bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sclerostin influences exercise-induced adaptations in body composition and white adipose tissue morphology in male mice
Authors: Kurgan N , Stoikos J , Baranowski BJ , Yumol J , Dhaliwal R , Sweezey-Munroe JB , Fajardo VA , Gittings W , MacPherson REK , Klentrou P 
Published: July 2022

AbstractSclerostin is an inhibitor of the osteogenic Wnt/β-catenin signalling pathway that has an endocrine role in regulating adipocyte differentiation and metabolism. Additionally, subcutaneous white adipose tissue (scWAT) sclerostin content decreases following exercise training (EXT). Therefore, we hypothesized that EXT-induced reductions in adipose tissue sclerostin may play a role in regulating adaptations in body composition and whole-body metabolism. To test this hypothesis, 10-week-old male C57BL/6J mice were either sedentary (SED) or performing 1h of treadmill running at ∼65-70% VO2max 5 d/week (EXT) for 4 weeks and had subcutaneous (s.c) injections of either saline (C) or recombinant sclerostin (S) (0.1 mg/kg body mass) 5 d/week; thus, making 4 groups (SED-C, EXT-C, SED-S, and EXT-S; n=12/group). No differences in body mass were observed between experimental groups, while food intake was higher in EXT (p=0.03) and S (p=0.08) groups. There was a higher resting energy expenditure in all groups compared to SED-C. EXT-C had a higher lean mass and lower fat mass percentage compared to SED-C and SED-S. No differences in body composition were observed in either the SED-S or EXT-S groups. Lower scWAT (inguinal), vWAT (epididymal) mass, and scWAT adipocyte cell size and increased percentage of multilocular cells in scWAT were observed in the EXT-C group compared to SED-C, while lower vWAT was only observed in the EXT-S group. EXT mice had increased iWAT Lrp4 and mitochondrial content and sclerostin treatment only inhibited increased Lrp4 content with EXT. Together, these results provide evidence that reductions in resting sclerostin with exercise training may influence associated alterations in energy metabolism and body composition, particularly in scWAT.
CanSeer: A Method for Development and Clinical Translation of Personalized Cancer Therapeutics
Authors: Butt Rida Nasir , Amina Bibi , Sultan Muhammad Umer , Tanveer Zain Bin , Hussain Risham , Akbar Rida , Khan Salaar , Gondal Mahnoor Naseer , Khalid Muhammad Farhan , Faisal Amir , Shoaib Muhammad , Chaudhary Safee Ullah 
Published: July 2022

ABSTRACTComputational modeling and analysis of biomolecular network models annotated with cancer patient-specific multi-omics data can enable the development of personalized therapies. Current endeavors aimed at employingin silicomodels towards personalized cancer therapeutics remain to be fully translated. In this work, we present “CanSeer” a novel multi-stage methodology for developingin silicomodels towards clinical translation of personalized cancer therapeutics. The proposed methodology integrates state-of-the-art dynamical analysis of biomolecular network models with patient-specific genomic and transcriptomic data to assess the individualized therapeutic responses to targeted drugs and their combinations.CanSeer’stranslational approach employs transcriptomic data (RNA-seq based gene expressions) with genomic profile (CNVs, SMs, and SVs). Specifically, patient-specific cancer driver genes are identified, followed by the selection of druggable and/or clinically actionable targets for therapeutic interventions. To exemplifyCanSeer, we have designed three case studies including (i) lung squamous cell carcinoma, (ii) breast invasive carcinoma, and (iii) ovarian serous cystadenocarcinoma. The case study on lung squamous cell carcinoma concluded that restoration of Tp53 activity together with an inhibition of EGFR as an efficacious combinatorial treatment for patients with Tp53 and EGFR cancer driver genes. The findings from the cancer case study helped identify personalized treatments including APR-246, APR-246+palbociclib, APR-246+osimertinib, APR-246+afatinib, APR-246+osimertinib+dinaciclib, and APR-246+afatinib+dinaciclib. The second case study on breast invasive carcinoma revealedCanSeer’s potential to elucidate drug resistance against targeted drugs and their combinations including KU-55933, afuresertib, ipatasertib, and KU-55933+afuresertib. Lastly, the ovarian cancer case study revealed the combinatorial efficacy of APR-246+carmustine, and APR-246+dinaciclib for treating ovarian serous cystadenocarcinoma. Taken together,CanSeeroutlines a novel method for systematic identification of optimal tailored treatments with mechanistic insights into patient-to-patient variability of therapeutic response, drug resistance mechanism, and cytotoxicity profiling towards personalized medicine.
Decision-making processes in perceptual learning depend on effectors
Authors: Ivanov Vladyslav , Manenti Giorgio L. , Plewe Sandrin S. , Kagan Igor , Schwiedrzik Caspar M. 
Published: July 2022

