bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hatching asynchrony and fitness in a neotropical seabird: second-hatched individuals from highly asynchronous broods are less fit but only during the rearing period
Authors: Ortega Santiago , Rodríguez Cristina , Drummond Hugh 
Published: May 2023

AbstractEarly-life conditions are important determinants of phenotype and fitness. In birds, hatching asynchrony can generate differences in early-life conditions within a brood, which, in turn, can have far reaching fitness consequences for offspring, particularly so for later-hatched nestlings. A plethora of literature has examined consequences of hatching asynchrony during the nestling phase; however, long-term effects remain poorly understood. Using a 33-year population study of the Blue-footed booby (Sula nebouxii) off the Pacific Coast of Mexico, we show that the level of hatching asynchrony affects early- life survival of second-hatched nestlings. Junior boobies from highly asynchronous broods died at younger ages during the rearing period and were less likely to fledge compared to first-hatched offspring. However, level of hatching asynchrony did not have long-term fitness effects on either senior- or junior juveniles or adults. Our results provide insight into how parentally imposed natal environments affect early-life survival and late-life fitness traits in a long-lived seabird.HighlightsParentally imposed natal conditions can have far reaching fitness consequences for offspring.In birds, hatching asynchrony can produce size hierarchies within a brood.The effects of natural variation in hatching asynchrony on fitness is poorly understood.High levels of hatching asynchrony are detrimental for junior booby nestlings.Hatching asynchrony does not affect fitness in the juvenile or adult periods.
Antimicrobial Resistance Profiles of Bacterial Contaminants from a Tertiary Hospital in Kenya: An Urgent Call for Action Against the Global Threat of Antimicrobial Resistance
Authors: Chester Kolek , Briton Kavulavu , Okalebo Faith , Singa Benson , Masheti Mary , Omuom Ian , Odhoch Ochieng , Oduol Chris , Musyimi Robert , Tigoi Caroline , Tickell Kirkby D 
Published: May 2023

ABSTRACTBackgroundHospital-acquired infections (HAIs) represent the most prevalent adverse event among patients in hospital settings. Contamination with pathogenic bacteria that are highly resistant in the hospital environment increases the risk of HAIs.ObjectiveThe antimicrobial resistance (AMR) patterns of hospital contaminants isolated from highly frequented surfaces in a tertiary hospital in Kenya.MethodsA total of 62 swabs were collected from selected surfaces, equipment, and health workers’ palms in April 2020. They were cultured and bacterial contaminants were identified using standard microbiological procedures and their AMR patterns were determined using recommended laboratory assays.ResultsOf the 62 swabs collected, 61.3% (n=38) yielded bacterial growth, from which 46 bacteria were isolated. Swab positivity varied across the departments as follows: gynecology wards (78.6%), New Born Unit (NBU) (56.2%), Pediatric ward (61.9%), and Renal Unit (45.5%). Gram negative species comprised 86.96%(n=40) while Gram positive species comprised 13.04%(n=6). Of all the 46 isolates obtained, 36.96% (n=17) were positive for the resistance markers screened. Specifically, 10.9% (n=5) showed both extended-spectrum beta-lactamases (ESBL)and carbapenem-resistant (CR) resistance, while 23.9%(n=11) were positive for ESBL production. The rest were non-resistant strains as shown by negative ESBL at 47.8% (n=22), methicillin sensitivity at 13% (n=6) and vancomycin sensitivity at 2.2% (n=1).Acinetobacterspecies which were most reported, had the highest resistance (36.84% (7/19).ConclusionThere was a high prevalence of contamination with resistant pathogenic bacteria species.Acinetobacterspecies were the most common pathogen. Interventions are needed to mitigate the problem of resistant HAI.
ADSC-EVs modulate primary human macrophages to an anti-inflammatory phenotypein vitro
Authors: Symonds Emma K C , Black Bianca , Brown Alexander , Meredith Ineke , Currie Margaret , Hally Kathryn E , Danielson Kirsty M 
Published: May 2023

