bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid degeneration and neurochemical plasticity of the lateral geniculate nucleus following lesions of the primary visual cortex in marmoset monkeys
Authors: Ma Gaoyuan , Chan Jonathan M. , Worthy Katrina H. , Rosa Marcello G.P. , Atapour Nafiseh 
Published: September 2023

AbstractLesions of the primary visual cortex (V1) cause retrograde neuronal degeneration, volume loss and neurochemical changes in the lateral geniculate nucleus (LGN). Here we characterise the timing of these processes, by comparing the LGN of adult marmoset monkeys following various recovery times after unilateral V1 lesions. Observations in NeuN-stained sections obtained from animals with very short (3 days) recoveries showed that the volume and neuronal density in the LGN ipsilateral to the lesions were similar to those in the contralateral hemispheres. However, neuronal density in the LGN lesion projection zones (LPZ) dropped rapidly thereafter, with a loss of ∼50% of the population occurring within a month of the lesions. This level of neuronal loss was then sustained for the remainder of the range of recovery times, up to >3 years post-lesion. In comparison, shrinkage of the LGN progressed more gradually, not reaching a stable value until 6 months post lesion. We also determined the time course of the expression of the calcium-binding protein calbindin (CB) in magnocellular (M) and parvocellular (P) layer neurons, a recently described form of neurochemical plasticity triggered by V1 lesions. We found that CB expression could be detected in surviving M and P neurons as early as 1 month after a lesion, with the percentage of neurons showing this neurochemical phenotype showing subtle changes over 6 months. Our study shows that there is a limited time window for any possible interventions aimed at reducing secondary neuronal loss in the visual afferent pathways following damage to V1.
Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes
Authors: Cooper Blake L. , Salameh Shatha , Posnack Nikki Gillum 
Published: September 2023

ABSTRACTBackgroundBisphenol A (BPA) is commonly used to manufacture consumer and medical-grade plastics. Due to health concerns, BPA substitutes are being incorporated – including bisphenol S (BPS) and bisphenol F (BPF) – without a comprehensive understanding of their toxicological profile.ObjectivePrevious studies suggest that bisphenol chemicals perturb cardiac electrophysiology in a manner that is similar to 17β-estradiol (E2). We aimed to compare the effects of E2 with BPA, BPF, and BPS using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM).MethodsCardiac parameters were evaluated using microelectrode array (MEA) technology and live-cell fluorescent imaging at baseline and in response to chemical exposure (0.001-100 μM).ResultsCardiac metrics remained relatively stable after exposure to nanomolar concentrations (1-1,000 nM) of E2, BPA, BPF, or BPS. At higher micromolar concentrations, chemical exposures resulted in a decrease in the depolarizing spike amplitude, shorter field potential and action potential duration, shorter calcium transient duration, and decrease in hiPSC-CM contractility (E2>BPA>BPF >> BPS). Cardiomyocyte physiology was largely undisturbed by BPS exposure. BPA-induced effects were exaggerated when co-administered with an L-type calcium channel antagonist (verapamil) or E2 - and reduced when co-administered with an L-type calcium channel agonist (Bay K8644) or an estrogen receptor alpha antagonist (MPP). E2-induced effects generally mirrored those of BPA, but were not exaggerated by co-administration with an L-type calcium channel antagonist.DiscussionCollectively across multiple cardiac endpoints, E2 was the most potent and BPS was the least potent disruptor of hiPSC-CM function. Although the observed cardiac effects of E2 and BPA were similar, a few distinct differences suggest that these chemicals may act (in part) through different mechanisms. hiPSC-CM are a useful model for screening cardiotoxic chemicals, nevertheless, the describedin vitrofindings should be validated using a more complexex vivoand/orin vivomodel.
Heat stress at the bicellular stage inhibits sperm cell development and their transport into pollen tubes
Authors: Li Xingli , Bruckmann Astrid , Dresselhaus Thomas , Begcy Kevin 
Published: September 2023

