bluuebunny/crossref_metadata_2025_split huggingface dataset:
Little evidence for inbreeding depression for birth mass, survival and growth in Antarctic fur seal pups
Authors: Paijmans A.J. , Berthelsen A.L. , Nagel R. , Cristaller F. , Kröcker N. , Forcada J. , Hoffman J.I. 
Published: January 2024

AbstractInbreeding depression, the loss of offspring fitness due to consanguineous mating, is generally detrimental for individual performance and population viability. We therefore investigated inbreeding effects in a declining population of Antarctic fur seals at Bird Island, South Georgia. Here, localised warming has reduced the availability of the seal’s staple diet, Antarctic krill, leading to a temporal increase in the strength of viability selection against inbred offspring, which are increasingly failing to recruit into the adult breeding population. However, it remains unclear whether viability selection operates before or after nutritional independence at weaning. We therefore used microsatellite data from 884 pups and their mothers, and SNP array data from 100 mother-offspring pairs, to quantify the effects of individual and maternal inbreeding on three important neonatal fitness traits: birth mass, survival and growth. We did not find any clear or consistent effects of inbreeding on any of these traits. This suggests that viability selection filters inbred individuals out of the population as juveniles during the time window between weaning and recruitment. Our study brings into focus a poorly understood life-history stage and emphasises the importance of understanding the ecology and threats facing juvenile pinnipeds.
Intrinsically disordered regions regulate RhlE RNA helicase functions in bacteria
Authors: Hausmann Stéphane , Geiser Johan , Allen George Edward , Geslain Sandra Amandine Marie , Valentini Martina 
Published: January 2024

AbstractRNA helicases—central enzymes in RNA metabolism— often feature intrinsically disordered regions (IDRs) that enable phase separation and complex molecular interactions. In the bacterial pathogenPseudomonas aeruginosa, the non-redundant RhlE1 and RhlE2 RNA helicases share a conserved REC catalytic core but differ in C-terminal IDRs. Here, we show how the IDR diversity defines RhlE RNA helicase specificity of function. Both IDRs facilitate RNA binding and phase separation, localizing proteins in cytoplasmic clusters. However, RhlE2 IDR is more efficient in enhancing REC core RNA unwinding, exhibits a greater tendency for phase separation, and interacts with the RNase E endonuclease, a crucial player in mRNA degradation. Swapping IDRs results in chimeric proteins that are biochemically active but functionally distinct as compared to their native counterparts. The RECRhlE1-IDRRhlE2chimera improves cold growth of arhlE1mutant, gains interaction with RNase E and affects a subset of both RhlE1 and RhlE2 RNA targets. The RECRhlE2-IDRRhlE1chimera instead hampers bacterial growth at low temperatures in the absence of RhlE1, with its detrimental effect linked to aberrant RNA droplets. By showing that IDRs modulate both protein core activities and subcellular localization, our study defines the impact of IDR diversity on the functional differentiation of RNA helicases.
Different metabolite profiles acrossPenicillium roquefortipopulations associated with ecological niche specialisation and domestication
Authors: Crequer Ewen , Coton Emmanuel , Cueff Gwennina , Cristiansen Johan V. , Frisvad Jens C. , de la Vega Ricardo Rodriguez , Giraud Tatiana , Jany Jean-Luc , Coton Monika 
Published: January 2024

AbstractFungi are known to produce many chemically diversified metabolites, yet their ecological roles are not always fully understood. The blue cheese making fungusPenicillium roquefortithrives in different ecological niches and is known to produce a wide range of metabolites, including mycotoxins. ThreeP. roquefortipopulations have been domesticated for cheese production and two populations thrive in other anthropized environments, i.e., spoiled food, lumber and silage. Here, we looked for differences in targeted and untargeted metabolite production profiles between populations using HPLC-HR-Q-TOF and UHPLC-Q-TOF-HR-MS/MS. The non-cheese populations produced several fatty acids and different terpenoids, lacking in cheese strains. The Termignon cheese population displayed intermediate metabolite profiles between cheese and non-cheese populations, as previously shown for other traits. The non-Roquefort population, the cheese population with the strongest domestication syndrome, produced the lowest quantities of measured metabolites, including known mycotoxins such as mycophenolic acid (MPA), andrastin A and PR toxin. Its inability to produce MPA was due to a deletion in thempaCgene, while a premature stop codon in ORF 11 of the PR toxin gene cluster explained its absence and the accumulation of its eremofortin A & B intermediates. In the Roquefort population, we detected no PR toxin nor eremofortins A or B, but found no indel or frameshift mutation, suggesting downregulation. Our results suggest that domesticated cheese populations were selected for lower toxin production while populations from other anthropized environments maintained high metabolite diversity, the bioactivities of these compounds being likely important in these ecological niches.
Droplet microfluidics for time-resolved serial crystallography
Authors: Stubbs Jack , Hornsey Theo , Hanrahan Niall , Esteban Luis Blay , Bolton Rachel , Malý Martin , Basu Shibom , Orlans Julien , de Sanctis Daniele , Shim Jung-uk , Stewart Patrick D. Shaw , Orville Allen M. , Tews Ivo , West Jonathan 
Published: January 2024

