bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat isolation diminishes potential of self-organised pattern formation to promote local diversity in metacommunities
Authors: Philipp Louica , Klauschies Toni , Guill Christian 
Published: February 2024

AbstractProgressive destruction and isolation of natural habitat is a major threat to biodiversity worldwide. In this study we use a trophic metacommunity model with complex, spatially explicit structure to address how the interaction of local and regional processes affects the functional diversity of autotroph (producer) communities within and between individual habitat patches. One important driver of biodiversity in metacommunities is spatial heterogeneity of the environment, as it enables source-sink dynamics between patches. Besides a-priori differences in the environmental conditions, heterogeneous distributions of resources and species biomasses can also emerge through self-organised pattern formation caused by scale-dependent feedback between local trophic and regional dispersal dynamics. We show that this emergent heterogeneity can enhance the functional diversity of local autotroph communities by jointly strengthening source-sink dynamics and reducing stabilising selection pressure. Our results indicate that this effect is particularly strong in highly connected metacommunities, while metacommunity size (number of patches) alone plays a lesser role. We demonstrate that the positive effect on local diversity is driven by an eco-evo-spatial feedback loop that is fueled by the asynchronous biomass- and trait dynamics between the patches created by self-organised pattern formation. In highly connected metacommunities, oscillatory biomass patterns with particularly large amplitude strengthen this feedback loop. Our findings are highly relevant in the light of anthropogenic habitat changes that often destroy dispersal pathways, thereby increasing habitat isolation, lowering overall connectance of metacommunities and ultimately threatening the biodiversity in local habitats. Only a joint investigation of the contributing ecological, evolutionary, and spatial mechanisms in complex model systems can yield comprehensive understanding of these processes, allowing for the development of strategies to mitigate adverse anthropogenic influence.
Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling via the intestinal peptide transporter PEPT-1
Authors: Muhammad Tahir , Edwards Stacey L. , Morphis Allison C. , Johnson Mary V. , Oliveira Vitor De , Chamera Tomasz , Liu Siyan , Nguyen Ngoc Gia Tuong , Li Jian 
Published: February 2024

AbstractGametogenesis involves active protein synthesis and heavily relies on proteostasis. How animals regulate germline proteostasis at the organismal level is poorly understood. TakingC. elegansas a model, we show that germline proteostasis requires coupled activities of HSF-1-dependent protein folding and insulin/IGF-1 signaling controlled protein synthesis. Depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, declines in fecundity and gamete quality. Reduced insulin/IGF-1 signaling confers germ cells’ resilience to limited protein folding capacity and proteotoxic stress by lowering ribosome biogenesis and the rate of translation. Interestingly, insulin/IGF-1 signaling promotes the expression of the evolutionarily conserved intestinal peptide transporter PEPT-1 via its downstream transcription factor FOXO/DAF-16, therefore allowing dietary proteins to be incorporated into an amino acid pool that fuels protein synthesis in the germline. We propose that this non-cell-autonomous pathway plays a critical role in regulating proteostasis in gametogenesis.TeaserInsulin/IGF-1 signaling regulates proteostasis in gametogenesis via the control of dietary protein absorption.
The MAP2Ks can use ADP to phosphorylate and activate their substrate MAPKsin vitro
Authors: Juyoux Pauline , von Velsen Jill , Pellegrini Erika , Bowler Matthew W. 
Published: February 2024