ABSTRACTFor a successful double fertilization process in flowering plants (angiosperms), pollen tubes each deliver two non-motile sperm cells towards female gametes (egg and central cell, respectively). Heatwaves especially during the reproduction period are threatening male gametophyte (pollen) development, which results in severe yield losses. By using maize as a crop and grass model system, we found strong seed set reduction when moderate heat stress was applied for two days during the uni- and bicellular stages of pollen development. We show that heat stress accelerates pollen development and impairs pollen germination capabilities, when applied at the unicellular stage. Heat stress at the bicellular stage impairs sperm cell development and their transport into pollen tubes. To understand the course of the latter defects, we used marker lines and analyzed the transcriptomes of isolated sperm cells. While heat stress also affects the expression of genes involved in transcription, RNA processing and translation, especially genes in DNA replication and the cell cycle were mis-regulated. This includes centromeric histone CENH3 and α-tubulin. Most mis-regulated genes are involved in transition from metaphase to anaphase during pollen mitosis II (PM II). Heat stress activates spindle assembly check point and meta-to anaphase transition genes in sperm cells. In summary, mis-regulation of the identified genes during heat stress at the bicellular stage explains sperm cell development and transport defects ultimately leading to sterility.
Complex relationship among vessel diameter, shear stress and blood pressure controlling vessel pruning during angiogenesis
Authors: Kumar Vivek , Kumar Prashant , Hikita Takao , Ding Mingqian , Kametani Yukinori , Nakayama Masanori , Hasegawa Yosuke 
Published: September 2023

AbstractBlood vessel pruning during angiogenesis is the optimization process of the branching pattern to improve the transport properties of a vascular network. Recent studies show that part of endothelial cells (ECs) subjected to lower shear stress migrate toward vessels with higher shear stress in opposition to the blood flow for vessel regression. While dynamic changes of blood flow and local mechano-stress could coordinately modulate EC migration for vessel regression within the closed circulatory system, the effect of complexity of haemodynamic forces and vessel properties on vessel pruning remains elusive. Here, we reconstructed a 3-dimentsional (3D) vessel structure from 2D confocal images of the growing vessels in the mouse retina, and numerically obtained the local information of blood flow, shear stress and blood pressure in the vasculature. Moreover, we developed a predictive model for vessel pruning based on machine learning. We found that the combination of shear stress and blood pressure with vessel radius was tightly corelated to vessel pruning sites. Our results highlighted that orchestrated contribution of local haemodynamic parameters was important for the vessel pruning.Authors SummaryBlood vessel networks formed by angiogenic vessel growth subsequently undergo extensive vascular remodeling process by regression of selected vascular branches. Optimization of the branching pattern in the vasculature is critical to ensure sufficient blood supply throughout the entire tissue. Recent studies have highlighted a strong relationship between the vessel remodeling and the shear stress acting on the vessel wall. However, its detailed mechanisms remain elusive due to the difficulties of estimating local haemodynamic parameters and relating them to vessel remodeling.Here, we have numerically simulated local haemodynamic parameters within the vascular network of the postnatal day 6 (P6) mouse retinal vasculature. Then, the relationship among the local shear stress, blood pressure, and vessel radius with the vessel pruning was examined. Moreover, we developed a predictive model for the vessel pruning based on the local haemodynamic parameters by a machine learning technique. Importantly, our results indicate that the combination of shear stress and blood pressure with vessel radius is tightly correlated to vessel pruning sites.Given the ongoing clinical approach to suppress tumor growth via blood vessel normalization, our results provide important knowledge for developing future medicine such as nanomedicine based on drug delivery systems.
Detection of prodromal Parkinson’s disease using a urine proteomics panel and machine learning
Authors: Hällqvist Jenny , Schreglmann Sebastian R. , Kulcsarova Kristina , Skorvanek Matej , Feketeova Eva , Rizig Mie , Mollenhauer Brit , Turano Paola , Bacalini Maria Giulia , Francheschi Claudio , Wood Nicholas , Bhatia Kailash P. , Mills Kevin 
Published: September 2023

