bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAG3 regulation of Rab35 mediates the Endosomal Sorting Complexes Required for Transport /endolysosome pathway and tau clearance
Authors: Lin Heng , Tang Maoping , Ji Changyi , Girardi Peter , Cvetojevic Gregor , Chen Yunpo , Koren Shon A. , Johnson Gail V. W. 
Published: January 2021

AbstractBackgroundDeclining proteostasis with aging contributes to increased susceptibility to neurodegenerative diseases, including Alzheimer’s disease (AD). Emerging studies implicate impairment of the endosome-lysosome pathway as a significant factor in the pathogenesis of these diseases. Our lab was the first to demonstrate that BAG3 regulates phosphorylated tau clearance. However, we did not fully define how BAG3 regulates endogenous tau proteostasis, especially in the early stages of disease progression.MethodsMass spectrometric analyses were performed to identify neuronal BAG3 interactors. Multiple biochemical assays were used to investigate the BAG3-HSP70-TBC1D10B-Rab35-Hrs regulatory networks. Live-cell imaging was used to study the dynamic of endosomal pathway. Immunohistochemistry and immunoblotting were performed in human AD brains and BAG3 overexpressed P301S tau transgenic mice.ResultsThe primary group of neuronal BAG3 interactors identified are involved in the endocytic pathway. Among them were key regulators of small GTPases, such as the Rab35 GTPase activating protein, TBC1D10B. We demonstrated that a BAG3-HSP70-TBC1D10B complex attenuates the ability of TBC1D10B to inactivate Rab35. Thus, BAG3 interacts with TBC1D10B to support the activation of Rab35 and recruitment of Hrs, initiating ESCRT-mediated endosomal tau clearance. Further, TBC1D10B shows significantly less co-localization with BAG3 in AD brains than in age-matched controls. Overexpression of BAG3 in P301S tau transgenic mice increased the co-localization of phospho-tau with the ESCRT III protein CHMP2B and reduced the levels of the mutant human tau.ConclusionWe identified a novel BAG3-TBC1D10B-Rab35 regulatory axis that modulates ESCRT-dependent protein degradation machinery and tau clearance. Dysregulation of BAG3 could contribute to the pathogenesis of AD.
Adherent and suspension baby hamster kidney cells have a different cytoskeleton and surface receptor repertoire
Authors: Dill Veronika , Pfaff Florian , Zimmer Aline , Beer Martin , Eschbaumer Michael 
Published: January 2021

AbstractAnimal cell culture, with single cells growing in suspension, ideally in a chemically defined environment, is a mainstay of biopharmaceutical production. The synthetic environment lacks exogenous growth factors and usually requires a time-consuming adaptation process to select cell clones that proliferate in suspension to high cell numbers. The molecular mechanisms that facilitate the adaptation and that take place inside the cell are largely unknown. Especially for cell lines that are used for virus antigen production such as baby hamster kidney (BHK) cells, the restriction of virus growth through the evolution of undesired cell characteristics is highly unwanted. The comparison between adherently growing BHK cells and suspension cells with different susceptibility to foot-and-mouth disease virus revealed differences in the expression of cellular receptors such as integrins and heparan sulfates, and in the organization of the actin cytoskeleton. Transcriptome analyses and growth kinetics demonstrated the diversity of BHK cell clones and confirmed the importance of well-characterized parental cell clones and mindful screening to make sure that essential cellular features do not get lost during adaptation.
Dendritic cell CX3CR1 and macrophages F4/80 play a central role in between gut micro biome and inflammation in Arsenic induced mice
Authors: Tikka Chiranjeevi , Manthari Ram Kumar , Niu Ruiyan , Sun Zilong , Wang Jundong 
Published: January 2021

