bluuebunny/crossref_metadata_2025_split huggingface dataset:
1,25-Dihydroxyvitamin D modulates L-type voltage-gated calcium channels in a subset of neurons in the developing mouse prefrontal cortex
Authors: Gooch Helen , Cui Xiaoying , Anggono Victor , Trzaskowski Maciej , Tan Men Chee , Eyles Darryl W. , Burne Thomas H. J. , Jang Se Eun , Mattheisen Manuel , Hougaard David M. , Pedersen Bent Nørgaard , Cohen Arieh , Mortensen Preben B. , Sah Pankaj , McGrath John J. 
Published: November 2019

AbstractSchizophrenia has been associated with a range of genetic and environmental risk factors. Here we explored a link between two risk factors that converge on a shared neurobiological pathway. Recent genome-wide association studies (GWAS) have identified risk variants in genes that code for L-type voltage-gated calcium channels (L-VGCCs), while epidemiological studies have found an increased risk of schizophrenia in those with neonatal vitamin D deficiency. The active form of vitamin D (1,25(OH)2D) is a secosteroid that rapidly modulates L-VGCCs via non-genomic mechanisms in a range of peripheral tissues, though its non-genomic effects within the brain remain largely unexplored. Here we used calcium imaging, electrophysiology and molecular biology to determine whether 1,25(OH)2D non-genomically modulated L-VGCCs in the developing prefrontal cortex, a region widely implicated in schizophrenia pathophysiology. Wide-field Ca2+ imaging revealed that physiological concentrations of 1,25(OH)2D rapidly enhanced activity-dependent somatic Ca2+ levels in a small subset of neurons in the developing PFC, termed vitamin D-responsive neurons (VDRNs). Somatic nucleated patch recordings revealed a rapid, 1,25(OH)2D-evoked increase in high-voltage-activated (HVA) Ca2+ currents. Enhanced activity-dependent Ca2+ levels were mediated by L-VGCC but not associated with any changes to Cacna1c (L-VGCC pore-forming subunit) mRNA expression. Since L-VGCC activity is critical to healthy neurodevelopment, these data suggest that suboptimal concentrations of 1,25(OH)2D could alter brain maturation through modulation of L-VGCC signalling and as such may provide a parsimonious link between epidemiologic and genetic risk factors for schizophrenia.
Vulnerability to bipolar disorder is linked to sleep and sleepiness
Authors: Hensch Tilman , Wozniak David , Spada Janek , Sander Christian , Ulke Christine , Wittekind Dirk Alexander , Thiery Joachim , Löffler Markus , Jawinski Philippe , Hegerl Ulrich 
Published: November 2019

AbstractSleep impairments are a hallmark of acute bipolar disorder (BD) episodes and are present even in the euthymic state. Studying healthy subjects who are vulnerable to BD can improve our understanding of whether sleep impairment is a predisposing factor. Therefore, we investigated whether vulnerability to BD, dimensionally assessed by the hypomanic personality scale (HPS), is associated with sleep disturbances in healthy subjects. We analyzed participants from a population-based cohort who had completed the HPS and had either a 7-day actigraphy recording or a Pittsburgh sleep quality index (PSQI) assessment. In addition, subjects had to be free of confounding diseases or medications. This resulted in 771 subjects for actigraphy and 1766 for PSQI analyses. We found strong evidence that higher HPS scores are associated with greater intraindividual sleep variability, more disturbed sleep and more daytime sleepiness. In addition, factor analyses revealed that core hypomanic features were especially associated with self-reported sleep impairments. Results support the assumption of disturbed sleep as a possibly predisposing factor for BD and suggest sleep improvement as a potential early prevention target.
Modulation of brain activation during executive functioning in autism with citalopram
Authors: Wichers Robert H. , Findon James L. , Jelsma Auke , Giampietro Vincent , Stoencheva Vladimira , Robertson Dene M. , Murphy Clodagh M. , McAlonan Grainne , Ecker Christine , Rubia Katya , Murphy Declan G. M. , Daly Eileen M. 
Published: November 2019

