bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population of the Paraná AntwrenFormicivora acutirostrisreassessed as being 64% smaller: Revision of its conservation status and assessment of its Green Status, with management proposals
Authors: Bornschein Marcos R. , Sandretti-Silva Giovanna , Sobotka Daiane D. , Corrêa Leandro , Reinert Bianca L. , Vannucchi Fabio Stucchi , Pie Marcio R. 
Published: October 2023

AbstractAssessing the conservation status of a species is important for designing effective conservation measures. Consequently, it is often vital to review it to update biodiversity management.Formicivora acutirostrisis a bird from coastal marshes and related habitats of Brazil’s southern flood plains. It is considered endangered in Brazil but near threatened globally. In 2007, its area of occupancy (AOO) and population size were estimated based on assessment of aerial photographs from 1978 and 1980. Since the species is threatened and occupies a small area scattered across a coastal pressured region, we aimed to reassess its conservation status and assess its Green Status. We compiled new records, conducted new density estimates, and compared the previous mapping with orbital imagery to estimate the current AOO, habitat loss, population size, and review its conservation status based on the International Union for Conservation of Nature criteria. The species is distributed across 10 populations, including two new populations from the southern coast of Santa Catarina to the northern coast of Rio Grande do Sul. We estimated the AOO at 4,102 ha and the population as 6,284 mature territorial individuals. The previously mapped AOO has decreased by 1,535 ha due to ecological succession. The loss of habitat due to invasion by exotic grasses is the main anthropogenic impact. We recommend that the species be considered vulnerable. The Green Status indicates that the Conservation Legacy of actions taken thus far and the Conservation Dependence of ongoing actions are null, but it highlights the importance of future actions for species conservation. We propose the establishment of exotic-free zones as small geographic areas with a significant amount of minimally invaded environments, which we suggest as priority areas for the conservation of the species due to their cost-effective management potential. We also propose assisted colonization to enhance its long-term conservation.
CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair
Authors: Hassan Dalia , Chen Jichao 
Published: October 2023

ABSTRACTCell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental plasticity. Here we show that the lung alveolar type 2 (AT2)-specific transcription factor (TF), CEBPA, restricts AT2 cell plasticity in the mouse lung. AT2 cells undergo transcriptional and epigenetic maturation postnatally. Without CEBPA, both neonatal and mature AT2 cells reduce the AT2 program, but only the former reactivate the SOX9 progenitor program. Sendai virus infection bestows mature AT2 cells with neonatal plasticity whereCebpamutant, but not wild type, AT2 cells express SOX9, as well as more readily proliferate and form KRT8/CLDN4+ transitional cells. CEBPA promotes the AT2 program by recruiting the lung lineage TF NKX2-1. The temporal change in CEBPA-dependent plasticity reflects AT2 cell developmental history. The ontogeny of AT2 cell plasticity and its transcriptional and epigenetic mechanisms have implications in lung regeneration and cancer.
A DOMON domain-cytochrome b561 protein acts as a ferric reductase in iron homeostasis and impacts primary root growth under phosphate deficiency
Authors: Clúa Joaquín , Montpetit Jonatan , Poirier Yves 
Published: October 2023