AbstractBackgroundEVs released by adipose derived stem cells (ADSCs) have shown promise as a therapeutic for tissue repair and regeneration because of their purported immune-regulatory properties. In this capacity, ADSC-EVs could be beneficial in improving graft retention rates for autologous fat grafting (AFG) post-mastectomy as, currently, grafted tissue rates are reported to be variable and low. Enriching grafted tissue with ADSC-EVs may improve retention rates by modulating macrophages resident within both the breast and lipoaspirate. We aimed to identify key macrophage phenotypes that are modulated by ADSC-EVsin vitro.MethodsADSCs were isolated from lipoaspirates of women undergoing AFG and characterised by flow cytometry and differentiation potential. ADSC-EVs were isolated from cell culture media and characterised by tunable resistive pulse sensing (TRPS), transmission electron microscopy (TEM), and Western blot. Primary monocyte-derived macrophages were polarized to an M1-like (GM-CSF, IFNγ) or M2-like phenotype (M-CSF, IL-4) or maintained (M0-like; M-CSF) and, at the time of polarization, ADSC-EVs were co-cultured with macrophages for 48 hrs. Flow cytometry coupled with high-dimensional analysis was used to cluster macrophages post co-culture. A manual gating strategy was generated to recapitulate these clusters and was applied to a repeat experimental run. Both runs were analysed to examine the prevalence of each cluster, representing a unique macrophage phenotype, with and without ADSC-EVs.ResultsFollowing the addition of ADSC-EVs, M0-like macrophages demonstrated a reciprocal shift of cell distribution from a cluster defined as having a ‘high inflammatory profile’ (CD36+++CD206+++CD86+++; 38.6±14.8% of M1-like macrophages without ADSC-EVs; 16.5±7.0% with ADSC-EVs; p<0.0001) to a cluster with a ‘lower inflammatory’ profile (CD36+CD206+CD86+; 16.6±11.2% to 35±21.5%; p<0.05). There was no shift in M2-like clusters following treatment with ADSC-EVs.ConclusionsADSC-EVs are complex regulators of macrophage phenotype that can shift macrophages away from a heightened pro-inflammatory state.
Suitability Evaluation of Toehold Switch and EXPAR for Cell-Free MicroRNA Biosensor Development
Authors: Copeland Caroline E. , Kwon Yong-Chan 
Published: May 2023

ABSTRACTThe development of a robust and cost-effective sensing platform for microRNA (miRNA) is of paramount importance in detecting and monitoring various diseases. Current miRNA detection methods are marred by low accuracy, high cost, and instability. The toehold switch riboregulator has shown promising results in detecting viral RNAs integrated with the cell-free system (CFS). This study aimed to leverage the toehold switch technology to detect miRNA in the CFS and to incorporate the exponential amplification reaction (EXPAR) to bring the detection to clinically relevant levels. We assessed various EXPAR DNA templates under different temperatures and additives to enhance the accuracy of the sensing platform. Furthermore, different structures of toehold switches were tested with either high-concentration synthetic miRNA or EXPAR product to assess sensitivity. Herein, we elucidated the mechanisms of the toehold switch and EXPAR, presented the findings of these optimizations, and discussed the potential benefits and drawbacks of their combined use.
Getting Personal: Brain Decoding of Spontaneous Thought Using Personal Narratives
Authors: Kim Hong Ji , Lux Byeol Kim , Finn Emily S. , Woo Choong-Wan 
Published: May 2023

AbstractThe contents of spontaneous thought and their dynamics are important factors for one’s personality traits and mental health. However, they are difficult to assess because spontaneous thought occurs voluntarily without conscious constraints. Here, we aimed to decode two important content dimensions of spontaneous thought—self-relevance and valence—directly from functional Magnetic Resonance Imaging (fMRI) signals. To train brain decoders, we induced a wide range of levels of self-relevance and emotional valence using individually generated personal stories as well as stories written by others to mimic narrative-like spontaneous thoughts (n= 49). We then tested the brain decoders on two resting-state fMRI datasets (n= 49 and 90) with and without intermittent thought sampling, achieving significant predictions. The default mode and ventral attention networks were important contributors to the predictions. Overall, this study paves the way for the brain decoding of spontaneous thought and its use for clinical applications.
Riding the Wave: Unveiling the Conformational Waves from RBD to ACE2
Authors: Maroli Nikhil 
Published: May 2023

