bluuebunny/crossref_metadata_2025_split huggingface dataset:
MLDAAPP: Machine Learning Data Acquisition for Assessing Population Phenotypes
Authors: Gabidulin Amir R. , Rudman Seth M. 
Published: September 2023

AbstractCollecting phenotypic data from many individuals is critical to numerous biological disciplines. Yet, organismal phenotypic or trait data are still often collected manually, limiting the scale of data collection, precluding reproducible workflows, and creating the potential for human bias. Computer vision could largely ameliorate these issues, but currently available packages only operate with specific inputs and hence are not scalable or accessible for many biologists. We present Machine Learning Data Acquisition for Assessing Population Phenotypes (MLDAAPP), a package of tools for collecting phenotypic data from groups of individuals. We demonstrate that MLDAAPP is both accurate and uniquely effective at measuring phenotypes in challenging conditions - particularly images and videos of varying quality derived from both lab and field environments. Employing MLDAAPP solves key issues of reproducibility, increases both the scale and scope of data generation, and reduces the potential for human bias.
Division of labor among H3K4 Methyltransferases Defines Distinct Facets of Homeostatic Plasticity
Authors: Tsukahara Takao , Kethireddy Saini , Bonefas Katherine , Chen Alex , Sutton Brendan LM , Dou Yali , Iwase Shigeki , Sutton Michael A. 
Published: September 2023

AbstractHeterozygous mutations in any of the six H3K4 methyltransferases (KMT2s) result in monogenic neurodevelopmental disorders, indicating nonredundant yet poorly understood roles of this enzyme family in neurodevelopment. Recent evidence suggests that histone methyltransferase activity may not be central to KMT2 functions; however, the enzymatic activity is evolutionarily conserved, implicating the presence of selective pressure to maintain the catalytic activity. Here, we show that H3K4 methylation is dynamically regulated during prolonged alteration of neuronal activity. The perturbation of H3K4me by the H3.3K4M mutant blocks synaptic scaling, a form of homeostatic plasticity that buffers the impact of prolonged reductions or increases in network activity. Unexpectedly, we found that the six individual enzymes are all necessary for synaptic scaling and that the roles of KMT2 enzymes segregate into evolutionary-defined subfamilies: KMT2A and KMT2B (fly-Trx homologs) for synaptic downscaling, KMT2C and KMT2D (Trr homologs) for upscaling, and KMT2F and KMT2G (dSet homologs) for both directions. Selective blocking of KMT2A enzymatic activity by a small molecule and targeted disruption of the enzymatic domain both blocked the synaptic downscaling and interfered with the activity-dependent transcriptional program. Furthermore, our study revealed specific phases of synaptic downscaling, i.e., induction and maintenance, in which KMT2A and KMT2B play distinct roles. These results suggest that mammalian brains have co-opted intricate H3K4me installation to achieve stability of the expanding neuronal circuits.
Contraceptive congruence: acknowledging pregnancy ambivalence in a novel measure of contraceptive use
Authors: Nelson Hallie N. , Lehman Erik , Horvath Sarah , Chuang Cynthia H. 
Published: September 2023

AbstractBackgroundThe historical view that pregnancy intention is dichotomous (i.e., intending or not intending pregnancy), and the notion that all individuals not intending pregnancy should be using highly effective contraceptive methods, oversimplifies how we view contraceptive decision-making. To better understand this, we studied contraceptive congruence as an alternative, 3-level measure describing methods as very congruent, somewhat congruent, or incongruent with one’s individual attitudes about becoming pregnant.MethodsSecondary data analysis included 982 MyNewOptions study participants who were not intending pregnancy within the next year. The cross-sectional survey assessed attitudes about how important it is to avoid pregnancy, how pleased/upset one would be if pregnant, and current contraceptive method use. Participant answers to attitudinal questions and effectiveness of current contraceptive method were used to determine congruence categories.ResultsContraceptive methods included LARC (8%), other prescription methods (50%), non-prescription methods (30%), and no method (12%). Methods for 23% of participants were very congruent, 48% somewhat congruent, and 29% incongruent with attitudes about becoming pregnant. Contraceptive congruence was significantly associated with contraceptive satisfaction in bivariate analysis. Predictors of contraceptive congruence included being married or living with partner, full-time employment, and intending future pregnancy in the next 1-5 years.ConclusionContraceptive congruence is a novel measure that acknowledges pregnancy ambivalence and is associated with higher contraceptive satisfaction scores. Future contraception research should strive for robust, patient-centered measures of contraceptive use that acknowledge the complex attitudes affecting individual contraceptive behavior and satisfaction.
A Wearable Fiber-Free Optical Sensor for Continuous Monitoring of Neonatal Cerebral Blood Flow and Oxygenation
Authors: Liu Xuhui , Mohtasebi Mehrana , Safavi Pegah , Fathi Faraneh , Haratbar Samaneh Rabienia , Chen Li , Chen Jin , Bada Henrietta S. , Chen Lei , Abu Jawdeh Elie G. , Yu Guoqiang 
Published: September 2023

