bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylome-wide association studies of traumatic injury identifies differential DNA methylation of synaptic plasticity and GABAergic-signalling
Authors: Brown Jodie P. , Marshall Sally , Walker Rosie M. , Campbell Archie , Hayward Caroline , McIntosh Andrew M. , Evans Kathryn L. , Thomson Pippa A. 
Published: November 2023

AbstractTraumatic physical injury is often associated with psychological trauma and is a risk factor for major depressive disorder (MDD). In Generation Scotland traumatic injury was significantly associated with recurrent major depression (OR = 2.10, 95% CI 1.33-3.33,PLJ=LJ0.0016). and schizotypal symptoms, particularly disorganised thought (βLJ=LJ0.111, 95% CI 0.049-0.177,PLJ=LJ0.0004). We performed methylome-wide analyses of traumatic injury in individuals with MDD and controls separately to investigate the link between traumatic injury and MDD. Nominally significant differences in differential DNA methylation between MDD and control groups were identified at 40 003 CpG sites (p < 0.05). Individuals with recurrent MDD showed significantly higher levels of DNA methylation associated with traumatic injury at CpG sites at the first exon and lower levels at exon boundaries, this was significant different to the association pattern at these sites in controls (mean difference in M-value = 0.0083,P= 21.1×10-10, and -0.0125,P= 2.1×10-174, respectively). Analyses at the level of CpG site, genes and gene ontologies implicated dysregulation of processes related to synaptic plasticity, including dendrite development, excitatory synapse and GABAergic signalling (normalised enrichment values > 2, FDR q-values < 0.01). Enrichment analyses for regional brain-expression in the recurrent MDD group highlight the limbic lobe and supraoptic nuclei (recurrent MDD FWER = 0.028 and 0.034, respectively). These results suggest that traumatic injury is associated with patterns of DNA methylation differentially in individuals with MDD compared to controls, highlighting the need for novel analysis approaches.
Photosymbiosis reduces the environmental stress response under a heat challenge in a facultatively symbiotic coral
Authors: Wuitchik DM , Aichelman HE , Atherton KF , Brown CM , Chen X , DiRoberts L , Pelose GE , Tramonte CA , Davies SW 
Published: November 2023

AbstractThe symbiosis between corals of the order Scleractinia and dinoflagellates of the family Symbiodiniaceae is sensitive to environmental stress. The oxidative bleaching hypothesis posits that extreme temperatures lead to accumulation of photobiont-derived reactive oxygen species ROS, which exacerbates the coral environmental stress response (ESR). To understand how photosymbiosis modulates coral ESRs, these responses must be explored in hosts in and out of symbiosis. We leveraged the facultatively symbiotic coralAstrangia poculata, which offers an opportunity to uncouple the ESR across its two symbiotic states (symbiotic, aposymbiotic). Colonies of both symbiotic states were exposed to three temperature treatments for 15 days: i) control (static 18°C), ii) heat challenge (increasing from 18 to 32°C), and iii) cold challenge (decreasing from 18 to 6°C) after which host gene expression was profiled. Cold challenged corals elicited widespread differential expression, however, there were no differences between symbiotic states. In contrast, symbiotic colonies exhibited greater gene expression plasticity under heat challenge, including enrichment of cell cycle pathways involved in controlling photobiont growth. Counter to the oxidative bleaching hypothesis, this plasticity did not include signatures of stress, and rather a dampened ESR under heat challenge was observed, suggesting that photobionts reduce the host’s ESR under elevated temperatures inA. poculata.
Phenological and epidemiological impacts of climate change on peach production
Authors: Vanalli Chiara , Radici Andrea , Casagrandi Renato , Gatto Marino , Bevacqua Daniele 
Published: November 2023

AbstractAgricultural food security is threatened by climate change impacts, which can distress crop growth and favor the spread of infectious diseases. Here, we examined the synergism of the two potentially most disruptive causes of future yield failure in peach production: the effects of global climate change on fruit growth and on the spread of fungal diseases. Coupling a phenological and epidemiological model across the French continental territory, we provided projections of yield losses for four peach cultivars (early, mid-early, mid-late, and late) in the XXI century under different climate change scenarios. Global warming is expected to impair fruit phenology with blooming failure events in the south-western part of the country. This will be less extreme under the more moderate emission scenario, even though sporadic blooming failures will still occur. In contrast, future warmer and drier conditions will decrease brown rot-induced yield loss in the historical locations devoted to peach cultivation. To adapt to these changes, the benefits of shifting peach production sites to new suitable areas are evaluated. Thanks to this strategy, the peach national yield could still be fulfilled even under the most extreme climate change scenario. Comprehensive mathematical frameworks, that concomitantly consider the climatic effects on the plant hosts and on their pathogens, are required to provide reliable future predictions of crop yields and to inform control and adaptation strategies to guarantee food security under global warming.
Regenerative Signatures in Bronchioalveolar Lavage of Acute Respiratory Distress Syndrome
Authors: Zhao Runzhen , Hadisurya Marco , Ndetan Harrison , Xi Nan Miles , Adduri Sitaramaraju , Konduru Nagarjun Venkata , Samten Buka , Tao W. Andy , Singh Karan P , Ji Hong-Long 
Published: November 2023

