bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes
Authors: Neel Brandon L. , Nisler Collin R. , Walujkar Sanket , Araya-Secchi Raul , Sotomayor Marcos 
Published: July 2021

AbstractCadherins are a superfamily of adhesion proteins involved in a variety of biological processes that include the formation of intercellular contacts, the maintenance of tissue integrity, and the development of neuronal circuits. These transmembrane proteins are characterized by ectodomains composed of a variable number of extracellular cadherin (EC) repeats that are similar but not identical in sequence and fold. E-cadherin, along with desmoglein and desmocollin proteins, are three classical-type cadherins that have slightly curved ectodomains and engage in homophilic and heterophilic interactions through an exchange of conserved tryptophan residues in their N-terminal EC1 repeat. In contrast, clustered protocadherins are straighter than classical cadherins and interact through an antiparallel homophilic binding interface that involves overlapped EC1 to EC4 repeats. Here we present molecular dynamics simulations that model the adhesive domains of these cadherins using available crystal structures, with systems encompassing up to 2.8 million atoms. Simulations of complete classical cadherin ectodomain dimers predict a two-phased elastic response to force in which these complexes first softly unbend and then stiffen to unbind without unfolding. Simulated α, β, and γ clustered protocadherin homodimers lack a two-phased elastic response, are brittle and stiffer than classical cadherins, and exhibit complex unbinding pathways that in some cases involve transient intermediates. We propose that these distinct mechanical responses are important for function, with classical cadherin ectodomains acting as molecular shock absorbers and with stiffer clustered protocadherin ectodomains facilitating overlap that favors binding specificity over mechanical resilience. Overall, our simulations provide insights into the molecular mechanics of single cadherin dimers relevant in the formation of cellular junctions essential for tissue function.Statement of SignificanceMulticellular organisms rely on cellular adhesion to survive, and this adhesion is mediated by diverse sets of proteins that include cadherins responsible for organ assembly and tissue integrity maintenance. As parts of cell-cell junctions in epithelial and cardiac tissues, classical cadherins experience forces and must be mechanically robust. In contrast, clustered protocadherins are responsible for neuronal connectivity and are exposed to more subtle mechanical stimuli. We used simulations to study the mechanics of isolated cadherin complexes and found that classical cadherins exhibit a two-phased elastic response that might prevent loss of adhesion during mild mechanical stress. Conversely, we predict that clustered protocadherin complexes are brittle. Our results suggest that each set of cadherins has evolved to adopt distinct mechanical properties.
Age-Related Differences in Ventral Striatal and Default Mode Network Function During Reciprocated Trust
Authors: Fareri Dominic S. , Hackett Katherine , Tepfer Lindsey J. , Kelly Victoria , Henninger Nicole , Reeck Crystal , Giovannetti Tania , Smith David V. 
Published: July 2021

AbstractSocial relationships change across the lifespan as social networks narrow and motivational priorities shift to the present. Interestingly, aging is also associated with changes in executive function, including decision-making abilities, but it remains unclear how age-related changes in both domains interact to impact financial decisions involving other people. To study this problem, we recruited 50 human participants (Nyounger= 26, ages 18-34; Nolder= 24, ages 63-80) to play an economic trust game as the investor with three partners (friend, stranger, and computer) who played the role of investee. Investors underwent functional magnetic resonance imaging (fMRI) during the trust game while investees were seated outside of the scanner. Building on our previous work with younger adults showing both enhanced striatal responses and altered default-mode network (DMN) connectivity as a function of social closeness during reciprocated trust, we predicted that these relations would exhibit age-related differences. We found that striatal responses to reciprocated trust from friends relative to strangers and computers were blunted in older adults relative to younger adults, thus supporting our primary pre-registered hypothesis regarding social closeness. We also found that older adults exhibited enhanced DMN connectivity with the temporoparietal junction (TPJ) during reciprocated trust from friends compared to computers while younger adults exhibited the opposite pattern. Taken together, these results advance our understanding of age-related differences in sensitivity to social closeness in the context of trusting others.
Stabilizing selection shapes variation in phenotypic plasticity
Authors: Becker Dörthe , Barnard-Kubow Karen , Porter Robert , Edwards Austin , Voss Erin , Beckerman Andrew P. , Bergland Alan O. 
Published: July 2021