AbstractSerial crystallography requires large numbers of microcrystals and robust strategies to rapidly apply substrates to initiate reactions in time-resolved studies. Here we report the use of droplet miniaturisation for the controlled production of uniform crystals, providing an avenue for controlled diffusion and synchronous reaction initiation. The approach was evaluated using two enzymatic systems, yielding 3-µm lysozyme crystals and 2-µm crystals of Pdx1, an Arabidopsis enzyme involved in vitamin B6 biosynthesis. A seeding strategy was used to overcome the improbability of Pdx1 nucleation occurring with diminishing droplet volumes. Convection within droplets was exploited for rapid crystal mixing with ligands. Mixing times of <2 milliseconds were achieved. Droplet microfluidics for crystal size engineering and rapid micromixing can be used to advance time-resolved serial crystallography.
Intestinal stearoyl-CoA desaturase-1 regulates energy balance via alterations in bile acid homeostasis
Authors: Burchat Natalie , Vidola Jeanine , Pfreundschuh Sarah , Sharma Priyanka , Rizzolo Daniel , Guo Grace L. , Sampath Harini 
Published: January 2024

AbstractBackground and AimsStearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids into monounsaturated fatty acids and plays an important regulatory role in lipid metabolism. Previous studies have demonstrated that mice deficient in SCD1 are protected from diet-induced obesity and hepatic steatosis due to altered lipid esterification and increased energy expenditure. Previous studies in our lab have shown that intestinal SCD1 modulates intestinal and plasma lipids and alters cholesterol metabolism. Here we investigated a novel role for intestinal SCD1 in the regulation of systemic energy balance.MethodsTo interrogate the role of intestinal SCD1 in modulating whole body metabolism, intestine-specificScd1knockout (iKO) mice were maintained on standard chow diet or challenged with a high-fat diet (HFD). Studies included analyses of bile acid content and composition, metabolic phenotyping including body composition, indirect calorimetry, glucose tolerance analyses, and assessment of bile acid signaling pathways.ResultsiKO mice displayed elevated plasma and hepatic bile acid content and decreased fecal bile acid excretion, associated with increased expression of the ileal bile acid uptake transporter,Asbt. These increases were associated with increased expression of TGR5 targets, includingDio2in brown adipose tissue and elevated plasma glucagon-like peptide-1 levels. Upon HFD challenge, iKO mice had reduced metabolic efficiency apparent through decreased weight gain despite higher food intake. Concomitantly, energy expenditure was increased, and glucose tolerance was improved in HFD-fed iKO mice.ConclusionOur results indicate that deletion of intestinal SCD1 has significant impacts on bile acid metabolism and whole-body energy balance, likely via activation of TGR5.
Divisome minimization shows that FtsZ and SepF can form an active Z-ring, and reveals BraB as a new cell division influencing protein inBacillus subtilis
Authors: Gulsoy Ilkay Celik , Saaki Terrens N. V. , Wenzel Michaela , Syvertsson Simon , Morimoto Taku , Hamoen Leendert W. 
Published: January 2024

