bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction
Authors: Awata Wanessa M.C. , Alves Juliano V. , Costa Rafael M. , Bruder-Nascimento Ariane , Singh Shubhnita , Barbosa Gabriela S. , Tirapelli Carlos Renato , Bruder-Nascimento Thiago 
Published: September 2023

AbstractBackgroundRenin-angiotensin (Ang II)-aldosterone system (RAAS) is crucial for the cardiovascular risk associated with excessive ethanol consumption. Disturbs in mitochondria have been implicated in multiple cardiovascular diseases. However, if mitochondria dysfunction contributes to ethanol-induced vascular dysfunction is still unknown. We investigated whether ethanol leads to vascular dysfunction via RAAS activation, mitochondria dysfunction, and mitochondrial reactive oxygen species (mtROS).MethodsMale C57/BL6J or mt-keima mice (6–8-weeks old) were treated with ethanol (20% vol./vol.) for 12 weeks with or without Losartan (10 mg/kg).ResultsEthanol induced aortic hypercontractility in an endothelium-dependent manner. PGC1α (a marker of biogenesis), Mfn2, (an essential protein for mitochondria fusion), as well as Pink-1 and Parkin (markers of mitophagy), were reduced in aortas from ethanol-treated mice. Disturb in mitophagy flux was further confirmed in arteries from mt-keima mice. Additionally, ethanol increased mtROS and reduced SOD2 expression. Strikingly, losartan prevented vascular hypercontractility, mitochondrial dysfunction, mtROS, and restored SOD2 expression. Both MnTMPyP (SOD2 mimetic) and CCCP (a mitochondrial uncoupler) reverted ethanol-induced vascular dysfunction. Moreover, L-NAME (NOS inhibitor) and EUK 134 (superoxide dismutase/catalase mimetic) did not affect vascular response in ethanol group, suggesting that ethanol reduces aortic nitric oxide (NO) and H2O2bioavailability. These responses were prevented by losartan.ConclusionAT1receptor modulates ethanol-induced vascular hypercontractility by promoting mitochondrial dysfunction, mtROS, and reduction of NO and H2O2bioavailability. Our findings shed a new light in our understanding of ethanol-induced vascular toxicity and open perspectives of new therapeutic approaches for patients with disorder associated with abusive ethanol drinking.
Evolutionarily conserved ovarian fluid proteins are responsible for extending egg viability in salmonid fish
Authors: Gueho Aurélie , Żarski Daniel , Rime Hélène , Guével Blandine , Com Emmanuelle , Lavigne Régis , Nguyen Thaovi , Montfort Jérôme , Pineau Charles , Bobe Julien 
Published: September 2023

AbstractIn contrast to most fish species, salmonids exhibit the unique ability to hold their eggs for several days after ovulation without significant loss of viability. During this period, eggs are held in the body cavity in a biological fluid, the coelomic fluid (CF) that is responsible for preserving egg viability. To identify CF proteins responsible for preserving egg viability, a proteomic comparison was performed using 3 salmonid species and 3 non-salmonid species to identify salmonid-specific highly abundant proteins. In parallel, rainbow trout CF fractions were purified and used in a biological test to estimate their egg viability preservation potential. The most biologically active CF fractions were then subjected to mass spectrometry analysis. We identified 50 CF proteins that are overabundant in a salmonid-specific manner and present in analytical fractions exhibiting the highest egg viability preservation potential. Here we show that salmonid CF is a complex biological fluid and that several proteins are responsible for preserving egg viability. Among these key players are proteins related to immunity, calcium binding, lipid metabolism, proteolysis, extracellular matrix and sialic acid metabolic pathway.
Unraveling the Structure of Meclizine Dihydrochloride with MicroED
Authors: Lin Jieye , Unge Johan , Gonen Tamir 
Published: September 2023