AbstractVisual perceptual learning is traditionally thought to arise in visual cortex. However, typical perceptual learning tasks also involve systematic mapping of visual information onto motor actions. Because the motor system contains both effector-specific and effector-unspecific representations, the question arises whether visual perceptual learning is effector-specific itself, or not. Here, we study this question in an orientation discrimination task. Subjects learn to indicate their choices either with joystick movements or with manual reaches. After training, we challenge them to perform the same task with eye movements. We dissect the decision-making process using the drift diffusion model. We find that learning effects on the rate of evidence accumulation depend on effectors, albeit not fully. This suggests that during perceptual learning, visual information is mapped onto effector-specific integrators. Overlap of the populations of neurons encoding motor plans for these effectors may explain partial generalization. Taken together, visual perceptual learning is not limited to visual cortex, but also affects sensorimotor mapping at the interface of visual processing and decision making.
Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome
Authors: Liu Shirelle X. , Fredrickson Tenille K. , Mancipe Natalia Calixto , Georgieff Michael K. , Tran Phu V. 
Published: July 2022

ABSTRACTBackgroundFetal-neonatal iron deficiency (ID) causes long-term neurocognitive and affective dysfunctions. Clinical and preclinical studies have shown that early-life ID produces sex-specific effects. However, little is known about the molecular mechanisms underlying these early-life ID-induced sex-specific effects on neural gene regulation.ObjectiveTo illustrate sex-specific transcriptome alteration in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment.MethodsPregnant rats were fed an iron-deficient (4 mg/kg Fe) or iron-sufficient (200 mg/kg Fe) diet from gestational day (G) 2 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline) from G11-18. Hippocampi were collected from P65 offspring of both sexes and analyzed for changes in gene expression.ResultsBoth early-life ID and choline treatment induced transcriptional changes in adult female and male rat hippocampus. Both sexes showed ID-induced alterations in gene networks leading to enhanced neuroinflammation. In females, ID-induced changes indicating enhanced activity of oxidative phosphorylation and fatty acid metabolism, which are contrary to the ID effect in males. Prenatal choline supplementation induced the most robust changes in gene expression, particularly in the iron-deficient animals where it partially rescued ID-induced dysregulations. Choline supplementation also altered hippocampal transcriptome in the iron-sufficient rats with indications for both beneficial and adverse effects.ConclusionsThis study provided unbiased global assessments of gene expression regulated by iron and choline status in a sex-specific manner, with greater effects in female than male rats. Our new findings highlight potential sex-specific gene networks regulated by iron and choline status for further investigation.
Terminal flourishes but not trills differ between urban and rural chaffinch song
Authors: Yelimlieş Alper , Atalas Berkay , Önsal Çağla , Akçay Çağlar 
Published: July 2022