AbstractIron (Fe) and phosphate (Pi) are essential nutrients for plant growth. Several interactions between Fe and Pi homeostasis have been described, such as the Fe-dependent inhibition of primary root growth under Pi deficiency. This response involves the formation of apoplastic Fe+3-malate complexes in the root meristem which implicates the oxidation of Fe+2by the LPR1 ferroxidase. However, how is the reduced Fe+2generated in the root meristem and the Fe+3/Fe+2ratio regulated is unknown. Here, we have identified a gene inArabidopsis thaliana, namedCRR, that is implicated in primary root growth under Pi deficiency. Under low-Pi conditions, thecrrmutant showed an enhanced reduction of primary root growth that was associated with increased accumulation of apoplastic Fe in the root meristem and a reduction in meristematic cell division. Conversely, CRR overexpression rendered primary root growth insensitive to low-Pi inhibition, reduced root apoplastic Fe deposition, and impacted the expression of genes involved in Fe and redox homeostasis. CRR is a member of an uncharacterized CYBDOM protein family possessing a cytochrome b561 (CYB561) with an N-terminal DOMON domain. We demonstrated that CRR localizes to the plasma membrane and possesses ascorbate-dependent ferric reductase activity. Thecrrsingle mutant and thecrr hyp1double mutant, which harbored a null allele in another member of the CYDOM family, showed increased tolerance to high-Fe stress upon germination and seedling growth. In contrast, CRR overexpression was associated with increased uptake and translocation of Fe to the shoot and resulted in plants highly sensitive to Fe excess toxicity. Our results thus identify a ferric reductase implicated in root Fe acquisition and homeostasis and reveal a biological role for CYBDOM proteins in plants.
Interaction of GAT1 with sodium ions: from efficient recruitment to stabilisation of substrate and conformation
Authors: Lazzarin Erika , Gradisch Ralph , Skopec Sophie M.C. , Alves da Silva Leticia , Sebastianelli-Schoditsch Chiara , Szöllősi Dániel , Maier Julian , Sucic Sonja , Roblek Marko , Kanner Baruch I. , Sitte Harald H. , Stockner Thomas 
Published: October 2023

AbstractThe human GABA transporter (GAT1) is a membrane transporter that mediates the reuptake of the neurotransmitter GABA from the synaptic cleft into neurons and glial cells. Dysregulation of the transport cycle has been associated with epilepsy and neuropsychiatric disorders, highlighting the crucial role of the transporter in maintaining homeostasis of brain GABA levels. GAT1 is a secondary active transporter that couples the movement of substrate to the simultaneous transport of sodium and chloride ions along their electrochemical gradients. Using MD simulations, we identified a novel sodium recruiting site at the entrance to the outer vestibule, which attracts positively charged ions and increases the local sodium concentration, thereby indirectly increasing sodium affinity. Mutations of negatively charged residues at the recruiting site slowed the binding kinetics, while experimental data revealed a change in sodium dependency of GABA uptake and a reduction of sodium affinity. Simulation showed that sodium displays a higher affinity for the sodium binding site NA2, which plays a role in stabilisation of the outward-open conformation. We directly show that the presence of a sodium ion bound to NA2 increases the stability of the closed inner gate and restrains motions of TM5. We find that sodium is only weakly bound to NA1 in the absence of GABA, while the presence of the substrate strengthens the interaction due to the completed ion coordinating shell, explaining cooperativity between GABA and sodium.
Increased circulating CD39+FoxP3+CD4+ regulatory T cells in Early Rheumatoid Arthritis facilitate the antiinflammatory action of methotrexate and associate with the clinical response
Authors: Villalba Alejandro , Nuño Laura , Benito-Miguel Marta , Nieto-Carvalhal Beatriz , Novella-Navarro Marta , Monjo Irene , Peiteado Diana , García-Carazo Sara , Balsa Alejandro , Miranda-Carús María-Eugenia 
Published: October 2023

ABSTRACTOBJECTIVESFoxP3+ regulatory T cells (Tregs) are key to the immune system homeostasis; their CD39+ subset (Treg39+) hydrolises adenine nucleotides released by stressed cells, rendering the antiinflammatory adenosine. Methotrexate (MTX), inhibiting AICAR transformylase (ATIC), enhances the extrusion of adenine nucleotides and hence may help Treg39+ cells control inflammation. Therefore, we examined the relation of CD39 expression on Tregs of early RA (ERA) patients with the effect of MTX.METHODSFreshly isolated lymphocytes from 72 untreated ERA patients (duration <24 weeks) and 72 healthy controls (HCs) were examined by cytometry. Treg cell potency was assessed in cocultures of CD4+CD25+CD127- Treg with CD4+CD25- CD127+ responder T cells (Tresp).RESULTSERA patients demonstrated a superior frequency of circulating Tregs containing increased proportions of Treg39+ cells. Total ERA Tregs were more potent than HC Tregs and MTX further heightened their potency, with greater amplification in ERA vs HC; differences were reduced by adenosine pathway blockade. The potency of isolated Treg39+ and its enhancement by MTX were comparable for ERA and HC suggesting that the differences seen with total Tregs are due to the increased ERA Treg39+ frequency. Basal Treg39+ cell proportions > 39.3 associated with a good 12 month EULAR response [RR 13.4 (2.9-75.6)]. At 12 months, the ERA Treg39+ frequency had decreased to HC levels but its association with the clinical response remained.CONCLUSIONMTX cooperates with Treg39+ cells and the basal Treg39+ frequency is a predictor of clinical response. The increased circulating Treg39+ cells in untreated ERA would further facilitate the action of MTX thereby providing a slot for prompt MTX initiation.
Phosphorylation Promotes DELLA Activity by Enhancing Its Binding to Histone H2A at Target Chromatin inArabidopsis
Authors: Huang Xu , Zentella Rodolfo , Park Jeongmoo , Reser Larry , Bai Dina L. , Ross Mark M. , Shabanowitz Jeffrey , Hunt Donald F. , Sun Tai-ping 
Published: October 2023