AbstractMicrobiota plays a crucial role to protect the intestine contrary to the harmful foreign microorganisms and organize the immune system via numerous mechanisms, which include either direct or indirect environmental factors. The underlying mechanism arsenic (As) influenced immune system and regulates inflammation by altering gut microbiome in ileum remains unclear. However, chronic exposure to arsenic (at doses of 0.15 mg or 1.5 mg or 15 mg As2O3/ L in drinking water) significantly increased mRNA and protein levels of F4/80 and CX3CR1, concurrently, the increased levels of mRNA and protein IFNγ, TNFα, IL-18 and decreased levels of IL-10 were found in both 3 and 6 months exposure periods. High-throughput sequencing analysis revealed that gut microbiota at phylum; family and taxonomical levels were showed the abundance of gut microbiota. Evidentially, the ultra-structure of intestinal villi, microbes engulfed and immune cell migration were showed by the transmission electron microscopy. Chronic exposure to As influenced the inflammation by changing immune system and altered gut microbiota. In this study we conclude that chronic exposure to As breakdown the normal gut microbial community and increase the pathogenicity, the resultant risk pathogen direct contact with intestinal immune system and regulate the inflammation.
Generalizable prediction of stimulus-independent, task-unrelated thought from functional brain networks
Authors: Kucyi Aaron , Esterman Michael , Capella James , Green Allison , Uchida Mai , Biederman Joseph , Gabrieli John D.E. , Valera Eve M. , Whitfield-Gabrieli Susan 
Published: January 2021

AbstractNeural substrates of “mind wandering” have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering—stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling—dominated by default-frontoparietal control subnetwork interactions—that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of attention-deficit/hyperactivity disorder (ADHD) adults. In three additional resting-state fMRI studies (totaln=1,115), including healthy and ADHD populations, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales, populations, and contexts.
Saccharide Analysis of Onion Outer Epidermal Walls
Authors: Wilson Liza A. , Deligey Fabien , Wang Tuo , Cosgrove Daniel J. 
Published: January 2021

AbstractBackgroundEpidermal cell walls have special structural and biological roles in the life of the plant. Typically they are multi-ply structures encrusted with waxes and cutin which protect the plant from dehydration and pathogen attack. These characteristics may also reduce chemical and enzymatic deconstruction of the wall for sugar analysis and conversion to biofuels. We have assessed the saccharide composition of the outer epidermal wall of onion scales with different analytical methods. This wall is a particularly useful model for cell wall imaging and mechanics.ResultsEpidermal walls were depolymerized by acidic methanolysis combined with 2 M trifluoracetic acid hydrolysis and the resultant sugars were analyzed by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Total sugar yields based on wall dry weight were low (53%). Removal of waxes with chloroform increased the sugar yields to 73% and enzymatic digestion did not improve these yields. Analysis by gas chromatography/mass spectrometry (GC/MS) of per-O-trimethylsilyl (TMS) derivatives of the sugar methyl glycosides produced by acidic methanolysis gave a high yield for galacturonic acid (GalA) but glucose (Glc) was severely reduced. In a complementary fashion, GC/MS analysis of methyl alditols produced by permethylation gave substantial yields for glucose and other neutral sugars, but GalA was severely reduced. Analysis of the walls by13C solid-state NMR confirmed and extended these results and revealed 15% lipid content after chloroform extraction (potentially cutin and unextractable waxes).ConclusionsAlthough exact values vary with the analytical method, our best estimate is that polysaccharide in the outer epidermal wall of onion scales is comprised of homogalacturonan (~50%), cellulose (~20%), galactan (~10%), xyloglucan (~10%) and smaller amounts of other polysaccharides. Low yields of specific monosaccharides by some methods may be exaggerated in epidermal walls impregnated with waxes and cutin and call for cautious interpretation of the results.
Nurse cell-derived small RNAs define paternal epigenetic inheritance inArabidopsis
Authors: Long Jincheng , Walker James , She Wenjing , Aldridge Billy , Gao Hongbo , Deans Samuel , Feng Xiaoqi 
Published: January 2021

AbstractThe plant male germline undergoes DNA methylation reprogramming, which methylates genesde novoand thereby alters gene expression and facilitates meiosis. Why reprogramming is limited to the germline and how specific genes are chosen is unknown. Here, we demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by germline-specific siRNAs transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) via activity of the tapetum-specific chromatin remodeler CLASSY3. Remarkably, tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Finally, we demonstrate that these nurse cell-derived siRNAs (niRNAs) silence germline transposons, thereby safeguarding genome integrity. Our results reveal that tapetal niRNAs are sufficient to reconstitute germline methylation patterns and drive extensive, functional methylation reprogramming analogous to piRNA-mediated reprogramming in animal germlines.
Defects in translation-dependent quality control pathways lead to convergent molecular and neurodevelopmental pathology
Authors: Terrey Markus , Adamson Scott I. , Chuang Jeffrey H. , Ackerman Susan L. 
Published: January 2021

