bluuebunny/crossref_metadata_2025_split huggingface dataset:
MscS inactivation and recovery are slow voltage-dependent processes sensitive to interactions with lipids
Authors: Britt Madolyn , Moller Elissa , Maramba Joseph , Anishkin Andriy , Sukharev Sergei 
Published: May 2023

AbstractMechanosensitive channel MscS, the major bacterial osmolyte release valve, shows a characteristic adaptive behavior. With a sharp onset of activating tension, the channel population readily opens, but under prolonged action of moderate near-threshold tension, it inactivates. The inactivated state is non-conductive and tension-insensitive, which suggests that the gate gets uncoupled from the lipid-facing domains. The kinetic rates for tension-driven opening-closing transitions are 4-6 orders of magnitude higher than the rates for inactivation and recovery. Here we show that inactivation is augmented and recovery is slowed down by depolarization. Hyperpolarization, conversely, impedes inactivation and speeds up recovery. We then address the question of whether protein-lipid interactions may set the rates and influence voltage dependence of inactivation and recovery. Mutations of conserved arginines 46 and 74 anchoring the lipid-facing helices to the inner membrane leaflet to tryptophans do not change the closing transitions, but instead change the kinetics of both inactivation and recovery and essentially eliminate their voltage-dependence. Uncharged polar substitutions (S or Q) for these anchors produce functional channels but increase the inactivation and reduce the recovery rates. The data suggest that it is not the activation and closing transitions, but rather the inactivation and recovery pathways that involve substantial rearrangements of the protein-lipid boundary associated with the separation of the lipid-facing helices from the gate. The discovery that hyperpolarization robustly assists MscS recovery indicates that membrane potential can regulate osmolyte release valves by putting them either on the ‘ready’ or ‘standby’ mode depending on the cell’s metabolic state.
STUSC: selection tests under size change
Authors: Wooding Stephen 
Published: May 2023

AbstractSummaryNatural selection leaves signatures in genetic diversity. A challenge in detecting these signatures is that demographic history can shape genetic variation in ways similar to selection, making their effects difficult to disentangle. STUSC takes a simulation based approach to the problem. It performs five widely used tests for natural selection, Tajima’s D, Fu and Li’s F and F*, and Fu and Li’s D and D*, which ordinarily require the assumption of constant population size, under any size history. It also provides methods for generating their statistical distributions, allowing their responses to demography to be studied and past results to be evaluated.Availability and implementationSTUSC is written in Java, and is freely available at the author’s website,woodinglab.org/stuscContactswooding@ucmerced.edu
Transmission mode shapes host specialization of the phyllosphere microbiome
Authors: Meyer Kyle M. , Muscettola Isabella E. , Vasconcelos Ana Luisa S. , Sherman Julia K. , Metcalf C. Jessica E. , Lindow Steven E. , Koskella Britt 
Published: May 2023

AbstractThe collection of microorganisms inhabiting aboveground plant tissue, termed the phyllosphere microbiome, is shaped by both microbial dispersal and host filtering effects. Because plants often occur in multispecies assemblages, microbiome diversity is likely shaped by plant community composition through microbial transmission between conspecific (same species) and heterospecific (different species) host plants. Although rarely examined, the relative incidence of con-versus heterospecific transmission should impact microbiome-level specialization. Using four species of plants we experimentally tested this idea by passaging an initially diverse microbial community either between conspecific or heterospecific plants in the greenhouse. While conspecific transmission lines exhibited persistent host effects, these effects decreased in the heterospecific transmission lines, suggesting a shift towards more generalist microbiomes. Similarly, when microbiomes were transplanted onto a set of novel host plant species, host effects were weaker for these heterospecific lines than the conspecific lines. Finally, microbiomes conspecifically passaged on tomato plants were found to outcompete those passaged on either bean or pepper when co-inoculated onto tomato hosts, suggesting microbiome-level host specialization under conspecific transmission. Overall, we find that both transmission mode and host association history shape microbiome diversity, that repeated conspecific transmission results in microbiome specialization, and that repeated heterospecific transmission can drive microbiomes to develop generalist characteristics.
RNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis
Authors: Kaye Emily G. , Nelson Geoffrey M. , Zomer Helena D. , Roy Debarun , Joseph Irene Infancy , Adelman Karen , Reddi Prabhakara P. 
Published: May 2023

