bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of cutaneous sex steroid hormone production through analysis of skin secretions
Authors: Pineider Juliana , Eckert Kaitlyn , McDonald Jeffrey , Harris-Tryon Tamia 
Published: September 2021

ABSTRACTImportanceSystemic sex steroid hormone aberrations often manifest in skin disease. The sebaceous, apocrine, and eccrine glands all play an important role in the response and production of these hormones in the skin. However, our ability to quantify hormonal secretions at the skin surface is limited.ObjectiveOur study aims to characterize the hormonal landscape of the skin at different anatomical sites and between the sexes through analysis of skin secretions.DesignIn this observational pilot study, we collected skin secretions from twelve male and ten female control subjects using commercially available, Sebutape®, from the antecubital fossa, forehead, back, and axilla. We then developed a method to extract and quantify the amount of sex steroid hormones from these secretions through liquid chromatography tandem mass spectrometry (LC-MS/MS).SettingOutpatient clinicParticipants34 participants were enrolled in the study, with 22 participants meeting criteria. Eligibility criteria included age of 18 to 40 and BMI between 15-35. Exclusion criteria included participants outside the ages of 18 to 40, use of antibiotics in the last 6 months, history of hormonal aberrations or chronic skin disorders, and use of hormone altering medications (except oral contraception).ResultsOur study detected anatomical site differences most notably in elevated dehydroepiandrosterone in the axilla and androstenedione in the forehead. Several hormonal differences were also detected between male and females consistent with known systemic hormone differences between the sexes.ConclusionsWe developed a method to quantify the hormonal levels in skin secretions using Sebutape®. Our approach found that hormonal composition varies based on sex and anatomical site. Additional studies will need to be completed to determine relevant hormonal shifts in clinical skin conditions.KEY POINTSSex steroid hormones of skin secretions varies between males and femalesDehydroepiandrosterone is produced in elevated amounts in the axillaAndrostenedione is produced in elevated amounts in the forehead
Generation of realistic synthetic data using multimodal neural ordinary differential equations
Authors: Wendland Philipp , Birkenbihl Colin , Gomez-Freixa Marc , Sood Meemansa , Kschischo Maik , Fröhlich Holger 
Published: September 2021

AbstractIndividual organizations, such as hospitals, pharmaceutical companies and health insurance providers are currently limited in their ability to collect data that is fully representative of a disease population. This can in turn negatively impact the generalization ability of statistical models and scientific insights. However, sharing data across different organizations is highly restricted by legal regulations. While federated data access concepts exist, they are technically and organizationally difficult to realize. An alternative approach would be to exchange synthetic patient data instead. In this work, we introduce the Multimodal Neural Ordinary Differential Equations (MultiNODEs), a hybrid, multimodal AI approach, which allows for generating highly realistic synthetic patient trajectories on a continuous time scale, hence enabling smooth interpolation and extrapolation of clinical studies. Our proposed method can integrate both static and longitudinal data, and implicitly handles missing values. We demonstrate the capabilities of MultiNODEs by applying them to real patient-level data from two independent clinical studies and simulated epidemiological data of an infectious disease.
COVID-19 Vaccination Strategies Considering Hesitancy Using Particle-Based Epidemic Simulation
Authors: Karabay Aknur , Kuzdeuov Askat , Varol Huseyin Atakan 
Published: September 2021

AbstractVaccine hesitancy is one of the critical factors in achieving herd immunity and suppressing the COVID-19 epidemic. Many countries face this as an acute public health issue that diminishes the efficacy of their vaccination campaigns. Epidemic modeling and simulation can be used to predict the effects of different vaccination strategies. In this work, we present an open-source particle-based COVID-19 simulator with a vaccination module capable of taking into account the vaccine hesitancy of the population. To demonstrate the efficacy of the simulator, we conducted extensive simulations for the province of Lecco, Italy. The results indicate that the combination of both high vaccination rate and low hesitancy leads to faster epidemic suppression.
Compartment-specific tuning of hippocampal dendritic feature selectivity by intracellular Ca2+ release
Authors: O’Hare Justin K. , Hirabayashi Yusuke , Hewitt Victoria L. , Blockus Heike , Szoboszlay Miklos , Rolotti Sebi V. , Geiller Tristan C. , Negrean Adrian , Chelur Vikas , Losonczy Attila , Polleux Franck 
Published: September 2021

