bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep pressure accumulates in a voltage-gated lipid peroxidation memory
Authors: Rorsman H. Olof , Müller Max A. , Liu Patrick Z. , Sanchez Laura Garmendia , Kempf Anissa , Gerbig Stefanie , Spengler Bernhard , Miesenböck Gero 
Published: February 2024

SummaryVoltage-gated potassium (KV) channels contain cytoplasmic β-subunits whose aldo-keto reductase activity is required for the homeostatic regulation of sleep. Here we show that Hyperkinetic, the β-subunit of the KV1 channel Shaker inDrosophila, forms a dynamic lipid peroxidation memory. Information is stored in the oxidation state of Hyperkinetic’s nicotinamide adenine dinucleotide phosphate (NADPH) cofactor, which changes when lipid-derived carbonyls, such as 4-oxo-2-nonenal or an endogenous analog generated by illuminating a membrane-bound photosensitizer, abstract an electron pair. NADP+remains locked in the active site of KVβ until membrane depolarization permits its release and replacement with NADPH. Sleep-inducing neurons use this voltage-gated oxidoreductase cycle to encode their recent lipid peroxidation history in the collective binary states of their KVβ-subunits; this biochemical memory influences—and is erased by—spike discharges driving sleep. The presence of a lipid peroxidation sensor at the core of homeostatic sleep control suggests that sleep protects neuronal membranes against oxidative damage. Indeed, brain phospholipids are depleted of vulnerable polyunsaturated fatty acyl chains after enforced waking, and slowing the removal of their carbonylic breakdown products increases the demand for sleep.
Extracellular chemosymbiont populations in a shallow-water thyasirid clam potentially shaped by priority effect
Authors: Li Menggong , Li Yunlong , Mao Shi-Hai , Liu Xu , Wang Hui , Chen Chong , Liu Xiaoshou , Zhuang Guang-Chao , Zhang Weipeng , Sun Jin 
Published: February 2024

AbstractChemosymbiosis is a highly successful strategy that evolved in several animal groups, best known for dominating chemosynthetic ecosystems such as deep-sea hot vents and hydrocarbon seeps but also found in other systems such as reducing sediments in shallow water. The symbiont population structure can be determined by the host genetic inheritance, geographic partitions, and environmental factors, among others if the symbionts are acquired horizontally from the environment. Here, we suggest that the earliest colonies can also influence the episymbiont population, known as the “priority effect”, using the thyasirid cleftclamThyasira tokunagai.This species is abundant in reducing sediments in Yellow Sea, hosting an extracellular sulfide-oxidizing symbiont (genusSedimenticola) in the pouch-like structure in the gill. From samples taken across the whole Yellow Sea, complete symbiont genomes revealed only two dominant strains which were also verified by phylogenomic analysis. The two strains share key functional genes but exhibit a single-base difference in the 16S rDNA. We found mutually exclusive communities of these two strains in the 30 individual hosts studied, typically dominated or even monopolized by one strain. Inconsistent phylogenetic relationships between hosts and symbiont indicate the genetic heterogeneity of the holobiont, and the mean fixation indexFSTof each symbiont population within sampling sites showed a lack of correlation with geographic distance and environmental factors, suggesting another driving force. We deduce that the likely scenario is 1) the dominant symbiont strain is determined during initial acquisition; 2) the propagation of this initial strain as the host develops; 3) the continuous but restricted recruitment of the other strain during the adult stage. Overall, our results highlight the importance of “priority effect” in shaping the chemosymbiont population structures even in the horizontally transmitted episymbiont in a whole marginal sea area.
Nano-clusters of ligand-activated integrins organize immobile, signalling active, nano-clusters of phosphorylated FAK required for mechanosignaling in focal adhesions
Authors: Jain Kashish , Minhaj Rida F. , Kanchanawong Pakorn , Sheetz Michael P. , Changede Rishita 
Published: February 2024