AbstractMale germ cell development requires precise regulation of gene activity in a cell-type and stage-specific manner, with perturbations in gene expression during spermatogenesis associated with infertility. Here, we use steady-state, nascent and single-cell RNA sequencing strategies to comprehensively characterize gene expression across male germ cell populations, to dissect the mechanisms of gene control and provide new insights towards therapy. We discover a requirement for pausing of RNA Polymerase II (Pol II) at the earliest stages of sperm differentiation to establish the landscape of gene activity across development. Accordingly, genetic knockout of the Pol II pause-inducing factor NELF in immature germ cells blocks differentiation to mature spermatids. Further, we uncover unanticipated roles for Pol II pausing in the regulation of meiosis during spermatogenesis, with the presence of paused Pol II associated with double strand break formation by SPO11, and disruption of SPO11 expression in germ cells lacking NELF.
POT1 recruits and regulates CST–Polα/Primase at human telomeres
Authors: Cai Sarah W. , Takai Hiroyuki , Walz Thomas , de Lange Titia 
Published: May 2023

SummaryTelomere maintenance requires extension of the G-rich telomeric repeat strand by telomerase and fill-in synthesis of the C-rich strand by Polα/Primase. Telomeric Polα/Primase is bound to Ctc1-Stn1-Ten1 (CST), a single-stranded DNA-binding complex. Like mutations in telomerase, mutations affecting CST–Polα/Primase result in pathological telomere shortening and cause a telomere biology disorder, Coats plus (CP). We determined cryogenic electron microscopy structures of human CST bound to the shelterin heterodimer POT1/TPP1 that reveal how CST is recruited to telomeres by POT1. Phosphorylation of POT1 is required for CST recruitment, and the complex is formed through conserved interactions involving several residues mutated in CP. Our structural and biochemical data suggest that phosphorylated POT1 holds CST–Polα/Primase in an inactive auto-inhibited state until telomerase has extended the telomere ends. We propose that dephosphorylation of POT1 releases CST–Polα/Primase into an active state that completes telomere replication through fill-in synthesis.
Jump-start and push-start: Mutual activation through crosstalk in coupled quorum sensing pathways
Authors: Sanders Joseph , Akl Hoda , Hagen Stephen J. , Xue BingKan 
Published: May 2023

AbstractMany bacterial species are able to coordinate population-wide phenotypic responses through the exchange of diffusible chemical signals, a behavior known as quorum sensing. A quorum sensing bacterium may employ multiple types of chemical signals and detect them using inter-connected pathways that crosstalk with each other. While there are many hypotheses for the advantages of sensing multiple signals, the prevalence and functional significance of crosstalk between the sensing pathways are much less understood. Here we explore the effect of intra-cellular signal crosstalk on a simple model of a quorum sensing circuit. The model captures key aspects of typical quorum sensing pathways, including detection of multiple signals that crosstalk at the receptor and promoter levels, positive feedback, and hierarchical positioning of sensing pathways. We find that a variety of behaviors can be tuned by modifying crosstalk and feedback strengths. These include activation or inhibition of one output by the non-cognate signal, broadening of dynamic range of the outputs, and the ability of either the upstream or downstream branch to modulate the feedback circuit of the other branch. Our findings show how crosstalk between quorum sensing pathways can be viewed not solely as a detriment to the flow of information but also as a mechanism that enhances the functional range of the full regulatory system: When positive feedback systems are coupled through crosstalk, several new modes of activation or deactivation become possible.
Gibberellin and the miRNA156-targetedSlSBPssynergistically regulate tomato floral meristem activity and fruit patterning
Authors: Ferigolo Leticia F. , Vicente Mateus H. , Correa Joao P. O. , Barrera-Rojas Carlos H. , Silva Eder M. , Silva Geraldo F.F. , Carvalho Airton , Peres Lazaro E.P. , Ambrosano Guilherme B. , Margarido Gabriel R. A. , Sablowski Robert , Nogueira Fabio T.S. 
Published: May 2023