AbstractMeclizine (Antivert, Bonine) is a first-generation H1 antihistamine used in the treatment of motion sickness and vertigo. Despite its wide medical use for over 70 years, its crystal structure and the details of protein-drug interactions remained unknown. In this study, we used microcrystal electron diffraction (MicroED) to determine the three-dimensional (3D) crystal structure of meclizine dihydrochloride directly from a seemingly amorphous powder. Two racemic enantiomers (R/S) were found in the unit cell, which packed as repetitive double layers in the crystal lattice. The packing was made of multiple strong N-H···Cl-hydrogen bonding interactions and weak interactions like C-H···Cl-and pi-stacking. Molecular docking revealed the binding mechanism of meclizine to the histamine H1 receptor. A comparison of the docking complexes between histamine H1 receptor and meclizine or levocetirizine (a second-generation antihistamine) showed the conserved binding sites. This research illustrates the combined use of MicroED and molecular docking in unraveling protein-drug interactions for precision drug design and optimization.
A common mechanism processes auditory and visual motion
Authors: Alais David , Folgueiras Uxía Fernández , Leung Johahn 
Published: September 2023

AbstractWe report behavioural findings implying common motion processing for auditory and visual motion. We presented brief translational motion stimuli drifting leftwards or rightwards in the visual or auditory modality at various speeds. Observers made a speed discrimination on each trial, comparing current speed against mean speed (i.e., method of single stimuli). Data were compiled into psychometric functions and means and slopes compared. Slopes between auditory and visual motion were identical, consistent with a common noise source, although mean speed for audition was veridical while visual speeds were significantly underestimated. An inter-trial analysis revealed clear motion priming in both audition and vision (i.e., faster perceived speed after a fast preceding speed, andvice versa– a positive serial dependence). Plotting priming as a function of preceding speed revealed the same slope for each modality. We also tested whether motion priming was modality specific. Whether vision preceded audition, or audition preceded vision, a positive serial bias (i.e., priming) was always observed. We conclude a common process underlies auditory and visual motion, and that this explains the closely matched data in vision and audition, as well as the crossmodal data showing equivalent motion priming regardless of the preceding trial’s modality.
Dynamics of associated microbiomes during algal bloom development: to see and to be seeing
Authors: Meirkhanova Ayagoz , Zhumakhanova Adina , Len Polina , Schoenbach Christian , Levi Eti E. , Jeppesen Erik , Davidson Thomas A. , Barteneva Natasha S. 
Published: September 2023

AbstractOur understanding of the interactions between bacteria and phytoplankton in the freshwater phycosphere, including the development of algal blooms, is very limited. To identify the taxa and compositional variation within microbial communities, we performed 16S rRNA amplicon sequencing research on samples collected weekly through summer from mesocosms that differed in temperature and mixing regimes. We investigated, for the first time, the abundance diversity of microalgae, including Chlorophyta, Cryptophyta, and Cyanobacteria species, using visualization-based FlowCAM analysis and classification of microbial communities to species level by nanopore next-generation sequencing. We found that nanopore metagenomics, in parallel with complementary imaging flow cytometry, can depict the fine temporal dynamics of microbiomes associated with visually identifiedMicrocystismorphospecies, Chlorophyta, and Cryptophyta during algal bloom development. Our results showed that the temporal characteristics of microbiomes combined with a visual approach may be a key tool to predict the metacommunity structure and dynamics of algal blooms in response to anthropogenic effects and climate change.
Investigating a causal role for neutrophil count onP. falciparumsevere malaria: a Mendelian Randomization study
Authors: Constantinescu Andrei-Emil , Hughes David A. , Bull Caroline J. , Fleming Kathryn , Mitchell Ruth E. , Zheng Jie , Kar Siddhartha , Timpson Nicholas J. , Amulic Borko , Vincent Emma E. 
Published: September 2023