ABSTRACTOne of the aims of synthetic biology is the construction of a minimal cell. Since bacteria are the simplest life forms, they are the preferred blueprint for such a cell. In this study, we tried to find the minimal set of proteins required for division of a cell wall containing cell, using the bacterial model systemBacillus subtilis. Bacterial cytokinesis begins with polymerization of the tubulin homologue FtsZ at midcell into the Z-ring, which recruits the late cell division protein that synthesize the division septum. Assembly of FtsZ is carefully regulated, involving a dozen conserved cell division proteins. These proteins are not essential, but removing more than one is in many cases lethal. We made use of known suppressor mutations to find a gene deletion route that eventually enabled us to remove eight conserved cell division proteins: ZapA, MinC, MinJ, UgtP, ClpX, Noc, EzrA and FtsA. Only FtsZ and its membrane anchor SepF appeared to be required for Z-ring formation. Interestingly, SepF is also the FtsZ anchor in archaea, and both proteins may date back to the Last Universal Common Ancestor (LUCA). Curiously, viability was not greatly affected by the multiple deletions, although the frequency of cell division was considerably reduced. However, genome sequencing exposed the accumulation of several suppressor mutations, and revealed an unexpected cell division regulation function for the branched chain amino acid transporter BraB. The implications of these findings for the role of SepF in cell division, and the construction of a minimal cell division machinery are discussed.
Endoplasmic reticulum stress delays choroid development in theHCAR1knock-out mouse
Authors: Modaresinejad Monir , Yang Xiaojuan , Nezhady Mohammad Ali Mohammad , Zhu Tang , Bajon Emmanuel , Hou Xin , Tahiri Houda , Hardy Pierre , Rivera José Carlos , Lachapelle Pierre , Chemtob Sylvain 
Published: January 2024

AbstractThe sub-retina, composed of the choroid and the retinal pigment epithelium (RPE), bears a critical role in proper vision. In addition to phagocytosis of photoreceptor debris, the RPE shuttles oxygen and nutrients to the neuroretina. For their own energy production, RPE cells mainly rely on lactate, a major by-product of glycolysis. Lactate in turn is believed to convey most of its biological effects via the HCAR1 receptor. Here, we show that the lactate-specific receptor, HCAR1, is exclusively expressed in the RPE cells and thatHcar1−/−mice exhibit a substantially thinner choroid vasculature during development. Notably, the angiogenic properties of lactate on the choroid are impacted by the absence ofHcar1.Hcar1-deficient mice exhibit elevated endoplasmic reticulum (ER) stress along with eIF2α phosphorylation, a significant decrease in the global protein translation rate, and a lower proliferation rate of choroidal vasculature. Strikingly, inhibition of the Integrated Stress Response using an inhibitor of eIF2α phosphorylation (ISRIB) restores protein translation and rescues choroidal thinning. These results provide evidence that lactate signalling via HCAR1 is important for choroidal development/angiogenesis and highlight the importance of this receptor in establishing mature vision.
Identification and quantification of human relaxin proteins by immunoaffinity-mass spectrometry
Authors: Rais Yasmine , Drabovich Andrei P. 
Published: January 2024

ABSTRACTThe human relaxins belong to the Insulin/IGF/Relaxin superfamily of peptide hormones, and their physiological function is primarily associated with reproduction. In this study, we focused on a prostate tissue-specific relaxin RLN1 (REL1_HUMAN protein), and a broader tissue specificity RLN2 (REL2_HUMAN). Due to their structural similarity, REL1 and REL2 proteins were collectively named a ‘human relaxin protein’ in previous studies and were exclusively measured by immunoassays. We hypothesized that the highly selective and sensitive immunoaffinity-selected reaction monitoring (IA-SRM) assays could reveal the identity and concentration of REL1 and REL2 in biological samples and facilitate evaluation of these proteins for diagnostic applications. RT-PCR revealed the high levels of RLN1 and RLN2 transcripts in prostate and breast cancer cell lines. However, no endogenous prorelaxin-1 or mature REL1 were detected by IA-SRM in numerous biological samples. IA-SRM assay of REL2 revealed its undetectable levels (<9 pg/mL) in control female and male sera, relatively high levels of REL2 in maternal sera (median 331 pg/mL, 120 patients), and a biphasic expression of REL2 across the gestational weeks. IA-SRM assays discovered potential cross-reactivity and false-positive measurements for relaxin immunoassays. The developed IA-SRM assays will facilitate investigation of physiological and pathological roles of REL1 and REL2 peptide hormones.
The lateral habenula integrates age and experience to promote social transitions in developing rats
Authors: Cobb-Lewis Dana , George Anne , Hu Shannon , Packard Katherine , Song Mingyuan , Nguyen-Lopez Oliver , Tesone Emily , Rowden Jhanay , Wang Julie , Opendak Maya 
Published: January 2024