SummaryKinases are a diverse group of enzymes that use ATP to phosphorylate a variety of substrates. Protein kinases evolved in eukaryotes as important mediators of cell signalling that target specific amino acid side chains to modulate downstream protein function. Among them, the MAPKs (mitogen-activated protein kinases) are a family of intracellular protein kinases that form signalling cascades responding to a number of stimuli, that control fundamental mechanisms such as proliferation, differentiation, inflammation and cell death. Signals propagate through consecutive kinases which eventually phosphorylate and activate a MAPK. Here, we show that the dual specificity threonine/tyrosine MAP kinase kinases (MAP2Ks or MEKs) are able to phosphorylate and activate their substrate MAPKs using ADP as well as ATPin vitro. As the pathways are involved in the stress response, we speculate that it would represent an advantage to be able to maintain signalling under conditions such as hypoxia, that occur under a number of cell stresses, including cancer and atherosclerosis, where the available pool of ATP could be depleted.HighlightsThe MAP2K dual-specificity protein kinases can phosphorylate their target MAPKs using ADPin vitroThe reaction with ADP is less efficient than with ATPFirst example of an enzyme that can use both ATP and ADPADP phosphorylation might be a potential mechanism to maintain signal integrity when cell energy resources are constrained, as during ischemia
Degradation of IKAROS prevents epigenetic progression of T cell exhaustion in a novel antigen-specific assay
Authors: Tay Tristan , Bommakanti Gayathri , Jaensch Elizabeth , Gorthi Aparna , Reddy Iswarya Karapa , Hu Yan , Zhang Ruochi , Doshi Aatman , Tan Sin Lih , Brucklacher-Waldert Verena , Prickett Laura , Kurasawa James , Overstreet Michael Glen , Criscione Steven , Buenrostro Jason Daniel , Mele Deanna A. 
Published: February 2024

AbstractIn cancer, chronic antigen stimulation drives effector T cells to exhaustion, limiting the efficacy of T cell therapies. Recent studies have demonstrated that epigenetic rewiring governs the transition of T cells from effector to exhausted states and makes a subset of exhausted T cells non-responsive to PD1 checkpoint blockade. Here, we describe an antigen-specific assay for T cell exhaustion that generates T cells that are phenotypically and transcriptionally similar to those found in human tumors. We performed a screen of human epigenetic regulators, identifying and validating IKAROS as a driver of T cell exhaustion. We found that the IKAROS degrader iberdomide prevents exhaustion by blocking chromatin remodeling at T cell effector enhancers and preserving binding of AP-1, NF-κB, and NFAT. Thus, our study uncovered a role for IKAROS as a driver of T cell exhaustion through epigenetic modulation, providing a rationale for the potential use of iberdomide in solid tumors to prevent T cell exhaustion.HighlightsNovelin vitroassay generates antigen-specific exhausted T cells from human T cellsIKAROS (IKZF1) is a key driver of T cell exhaustionIberdomide (IKZF1/3 degrader) prevents the progression of exhaustionTF footprinting reveals IKAROS silences effector genes by inhibiting AP-1, NF-κB and NFAT binding
O6-Alkylguanine-DNA Alkyltransferase Maintains Genomic Integrity During Peroxynitrite-Mediated DNA Damage by Forming DNA-Protein Crosslinks
Authors: Chakraborty Shayantani , Mukherjee Gargi , Chakrabarty Anindita , Chowdhury Goutam 
Published: February 2024

AbstractInflammation is an early immune response against invading pathogens and damaged tissue. Although beneficial, uncontrolled inflammation leads to various diseases and may be fatal. Peroxynitrite (PN) is a major reactive nitrogen species (RNS) generated during inflammation. It produces various DNA lesions including labile 8-nitroguanine which spontaneously converts into abasic sites resulting in DNA strand breakage. Here, we report the discovery of a previously unrecognized function of the human repair proteinO6-alkylguanine-DNA alkyltransferase (hAGT or MGMT). We showed that hAGT through its active site nucleophilic Cys145 thiolate can spontaneously react with 8-nitroguanine in DNA to form a stable DNA-protein crosslink (DPC). Interestingly, the process of DPC formation provides protection from PN-mediated genome instability. The Cys145-mutant of hAGT failed to form DPC and provide protection against inflammation-associated, PN-mediated cytotoxicity. Gel shift, dot blot and UV-Vis assays showed formation of a covalent linkage between PN-damaged DNA and hAGT through its active site Cys145. Finally, expression of hAGT was found to be significantly increased by induced macrophages and PN. The data presented here clearly demonstrated hAGT as a dual function protein that along with DNA repair is capable of maintaining genomic integrity and providing protection from the toxicity caused by PN-mediated DNA damage. Although DPCs may seem detrimental, there are multiple systems in place in normal cells for their repair.
An experimental validation test of ecological coexistence theory to forecast extinction under rising temperatures
Authors: Terry J. Christopher D. 
Published: February 2024