AbstractParkinson’s disease is a progressive neurodegenerative disorder and idiopathic REM-sleep behaviour disorder (iRBD) has been identified as its single most specific early symptom. To facilitate the screening of individuals at high risk to develop Parkinson’s disease, we developed a multiplexed panel of urine proteomics using machine learning and targeted mass spectrometry to detect iRBD. Random urine samples from clinically and genetically well characterized patients with iRBD, idiopathic and hereditary forms of Parkinson’s disease, and matching controls, collected in two academic centres, were analysed in a standardized way.First, a biomarker discovery and exploratory comparison of samples from randomly selected idiopathic Parkinson’s patients and age/sex-matched healthy controls were proteomically profiled and quantified (> 2500 proteins). The most differentially expressed biomarkers were combined into a high-throughput, multiplexed assay using targeted proteomics designed for use of tandem mass spectrometers for potential translation into clinical practise. This was then validated on independent patient and control samples (n=184). After detecting a major influence of sex on the proteome, we focused subsequent analyses on the larger group of available male samples (n= 114) and report results based on iRBD (n= 14), idiopathic (n= 35) and young-onset Parkinson’s disease (n= 15), carriers of LRRK2 (n= 10), PARKIN-gene mutations (n= 5), and healthy control subjects (n= 35). After establishing excellent compatibility between the two study sites, orthogonal partial least squares discriminant analysis (OPLS-DA) excluded a relevant effect of aging, but detected significant differences between iRBD and healthy controls (ANOVA-CVP= 0.002), as well as the combination of iPD/iRBD and healthy controls (ANOVA-CVP= 0.01).Uni- and multivariate analyses detected a shared expression pattern for the protein biomarkers UBC, NCAM1, MIEN1, SPP2, REG1B, ITIH2, BCHE and C3 between iRBD and idiopathic Parkinson’s disease. Utilizing split train/test-datasets in a multiple-regression classifier model resulted in a mean accuracy of 78% to detect iRBD, matching iRBD’s conversion rate to Parkinson’s disease. Hierarchical clustering revealed greater similarities in urine proteomic changes between iRBD and idiopathic than monogenic Parkinson’s disease. Several proteins identified correlated either with clinical severity (e.g. VCAM1, MSN, HPX), or risk for future conversion to Parkinson’s disease (VCAM1, MSN, MYO10, HSPAIL).This demonstrates the power of machine learning and urine biomarkers to identify iRBD patients. As we develop new therapies and interventions, the ability to detect individuals at-risk of neurodegeneration in very early disease stage will be invaluable for treatment success.
Optimal environmental testing frequency for outbreak surveillance
Authors: Olejarz Jason W. , Roster Kirstin I. Oliveira , Kissler Stephen M. , Lipsitch Marc , Grad Yonatan H. 
Published: September 2023

AbstractPublic health surveillance for pathogens presents an optimization problem: we require enough sampling to identify intervention-triggering shifts in pathogen epidemiology, such as new introductions or sudden increases in prevalence, but not so much that costs due to surveillance itself outweigh those from pathogen-associated illness. To determine this optimal sampling frequency, we developed a general mathematical model for the introduction of a new pathogen that, once introduced, increases in prevalence exponentially. Given the relative cost of infectionvs. sampling, we derived equations for the expected combined cost of disease burden and surveillance given a sampling frequency and thus the sampling frequency for which the expected total cost is lowest.
Relationships Among Knee Injuries, Q-angles, and Competition Levels in Female Ski Racers
Authors: Taylor Danielle , Bevier Catherine 
Published: September 2023