AbstractDendritic Ca2+ signaling is central to neural plasticity mechanisms allowing animals to adapt to the environment. Intracellular Ca2+ release (ICR) from endoplasmic reticulum has long been thought to shape these mechanisms. However, ICR has not been investigated in mammalian neurons in vivo. We combined electroporation of single CA1 pyramidal neurons, simultaneous imaging of dendritic and somatic activity during spatial navigation, optogenetic place field induction, and acute genetic augmentation of ICR cytosolic impact to reveal that ICR supports the establishment of dendritic feature selectivity and shapes integrative properties determining output-level receptive fields. This role for ICR was more prominent in apical than in basal dendrites. Thus, ICR cooperates with circuit-level architecture in vivo to promote the emergence of behaviorally-relevant plasticity in a compartment-specific manner.
OnePetri: accelerating common bacteriophage Petri dish assays with computer vision
Authors: Shamash Michael , Maurice Corinne F. 
Published: September 2021

AbstractIntroductionBacteriophage plaque enumeration is a critical step in a wide array of protocols. The current gold standard for plaque enumeration on Petri dishes is through manual counting. This approach is time-intensive, has low-throughput, is limited to Petri dishes which have a countable number of plaques, and can have variable results upon recount due to human error.MethodsWe present OnePetri, a collection of trained machine learning models and open-source mobile application for the rapid enumeration of bacteriophage plaques on circular Petri dishes.ResultsWhen compared against the current gold standard of manual counting, OnePetri was significantly faster, with minimal error. Compared against two other similar tools, Plaque Size Tool and CFU.AI, OnePetri had higher plaque recall and reduced detection times on most test images.ConclusionsThe OnePetri application can rapidly enumerate phage plaques on circular Petri dishes with high precision and recall.
Targeting interactions between the Galectin-3 intrinsically disordered and structured domains based on long time-scale accelerated molecular dynamics
Authors: Bhattacharya Supriyo , Zhang Mingfeng , Hu Weidong , Qi Tong , Heisterkamp Nora 
Published: September 2021

AbstractIntrinsically disordered regions (IDRs) are common and important functional domains in many proteins. However, IDRs are difficult to target for drug development due to the lack of defined structures which would facilitate the identification of possible drug-binding pockets. Galectin-3 is a carbohydrate-binding protein of which overexpression has been implicated in a wide variety of disorders including cancer and inflammation. Apart from its carbohydrate recognition/binding domain (CRD), Galectin-3 also contains a functionally important disordered N-terminal domain (NTD) that contacts the C-terminal domain (CTD) and could be a target for drug development. To overcome challenges involved in inhibitor design due to lack of structure and the highly dynamic nature of the NTD, we used a novel protocol combining nuclear magnetic resonance data from recombinant Galectin-3 with accelerated molecular dynamics (MD) simulations. This approach identified a pocket in the CTD with which the NTD makes frequent contact. In accordance with this model, mutation of residues L131 and L203 in this pocket caused loss of Galectin-3 agglutination ability, signifying the functional relevance of the cavity. In-silico screening was used to design candidate inhibitory peptides targeting the newly discovered cavity and experimental testing of only 3 of these yielded one peptide that inhibits the agglutination promoted by wild type Galectin-3. NMR experiments further confirmed that this peptide indeed binds to a cavity in the CTD not within the actual CRD. Our results show that it is possible to apply a combination of MD simulations and NMR experiments to precisely predict the binding interface of a disordered domain with a structured domain, and furthermore use this predicted interface for designing inhibitors. This procedure can be potentially extended to many other targets in which similar IDR interactions play a vital functional role.
Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making
Authors: Musall Simon , Sun Xiaonan R. , Mohan Hemanth , An Xu , Gluf Steven , Li Shujing , Drewes Rhonda , Cravo Emma , Lenzi Irene , Yin Chaoqun , Kampa Björn M. , Churchland Anne K. 
Published: September 2021

AbstractUnderstanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract (PT), intratelencephalic (IT) and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scale. Cortical activity and optogenetic inactivation during an auditory decision task also revealed distinct functional roles: all PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, PT neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice-tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.
Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes
Authors: Krzisch Marine A. , Wu Hao , Yuan Bingbing , Whitfield Troy W. , Shawn Liu X. , Fu Dongdong , Shih Jennifer , Garrett-Engele Carrie M. , Chang Aaron N. , Warren Stephen , Cacace Angela , Andrykovich Kristin R. , Rietjens Rosalie G. J. , Jain Bhav , Wallace Owen , Sur Mriganka , Jaenisch Rudolf 
Published: September 2021

AbstractAbnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.
Global Metabolome Analysis of Dunaliella tertiolecta, Phaeobacter italicus R11 Co-cultures using Thermal Desoprtion - Comprehensive Two-dimensional Gas Chromatography - Time-of-Flight Mass Spectrometry (TD-GC×GC-TOFMS)
Authors: Armstrong Michael D. Sorochan , Arredondo Campos René Oscar , Bannon Catherine C. , de la Mata A. Paulina , Case Rebecca J. , Harynuk James J. 
Published: September 2021

AbstractDunaliella tertiolecta is a marine microalgae that has been studied extensively as a potential carbon-neutral biofuel source [1]. Microalgae oil contains high quantities of energy-rich fatty acids and lipids, but is not yet commercially viable as an alternative fuel. Carefully optimised growth conditions, and more recently, algal-bacterial co-cultures have been explored as a way of improving the yield of Dunaliella tertiolecta microalgae oils. The relationship between the host microalgae and bacterial co-cultures is currently poorly understood. Here, a complete workflow is proposed to analyse the global metabolomic profile of co-cultured Dunaliella tertiolectra and Phaeobacter italicus R11, which will enable researchers to explore the chemical nature of this relationship in more detail.Graphical AbstractHighlightsA method for direct microalgae sample introduction is proposed.Advanced chemometric tools can extract, useful and discriminating metabolomic features even from very noisy complex datasets.
Role of type I interferon signaling and microglia in the abnormal long term potentiation and object place recognition deficits of male mice with a mutation of the Tuberous Sclerosis 2 gene
Authors: López-Aranda Manuel F. , Boxx Gayle M. , Phan Miranda , Bach Karen , Mandanas Rochelle , Herrera Isaiah , Taloma Sunrae , Thadani Chirag , Lu Odilia , Bui Raymond , Liu Shuhan , Li Nan , Zhou Yu , Cheng Genhong , Silva Alcino J. 
Published: September 2021

AbstractTuberous Sclerosis Complex (TSC) is a genetic disorder associated with high rates of intellectual disability and autism. Although previous studies focused on the role of neuronal deficits in the memory phenotypes of rodent models of TSC, the results presented here demonstrate a role for microglia in these deficits. Mice with a heterozygous null mutation of the Tsc2 gene (Tsc2+/-), show deficits in hippocampal dependent tasks, as well as abnormal long-term potentiation (LTP) in the hippocampal CA1 region. Here, we show that microglia and type I interferon signaling (IFN1) have a key role in the object place recognition (OPR; a hippocampal dependent task) deficits and abnormal LTP of Tsc2+/-male mice. Unexpectedly, we demonstrate that male, but not female, Tsc2+/-mice showed OPR deficits. Importantly, these deficits can be rescued by depletion of microglia, as well as by a genetic manipulation of a signaling pathway known to modulate microglia function (interferon-alpha/beta receptor alpha chain null mutation). In addition to rescuing the OPR deficits, depletion of microglia also reversed the abnormal LTP of the Tsc2+/-mice. Altogether, our results suggest that altered IFN1 signaling in microglia cause the abnormal LTP and OPR deficits of male Tsc2+/-mice.
Spatiotemporal co-dependency between macrophages and exhausted CD8+T cells in cancer
Authors: Kersten Kelly , Hu Kenneth H. , Combes Alexis J. , Samad Bushra , Harwin Tory , Ray Arja , Rao Arjun Arkal , Cai En , Marchuk Kyle , Artichoker Jordan , Courau Tristan , Shi Quanming , Belk Julia , Satpathy Ansuman T. , Krummel Matthew F. 
Published: September 2021

SummaryT cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here we show that the biology of tumor-associated macrophages (TAM) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate thatin vivodepletion of TAM reduces exhaustion programs in tumor-infiltrating CD8+T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that Texexpress factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8+T cells engage in unique long-lasting antigen-specific synaptic interactions that fail to activate T cells, but prime them for exhaustion, which is then accelerated in hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcing positive feedback circuit that is aligned to protect rather than destroy a tumor.Graphical Abstract
Interactions of cytosolic termini of the Jen1 monocarboxylate transporter are critical for trafficking, transport activity and endocytosis
Authors: Barata-Antunes Cláudia , Talaia Gabriel , Broutzakis George , Ribas David , De Beule Pieter , Casal Margarida , Stefan Christopher J. , Diallinas George , Paiva Sandra 
Published: September 2021

