bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program
Authors: Burton Oliver , Bricard Orian , Tareen Samar , Gergelits Vaclav , Andrews Simon , Roca Carlos P. , Whyte Carly , Junius Steffie , Brajic Aleksandra , Pasciuto Emanuela , Ali Magda , Lemaitre Pierre , Schlenner Susan M. , Ishigame Harumichi , Brown Brian D. , Dooley James , Liston Adrian 
Published: August 2023

AbstractThe tissues are the site of many of the most important immunological reactions, yet the immunology of the tissues has remained relatively opaque. Recent studies have identified Foxp3+regulatory T cells (Tregs) in several non-lymphoid tissues. These tissue-resident populations have been ascribed unique characteristics based on comparisons to lymphoid Tregs. Here we performed a systematic analysis of the Treg population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency and common molecular dependencies. Further, tissue Tregs from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg entry. Finally, tissue Tregs extracted from non-lymphoid organs were tissue-agnostic on re-entry, without homing preference for their tissue of origin. Together these results demonstrate that the tissue-resident Treg pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Tregs, characterised by transient multi-tissue migration and a common residency program.
Organisation of the nervous system in cysts of the freshwater tardigradeThulinius ruffoi(Parachela, Isohypsibioidea: Doryphoribiidae)
Authors: Janelt Kamil , Poprawa Izabela 
Published: August 2023

AbstractEncystment is a natural process that involves cyst formation, and at least some species of tardigrades can form cysts. However, the encystment process and cyst structure among tardigrades are still poorly understood. Despite some aspects of the encysted animals’ system organisation being examined in the past, the morphology and structure of the nervous system have never been thoroughly investigated. The present study covers anatomical, histological and morphological details and proposes physiological aspects of the nervous system in encystedThulinius ruffoiup to 11 months duration in encystment. This is the first record of the nervous system organisation in a species belonging to the family Doryphoribiidae and describes morphological changes that occur during cyst formation.
Fecal pH and redox as functional markers in the premature infant gut microbiome
Authors: Letourneau Jeffrey , Walker LaShawndra , Han Se Hyang , David Lawrence A , Younge Noelle 
Published: August 2023

ABSTRACTThe infant gut microbiome is a crucial factor in health and development. In preterm infants, altered gut microbiome composition and function have been linked to serious neonatal complications such as necrotizing enterocolitis and sepsis, which can lead to long-term disability. Although many studies have described links between microbiome composition and disease risk, there is a need for biomarkers to identify infants at risk of these complications in practice. In this study, we obtained stool samples from preterm infant participants longitudinally during the first postnatal months, and measured pH and redox, as well as SCFA content and microbiome composition by 16S rRNA gene amplicon sequencing. These outcomes were compared to clinical data to better understand the role of pH and redox in infant gut microbiome development and overall health, and to assess the potential utility of pH and redox as biomarkers. We found that infants born earlier or exposed to antibiotics exhibited increased fecal pH, and that redox potential increased with postnatal age. These differences may be linked to changes in SCFA content, which was correlated with pH and increased with age. Microbiome composition was also related to birth weight, age, pH, and redox. Our findings suggest that pH and redox may serve as biomarkers of metabolic state in the preterm infant gut.
Field application of de novo transcriptomic analysis to evaluate the effects of sublethal freshwater salinization onGasterosteus aculeatusin urban streams
Authors: Escobar-Sierra Camilo , Lampert Kathrin P. 
Published: August 2023

