of 245 currently enrolled college students with disabilities regarding their comfort taking a COVID-19 vaccine. Results suggest most college students with disabilities are willing to take a COVID-19 vaccine if their institution requires it to return to campus in subsequent semesters. However, many students with disabilities would not feel comfortable with a vaccine mandate mid-semester and would consider withdrawing, especially among older students with disabilities and first-generation college students with disabilities. Implications for postsecondary policy and leadership are addressed.
Geographical Distribution of Biomphalaria snails in East Africa
Authors: Magero Victor O. , Kisara Sammy , Wade Christopher M. 
Published: November 2021

ABSTRACTThere is limited information on the distribution of Biomphalaria snails, an important snail intermediate host of schistosomiasis, in East Africa. This study assessed the incidence and geographical distribution of Biomphalaria snails in Kenya, Uganda and Tanzania. Maximum Entropy modeling was used to predict the potential distribution of Biomphalaria snails, in line with habitat suitability. Malacological surveys were then conducted guided by MaxEnt predictions and information obtained from previous research papers. The surveys were conducted at a total of 156 sites including streams, rivers, lake shores, dams and irrigation canals over a 3-year period (2018 to 2020). Geographical coordinates, ecological and physicochemical information was recorded for the sites visited. Snails were identified morphologically, based on shell characters using established identification keys. Biomphalaria snails were found at 23.07% (36/156) of the sites sampled. Streams proved to be the habitats most preferred by Biomphalaria snails (50% of all of the sites where the snails were found were streams), followed by rivers (20.6%), irrigation canals (8.8%), lake shores (8.8%), springs (5.9%), and dams (5.9%) with snail abundance increasing with increase in temperature and decrease in water depth. Biomphalaria snails were found in the Lake Victoria basin, Mwea Irrigation Scheme and Eastern Province of Kenya, the Lake Albert region, Lango region, Soroti district, Lower Moshi irrigation scheme, Babati district, Iringa region, Tabora region and Kigoma region. Information on the distribution of Biomphalaria snails in East Africa will aid in developing prevention and control strategies for schistosomiasis.AUTHOR SUMMARYFew studies have been conducted on the distribution of Biomphalaria snails in East Africa with previous studies mostly isolated projects restricted to single divisions, districts and regions. Knowledge on the distribution of snail intermediate hosts can be helpful in establishing schistosomiasis transmission surveillance systems for detecting emerging and prevailing incidences of schistosomiasis. We undertook malacological surveys of freshwater sites across Kenya, Uganda and Tanzania. A total of 156 sites were sampled and Biomphalaria snails were found at 36 of the sites. Streams yielded the highest number of snails, in comparison to the other habitats that were sampled. Temperature and water depth were established to be statistically significant ecological and physicochemical factors that influence incidences and abundance of the snails. This study provides important information on the distribution of an important snail intermediate host in East Africa and the knowledge obtained herein can be helpful in establishing appropriate schistosomiasis control initiatives.
Density-dependent migration characteristics of cancer cells driven by pseudopod coordination
Authors: Burger Gerhard A. , van de Water Bob , Le Dévédec Sylvia E. , Beltman Joost B. 
Published: November 2021

AbstractThe ability of cancer cells to invade neighboring tissue from primary tumors is an important determinant of metastatic behavior. Quantification of cell migration characteristics such as migration speed and persistence helps to understand the requirements for such invasiveness. One factor that may influence invasion is how local tumor cell density shapes cell migration characteristics, which we here investigate with a combined experimental and computational modeling approach. First, we generated and analyzed time-lapse imaging data on two aggressive Triple-Negative Breast Cancer (TNBC) cell lines, HCC38 and Hs578T, during 2D migration assays at various cell densities. HCC38 cells exhibited a counter-intuitive increase in speed and persistence with increasing density, whereas Hs578T did not exhibit such an increase. Moreover, HCC38 cells exhibited strong cluster formation with active pseudopod-driven migration, especially at low densities, whereas Hs578T cells maintained a dispersed positioning. In order to obtain a mechanistic understanding of the density-dependent cell migration characteristics and cluster formation, we developed realistic spatial simulations using a Cellular Potts Model (CPM) with an explicit description of pseudopod dynamics. Model analysis demonstrated that strong coordination between pseudopods within single cells could explain the experimentally observed increase in speed and persistence with increasing density in HCC38 cells. Thus, the density-dependent migratory behavior could be an emergent property of single-cell characteristics without the need for additional mechanisms. This implies that coordination amongst pseudopods may play a role in the aggressive nature of cancers through mediating dispersal.
The role of risk rationing in rural credit demand and uptake: lessons from Kyrgyzstan
Authors: Kuhn Lena , Bobojonov Ihtiyor 
Published: November 2021