AbstractDELLA proteins are conserved master growth regulators that play a central role in controlling plant development in response to internal and environmental cues. DELLAs function as transcription regulators, which are recruited to target promoters by binding to transcription factors (TFs) and histone H2A via its GRAS domain. Recent studies showed that DELLA stability is regulated post-translationally via two mechanisms, phytohormone gibberellin-induced polyubiquitination for its rapid degradation, and Small Ubiquitin-like Modifier (SUMO)- conjugation to alter its accumulation. Moreover, DELLA activity is dynamically modulated by two distinct glycosylations: DELLA-TF interactions are enhanced byO-fucosylation, but inhibited byO-linkedN-acetylglucosamine (O-GlcNAc) modification. However, the role of DELLA phosphorylation remains unclear. Here, we identified phosphorylation sites in REPRESSOR OFga1-3(RGA, an AtDELLA) purified fromArabidopsisby tandem mass spectrometry analysis, and showed that phosphorylation of the RGA LKS-peptide in the poly- S/T region enhances RGA-H2A interaction and RGA association with target promoters. Interestingly, phosphorylation does not affect RGA-TF interactions. Our study has uncovered that phosphorylation is a new regulatory mechanism of DELLA activity.
Full genome sequence analysis of African swine fever virus isolates from Cameroon
Authors: Goatley Lynnette C , Freimanis Graham , Tennakoon Chandana , Foster Thomas J , Quershi Mehnaz , Dixon Linda K , Batten Carrie , Forth Jan Hendrik , Wade Abel , Netherton Christopher L 
Published: October 2023

AbstractAfrican swine fever is a devastating disease of domestic pigs that has spread across the globe since its introduction into Georgia in 2007. The etiological agent is a large double-stranded DNA virus with a genome of 170 to 180 kb in length depending on the isolate. Much of the differences in genome length between isolates are due to variations in the copy number of five different multigene families that are encoded in repetitive regions that are towards the termini of the covalently closed ends of the genome. Molecular epidemiology of ASFV is primarily based on Sanger sequencing of a few conserved and variable regions, but due to the stability of the dsDNA genome changes in the variable regions occur relatively slowly. Observations in Europe and Asia have shown that changes in other genetic loci can occur and that this could be useful in molecular tracking. ASFV has been circulating in Western Africa for at least forty years. It is therefore reasonable to assume that changes may have accumulated in regions of the genome other than the standard targets over the years. At present only one full genome sequence is available for an isolate from Western Africa, that of a highly virulent isolate collected from Benin during an outbreak in 1997. In Cameroon, ASFV was first reported in 1981 and outbreaks have been reported to the present day and is considered endemic. Here we report three full genome sequences from Cameroon isolates of 1982, 1994 and 2018 outbreaks and identify novel single nucleotide polymorphisms and insertion-deletions that may prove useful for molecular epidemiology studies in Western Africa and beyond.
Multigenerational inheritance of parasitic stress memory inDrosophila melanogaster
Authors: Khan Shagufta , Saini Ravina , Hamid Runa , Mishra Rakesh K 
Published: October 2023

