bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal dynamics of Na/K pump mediated memory traces: insights from conductance-based models ofDrosophilaneurons
Authors: Megwa Obinna F. , Pascual Leila May , Günay Cengiz , Pulver Stefan R. , Prinz Astrid A. 
Published: March 2023

AbstractSodium potassium ATPases (Na/K pumps) mediate long-lasting, dynamic cellular memories that can last tens of seconds. The mechanisms controlling the dynamics of this type of cellular memory are not well understood and can be counterintuitive. Here, we use computational modeling to examine how Na/K pumps and the ion concentration dynamics they influence shape cellular excitability. In aDrosophilalarval motor neuron model, we incorporate a Na/K pump, a dynamic intracellular Na+concentration, and a dynamic Na+reversal potential. We probe neuronal excitability with a variety of stimuli, including step currents, ramp currents, and zap currents, then monitor the sub- and suprathreshold voltage responses on a range of time scales. We find that the interactions of a Na+-dependent pump current with a dynamic Na+concentration and reversal potential endow the neuron with rich response properties that are absent when the role of the pump is reduced to the maintenance of constant ion concentration gradients. In particular, these dynamic pump-Na+interactions contribute to spike rate adaptation and result in long-lasting excitability changes after spiking and even after sub-threshold voltage fluctuations on multiple time scales. We further show that modulation of pump properties can profoundly alter a neuron’s spontaneous activity and response to stimuli by providing a mechanism for bursting oscillations. Our work has implications for experimental studies and computational modeling of the role of Na/K pumps in neuronal activity, information processing in neural circuits and the neural control of animal behavior.
Logging disrupts the ecology of molecules in headwater streams
Authors: Freeman Erika C , Emilson Erik JS , Webster Kara , Dittmar Thorsten , Tanentzap Andrew J 
Published: March 2023

AbstractGlobal demand for wood products is increasing forest harvest. One understudied consequence of logging is that it accelerates mobilization of dissolved organic matter (DOM) from soils to aquatic ecosystems. Here, we tested how logging changed DOM in headwaters of hardwood-dominated catchments in northern Ontario, Canada. We apply a before-after control-impact experiment across four catchments for three years. DOM concentration in streams from logged catchments quadrupled, on average, after the first year post-harvest, but resulting changes to the molecular composition of DOM persisted for at least two-years. Ultrahigh-resolution mass spectrometry revealed that DOM within logged catchments was more energy-rich and chemically diverse than in controls, with novel highly unsaturated polyphenols, carboxylic-rich alicyclic, and nitrogen-containing formulae. The molecular composition of stream DOM measured fortnightly post-harvest was most strongly associated with DOM composition within intermediate and deeper layers of contributing soils, likely due to increased hydrological connectivity post-harvest. We estimate logging increased the total annual flux of dissolved organic carbon in streams by 6.4% of extracted wood carbon, and this carbon was more likely to be released into the atmosphere. Carbon accounting of forestry, including as a natural climate solution, must now consider the transport and fate of DOM from land into water.
Spatial positioning of preimplantation mouse embryo blastomeres is regulated by mTORC1 and 7mG-cap dependent translation at the 8- to 16-cell transition
Authors: Gahurova Lenka , Tomankova Jana , Cerna Pavlina , Bora Pablo , Kubickova Michaela , Virnicchi Giorgio , Kovacicova Kristina , Potesil David , Hruska Pavel , Zdrahal Zbynek , Anger Martin , Susor Andrej , Bruce Alexander W. 
Published: March 2023