AbstractThe adaptive nature of phenotypic plasticity is widely documented in natural populations. However, little is known about the evolutionary forces that shape genetic variation in plasticity within populations. Here we empirically address this issue by testing the hypothesis that stabilizing selection shapes genetic variation in the anti-predator developmental plasticity ofDaphnia pulex. The anti-predator morphological defense is characterized by pedestal and spikes that grow on the back of theDaphnianeck following exposure to predator cure. We characterized variation in this plasticity using a novel, high-throughput phenotyping method that describes the entire dorsal shape amongst >100D. pulexstrains originating from a natural population in the UK. We found low genetic diversity for morphological defenses among genetically diverse clones upon predation risk exposure. The strongest reduction in genetic variation was observed in areas of greatest phenotypic plasticity, which we interpret as evidence of stabilizing selection. By assessing among-clone variance in clonally related, field derived strains, we contrasted mutational variation (Vm) to standing variation (Vg). We found that Vg/Vmis lowest in areas of greatest plasticity. These data strongly suggest that stabilizing selection operates directly on phenotypic plasticity, providing a rare glimpse into the evolution of fitness related traits in natural populations.
A cohesin traffic pattern genetically linked to gene regulation
Authors: Valton Anne-Laure , Venev Sergey V. , Mair Barbara , Khokhar Eraj , Tong Amy H. Y. , Usaj Matej , Chan Katherine S. K. , Pai Athma A. , Moffat Jason , Dekker Job 
Published: July 2021

SUMMARYCohesin-mediated loop extrusion folds interphase chromosomes at the ten to hundreds kilobases scale. This process produces structural features such as loops and topologically associating domains. We identify three types of cis-elements that define the chromatin folding landscape generated by loop extrusion. First, CTCF sites form boundaries by stalling extruding cohesin, as shown before. Second, transcription termination sites form boundaries by acting as cohesin unloading sites. RNA polymerase II contributes to boundary formation at transcription termination sites. Third, transcription start sites form boundaries that are mostly independent of cohesin, but are sites where cohesin can pause. Together with cohesin loading at enhancers, and possibly other cis-elements, these loci create a dynamic pattern of cohesin traffic along the genome that guides enhancer-promoter interactions. Disturbing this traffic pattern, by removing CTCF barriers, renders cells sensitive to knock-out of genes involved in transcription initiation, such as the SAGA and TFIID complexes, and RNA processing such DEAD-Box RNA helicases. In the absence of CTCF, several of these factors fail to be efficiently recruited to active promoters. We propose that the complex pattern of cohesin movement along chromatin contributes to appropriate promoter-enhancer interactions and localization of transcription and RNA processing factors to active genes.HIGHLIGHTSAt least three types of chromatin boundaries regulate a cohesin traffic pattern.The cohesin traffic pattern guides enhancer-promoter interactions.Removing CTCF renders cells sensitive to deletion of RNA processing and gene regulation genes.Depleting CTCF affects localization of RNA processing and gene regulatory proteins.
ASSEMBLY AND DYNAMICS OF MICROBIAL COMMUNITIES IN GRANULAR, FIXED-BIOFILM AND PLANKTONIC METHANOGENIC MICROBIOMES VALORIZING LONG CHAIN FATTY ACID (LCFA)-RICH WASTEWATER
Authors: Singh Suniti , Rinta-Kanto Johanna M. , Lens Piet N. L. , Kokko Marika , Rintala Jukka , O’Flaherty Vincent , Ijaz Umer Zeeshan , Collins Gavin 
Published: July 2021