AbstractTransmembrane signalling receptors, such as integrins, organise as nanoclusters that are thought to provide several advantages including, increasing avidity, sensitivity (increasing the signal-to-noise ratio) and robustness (signalling above a threshold rather than activation by a single receptor) of the signal compared to signalling by single receptors. Compared to large micron-sized clusters, nanoclusters offer the advantage of rapid turnover for the disassembly of the signal. However, if nanoclusters function as signalling hubs remains poorly understood. Here, we employ fluorescence nanoscopy combined with photoactivation and photobleaching at sub-diffraction limited resolution of ∼100nm length scale within a focal adhesion to examine the dynamics of diverse focal adhesion proteins. We show that (i) subregions of focal adhesions are enriched in immobile population of integrin β3 organised as nanoclusters, which (ii) in turn serve to organise nanoclusters of associated key adhesome proteins-vinculin, focal adhesion kinase (FAK) and paxillin, demonstrating that signalling proceeds by formation of nanoclusters rather than through individual proteins. (iii) Distinct focal adhesion protein nanoclusters exhibit distinct dynamics dependent on function. (iv) long-lived nanoclusters function as signalling hubs-wherein phosphorylated FAK and paxillin formed stable nanoclusters in close proximity to immobile integrin nanoclusters which are disassembled in response to inactivation signal by phosphatase PTPN12 (v) signalling takes place in response to an external signal such as force or geometric arrangement of the nanoclusters and when the signal is removed, these nanoclusters disassemble. Taken together, these results demonstrate that signalling downstream of transmembrane receptors is organised as hubs of signalling proteins (FAK, paxillin, vinculin) seeded by nanoclusters of the transmembrane receptor (integrin).
Improved potential analysis for inadequate ecological data
Authors: Arani Babak M. S. , van Nes Egbert H. , Scheffer Marten 
Published: February 2024

AbstractPotential analysis is used in many ecological studies to infer whether or not an ecosystem can have alternative stable states, to estimate the tipping points and, to assess the resilience of ecosystems. The main reason behind its frequent use is that such a frequency-based analysis is a minimalistic modelling strategy and therefore, is well-suited for limited ecological data with measurement errors. It has been used extensively in tree cover studies to discern alternative states of savannah and forest, the regime upon which savannah and forest coexist and, their corresponding resilience. Classical potential analysis may produce biased results due to inherent theoretical and practical limitations. This letter introduces a more sophisticated approach to address these shortcomings and enhance predictive capabilities regarding ecological dynamics, especially when working with insufficient data whose incorrect analysis can significantly impact management strategies.
Cold hardiness-informed budbreak reveals role of freezing temperatures and daily fluctuation in chill accumulation model
Authors: North Michael G. , Workmaster Beth Ann , Atucha Amaya , Kovaleski Al P. 
Published: February 2024

AbstractFundamental questions in bud dormancy remain, including what temperatures fulfill dormancy requirements (i.e., chill accumulation). Recent studies demonstrate freezing temperatures promote chill accumulation and cold hardiness influences time to budbreak – the phenotype used for dormancy evaluations. Here we evaluated bud cold hardiness (CH) and budbreak responses of grapevines (Vitishybrids) throughout chill accumulation under three treatments: constant (5°C), fluctuating (−3.5 to 6.5 °C daily), and field conditions (Madison, WI, USA). Chill treatments experiencing lower temperatures promoted greater gains in cold hardiness (CHfield>CHfluctuating>CHconstant). All treatments decreased observed time to budbreak with increased chill accumulation. However, perceived treatment effectiveness changed when time to budbreak was adjusted to remove cold acclimation effects. Among three classic chill models (North Carolina, Utah, and Dynamic), none were able to correctly describe adjusted time to budbreak responses to chill accumulation. Thus, a new model is proposed that expands the range of chill accumulation temperatures to include freezing temperatures and enhances chill accumulation under fluctuating temperature conditions. Most importantly, our analysis demonstrates adjustments for uneven acclimation change the perceived effectiveness of chill treatments. Therefore, future work in bud dormancy would benefit from simultaneously evaluating cold hardiness.HighlightA new chill accumulation model demonstrates how bud cold hardiness changes elicited by chill treatments affect the interpretation of thermal effectiveness in promoting dormancy progression and release.
A Fluorogenic Green Merocyanine-Based Probe to Detect Heparanase-1 Activity
Authors: Rabinowitz Zachary M. , Wang Zhishen , Liu Jun , Zhang Yuzhao , Ybargollin Alberto Jimenez , Saketkhou Mayrav , Cui Lina 
Published: February 2024