ABSTRACTMany developmental processes associated with fruit development take place at the floral meristem (FM). Age-regulated microRNA156 (miR156) and gibberellins (GA) interact to control flowering time, but their interplay in subsequent stages of reproductive development is poorly understood. Here, we show that GA and miR156 function in tomato FM and fruit patterning. High GA responses or overexpression of miR156 (156OE), which leads to low levels of miR156-targetedSQUAMOSA PROMOTER BINDING PROTEIN– LIKE(SPL/SBP), resulted in enlarged FMs, defects in FM determinacy and fruits with increased locule number. Conversely, low GA responses reduced fruit indeterminacy and locule number, and overexpression of a miR156-resistantSlSBP15allele (rSBP15) reduced cell number and size in the FM, as well as locule number. GA responses were partially required for the fruit defects observed in 156OE andrSBP15plants. Transcriptome analysis and genetic interactions revealed shared and divergent functions of miR156-targetedSlSBPs, PROCERA/DELLAand the classicalWUSCHEL/CLAVATApathway, which has been previously associated with meristem size and determinacy. Our findings reveal that the miR156/SlSBP/GA regulatory module is deployed differently depending on developmental stage and create novel opportunities to genetically fine-tune aspects of fruit development that have been important for tomato domestication.
Herbarium specimens as tools for exploring the evolution of biosynthetic pathways to fatty acid-derived natural products in plants
Authors: Fitzgibbons Emma , Lastovich Jacob , Scott Samuel , Grusz Amanda L. , Busta Lucas 
Published: May 2023

AbstractPlants synthesize natural products via lineage-specific offshoots of their core metabolic pathways, including fatty acid synthesis. Recent studies have shed light on new fatty acid-derived natural products and their biosynthetic pathways in disparate plant species. Inspired by this progress, we set out to expand the tools available for exploring the evolution of biosynthetic pathways to fatty-acid derived products. We sampled representative species from all major clades of euphyllophytes, including ferns, gymnosperms, and angiosperms (monocots and eudicots), and we show that quantitative profiles of fatty-acid derived surface waxes from preserved plant specimens are consistent with those obtained from freshly collected tissue. We then sampled herbarium specimens representing >50 monocot species to assess the phylogenetic distribution and infer the evolutionary origins of two fatty acid-derived natural products found in that clade: beta-diketones and alkyl resorcinols. These chemical data, combined with analyses of 26 monocot genomes, suggest whole genome duplication as a likely mechanism by which both diketone and alkylresorcinol synthesis evolved from an ancestral alkylresorcinol synthase-like polyketide synthase. This work reinforces the widespread utility of herbarium specimens for studying leaf surface waxes (and possibly other chemical classes) and reveals the evolutionary origins of fatty acid-derived natural products within monocots.Significance StatementPlant chemicals are key components in our food and medicine, and advances in genomic technologies are accelerating plant chemical research. However, access to tissue from specific plant species can still be rate-limiting, especially for species that are difficult to cultivate, endangered, or inaccessible. Here, we demonstrate that herbarium specimens provide a semiquantitative proxy for the cuticular wax profiles of their fresh counterparts, thus reducing the need to collect fresh tissue for studies of wax chemicals and suggesting the same may also be true of other plant chemical classes. We also demonstrate the utility of combining herbarium-based plant chemical profiling with genomic analyses to understand the evolution of plant natural products.
Evolving spike-proteinN-glycosylation in SARS-CoV-2 variants
Authors: Baboo Sabyasachi , Diedrich Jolene K. , Torres Jonathan L. , Copps Jeffrey , Singh Bhavya , Garrett Patrick T. , Ward Andrew B. , Paulson James C. , Yates John R. 
Published: May 2023

AbstractSince >3 years, SARS-CoV-2 has plunged humans into a colossal pandemic. Henceforth, multiple waves of infection have swept through the human population, led by variants that were able to partially evade acquired immunity. The co-evolution of SARS-CoV-2 variants with human immunity provides an excellent opportunity to study the interaction between viral pathogens and their human hosts. The heavilyN-glycosylated spike-protein of SARS-CoV-2 plays a pivotal role in initiating infection and is the target for host immune-response, both of which are impacted by host-installedN-glycans. Using highly-sensitive DeGlyPHER approach, we compared theN-glycan landscape on spikes of the SARS-CoV-2 Wuhan-Hu-1 strain to seven WHO-defined variants of concern/interest, using recombinantly expressed, soluble spike-protein trimers, sharing same stabilizing-mutations. We found thatN-glycan processing is conserved at most sites. However, in multiple variants, processing ofN-glycans from high mannose- to complex-type is reduced at sites N165, N343 and N616, implicated in spike-protein function.
Endo-Lysosome-Targeted Nanoparticle Delivery of Antiviral Therapy for Coronavirus Infections
Authors: Petcherski Anton , Tingley Brett M , Martin Andrew , Adams Sarah , Brownstein Alexandra J , Steinberg Ross A , Shabane Byourak , Ngo Jennifer , Osto Corey , Garcia Gustavo , Veliova Michaela , Arumugaswami Vaithilingaraja , Colby Aaron H , Shirihai Orian S , Grinstaff Mark W 
Published: May 2023

