bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nest site selection and productivity of a critically endangered parrot, the great green macaw (Ara ambiguus), in an anthropogenic landscape
Authors: Lewis Thomas C. , Gutiérrez Vargas Ignacio , Vredenbregt Claire , Jimenez Mario , Hatchwell Ben , Beckerman Andrew P. , Childs Dylan Z. 
Published: January 2023

AbstractNest site selection is the principal way secondary cavity-nesting species mitigate the negative effects of factors such as predation, parasitism and exposure on productivity. High-quality cavities could then be expected to be selected in response to the primary threat to nest success. Understanding how demographic rates are affected by anthropogenic changes to ecosystems is vital if effective conservation management strategies are to be developed and implemented. Large-bodied secondary cavity-nesting birds rely on large cavities in mature trees that are often absent or reduced in anthropogenically disturbed forests. Thus, the availability of high-quality nest sites may be limited for these species, potentially reducing productivity. The aim of this study was to investigate nest-site selection and the effect of nest-site features on productivity in the critically endangered great green macaw (Ara ambiguus) in northern Costa Rica. We show that great green macaws select nest sites according to the characteristics of the cavity and of the tree in which they are located. Moreover, productivity was a function of certain cavity features. We conclude that great green macaws are not reliant on primary forest for nest sites and typically choose cavities in remnant, isolated trees in pasture or young secondary forests.
Multimodal Data Integration Advances Longitudinal Prediction of the Naturalistic Course of Depression and Reveals a Multimodal Signature of Disease Chronicity
Authors: Habets Philippe C. , Thomas Rajat M , Milaneschi Yuri , Jansen Rick , Pool Rene , Peyrot Wouter J , Penninx Brenda WJH , Meijer Onno C , van Wingen Guido A , Vinkers Christiaan H. 
Published: January 2023

AbstractThe ability to individually predict disease course of major depressive disorder (MDD) is essential for optimal treatment planning. Here, we use a data-driven machine learning approach to assess the predictive value of different sets of biological data (whole-blood proteomics, lipid-metabolomics, transcriptomics, genetics), both separately and added to clinical baseline variables, for the longitudinal prediction of 2-year MDD chronicity (defined as presence of MDD diagnosis after 2 years) at the individual subject level. Prediction models were trained and cross-validated in a sample of 643 patients with current MDD (2-year chronicity n = 318) and subsequently tested for performance in 161 MDD individuals (2-year chronicity n = 79). Proteomics data showed best unimodal data predictions (AUROC = 0.68). Adding proteomic to clinical data at baseline significantly improved 2-year MDD chronicity predictions (AUROC = 0.63 vs AUROC = 0.78, p = 0.013), while the addition of other -omics data to clinical data did not yield significantly increased model performance. SHAP and enrichment analysis revealed proteomic analytes involved in inflammatory response and lipid metabolism, with fibrinogen levels showing the highest variable importance, followed by symptom severity. Machine learning models outperformed psychiatrists’ ability to predict two-year chronicity (balanced accuracy = 71% vs 55%). This study showed the added predictive value of combining proteomic, but not other -omic data, with clinical data. Adding other -omic data to proteomics did not further improve predictions. Our results reveal a novel multimodal signature of MDD chronicity that shows clinical potential for individual MDD disease course predictions from baseline measurements.
Steady-state polypeptide transfer from the translocon to the membrane
Authors: Knyazev Denis G. , Schaur Mirjam , Kuttner Roland , Siligan Christine , Gössweiner-Mohr Nikolaus , Hagleitner-Ertugrul Nora , Pohl Peter 
Published: January 2023

