bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAIN-DERIVED NEUROTROPHIC FACTOR IN AN ORBITOFRONTAL CORTICAL-DORSOLATERAL STRIATAL CIRCUIT GATES ALCOHOL CONSUMPTION
Authors: Moffat Jeffrey J. , Sakhai Samuel A. , Ehinger Yann , Phamluong Khanhky , Ron Dorit 
Published: September 2021

AbstractBrain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) gates alcohol self-administration in rodents. The major source of BDNF in the striatum is the cortex, and we recently found that BDNF-expressing neurons in the ventrolateral orbitofrontal cortex (vlOFC) extend axonal projections to the DLS. We therefore hypothesized that BDNF in the vlOFC to DLS circuit moderates alcohol intake. We show that overexpression of BDNF in the vlOFC, which activates BDNF signaling in the DLS, is sufficient to attenuate voluntary consumption and seeking of 20% alcohol in the home cage using a two-bottle choice paradigm. Overexpressing BDNF in the vlOFC had no effect on the consumption of a sweetened saccharin solution. In addition, BDNF overexpression in the neighboring motor cortex did not alter alcohol intake. Finally, pathway-specific overexpression of BDNF in DLS-projecting vlOFC neurons significantly reduced alcohol intake and preference. Overall, BDNF in the vlOFC, and specifically in a vlOFC-DLS pathway, keeps alcohol drinking in moderation.
High-fat diet feeding reduces the expression of Rab3a, Rab3gap1, and Rab3Gap2 genes that are pivotal to neuronal exocytosis
Authors: Ferreira Luana Assis , Rubatino Fernando Victor Martins , de Freitas Mariana Lacerda , de Oliveira Leonardo Rossi , de Castro Junior Célio Jose , Jehee Fernanda Sarquis , Bosco Adriana Aparecida , Fernandes Karla Silva 
Published: September 2021

AbstractThe Rab3A and Rab3gaps are essential to the Ca+2-dependent neuronal exocytosis in the hypothalamus. The arcuate nucleus of the hypothalamus (ARC) controls food intake and energy expenditure. We have earlier described that the high-fat diet (HFD) feeding induces an obesity phenotype with high leptin production and alteration of proteins related to endosome sorting, and ubiquitination in the ARC of mice. In this study, real-time PCR data analysis revealed that HFD feeding decreases significantly Rab3a, Rab3gap1, and Rab3gap2 transcript levels in the ARC when compared to the group receiving a control diet. The decrease of Rab3gap1/2 transcript levels in the ARC was strongly associated with an increase in plasma leptin. Altogether, our studies demonstrate that HFD feeding could be altering the general network of endosome compartmentalization in the ARC of mice, contributing to a failure in exocytosis and receptor recycling.Graphical abstract
Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)-mediated plasticity in the paraventricular thalamic nucleus promotes a fundamental adaptation to stress
Authors: Corbett Brian F. , Luz Sandra , Arner Jay , Vigderman Abigail , Urban Kimberly , Bhatnagar Seema 
Published: September 2021

AbstractBACKGROUNDHabituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of post-traumatic stress disorder (PTSD). In rodents, habituation is observed in neural, neuroendocrine and behavioral responses to repeated exposure to the predictable and moderately intense stress or restraint. We previously demonstrated that lesions to the posterior division of the paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown.METHODSBehavioral and neuroendocrine habituation was assessed in adult male Sprague-Dawley restraints using the repeated restraint paradigm. Pan neuronal and Cre-dependent Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using siRNA directed towards Arc. Golgi staining was used to assess structural plasticity of pPVT neurons. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set-shifting task was used to assess mPFC-dependent behavior.RESULTSHere, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility.CONCLUSIONOur results demonstrate that Arc induction in the pPVT regulates habituation to repeated restraint and mPFC function.One Sentence SummaryWe demonstrate that Arc in the posterior division of the paraventricular thalamic nucleus promotes habituation to repeated stress by increasing dendritic spines.
Dopamine biases sensitivity to personal goals and social influence in self-control over everyday desires
Authors: Castrellon Jaime J. , Young Jacob S. , Dang Linh C. , Smith Christopher T. , Cowan Ronald L. , Zald David H. , Samanez-Larkin Gregory R. 
Published: September 2021