AbstractFreshwater salinization poses global challenges for aquatic organisms, impacting their physiology and ecology. However, current salinization research predominantly focuses on mortality endpoints in limited model species, overlooking the sublethal effects on a broader spectrum of organisms and the exploration of adaptive mechanisms and pathways under natural field conditions. To address these gaps, we conducted high-throughput sequencing transcriptomic analysis on the gill tissue of the euryhaline fishGasterosteus aculeatus, investigating its molecular response to salinity stress in the highly urbanized river Boye, Germany. We found that even sublethal concentrations of chloride led to the activation of the energetically costly osmoregulatory system inG. aculeatus, evidenced by the differential expression of genes related to osmoregulation. Our enrichment analysis revealed differentially expressed genes (DEGs) related to transmembrane transport and regulation of transport and other osmoregulation pathways, which aligns with the crucial role of these pathways in maintaining biological homeostasis. Notably, we identified candidate genes involved in increased osmoregulatory activity under salinity stress, including those responsible for moving ions across membranes: ion channels, ion pumps, and ion transporters. Particularly, genes from the solute carrier family SLC, aquaporinAQP1, chloride channelCLC7, ATP-binding cassette transporterABCE1, and ATPases member ATAD2 exhibited prominent differential expression. These findings provide insights into the molecular mechanisms underlying the adaptive response of euryhaline fish to salinity stress and have implications for their conservation and management in the face of freshwater salinization.
A molecular proximity sensor based on an engineered, dual-component guide RNA
Authors: Choi Junhong , Chen Wei , Liao Hanna , Li Xiaoyi , Shendure Jay 
Published: August 2023

AbstractOne of the goals of synthetic biology is to enable the design of arbitrary molecular circuits with programmable inputs and outputs. Such circuits bridge the properties of electronic and natural circuits, processing information in a predictable manner within living cells. Genome editing is a potentially powerful component of synthetic molecular circuits, whether for modulating the expression of a target gene or for stably recording information to genomic DNA. However, programming molecular events such as protein-protein interactions or induced proximity as triggers for genome editing remains challenging. Here we demonstrate a strategy termed “P3 editing”, which linksprotein-proteinproximity to the formation of a functional CRISPR-Cas9 dual-component guide RNA. By engineering the crRNA:tracrRNA interaction, we demonstrate that various known protein-protein interactions, as well as the chemically-induced dimerization of protein domains, can be used to activate prime editing or base editing in human cells. Additionally, we explore how P3 editing can incorporate outputs from ADAR-based RNA sensors, potentially allowing specific RNAs to induce specific genome edits within a larger circuit. Our strategy enhances the controllability of CRISPR-based genome editing, facilitating its use in synthetic molecular circuits deployed in living cells.
Developmental transcriptomes predict adult social behaviors in the socially flexible sweat bee,Lasioglossum baleicum
Authors: Omufwoko Kennedy S. , Cronin Adam L. , Nguyen Thi Thu Ha , Webb Andrew E. , Traniello Ian M. , Kocher Sarah D. 
Published: August 2023

AbstractNatural variation can provide important insights into the genetic and environmental factors that shape social behavior and its evolution. The sweat bee,Lasioglossum baleicum, is a socially flexible bee capable of producing both solitary and eusocial nests. We demonstrate that within a single nesting aggregation, soil temperatures are a strong predictor of the social structure of nests. Sites with warmer temperatures in the spring have a higher frequency of social nests than cooler sites, perhaps because warmer temperatures provide a longer reproductive window for those nests. To identify the molecular correlates of this behavioral variation, we generated ade novogenome assembly forL. baleicum, and we used transcriptomic profiling to compare adults and developing offspring from eusocial and solitary nests. We find that adult, reproductive females have similar expression profiles regardless of social structure in the nest, but that there are strong differences between reproductive females and workers from social nests. We also find substantial differences in the transcriptomic profiles of stage-matched pupae from warmer, social-biased sites compared to cooler, solitary-biased sites. These transcriptional differences are strongly predictive of adult reproductive state, suggesting that the developmental environment may set the stage for adult behaviors inL. baleicum. Together, our results help to characterize the molecular mechanisms shaping variation in social behavior and highlight a potential role of environmental tuning during development as a factor shaping adult behavior and physiology in this socially flexible bee.
Bacterial degradation of ctenophoreMnemiopsis leidyiorganic matter
Authors: Fadeev Eduard , Hennenfeind Jennifer H , Amano Chie , Zhao Zihao , Klun Katja , Herndl Gerhard J , Tinta Tinkara 
Published: August 2023