AbstractAdults with autism spectrum disorder (ASD) are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). However, there is limited evidence to support this practice. Therefore, it is crucial to understand the impact of SSRIs on brain function abnormalities in ASD. It has been suggested that some core symptoms in ASD are underpinned by deficits in executive functioning (EF). Hence, we investigated the role of the SSRI citalopram on EF networks in 19 right-handed adult males with ASD and 19 controls who did not differ in gender, age, IQ or handedness. We performed pharmacological functional magnetic resonance imaging to compare brain activity during two EF tasks (of response inhibition and sustained attention) after an acute dose of 20 mg citalopram or placebo using a randomised, double-blind, crossover design. Under placebo condition, individuals with ASD had abnormal brain activation in response inhibition regions, including inferior frontal, precentral and postcentral cortices and cerebellum. During sustained attention, individuals with ASD had abnormal brain activation in middle temporal cortex and (pre)cuneus. After citalopram administration, abnormal brain activation in inferior frontal cortex was ‘normalised’ and most of the other brain functional differences were ‘abolished’. Also, within ASD, the degree of responsivity in inferior frontal and postcentral cortices to SSRI challenge was related to plasma serotonin levels. These findings suggest that citalopram can ‘normalise’ atypical brain activation during EF in ASD. Future trials should investigate whether this shift in the biology of ASD is maintained after prolonged citalopram treatment, and if peripheral measures of serotonin predict treatment response.
Meta-analysis of reward processing in major depressive disorder reveals distinct abnormalities within the reward circuit
Authors: Ng Tommy H. , Alloy Lauren B. , Smith David V. 
Published: November 2019

AbstractMany neuroimaging studies have investigated reward processing dysfunction in major depressive disorder. These studies have led to the common idea that major depressive disorder is associated with blunted responses within the reward circuit, particularly in the ventral striatum. Yet, the link between major depressive disorder and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of major depressive disorder. To address this issue, we performed a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder and 803 healthy controls. Our findings argue against the common idea that major depressive disorder is primarily linked to deficits within the reward system. Instead, our results demonstrate that major depressive disorder is associated with opposing abnormalities in the reward circuit: hypo-responses in the ventral striatum and hyper-responses in the orbitofrontal cortex. The current findings suggest that dysregulated corticostriatal connectivity may underlie reward-processing abnormalities in major depressive disorder, providing an empirical foundation for a more refined understanding of abnormalities in the reward circuitry in major depressive disorder.
Long noncoding RNA LINC00518 acts as a competing endogenous RNA to promote the metastasis of malignant melanoma via miR-204-5p/AP1S2 axis
Authors: Luan Wenkang , Ding Yuting , Ma Shaojun , Ruan Hongru , Wang Jinlong , Lu Feng 
Published: November 2019

AbstractLong intergenic nonprotein coding RNA 518 (LINC00518) has been shown to promote cancer cell growth and metastasis in some human tumors. Although it has been reported that LINC00518 is dysregulated in melanoma, its exact role and molecular mechanism in melanoma remain unclear. RNA-seq analysis and qRT-PCR was used to detect the expression of LINC00518 in melanoma tissues. Melanoma cases from The Cancer Genome Atlas (TCGA), GEO#GSE15605 and GEO#GSE24469 were included in this study. 3D migration, transwell and scratch wound assay were used to explore the role of LINC00518 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP assay, RNA pull-down assay and RNA-ChIP assay were used to demonstrate the mechanism of LINC00518 in melanoma. We found that LICN00518 was significantly upregulated in melanoma tissue, and high LICN00518 level was an independent risk factor for melanoma patients. LICN00518 promoted the invasion and migration of melanoma cells. LICN00518 exerted its role by decoying miR-204-5p to upregulate Adaptor Related Protein Complex 1 Sigma 2 Subunit (AP1S2) expression. We also demonstrated that LICN00518 promoted melanoma metastasis in vivo through pulmonary metastasis assay. This result elucidates a new mechanism for LICN00518 in the metastasis of melanoma. LICN00518 may serve as a survival indicator and potential therapeutic target in melanoma patients.
Cation-induced chirality in a bifunctional metal-organic framework for quantitative enantioselective recognition
Authors: Han Zongsu , Wang Kunyu , Guo Yifan , Chen Wenjie , Zhang Jiale , Zhang Xinran , Siligardi Giuliano , Yang Sihai , Zhou Zhen , Sun Pingchuan , Shi Wei , Cheng Peng 
Published: November 2019