AbstractAnthropogenic noise interrupts the acoustic communication between animals living in urban habitats. Accumulating evidence suggests that animals can evade this interruption using various strategies such as shifting frequencies upwards or increasing the duration of their signals. In this study, we compared the time and frequency-related characteristics of songs and rain calls of common chaffinches (Fringilla coelebs) inhabiting rural forests and an urban park in Turkey. Most of the song phrases and rain calls did not differ in any of the characteristics measured between urban and rural chaffinches. Terminal flourish phrases of the songs, however, had lower minimum frequencies and broader bandwidth in urban territories, contrary to our predictions. We discuss this finding in relation to its potential adaptive significance.
Cell type- and state- resolved immune transcriptomic profiling identifies glucocorticoid-responsive molecular defects in multiple sclerosis T cells
Authors: Roostaei Tina , Sabrin Afsana , Kivisäkk Pia , McCabe Cristin , Nejad Parham , Felsky Daniel , Touil Hanane , Vlachos Ioannis S. , Hui Daniel , Fransson Jennifer , Patsopoulos Nikolaos A. , Kuchroo Vijay K. , Zujovic Violetta , Weiner Howard L. , Klein Hans-Ulrich , De Jager Philip L. 
Published: July 2022

AbstractThe polygenic and multi-cellular nature of multiple sclerosis (MS) immunopathology necessitates cell-type-specific molecular studies in order to improve our understanding of the diverse mechanisms underlying immune cell dysfunction in MS. Here, by generating a dataset of 1,075 transcriptomes from 209 participants (167 MS and 42 healthy), we assessed MS-associated transcriptional changes in six implicated cell-type-states: naïve and memory helper T cells and classical monocytes purified from peripheral blood, each in their primary (ex vivo, unstimulated) andin vitrostimulated states. Our data suggest that primary profiles show larger MS-associated differences than the post-stimulation contexts. We further identified shared and distinct changes in individual genes, biological pathways, and co-expressed gene modules in MS T cells and monocytes, and prioritized genes such asZBTB16as MS-associated regulators in both cell types. Of six identified MS-associated co-expressed gene modules, three (two lymphoid and one myeloid) were replicated in independent data from peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages. A subsequentin silicodrug screen prioritized small-molecule compounds for reversing the perturbation of the MS-associated modules. The effects of glucocorticoid receptor agonists as the top-identified therapeutic class for the replicated T cell modules were validated using targetedin silicoanalyses andin vitroexperiments, suggesting the coordinated dysregulation of glucocorticoid-responsive genes in MS T cells. In summary, our study identifies and validates individual genes and co-expressed gene modules from T and myeloid cells that are perturbed in MS, offering new targets for therapeutic discovery and biomarker development to guide the management of MS.
A brain-wide form of presynaptic active zone plasticity orchestrates resilience to brain aging in Drosophila
Authors: Huang Sheng , Piao Chengji , Beuschel Christine B. , Sigrist Stephan J. 
Published: July 2022

SUMMARYThe brain as a central regulator of stress integration determines what is threatening, stores memories and regulates physiological adaptations across the aging trajectory. While sleep homeostasis is linked to brain resilience, how age-associated changes intersect to adapt brain resilience remains enigmatic. We here provide evidence that a brain-wide form of presynaptic active zone plasticity (“PreScale”) promotes resilience by coupling sleep, longevity and memory during aging. PreScale increased until mid-age and contributed to the age-adaption of sleep patterns, in effect promoting longevity but not memory of aging flies. Mechanistically, imaging and electrophysiology suggest that genetically-encoded PreScale reprograms neuronal activity, membrane firing patterns and excitability of the sleep-promoting dorsal fan-shaped body neurons, qualitatively similar to aging. Flies metabolically reprogrammed by spermidine towards extended longevity and preserved memory skipped PreScale and subsequently age-associated sleep pattern changes. Acute deep sleep induction in mid-age flies reset PreScale back to juvenile levels and restored memory. Taken together, early along aging trajectory, PreScale seems to steer trade-offs between longevity and memory, illustrating how life strategy manifests on circuit and synaptic plasticity levels.GRAPHIC ABSTRACT
Presynaptic plasticity at the active zone (AZ) during early aging triggers sleep pattern changes, and subsequently steers trade-offs between memory formation and longevity. Interventions like spermidine (Spd) and Gaboxadol (THIP) supplementation suppress PreScale and allow for new memory formation and lifespan extension.
Structural spine plasticity: learning and forgetting of odor-specific subnetworks in the olfactory bulb
Authors: Meng John Hongyu , Riecke Hermann 
Published: July 2022