AbstractInteractions between species pose considerable challenges for forecasting the response of ecological communities to global changes. Coexistence theory could address this challenge by defining the conditions species can or cannot persist alongside competitors. However, although coexistence theory is increasingly deployed for projections, these frameworks have rarely been subjected to critical multigenerational validation tests. Here, using a highly replicated mesocosm experiment, I directly test if the modern coexistence theory approach can predict time-to-extirpation in the face of rising temperatures within the context of competition from a heat-tolerant species. Competition hastened expiration and the modelled point of coexistence breakdown overlapped with mean observations under both steady temperature increases and with additional environmental stochasticity. That said, although the theory identified the interactive effect between the stressors, predictive precision was low even in this simplified system. Nonetheless, these results support the careful use of coexistence modelling for forecasts and understanding drivers of change.
Stomatal patterning is differently regulated in adaxial and abaxial epidermis in Arabidopsis
Authors: Jalakas Pirko , Tulva Ingmar , Bērziņa Nele Malvīne , Hõrak Hanna 
Published: February 2024

AbstractStomatal pores in leaves mediate CO2uptake into the plant and water loss via transpiration. Most plants are hypostomatous with stomata present only in the lower leaf surface (abaxial epidermis). Many herbs, including the model plantArabidopsis thaliana, have substantial numbers of stomata also on the upper (adaxial) leaf surface. Studies of stomatal development have mostly focused on abaxial stomata and very little is known of adaxial stomatal formation. We addressed the role of leaf number in determination of stomatal density and stomatal ratio, and studied adaxial and abaxial stomatal patterns in mutants deficient in known abaxial stomatal development regulators. We found that stomatal density in some genetic backgrounds varies between different fully expanded leaves and recommend using defined leaves for analyses of stomatal patterning. Our results indicate that stomatal development is at least partly independently regulated in adaxial and abaxial epidermis, as i) plants deficient in ABA biosynthesis and perception have increased stomatal ratios, ii) theepf1epf2,tmmandsdd1mutants have reduced stomatal ratios, iii)erl2mutants have increased adaxial but not abaxial stomatal index, and iv) stomatal precursors preferentially occur in abaxial epidermis. Further studies of adaxial stomata can reveal new insights into stomatal form and function.
The evolution of reduced facilitation in a four-species bacterial community
Authors: Piccardi Philippe , Ulrich Eric , Garcia-Garcerà Marc , Martino Rita Di , Testa Samuele E. A. , Mitri Sara 
Published: February 2024

AbstractMicrobial evolution is typically studied in mono-cultures or in communities of competing species. But microbes do not always compete and how positive inter-species interactions drive evolution is less clear: Initially facilitative communities may either evolve increased mutualism, increased reliance on certain species according to the Black Queen Hypothesis (BQH), or weaker interactions and resource specialization. To distinguish between these outcomes, we evolved four species for 44 weeks either alone or together in a toxic pollutant. These species initially facilitated each other, promoting each other’s survival and pollutant degradation. After evolution, two species (Microbacterium liquefaciensandOchrobactrum anthropi) that initially relied fully on others to survive continued to do so, with no evidence for increased mutualism. Instead,Agrobacterium tumefaciensandComamonas testosteroni(Ct) whose ancestors interacted positively, evolved in community to interact more neutrally and grew less well than when they had evolved alone, suggesting that the community limited their adaptation. We detected several gene loss events inCtwhen evolving with others, but these events did not increase its reliance on other species, contrary to expectations under the BQH. We hypothesize instead that these gene loss events are a consequence of resource specialization. Finally, co-evolved communities degraded the pollutant worse than their ancestors. Together, our results support the evolution of weakened interactions and resource specialization, similar to what has been observed in competitive communities.
MaizeCODE reveals bi-directionally expressed enhancers that harbor molecular signatures of maize domestication
Authors: Cahn Jonathan , Regulski Michael , Lynn Jason , Ernst Evan , Alves Cristiane de Santis , Ramakrishnan Srividya , Chougule Kapeel , Wei Sharon , Lu Zhenyuan , Xu Xiaosa , Drenkow Jorg , Kramer Melissa , Seetharam Arun , Hufford Matthew B. , McCombie W. Richard , Ware Doreen , Jackson David , Schatz Michael C. , Gingeras Thomas R. , Martienssen Robert A. 
Published: February 2024