AbstractThe integration of luminescence and chirality in easy-scalable metal-organic frameworks gives rise to the development of advanced luminescent sensors. To date, the synthesis of chiral metal-organic frameworks is poorly predictable and their chirality primarily originates from components that constitute the frameworks. By contrast, the introduction of chirality into the pores of metal-organic frameworks has not been explored to the best of our knowledge. Here, we demonstrate that chirality can be introduced into an anionic Zn-based metal-organic framework via simple cation exchange, yielding dual luminescent centers comprised of the ligand and Tb3+ ions, accompanied by a chiral center in the pores. This bifunctional material shows enantioselectivity luminescent sensing for a mixture of stereoisomers, demonstrated for Cinchonine and Cinchonidine epimers and amino alcohol enantiomers, from which the quantitative determination of the stereoisomeric excess has been obtained. This study paves a pathway for the design of multifunctional metal-organic framework systems as a useful method for rapid sensing of chiral molecules.
Proteomic analysis of eleven tissues in the Chinese giant salamander (Andrias davidianus)
Authors: Geng Xiaofang , Guo Jianlin , Zang Xiayan , Chang Cuifang , Shang Haitao , Wei Hong , Xu Cunshuan 
Published: November 2019

AbstractThe Chinese giant salamander (Andrias davidianus, CGS) is the largest extant amphibian species in the world. Global quantitative proteome analysis of multiple tissues would indicate tissue-specific physiological processes and clarify the function of each protein from a whole-organism perspective. This study performed proteome analysis of eleven tissues collected from adult CGSs using iTRAQ coupled with LC-MS/MS technology. Based on the predicted protein database from previously obtained CGS transcriptome data, 2153 proteins were identified for subsequent analysis. A weighted gene co-expression network analysis (WGCNA) clustered 2153 proteins into 17 co-expressed modules, which will be useful for predicting the functions of unannotated proteins. The protein levels of molecular complexes with housekeeping functions, such as ribosomes, spliceosomes and mitochondrial respiratory chain complexes, were tightly regulated in different tissues of the CGS, as they are in mammalian tissues. Transcription regulator, pathway and bio-functional analysis of tissue-specific proteins showed that highly expressed proteins largely reflected the physiological functions of specific tissues. Our data, as an initial atlas of protein expression of an amphibian species, will be useful for further molecular biology research on CGS.
Effects of the duration of postresuscitation hyperoxic ventilation on neurological outcome and survival in an asphyxial cardiac arrest rat model
Authors: Hu Tongyi , Wang Jianjie , Wang Shuangwei , Li Jingru , Chen Bihua , Zuo Feng , Zhang Lei , Huang Yuanyuan , Li Yongqin 
Published: November 2019

AbstractCardiac arrest leads to sudden cessation of oxygen supply and cerebral hypoxia occurs when there is not sufficient oxygen supplied to the brain. Current Guidelines for adult cardiopulmonary resuscitation (CPR) and emergency cardiovascular care recommend the use of 100% oxygen during resuscitative efforts to maximize the probability of achieving the return of spontaneous circulation (ROSC). However, the optimal strategy for oxygen management after ROSC is still debatable. The aim of the present study was to evaluate the effects of the duration of post-resuscitation hyperoxic ventilation on neurological outcomes in asphyxial cardiac arrest rats treated with targeted temperature management (TTM). Asphyxia was induced by blocking the endotracheal tube in 80 adult male Sprague-Dawley rats. CPR begun after 7 min of untreated cardiac arrest. Animals were randomized to either the normoxic control under normothermia (NNC) group or to one of the 4 experimental groups (n = 16 each) immediately after ROSC: ventilated with 100% oxygen for 0 (O2_0h), 1 (O2_1h), 3 (O2_3h), or 5 (O2_5h) h and ventilated with room air thereafter under TTM. Physiological variables were recorded at baseline and during the 6 h postresuscitation monitoring period. Animals were closely observed for 96 h to assess neurologic recovery and survival. There were no significant differences in baseline measurements between groups, and all animals were successfully resuscitated. There were significant interactions between the duration of 100% oxygen administration and hemodynamics as well as, myocardial and cerebral injuries. Among all the durations of hyperoxic ventilation investigated, significantly lower neurological deficit scores and higher survival rates were observed in the O2_3h group than in the NNC group. In conclusion, postresuscitation hyperoxic ventilation leads to improved PaO2, PaCO2, hemodynamic, myocardial and cerebral recovery in asphyxial cardiac arrest rats treated with TTM. However, the beneficial effects of high concentration-oxygen are duration dependent and ventilation with 100% oxygen during induced hypothermia contributes to improved neurological recovery and survival after 96 h.
Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes
Authors: Sharma Rupali , Cramer Nathan P. , Perry Bayley , Adahman Zahra , Murphy Erin K. , Xu Xiufen , Dardzinski Bernard J. , Galdzicki Zygmunt , Perl Daniel P. , Dickstein Dara L. , Iacono Diego 
Published: November 2019