AbstractDistinct microbial assemblages are engineered in anaerobic digestion (AD) reactors to drive sequential conversions of organics to methane. The spatio-temporal development of three such assemblages (granules, biofilms, planktonic) derived from the same inoculum was studied in replicated bioreactors treating long-chain fatty acids (LCFA)-rich wastewater at 20°C at hydraulic retention times (HRTs) of 12-72 h. We found granular, biofilm and planktonic assemblages differentiated by diversity, structure, and assembly mechanisms; demonstrating a spatial compartmentalisation of the microbiomes from the initial community reservoir. Our analysis linked abundant Methanosaeta and Syntrophaceae-affiliated taxa (Syntrophus and uncultured) to their putative, active roles in syntrophic LCFA bioconversion. LCFA loading rates (stearate, palmitate), and HRT, were significant drivers shaping microbial community dynamics and assembly. This study of the archaea and syntrophic bacteria actively valorising LCFAs at short HRTs and 20°C will help uncover the microbiology underpinning anaerobic bioconversions of fats, oil and grease.HighlightsGranular, biofilm and planktonic assemblages developed from the same seed reservoirThree assemblages forming metacommunity differed in diversity and compositionMultiple null models applied to quantify deterministic and stochastic mechanismsDominant, active role of acetoclastic Methanosaeta confirmed in granules and biofilmDynamic, non-core-microbiome taxa correlated with environmental variables
Increasing cell size remodels the proteome and promotes senescence
Authors: Lanz Michael C. , Zatulovskiy Evgeny , Swaffer Matthew P. , Zhang Lichao , Ilerten Ilayda , Zhang Shuyuan , You Dong Shin , Marinov Georgi , McAlpine Patrick , Elias Josh E. , Skotheim Jan M. 
Published: July 2021

AbstractCell size is tightly controlled in healthy tissues, but it is poorly understood how variations in cell size affect cell physiology. To address this, we employed a high-accuracy mass spectrometry-based approach to measure how the proteome changes with cell size. Protein concentration changes are widespread, measurable in both asynchronous and G1-arrested cell populations, and predicted by subcellular localization, size-dependent changes in mRNA concentrations, and protein turnover. As proliferating cells grow larger, protein concentration changes typically associated with cellular senescence are increasingly pronounced. This suggests that large size is a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative, DNA damage-, and CDK4/6i-induced senescence. Size-dependent changes to the proteome, including those associated with senescence, are not observed when an increase in cell size is accompanied by a similar increase in ploidy. This shows that proteome composition is determined by the DNA-to-ploidy ratio rather than cell size per se and that polyploidization is an elegant method to generate large non-senescent cells as is commonly found in nature. Together, our findings show how cell size could impact many aspects of cell physiology through remodeling the proteome, thereby providing a rationale for cell size control and polyploidization.
TRPM2 deficiency protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages
Authors: Zong Pengyu , Feng Jianlin , Yue Zhichao , Yu Albert S. , Mori Yasuo , Yue Lixia 
Published: July 2021