AbstractBackgroundMalaria caused byP. falciparumimposes a tremendous public health burden on people living in sub-Saharan Africa. Severe malaria is associated with high morbidity and mortality and results from complications such as cerebral malaria, severe anaemia or respiratory distress. Individuals living in malaria endemic regions often have a reduced circulating neutrophil count due to a heritable phenomenon called ‘benign ethnic neutropenia’ (BEN). Neutrophils defend against bacterial infections but have been shown to be detrimental in pre-clinical malaria models, raising the possibility that reduced neutrophil counts modulate severity of malaria in susceptible populations. We tested this hypothesis by performing a genome-wide association study (GWAS) of circulating neutrophil count and a Mendelian randomization (MR) analysis of neutrophil counts on severe malaria in individuals of predominantly African ancestry.ResultsWe carried out a GWAS of neutrophil count in individuals associated to an African continental ancestry group within UK Biobank (N=5,976). We identified previously unknown loci regulating neutrophil count in a non-European population. This was followed by a two-sample bi-directional MR analysis between neutrophil count and severe malaria (MalariaGEN, N=17,056). We identified 73 loci (r2=0.1) associated with neutrophil count, including the well-known rs2814778 variant responsible for BEN. The greatest evidence for an effect was found between neutrophil count and severe anaemia, although the confidence intervals crossed the null. MR analyses failed to suggest evidence for an effect of the combined severe malaria syndromes or individual subtypes (severe malaria anaemia, cerebral malaria, other severe malaria) on neutrophil count.ConclusionOur GWAS of neutrophil count revealed unique loci present in individuals of African ancestry. We note that a small sample-size reduced our power to identify variants with low allele frequencies and/or low effect sizes in our GWAS. Our work highlights the need for conducting large-scale biobank studies in Africa and for further exploring the link between neutrophils and severe malarial anemia.
Intragastric behavior of an experimental infant formula may better mimic intragastric behavior of human milk as compared to a control formula
Authors: Roelofs Julia J.M. , Tjoelker Reina S. , Lambers Tim T. , Smeets Paul A.M. 
Published: September 2023

AbstractBackgroundDuring breastfeeding the macronutrient composition of breastmilk changes gradually from relatively low-fat (foremilk) to relatively high-fat (hindmilk), initially exposing the gastrointestinal tract to a relatively low fat concentration. In contrast, infant formulae (IF) are homogenous. Mild processing and addition of milk fat globule membrane (MFGM) may impact gastric emulsion instability, potentially impacting the phased release of nutrients as observed during breastfeeding.ObjectiveTo assess gastric emulsion stability, gastric emptying, and the postprandial plasma metabolome of an experimental minimally processed IF (EF) with an altered fat-globule interface and a control IF (CF).MethodsTwenty healthy males participated in this double-blind randomized crossover trial. Gastric MRI scans and blood samples were obtained before and after consumption of 600 ml CF or EF over a 2-h period. Outcomes included gastric top layer formation, total gastric volume, and blood parameters (FFA, insulin, glucose, and NMR-metabolomics).ResultsEF showed an earlier onset (13.4 min, p=0.017), smaller maximum volume (49.0 ml, p= 0.033), and a shorter time to maximum top layer volume (13.9 min, p=0.022), but similar AUC (p=0.915) compared to CF. Total gastric volume did not show a treatment*time effect. Insulin concentrations were lower for EF. FFA and glucose did not differ. EF yielded higher serum concentrations of phospholipid-and cholesterol-related metabolites.ConclusionAn EF displayed faster gastric creaming than a CF, thereby potentially better mimicking the behavior of breastmilk which leads to phased release of nutrients into the intestine. Overall physiological benefits of this difference in gastric behavior remain to be studied further in infants.
Social Context and Drug Cues Modulate Inhibitory Control in Cocaine Addiction: involvement of the STN evidenced through Functional Magnetic Resonance Imaging
Authors: Terenzi Damiano , Simon Nicolas , Gachomba Michael Joe Munyua , de Peretti Jeanne Laure , Nazarian Bruno , Sein Julien , Anton Jean-Luc , Grandjean Didier , Baunez Christelle , Chaminade Thierry 
Published: September 2023