ABSTRACTPreimplantation stages of mouse embryo development involve temporal and spatial specification and segregation of three late blastocyst cell lineages; trophectoderm (TE), primitive endoderm (PrE) and epiblast (EPI). Spatial separation of the outer TE lineage from the two inner cell mass (ICM) lineages (PrE and EPI) starts with the 8- to 16-cell transition and concludes following transit through the 16- to 32-cell stages. This results in an early blastocyst ICM derived from descendants of primary founding inner cells and a secondarily contributed population, of which subsequent relative EPI versus PrE potencies are subject to debate. Here, we report generation of primary but not the secondary ICM populations is highly dependent on temporally discreet activation of the mammalian target of Rapamycin (mTOR – specifically mTORC1) during M-phase entry at the 8-cell stage. This role is mediated via regulation of the 7-methylguanosine-(7mG) cap binding initiation complex (EIF4F), linked to translation of a subset of key mRNAs containing 5’ UTR terminal oligopyrimidine (TOP-) or TOP-like sequence motifs; as knockdown of identified TOP-like motif containing transcripts also impairs generation of 16-cell stage primary ICM founders. However, mTOR inhibition induced ICM cell number deficits at the early blastocyst stage can be compensated by the late blastocyst stage, in the absence of inhibition. This compensation is likely initiated at the 32-cell stage when supernumerary outer cells in mTOR-inhibited embryos exhibit molecular characteristics of inner cells. Collectively, the data identify a novel mechanism specifically governing initial spatial segregation of blastomeres in the mouse embryo, that is distinct from those directing subsequent inner cell formation and contributes to germane segregation of late blastocyst lineages.
A host recognition module shared among distantAlteromonasbacteriophage families features tail fibers with transient chaperone “caps”
Authors: Gonzalez-Serrano Rafael , Rosselli Riccardo , Roda-Garcia Juan J. , Martin-Cuadrado Ana-Belen , Rodriguez-Valera Francisco , Dunne Matthew 
Published: March 2023

AbstractThe host recognition modules encoding the injection machinery and receptor binding proteins (RBPs) of bacteriophages are variable genomic units predisposed to mutation and recombination to maintain infectivity toward co-evolving bacterial hosts. In this study, we reveal howAlteromonas mediterraneaschitovirus A5 shares its host recognition module, including tail fiber (TF) and cognate chaperone, with phages from distantly related families includingAlteromonasmyovirus, V22. While the chaperone of V22 is essential for producing active TFs, here we demonstrate production of functional A5 TFs regardless of chaperone co-expression. AlphaFold-generated models of TF and chaperone pairs from phages A5, V22, and otherAlteromonasphages reveal how amino acid insertions within both A5-like proteins results in a knob domain duplication in the TF and a β-hairpin “tentacle” extension of the chaperone. These structural modifications are linked to chaperone dependency differences between the A5 and V22 TFs. Structural similarity between the chaperones and intramolecular chaperone domains of other phage RBPs suggests an additional function of these chaperones as transient TF “caps”. Finally, our identification of homologous host recognition modules used by morphologically distinct phages implies that HGT and recombination events between unrelated phages may be a more common process than previously thought amongCaudoviricetesphages.
Dissecting embryonic and extra-embryonic lineage crosstalk with stem cell co-culture
Authors: Wei Yulei , Zhang E , Yu Leqian , Ci Baiquan , Guo Lei , Sakurai Masahiro , Takii Shino , Liu Jian , Schmitz Daniel A. , Ding Yi , Zhan Linfeng , Zheng Canbin , Sun Hai-Xi , Xu Lin , Okamura Daiji , Ji Weizhi , Tan Tao , Wu Jun 
Published: March 2023

SUMMARYFaithful embryogenesis requires precise coordination between embryonic and extraembryonic tissues. Although stem cells from embryonic and extraembryonic origins have been generated for several mammalian species(Bogliotti et al., 2018; Choi et al., 2019; Cui et al., 2019; Evans and Kaufman, 1981; Kunath et al., 2005; Li et al., 2008; Martin, 1981; Okae et al., 2018; Tanaka et al., 1998; Thomson et al., 1998; Vandevoort et al., 2007; Vilarino et al., 2020; Yu et al., 2021b; Zhong et al., 2018), they are grown in different culture conditions with diverse media composition, which makes it difficult to study cross-lineage communication. Here, by using the same culture condition that activates FGF, TGF-β and WNT signaling pathways, we derived stable embryonic stem cells (ESCs), extraembryonic endoderm stem cells (XENs) and trophoblast stem cells (TSCs) from all three founding tissues of mouse and cynomolgus monkey blastocysts. This allowed us to establish embryonic and extraembryonic stem cell co-cultures to dissect lineage crosstalk during early mammalian development. Co-cultures of ESCs and XENs uncovered a conserved and previously unrecognized growth inhibition of pluripotent cells by extraembryonic endoderm cells, which is in part mediated through extracellular matrix signaling. Our study unveils a more universal state of stem cell self-renewal stabilized by activation, as opposed to inhibition, of developmental signaling pathways. The embryonic and extraembryonic stem cell co-culture strategy developed here will open new avenues for creating more faithful embryo models and developing more developmentally relevant differentiation protocols.
Development of Fully Human, Bispecific Antibodies that Effectively Block Omicron Variant Pseudovirus Infections
Authors: Allen Jason , Gonzalez Michelle , Kaur Jasbir , Smith Melinda , You Junping , Yang Guojun , Zha Dongxing , Tian Ze , Al-Shami Amin , Shi Chunhua , Molldrem Jeffrey , Heffernan Tim 
Published: March 2023

