bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal sensitivity and seasonal change in the gut microbiome of a desert ant, Cephalotes rohweri
Authors: McMunn Marshall S. , Hudson Asher I. , Zemenick Ash T. , Egerer Monika , Philpott Stacy M. , Vannette Rachel L. 
Published: December 2021

AbstractMicroorganisms within ectotherms must withstand the variable body temperatures of their hosts. Shifts in host body temperature resulting from climate change have the potential to shape ectotherm microbiome composition. Microbiome compositional changes occurring in response to temperature in nature have not been frequently examined, restricting our ability to predict microbe-mediated ectotherm responses to climate change. In a set of field-based observations, we characterized gut bacterial communities and thermal exposure across a population of desert arboreal ants (Cephalotes rohweri). In a paired growth chamber experiment, we exposed ant colonies to variable temperature regimes differing by 5 °C for three months. We found that the abundance and composition of ant-associated bacteria were sensitive to elevated temperatures in both field and laboratory experiments. We observed a subset of taxa that responded similarly to temperature in the experimental and observational study, suggesting a role of seasonal temperature and local temperature differences amongst nests in shaping microbiomes within the ant population. Bacterial mutualists in the genus Cephalotococcus (Opitutales: Opitutaceae) were especially sensitive to change in temperature—decreasing in abundance in naturally warm summer nests and warm growth chambers. We also report the discovery of a member of the Candidate Phlya Radiation (Phylum: Gracilibacteria), a suspected epibiont, found in low abundance within the guts of this ant species.
Ret loss-of-function decreases neural crest progenitor proliferation and restricts developmental fate potential during enteric nervous system development
Authors: Vincent Elizabeth , Chatterjee Sumantra , Cannon Gabrielle H. , Auer Dallas , Ross Holly , Chakravarti Aravinda , Goff Loyal A. 
Published: December 2021

AbstractThe receptor tyrosine kinase gene RET plays a critical role in the fate specification of enteric neural crest-derived cells (ENCDCs) during enteric nervous system (ENS) development. Pathogenic RET loss of function (LoF) alleles are associated with Hirschsprung disease (HSCR), which is marked by aganglionosis of the gastrointestinal (GI) tract. ENCDCs invade the developing GI tract, proliferate, migrate caudally, and differentiate into all of the major ENS cell types. Although the major phenotypic consequences and the underlying transcriptional changes from Ret LoF in the developing ENS have been described, its cell type and state-specific effects are unknown. Consequently, we performed single- cell RNA sequencing (scRNA-seq) on an enriched population of ENCDCs isolated from the developing GI tract of Ret null heterozygous and homozygous mouse embryos at embryonic day (E)12.5 and E14.5. We demonstrate four significant findings: (1) Ret-expressing ENCDCs are a heterogeneous population composed of ENS progenitors as well as glial and neuronal committed cells; (2) neurons committed to a predominantly inhibitory motor neuron developmental trajectory are not produced under Ret LoF, leaving behind a mostly excitatory motor neuron developmental program; (3) HSCR-associated and Ret gene regulatory network genes exhibit distinct expression patterns across Ret-expressing ENCDC with their expression impacted by Ret LoF; and (4) Ret deficiency leads to precocious differentiation and reduction in the number of proliferating ENS precursors. Our results support a model in which Ret contributes to multiple distinct cellular phenotypes associated with the proper development of the ENS, including the specification of inhibitory neuron subtypes, cell cycle dynamics of ENS progenitors, and the developmental timing of neuronal and glial commitment.Summary StatementRet LoF affects proper development of the mouse ENS through multiple distinct cellular phenotypes including restriction of neuronal fate potential, disruption of ENCDC migration, and modulation of progenitor proliferation rate.
A transient apical extracellular matrix relays cytoskeletal patterns to shape permanent acellular ridges on the surface of adult C. elegans
Authors: Katz Sophie S. , Barker Trevor J. , Maul-Newby Hannah M. , Sparacio Alessandro P. , Nguyen Ken C.Q. , Maybrun Chloe L. , Belfi Alexandra , Cohen Jennifer D. , Hall David H. , Sundaram Meera V. , Frand Alison R. 
Published: December 2021