AbstractModern maize was domesticated fromTeosinte parviglumis, with subsequent introgressions fromTeosinte mexicana, yielding increased kernel row number, loss of the hard fruit case and dissociation from the cob upon maturity, as well as fewer tillers. Molecular approaches have identified several transcription factors involved in the development of these traits, yet revealed that a complex regulatory network is at play. MaizeCODE deploys ENCODE strategies to catalog regulatory regions in the maize genome, generating histone modification and transcription factor ChIP-seq in parallel with transcriptomics datasets in 5 tissues of 3 inbred lines which span the phenotypic diversity of maize, as well as the teosinte inbred TIL11. Integrated analysis of these datasets resulted in the identification of a comprehensive set of regulatory regions in each inbred, and notably of distal enhancers which were differentiated from gene bodies by their lack of H3K4me1. Many of these distal enhancers expressed non- coding enhancer RNAs bi-directionally, reminiscent of “super enhancers” in animal genomes. We show that pollen grains are the most differentiated tissue at the transcriptomic level, and share features with endosperm that may be related to McClintock’s chromosome breakage- fusion-bridge cycle. Conversely, ears have the least conservation between maize and teosinte, both in gene expression and within regulatory regions, reflecting conspicuous morphological differences selected during domestication. The identification of molecular signatures of domestication in transcriptional regulatory regions provides a framework for directed breeding strategies in maize.
Living in a multi-stressor world: nitrate pollution and thermal stress interact to affect amphibian larvae
Authors: Sinai Noa , Eterovick Paula C. , Kruger Natasha , Oetken Ben , Ruthsatz Katharina 
Published: February 2024

AbstractThe interaction of widespread stressors such as nitrate pollution and increasing temperatures associated with climate change are likely to affect aquatic ectotherms such as amphibians. The metamorphic and physiological traits of amphibian larvae during the critical onset of metamorphosis are particularly susceptible to these stressors. We conducted a common-garden experiment usingRana temporarialarvae subjected to four constant acclimation temperatures (18, 22, 26, 28 °C) crossed with three environmentally relevant nitrate concentrations (0, 50, 100 mg × L-1) to investigate the interactive and individual effects of these stressors on metamorphic (i.e., growth and development) and physiological traits (i.e., metabolism and heat tolerance) at the onset of metamorphosis. Larvae exposed to elevated nitrate concentrations and thermal stress displayed increased metabolic rates but decreased developmental rate, highlighting interactive effects of these stressors. However, nitrate pollution alone had no effect on either metamorphic or physiological traits, suggesting that detoxification processes were sufficient to maintain homeostasis but not in combination with increased acclimation temperatures. Furthermore, larvae exposed to nitrate displayed diminished abilities to exhibit temperature-induced plasticity in metamorphosis timing and heat tolerance, as well as reduced acclimation capacity in metabolic rate and heat tolerance to higher temperatures. These results highlight the importance of considering the exposure to multiple stressors when investigating how natural populations respond to global change.
Individualized temporal patterns dominate cortical upstate and sleep depth in driving human sleep spindle timing
Authors: Chen Shuqiang , He Mingjian , Brown Ritchie E. , Eden Uri T. , Prerau Michael J. 
Published: February 2024