ABSTRACTAtherosclerosis is the major cause of ischemic heart diseases and ischemic brain stroke, which are the leading causes of mortality worldwide. The central pathological features of atherosclerosis include macrophage infiltration and foam cell formation. However, the detailed mechanisms regulating these two processes remain unclear. Here we show that oxidative stress-activated Ca2+-permeable TRPM2 plays a key role in the pathogenesis of atherosclerosis. Trpm2 deletion produces a potent protective effect against atherosclerosis in ApoE-/- mice fed with a high-fat diet (HFD), as evidenced by reduced atherosclerotic plaque burden, decreased macrophage load and suppressed inflammasome activation in the vessel wall. Moreover, we show that Trpm2 deletion or inhibition reduces oxidized low-density lipoprotein (oxLDL) uptake by macrophages, suppresses macrophage infiltration induced by monocyte chemoattractant protein-1 (MCP1), and prevents the impairment of macrophage emigration caused by oxLDL. Intriguingly, we uncover that activation of CD36, an oxLDL receptor, can promote the activation of TRPM2, and vice versa, the CD36-mediated inflammatory cascade in atherosclerosis is dependent on TRPM2. In transfected HEK293T cells, CD36 ligands oxLDL and TSP1 induce TRPM2 activation in a CD36-dependent manner. Deleting Trpm2 or inhibiting TRPM2 activity in cultured macrophages suppresses the CD36 signaling cascade induced by oxLDL and TSP1. Our studies establish TRPM2-CD36 axis as a new mechanism underlying atherogenesis, and suggest TRPM2 as an effective therapeutic target for atherosclerosis.HIGHLIGHTSTrpm2 deletion protects against atherosclerosis in ApoE-/- mice fed with a high-fat diet (HFD)Trpm2 deficiency reduces atherosclerotic lesions by minimizing foam cell formation, inhibiting macrophage infiltration and preserving macrophage emigrationTRPM2 activation is required for CD36-induced oxLDL uptake and subsequent inflammatory responsesThe ligands of CD36, oxLDL and TSP1, activate TRPM2, thereby perpetuating TRPM2-CD36 inflammatory cycle in atherogenesis cascadeOur data establish TRPM2-CD36 axis as a new atherogenesis mechanism and TRPM2 as a novel therapeutic target for atherosclerosisTRPM2-mediated Ca2+ signal is essential for CD36 induced oxLDL uptake and atherosclerosis in ApoE-/- mice fed with a high-fat diet (HFD). The activation of CD36 and TRPM2 form a positive feedback loop in atherogenesis.
Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law
Authors: Day Thomas C. , Höhn Stephanie S. , Zamani-Dahaj Seyed A. , Yanni David , Burnetti Anthony , Pentz Jennifer , Honerkamp-Smith Aurelia R. , Wioland Hugo , Sleath Hannah R. , Ratcliff William C. , Goldstein Raymond E. , Yunker Peter J. 
Published: July 2021

AbstractThe prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved “snowflake” yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This ‘entropic’ cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.
A multimodal neuroprosthetic interface to record, modulate and classify electrophysiological correlates of cognitive function
Authors: Habelt Bettina , Wirth Christopher , Afanasenkau Dzmitry , Mihaylova Lyudmila , Winter Christine , Arvaneh Mahnaz , Minev Ivan R. , Bernhardt Nadine 
Published: July 2021

AbstractMost mental disorders are characterised by impaired cognitive function and behaviour control. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox, whose suitability for diagnosis and therapy of mental disorders has not yet been explored. Here, we developed a soft and multimodal neuroprosthesis to measure and modulate prefrontal neurophysiological features of neuropsychiatric symptoms. We implanted the device epidurally above the medial prefrontal cortex of rats and obtained auditory event-related brain potentials reflecting intact neural stimulus processing and alcohol-induced neural impairments. Moreover, implant-driven electrical and pharmacological stimulation enabled successful modulation of neural activity. Finally, we developed machine learning algorithms which can deal with sparsity in the data and distinguish effects with high accuracy. Our work underlines the potential of multimodal bioelectronic systems to enable a personalised and optimised therapy.
Automated Feeding and Fermentation Phase Transitions for the Production of Unspecific Peroxygenase by Pichia pastoris
Authors: Hobisch Markus , Kara Selin 
Published: July 2021

AbstractFungal peroxygenases are promising biocatalysts for hydroxylation steps in various industry-relevant synthesis pathways. In this application note we describe a bioprocess for the production of unspecific peroxygenase (UPO) in Pichia pastoris. The process was divided in four phases, with different carbon requirements. Precise timing of culture feeding was crucial for optimal cell growth and protein expression. We demonstrate how the automation of culture feeding reduced manual work as well as the risk of process failure due to operator error.
Natural interploidy hybridization among the key taxa involved in the origin of horticultural chrysanthemums
Authors: Qi Shuai , Twyford Alex D. , Ding Junyi , Borrell James S. , Ma Yueping , Wang Nian 
Published: July 2021