AbstractBackgroundAddictions often develop in a social context, although the influence of social factors did not receive much attention in the neuroscience of addiction. Recent animal studies suggest that peer presence can reduce cocaine intake, an influence potentially mediated, among others, by the subthalamic nucleus (STN). However, there is to date no such neurobiological study in humans.MethodsThis study investigated the impact of social context and drug cues on brain correlates of inhibitory control in individuals with and without cocaine use disorder (CUD) using functional Magnetic Resonance Imaging (fMRI). Seventeen CUD participants and 17 healthy controls (HC) performed a novel fMRI Stop-Signal task in the presence and absence of an observer while being exposed to cocaine-related and neutral pictures as cues.ResultsThe results showed that CUD participants, while slower at stopping with neutral cues, recovered control level stopping abilities with cocaine cues, while HC did not show any difference. Neuroimaging revealed the involvement of frontal cortical regions and of the subthalamic nucleus (STN) in inhibitory control, which was modulated by both social context and drug cues in CUD participants but not in HC.ConclusionsThese findings highlight the impact of social context and drug cues on inhibitory control in CUD and suggest potential targets for intervention such as the STN, also emphasizing the importance of considering the social context in addiction research and treatment.
Super Bowl, an open platform for visual stimulation of insects
Authors: Prech Stefan , Groschner Lukas N. , Borst Alexander 
Published: September 2023

AbstractTo study how the nervous system processes visual information, experimenters must record neural activity while delivering visual stimuli in a controlled fashion. In animals with a nearly panoramic field of view, such as flies, precise stimulation of the entire visual field is challenging. We describe a projector-based device for stimulation of the insect visual system under a microscope. The device is based on a bowl-shaped screen that provides a wide and nearly distortion-free field of view. It is compact, cheap, easy to assemble, and easy to operate using the included open-source software for stimulus generation. We validate the virtual reality system technically and demonstrate its capabilities in a series of experiments at two levels: the cellular, by measuring the membrane potential responses of visual interneurons; and the organismal, by recording optomotor and fixation behavior ofDrosophila melanogasterin tethered flight. Our experiments reveal the importance of stimulating the visual system of an insect with a wide field of view, and we provide a simple solution to do so.
The structure of aC. neoformanspolysaccharide motif recognized by protective antibodies: A combined NMR and MD study
Authors: Hargett Audra A. , Azurmendi Hugo F. , Crawford Conor J. , Wear Maggie P. , Oscarson Stefan , Casadevall Arturo , Freedberg Darόn I. 
Published: September 2023

AbstractCryptococcus neoformansis a fungal pathogen responsible for cryptococcosis and cryptococcal meningitis. TheC. neoformanscapsular polysaccharide and shed exopolysaccharide functions both as a key virulence factor and to protect the fungal cell from phagocytosis. Currently, a glycoconjugate of these polysaccharides is being explored as a vaccine to protect againstC. neoformansinfection. In this combined NMR and MD study, experimentally determined NOEs andJ-couplings support a structure of the synthetic decasaccharide, GXM10-Ac3, obtained by MD. GXM10-Ac3was designed as an extension of glucuronoxylomannan (GXM) polysaccharide motif (M2) which is common in the clinically predominant serotype A strains and is recognized by protective forms of GXM-specific monoclonal antibodies. The M2 motif is characterized by a 6-residue α-mannan backbone repeating unit, consisting of a triad of α-(1→3)-mannoses, modified by β-(1→2)-xyloses on the first two mannoses and a β-(1→2)-glucuronic acid on the third mannose. The combined NMR and MD analyses reveal that GXM10-Ac3adopts an extended structure, with xylose/glucuronic acid branches alternating sides along the α-mannan backbone.O-acetyl esters also alternate sides and are grouped in pairs. MD analysis of a twelve M2-repeating unit polymer supports the notion that the GXM10-Ac3structure is uniformly represented throughout the polysaccharide. This experimentally consistent GXM model displays high flexibility while maintaining a structural identity, yielding new insights to further explore intermolecular interactions between polysaccharides, interactions with anti-GXM mAbs, and the cryptococcal polysaccharide architecture.Significance StatementThis study utilized a combined NMR and MD approach to elucidate the structure of aCryptococcus neoformansGXM synthetic decasaccharide (GXM10-Ac3), recognized by protective anti-GXM mAbs. The data revealed an extended structure in which the xylose/glucuronic acid branches and pairs of 6-O-acetyl esters predominantly alternate sides along the α-mannan backbone. MD analysis of a GXM polysaccharide predicts that the decasaccharide structure is uniformly represented in the polysaccharide. Additionally, the GXM exhibits high flexibility while maintaining structural identity. These findings lay the foundation for future studies aimed at understanding anti-GXM antibody-polysaccharide interactions.
Structured RhoGEF recruitment drives myosin II organization on large exocytotic vesicles
Authors: Kamalesh Kumari , Segal Dagan , Avinoam Ori , Schejter Eyal D. , Shilo Ben-Zion 
Published: September 2023