SUMMARYApical extracellular matrices can form protruding structures such as denticles, ridges, scales, or teeth on the surfaces of epithelia. The mechanisms that shape these structures remain poorly understood. Here, we show how the actin cytoskeleton and a provisional matrix work together to sculpt acellular longitudinal alae ridges in the cuticle of adult C. elegans. Transient actomyosin-dependent constriction of the underlying lateral epidermis accompanies deposition of the provisional matrix at the earliest stages of alae formation. Actin is required to pattern the provisional matrix into longitudinal bands that are initially offset from the pattern of longitudinal actin filaments. These bands appear ultrastructurally as alternating regions of adhesion and separation within laminated provisional matrix layers. The provisional matrix is required to establish these demarcated zones of adhesion and separation, which ultimately give rise to alae ridges and their intervening valleys, respectively. Provisional matrix proteins shape the alae ridges and valleys but are not present within the final structure. We propose a morphogenetic mechanism wherein cortical actin patterns are relayed mechanically to the laminated provisional matrix to set up distinct zones of matrix layer separation and accretion that shape a permanent and acellular matrix structure.
Thresholding Approach For Low-Rank Correlation Matrix Based On Mm Algorithm
Authors: Tanioka Kensuke , Furotani Yuki , Hiwa Satoru 
Published: December 2021

ABSTRACTBackgroundLow-rank approximation is used for interpreting the features of a correlation matrix using visualization tools; however, a low-rank approximation may result in estimation that is far from zero even if the corresponding original value is zero. In such a case, the results lead to a misinterpretation.MethodsTo overcome this, we propose a novel approach to estimate a sparse low-rank correlation matrix based on threshold values. We introduce a new cross-validation function to tune the corresponding threshold values. To calculate the value of a function, the MM algorithm is used to estimate the sparse low-rank correlation matrix, and a grid search was performed to select the threshold values.ResultsThrough numerical simulation, we found that the false positive rate (FPR) and average relative error of the proposed method were superior to those of the tandem approach. For the application of microarray gene expression, the FPRs of the proposed approach withd= 2, 3, and 5 were 0.128, 0.139, and 0.197, respectively, whereas the FPR of the tandem approach was 0.285.ConclusionsWe propose a novel approach to estimate sparse low-rank correlation matrices. The advantage of the proposed method is that it provides results that are interpretable through the use of a heatmap, thereby avoiding result misinterpretations. We demonstrated the superiority of the proposed method through both numerical simulations and real examples.
Forecasting COVID-19 infection trends and new hospital admissions in England due to SARS-CoV-2 Variant of Concern Omicron
Authors: Gerli Alberto Giovanni , Centanni Stefano , Soriano Joan B , Ancochea Julio 
Published: December 2021

AbstractObjectivesOn November 26, 2021, WHO designated the variant B.1.1.529 as a new SARS-CoV-2 variant of concern (VoC), named Omicron, originally identified in South Africa. Several mutations in Omicron indicate that it may have an impact on how it spreads, resistance to vaccination, or the severity of illness it causes. We used our previous modelling algorithms to forecast the spread of Omicron in England.DesignWe followed EQUATOR’s TRIPOD guidance for multivariable prediction models.SettingEngland.ParticipantsNot applicable.InterventionsNon-interventional, observational study with a predicted forecast of outcomes.Main outcome measuresTrends in daily COVID-19 cases with a 7-day moving average and of new hospital admissions.MethodsModelling included a third-degree polynomial curve in existing epidemiological trends on the spread of Omicron and a new Gaussian curve to estimate a downward trend after a peak in England.ResultsUp to February 15, 2022, we estimated a projection of 250,000 COVID-19 daily cases of Omicron spread in the worse scenario, and 170,000 in the “best” scenario. Omicron might represent a relative increase from the background daily rates of COVID-19 infection in England of mid December 2021 of 1.9 to 2.8-fold. With a 5-day lag-time, daily new hospital admissions would peak at around 5,063 on January 23, 2022 in the worse scenario.ConclusionThis warning of pandemic surge of COVID-19 due to Omicron is calling for further reinforcing in England and elsewhere of universal hygiene interventions (indoor ventilation, social distance, and face masks), and anticipating the need of new total or partial lockdowns in England.
Diversity of microglial transcriptional responses during opioid exposure and neuropathic pain
Authors: Sypek Elizabeth I , Collins Hannah Y , McCallum William M , Bourdillon Alexandra T , Barres Ben A , Bohlen Christopher J , Scherrer Grégory 
Published: December 2021

AbstractMicroglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Following chronic opioid treatment and peripheral nerve injury (PNI) microglia in the spinal cord display similar morphological responses. Consistent with this observation, functional studies have suggested that microglia activated by PNI or opioids engage common molecular mechanisms to induce hypersensitivity. Here we conducted deep RNA sequencing of acutely isolated spinal cord microglia from male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple OIH and PNI models. Following PNI, we identify a common early proliferative transcriptional event across models that precedes the upregulation of histological markers of activation, followed by a delayed and injury-specific transcriptional response. Strikingly, we found no such transcriptional responses associated with opioid-induced microglial activation, consistent with histological data indicating that microglia number remain stable during morphine treatment. Collectively, these results reveal the diversity of pain-associated microglial transcriptomes and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other CNS pathologies.
Structural and functional characterizations of altered infectivity and immune evasion of SARS-CoV-2 Omicron variant
Authors: Cui Zhen , Liu Pan , Wang Nan , Wang Lei , Fan Kaiyue , Zhu Qianhui , Wang Kang , Chen Ruihong , Feng Rui , Jia Zijing , Yang Minnan , Xu Ge , Zhu Boling , Fu Wangjun , Chu Tianming , Feng Leilei , Wang Yide , Pei Xinran , Yang Peng , Xie Xiaoliang Sunney , Cao Lei , Cao Yunlong , Wang Xiangxi 
Published: December 2021

SummaryThe SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an “active” conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.
Computational analysis of transition temperatures (Tts) of proteins fused to elastin-like polypeptide (ELP): deep fake evaluation of proteins, linkers, and trailers features
Authors: Ghafari Mohammad Davoud , Rasooli Iraj , Khajeh Khosro , Dabirmanesh Bahareh , Ghafari Mohammadreza , Owlia Parviz 
Published: December 2021

AbstractThe phase transition temperature (Tt) prediction of the Elastin-like polypeptides (ELPs) is not trivial because it is related to complex sets of variables such as composition, sequence length, hydrophobic characterization, hydrophilic characterization, the sequence order in the fused proteins, linkers and trailer constructs. In this paper, two unique quantitative models are presented for the prediction of the Tt of a family of ELPs that could be fused to different proteins, linkers, and trailers. The lack of need to use multiple software, peptide information, such as PDB file, as well as knowing the second and third structures of proteins are the advantages of this model besides its high accuracy and speed. One of our models could predict the Tt values of the fused ELPs by entering the protein, linker, and trailer features with R2=99%. Also, another model is able to predict the Tt value by entering the fused protein feature with R2=96%. For more reliability, our method is enriched by Artificial Intelligence (AI) to generate similar proteins. In this regard, Generative Adversarial Network (GAN) is our AI method to create fake proteins and similar values. The experimental results show that our strategy for prediction of Tt is reliable in large data.Author SummaryThe application of Elastin-like polypeptides (ELPs) as a protein tag is now developed in a variety of biotechnology aspects especially in proteins purification and drug delivery. ELPs application as a protein tag is owed to retain the phase transition behavior when ELPs fused to other proteins, linkers and tags. ELPs undergo the phase transition behavior by changing from soluble phase to insoluble phase above its inverse transition temperature (Tt) within a short time span. This biophysical behavior is usually reversible at the temperature below the Tt. There are few reports for evaluation of the Tt of ELPs types by using the dissimilar equations and algorithms. Our current predictions are the most accurate calculations presented so far by using the protein, linker and trailer effects and the results were evaluated in accordance with the available experimental data. Furthermore, our results also show that our strategy for prediction of Tt is reliable in large data.
Multi-Wavelength Analytical Ultracentrifugation of Biopolymer Mixtures and Interactions
Authors: Henrickson Amy , Gorbet Gary E. , Savelyev Alexey , Kim Minji , Schultz Sarah K. , Ding Xiaozhe , Hargreaves Jason , Gradinaru Viviana , Kothe Ute , Demeler Borries 
Published: December 2021