ABSTRACTSARS-CoV-2 can infect cells through endocytic uptake, a process which is targeted by inhibition of lysosomal proteases. However, clinically this approach to treat viral infections has afforded mixed results, with some studies detailing an oral regimen of hydroxychloroquine accompanied by significant off-target toxicities. We rationalized that an organelle-targeted approach will avoid toxicity while increasing the concentration of the drug at the target. Here we describe a lysosome-targeted, mefloquine-loaded poly(glycerol monostearate-co-ε-caprolactone) nanoparticle (MFQ-NP) for pulmonary delivery via inhalation. Mefloquine is a more effective inhibitor of viral endocytosis than hydroxychloroquine in cellular models of COVID-19. MFQ-NPs are less toxic than molecular mefloquine, 100-150 nm in diameter, and possess a negative surface charge which facilitates uptake via endocytosis allowing inhibition of lysosomal proteases. MFQ-NPs inhibit coronavirus infection in mouse MHV-A59 and human OC43 coronavirus model systems and inhibit SARS-CoV-2-WA1 and its Omicron variant in a human lung epithelium model. This study demonstrates that organelle-targeted delivery is an effective means to inhibit viral infection.
Ivermectin resistance in dung beetles exposed for multiple generations
Authors: González-Tokman Daniel , Arellano-Torres Antonio , Baena-Díaz Fernanda , Bustos-Segura Carlos , Martínez M. Imelda 
Published: May 2023

AbstractIvermectin is an antiparasitic drug commonly used in cattle, that is excreted in dung, causing lethal and sub-lethal effects on coprophagous non-target fauna. Given that cattle parasites generate resistance to ivermectin, farmers have increased the used doses, with a consequent threat to wild fauna. The dung beetle speciesEuoniticellus intermediusprovides ecosystem services by burying dung in cattle pastures, however it is highly threatened by ivermectin. Here we experimentally tested whetherE. intermediusgenerates resistance against ivermectin after being exposed for several generations to a sublethal dose. We generated two laboratory lines where beetles were exposed to either ivermectin-treated or ivermectin-free dung for 18 generations. We compared reproductive success (total brood balls, emerged beetles, proportion emerged and days to emergence) of beetles from both lines across generations. Additionally, for each line, we carried-out toxicity experiments with increasing ivermectin concentrations to determine if sensitivity to ivermectin was reduced after some generations of exposure (i. e. if beetles acquired ivermectin resistance by means of transgenerational effects). Our results show that dung beetles do not generate resistance to ivermectin after 18 generations of continuous exposure and quantitative genetic analyses show low genetic variation in response to ivermectin across generations. Together, these results indicate low potential for adaptation to the contaminant in the short term. Although we cannot exclude that adaptation could occur in the long term, our results and comparative evidence in other insects indicate that dung beetles, and probably other species, are at risk of extinction in ivermectin-contaminated pastures unless they are pre-adapted to tolerate high ivermectin concentrations.
Lévy movements and a slowly decaying memory allow efficient collective learning in groups of interacting foragers
Authors: Falcón-Cortés Andrea , Boyer Denis , Aldana Maximino , Ramos-Fernández Gabriel 
Published: May 2023