AbstractThe Rho family of GTPases plays a crucial role in cellular mechanics, by regulating actomyosin contractility through the parallel induction of actin and myosin assembly and function. Using exocytosis of large vesicles in theDrosophilalarval salivary gland as a model, we followed the spatiotemporal regulation of Rho1, that in turn creates distinct organization patterns of actin and myosin. After vesicle fusion, low levels of activated Rho1 diffuse to the vesicle membrane and drive actin nucleation in an uneven, spread-out pattern. Subsequently, the Rho1 activator RhoGEF2 distributes as an irregular meshwork on the vesicle membrane, activating Rho1 in a corresponding punctate pattern and driving local myosin II recruitment, resulting in vesicle constriction. Vesicle membrane buckling and subsequent crumpling occur at local sites of high myosin II concentrations. These findings indicate that distinct thresholds for activated Rho1 create a biphasic mode of actomyosin assembly, inducing anisotropic membrane crumpling during exocrine secretion.
Loss of ATP-sensitive channel expression and function decreases opioid sensitivity in a mouse model of type 2 diabetes
Authors: Fisher Cole , Johnson Kayla , Moore Madelyn , Sadrati Amir , Janecek Jody L. , Graham Melanie L. , Klein Amanda H. 
Published: September 2023

AbstractDuring diabetes, β-cell dysfunction due to loss of potassium channels sensitive to ATP, known as KATPchannels occurs progressively over time contributing to hyperglycemia. KATPchannels are additionally present in the central and peripheral nervous systems and are downstream targets of opioid receptor signaling. The aim of this study is to investigate if KATPchannel expression or activity in the nervous system changes in diabetic mice and if morphine antinociception changes in mice fed a high fat diet (HFD) for 16 weeks compared to controls. Mechanical thresholds were also monitored before and after administration of glyburide or nateglinide, KATPchannel antagonists, for four weeks. HFD mice have decreased antinociception to systemic morphine, which is exacerbated after systemic treatment with glyburide or nateglinide. HFD mice also have lower rotarod scores, decreased mobility in an open field test, and lower burrowing behavior compared to their control diet counterparts, which is unaffected by KATPchannel antagonist delivery. Expression of KATPchannel subunits, Kcnj11 (Kir6.2) and Abcc8 (SUR1), were decreased in the peripheral and central nervous system in HFD mice, which is significantly correlated with baseline paw withdrawal thresholds. Upregulation of SUR1 through an adenovirus delivered intrathecally increased morphine antinociception in HFD mice, whereas Kir6.2 upregulation improved morphine antinociception only marginally. Perspective: This article presents the potential link between KATPchannel function and neuropathy during diabetes. There is a need for increased knowledge in how diabetes affects structural and molecular changes in the nervous system to lead to the progression of chronic pain and sensory issues.