AbstractIn concert with irreversible non-equilibrium peptide translation by the ribosome, the nascent polypeptide chain may integrate into the membrane or translocate to the other side of the membrane, facilitated by the conserved protein translocation channel SecYEG in bacteria and Sec61 in eukaryotes. Assuming equilibrium for the decision processes yielded the biological hydrophobicity scale, reflecting free-energy differences ΔG between the pore interior and membrane. Yet kinetic effects and molecular dynamic simulations suggested that a nascent polypeptide could not sample the two separate environments a sufficient number of times for partitioning in equilibrium. Here we tested the hypothesis employing purified and reconstituted SecYEG harboring a stalled ribosome nascent chain (RNC). The SecYEG-RNC complex was open in a de-energized membrane, allowing ion flow. Application of a membrane potential closed the channel if nascent chain hydrophobicity permitted membrane integration. Taking the ratio of steady-state to initial ion conductances as a measure of nascent chain hydrophobicity, we found ΔG for KvAP’s voltage sensor (4thhelix harboring four arginines) and FtsQ’s transmembrane helix to be equal to 0.3 and –2.1 kcal/mol, respectively. Thus, ΔG observed in our minimalistic system agrees very well with the position-dependent amino acid contribution of the biological hydrophobicity scale. Characteristic sampling times of ~2 s appear sufficient to reach a steady state for a ~20 amino acid-long segment invalidating the hypothesis of insufficient sampling.
Next-generation diarylquinolines improve sterilizing activity of regimens with pretomanid and the novel oxazolidinone TBI-223 in a mouse tuberculosis model
Authors: Li Si-Yang , Converse Paul J. , Betoudji Fabrice , Lee Jin , Mdluli Khisimuzi , Upton Anna , Fotouhi Nader , Nuermberger Eric L. 
Published: January 2023

ABSTRACTA regimen comprised of bedaquiline, pretomanid and linezolid (BPaL) is the first oral 6-month regimen approved by the US Food and Drug Administration and recommended by the World Health Organization for treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines in early clinical trials, TBAJ-587 and TBAJ-876. We also evaluated the effect of replacing linezolid with a new oxazolidinone, TBI-223, exhibiting a larger safety margin with respect to mitochondrial toxicity in preclinical studies. Replacing bedaquiline with TBAJ-587 at the same 25 mg/kg dose significantly reduced the proportion of mice relapsing after 2 months of treatment, while replacing linezolid with TBI-223 at the same 100 mg/kg dose did not significantly change the proportion of mice relapsing. Replacing linezolid or TBI-223 with sutezolid in combination with TBAJ-587 and pretomanid significantly reduced the proportion of mice relapsing. In combination with pretomanid and TBI-223, TBAJ-876 at 6.25 mg/kg was equipotent to TBAJ-587 at 25 mg/kg. We conclude that replacement of bedaquiline with these more efficacious and potentially safer diarylquinolines and replacement of linezolid with potentially safer and at least as efficacious oxazolidinones in the clinically successful BPaL regimen may lead to superior regimens capable of treating both drug-susceptible and drug-resistant TB more effectively and safely.
SwissGenVar: A platform for clinical grade interpretation of genetic variants to foster personalized health care in Switzerland
Authors: Kraemer Dennis , Terumalai Dillenn , Famiglietti Maria Livia , Filges Isabel , Joset Pascal , Koller Samuel , Maurer Fabienne , Meier Stéphanie , Nouspikel Thierry , Sanz Javier , Zweier Christiane , Abramowicz Marc , Berger Wolfgang , Cichon Sven , Schaller André , Superti-Furga Andrea , Barbié Valérie , Rauch Anita 
Published: January 2023

AbstractLarge-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows including the extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUS) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of standards used to describe genetic variants and associated phenotypes when searching for relevant information to inform clinical decision-making.For this purpose, all five Swiss academic Medical Genetics Institutions joined forces with the Swiss Institute of Bioinformatics (SIB) to createSwissGenVaras a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its objective is to provide a protected environment for expert evidence sharing about individual variants to harmonize and up-scale their significance interpretation at clinical grade following international standards. To corroborate the clinical assessment, the variant-related data are combined with consented high-quality clinical information. Broader visibility will be gained by interfacing with international databases, thus supporting global initiatives in personalized health care.
Inflammatory biomarkers and perinatal depression: a systematic review
Authors: Silva-Fernandes Anabela , Conde Ana , Marques Margarida , Caparros-Gonzalez Rafael A. , Fransson Emma , Mesquita Ana Raquel , Figueiredo Bárbara , Skalkidou Alkistis 
Published: January 2023