AbstractImpactThe innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units.Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results.No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events.Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.BackgroundUnstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants.MethodsDSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events.ResultsConsistent results between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters.ConclusionsThis pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations.
Impaired bone morphogenetic protein signaling pathways disrupt decidualization in endometriosis
Authors: Liao Zian , Tang Suni , Jiang Peixin , Geng Ting , Cope Dominique I. , Dunn Timothy N. , Guner Joie , Alpuing Radilla Linda , Guan Xiaoming , Monsivais Diana 
Published: September 2023

ABSTRACTIt is hypothesized that impaired endometrial decidualization contributes to decreased fertility in individuals with endometriosis. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from individuals with or without endometriosis to time coursein vitrodecidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified differences in key pathways between the two groups, including defective bone morphogenetic protein (BMP)/SMAD4 signaling (ID2, ID3, FST), oxidate stress response (NFE2L2, ALOX15, SLC40A1), and retinoic acid signaling pathways (RARRES, RARB, ALDH1B1). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 and H3K27Ac in the decidualized stromal cells from individuals without endometriosis relative to those with endometriosis, with target genes enriched in pathways related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation in endometriosis patient-derived assembloids elevated the expression of decidualization markers. In summary, transcriptomic and genome-wide binding analyses of patient-derived endometrial cells and assembloids identified that a functional BMP/SMAD1/5/4 signaling program is crucial for engaging decidualization.
Germline-targeting chimpanzee SIV Envelopes induce V2-apex broadly neutralizing-like B cell precursors in a rhesus macaque infection model
Authors: Musharrafieh Rami , Safonova Yana , Song Ge , Roark Ryan S. , Lee Fang-Hua , Zhang Shiyu , Hurtado Jonathan , Yong Peter , Wang Shuyi , Russell Ronnie M. , Ding Wenge , Li Yingying , Rando Juliette , Murphy Alexander I. , Lindemuth Emily , Zhao Chengyan , Connell Andrew Jesse , Lee Wen-Hsin , Mishra Nitesh , Avillion Gabriel , He Wanting , Callaghan Sean , Dueker Katharina , Vo Anh L. , Li Xuduo , Capozzola Tazio , Joyce Collin , Zhao Fangzhu , Anzanello Fabio , Liu Weimin , Bibollet-Ruche Frederic , Ramos Alejandra , Li Hui , Lewis Mark G. , Ozorowski Gabriel , Landais Elise , Foley Brian T. , Wagh Kshitij , Sok Devin , Briney Bryan , Ward Andrew B. , Hahn Beatrice H. , Burton Dennis R. , Shaw George M. , Andrabi Raiees 
Published: September 2023

SUMMARYEliciting broadly neutralizing antibodies-(bnAbs) remains a major goal of HIV-1 vaccine research. Previously, we showed that a soluble chimpanzee SIV Envelope-(Env) trimer, MT145K, bound several human V2-apex bnAb-precursors and stimulated an appropriate response in V2-apex bnAb precursor-expressing knock-in mice. Here, we tested the immunogenicity of three MT145 variants (MT145, MT145K, MT145K.dV5) expressed as chimeric simian-chimpanzee-immunodeficiency-viruses-(SCIVs) in rhesus macaques-(RMs). All three viruses established productive infections with high setpoint vRNA titers. RMs infected with the germline-targeting SCIV_MT145K and SCIV_MT145K.dV5 exhibited larger and more clonally expanded B cell lineages featuring long anionic heavy chain complementary-determining-regions-(HCDR3s) compared with wildtype SCIV_MT145. Moreover, antigen-specific B cell analysis revealed enrichment for long-CDHR3-bearing antibodies in SCIV_MT145K.dV5 infected animals with paratope features resembling prototypic V2-apex bnAbs and their precursors. Although none of the animals developed bnAbs, these results show that germline-targeting SCIVs can activate and preferentially expand B cells expressing V2-apex bnAb-like precursors, the first step in bnAb elicitation.Graphical Abstract
The effect of common paralytic agents used for fluorescence imaging on redox tone and ATP levels inCaenorhabditis elegans
Authors: Morton Katherine S , Wahl Ashlyn K , Meyer Joel N 
Published: September 2023