ABSTRACTSleep spindles are critical for memory consolidation and strongly linked to neurological disease and aging. Despite their significance, the relative influences of factors like sleep depth, cortical up/down states, and spindle temporal patterns on individual spindle production remain poorly understood. Moreover, spindle temporal patterns are typically ignored in favor of an average spindle rate. Here, we analyze spindle dynamics in 1008 participants from the Multi-Ethnic Study of Atherosclerosis using a point process framework. Results reveal fingerprint-like temporal patterns, characterized by a refractory period followed by a period of increased spindle activity, which are highly individualized yet consistent night-to-night. We observe increased timing variability with age and distinct gender/age differences. Strikingly, and in contrast to the prevailing notion, individualized spindle patterns are the dominant determinant of spindle timing, accounting for over 70% of the statistical deviance explained by all of the factors we assessed, surpassing the contribution of slow oscillation (SO) phase (∼14%) and sleep depth (∼16%). Furthermore, we show spindle/SO coupling dynamics with sleep depth are preserved across age, with a global negative shift towards the SO rising slope. These findings offer novel mechanistic insights into spindle dynamics with direct experimental implications and applications to individualized electroencephalography biomarker identification.
Distinct impacts of each anti-anti-sigma factor ortholog of the chlamydial Rsb partner switching mechanism on development inChlamydia trachomatis
Authors: Junker Shiomi , Singh Vandana , Al-Saadi Aamal G.M. , Wood Nicholas A. , Hamilton-Brehm Scott D. , Ouellette Scot P. , Fisher Derek J. 
Published: February 2024

AbstractPartner Switching Mechanisms (PSM) are signal transduction systems comprised of a sensor phosphatase (RsbU), an anti-sigma factor (RsbW, kinase), an anti-anti-sigma factor (RsbV, the RsbW substrate), and a target sigma factor.Chlamydiaspp. are obligate intracellular bacterial pathogens of animals that undergo a developmental cycle transitioning between the infectious elementary body (EB) and replicative reticulate body (RB) within a host-cell derived vacuole (inclusion). Secondary differentiation events (RB to EB) are transcriptionally regulated, in part, by the house-keeping sigma factor (σ66) and two late-gene sigma factors (σ54and σ28). Prior research supports that the PSM inChlamydia trachomatisregulates availability of σ66. Pan-genome analysis revealed that PSM components are conserved across the phylum Chlamydiota, withChlamydiaspp. possessing an atypical arrangement of two anti-anti-sigma factors, RsbV1 and RsbV2. Bioinformatic analyses support RsbV2 as the homolog to the pan-genome conserved RsbV with RsbV1 as an outlier. This, combined within vitrodata, indicates that RsbV1 and RsbV2 are structurally and biochemically distinct. Reduced levels or overexpression of RsbV1/RsbV2 did not significantly impactC. trachomatisgrowth or development. In contrast, overexpression of a non-phosphorylatable RsbV2 S55A mutant, but not overexpression of an RsbV1 S56A mutant, resulted in a 3 log reduction in infectious EB production without reduction in genomic DNA (total bacteria) or inclusion size, suggesting a block in secondary differentiation. The block was corroborated by reduced production of σ54/28-regulated late proteins and via transmission electron microscopy.ImportanceC. trachomatisis the leading cause of reportable bacterial sexually transmitted infections (STIs) and causes the eye infection trachoma, a neglected tropical disease. Broad-spectrum antibiotics used for treatment can lead to microbiome dysbiosis and increased antibiotic resistance development in other bacteria, and treatment failure for chlamydial STIs is a recognized clinical problem. Here, we show that disruption of a partner switching mechanism (PSM) significantly reduces infectious progeny production via blockage of RB to EB differentiation. We also reveal a novel PSM expansion largely restricted to the species infecting animals, suggesting a role in pathogen evolution. Collectively, our results highlight the chlamydial PSM as a key regulator of development and as a potential target for the development of novel therapeutics to treat infections.