AbstractBlooms of gelatinous zooplankton, an important source of protein-rich biomass in coastal waters, often collapse rapidly, releasing large amounts of labile detrital organic matter (OM) into the surrounding water. Although these blooms have the potential to cause major perturbations in the marine ecosystem, their effects on the microbial community and hence on the biogeochemical cycles have yet to be elucidated. We conducted microcosm experiments simulating the scenario experienced by coastal bacterial communities after the decay of a ctenophore (Mnemiopsis leidyi) bloom in the northern Adriatic Sea. Within 24 h, a rapid response of bacterial communities to theM. leidyiOM was observed, characterized by elevated bacterial biomass production and respiration rates. Compared to our previous microcosm study of jellyfish (Aurelia aurita s.l.),M. leidyiOM degradation revealed that, despite the fundamental genetic and biochemical differences between the two species, a similar pattern in the bacterial community response was observed. Combined metagenomic and metaproteomic analysis indicated that the degradation activity was mainly performed byPseudoalteromonas, producing a large amount of proteolytic exoenzymes and exhibiting high metabolic activity. Interestingly, the reconstructed metagenome-assembled genome (MAG) ofPseudoalteromonas phenolicawas almost identical (average nucleotide identity >99%) to the MAG previously reconstructed in ourA. auritamicrocosm study. Taken together our data suggest that blooms of different gelatinous zooplankton are likely triggering a consistent response from natural bacterial communities, with specific bacterial lineages driving the remineralization of the gelatinous OM.ImportanceJellyfish blooms are increasingly becoming a recurring seasonal event in marine ecosystems, characterised by a rapid build-up of gelatinous biomass that collapses rapidly. Although these blooms have the potential to cause major perturbations, their impact on marine microbial communities is largely unknown. We conducted an incubation experiment simulating a bloom of the ctenophoreMnemiopsis leidyiin the Northern Adriatic, where we investigated the bacterial response to the gelatinous biomass. We found that the bacterial communities actively degraded the gelatinous organic matter, and overall showed a striking similarity to the dynamics previously observed after a simulated bloom of the jellyfishAurelia aurita s.l. In both cases we found that a single bacterial species,Pseudoalteromonas phenolica, was responsible for most of the degradation activity. This suggests that blooms of different jellyfish are likely to trigger a consistent response from natural bacterial communities, with specific bacterial species driving the remineralisation of gelatinous biomass.
Development of Gemcitabine-Modified miRNA Mimics as Cancer Therapeutics for Pancreatic Ductal Adenocarcinoma
Authors: Yuen John G. , Hwang Ga-Ram , Fesler Andrew , Intriago Erick , Pal Amartya , Ojha Anushka , Ju Jingfang 
Published: August 2023

AbstractPancreatic cancer, including its most common subtype, pancreatic adenocarcinoma (PDAC), has the lowest five-year survival rate among patients with pancreatic cancer in the United States. Despite advancements in anticancer treatment, the overall median survival for patients with PDAC has not dramatically improved. Therefore, there is an urgent need to develop new strategies of treatment to address this issue. Non-coding RNAs, including microRNAs (miRNAs), have been found to have major roles in carcinogenesis and the subsequent treatment of various cancer types like PDAC. In this study, we developed a treatment strategy by modifying tumor suppressor miRNAs,hsa-miRNA-15a(miR-15a) andhsa-miRNA-194-1(miR-194), with the nucleoside analog chemotherapeutic gemcitabine (Gem) to create Gem-modified mimics of miR-15a (Gem-miR-15a) and miR-194 (Gem-miR-194). In a panel of PDAC cell lines, we found that Gem-miR-15a and Gem-miR-194 induce cell cycle arrest and apoptosis, and these mimics are potent inhibitors with IC50values up to several hundred fold less than their native counterparts or Gem alone. Furthermore, we found that Gem-miR-15a and Gem-miR-194 retained miRNA function by downregulating the expression of several key targets including WEE1, CHK1, BMI1, and YAP1 for Gem-miR-15a, and FOXA1 for Gem-miR-194. We also found that our Gem-modified miRNA mimics exhibit an enhanced efficacy compared to Gem alone in patient-derived PDAC organoids. Furthermore, we observed that Gem-miR-15a significantly inhibits PDAC tumor growthin vivowithout observing any noticeable signs of toxicity. Overall, our results demonstrate the therapeutic potential of Gem-modified miRNAs as a treatment strategy for PDAC.One Sentence SummaryYuen and Hwanget. al.have developed a potent therapeutic strategy for patients with pancreatic cancer by modifying microRNAs with gemcitabine.
Electrically controlled interaction between cable bacteria and carbon electrodes
Authors: Bonné Robin , Marshall Ian P.G. , Bjerg Jesper , Marzocchi Ugo , Manca Jean , Nielsen Lars Peter , Aiyer Kartik 
Published: August 2023