ABSTRACTHeparanase-1 (HPSE-1), an endo-β-D-glucuronidase, is an extracellular matrix (ECM) remodeling enzyme that degrades heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs). HPSE-1 functions to remodel the ECM and thereby disseminate cells, liberate HS-bound bioactive molecules, and release biologically active HS fragments. Being the only known enzyme for the cleavage of HS, HPSE-1 regulates a number of fundamental cellular processes including cell migration, cytokine regulation, angiogenesis, and wound healing. Overexpression of HPSE-1 has been discovered in most cancers, inflammatory diseases, viral infections, among others. As an emerging therapeutic target, the biological role of HPSE-1 remains to be explored but is hampered by a lack of research tools. To expand the chemical tool-kit of fluorogenic probes to interrogate HPSE-1 activity, we design and synthesized a fluorogenic green disaccharide-based HPSE-1 probe using our design strategy of tuning the electronic effect of the aryl aglycon. The novel probe exhibits a highly sensitive 278-fold fluorescence turn-on response in the presence of recombinant human HPSE-1, while emitting green light at 560 nm, enabling the fluorescence imaging of HPSE-1 activity in cells.
Blood-based DNA methylation study of alcohol consumption
Authors: Bernabeu Elena , Chybowska Aleksandra D , Kresovich Jacob K. , Suderman Matthew , McCartney Daniel L , Hillary Robert F , Corley Janie , Valdés-Hernández Maria Del C. , Muñoz Maniega Susana , Bastin Mark E. , Wardlaw Joanna M. , Xu Zongli , Sandler Dale P. , Campbell Archie , Harris Sarah E , McIntosh Andrew M , Taylor Jack A. , Yousefi Paul , Cox Simon R , Evans Kathryn L , Robinson Matthew R , Vallejos Catalina A , Marioni Riccardo E 
Published: February 2024

AbstractAlcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error and bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait. Here, we explore the epigenetic architecture of self-reported weekly units of alcohol consumption in the Generation Scotland study. We first create a blood-based epigenetic score (EpiScore) of alcohol consumption using elastic net penalised linear regression. We explore the effect of pre-filtering for CpG features ahead of elastic net, as well as differential patterns by sex and by units consumed in the last week relative to an average week. The final EpiScore was trained on 16,717 individuals and tested in four external cohorts: the Lothian Birth Cohorts (LBC) of 1921 and 1936, the Sister Study, and the Avon Longitudinal Study of Parents and Children (total N across studies > 10,000). The maximum Pearson correlation between the EpiScore and self-reported alcohol consumption within cohort ranged from 0.41 to 0.53. In LBC1936, higher EpiScore levels had significant associations with poorer global brain imaging metrics, whereas self-reported alcohol consumption did not. Finally, we identified two novel CpG loci via a Bayesian penalized regression epigenome-wide association study (EWAS) of alcohol consumption. Together, these findings show how DNAm can objectively characterize patterns of alcohol consumption that associate with brain health, unlike self-reported estimates.
TheChlamydia trachomatisInc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners
Authors: Herrera Clara M. , McMahon Eleanor , Swaney Danielle L. , Sherry Jessica , Pha Khavong , Adams-Boone Kathleen , Johnson Jeffrey R. , Krogan Nevan J. , Stevers Meredith , Solomon David , Elwell Cherilyn , Engel Joanne 
Published: February 2024

AbstractChlamydia trachomatisis the leading cause of bacterial sexually transmitted infections in the US and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood.C. trachomatisaccomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, theinclusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated withC. trachomatisinfection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen activated protein kinase kinase kinase 2 (MEKK2) and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling duringC. trachomatisinfection.ImportanceChlamydia trachomatisis the leading cause of bacterial sexually transmitted infections in the US and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between aC. trachomatissecreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrate that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis ofC. trachomatisinfections, but also in understanding the role of TRAF7 in cancer.
Natural products from food sources can alter the spread of AMR plasmids inEnterobacterales
Authors: Alav Ilyas , Pordelkhaki Parisa , Rodriguez-Navarro Judith , Neo Onalenna , Kessler Celia , Awodipe Ruth Jesujobalayemi , Cliffe Poppea , Marton Huba , Gibbons Simon , Buckner Michelle M.C. 
Published: February 2024

AbstractAntimicrobial resistance (AMR) poses a significant threat to global public health. Notably, resistance to carbapenem and extended-spectrum β-lactam antibiotics in Gram-negative bacteria is a major impediment for the treatment of infections. Genes responsible for resistance to these antibiotics are frequently carried on plasmids, which can transfer between bacteria. Therefore, exploring strategies to prevent this transfer and/or the prevalence of AMR plasmids is timely and pertinent. Here, we show that certain natural product extracts and associated pure compounds can reduce the transmission of AMR plasmids into new bacterial hosts. Using our established high-throughput fluorescence-based screen we found that the natural products were more active in reducing transmission of the IncK plasmid pCT inEscherichia coliST131, compared toKlebsiella pneumoniaeEcl8 carrying the IncFII plasmid pKpQIL. Furthermore, we found that the natural product rottlerin was more active inK. pneumoniaethan inE. coli. Importantly, rottlerin was also associated with a reduced number of transconjugant bacteria in a clinicalK. pneumoniaeisolate harbouring ablaNDM-1plasmid. Together, these results demonstrate the potential of natural products as promising anti-plasmid agents.
SREBP-mediated gene expression regulation is essential for the intrinsic fungicide tolerance and antagonism in the fungal biocontrol agentClonostachys rosea
Authors: Piombo Edoardo , Tzelepis Georgios , Ruus Alma Gustavsson , Rafiei Vahideh , Jensen Dan Funck , Karlsson Magnus , Dubey Mukesh 
Published: February 2024