ABSTRACTSocial behavior deficits are an early-emerging marker of psychopathology and are linked with early caregiving quality. However, the infant neural substrates linking early care to social development are poorly understood. Here, we focused on the infant lateral habenula (LHb), a highly-conserved brain region at the nexus between forebrain and monoaminergic circuits. Despite its consistent links to adult psychopathology, this brain region has been understudied in development when the brain is most vulnerable to environmental impacts. In a task combining social and threat cues, suppressing LHb principal neurons had opposing effects in infants versus juveniles, suggesting the LHb promotes a developmental switch in social approach behavior under threat. We observed that early caregiving adversity (ECA) disrupts typical growth curves of LHb baseline structure and function, including volume, firing patterns, neuromodulatory receptor expression, and functional connectivity with cortical regions. Further, we observed that suppressing cortical projections to the LHb rescued social approach deficits following ECA, identifying this microcircuit as a substrate for disrupted social behavior. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control.
Identification of extracellular membrane protein ENPP3 as a major cGAMP hydrolase, cementing cGAMP’s role as an immunotransmitter
Authors: Mardjuki Rachel , Wang Songnan , Carozza Jacqueline A. , Abhiraman Gita C. , Lyu Xuchao , Li Lingyin 
Published: January 2024

AbstractcGAMP is a second messenger that is synthesized in the cytosol upon detection of cytosolic dsDNA and passed between cells to facilitate downstream immune signaling. ENPP1, an extracellular enzyme, was the only metazoan cGAMP hydrolase known to regulate cGAMP levels to dampen anti-cancer immunity. Here, we uncover ENPP3 as the second and only other metazoan cGAMP hydrolase under homeostatic conditions. ENPP3 has a tissue expression pattern distinct from that of ENPP1 and accounts for all remaining cGAMP hydrolysis activity in mice lacking ENPP1. Importantly, we also show that as with ENPP1, selectively abolishing ENPP3’s cGAMP hydrolase activity results in diminished cancer growth and metastasis of certain tumor types. Both ENPP1 and ENPP3 are extracellular enzymes, suggesting the dominant role that extracellular cGAMP must play as a mediator of cell-cell innate immune communication. Our work clearly shows that ENPP1 and ENPP3 non-redundantly dampen extracellular cGAMP-STING signaling, pointing to ENPP3 as a new target for cancer immunotherapy.
Transformation of human chondrocytes with copper-containing metal-organic biohybrids (MOBs)
Authors: Khasru Tasneem , McKenzie Katie , Rugg Kyle , Boudreaux Shaylee , McMahen Kelly , Uppu Navya , DeCoster Mark A. 
Published: January 2024

AbstractCopper is involved in the biosynthesis of collagen, however soluble copper salts dissipate quickly and copper nanoparticles are cytotoxic. Here we added a novel copper-containing nanomaterial (CuHARS) to assess human chondrocyte function in the presence of copper. Human dermal fibroblasts (HDFs) were also treated as a control. Chondrocyte response to CuHARS was assessed by chronic nanomaterial treatment (30 µg/ml) followed by digital microscopy and image analysis of cellular features compared to normal chondrocytes. Unexpectedly, chronic CuHARS treatment of human chondrocytes transformed cells over time to cells with extremely elongated and variegated processes and lower proliferation rates compared to normal chondrocytes. In these transformed cells, which we named 3G, shedding of fine processes was observed over time and collected supernatants demonstrated elevated collagen levels compared to normal cell culture media. In contrast to chondrocytes, HDFs treated with CuHARS showed attenuated changes in morphology, and notably retained a prominent ability for continued proliferation. These results demonstrate that a copper-containing biohybrid material (CuHARS) can stably transform human chondrocytes with highly altered morphology, lower proliferation rates, and altered membrane dynamics compared to normal chondrocytes. In contrast, human dermal fibroblasts demonstrated attenuated changes in morphology, and retained an enhanced ability for proliferation.
Investigating the molecular basis of cleptobiosis in eusocial stingless bees (Apidae: Hymenoptera)
Authors: Ricardo Paulo Cseri , Araujo Natalia De Souza , Arias Maria Cristina 
Published: January 2024