AbstractCable bacteria couple the oxidation of sulphide in sediments to the reduction of oxygen via long-distance electron transfer through periplasmic wires. While direct electron transfer between cable bacteria cells belonging to the same filament is a well-known phenomenon, electron transfer from the filament to electrodes has remained elusive. In this study, we demonstrate that living cable bacteria are attracted to electrodes in different bioelectrochemical systems. Carbon felt and carbon fibre electrodes poised at +200 mV against an Ag/AgCl reference attracted live cable bacteria from the sediment. When the applied potential was switched off, cable bacteria retracted from the electrode. qPCR and scanning electron microscopy corroborated this finding and revealed cable bacteria adhered onto the electrode surface. These experiments raise new possibilities to cultivate cable bacteria and utilise them for important applications in bioelectrochemical systems.
From paralogy to hybridization: Investigating causes of underlying phylogenomic discordance using the complex genusPackera(Senecioneae; Asteraceae)
Authors: Moore-Pollard Erika R. , Mandel Jennifer R. 
Published: August 2023

ABSTRACTPremise of the studyUnderlying discordance in phylogenomic studies is becoming more common, and the answer is not as simple as adding more data. Biological processes such as polyploidy, hybridization, and incomplete lineage sorting are main contributors to these issues and must be considered when generating phylogenies. Otherwise, interpretations of evolutionary relationships could be misleading.MethodsTo obtain a better understanding of potential gene flow and its effect on phylogenetic trees, we investigated the causes and consequences of nuclear discordance using the genusPackerato understand how they influence the phylogenetic patterns seen in this complex group. To do this, we compared the topology and support values ofPackeraphylogenies resulting from various paralog selection or pruning methods. We then investigated whether pruning the paralogs instead of performing a selection process affected the topology and support of our phylogeny. To investigate hybridization and its effect on species relationships in our tree, we used likelihood methods to infer phylogenetic networks to find any evidence of gene flow among species lineages in this complicated genus.Key resultsWe found that performing different paralog selection or pruning methods does impact our understanding of the evolutionary relationships withinPackera, and that addressing these paralogs with more rigorous methods than the typical pipeline increases concordance within the resulting phylogenies. Additionally, investigating reticulation events within highly discordant clades showed that ancestral hybridization and reticulation events are common throughoutPackera.ConclusionsInvestigating underlying biological processes by testing various methods can provide further insight into complex species relationships and levels of discordance within phylogenomic studies.
Gut mucosal cells transfer α-synuclein to the vagus nerve
Authors: Chandra Rashmi , Sokratian Arpine , Chavez Katherine R. , King Stephanie , Swain Sandip M. , Snyder Joshua C. , West Andrew B. , Liddle Rodger A. 
Published: August 2023

AbstractEpidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson’s disease (PD). While past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut to brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of the gut mucosa express α-synuclein. In this study, we employed mouse intestinal organoids expressing human α-synuclein to observe the transfer of α-synuclein protein from gut epithelial cells in organoids co-cultured with vagal nodose neurons that are otherwise devoid of α-synuclein expression. In intact mice that express pathological human α-synuclein, but no mouse α-synuclein, α-synuclein fibril templating activity emerges in α-synuclein seeded fibril aggregation assays in tissues from the gut, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human α-synuclein expression to intestinal epithelial cells, α-synuclein fibril-templating activity transfers to the vagus nerve and to the dorsal motor nucleus. Subdiaphragmatic vagotomy prior to the induction of α-synuclein expression in the gut epithelial cells effectively protects the hindbrain from the emergence of α-synuclein fibril templating activity. Overall, these findings highlight a novel potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells.
Pseudomonas aeruginosaMipA-MipB envelope proteins act as new sensors of polymyxin
Authors: Janet-Maitre Manon , Job Viviana , Bour Maxime , Brugière Sabine , Robert-Genthon Mylène , Cobessi David , Couté Yohann , Jeannot Katy , Attrée Ina 
Published: August 2023

AbstractDue to the rising incidence of antibiotic resistant infections, the last-line antibiotics polymyxins have resurged in the clinics in parallel with new bacterial strategies of escape. The Gram-negative opportunistic pathogenPseudomonas aeruginosadevelops resistance to colistin/polymyxin by distinct molecular mechanisms, mostly through modification of the lipid A component of the LPS by proteins encoded within thearnBCDATEF-ugd(arn) operon. In this work, we characterized a polymyxin-induced operon, namedmipBA, notably present inP. aeruginosastrains devoid of thearnoperon. We showed thatmipBAis activated by ParR/ParS two-component regulatory system in response to polymyxin. MipA and MipB localize to bacterial outer membrane and form a complexin vitro. Structural modeling revealed that the lipoprotein MipB adopts a β-lactamase fold with two additional C-terminal domains,while MipA folds as an outer-membrane β-barrel, harboring an internal negatively charged channel, able to host a polymyxin molecule. Nano differential scanning fluorimetry (DSF) showed that polymyxin stabilized MipA proteinin vitro. Mass spectrometry-based quantitative proteomics on whole bacterial membranes demonstrated that the ΔmipBAmutant synthesized less MexXY-OprA proteins in response to polymyxin compared to the wild-type strain, as a consequence of impaired transcriptional activation of themexoperon. We propose MipA/MipB to act as membrane (co)sensors working in concert to activate ParS histidine kinase and help the bacterium to cope with polymyxin-mediated envelope stress through synthesis of the efflux pomp, MexXY-OprA.
Global nuclear reorganization during heterochromatin replication in the giant-genome plantNigella damascenaL.
Authors: Arifulin Eugene A. , Sorokin Dmitry V. , Anoshina Nadezhda A. , Kuznetsova Maria A. , Valyaeva Anna A. , Potashnikova Daria M. , Omelchenko Denis O. , Schubert Veit , Kolesnikova Tatyana D. , Sheval Eugene V. 
Published: August 2023

ABSTRACTAmong flowering plants, genome size varies remarkably, by >2200-fold, and this variation depends on the loss and gain of non-coding DNA sequences that form distinct heterochromatin complexes during interphase. In plants with giant genomes, most chromatin remains condensed during interphase, forming a dense network of heterochromatin threads called interphase chromonemata. Using super-resolution light and electron microscopy, we studied the ultrastructure of chromonemata during and after replication in root meristem nuclei ofNigella damascenaL. During S-phase, heterochromatin undergoes transient decondensation locally at DNA replication sites. Due to the abundance of heterochromatin, the replication leads to a robust disassembly of the chromonema meshwork and a general reorganization of the nuclear morphology visible even by conventional light microscopy. After replication, heterochromatin recondenses, restoring the chromonema structure. Thus, we show that heterochromatin replication in interphase nuclei of giant-genome plants induces a global nuclear reorganization.