AbstractTranslation-dependent quality control pathways such as no-go decay (NGD), non-stop decay (NSD) and nonsense-mediated decay (NMD) govern protein synthesis and proteostasis by resolving non-translating ribosomes and preventing the production of potentially toxic peptides derived from faulty and aberrant mRNAs. However, how translation is altered and thein vivodefects that arise in the absence of these pathways are poorly understood. Here, we show that the NGD/NSD factorsPeloandHbs1lare critical for cerebellar neurogenesis but expendable for survival of these neurons after development. Analysis of mutant embryonic fibroblasts revealed translational pauses, alteration of signaling pathways, and translational reprogramming. Similar effects on signaling pathways, the translatome and cerebellar development were observed upon deletion of the NMD factorUpf2.These data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses.
Benchmarking of lightweight-mapping based single-cell RNA-seq pre-processing
Authors: Booeshaghi A. Sina , Pachter Lior 
Published: January 2021

AbstractWe compare and benchmark the two lightweight-mapping tools that have been developed for pre-processing single-cell RNA-seq data, namely the kallisto-bustools and Salmon-Alevin-fry programs. We find that they output similar results, and to the extent that there are differences, they are irrelevant for downstream analysis. However, the Salmon-Alevin-fry program is significantly slower and requires much more memory to run, making it much more expensive to process large datasets limiting its use to larger servers.
Identification and analysis of novel variants in SARS-COV-2 genomes isolated from the Kingdom of Bahrain
Authors: bindayna Khalid M , Deifalla Abdel Halim , Mokbel Hicham Ezzat Mohammed 
Published: January 2021

AbstractThe challenges imposed by the ongoing outbreak of severe acute respiratory syndrome coronavirus-2 affects every aspect of our modern world, ranging from our health to our socio-economic needs. Our existence highly depends on the vaccine’s availability, which demands in-depth research of the available strains and their mutations. In this work, we have analyzed all the available SERS-CoV2 genomes isolated from the Kingdom of Bahrain in terms of their variance and origin analysis. We have predicted various known and unique mutations in the SERS-CoV2 isolated from Bahrain. The complexity of the phylogenetic tree and dot plot representation of the strains mentioned above with other isolates of Asia indicates the versatility and multiple origins of Bahrain’s SERS-CoV2 isolates. We have also identified two high impact spike mutations from these strains which increase the virulence of SARS-CoV2. Our research could have a high impact on vaccine development and distinguishes the source of SERS-CoV2 in the Kingdom of Bahrain.
COVID-19 Test Positivity Rate as a marker for hospital overload
Authors: Gaspari Mauro 
Published: January 2021

AbstractThe use of antigen tests for the diagnosis of COVID-19 in Italy has risen sharply in autumn 2020. Although, Italian regions like Alto Adige, Veneto, Toscana, Lazio, Piemonte and Marche did a large use of these tests for screening and surveillance purposes or for implementing diagnosis protocols, in addition to molecular tests, they were not reported in the statistics in the last months of 2020. As a consequence of this situation the test positivity rate (TPR) index, defined as the number of new positive cases divided by the number of tests, has lost in accuracy. Only in the recent days, starting from the 15th of January 2021, antigen tests have become part of the statistics for all the Italian regions. Despite the lack of data, we have noticed that TPR has a strong correlation with the number of patients admitted in hospitals, and that TPR peaks in general precede the peaks of hospitalized people which occur on average about 15 days later.In this paper, we have deepened this intuition, analysing the TPR course and its relationship with the number of hospitalized people. To conduct the study we have defined a novel version of the TPR index which takes into account the number of tests done with respect to the population (considering both molecular and antigen tests), the number of infected individuals, and the number of patients healed. Successively, starting from a limited set of data which were made available in November 2020, we have reconstructed the antigen tests time series of four Italian regions, and we computed the TPR index for them.The results show that TPR peaks precede peaks of hospitalized people in both the first and the second phases of the pandemic in Italy, provided that antigen tests are considered. Moreover, the TPR index trend, can be used to deduct important information on the course of the epidemic, and on the impact of COVID-19 in the health care system, which can be monitored in advance.
Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries
Authors: Landier Jordi , Paireau Juliette , Rebaudet Stanislas , Legendre Eva , Lehot Laurent , Fontanet Arnaud , Cauchemez Simon , Gaudart Jean 
Published: January 2021