AbstractMany animal species benefit from spatial learning to adapt their foraging movements to the distribution of resources. Learning involves the collection, storage and retrieval of information, and depends on both the random search strategies employed and the memory capacities of the individual. For animals living in social groups, spatial learning can be further enhanced by information transfer among group members. However, how individual behavior affects the emergence of collective states of learning is still poorly understood. Here, with the help of a spatially explicit agent-based model where individuals transfer information to their peers, we analyze the effects on the use of resources of varying memory capacities in combination with different exploration strategies, such as ordinary random walks and Lévy flights. We find that individual Lévy displacements associated with a slow memory decay lead to a very rapid collective response, a high group cohesion and to an optimal exploitation of the best resource patches in static but complex environments, even when the interaction rate among individuals is low.Author SummaryHow groups of social animals collectively learn to find and exploit resources in complex environments is not well-understood. By means of a computational model where individuals are initially spread out across a landscape, we study the effects of individual exploratory behaviors and memory capacities on the emergence of spatial learning. Collective learning emerges spontaneously only if group members transfer information between each other at a sufficiently high rate, so that individual experiences can be used by others. In static but heterogeneous environments with many resource sites of varying attractiveness, we find that random displacements over many spatial scales combined with a slow memory decay lead to a rapid collective response and highly cohesive groups. Collective learning is noticeable through an optimal exploitation of the best resource sites, which far exceeds what individuals would achieve on their own. Our study sheds light on important mechanisms responsible for collective learning in ecology, with potential applications in other areas of science.
Linking bacterial tetrabromopyrrole biosynthesis to coral metamorphosis
Authors: Alker Amanda T. , Farrell Morgan V. , Demko Alyssa M. , Purdy Trevor N. , Adak Sanjoy , Moore Bradley S. , Sneed Jennifer M. , Paul Valerie J. , Shikuma Nicholas J. 
Published: May 2023

ABSTRACTAn important factor dictating coral fitness is the quality of bacteria associated with corals and coral reefs. One way that bacteria benefit corals is by stimulating the larval to juvenile life cycle transition of settlement and metamorphosis. Tetrabromopyrrole (TBP) is a small molecule produced by bacteria that stimulates metamorphosis in a range of coral species. A standing debate remains, however, about whether TBP biosynthesis from livePseudoalteromonasbacteria is the primary stimulant of coral metamorphosis. In this study, we create aPseudoalteromonassp. PS5 mutant lacking the TBP brominase gene,bmp2. Using this mutant, we confirm that thebmp2gene is critical for TBP biosynthesis inPseudoalteromonassp. PS5. Mutation of this gene ablates the bacterium’s ability in live cultures to stimulate the metamorphosis of the stony coralPorites astreoides. We further demonstrate that expression of TBP biosynthesis genes is strongest in stationary and biofilm modes of growth, wherePseudoalteromonassp. PS5 might exist within surface-attached biofilms on the sea floor. Finally, we create a modular transposon plasmid for genomic integration and fluorescent labeling ofPseudoalteromonassp. PS5 cells. Our results functionally link a TBP biosynthesis gene from live bacteria to a morphogenic effect in corals. The genetic techniques established here provide new tools to explore coral-bacteria interactions and could help to inform future decisions about utilizing marine bacteria or their products for restoring degraded coral reefs.
Succinylation of a KEAP1 sensor lysine promotes NRF2 activation
Authors: Ibrahim Lara , Stanton Caroline , Nutsch Kayla , Nguyen Thu , Li-Ma Chloris , Ko Yeonjin , Lander Gabriel C. , Wiseman R. Luke , Bollong Michael J. 
Published: May 2023

SummaryCrosstalk between metabolism and stress-responsive signaling is essential to maintaining cellular homeostasis. One way this crosstalk is achieved is through the covalent modification of proteins by endogenous, reactive metabolites that regulate the activity of key stress-responsive transcription factors such as NRF2. Several metabolites including methylglyoxal, glyceraldehyde 3-phosphate, fumarate, and itaconate covalently modify sensor cysteines of the NRF2 regulatory protein KEAP1, resulting in stabilization of NRF2 and activation of its cytoprotective transcriptional program. Here, we employed a shRNA-based screen targeting the enzymes of central carbon metabolism to identify additional regulatory nodes bridging metabolic pathways to NRF2 activation. We found that succinic anhydride, increased by genetic depletion of the TCA cycle enzyme succinyl-CoA synthetase or by direct administration, results in N-succinylation of lysine 131 of KEAP1 to activate NRF2 transcriptional signaling. This study identifies KEAP1 as capable of sensing reactive metabolites not only by several cysteine residues but also by a conserved lysine residue, indicating its potential to sense an expanded repertoire of reactive metabolic messengers.