AbstractOne aspect ofCaenorhabditis elegansthat makes it a highly valuable model organism is the ease of use ofin vivogenetic reporters, facilitated by its transparent cuticle and highly tractable genetics. Despite the rapid advancement of these technologies, worms must be paralyzed for most imaging applications, and few investigations have characterized the impacts of common chemical anesthetic methods on the parameters measured, in particular biochemical measurements such as cellular energetics and redox tone. Using two dynamic reporters, QUEEN-2m for relative ATP levels and reduction-oxidation sensitive GFP (roGFP) for redox tone, we assess the impact of commonly used chemical paralytics. We report that no chemical anesthetic is entirely effective at doses required for full paralysis without altering redox tone or ATP levels, though 100 mM 2,3-Butadione monoxime appears to be the least problematic. We also assess the use of cold shock, commonly used in combination with physical restraint methods, and find that cold shock does not alter either ATP levels or redox tone. In addition to informing which paralytics are most appropriate for research in these topics, we highlight the need for tailoring the use of anesthetics to different endpoints and experimental questions. Further, we reinforce the need for developing less disruptive paralytic methods for optimal imaging of dynamicin vivoreporters.
The influence of birthweight, socioeconomic status, and adult health on brain volumes during aging
Authors: McNeil Christopher J , Habota Tina , Sandu Anca-Larisa , Waiter Gordon , Whalley Heather , Murray Alison D. 
Published: September 2023

AbstractPreserved late-life brain volume is associated with resilience to dementia. We examined relationships between birthweight, socioeconomic status and adult health with late-life brain volumes. We hypothesised that early-life factors have direct and indirect effects on the aging brain. Neurotypical adults aged 61-67y underwent MRI and brain volumes measured. Birthweight, health and socioeconomic status were assessed by historical data or contemporary assessment. Measures of health and socioeconomic status were extracted using principal component analysis. Relationships between variables were explored by linear regression and structural equation models. Birthweight (β=0.095, p=0.017, n=280) and childhood socioeconomic status (β=0.091, p=0.033, n=280) were directly associated with late-life brain volume. Childhood socioeconomic status was associated with additional increase in grey matter volume (β=0.04, p=0.047, n=280). Better adult health was linked to increased late-life brain volume (β=0.15, p=0.003, n=280). Birthweight and childhood socioeconomic status are associated with whole and regional brain volume through direct and indirect mechanisms. Optimal fetal development, good adult health and reduced poverty, may prevent brain atrophy and decrease dementia risk in late-life.
Gcm alleviates the inflammatory phenotype induced by Toll activation inDrosophilahemocytes
Authors: Bazzi Wael , Monticelli Sara , Delaporte Claude , Riet Céline , Giangrande Angela , Cattenoz Pierre B. 
Published: September 2023

AbstractHemocytes, the myeloid-like immune cells ofDrosophila, fulfil a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glide/Gcm transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S transferase, suggesting an implication of Glide/Gcm in ROS signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. We show the expression of neurotransmitter receptors in hemocytes and that Toll activation affects their expressions, disclosing a novel aspect of the inflammatory response mediated by neurotransmitters. Finally, we provide evidence for acetylcholine receptor nAchRalpha6 regulating hemocyte proliferation. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response.
Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection
Authors: Ngo Vu L. , Lieber Carolin M. , Kang Hae-ji , Sakamoto Kaori , Kuczma Michal , Plemper Richard K. , Gewirtz Andrew T. 
Published: September 2023

AbstractSusceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and SARS-CoV-2, was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AM). In SFB-negative mice, AM were quickly depleted as RVI progressed. In contrast, AM from SFB-colonized mice were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AM from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Accordingly, transfer of SFB-transformed AM into SFB-free hosts recapitulated SFB-mediated protection against IAV. These findings uncover complex interactions that mechanistically link the intestinal microbiota with AM functionality and RVI severity.One sentence summaryIntestinal segmented filamentous bacteria reprogram alveolar macrophages promoting nonphlogistic defense against respiratory viruses.
Phenotypic divergence and genomic architecture between parallel ecotypes at two different points on the speciation continuum in a marine snail
Authors: Raffini Francesca , De Jode Aurélien , Johannesson Kerstin , Faria Rui , Zagrodzka Zuzanna B. , Westram Anja M. , Galindo Juan , Rolán-Alvarez Emilio , Butlin Roger K. 
Published: September 2023