AbstractHigher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low.During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated to SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1g/m3 was associated with a 0.15-unit increase of R0. Below 10°C, a temperature reduction of 1°C was associated with a 0.16-unit increase of R0.Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer-to winter-like conditions likely contributed to the intensification of the second wave in north-west hemisphere countries. Adjustments of the levels of social mobility restrictions need to account for increased SARS-CoV-2 transmissibility in winter conditions.
High infection attack rates of SARS-CoV-2 in Dutch households revealed by dense sampling
Authors: Reukers Daphne F.M. , van Boven Michiel , Meijer Adam , Rots Nynke , Reusken Chantal , Roof Inge , van Gageldonk-Lafeber Arianne B. , van der Hoek Wim , van den Hof Susan 
Published: January 2021

AbstractBackgroundIndoor environments are considered a main setting for transmission of SARS-CoV-2. Households in particular present a close-contact environment with high probability of transmission between persons of different ages and with different roles in society.MethodsComplete households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least three home visits were performed during 4-6 week of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, faeces and blood samples for molecular and serological analyses of all household members. Symptoms were recorded from two weeks before the first visit up to the last visit. Secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess transmission routes in the household.ResultsA total of 55 households with 187 household contacts were included. In 17 households no transmission took place, and in 11 households all persons were infected. Estimated SARs were high, ranging from 35% (95%CI: 24%-46%) in children to 51% (95%CI: 39%-63%) in adults. Estimated transmission rates in the household were high, with reduced susceptibility of children compared to adolescents and adults (0.67; 95%CI: 0.40-1.1).ConclusionEstimated SARs were higher than reported in earlier household studies, presumably owing to a dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated SAR in children was still high. Our results reinforce the role of households as main multiplier of SARS-CoV-2 infection in the population.Key pointsWe analyze data from a SARS-CoV-2 household study and find higher secondary attack rates than reported earlier. We argue that this is due to a dense sampling strategy that includes sampling at multiple time points and of multiple anatomical sites.
Neutralization of UK-variant VUI-202012/01 with COVAXIN vaccinated human serum
Authors: Sapkal Gajanan N. , Yadav Pragya D. , Ella Raches , Deshpande Gururaj R. , Sahay Rima R. , Gupta Nivedita , Mohan V Krishna , Abraham Priya , Panda Samiran , Bhargava Balram 
Published: January 2021

AbstractWe performed the plaque reduction neutralization test (PRNT50) using sera collected from the recipients of BBV152/COVAXIN™ against hCoV-19/India/20203522 (UK-variant) and hCoV27 19/India/2020Q111 (heterologous strain). A comparable neutralization activity of the vaccinated individuals sera showed against UK-variant and the heterologous strain with similar efficiency, dispel the uncertainty of possible neutralization escape.
An auxin-inducible, GAL4-compatible, gene expression system forDrosophila
Authors: McClure Colin D. , Hassan Amira , Aughey Gabriel N. , Butt Khushbakht , Estacio-Gómez Alicia , Duggal Aneisha , Sia Chee Ying , Barber Annika F. , Southall Tony D. 
Published: January 2021

AbstractThe ability to control transgene expression, both spatially and temporally, is essential for studying model organisms. InDrosophila, spatial control is primarily provided by the GAL4/UAS system, whilst temporal control relies on a temperature-sensitive GAL80 (which inhibits GAL4) and drug-inducible systems. However, these are not ideal. Shifting temperature can impact on many physiological and behavioural traits, and the current drug-inducible systems are either leaky, toxic, incompatible with existing GAL4-driver lines, or do not generate effective levels of expression. Here we describe the Auxin-inducible Gene Expression System (AGES). AGES relies on the auxin-dependent degradation of a ubiquitously expressed GAL80, and therefore, is compatible with existing GAL4-driver lines. Water-soluble auxin is added to fly food at a low, non-lethal, concentration, which induces expression comparable to uninhibited GAL4 expression. The system works in both larvae and adults, providing a stringent, non-lethal, cost-effective, and convenient method for temporally controlling GAL4 activity inDrosophila.
A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques
Authors: Hassan Ahmed O. , Feldmann Friederike , Zhao Haiyan , Curiel David T. , Okumura Atsushi , Tang-Huau Tsing-Lee , Case James Brett , Meade-White Kimberly , Callison Julie , Lovaglio Jamie , Hanley Patrick W. , Scott Dana P. , Fremont Daved H. , Feldmann Heinz , Diamond Michael S. 
Published: January 2021

SUMMARYThe deployment of a vaccine that limits transmission and disease likely will be required to end the Coronavirus Disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged one month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after SARS-CoV-2 challenge. As this single intranasal dose vaccine confers protection against SARS-CoV-2 in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.