SummaryBackgroundIn patients with severe acute respiratory distress syndrome (ARDS) associated with sepsis, lung recovery is considerably delayed, and mortality is much high. More insight into the process of lung regeneration in ARDS patients is needed. Exosomes are important cargos for intercellular communication by serving as autocrine and/or paracrine. Cutting-edge exomics (exosomal proteomics) makes it possible to study the mechanisms of re-alveolarization in ARDS lungs.AimsThis study aimed to identify potential regenerative niches by characterizing differentially expressed proteins in the exosomes of bronchioalveolar lavage (BAL) in ARDS patients.MethodsWe purified exosomes from BAL samples collected from ARDS patients by NIH-supported ALTA and SPIROMICS trials. The abundance of exosomal proteins/peptides was quantified using liquid chromatography-mass spectrometry (LC-MS). Differentially expressed exosomal proteins between healthy controls and ARDS patients were profiled for functional annotations, cell origins, signaling pathways, networks, and clinical correlations.ResultsOur results show that more exosomal proteins were identified in the lungs of late-stage ARDS patients. Immune cells and lung epithelial stem cells were major contributors to BAL exosomes in addition to those from other organs. We enriched a wide range of functions, stem cell signals, growth factors, and immune niches in both mild and severe patients. The differentially expressed proteins that we identified were associated with key clinical variables. The severity-associated differences in protein-protein interaction, RNA crosstalk, and epigenetic network were observed between mild and severe groups. Moreover, alveolar type 2 epithelial cells could serve as both exosome donors and recipients via autocrine and paracrine mechanisms.ConclusionsThis study identifies novel exosomal proteins associated with diverse functions, signaling pathways, and cell origins in ARDS lavage samples. These differentiated proteins may serve as regenerative niches for re-alveolarization in injured lungs.
Can non-invasive brain stimulation modulate peak alpha frequency in the human brain? A systematic review and meta-analysis
Authors: Millard S.K. , Speis D.B. , Skippen P. , Chiang A.K.I. , Chang W.J. , Lin A.J. , Furman A.J. , Mazaheri A. , Seminowicz D.A. , Schabrun S.M. 
Published: November 2023

AbstractPeak alpha frequency, the dominant oscillatory frequency within the alpha range (8–12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions and provide new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non-invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre- and post-NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk-of-bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta-analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk-of-bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta-analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = -0.12, 95% CI = -0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. There is limited evidence that NIBS can modulate PAF, and existing evidence does not demonstrate robust effects. Further studies employing standardised stimulation protocols are necessary to determine the potential of NIBS to modulate PAF.
Quality Matters: Deep Learning-Based Analysis of Protein-Ligand Interactions with Focus on Avoiding Bias
Authors: Sellner Manuel S. , Lill Markus A. , Smieško Martin 
Published: November 2023

AbstractThe efficient and accurate prediction of protein-ligand binding affinities is an extremely appealing yet still unresolved goal in computational pharmacy. In recent years, many scientists have taken advantage of the remarkable progress of deep learning and applied it to address this issue. Despite all the advances in this field, there is increasing evidence that the typically applied validation of these methods is not suitable for medicinal chemistry applications. This work assesses the importance of dataset quality and proper dataset splitting techniques demonstrated on the example of the PDBbind dataset. We also introduce a new tool for the analysis of protein-ligand complexes, called po-sco. Po-sco allows the extraction of interaction information with much higher detail and comprehensibility than the tools available to date. We trained a transformer-based deep learning model to generate protein-ligand interaction fingerprints that can be utilized for downstream predictions, such as binding affinity. When using po-sco, this model generated predictions that were superior to those based on commonly used PLIP and ProLIF tools. We also demonstrate that the quality of the dataset is more important than the number of data points and that suboptimal dataset splitting can lead to a significant overestimation of model performance.
“A Man Never Cries”: A Mixed-Methods Analysis of Gender Differences in Depression and Alcohol Use in Moshi, Tanzania
Authors: Pauley Alena , Buono Mia , Metcalf Madeline , West Kirstin , Rent Sharla , Nkenguye William , Sawe Yvonne , Mikindo Mariana , Kilasara Joseph , Boshe Judith , Knettel Brandon A. , Mmbaga Blandina T. , Staton Catherine A. 
Published: November 2023