AbstractBackgroundApproximately 10 to 20% of pregnant women worldwide experience perinatal depression (PND), a depressive episode with onset during pregnancy or after childbirth. We performed a systematic review to identify, summarize and discuss studies on inflammatory biomarkers described in relation to PND.MethodsInclusion criteria defined the selection of observational studies written in English, French, Spanish or Portuguese, that evaluate analytical levels of inflammatory molecules (protein levels) in biological fluids in women, with a diagnosis of depression using ICD/DSM diagnostic criteria or depressive symptoms assessed by standardized psychometric instruments, during pregnancy and/or postpartum. Case reports, experimental studies, reviews, qualitative analysis, meta-analysis, gray literature or replicated data were excluded. Three electronic databases were used for search (Pubmed, Web of Science and PsychInfo) and quality assessment of selected studies were performed using the Newcastle-Ottawa Scale. Data extraction included study design; number of subjects; obstetric information; tools and timepoints of depression and inflammatory markers assessment.Results56 studies where the major aim was to analyze the association between depression and inflammatory biomarkers during pregnancy and postpartum period were included in this systematic review. Overall, the findings of our systematic review lend support to the hypothesis that several inflammatory markers may be associated with peripartum depressive symptoms. The associations were somewhat different looking at pregnancy compared to the delivery time-point and postpartum, and mainly referred to increased levels of IL-6, IL-8, CRP and TNF-α among depressed.DiscussionOur results revealed high heterogeneity in relation to the timing of biological sampling for markers, as well as timing and instruments used for depression assessment within the perinatal period for the different studies. Studies differed also in relation to use of biomarkers or depression as exposure and outcome respectively, and whether these were addressed at the same timepoint or separate ones.Given the high burden of PND on women, children and families, it is crucial to try to harmonize methods used in related studies, in order to be able to pool results that could give us insights into the pathophysiological mechanisms behind how the immune system and PND are connected; this could have great impact on early detection, prevention and even treatment of PND.
Using traditional rhyme (folk song) as a tool for oral hygiene promotion (UTRATOHP) among children in rural communities in Nigeria: a protocol for a randomised controlled trial
Authors: Fagbule Omotayo F. , Emenyonu Urenna , Idiga Ejiro , Oni Olubunmi O. , Ijarogbe Olabode A. , Osuh Mary E. , Lawal Folake B. , Owoaje Tolulope O. , Ibiyemi Olushola 
Published: January 2023

AbstractBackgroundMost oral diseases are caused by poor oral hygiene, and with adequate oral hygiene measures, they are easily preventable. The use of folk songs to deliver oral health education may likely hold a huge potential for success and an increased likelihood of acceptability and sustainability among school children. Therefore, an investigation into the effectiveness of methods that would be culturally appropriate and sustainable, such as folk songs, is essential.AimTo determine the effect of traditional rhyme (folk song) as a tool for oral hygiene education among children in rural communities in Nigeria.Materials and methodsThis is a school-based, assessor-blinded, two-arm cluster-randomised controlled trial that will assess the effectiveness of oral hygiene messages delivered through traditional rhyme (folk song) on children’s oral hygiene knowledge, attitude, practices, and oral hygiene status in two rural communities (Igboora and Idere) in Nigeria. The study will involve a minimum of 424 participants (aged 7-9 years) selected from eight primary schools using the cluster sampling technique. Four schools will be randomised into the test group to receive oral hygiene messages through folk songs, and the participants will sing the song for two weeks. The other four schools will be assigned to the control group, and the participants will receive the usual oral health talk on oral hygiene practices by a dentist.The participants’ oral hygiene knowledge, attitude, practice and status will be assessed at baseline, immediate, six, and twelve-month post-intervention. A modified World Health Organization (WHO) Children’s oral health survey questionnaire will be utilised for data collection. Oral examinations will be conducted to assess the participants’ dental caries experience and oral hygiene status using the dmft/DMFT and simplified oral hygiene indices, respectively.DiscussionFolk songs are popular means of conveying messages in Nigeria, and using them to deliver oral health messages may be an effective, acceptable, and sustainable method among children. This study will provide empirical information about this innovative intervention to guide policy development, dental public health practice, and future studies.Trial registrationPan African Clinical Trial Registry-PACTR202010863892797 (October 2020)
Faecal glucocorticoid metabolite levels of intensive captive, free-range captive, and wild Tasmanian devils
Authors: Florent Stevie Nicole , Clarke Judy , Bashaw Meredith J. , Hamede Rodrigo , Jones Menna E. , Cameron Elissa Z 
Published: January 2023