AbstractThe emergence of highly immune invasive and transmissible variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has decreased the effectiveness of existing vaccines. It is, therefore, critical to develop effective and safe therapeutics for SARS-CoV-2 infections, especially for the most vulnerable and immunocompromised patients. Neutralizing antibodies have been shown to be successful at preventing severe disease from early SARS-CoV-2 strains, although their efficacy has diminished with the emergence of new variants. Here, we aim to develop fully human and broadly neutralizing monoclonal (mAb) and bispecific (BsAb) antibodies against SARS-CoV-2 and its variants. Specifically, we first identified two antibodies from human transgenic mice that bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and are capable of neutralizing SARS-CoV-2 and variants of concern with high to moderate affinity. Two non-competing clones with the highest affinity and functional blocking of ACE2 binding were then selected to be engineered into two BsAbs, which were then demonstrated to have relatively improved affinity, ACE2 blocking ability, and pseudovirus inhibition against several variants, including Omicron (B.1.1.529). Our findings provide one mAb candidate and two bsAb candidates for consideration of further clinical development and suggest that the bispecific format may be more effective than mAbs for SARS-CoV-2 treatment.
An innate granuloma eradicates an environmental pathogen usingGsdmdandNos2
Authors: Harvest Carissa K. , Abele Taylor J. , Yu Chen , Beatty Cole J. , Amason Megan E. , Billman Zachary P. , DePrizio Morgan A. , Lacey Carolyn A. , Maltez Vivien I. , Larson Heather N. , McGlaughon Benjamin D. , Saban Daniel R. , Montgomery Stephanie A. , Miao Edward A. 
Published: March 2023

SUMMARYGranulomas often form around pathogens that cause chronic infections. Here, we discover a novel granuloma model in mice.Chromobacterium violaceumis an environmental bacterium that stimulates granuloma formation that not only successfully walls off but also clears the infection. The infected lesion can arise from a single bacterium that replicates in the presence of a neutrophil swarm. Bacterial replication ceases when macrophages organize around the infection and form a granuloma. This granuloma response is accomplished independently of adaptive immunity that is typically required to organize granulomas. TheC. violaceum-induced granuloma requires at least two separate defense pathways, gasdermin D and iNOS, to maintain the integrity of the granuloma architecture. These innate granulomas successfully eradicateC. violaceuminfection. Therefore, this newC. violaceum-induced granuloma model demonstrates that innate immune cells successfully organize a granuloma and thereby eradicate infection by an environmental pathogen.
O-GlcNAc modification forces the formation of an α-Synuclein amyloid-strain with notably diminished seeding activity and pathology
Authors: Balana Aaron T. , Mahul-Mellier Anne-Laure , Nguyen Binh A , Horvath Mian , Javed Afraah , Hard Eldon R. , Jasiqi Yllza , Singh Preeti , Afrin Shumaila , Pedretti Rose , Singh Virender , Lee Virginia M.-Y. , Luk Kelvin C. , Saelices Lorena , Lashuel Hilal A. , Pratt Matthew R. 
Published: March 2023