AbstractPeople regularly give in to daily temptations in spite of conflict with personal goals. To test hypotheses about neuropharmacological influences on self-control, we used positron emission tomography to measure dopamine D2-like receptors (D2R) and experience sampling surveys to naturalistically track daily desires outside the laboratory in everyday life in a sample of 103 adults. Higher D2R availability in the ventral striatum was associated with increased sensitivity to personal goal conflict but not desire strength in deciding whether to attempt to resist a desire. The influence of D2Rs on sensitivity to personal goal conflict depended on whether desires were experienced in a social context. D2R availability in the midbrain (but not the ventral striatum) influenced whether desires were enacted. These findings provide unique evidence that the dopamine system influences decision making and regulatory behavior and provides new insights into how these mechanisms interact with personal goals and social contexts.
Using BERT to identify drug-target interactions from whole PubMed
Authors: Aldahdooh Jehad , Vähä-Koskela Markus , Tang Jing , Tanoli Ziaurrehman 
Published: September 2021

ABSTRACTBackgroundDrug-target interactions (DTIs) are critical for drug repurposing and elucidation of drug mechanisms, and they are collected in large databases, such as ChEMBL, BindingDB, DrugBank and DrugTargetCommons. However, the number of studies providing this data (~0.1 million) likely constitutes only a fraction of all studies on PubMed that contain experimental DTI data. Finding such studies and extracting the experimental information is a challenging task, and there is a pressing need for machine learning for the extraction and curation of DTIs. To this end, we developed new text mining document classifiers based on the Bidirectional Encoder Representations from Transformers (BERT) algorithm. Because DTI data intimately depends on the type of assays used to generate it, we also aimed to incorporate functions to predict the assay format.ResultsOur novel method identified and extracted DTIs from 2.1 million studies not previously included in public DTI databases. Using 10-fold cross-validation, we obtained ~99% accuracy for identifying studies containing drug-target pairs. The accuracy for the prediction of assay format is ~90%, which leaves room for improvement in future studies.ConclusionThe BERT model in this study is robust and the proposed pipeline can be used to identify new and previously overlooked studies containing DTIs and automatically extract the DTI data points. The tabular output facilitates validation of the extracted data and assay format information. Overall, our method provides a significant advancement in machine-assisted DTI extraction and curation. We expect it to be a useful addition to drug mechanism discovery and repurposing.
Estimating movement rates between Eurasian and North American birds that are vectors of avian influenza (AI)
Authors: Spaulding Fern , McLaughlin Jessica F. , Glenn Travis C. , Winker Kevin 
Published: September 2021

1.1AbstractAvian influenza (AI) is an emerging zoonotic disease that will likely be involved in future pandemics. Because waterbird movements are difficult to quantify, determining the host-specific risk of Eurasian-origin AI movements into North America is challenging. We estimated relative rates of movements, based on long-term evolutionary averages of gene flow, between Eurasian and North American waterbird populations to obtain bidirectional baseline rates of the intercontinental movements of these AI hosts. We used population genomics and coalescent-based demographic models to obtain these gene-flow-based movement estimates. Inferred rates of movement between these populations varies greatly among species. Within dabbling ducks, gene flow, relative to effective population size, varies from ∼3-24 individuals/generation between Eurasian and American wigeons (Mareca penelope – M. americana) to ∼100-300 individuals/generation between continental populations of northern pintails (Anas acuta). These are evolutionary long-term averages and provide a solid foundation for understanding the relative risks of each of these host species in potential intercontinental AI movements. We scale these values to census size for evaluation in that context. In addition to being AI hosts, many of these species are also important in the subsistence diets of Alaskans, increasing the risk of direct bird-to-human exposure to Eurasian-origin AI virus. We contrast species-specific rates of intercontinental movements with the importance of each species in Alaskan diets to understand the relative risk of these taxa to humans. Greater scaup (Aythya marila), mallard (Anas platyrhynchos), and northern pintail (Anas acuta) were the top three species presenting the highest risks for intercontinental AI movement both within the natural system and through exposure to subsistence hunters. These directly comparable, species-based intercontinental movement rates and relative risk rankings should help in modeling, monitoring, and mitigating the impacts of intercontinental host and AI movements.
Population genomics indicate three different modes of divergence and speciation with gene flow in the green-winged teal duck complex
Authors: Spaulding Fern , McLaughlin Jessica F. , McCracken Kevin G. , Glenn Travis C. , Winker Kevin 
Published: September 2021