AbstractThe binding affinity between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) plays a crucial role in the transmission and re-infection of SARS-CoV2. Here, microsecond molecular dynamics simulations revealed that point mutations in the RBD domain induced conformational transitions that determined the binding affinity between ACE2 and RBD. These structural changes propagate through the RBD domain, altering the orientation of both ACE2 and RBD residues at the binding site. ACE2 receptor shows significant structural heterogeneity, whereas its binding to the RBD domain indicates a much greater degree of structural homogeneity. The receptor was more flexible in its unbound state, with the binding of RBD domains inducing structural transitions. The structural heterogeneity observed in the ACE2 unbound form plays a role in the promiscuity of viral entry as it may allow the receptor to interact with various related and unrelated ligands. Furthermore, rigidity may be important for stabilizing the complex and ensuring the proper orientation of the RBD-binding interface with ACE2. The greater structural homogeneity observed in the ACE2-RBD complex revealed the effectiveness of neutralizing antibodies and vaccines that are primarily directed towards the RBD-binding interface. The binding of the B38 monoclonal antibody revealed restricted conformational transitions in the RBD and ACE2 receptor, attributed to its potent binding interaction.
The Host Adapted Fungal Pathogens ofPneumocystisGenus Utilize Genic Regional Centromeres
Authors: Cissé Ousmane H. , Curran Shelly , Folco H. Diego , Liu Yueqin , Bishop Lisa , Wang Honghui , Fischer Elizabeth R. , Davis A Sally , Babb-Biernacki Spenser , Doyle Vinson P. , Richards Jonathan K. , Hassan Sergio A. , Dekker John P. , Khil Pavel P. , Brenchley Jason M. , Grewal Shiv , Cushion Melanie , Ma Liang , Kovacs Joseph A. 
Published: May 2023

AbstractCentromeres are genomic regions that coordinate accurate chromosomal segregation during mitosis and meiosis. Yet, despite their essential function, centromeres evolve rapidly across eukaryotes. Centromeres are often the sites of chromosomal breaks which contribute to genome shuffling and promote speciation by inhibiting gene flow. How centromeres form in strongly host-adapted fungal pathogens has yet to be investigated. Here, we characterized the centromere structures in closely related species of mammalian-specific pathogens of the fungal phylum of Ascomycota. Methods allowing reliable continuous culture ofPneumocystisspecies do not currently exist, precluding genetic manipulation. CENP-A, a variant of histone H3, is the epigenetic marker that defines centromeres in most eukaryotes. Using heterologous complementation, we show that thePneumocystisCENP-A ortholog is functionally equivalent to CENP-ACnp1ofSchizosaccharomyces pombe. Using organisms from a short-termin vitroculture or infected animal models and ChIP-seq, we identified centromeres in threePneumocystisspecies that diverged ~100 million years ago. Each species has a unique short regional centromere (< 10kb) flanked by heterochromatin in 16-17 monocentric chromosomes. They span active genes and lack conserved DNA sequence motifs and repeats. CENP-C, a scaffold protein that links the inner centromere to the kinetochore appears dispensable in one species, suggesting a kinetochore rewiring. Despite the loss of DNA methyltransferases, 5-methylcytosine DNA methylation occurs in these species, though not related to centromere function. These features suggest an epigenetic specification of centromere function.Short summaryPneumocystisspecies offer a suitable genetic system to study centromere evolution in pathogens during host adaptation because of their unique specificity for mammals, and their phylogenetic proximity with the nonpathogenic yeastSchizosaccharomyces pombe, a popular model for cell biology. We used this system to explore how centromeres have evolved after divergence of the two clades ~460 million years ago. To address this question, we established a protocol combining short-term culture and ChIP-seq to characterize centromeres in multiplePneumocystisspecies. We show thatPneumocystishave short epigenetic centromeres that function differently from those inS. pombeand exhibit similarities to centromeres in more distantly related host adapted fungal pathogens.
Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer’s disease
Authors: Chartampila Elissavet , Elayouby Karim S. , Leary Paige , LaFrancois John J. , Alcantara-Gonzalez David , Jain Swati , Gerencer Kasey , Botterill Justin J. , Ginsberg Stephen D. , Scharfman Helen E. 
Published: May 2023

ABSTRACTMaternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes; IIS). IIS also are common in other mouse models and occur in AD patients. Im mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ΔFosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore we studied ΔFosB expression in GCs. We also studied the the neuronal marker NeuN within hilar neurons of the DG because other studies have reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability.Tg2576 breeding pairs received a diet with a relatively low, intermediate or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ΔFosB expression was reduced, and NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB and spatial memory in an animal model of AD.
Meta-analysis of behavioural research in lizards reveals that phylogeny and viviparity contribute better to animal personality than secretory glands
Authors: Ruiz-Monachesi M.R. , Martínez J.J. 
Published: May 2023

AbstractAnimal personality is defined as an individual’s behavioural consistency across contexts, situations, and time. Understanding the evolution of animal personality requires the integration of macroevolutionary patterns with intraspecific promoters of individual behavioural consistency. In this study, we conducted a meta-analysis to assess the association between lizards’ animal personality and different indicators of sociability (a personality promotor) in a phylogenetic context. In lizards, the presence of both, secretory glands and viviparity have been associated with higher sociability levels. We analysed behavioural repeatability data, including 490 effect sizes from 37 species and 63 studies, considering five categories (activity, aggressivity, boldness, exploration, sociability) while controlling for phylogenetic constraints. For each species, we obtained data on the number of secretory glands and the reproductive mode (oviparous or viviparous). The results showed similar values of repeatability for species with and without glands and an absence of correlation between the number of glands and repeatability data. However, higher repeatability was present in viviparous species than in oviparous species. When we conducted separate analyses for each behavioural type, we found two contrasting patterns for exploration and boldness. Species without glands were more exploratory, while species with glands were bolder. In general, phylogeny explained the observed patterns of repeatability, but boldness, exploration and sociability were poorly explained by evolutionary history among species. This study represents a first step in disentangling the integration among animal personality, life-history and morphology traits under a broad evolutionary context.
Task-anchored grid cell firing is selectively associated with successful path integration-dependent behaviour
Authors: Clark Harry , Nolan Matthew F. 
Published: May 2023

AbstractGrid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. While there are theoretical arguments to support each possibility, it has been challenging to directly test whether and when grid cells contribute to behaviours. Here, we investigate firing of grid and non-grid cells in the medial entorhinal cortex during a location memory task. We find that grid firing can either be anchored to the task environment, or can encode distance travelled independently of the task reference frame. Anchoring varied between and within sessions, while spatial firing of non-grid cells was either coherent with the grid population, or was stably anchored to the task environment. We took advantage of the variability in task-anchoring to evaluate whether and when encoding of location by grid cells might contribute to behaviour. We find that when reward location is indicated by a visual cue performance is similar regardless of whether grid cells are task-anchored or not, arguing against a role for grid representations when location cues are available. By contrast, in the absence of the visual cue, performance was enhanced when grid cells were anchored to the task environment. Our results suggest that anchoring of grid cells to task reference frames selectively enhances performance when path integration is required.
High number of HPAI H5 Virus Infections and Antibodies in Wild Carnivores in the Netherlands, 2020-2022
Authors: Chestakova Irina V. , van der Linden Anne , Martin Beatriz Bellido , Caliendo Valentina , Vuong Oanh , Thewessen Sanne , Hartung Tijmen , Bestebroer Theo , Dekker Jasja , Poerink Bob Jonge , Gröne Andrea , Koopmans Marion , Fouchier Ron , van den Brand Judith M.A. , Sikkema Reina S. 
Published: May 2023