ABSTRACTThe process of amyloid fibril formation remains one of the primary targets for developing diagnostics and treatments for several neurodegenerative diseases (NDDs). Amyloid-forming proteins such α-Synuclein and Tau, which are implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, can form different types of fibril structure, or strains, that exhibit distinct structures, toxic properties, seeding activities, and pathology spreading patterns in the brain. Therefore, understanding the molecular and structural determinants contributing to the formation of different amyloid strains or their distinct features could open new avenues for developing disease-specific diagnostics and therapies. In this work, we report that O-GlcNAc modification of α-Synuclein monomers results in the formation of amyloid fibril with distinct core structure, as revealed by Cryo-EM, and diminished seeding activity in seeding-based neuronal and rodent models of Parkinson’s disease. Although the mechanisms underpinning the seeding neutralization activity of the O-GlcNAc modified fibrils remain unclear, ourin vitromechanistic studies indicate that heat shock proteins interactions with O-GlcNAc fibril inhibit their seeding activity, suggesting that the O-GlcNAc modification may alter the interactome of the α-Synuclein fibrils in ways that lead to reduce seeding activity in vivo. Our results show that post-translational modifications, such as O-GlcNAc modification, of α-Synuclein are key determinants of α-Synuclein amyloid strains and pathogenicity. These findings have significant implications for how we investigate and target amyloids in the brain and could possibly explain the lack of correlation between amyloid burden and neurodegeneration or cognitive decline in some subtypes of NDDs.
Insulin secretion chip (InS-chip) reveals two peaks within first-phase that temporally coincide with a transition in glucose metabolism
Authors: Wang Yufeng , Regeenes Romario , Memon Mahnoor , Rocheleau Jonathan V. 
Published: March 2023

AbstractFirst-phase glucose-stimulated insulin secretion is mechanistically linked to type 2 diabetes yet the underlying metabolism driving this early stage of secretion is difficult to discern due to significant islet-to-islet variability. Here, we miniaturize a fluorescence anisotropy immunoassay onto a microfluidic device to measure C-peptide secretion from individual islets as a surrogate for insulin (InS-chip). This method measures secretion from up to four islets at a time with ∼7 s resolution while providing an optical window for real-time live cell imaging. Using the InS-chip, we reveal for the first time two glucose-dependent peaks of insulin secretion (i.e., a double peak) within the first phase (<10 min). By combining real-time secretion and live cell imaging, we show that islets transition from glycolytic to OxPhos-driven metabolism at the nadir of the peaks. Overall, these data validate the InS-chip to measure glucose-stimulated insulin secretion while revealing the first-phase secretion contains two peaks defined by a shift in glucose metabolism.Significance StatementLoss of the first phase of glucose-stimulated insulin secretion is one of the earliest signs of type 2 diabetes (T2D). Yet current strategies to measure the early dynamics are inadequate due to the need to pool secretion from multiple islets. In this study, we designed an islet-on-a-chip microfluidic device (InS-chip) to measure insulin secretion from individual islets with <7 s temporal resolution. Our design leaves an optical window for coupled live cell imaging to tease apart the metabolism underlying secretion. Our data reveal that first-phase insulin secretion is composed of two peaks that coincide with a shift in glucose metabolism.
Modulating Factors Affecting Sports-Related Concussion Exposures: A Systematic Review and Analysis
Authors: Edelstein Rachel , Van Horn John Darrell 
Published: March 2023

ABSTRACTIn the United States, the Centers for Disease Control and Prevention estimates that 1.6-to-3.8 million concussions occur annually in sports. This quantitative meta-analysis of one hundred and twenty-one sports-related concussion studies, across fourteen youth sports, investigated the contributions of statistical constructs, and diagnostic methods, considering the impact of nationwide laws and education, as well as distinguished injury surveillance techniques, in this widely diverse literature. Concussion study research designs were found to have differing diagnostic, statistical, and methodological techniques. Among less frequently studied, non-high-contact, sports, a meta-analysis investigated relative rates of concussion and sex differences. Findings indicated considerable variation in reported concussion incidence rates due to the sport played, but also due to the number of study authors listed and the proportion of female athletes represented. Such factors likely influence the reported incidence of sports-related concussions, especially in sports not typically associated with a high risk of head injuries. To better capture the incidence of sports-related head injuries and concussion, a universal data repository for youth concussions might be established to provide an ongoing, comprehensive, and accurate picture of concussions in youth and collegiate athletics.
Reliability and validity of clinical tests of cardiorespiratory fitness: A systematic review and meta-analysis
Authors: Harkin Samuel , Cousins Stephen , Locke Simon , Gordon Brett 
Published: March 2023