AbstractLong-term operations carried out at high altitude (HA) by military personnel, pilots, and astronauts may trigger health complications. In particular, chronic exposure to high altitude (CEHA) has been associated with deficits in cognitive function. In this study, we found that mice exposed to chronic HA (5000 m for 12 weeks) exhibited deficits in learning and memory associated with hippocampal function and were linked with changes in the expression of synaptic proteins across various regions of the brain. Specifically, we found decreased levels of synaptophysin (SYP) (p < 0.05) and spinophilin (SPH) (p < 0.05) in the olfactory cortex, post synaptic density−95 (PSD-95) (p < 0.05), growth associated protein 43 (GAP43) (p < 0.05), glial fibrillary acidic protein (GFAP) (p < 0.05) in the cerebellum, and SYP (p < 0.05) and PSD-95 (p < 0.05) in the brainstem. Ultrastructural analyses of synaptic density and morphology in the hippocampus did not reveal any differences in CEHA mice compared to SL mice. Our data are novel and suggest that CEHA exposure leads to cognitive impairment in conjunction with neuroanatomically-based molecular changes in synaptic protein levels and astroglial cell marker in a region specific manner. We hypothesize that these new findings are part of highly complex molecular and neuroplasticity mechanisms underlying neuroadaptation response that occurs in brains when chronically exposed to HA.
Draft genome assembly of Tenualosa ilisha, Hilsa shad, provides resource for osmoregulation studies
Authors: Mohindra Vindhya , Dangi Tanushree , Tripathi Ratnesh K. , Kumar Rajesh , Singh Rajeev K. , Jena J. K. , Mohapatra T. 
Published: November 2019

AbstractThis study provides the first high-quality draft genome assembly (762.5 Mb) of Tenualosa ilisha that is highly contiguous and nearly complete. We observed a total of 2,864 contigs, with 96.4% completeness with N50 of 2.65 Mbp and the largest contig length of 17.4 Mbp, along with a complete mitochondrial genome of 16,745 bases. A total number of 33,042 protein coding genes were predicted, among these, 512 genes were classified under 61 Gene Ontology (GO) terms, associated with various homeostasis processes. Highest number of genes belongs to cellular calcium ion homeostasis, followed by tissue homeostasis. A total of 97 genes were identified, with 16 GO terms related to water homeostasis. Claudins, Aquaporins, Connexins/Gap junctions, Adenylate cyclase, Solute carriers and Voltage gated potassium channel genes were observed to be higher in number in T. ilisha, as compared to that in other teleost species. Seven novel gene variants, in addition to claudin gene (CLDZ), were found in T. ilisha. The present study also identified two putative novel genes, NKAIN3 and L4AM1, for the first time in fish, for which further studies are required for pinpointing their functions in fish. In addition, 1.6 million simple sequence repeats were mined from draft genome assembly. The study provides a valuable genomic resource for the anadromous Hilsa. It will form a basis for future studies, pertaining to its adaptation mechanisms to different salinity levels during migration, which in turn would facilitate in its domestication.
Serum CXCL13 reflects local B-cell mediated inflammatory demyelinating peripheral neuropathy
Authors: Kim Young Hee , Jang So Young , Shin Yoon Kyung , Jo Young Rae , Yoon Byeol-A. , Nam Soo Hyun , Choi Byung-Ok , Shin Ha Young , Kim Seung Woo , Kim Se Hoon , Kim Jong Kuk , Park Hwan Tae 
Published: November 2019