AbstractIn October 2020, a new lineage of clade 2.3.4.4b HPAI virus of the H5 subtype emerged in Europe, resulting in the largest global outbreak of HPAI to date, with unprecedented mortality in wild birds and poultry. The virus appears to have become enzootic in birds, continuously yielding novel HPAI virus variants. The recently increased abundance of infected birds worldwide increases the probability of bird-mammal contact, particularly in wild carnivores. Here, we performed molecular and serological screening of over 500 dead wild carnivores for H5 HPAI virus infection and sequencing of positive materials. We show virological evidence for HPAI H5 virus infection in 0.8%, 1.4% and 9.9% of animals tested in 2020, 2021 and 2022 respectively, with the highest proportion of positives in foxes, polecats and stone martens. We obtained near full genome sequences for seven viruses and detected PB2 amino acid substitutions known to play a role in mammalian adaptation in three of these. Infections were also found in animals without associated neurological signs or mortality. Serological evidence for infection was detected in 20% of the study population. These findings suggest that a higher number of wild carnivores are infected but undetected in current surveillance programs. We recommend increased surveillance in susceptible mammals, irrespective of the presence of neurological signs or encephalitis.
Quantifying the relationship between cell proliferation and morphology during development of the face
Authors: Green Rebecca M. , Lo Vercio Lucas D. , Dauter Andreas , Barretto Elizabeth C. , Devine Jay , Vidal-García Marta , Marchini Marta , Robertson Samuel , Zhao Xiang , Mahika Anandita , Shakir M. Bilal , Guo Sienna , Boughner Julia C. , Dean Wendy , Lander Arthur D. , Marcucio Ralph S. , Forkert Nils D. , Hallgrímsson Benedikt 
Published: May 2023

ABSTRACTMorphogenesis requires highly coordinated, complex interactions between cellular processes: proliferation, migration, and apoptosis, along with physical tissue interactions. How these cellular and tissue dynamics drive morphogenesis remains elusive. Three dimensional (3D) microscopic imaging poses great promise, and generates elegant images. However, generating even moderate through-put quantified images is challenging for many reasons. As a result, the association between morphogenesis and cellular processes in 3D developing tissues has not been fully explored. To address this critical gap, we have developed an imaging and image analysis pipeline to enable 3D quantification of cellular dynamics along with 3D morphology for the same individual embryo. Specifically, we focus on how 3D distribution of proliferation relates to morphogenesis during mouse facial development. Our method involves imaging with light-sheet microscopy, automated segmentation of cells and tissues using machine learning-based tools, and quantification of external morphology via geometric morphometrics. Applying this framework, we show that changes in proliferation are tightly correlated to changes in morphology over the course of facial morphogenesis. These analyses illustrate the potential of this pipeline to investigate mechanistic relationships between cellular dynamics and morphogenesis during embryonic development.
The essential domain of FtsN triggers cell division by promoting interaction between FtsL and FtsI
Authors: Park Kyung-Tae , Park David Johnson , Pichoff Sebastien , Du Shishen , Lutkenhaus Joe 
Published: May 2023

AbstractCell division in bacteria requires the activation of FtsWI at the division site to synthesize septal peptidoglycan. InE. coliFtsN activates FtsWI and a previous model posited that the essential domain of FtsN (EFtsN) acts on FtsQLB causing conformational changes so that a domain of FtsL, called AWI (AWIFtsL), contacts FtsI resulting in activation of FtsW. In this study we use genetic analysis along with an AlphaFold2 model to test this activation model. Based on our findings we propose an updated model wherein theAWIFtsL and FtsI interaction is stabilized byEFtsN to activate FtsW and that this interaction is enhanced by theCytoFtsN-FtsA interaction. Thus, FtsN acts as both a sensor for divisome assembly and an activator. In addition, we elucidate the role played by two critical FtsL residues in FtsW activation.