AbstractCleptobiosis is a widespread strategy among animals in which members of one species raid for food or other valuable resources that were obtained by another species. Obligate cleptobiotic species are however rare, and the eusocial stingless beeLestrimelitta limaofeatures amongst these rare species. This bee pillages other stingless bee colonies. To provide some insights into the molecular basis and evolution of cleptobiosis in eusocial bees, here we compare transcriptomic data of foraging workers of the robber beeL. limaoand three non-robber stingless bees:Nannotrigona testaceicornis, Scaptotrigona depilis, andTetragonisca angustula. Our findings demonstrate that most of the orthologs identified as differentially expressed (DE) among the robber and the non-robber bees are downregulated inL. limaoworkers, showing a reduced expression activity in the cleptobiont during foraging. Several DE orthologs potentially regulate neuronal and synaptic activities in addition to other critical cellular functions. Additionally, differentially expressed orthologs associated with floral resource exploration and energetic metabolism were identified. These genes warrant further investigation to enhance our understanding of the specific molecular adaptations associated with cleptobiosis in eusocial terms.
Forget and Forgive: A Neurocognitive Mechanism for Increased Cooperation During Group Formation
Authors: Zajkowski Wojciech , Badman Ryan P. , Haruno Masahiko , Akaishi Rei 
Published: January 2024

AbstractHow do group size changes influence cooperation within groups? To examine this question, we performed a dynamic, network-based prisoner’s dilemma experiment with fMRI. Across 83 human subjects, we observed increased cooperation as group size increased. However, our computational modeling analysis of behavior and fMRI revealed that group size itself did not increase cooperation. Rather, interaction between (1) subjects’ stable prosocial tendencies, and (2) dynamic reciprocal strategy weighted by memory confidence, underlies the group size-modulated increase in cooperation because the balance between them shifts toward the prosocial tendency with higher memory demands in the larger groups. We found that memory confidence was encoded in fusiform gyrus and precuneus, whereas its integration with prosocial tendencies was reflected in the left DLPFC and dACC. Therefore, interaction between recall uncertainty during reciprocal interaction (i.e., forgetting) and one’s individual prosocial preference is a core pillar of emergent cooperation in more naturalistic and dynamic group formation.
Discovering Root Causal Genes with High Throughput Perturbations
Authors: Strobl Eric V , Gamazon Eric R 
Published: January 2024

AbstractRoot causal gene expression levels – orroot causal genesfor short – correspond to the initial changes to gene expression that generate patient symptoms as a downstream effect. Identifying root causal genes is critical towards developing treatments that modify disease near its onset, but no existing algorithms attempt to identify root causal genes from data. RNA-sequencing (RNA-seq) data introduces challenges such as measurement error, high dimensionality and non-linearity that compromise accurate estimation of root causal effects even with state-of-the-art approaches. We therefore instead leverage Perturb-seq, or high throughput perturbations with single cell RNA-seq readout, to learn the causal order between the genes. We then transfer the causal order to bulk RNA-seq and identify root causal genes specific to a given patient for the first time using a novel statistic. Experiments demonstrate large improvements in performance. Applications to macular degeneration and multiple sclerosis also reveal root causal genes that lie on known pathogenic pathways, delineate patient subgroups and implicate a newly defined omnigenic root causal model.
Genome sequence resources from three isolates of the apple canker pathogenNeonectria ditissimainfecting forest trees
Authors: Bourras Salim , Vélëz Heriberto , Ihrmark Katarina , Corrales Gutiérrez Miguel Ángel , Elfstrand Malin , Garkava-Gustavsson Larisa , Dalman Falk Kerstin 
Published: January 2024

AbstractNeonectria ditissimais a generalist ascomycete plant pathogen causing canker diseases on a variety of hardwood tree species and can cross-infect many of them. The fungus enters the plants through wounds throughout the year.N. ditissimais considered a major threat to apple production responsible for the fruit tree canker disease which damages trees and causes rotting of fruits in storage. Nearby forests and shelter belts can serve as source of inoculum for well-managed apple orchards. Thus, knowledge about theN. ditissimaisolates infecting different host species is essential for designing integrated pest management strategies. Here, we describe the genomes of threeN. ditissimaisolates, Nd_iso34, Nd_iso35, and Nd_iso36, infecting European beech, American tulip tree, and American beech, respectively. We obtained genome assemblies of ca. 45 megabases for all isolates, covering 94% of theN. ditissimareference annotation, and 97% of the universal single-copy orthologs (BUSCOs). We conclude that these genome assemblies are a highly relevant resource considering the scarcity of genomic data available forN. ditissima.