AbstractBackgroundUnhealthy alcohol use negatively impacts many components of health and wellness, including mental health conditions like major depressive disorder (MDD). Globally, gender differences are common for both alcohol use behaviors and MDD, but these differences have not been studied within Moshi, Tanzania. To provide more effective and culturally appropriate mental health treatments, gender nuances around these conditions must be known. As such, this study aims to explore gender differences in MDD, alcohol use, and other aspects of mental well-being among patients at Kilimanjaro Christian Medical Center (KCMC) in Moshi.MethodsSix hundred and seventy-six patients presenting for care at the KCMC Emergency Department (ED) and Reproductive Health Centre (RHC) were enrolled in this mixed-methods study between October 2021 and May 2022. Patients were selected through systematic random sampling and completed quantitative surveys including the Alcohol Use Disorder Identification Test (AUDIT) and the Patient Health Questionnaire 9 (PHQ-9). Nineteen patients were purposively chosen from the study population to participate in in-depth interviews (IDIs) exploring topics related to alcohol use, gender, and depression. Descriptive frequencies, univariate log-binomial regressions, and a linear regression model were used to analyze quantitative data, all of which were analyzed in RStudio. A grounded theory approach was used to analyze all IDIs in NVivo.ResultsAverage [SD] PHQ-9 scores were 7.22 [5.07] for ED women, 4.91 [4.11] for RHC women, and 3.75 [4.38] among ED men. Similarly, ED women held the highest prevalence of MDD (25%) as compared to RHC women (11%) and ED men (7.9%) (p<0.001). Depressive symptoms were associated with higher AUDIT scores only for ED men (R2 = 0.11, p<0.001). Our qualitative analysis showed that while present for women, social support networks were notably absent for men in Moshi, the lack of which was seen to play a role in alcohol use. For men, alcohol was described as a coping mechanism for stress.ConclusionIntersectionality of gender, alcohol use, and depression is influenced by sociocultural and behavioral norms in Moshi. As such, multi-layered, gender-differentiated programming should be considered for the treatment of substance use and mental health conditions in this region.
Olfaction foraging in visually oriented tropical arboreal antsOecophylla smaragdina: Implications for insect predation studies using artificial sentinel prey
Authors: Yan Lin , Kagame Samuel Paul , Liu Yang , Mizuno Takafumi , Nakamura Akihiro 
Published: November 2023

AbstractPredation is the key to understanding trophic interactions. Because of the brief and cryptic nature of predatory behavior, sentinel prey has been widely adopted as an indirect way to identify predators and understand trophic interactions. However, sentinel prey presents only static visual cues, potentially biasing toward visually oriented predators whilst ignoring those that require other sensory cues to forage. Despite this, the effectiveness of sentinel prey has rarely been tested. Here, we focused on the weaver ant,Oecophylla smaragdina, a keystone predator widespread in the Asian and Australian tropics. As this species has large eyes and is known to visually navigate in their arboreal habitats, we hypothesized that they rely on visual cues to forage and that their predatory behavior will be captured by caterpillar-shaped sentinel prey. Ants were collected as colonies, and preference trials on baits were conducted using combinations of olfactory and static visual cues including the caterpillar shape. Surprisingly,O. smaragdinashowed little or no preference for baits in the absence of olfactory cues and did not differentiate the shapes of baits regardless of the presence of olfactory cues. Our results indicate thatO. smaragdinais likely to make predatory decisions based primarily on olfactory cues, while visual cues might be used for other behaviors. Furthermore,O. smaragdinais likely to be left out by the predation studies using sentinel prey models which is particularly alarming considering the dominant role of this species in the trophic interactions of tropical rainforests. Our study demonstrates that morphological characteristics, arboreal habitats, and visually oriented behavior do not necessarily suggest the use of static visual cues for predatory decisions. We suggest that sentinel prey models should not be used alone when the dominant predators are unlikely to use visual cues to make predatory decisions.
Simultaneous single-cell calcium imaging of neuronal population activity and brain-wide BOLD fMRI
Authors: Ubaghs Rik L.E.M. , Boehringer Roman , Marks Markus , Hesse Helke K. , Yanik Mehmet Fatih , Zerbi Valerio , Grewe Benjamin F. 
Published: November 2023