AbstractMulti-wavelength analytical ultracentrifugation (MW-AUC) is a recent development made possible by new analytical ultracentrifuge optical systems. MW-AUC is suitable for a wide range of applications and biopolymer systems and is poised to become an essential tool to characterize macromolecular interactions. It adds an orthogonal spectral dimension to the traditional hydrodynamic characterization by exploiting unique chromophores in analyte mixtures that may or may not interact. Here we illustrate the utility of MW-AUC for representative classes of challenging biopolymer systems, including interactions between mixtures of different sized proteins with small molecules, mixtures of loaded and empty viral AAV capsids contaminated with free DNA, and mixtures of different proteins, where some have identical hydrodynamic properties, all of which are difficult to resolve with traditional AUC methods. We explain the improvement in resolution and information content obtained by this technique compared to traditional single- or dual-wavelength approaches. We discuss experimental design considerations and limitations of the method, and address the advantages and disadvantages of the two MW optical systems available today, and the differences in data analysis strategies between the two systems.
Efficient CRISPR/Cas12a-based genome editing toolbox for metabolic engineering in Methanococcus maripaludis
Authors: Bao Jichen , de Dios Mateos Enrique , Scheller Silvan 
Published: December 2021

ABSTRACTThe rapid-growing and genetically tractable methanogen Methanococcus maripaludis is a promising host organism for the biotechnological conversion of carbon dioxide and renewable hydrogen to fuels and value-added products. Expansion of its product scope through metabolic engineering necessitates reliable and efficient genetic tools, particularly for genome edits to the primary metabolism that affect cell growth. Here, we have designed a genome editing toolbox by utilizing Cas12a from Lachnospiraceae bacterium ND2006 (LbCas12a) in combination with the homology-directed repair machinery endogenously present in M. maripaludis. Remarkably, this toolbox can knock out target genes with a success rate of up to 95%, despite the hyper-polyploidy of M. maripaludis. For the purposes of demonstrating a large-sized deletion, we have replaced the flagellum operon (ca. 8.9 kbp) by the β-glucuronidase gene. To facilitate metabolic engineering and flux balancing in M. maripaludis, the relative strength of 15 different promoters were quantified in the presence of the two common growth substrates, formate or carbon dioxide and hydrogen. This CRISPR/LbCas12a toolbox can be regarded as a reliable and fast method for genome editing in a methanogen.
m7G cap-eIF4E interaction stimulates polysome formation by enhancing first-round initiation kinetics
Authors: Sun Lexi , Gaba Anthony , Wang Hongyun , Qu Xiaohui 
Published: December 2021