AbstractPrior research has focused solely on the prevalence of anterior cruciate ligament (ACL) injuries in male and female alpine ski racers and on the Q-angle, the angle created between the quadriceps muscles and the patella tendon, in ways unrelated to alpine ski racing. A survey was sent to female alpine ski racers who represent the academy U16 level through World Cup professionals that included questions regarding the athlete’s racing level, Q- angle, and past knee injuries. A total of 124 responses were collected. Just under half (45.16%) of the survey participants reported a history of at least one knee injury. A great majority, 83.33%, of the Professional athletes reported tearing their knee at least once, which is 3.04 and 1.90 times more than athletes of the Pre Professional and U16 levels respectively. Athletes with a Q-angle of 15° or 20° had torn 85.26% of the total ligaments with the ACL, MCL, and meniscus being the most frequently torn ligaments. From this self-reported data, it is clear that Q-angles and racing level both influence the frequency of ligament tears in female alpine ski racers. An athlete competing at a higher level of competitive ski racing is more likely to tear a knee ligament than those at lower levels, and larger Q- angles influence the risk of injury as well as injury to specific ligaments within the knee.
Analyzing the Spatial Distribution and Language Abilities of Physicians in Alberta, Canada
Authors: Belanger Christopher , Bjerre Lise M. 
Published: September 2023

AbstractThis study combined public data and geospatial analysis to examine physicians’ language abilities and locations in Alberta, Canada, and produced an interactive map to allow patients and policymakers to view the data. We identified n=11,370 active physicians in the province of Alberta, of whom we further identified n=194 (1.7%) as University of Ottawa (uOttawa) graduates, n=955 (8.4%) as French-speaking, and n=4,965 (43.7%) as community-based family physicians. French-speaking physicians were concentrated in Census Division 6 (n=464, 48.6%) surrounding Calgary and Census Division 11 (n=356, 37.3%) surrounding Edmonton. Overall reported French-language ability was low, with just 955 (8.4%) of all active physicians reporting competency in French. uOttawa graduates (n=70, 36.1%) were much more likely to report French ability than graduates of other schools (n=885, 7.9%), women (n=457, 9.6%) were slightly more likely than men (n=497, 7.6%), and specialists (n=666, 10.4%) were more likely than family physicians (n=289, 5.8%).
Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli inDrosophilalarvae
Authors: Luedke Kory P. , Yoshino Jiro , Yin Chang , Jiang Nan , Huang Jessica M. , Huynh Kevin , Parrish Jay Z. 
Published: September 2023

AbstractAn animal’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity ofDrosophilalarvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identifiedmiR-14as a regulator of dendrite positioning in the epidermis:miR-14is expressed broadly in the epidermis but not in apodemes, andmiR-14inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found thatmiR- 14regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation.Author SummaryOur skin provides a first point of contact for a variety of sensory inputs, including noxious cues that elicit pain. Although specialized interactions between skin cells and sensory neurons are known to shape responses to a variety of mechanosensory stimuli including gentle touch and vibration, interactions with skin cells that shape responses to painful mechanical inputs are less well defined. Using the fruit flyDrosophila melanogasteras a model system, we demonstrate that the pattern of epidermal innervation, specifically the extent of dendrite intercalation between epidermal cells, tunes the animal’s sensitivity to noxious mechanical stimuli. Similar mechanisms may regulate sensitivity to painful mechanical inputs in both pathological and physiological states in vertebrates.
A fourth locus in thePlasmodium falciparumgenome associated with sickle haemoglobin
Authors: Hamilton William L. , Band Gavin , Aniweh Yaw , Asoala Victor , Drury Eleanor , Rockett Kirk A. , Awandare Gordon A. , Kwiatkowski Dominic P. , Amenga-Etego Lucas N. 
Published: September 2023