AbstractSpeciation typically occurs over too long a time frame to be observed directly. A way forward is to compare pairs of ecotypes that evolved in parallel in similar contexts but have reached different degrees of reproductive isolation. Such comparisons are possible in the marine snailLittorina saxatilisby contrasting barriers to gene flow between parallel ecotypes in Spain and Sweden. In both countries, divergent ecotypes have evolved to withstand either crab predation or wave action. Here, we explore transects spanning contact zones between the Crab and the Wave ecotypes using low-coverage whole-genome sequencing, morphological and behavioural traits. Despite parallel phenotypic divergence, distinct patterns of differentiation between the ecotypes emerged: a continuous cline in Sweden indicating a weak barrier to gene flow, but two highly genetically and phenotypically divergent, and partly spatially-overlapping clusters in Spain suggesting a much stronger barrier to gene flow. Absence of Spanish early-generation hybrids supported strong isolation, but a low level of gene flow is evident from molecular data. In both countries, highly differentiated loci were located in both shared and private chromosomal inversions but were also present in collinear regions. Despite being considered the same species and showing similar levels of phenotypic divergence, the Spanish ecotypes are much closer to full reproductive isolation than the Swedish ones. Barriers to gene flow of very different strengths between ecotypes within the same species might be explained by dissimilarities in the spatial arrangement of habitats, the selection gradients or the ages of the systems.Abstract FigureGraphical abstract.Distinct patterns of divergence between parallel ecotypes in Sweden and Spain.
Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain
Authors: Botvinik-Nezer Rotem , Petre Bogdan , Ceko Marta , Lindquist Martin A. , Friedman Naomi P. , Wager Tor D. 
Published: September 2023

AbstractPlacebo analgesia is a replicable and well-studied phenomenon, yet it remains unclear to what degree it includes modulation of nociceptive processes. Some studies find effects consistent with nociceptive effects, but meta-analyses show that these effects are often small. We analyzed placebo analgesia in a large fMRI study (N = 392), including placebo effects on brain responses to noxious stimuli. Placebo treatment caused robust analgesia in both conditioned thermal and unconditioned mechanical pain. Placebo did not decrease fMRI activity in nociceptive pain regions, including the Neurologic Pain Signature (NPS) and pre-registered spinothalamic pathway regions, with strong support from Bayes Factor analyses. However, placebo treatment affected activity in pre-registered analyses of a second neuromarker, the Stimulus Intensity Independent Pain Signature (SIIPS), and several associated a priori brain regions related to motivation and value, in both thermal and mechanical pain. Individual differences in behavioral analgesia were correlated with neural changes in both thermal and mechanical pain. Our results indicate that processes related to affective and cognitive aspects of pain primarily drive placebo analgesia.
Periodic and aperiodic changes to cortical EEG in response to pharmacological manipulation
Authors: Salvatore Sofia V. , Lambert Peter M. , Benz Ann , Rensing Nicholas R. , Wong Michael , Zorumski Charles F. , Mennerick Steven 
Published: September 2023

AbstractCortical electroencephalograms (EEG) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/f) of EEG power spectra is often treated as noise, but recent studies suggest that changes to the aperiodic exponent of power spectra may reflect changes in excitation/inhibition (E/I) balance, a concept linked to antidepressant effects, epilepsy, autism, and other clinical conditions. One confound of previous studies is behavioral state, because factors associated with behavioral state other than E/I ratio may alter EEG parameters. Thus, to test the robustness of the aperiodic exponent as a predictor of E/I ratio, we analyzed active exploration in mice using video EEG following various pharmacological manipulations with the Fitting Oscillations & One Over F (FOOOF) algorithm. We found that GABAAreceptor (GABAAR) positive allosteric modulators increased the aperiodic exponent, consistent with the hypothesis that an increased exponent signals enhanced cortical inhibition, but other drugs (ketamine and GABAAR antagonists at sub-convulsive doses) did not follow the prediction. To tilt E/I ratio more selectively toward excitation, we suppressed the activity of parvalbumin (PV) interneurons with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Contrary to our expectations and studies demonstrating increased cortical activity following PV suppression, circuit disinhibition with the DREADD increased the aperiodic exponent. We conclude that the aperiodic exponent of EEG power spectra does not yield a universally reliable marker of E/I ratio. Alternatively, the concept of E/I state may be sufficiently oversimplified that it cannot be mapped readily onto an EEG parameter.Significance StateBmentNeuropsychiatric illness is widely prevalent and debilitating. Causes are not well understood, but some hypotheses point toward altered excitation/inhibition (E/I) balance. Here, we use cortical electroencephalograms (EEG) in mice, given applicability of cortical EEG across species, and evaluate the impact of validated drugs, including anxiolytics (pentobarbital and diazepam), along with novel rapid-acting antidepressants (ketamine and allopregnanolone). We focus on analyzing the aperiodic component of EEG power spectra, which may be associated with changes in E/I ratio. We show that aperiodic exponent of EEG power spectra is not a reliable marker of E/I ratio. Moreover, the concept of E/I ratio may be too broad and complex to be defined by an EEG parameter.