PurposeLack of access to credit is commonly held responsible for slow agricultural and rural development in low- and middle-income countries. This paper aims to investigate the contribution of demand- and supply-side factors, particularly the role of risk rationing, on credit application and uptake in the case example of Kyrgyzstan.Design/methodology/approachToward this aim, the study explores the determinants of credit behavior of 1,738 Kyrgyz sample farm households from 2013 to 2016 waves of the nationally representative “Life in Kyrgyzstan” (LIK) dataset along a hierarchical regression model, differentiating between factors influencing individual demand for credit and factors influencing supply for credit.FindingsThe results of our analysis indicate the relative importance of demand-side factors for credit applications, reflecting farmers' perceived risk of credit default and loss of collateral. Meanwhile, supply-side factors, such as real credit constraints and collateral requests, have a stronger influence on credit uptake rates and overall loan sums. These findings highlight the role of risk rationing for agricultural investment, suggesting a stronger focus of development policy on improving risk-sharing mechanisms for farmers, e.g. by developing the agricultural insurance sector.Originality/valueThe paper contributes novel evidence on the role of risk rationing in shaping the demand for formal credits for increasing agricultural and rural investment in low-income transition economies. Previous research has mostly focused on the role of credit supply, thus underrating the potential contribution of individual risk attitude, risk experience and risk sharing.
Pyocin‐mediated antagonistic interactions in Pseudomonas spp. isolated in James Ross Island, Antarctica
Authors: Snopková Kateřina , Dufková Kristýna , Chamrád Ivo , Lenobel René , Čejková Darina , Kosina Marcel , Hrala Matěj , Holá Veronika , Sedláček Ivo , Šmajs David 
Published: November 2021

SummaryInteractions within bacterial communities are frequently mediated by the production of antimicrobial agents. Despite the increasing interest in research of new antimicrobials, studies describing antagonistic interactions among cold‐adapted microorganisms are still rare. Our study assessed the antimicrobial interactions of 36 Antarctic Pseudomonas spp. and described the genetic background of these interactions in selected strains. The overall bacteriocinogeny was greater compared to mesophilic Pseudomonas non‐aeruginosa species. R‐type tailocins were detected on transmission electron micrographs in 16 strains (44.4%); phylogenetic analysis of the corresponding gene clusters revealed that the P. prosekii CCM 8878 tailocin was related to the Rp3 group, whereas the tailocin in Pseudomonas sp. CCM 8880 to the Rp4 group. Soluble antimicrobials were produced by eight strains (22.‐2%); gene mining found pyocin L homologues in the genomes of P. prosekii CCM 8881 and CCM 8879 and pyocin S9‐like homologues in P. prosekii CCM 8881 and Pseudomonas sp. CCM 8880. Analysis of secretomes confirmed the production of all S‐ and L‐type pyocin genes. Our results suggest that bacteriocin‐based inhibition plays an important role in interactions among Antarctic soil bacteria, and these native, cold‐adapted microorganisms could be a promising source of new antimicrobials.
Discovery of a New Middle Jurassic Dinosaur Site in Sichuan, China
Authors: HAO Baoqiao , ZHANG Qiannan , PENG Guangzhao , YE Yong 
Published: November 2021

AbstractThe Sichuan Basin, also known as the ‘Red Basin', is famous for its abundance of Mesozoic dinosaur fossils, especially in the Zigong area during the Jurassic era; the Middle Jurassic Shunosaurus and the Late Jurassic Mamenchisaurus faunal assemblages are the most representative. The Qinglongshan dinosaur fossil site is located in Fuxing, to the northwest of Rong County, Zigong City. This new site is situated within the Middle Jurassic Xiashaximiao Formation, and geologically is roughly equivalent to the well‐known Dashanpu dinosaur fossil site. More than 600 dinosaur fossils were found concentrated in the excavation area, including teeth; cervical, dorsal and caudal vertebrae; and various parts of appendicular skeletons. This fossil site is also most significant as it provides new information on non‐avian dinosaur life during the poorly understood Middle Jurassic.