AbstractThe processes leading to divergence and speciation can differ broadly among taxa with different life histories. We examine these processes in a small clade of ducks with historically uncertain relationships and species limits. The green-winged teal (Anas crecca) complex is a Holarctic species of dabbling duck currently categorized as three subspecies (Anas crecca crecca,A. c. nimia, andA. c. carolinensis) with a close relative, the yellow-billed teal (Anas flavirostris) from South America. We examined divergence and speciation patterns in this group, determining their phylogenetic relationships and the presence and levels of gene flow among lineages using both mitochondrial and genome-wide nuclear DNA obtained from 1,393 ultraconserved element (UCE) loci. Phylogenetic relationships using nuclear DNA among these taxa showedA. c. crecca,A. c. nimia, andA. c. carolinensisclustering together to form one polytomous clade, withA.flavirostrissister to this clade. This relationship can be summarized as (crecca,nimia,carolinensis)(flavirostris). However, whole mitogenomes revealed a different phylogeny: (crecca,nimia)(carolinensis,flavirostris). The best demographic model for key pairwise comparisons supported divergence with gene flow as the probable speciation mechanism in all three contrasts (crecca−nimia,crecca−carolinensis, andcarolinensis−flavirostris). Given prior work, gene flow was expected among the Holarctic taxa, but gene flow between North Americancarolinensisand South Americanflavirostris(M∼0.1 - 0.4 individuals/generation), albeit low, was not expected. Three geographically oriented modes of divergence are likely involved in the diversification of this complex: heteropatric (crecca−nimia), parapatric (crecca−carolinensis), and (mostly) allopatric (carolinensis−flavirostris). Ultraconserved elements are a powerful tool for simultaneously studying systematics and population genomics in systems like this.Graphical Abstract
Probing neuropeptide volume transmission in vivo by a novel all-optical approach
Authors: Xiong Hejian , Lacin Emre , Ouyang Hui , Naik Aditi , Xu Xueqi , Xie Chen , Youn Jonghae , Kumar Krutin , Kern Tyler , Aisenberg Erin , Kircher Daniel , Li Xiuying , Zasadzinski Joseph A. , Mateo Celine , Kleinfeld David , Hrabetova Sabina , Slesinger Paul A. , Qin Zhenpeng 
Published: September 2021

AbstractNeuropeptides are essential signaling molecules in the nervous system involved in modulating neural circuits and behavior. Although hypothesized to signal via volume transmission through G-protein coupled receptors (GPCR), remarkably little is known about their extrasynaptic diffusion. Here, we developed an all-optical approach to probe neuropeptide volume transmission in mouse neocortex. To control neuropeptide release, we engineered photosensitive nanovesicles with somatostatin-14 (SST) that is released with near-infrared light stimulation. To detect SST, we created a new cell-based neurotransmitter fluorescent engineered reporter (CNiFER) using the SST2 GPCR. Under two-photon imaging, we determined the time to activate SST2R at defined distances as well as the maximal distance and loss rate for SST volume transmission in neocortex. Importantly, we determined that SST transmission is significantly faster in neocortex with a chemically degraded extracellular matrix, a diseased condition indicated in neuroinflammation and Parkinson’s disease. These new neurotechnologies can reveal important biological signaling processes previously not possible, and provide new opportunities to investigate volume transmission in the brain.
Deficits in decision-making induced by parietal cortex inactivation are compensated at two time scales
Authors: Jeurissen Danique , Shushruth S , El-Shamayleh Yasmine , Horwitz Gregory D , Shadlen Michael N 
Published: September 2021