SUMMARYOrganisms sense harmful environmental conditions and employ strategies to safeguard themselves. Moreover, they can communicate this experience to the next generation or beyond via non-DNA sequence-based mechanisms, referred to as intergenerational or transgenerational epigenetic inheritance, respectively. Using a specialist larval parasitoid,Leptopilina boulardi, and its host,Drosophila melanogaster, we show that the parental experience of parasitic stress results in an increased survivability of the immediate offspring of the host. Furthermore, we observe that the increased survivability in response to the parasitic stress is transmitted transgenerationally where the grandparents have been exposed to the parasitoid but not the parents. The increased survivability is primarily inherited through male parents, and at least one of the forms of the memory is better immune priming at larval stage. Our study suggests that the stress exposure during the pre-adult stage of the host has lifetime benefits for its progeny to deal with the future parasitic attack.
Prolonged metaphase II arrest weakens Aurora B/C- dependent error correction in mouse oocytes
Authors: Langeoire Antoine , Kem-Seng Alison , Cladière Damien , Wassmann Katja , Buffin Eulalie 
Published: October 2023

SUMMARYChromosome segregation during meiosis is highly error-prone in mammalian oocytes. The mechanisms controlling chromosome attachments and the Spindle Assembly Checkpoint (SAC) have been extensively studied in meiosis I, but our knowledge of these mechanisms during meiosis II is rather limited. Although mammalian oocytes arrest in metaphase II for an extended period awaiting fertilization, some misattached chromosomes may persist. This suggests that the mechanism correcting misattachments is not fully functional during the arrest. In this study, we investigated whether low inter-kinetochore tension, which characterizes incorrect attachments, can be detected by Aurora B/C-dependent error correction in meiosis II. We found that low tension in early metaphase II does indeed mediate microtubule detachment by Aurora B/C and consequently, anaphase II delay through SAC activation. Surprisingly, we also found that during prolonged metaphase II arrest, Aurora B/C activity is no longer sufficient to detach low-tension attachments, concomitantly with high accumulation of PP2A at kinetochores. As a result, the SAC is not activated and sister chromatids segregate in anaphase II without delay even in the presence of low tension. Hence, during the prolonged metaphase II arrest to await fertilization, oocytes become unable to discriminate between correct and incorrect attachments and may allow errors to persist.
An exploration of mechanisms underlyingDesemzia incertacolonization resistance to methicillin-resistantStaphylococcus aureuson the skin
Authors: Wei Monica , Knight Simon AB , Fazelinia Hossein , Spruce Lynn , Roof Jennifer , Chu Emily , Walsh Jasmine , Flowers Laurice , Kim Daniel Y. , Zhu Jun , Grice Elizabeth A. 
Published: October 2023

ABSTRACTColonization of human skin and nares by methicillin-resistantStaphylococcus aureus(MRSA) leads to community spread of MRSA. This spread is exacerbated by transfer of MRSA between humans and livestock, particularly swine. Here we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial speciesDesemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in anin vivomurine skin model. Using parallel genomic and biochemical investigation, we discovered thatD. incertasecretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis ofD. incertaand MRSA cocultures, we found that exposure toD. incertaleads to decreased MRSA biofilm production. These results emphasize the value in exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as increased understanding of microbial competition.IMPORTANCEMethicillin-resistantStaphylococcus aureuscauses significant healthcare burden and can be spread to the human population via livestock transmission. Members of the skin microbiome can prevent MRSA colonization via a poorly-understood phenomenon known as colonization resistance. Here, we studied colonization resistance ofS. aureusby bacterial inhibitors previously identified from a porcine skin model. We identify a pig skin commensal,Desemzia incerta, that reduced MRSA colonization in a murine model. We employ a combination of genomic, proteomic, and transcriptomic analyses to explore the mechanisms of inhibition betweenD. incertaandS. aureus. We identify 24 candidate antimicrobial proteins secreted byD. incertathat could be responsible for its antimicrobial activity. We also find that exposure toD. incertaleads to decreasedS. aureusbiofilm formation. These findings show that the livestock transmission of MRSA can be exploited to uncover novel mechanisms of MRSA colonization resistance.
Laser Desorption Rapid Evaporative Ionisation Mass Spectrometry (LD-REIMS) demonstrates a direct impact of hypochlorous acid stress on PQS-mediated quorum sensing inPseudomonas aeruginosa
Authors: Bradley Rob , Simon Daniel , Spiga Livia , Xiang Yuchen , Takats Zoltan , Williams Huw 
Published: October 2023