AbstractLearning to discriminate between different sensory stimuli is essential for survival. In rodents, the olfactory bulb, which contributes to odor discrimination via pattern separation, exhibits extensive structural synaptic plasticity involving the formation and removal of synaptic spines, even in adult animals. The network connectivity resulting from this plasticity is still poorly understood. To gain insight into this connectivity we present here a computational model for the structural plasticity of the reciprocal synapses between the dominant population of excitatory principal neurons and inhibitory interneurons. It incorporates the observed modulation of spine stability by odor exposure. The model captures the striking experimental observation that the exposure to odors does not always enhance their discriminability: while training with similar odors enhanced their discriminability, training with dissimilar odors actually reduced the discriminability of the training stimuli (Chu et al, 2016). Strikingly, this differential learning does not require the activity-dependence of the spine stability and occurs also in a model with purely random spine dynamics in which the spine density is changed homogeneously, e.g., due to a global signal. However, the experimentally observed odor-specific reduction in the response of principal cells as a result of extended odor exposure (Kato et al. 2012) and the concurrent disinhibition of a subset of principal cells arise only in the activity-dependent model. Moreover, this model predicts the experimentally testable recovery of odor response through weak but not through strong odor re-exposure and the forgetting of odors via exposure to interfering odors. Combined with the experimental observations, the computational model provides strong support for the prediction that odor exposure leads to the formation of odor-specific subnetworks in the olfactory bulb.Author SummaryA key feature of the brain is its ability to learn through the plasticity of its network. The olfactory bulb in the olfactory system is a remarkable brain area whose anatomical structure evolves substantially still in adult animals by establishing new synaptic connections and removing existing ones. We present a computational model for this process and employ it to interpret recent experimental results. By comparing the results of our model with those of a random control model we identify various experimental observations that lend strong support to the notion that the network of the olfactory bulb comprises learned, odor-specific subnetworks. Moreover, our model explains the recent observation that the learning of odors does not always improve their discriminability and provides testable predictions for the recovery of odor response after repeated odor exposure and for when the learning of new odors interferes with retaining the memory of familiar odors.
DOPA pheomelanin is increased in nigral neuromelanin of Parkinson’s disease and it exacerbates alpha-synuclein neurotoxicity
Authors: Cai Waijiao , Wakamatsu Kazumasa , Zucca Fabio A. , Yang Kai , Mohamadzadehhonarvar Niyaz , Srivastava Pranay , Holly Gabriel , Casella Luigi , Ito Shosuke , Zecca Luigi , Chen Xiqun 
Published: July 2022

AbstractObjectiveNeuromelanin (NM) of the human substantia nigra (SN) has long been proposed as a key factor contributing to dopaminergic neuron vulnerability in Parkinson’s disease (PD). NM consists of pheomelanin and eumelanin moieties. Evidence supports that pheomelanin and eumelanin possess distinct chemical and biological characteristics. The present study aimed to investigate the relative composition and specific roles of pheomelanin and eumelanin moieties of NM in PD.MethodsPheomelanin and eumelanin components of NM in postmortem SN tissues from patients with PD were assessed by chemical degradation methods and compared with those from control subjects as well as patients with Alzheimer’s disease (AD). Additionally, synthetic pheomelanin and eumelanin were used to investigate their differential impacts on dopaminergic neuronal survival in a mouse model of PD overexpressing alpha-synuclein in the SN.ResultsWe identified increased L-3,4-dihydroxyphenylalanine (DOPA) pheomelanin and increased ratios of dopamine (DA) pheomelanin markers to DA in PD SN compared to the controls. Eumelanins derived from both DOPA and DA were reduced in PD group. Melanin markers were unaltered in AD SN compared to the controls. Furthermore, we showed exacerbated dopaminergic neurodegeneration by synthetic DOPA pheomelanin and attenuated DA deficit by synthetic DOPA eumelanin in an alpha-synuclein mouse model of PD.ConclusionOur study provides insights into the different roles of pheomelanin and eumelanin moieties in PD pathophysiology. It forms a foundation for further investigations on pheomelanin and eumelanin individually as biomarkers and therapeutic targets for PD.
Pathway Analysis Through Mutual Information
Authors: Jeuken Gustavo S. , Käll Lukas 
Published: July 2022