AbstractPerceptual decisions arise through the transformation of samples of evidence into a commitment to a proposition or plan of action. Such transformation is thought to involve cortical circuits capable of computation over time scales associated with working memory, attention, and planning. Neurons in the lateral intraparietal area (LIP) are thought to play a role in all of these functions, and much of what is known about the neurobiology of decision making has been influenced by studies of LIP and its network of cortical and subcortical connections. However a causal role of neurons in LIP remains controversial. We used pharmacological and chemogenetic methods to inactivate LIP in one hemisphere of four rhesus monkeys. Inactivation produced clear biases in decisions, but the effects dissipated despite the persistence of neural inactivation, implying compensation by other unaffected areas. Compensation occurs on a rapid times scale, within an experimental session, and more gradually, across sessions. The findings resolve disparate studies and inform interpretation of focal perturbations of brain function.
A Model for DHX15 Mediated Disassembly of A-Complex Spliceosomes
Authors: Maul-Newby Hannah M. , Amorello Angela N. , Sharma Turvi , Kim John H. , Modena Matthew S. , Prichard Beth , Jurica Melissa S. 
Published: September 2021

AbstractA critical step of pre-mRNA splicing is the recruitment of U2 snRNP to the branch point sequence of an intron. U2 snRNP conformation changes extensively during branch helix formation and several RNA-dependent-ATPases are implicated in the process. However, the molecular mechanisms involved remain to be fully dissected. We took advantage of the differential nucleotide triphosphates requirements for DExD/H-box enzymes to probe their contributions to in vitro spliceosome assembly. Both ATP and GTP hydrolysis support the formation of A-complex, indicating the activity of a DEAH-enzyme because DEAD-enzymes are selective for ATP. We immunodepleted DHX15 to assess its involvement and although splicing efficiency decreases with reduced DHX15, A-complex accumulation incongruently increases. DHX15 depletion also results in the persistence of the atypical ATP-independent interaction between U2 snRNP and a minimal substrate that is otherwise destabilized in the presence of either ATP or GTP. These results lead us to hypothesize that DHX15 plays a quality control function in U2 snRNP’s engagement with an intron. In efforts to identify the RNA target of DHX15, we determined that an extended polypyrimidine tract is not necessary for disruption of the atypical interaction between U2 snRNP and the minimal substrate. We also examined U2 snRNA by RNase H digestion and identified nucleotides in the branch binding region that become accessible with both ATP and GTP hydrolysis, again implicating a DEAH-enzyme. Together, our results demonstrate that multiple ATP-dependent rearrangements are likely involved in U2 snRNP addition to the spliceosome and that DHX15 can have an expanded role in splicing.
Convergent patterns of gene expression and protein evolution associated with adaptation to desert environments in rodents
Authors: Bittner Noëlle K. J. , Mack Katya L. , Nachman Michael W. 
Published: September 2021