ABSTRACTTo establish infections in human hosts,Pseudomonas aeruginosamust overcome innate immune generated oxidative stress, such as the hypochlorous acid (HOCl) produced by neutrophils. We set out to find specific biomarkers of oxidative stress through the development of a protocol for the metabolic profiling ofP. aeruginosacultures grown in the presence of different oxidants using a novel ionisation technique for mass spectrometry, laser desorption rapid evaporative ionisation mass spectrometry (LD-REIMS). We demonstrated the ability of LD-REIMS to classify samples as untreated or treated with a specific oxidant with 100 % accuracy and identified a panel of 54 metabolites with significantly altered concentrations after exposure to one or more of the oxidants. Key metabolic changes were conserved inP. aeruginosaclinical strains isolated from patients with cystic fibrosis lung infections. These data demonstrated that HOCl stress impacted the Pseudomonas Quinolone Signal (PQS) quorum sensing system. Ten 2-alkyl-4-quinolones (AHQs) associated with the PQS system were significantly lower in concentration in HOCl-stressedP. aeruginosacultures, including 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), the most active signal molecule of the PQS system. The PQS system regulates the production of virulence factors, including pyocyanin and elastase, and their levels were markedly affected by HOCl stress. No pyocyanin was detectable and elastase concentrations were significantly reduced in cultures grown with sub-lethal concentrations of HOCl, suggesting that this neutrophil-derived oxidant may disrupt the ability ofP. aeruginosato establish infections through interference with production of PQS-associated virulence factors.IMPORTANCEThis work demonstrates that a high-throughput ambient ionisation mass spectrometry method can be used successfully to study a bacterial stress response. Its application to the opportunistic pathogenPseudomonas aeruginosaled to the identification of specific oxidative stress biomarkers, and demonstrated that hypochlorous acid, an oxidant specifically produced by human neutrophils during infection, affects quorum sensing and markedly reduces production of the virulence factors pyocyanin and elastase in this bacterium. This approach has the potential to be widely applicable to the characterisation of the stress responses of bacteria.
Variation in monitoring: Glucose measurement in the ICU as a case study to preempt spurious correlations
Authors: Teotia Khushboo , Jia Yueran , Woite Naira Link , Celi Leo Anthony , Matos João , Struja Tristan 
Published: October 2023

ABSTRACTObjectiveHealth inequities can be influenced by demographic factors such as race and ethnicity, proficiency in English, and biological sex. Disparities may manifest as differential likelihood of testing which correlates directly with the likelihood of an intervention to address an abnormal finding. Our retrospective observational study evaluated the presence of variation in glucose measurements in the Intensive Care Unit (ICU).MethodsUsing the MIMIC-IV database (2008-2019), a single-center, academic referral hospital in Boston (USA), we identified adult patients meeting sepsis-3 criteria. Exclusion criteria were diabetic ketoacidosis, ICU length of stay under 1 day, and unknown race or ethnicity. We performed a logistic regression analysis to assess differential likelihoods of glucose measurements on day 1. A negative binomial regression was fitted to assess the frequency of subsequent glucose readings. Analyses were adjusted for relevant clinical confounders, and performed across three disparity proxy axes: race and ethnicity, sex, and English proficiency.ResultsWe studied 24,927 patients, of which 19.5% represented racial and ethnic minority groups, 42.4% were female, and 9.8% had limited English proficiency. No significant differences were found for glucose measurement on day 1 in the ICU. This pattern was consistent irrespective of the axis of analysis, i.e. race and ethnicity, sex, or English proficiency. Conversely, subsequent measurement frequency revealed potential disparities. Specifically, males (incidence rate ratio (IRR) 1.06, 95% confidence interval (CI) 1.01 - 1.21), patients who identify themselves as Hispanic (IRR 1.11, 95% CI 1.01 - 1.21), or Black (IRR 1.06, 95% CI 1.01 - 1.12), and patients being English proficient (IRR 1.08, 95% CI 1.01 - 1.15) had higher chances of subsequent glucose readings.ConclusionWe found disparities in ICU glucose measurements among patients with sepsis, albeit the magnitude was small. Variation in disease monitoring is a source of data bias that may lead to spurious correlations when modeling health data.