AbstractUnderstanding hybridization and introgression between natural plant populations can give important insights into the origins of cultivated species. Recent studies suggest differences in ploidy may not create such strong reproductive barriers as once thought, and thus studies into cultivated origins should examine all co-occurring taxa, including those with contrasting ploidy levels. Here, we characterized hybridization between Chrysanthemum indicum, Chrysanthemum vestitum and Chrysanthemum vestitum var. latifolium, the most important wild species involved in the origins of cultivated chrysanthemums. We analysed population structure of 317 Chrysanthemum accessions based on 13 microsatellite markers and sequenced chloroplast trnL-trnF for a subset of 103 Chrysanthemum accessions. We identified three distinct genetic clusters, corresponding to the three taxa. We detected 20 hybrids between species of different ploidy levels, of which 19 were between C. indicum (4x) and C. vestitum (6x) and one was between C. indicum and C. vestitum var. latifolium (6x). Fourteen hybrids between C. indicum and C. vestitum were from one of the five study sites. Chrysanthemum vestitum and C. vestitum var. latifolium share only one chloroplast haplotype. The substantially different number of hybrids between hybridizing species was likely due to different levels of reproductive isolation coupled with environmental selection against hybrids. In addition, human activities may play a role in the different patterns of hybridization among populations.
HEPG2 EXPRESSION OF MIR-202 & TRIB-1 UNDER METABOLIC AND INFLAMMATORY STRESS
Authors: Phillip Iquo O. , Phillip Julius O. 
Published: July 2021

AbstractBackgroundThe burden of cardiovascular disease (CVD) is such that affects both developed and developing countries with high rates of mortality and morbidity. Cardiovascular diseases are highly polymorphic across its various risk factors. Human polymorphisms of trib-1 gene have been implicated to be associated with risk factors for CVD. Trib-1 gene is a known target for microRNA-202 which consequently could have an effect on its stability. The objective of this study was to evaluate the expression of miR-202 in an hepatic cell line under in vitro conditions of metabolic and inflammatory stress and the effect on trib-1 level.Materials and MethodsHepG2 cells cultured under in vitro conditions of high glucose and cytokine stimulation of concentrations of varying time intervals were harvested and mRNA/microRNA extracted using the spin column-based centrifugation, reversed transcribed and analysed for endogenous expressions of trib-1 and miR-202 using qPCR. One-ANOVA followed by Dunnett’s multiple comparison test was used to test for significance (P<0.05) across samples.ResultsIt was observed that there was a significant decrease in trib-1 levels under these conditions of high glucose and cytokine stimulation and also with the combination of both whilst there was a consistent pattern of upregulation of MIR-202 under this conditions.ConclusionTaken together this study reveals that miR-202 is expressed in HepG2 cells, and a possible interaction between trib-1 and MIR-202 which could affect trib-1 stability and also the potentials for MIR-202 to be involved in some cellular activities in HepG2 cells relating to these conditions.
GCAT dotplots characterize precisely and imprecisely defined topological features of DNA
Authors: Collett J.I. , Pearce S.R. 
Published: July 2021

AbstractTwo-dimensional graphical dotplotting is adopted to identify sequence elements and their variants in lengths of DNA of up to 10 kb. Named GCAT for identification of precisely defined short sequences and their variants, its use complements the precise matching of many computational programs, including BLAST. Short reiterated “search” sequences are entered in the Y-axis of the dotplot program to be matched at their identical and near identical (variant) sites in a sequence of interest entered in the X-axis. The result is a barcode-like representation of the identified sequence elements along the X-axis of the dotplot. Alignments of searches and sequence landmarks provide visualization of composition and juxtapositions. The method is described here by example of characterizations of three distinctive sequences available in the annotated Drosophila melanogaster reference genome (www.flybase.org): the Jonah 99C gene region, the transcript of Dipeptidase B and the transposable element roo. Surprising observations emerging from these explorations include in-frame STOP codons in the large exonic intron of Dip-B, high A-content of the replicative strand of roo as TE example and similarities of its ORF and the large intron of Dip-B.