AbstractHeterozygosity for sickle haemoglobin (HbS) confers protection against severe malaria caused by the parasitePlasmodium falciparum. Recent work suggests that this protective effect can depend on the parasite genotype. Here, we performed a genome-wide association analysis ofP. falciparumagainst human β-globin genotypes in a sample of 1,368 people with mild malaria in northern Ghana. We replicated the previously identified associations with HbS at two parasite loci. However, a newly identified locus within the serine/threonine kinaseFIKK4.2, which we termPfsa4, was also associated with HbS; this finding replicated in a published sample from Mali. ThePfsa1-4mutations vary widely in frequencies across Africa, are absent from Asia, and are highly correlated with each-other across multiple populations. We found no strong associations with haemoglobin C. These findings add new complexity to the emerging picture of association between human and co-evolving malaria parasite genomes, suggesting new avenues for functional exploration.
A novel, tissue-associated and vertically transmitted bacterial symbiont in the coralPocillopora acuta
Authors: Maire Justin , Tsang Min Ching Sarah Jane , Damjanovic Katarina , Epstein Hannah E. , Judd Louise M. , Blackall Linda L. , van Oppen Madeleine J. H. 
Published: September 2023

AbstractCoral microhabitats are colonized by a myriad of microorganisms, including diverse bacteria which are essential for host functioning and survival. However, the location, transmission, and functions of individual bacterial species living inside the coral tissues remain poorly studied. Here, we show that a previously undescribed bacterial symbiont of the coralPocillopora acutaforms cell-associated microbial aggregates (CAMAs) within the mesenterial filaments. CAMAs were found in both adults and larval offspring, providing evidence of vertical transmission.In situlaser capture microdissection of CAMAs followed by 16S rRNA gene metabarcoding and shotgun metagenomics produced a near complete metagenome-assembled genome. We subsequently cultured the CAMA bacteria fromP. acutacolonies, and sequenced and assembled their genomes. Phylogenetic analyses showed that the CAMA bacteria belong to an undescribed Endozoicomonadaceae genus and species, which we propose to nameSororendozoicomonas aggregatagen. nov sp. nov. Metabolic pathway reconstruction from its genome sequence suggests this species can synthesize most amino acids, several B vitamins, and antioxidants, which may be beneficial to its coral hosts. This study provides detailed insights into a new member of the widespread Endozoicomonadaceae family, thereby improving our understanding of coral holobiont functioning. Vertically transmitted, tissue-associated bacteria, such asS. aggregatamay be key candidates for the development of microbiome manipulation approaches with long-term positive effects on the coral host.
Sodium chloride in the tumor microenvironment enhances T-cell metabolic fitness and cytotoxicity
Authors: Soll Dominik , Arunkumar Mahima , Alissa-Alkhalaf Maha , Sun Shan , Nguyen Trang , Chu Chang-Feng , Lutz Veronika , Schäuble Sascha , Garcia-Ribelles Ignacio , Mueller Michael , Michalke Bernhard , Panagiotou Gianni , Schatzlmaier Philipp , Stockinger Hannes , Schamel Wolfgang W. , Huber Magdalena , Zielinski Christina E. 
Published: September 2023

AbstractAdoptive T-cell therapy has become a powerful weapon for cancer treatment. The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is highly sensitive to the tumor microenvironment. It is therefore of considerable interest to bypass immunosuppressive signals in the tumor microenvironment and to identify factors that augment cytotoxic effector functions and ultimately tumor killing. Whether ionic signals serve as aberrant immune signals and influence the adaptive human antitumor immune response is still largely unexplored. We therefore investigated the effect of sodium on the phenotype, function and metabolic regulation of human CD8+T cells using transcriptomic, metabolomic, high-dimensional flow cytometric and functional assays. We demonstrate a significant enrichment of sodium in solid tumors from patients with breast cancer, which leaves a transcriptomic imprint on intratumoral immune cells. Sodium chloride (NaCl) enhanced the activation state and effector functions of human CD8+memory T cells. These functional alterations were associated with enhanced metabolic fitness, particularly increases in glycolysis, oxidative phosphorylation and overall nutrient uptake. These NaCl-induced effects translated into increased tumor cell killingin vitroand in a tumor mouse modelin vivo.We therefore propose NaCl as a positive regulator of acute antitumor immunity that could be harnessed forex vivoconditioning of adoptively transferred T cells, such as CAR T-cells.