AbstractTranslation in eukaryotic cells occurs predominantly through a 7-methylguanosine (m7G) cap-dependent mechanism. m7G cap interactions with eukaryotic initiation factor 4E (eIF4E) facilitates 43S recruitment to the mRNA 5’ end and enhances the translation efficiency of mRNA. However, it remains poorly understood how m7G cap-eIF4E interactions affect polysome formation kinetics. Here, we examine the role of the m7G cap in polysome formation by utilizing a single-molecule approach to track individual ribosomes during active translation. Translation was monitored in wheat germ extract with capped and uncapped synthetic mRNAs and in HeLa extract with purified human eIF4E titration. The presence of the m7G cap and the supplementation of eIF4E to eIF4E-deficient extract enhanced the kinetics of the first initiation event of polysomes. Subsequent to the first initiation event, efficient polysome-forming initiation events occurred independent of mRNA m7G capping status and eIF4E concentration. Our results indicate that m7G cap-eIF4E interactions in wheat germ and HeLa extracts promote polysome formation by enhancing first-round initiation kinetics. The dynamics of individual translation events on polysomal mRNAs suggest that first-round initiation events activate mRNAs for efficient subsequent rounds of polysome-forming initiation.
Effect of lipopolysaccharide (LPS) on HAEC cells. Does nicotinamide N-methyltransferase sensitize HAEC cells to LPS?
Authors: Stępińska Oksana , Dymkowska Dorota , Mateuszuk Łukasz , Zabłocki Krzysztof 
Published: December 2021

AbstractTreatment of endothelial cells with bacterial lipopolysaccharide (LPS) evokes a number of metabolic and functional consequences which built a multifaceted physiological response of endothelium to bacterial infection. Here effects of LPS on human aortic endothelial cells (HAEC) have been investigated. Among the spectrum of biochemical changes substantially elevated N-nicotinamide methyltransferase (NNMT) protein level was particularly intriguing. This important enzyme may potentially affect cellular metabolism by two means: direct regulation of methylnicotinamide level and availability of nicotinamide, that at least potentially may influence NAD+ synthesis, and regulation of S-adenosylmethionine concentration and therefore controlling methylation of many proteins including chromatin. This may have epigenetic consequences. This paper is focused on NNMT, despite the fact that in the presence of LPS additional effects of this compound mask pure (canonical) consequences of the elevated NNMT protein which are an increased MNA synthesis or reduced NAD+ level. On the other hand, however, it has been shown that silencing of the NNMT-encoding gene prevents several changes which are observed in control HAECs treated with LPS. They include significantly increased calcium response to thapsigargin (store-operated calcium entry), altered energy metabolism which is switched to anaerobic glycolysis and rearrangement of the mitochondrial network. However, a biochemical mechanism behind the protective consequences of the NNMT deficiency in cells treated with LPS remains unexplained.
A Combined Immunophenotypic And Transcriptional Single-Cell Map Of First Trimester Human Fetal Liver Hematopoiesis
Authors: Sommarin Mikael N.E. , Olofzon Rasmus , Palo Sara , Dhapola Parashar , Karlsson Göran , Böiers Charlotta 
Published: December 2021

ABSTRACTKnowledge of human fetal blood development and how it differs from adult is highly relevant for our understanding of congenital blood and immune disorders as well as childhood leukemia, the latter known to originate in utero. Blood production during development occurs in waves that overlap in time and space adding to heterogeneity, which necessitates single cell approaches. Here, a combined single cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) the molecular profile of established immunophenotypic gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs) such as CD90 and CD49F were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow (BM) data set revealed that HSC-like cells were less frequent in FL, whereas cells with a lympho-myeloid signature were more abundant. Furthermore, an erythro-myeloid primed multipotent progenitor cluster was identified, potentially representing a transient, FL-specific progenitor. Based on the projection performed, up- and downregulated genes between fetal and adult cells were analyzed. In general, cell cycle pathways, including MYC targets were shown to be upregulated in fetal cells, whereas gene sets involved in inflammation and human leukocyte antigen (HLA) complex were downregulated. Importantly, a fetal core molecular signature was identified that could discriminate certain types of infant and childhood leukemia from adult counterparts.Our detailed single cell map presented herein emphasizes molecular as well as immunophenotypic differences between fetal and adult primitive blood cells, of significance for future studies of pediatric leukemia and blood development in general.