AbstractIntroductionInsufficient physical activity is a significant contributor to non-communicable disease amongst the global population. Insufficient physical activity is directly linked with reduced cardiorespiratory fitness (CRF). CRF is as strong a predictor of mortality as well-established risk-factors such as smoking, hypertension, dyslipidaemia, and type 2 diabetes mellitus, however, it remains the only major risk factor not routinely assessed in primary health care settings. The aim of this review was to assess the validity and reliability of existing submaximal tests of CRF which can be employed in a standard medical consultation for the estimation of CRF and physical function in adults.MethodsA systematic review of the scientific literature was undertaken to find all studies reporting the reliability and/or validity of submaximal tests of CRF and physical function. Studies published up to 12 January 2023 were included in the search of the Medline, Embase, Cinahl, SPORTdiscus, Cochrane library, Informit Health and Web of Science databases. Risk of bias was assessed using the JBI critical appraisal checklist for analytical cross-sectional studies. Data including reliability of the submaximal protocols as measured by test-retest Pearson’sr(r) or Intraclass co-efficient (ICC); and validity as measured by the correlation between the submaximal protocol results and the graded exercise test results (r) was extracted. Meta-analyses were performed to determine the overall mean r of the correlation coefficients.ResultsIn total 1754 studies were identified. Following screening, 143 studies including 15,760 participants were included. All clinical tests included in meta-analysis demonstrated strong reliability. The Siconolfi step test (r=0.81), Incremental shuttle walk test (r=0.768) and 1- minute sit-to-stand test (r=0.65) demonstrated strongest validity following meta-analysis.ConclusionBased on the validity of the tests outlined, these can be used as an acceptable method of estimating VO2peak in a broad population, without the cost and access issues of formal GXT.
Comparison of cold sprayed and arc sprayed Zn15Al alloy coating on AZ91D magnesium substrate
Authors: Huang Guosheng , Fu Wei , Zhou Juan , Ma Li , Wang Hongren , Li Xiangbo 
Published: March 2023

Purpose
The purpose of this paper is to examine the performance of cold-sprayed Zn15Al alloy coating whether it is capable of protecting magnesium alloy from corrosion, and to compare it with arc-sprayed Zn15Al alloy coating.

Design/methodology/approach
In this paper, Zn15Al alloy coating was prepared with CS-6000 cold spraying system and HDX-800 arc-sprayed system. Corrosion behaviors of the two kinds of coatings were examined with potentiodynamic polarization curves methods combined with SEM, EDS, XRD, etc.

Findings
Corrosion behavior of cold-sprayed Zn15Al alloy coating is superior to arc-sprayed Zn15Al alloy coating. The bonding strength and density of cold-sprayed Zn15Al alloy coating is much higher than that of arc-sprayed Zn15Al alloy coating. The cold-sprayed coating has a dense structure which separate magnesium from corrosion medium completely. The samples behave as Zn15Al instead of AZ91D alloy. The coating has a low probability of pitting corrosion comparing with cold sprayed Al coating through potentiodynamic polarization curve.

Practical implications
Cold-sprayed Zn15Al coating can be used to improve the anticorrosion performance of magnesium significantly and low down the risk of pitting corrosion of coating.

Social implications
Cold-sprayed Zn15Al coating is an environmentally friendly anticorrosion method for light alloy, which is also the most effective way among thermal spray, chemical vapor deposition, sol–gel, plating and anodizing or microarc oxidation.

Originality/value
The present paper used cold spray method to deposit Zn15Al coating, which has an overwhelming performance both in physical and anticorrosion to traditional thermal spray method.