AbstractImmune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. The serum levels of CXCL13 were also higher in inflammatory demyelinating neuropathic patients but not in acute motor axonal neuropathy or a hereditary demyelinating neuropathy, Charcot-Marie-Tooth disease type 1a. In addition, CXCL13-expressing macrophages were not observed in the sciatic nerves after axonal injury, which causes the activation of innate immunity and Wallerian demyelination. Our findings indicate that the detection of serum CXCL13 will be useful to specifically recognize inflammatory demyelinating neuropathies in human.
Suppression of BCL6 function by HDAC inhibitor mediated acetylation and chromatin modification enhances BET inhibitor effects in B-cell lymphoma cells
Authors: Cortiguera María G. , García-Gaipo Lorena , Wagner Simon D. , León Javier , Batlle-López Ana , Delgado M. Dolores 
Published: November 2019

AbstractMultiple genetic aberrations in the regulation of BCL6, including in acetyltransferase genes, occur in clinically aggressive B-cell lymphomas and lead to higher expression levels and activity of this transcriptional repressor. BCL6 is, therefore, an attractive target for therapy in aggressive lymphomas. In this study romidepsin, a potent histone deacetylase inhibitor (HDACi), induced apoptosis and cell cycle arrest in Burkitt and diffuse large B-cell lymphoma cell lines, which are model cells for studying the mechanism of action of BCL6. Romidepsin caused BCL6 acetylation at early timepoints inhibiting its function, while at later timepoints BCL6 expression was reduced and target gene expression increased due to chromatin modification. MYC contributes to poor prognosis in aggressive lymphoma. MYC function is reduced by inhibition of chromatin readers of the bromodomain and extra-terminal repeat (BET) family, which includes BRD4. The novel combination of romidepsin and JQ1, a BRD4 inhibitor was investigated and showed synergy. Collectively we suggest that the combination of HDACi and BRD4i should be pursued in further pre-clinical testing.
A feedback loop of conditionally stable circuits drives the cell cycle from checkpoint to checkpoint
Authors: Deritei Dávid , Rozum Jordan , Ravasz Regan Erzsébet , Albert Réka 
Published: November 2019

AbstractWe perform logic-based network analysis on a model of the mammalian cell cycle. This model is composed of a Restriction Switch driving cell cycle commitment and a Phase Switch driving mitotic entry and exit. By generalizing the concept of stable motif, i.e., a self-sustaining positive feedback loop that maintains an associated state, we introduce the concept of a conditionally stable motif, the stability of which is contingent on external conditions. We show that the stable motifs of the Phase Switch are contingent on the state of three nodes through which it receives input from the rest of the network. Biologically, these conditions correspond to cell cycle checkpoints. Holding these nodes locked (akin to a checkpoint-free cell) transforms the Phase Switch into an autonomous oscillator that robustly toggles through the cell cycle phases G1, G2 and mitosis. The conditionally stable motifs of the Phase Switch Oscillator are organized into an ordered sequence, such that they serially stabilize each other but also cause their own destabilization. Along the way they channel the dynamics of the module onto a narrow path in state space, lending robustness to the oscillation. Self-destabilizing conditionally stable motifs suggest a general negative feedback mechanism leading to sustained oscillations.
Auditory motion perception emerges from successive sound localizations integrated over time
Authors: Roggerone Vincent , Vacher Jonathan , Tarlao Cynthia , Guastavino Catherine 
Published: November 2019

AbstractHumans rely on auditory information to estimate the path of moving sound sources. But unlike in vision, the existence of motion-sensitive mechanisms in audition is still open to debate. Psychophysical studies indicate that auditory motion perception emerges from successive localization, but existing models fail to predict experimental results. However, these models do not account for any temporal integration. We propose a new model tracking motion using successive localization snapshots but integrated over time. This model is derived from psychophysical experiments on the upper limit for circular auditory motion perception (UL), defined as the speed above which humans no longer identify the direction of sounds spinning around them. Our model predicts ULs measured with different stimuli using solely static localization cues. The temporal integration blurs these localization cues rendering them unreliable at high speeds, which results in the UL. Our findings indicate that auditory motion perception does not require motion-sensitive mechanisms.