AbstractPathway analysis comes in many forms. Most are seeking to establish a connection between the activity of a certain biological pathway and a difference in phenotype, often relying on an upstream differential expression analysis to establish the difference between case and control. This process usually models this relationship using many assumptions, often of a linear nature, and may also involve statistical tests where the calculation of false discovery rates is not trivial.Here, we propose a new method for pathway analysis, MIPath, that relies on information theoretical principles, and therefore is absent of a model for the nature of the association between pathway activity and phenotype, resulting on a very minimal set of assumptions. For this, we construct a different graph of samples for each pathway and score the association between the structure of this graph and any phenotype variable using Mutual Information, while adjusting for the effects of random chance in each score.Our experiments show that this method produces robust and reproducible scores that successfully result in a high rank for target pathways on single cell datasets, outperforming established methods for pathway analysis on these same conditions.
Nitrogen competition is the general mechanism underlying cnidarian-Symbiodiniaceae symbioses
Authors: Cui Guoxin , Mi Jianing , Moret Alessandro , Zhong Huawen , Hung Shiou-Han , Al-Babili Salim , Aranda Manuel 
Published: July 2022

AbstractSymbiotic associations with Symbiodiniaceae have evolved independently across a diverse range of cnidarian taxa including reef-building corals, anemones and jellyfish, yet the molecular mechanisms underlying their regulation and repeated evolution are still elusive. Here we show that despite their independent evolution, cnidarian hosts employ the same mechanism of symbiont control in which symbiont-derived glucose is used to assimilate nitrogenous waste via amino acid biosynthesis to limit the availability of nitrogen to the symbionts. In this metabolic interaction, glucose significantly reduces symbiont density while ammonium promotes symbiont proliferation. We show that glucose-derived 13C and ammonium-derived 15N are co-incorporated into amino acids by the hosts. Metabolic differences between the hosts further suggest that corals are more susceptible to environmental stress and symbiosis breakdown due to their increased energy demands to satisfy calcification. Our results reveal the general metabolic interaction underlying these symbioses and provide a parsimonious explanation for their repeated evolution.
Photosynthetic-product-dependent Activation of Plasma Membrane H+-ATPase and Nitrate Uptake in Arabidopsis Leaves
Authors: Kinoshita Satoru N. , Suzuki Takamasa , Kiba Takatoshi , Sakakibara Hitoshi , Kinoshita Toshinori 
Published: July 2022

AbstractPlasma membrane (PM) H+-ATPase is a pivotal enzyme for plant growth and development that acts as a primary transporter and is activated by phosphorylation of the penultimate residue, threonine, at the C-terminus. Photosynthetically active radiation activates PM H+-ATPase via phosphorylation in mesophyll cells ofArabidopsis thaliana, and phosphorylation of PM H+-ATPase depends on photosynthesis and photosynthesis-related sugar supplementation, such as sucrose, fructose and glucose. However, the molecular mechanism and the physiological role of photosynthesis-dependent PM H+-ATPase activation are still unknown. Analysis using sugar analogues, such as palatinose, turanose, and 2-deoxy glucose, revealed that sucrose metabolites and products of glycolysis such as pyruvate induce phosphorylation of PM H+-ATPase. Transcriptome analysis showed that novel isoform of theSmall Auxin Up RNAgenes,SAUR30, is upregulated in a light- and sucrose-dependent manner. Time course analyzes of sucrose supplementation showed that phosphorylation level of PM H+-ATPase increased within 10 min, but expression level ofSAUR30increased later than 10 min. The results suggest two temporal regulations may participate in the regulation of PM H+-ATPase. Interestingly, a15NO3-uptake assay in leaves showed that light increases15NO3-uptake, and that increment of15NO3-uptake depends on PM H+-ATPase activity. The results opened the possibility of physiological role of photosynthesis-dependent PM H+-ATPase activation in the uptake of NO3-. We speculate that PM H+-ATPase may connect photosynthesis and nitrogen metabolism in leaves.