AbstractDesert specialization has arisen multiple times across rodents and is often associated with a suite of convergent phenotypes, including modification of the kidneys to mitigate water loss. However, the extent to which phenotypic convergence in desert rodents is mirrored at the molecular level is unknown. Here, we sequenced kidney mRNA and assembled transcriptomes for three pairs of rodent species to search for convergence in gene expression and amino acid sequence associated with adaptation to deserts. We conducted phylogenetically-independent comparisons between a desert specialist and a non-desert relative in three families representing ∼70 million years of evolution. Overall, patterns of gene expression faithfully recapitulated the phylogeny of these six taxa. However, we found that 8.6% of all genes showed convergent patterns of expression evolution between desert and non-desert taxa, a proportion that is much higher than expected by chance. In addition to these convergent changes, we observed many species-pair specific changes in gene expression indicating that different instances of adaptation to deserts include a combination of unique and shared changes. Patterns of protein evolution revealed a small number of genes showing evidence of positive selection, the majority of which did not show convergent changes in gene expression. Overall, our results suggest convergent changes in gene regulation play a primary role in the complex trait of desert adaptation in rodents.
Exosomal MFGE8 from high glucose induced endothelial cells is involved in calcification/senescence of vascular smooth muscle cells
Authors: Ni Yu-Qing , Li Shuang , Lin Xiao , Wang Yan-Jiao , He Jie-Yu , Song Wan-Ling , Xiang Qun-Yan , Zhao Yan , Li Chen , Wang Yi , Li Hua-Hua , Liang Zhen , Zhan Jun-Kun , Liu You-Shuo 
Published: September 2021

AbstractVascular calcification/aging is a crucial feature of diabetic macro vasculopathy, resulting in serious cardiovascular diseases. The calcification/senescence of vascular smooth muscle cells (VSMCs) induced by hyperglycemia can cause diabetic vascular calcification/aging. However, the mechanism of VSMCs calcification/senescence involved in diabetic vascular calcification/aging remains unknown. The purpose of this study was to determine how the high glucose (HG) information in circulating blood is transmitted from vascular endothelial cells (ECs) to VSMCs, which are not contacted with blood directly. Exosomes have attracted much attention for their vital roles in regulating cell-to-cell communication. In this study, we found that milk fat globule epidermal growth factor 8 (MFGE8) was enriched in high glucose induced human umbilical vein endothelial cell exosomes (HG-HUVEC-Exo) and regulate VSMCs calcification/senescence, characterized by up-regulated expressions of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as the increased mineralized nodules and senescence-associated β-galactosidase (SA-β-gal) positive cells. Upstream mechanism studies showed that sirtuin1 (SIRT1) was involved in VSMCs calcification/senescence by affecting the expression of MFGE8. We also found that inflammatory response mediated by IL-1β, IL-6, and IL-8 was closely associated with MFGE8 and played a key role in regulating HG-HUVEC-Exo-induced VSMCs calcification/senescence. These findings provide a new insight into the mechanism of exosomal MFGE8 as a potential preventive and therapeutic target for the intervention of diabetic vascular calcification/aging.
Even allocation of benefits stabilizes microbial community engaged in metabolic division of labor
Authors: Wang Miaoxiao , Chen Xiaoli , Liu Xiao-nan , Fang Yuan , Zheng Xin , Huang Ting , Tang Yue-Qin , Nie Yong , Wu Xiao-Lei 
Published: September 2021

AbstractMetabolic division of labor (MDOL) is commonly observed in microbial communities, where a metabolic pathway is sequentially implemented by several members similar to an assembly line. Uncovering the assembly rules of the community engaged in MDOL is crucial for understanding its ecological contribution, as well as for engineering high-performance microbial communities. To investigate the assembly of the community engaged in MDOL, we combined mathematical modelling with experimentations using synthetic microbial consortia. We built a theoretical framework predict the assembly of MDOL system, and derived a simple rule: to maintain co-existence of the MDOL members, the populations responsible for former steps should hold a growth advantage (m) over the ‘private benefit’ (n) of the population responsible for last step, and the steady-state frequency of the last population is determined by the quotient of n and m. Our experiments further indicated that our theoretical framework accurately predicted the stability and assembly of our engineered synthetic consortia that degrade naphthalene through two-step or multi-step MDOL. Our results demonstrate that the assembly of microbial community engaged in MDOL is determined by a limited number of parameters. This quantitative understanding provides novel insights on designing and managing stable microbial systems to address grand challenges facing human society in agriculture, degradation of the environment, and human health.