ABSTRACTCaptivity can alter the stress physiology and behaviour of an animal in both the short- and long-term through repetitive exposure to novel stressors and, subsequently, may reduce the success of conservation efforts such as translocation and reintroduction. The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction from a fatal facial tumour disease which has led to the establishment of an insurance meta-population designed for future reintroductions of disease-free devils. The meta-population is comprised of intensive captive and free-range captive environments; however, no study has yet examined the long-term physiological implications of captivity on devils. We used non-invasive faecal glucocorticoid metabolite (FGM) monitoring to determine if there were any differences in adrenal activity between intensive captive, free-range captive, and wild devils. FGMs were not age- or sexdependent, and we found that all population-types had similar intra-population variability and mean FGMs. In conclusion, both types of captive environment maintain stress profiles similar to wild devils.
Indirect enrichment of desirable, but less fit phenotypes, from a synthetic microbial community using microdroplet confinement
Authors: Prabhakar Ramya Ganiga , Fan Gaoyang , Alnahhas Razan N , Hirning Andrew J , Bennett Matthew R , Shamoo Yousif 
Published: January 2023

Spatial structure within microbial communities can provide nearly limitless opportunities for social interactions and are an important driver for evolution. As metabolites are often molecular signals, metabolite diffusion within microbial communities can affect the composition and dynamics of the community in a manner that can be challenging to deconstruct. We used encapsulation of a synthetic microbial community within microdroplets to investigate the effects of spatial structure and metabolite diffusion on population dynamics and to examine the effects of cheating by one member of the community. The synthetic community was comprised of three strains: a ‘Producer’ that makes the diffusible quorum sensing molecule (N-(3-Oxododecanoyl)-L-homoserine lactone, C12-oxo-HSL) or AHL; a ‘Receiver’ that is killed by AHL and a Non-Producer or ‘cheater’ that benefits from the extinction of the Receivers, but without the costs associated with the AHL synthesis. We demonstrate that despite rapid diffusion of AHL between microdroplets, the spatial structure imposed by the microdroplets allow a more efficient but transient enrichment of more rare and slower growing ‘Producer’ subpopulations. Eventually, the Non-Producer population drove the Producers to extinction. By including fluorescence-activated microdroplet sorting and providing sustained competition by the Receiver strain, we demonstrate a strategy for indirect enrichment of a rare and unlabeled Producer. The ability to screen and enrich metabolite Producers from a much larger population under conditions of rapid diffusion provides an important framework for the development of applications in synthetic ecology and biotechnology.Abstract Figure
Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis inToxoplasma
Authors: Chan Alex W , Broncel Malgorzata , Yifrach Eden , Haseley Nicole , Chakladar Sundeep , Andree Elena , Herneisen Alice L , Shortt Emily , Treeck Moritz , Lourido Sebastian 
Published: January 2023