AbstractBlood Oxygen Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) allows for non-invasive, indirect recordings of neural activity across the whole brain in both humans and animals. However, the relationship between the local neural population activity and the vascular activity is not completely understood. To investigate this relationship, we present a novel MRI compatible single-photon microscope capable of measuring cellular resolution Ca2+activity of genetically defined neurons during whole-brain BOLD fMRI in awake behaving mice. Using this combined imaging approach, we found a difference in activity patterns between cells which was dependent on their location with respect to the vasculature. Notably, neurons near the vasculature showed pronounced negative activity during contralateral whisker movements at 3 Hz. In a second proof of concept experiment, we demonstrate the potential of recording both local neural activities, like those in the barrel field (SSp-bfd), and BOLD fMRI readings from interlinked brain regions. In sum, the presented technological advancement paves the way for studies examining the interplay between local brain circuits and overarching brain functions. In addition, the new approach enhances our understanding of the vascular BOLD fMRI signal, providing insights into the determinants of local neurovascular functions and the brain’s organizational framework across various scales.
Unravelling the metastasis-preventing effect of miR-200cin vitroandin vivo
Authors: Köhler Bianca , Brieger Emily , Brandstätter Tom , Hörterer Elisa , Wilk Ulrich , Pöhmerer Jana , Jötten Anna , Paulitschke Philipp , Broedersz Chase P , Zahler Stefan , Rädler Joachim O , Wagner Ernst , Roidl Andreas 
Published: November 2023

AbstractAdvanced breast cancer as well as insufficient treatment can lead to the dissemination of malignant cells from the primary tumor to distant organs. Recent research has shown that miR-200c can hamper certain steps of the invasion-metastasis cascade. However, it is still unclear, whether sole miR-200c expression is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR-200c expression in MDA-MB 231 cells. Theex vivoanalysis of metastatic sites in a multitude of organs including lung, liver, brain, and spleen has revealed a dramatically reduced metastatic burden of mice with miR-200c expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR-200c on collective and single cell migrationin vitro, utilizing MDA-MB 231 and MCF7 cell systems with genetically modified miR-200c expression. Analysis of collective cell migration has resulted in confluence dependent motility of cells with altered miR-200c expression. Additionally, scratch assays have shown enhanced predisposition of miR-200c negative cells to leave cell clusters. The in-between stage of collective and single cell migration was validated using transwell assays, which have displayed reduced migration of miR-200c positive cells. Finally, to measure migration on single cell level, a novel assay on dumbbell shaped micropatterns was performed, which revealed that miR-200c critically determines confined cell motility. All of these results demonstrate that exclusive expression of miR-200c impedes metastasis formationin vivoand migrationin vitroand highlight miR-200c as metastatic suppressor in breast cancer.
Dorsal Motor Vagal Neurons Can Elicit Bradycardia and Reduce Anxiety-Like Behavior
Authors: Strain Misty M. , Conley Nicholas J. , Kauffman Lily S. , Espinoza Liliana , Fedorchak Stephanie , Martinez Patricia Castro , Crook Maisie E. , Jalil Maira , Hodes Georgia E. , Abbott Stephen B. G. , Güler Ali D. , Campbell John N. , Boychuk Carie R. 
Published: November 2023

SummaryCardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVNNA) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVNDMV) is less clear. We therefore aimed to characterize CVNDMVanatomically, physiologically, and functionally. Optogenetically activating cholinergic DMV neurons resulted in robust bradycardia through peripheral muscarinic (parasympathetic) and nicotinic (ganglionic) acetylcholine receptors, but not beta-1-adrenergic (sympathetic) receptors. Retrograde tracing from the cardiac fat pad labeled CVNNAand CVNDMVthrough the vagus nerve. Using whole cell patch clamp, CVNDMVdemonstrated greater hyperexcitability and spontaneous action potential firingex vivodespite similar resting membrane potentials, compared to CVNNA. Chemogenetically activating DMV also caused significant bradycardia with a correlated reduction in anxiety-like behavior. Thus, DMV contains uniquely hyperexcitable CVNs capable of cardioinhibition and robust anxiolysis.
Gray matter volume in women with the BRCA mutation with and without ovarian removal
Authors: Witt Suzanne T , Brown Alana , Gravelsins Laura , Engström Maria , Classon Elisabet , Lykke Nina , Lundqvist Elisabeth Åvall , Theordorsson Elvar , Ernerudh Jan , Kjölhede Preben , Einstein Gillian 
Published: November 2023

ABSTRACTObjectiveOvarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer’s disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counselled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM and this is in women without the BRCAm showing cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and BSO noted changes in cognition.MethodsThe present study looked at whole-brain changes in gray matter volume using high-resolution, quantitative MRI in women with BRCAm and intact ovaries (BRCA-preBSO) and after surgery with (BSO+ERT) and without (BSO) post-surgical estradiol hormone replacement therapy compared with agematched women (AMC) with their ovaries.ResultsThe BRCA-preBSO and BSO groups showed significant gray matter loss in left medial temporal and frontal lobe structures. BSO+ERT exhibited few areas of gray matter reductions compared to AMC. Novel to this study, we also observed that all three BRCAm groups exhibited gray matter increases compared with AMC, suggesting continued plasticity.ConclusionsThe present study provides evidence, through gray matter volume reductions, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, post-surgical ERT seems to ameliorate gray matter losses.