AbstractSterol regulatory element-binding proteins (SREBPs) are a family of transcription factors known to regulate sterol biosynthesis and homeostasis in fungi. For this reason they have a role in several biological processes, including virulence, fungicide tolerance, hypoxia adaptation, lipid and carbohydrate metabolisms, and iron homeostasis. While the biological function of SREBPs in yeast and filamentous fungal species pathogenic to humans and plants is known, their role in fungal biocontrol agents (BCAs) is still elusive. This study aimed to investigate the biological and regulatory function of SREBPs in the BCAClonostachys rosea, with a focus on their role in fungicide tolerance, hypoxia adaptation and antagonisms. TheC. roseagenome contains two genes (sre1andsre2) coding for SREBPs and one gene each coding for Insulin induced gene (INSIG) and SREBP cleavage-activating protein (SCAP), required for SREBP-mediated ergosterol biosynthesis in fungi. Deletion ofsre1resulted in mutants with pleiotropic effects, including the reduced ability to grow on media supplemented with proline (active ingredient prothioconazole) and cantus (active ingredient boscalid) fungicides, hypoxia mimicking agent CoCl2, cell wall stressor SDS, and increased growth rate on medium supplemented with caffeine, compared withC. roseawild type (WT). In addition, the antagonistic ability against the fungal hostsBotrytis cinereaandRhizoctonia solaniwas affected whensre1was deleted. However, no significant difference betweensre2deletion strains andC. roseaWT was found for any of the tested phenotypes. To investigate the regulatory role of SRE1, the transcriptome ofC. roseaWT and asre1deletion strain was analyzed. The transcriptome analysis identified differentially expressed genes in thesre1deletion strain associated with carbohydrate and lipid metabolism, respiration, iron homeostasis, and xenobiotic tolerance. Moreover, genes coding for polyketide synthases and chitinases with a proven antimicrobial role were downregulated in the mutant, corroborating the reduced antagonism phenotypes. In summary, this work sheds light on the regulation role of transcription factor SRE1 while also exploring its effect on regulating the antagonistic activity and fungicide resistance ofC. rosea, giving us helpful knowledge to design applications of this organism in IPM strategies.
Short-term memory, attentional control and brain size in primates
Authors: van Schaik Carel P. , Jacobs Ivo , Burkart Judith M. , Sauciuc Gabriela-Alina , Schuppli Caroline , Persson Tomas , Song Zitan 
Published: February 2024

AbstractBrain size variability in primates has been attributed to various domain-specific socio-ecological factors. A recently published large-scale study of short-term memory abilities in 41 primate species [1] did not find any correlations with 11 different proxies of external cognitive demands. Here we found that the interspecific variation in test performance shows correlated evolution with total brain size, with the relationship becoming tighter as species with small sample sizes were successively removed, whereas it was not predicted by the often-used encephalization quotient (EQ). In a subsample, we also found that the sizes of brain region thought to be involved in short-term memory did not predict performance better than did overall brain size. The dependence on brain size suggests that domain-general cognitive processes underlie short-term memory as tested in [1]. These results support the emerging notion that comparative studies of brain size do not generally identify domain-specific cognitive adaptations, but rather reveal varying selection on domain-general cognitive abilities. Finally, because attentional processes beyond short- term memory also affected test performance, we suggest that the delayed response test can be refined.
Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation inMycobacterium tuberculosis
Authors: Apiche Elizabeth A. , Yee Eaindra , Damodaran Anoop Rama , Bhagi-Damodaran Ambika 
Published: February 2024

AbstractDosT and DosS are heme-based kinases involved in sensing and signaling O2tension in the microenvironment ofMycobacterium tuberculosis(Mtb). Under conditions of low O2, they activate >50 dormancy-related genes and play a pivotal role in the induction of dormancy and associated drug resistance during tuberculosis infection. In this work, we reexamine the O2binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.3±1 μM and 0.46±0.08 μM respectively, which are six to eight-fold stronger than what has been widely referred to in literature. Furthermore, stopped-flow kinetic studies reveal association and dissociation rate constants of 0.84 μM-1s-1and 2.8 s-1, respectively for DosT, and 7.2 μM-1s-1and 3.3 s-1, respectively for DosS. Remarkably, these tighter O2binding constants correlate with distinct stages of hypoxia-induced non-replicating persistence in the Wayne model ofMtb. This knowledge opens doors to deconvoluting the intricate interplay between hypoxia adaptation stages and the signal transduction capabilities of these important heme-based O2sensors.