ABSTRACTApicomplexan parasites use Ca2+-regulated exocytosis to secrete essential virulence factors from specialized organelles called micronemes. Ca2+-dependent protein kinases (CDPKs) are required for microneme exocytosis; however, the molecular events that regulate trafficking and fusion of micronemes with the plasma membrane remain unresolved. Here, we combine sub-minute resolution phosphoproteomics and bio-orthogonal labeling of kinase substrates inToxoplasma gondiito identify 163 proteins phosphorylated in a CDPK1-dependent manner. In addition to known regulators of secretion, we identify uncharacterized targets with predicted functions across signaling, gene expression, trafficking, metabolism, and ion homeostasis. One of the CDPK1 targets is a putative HOOK activating adaptor. In other eukaryotes, HOOK homologs form the FHF complex with FTS and FHIP to activate dynein-mediated trafficking of endosomes along microtubules. We show the FHF complex is partially conserved inT. gondii, consisting of HOOK, an FTS homolog, and two parasite-specific proteins (TGGT1_306920 and TGGT1_316650). CDPK1 kinase activity and HOOK are required for the rapid apical trafficking of micronemes as parasites initiate motility. Moreover, parasites lacking HOOK or FTS display impaired microneme protein secretion, leading to a block in the invasion of host cells. Taken together, our work provides a comprehensive catalog of CDPK1 targets and reveals how vesicular trafficking has been tuned to support a parasitic lifestyle.
Bacterial meningitis in the early postnatal mouse studied at single-cell resolution
Authors: Wang Jie , Rattner Amir , Nathans Jeremy 
Published: January 2023

AbstractBacterial meningitis is a major cause of morbidity and mortality, especially among infants and the elderly. Here we study mice to assess the response of each of the major meningeal cell types to early postnatalE. coliinfection using single nucleus RNA sequencing (snRNAseq), immunostaining, and genetic and pharamacologic perturbations of immune cells and immune signaling. Flat mounts of the dissected arachnoid and dura were used to facilitiate high-quality confocal imaging and quantification of cell abundances and morphologies. Upon infection, the major meningeal cell types – including endothelial cells (ECs), macrophages, and fibroblasts – exhibit distinctive changes in their transcriptomes. Additionally, ECs in the arachnoid redistribute CLDN5 and PECAM1, and arachnoid capillaries exhibit foci with reduced blood-brain barrier integrity. The vascular response to infection appears to be largely driven by TLR4 signaling, as determined by the nearly identical response induced by LPS administration and by the blunted response to infection inTlr4-/-mice.
Susceptible bacteria survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance
Authors: Rodrigues Marinelle , Sabaeifard Parastoo , Yildiz Muhammed Sadik , Coughlin Laura , Ahmed Sara , Behrendt Cassie , Wang Xiaoyu , Monogue Marguerite , Kim Jiwoong , Gan Shuheng , Zhan Xiaowei , Filkins Laura , Williams Noelle S. , Hooper Lora V. , Koh Andrew Y. , Toprak Erdal 
Published: January 2023

AbstractIn vitrosystems have provided great insight into the mechanisms of antibiotic resistance. Yet,in vitroapproaches cannot reflect the full complexity of what transpires within a host. As the mammalian gut is host to trillions of resident bacteria and thus a potential breeding ground for antibiotic resistance, we sought to better understand how gut bacteria respond to antibiotic treatmentin vivo. Here, we colonized germ-free mice with a genetically barcoded antibiotic pan-susceptibleEscherichia coliclinical isolate and then administered the antibiotic cefepime via programmable subcutaneous pumps which allowed for closer emulation of human parenteral antibiotic pharmacokinetics/dynamics. After seven days of antibiotics, we were unable to cultureE. colifrom feces. We were, however, able to recover barcodedE. colifrom harvested gastrointestinal (GI) tissue, despite high GI tract and plasma cefepime concentrations. Strikingly, theseE. coliisolates were not resistant to cefepime but had acquired mutations – most notably in thewbaPgene, which encodes an enzyme required for the initiation of the synthesis of the polysaccharide capsule and lipopolysaccharide O antigen - that increased their ability to invade and survive within intestinal cells, including cultured human colonocytes. Further, theseE. colimutants exhibited a persister phenotype when exposed to cefepime, allowing for greater survival to pulses of cefepime treatment when compared to the wildtype strain. Our findings highlight a mechanism by which bacteria in the gastrointestinal tract can adapt to antibiotic treatment by increasing their ability to persist during antibiotic treatment and invade intestinal epithelial cells where antibiotic concentrations are substantially reduced.