AbstractPlasma membrane (PM) transporters of the major facilitator superfamily (MFS) are essential for cell metabolism and growth, as well as for survival in response to stress or cytotoxic drugs, in both prokaryotes and eukaryotes. In the yeast Saccharomyces cerevisiae, Jen1 is a monocarboxylate/H+ symporter that has been used to dissect the molecular details underlying control of cellular expression, transport mechanism and turnover of MFS transporters. Here, we present evidence supporting previously non-described roles of the cytosolic N- and C- termini in Jen1 biogenesis, PM stability and activity, through functional analyses of rationally designed truncations and chimeric constructs with UapA, a S. cerevisiae endocytosis-insensitive purine transporter from Aspergillus nidulans. Our results reveal a cryptic role of the N-terminal region and thus show that both cytosolic N- and C-termini are critical for Jen1 trafficking to the PM, transport activity and endocytosis. In particular, we provide evidence that the N- and the C-cytosolic termini of Jen1 undergo transport-dependent dynamic intra-molecular interactions, which critically affect the mechanism of transport and turnover of Jen1. Our results support an emerging concept where the cytosolic tails of PM transporters control transporter expression and function, through flexible intra-molecular interactions with each other and the transmembrane core of the protein. This idea may be extended to other MFS members providing a deeper understanding of conserved, but also evolving, mechanisms underlying MFS transporter structure-function relationships.
Community assessment of crustose calcifying red algae as coral recruitment substrates
Authors: Deinhart Mari E. , Mills Matthew S. , Schils Tom 
Published: September 2021

AbstractSuccessful recruitment of invertebrate larvae to reef substrates is essential to the health of tropical coral reef ecosystems and their capacity to recover from disturbances. Crustose calcifying red algae (CCRA) have been identified as important recruitment substrates for scleractinian corals. As such, CCRA as a whole or subgroups (e.g., crustose coralline algae, CCA) are often used at the functional group level in experimental, ecological, and monitoring studies. Species of CCRA, however, differ in their ecological roles and their value as coral recruitment substrates. Here, we (1) investigate the species richness and community composition of CCRA on experimental coral recruitment tiles, and (2) assess if there is a recruitment preference of the coralAcropora surculosafor any of these CCRA species. 27 species of two orders of CCRA (Corallinales and Peyssonneliales) were identified from the recruit tiles. None of the DNA sequences of these species matched released sequences in GenBank or sequences of CCRA collected from natural reef systems in Guam. The similarity in CCRA communities between the recruitment tiles was high. Two species of CCRA were significantly preferred as recruitment substrates over the other CCRA species. Both of these species belonged to the subfamily of the Lithophylloideae. These two species are closely related to Pacific species that have been referred to asTitanoderma-but probably have to be assigned to another genus- and many of the latter have been attributed to be preferred coral recruitment substrates. Of all CCRA, Lithophylloideae sp. 1 had the highest benthic cover on the recruitment tiles and was the most preferred recruitment substrate. These findings highlight the high taxonomic diversity of CCRA communities and provide insight into species-specific ecological roles of CCRA that are often overlooked.
HSD11β1 promotes EMT-mediated breast cancer metastasis
Authors: Nakayama Joji , Ishikawa Takamasa , Nishimura Tatsunori , Yamanaka Sanae , Gotoh Noriko , Yamauchi Chisako , Ohnishi Tatsuya , Soga Tomoyoshi , Fujii Satoshi , Makinoshima Hideki 
Published: September 2021

AbstractAbnormal biosyntheses of steroid hormones and dysregulation of steroid hormone receptors contribute to breast cancer metastasis but the mechanisms of that are poorly understand. Here we report a stress hormone producing enzyme, Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11β1) promotes breast cancer metastasis. HSD11β1 was ectopically expressed in seventy-one percent of triple-negative breast tumors and correlated with shorter overall survival. HSD11β1 significantly promoted breast cancer metastasis through induction of epithelial-to-mesenchymal transition (EMT); conversely, pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic progression of breast cancer cells. Moreover, 11-hydroxyprogesterone (11-OHP) whom HSD11β1 produced in breast cancer cells, conferred metastatic properties on non-metastatic breast cancer cells through induction of EMT. We identified Peroxisome Proliferator-activated Receptor Alpha (PPAR-α) as essential for both HSD11β1 and 11OHP-driven EMT. Knockdown of PPAR-α induced MET on HSD11β1-expressing breast cancer cells. Taken together, HSD11β1 promotes breast cancer metastasis and would be a novel target for suppressing breast cancer metastasis.