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Lv, J.

Publications and source records attributed to Lv, J..

4 recordsLinked to original sources
bioRxiv2018

Apigenin relaxes rat intrarenal arteries: involvement of Cl- channels and K+ channels

The vasodilator effect of apigenin (API) was demonstrated in a number of vascular beds. We aimed to characterize the vasospasmolytic and electrophysiological effects of apigenin (API) in intrarenal arteries (IRAs). The vascular tone of male rat isolated IRAs was recorded with a myograph. Transmembrane Cl- currents through Ca2+-activated Cl- channels (CaCCs), K+ currents through voltage-gated K+ (Kv) channels and inwardly rectifier K+ (Kir) channels were recorded with patch clamp in the freshly isolated arterial smooth muscle cells (ASMCs). Preincubation with API (10-100 M) concentration-dependently depressed the contractions induced by KCl, 9,11-dideoxy-9,11-methanoepoxy prostaglandin F2 (U46619), phenylephrine and vasopressin without significant preference and the IC50 values were 13.27-26.26 M. Acute application of API elicited instant relaxations in the IRAs precontracted with these vasoconstrictors and the RC50 values were 5.80-24.33 M. API relaxation was attenuated by chloride deprivation, CaCC blockers, Kv blocker and nitric oxide synthase inhibitor, but not by Kir blocker and cyclooxygenase inhibitor. At 10-100 M, API depressed CaCC currents and Kir currents while enhanced Kv currents of IRA ASMCs. The present results demonstrate that API counteracts various vasoconstrictors noncompetitively and nonspecifically and suggest that modulation of CaCCs, Kv and Kir channels of IRA ASMCs is involved in its vasospasmolytic effects.

pharmacology and toxicology↗
bioRxiv2017

Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts

Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location, regulation and function. Here, we develop a base-resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in 5-UTR, particularly those at the first nucleotide of mRNA, associate with increased translation efficiency. A different subset of m1A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome and are dependent on the methyltransferase TRMT6/61A. Additionally, we show for the first time that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation.

biochemistry↗
bioRxiv2017

Brain-behavior patterns define a dimensional biotype in medication-naïve adults with attention-deficit hyperactivity disorder

BackgroundChildhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD.\n\nMethodsWe first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naive adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype.\n\nResultsAdults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain-symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD.\n\nConclusionsOverall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain-symptom mediators.

neuroscience↗
bioRxiv2017

Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice

Here, we demonstrate that the voltage-gated proton channel Hv1 represents a regulatory mechanism for insulin secretion of pancreatic islet {beta} cell. In vivo, Hv1-de[fi]cient mice display hyperglycemia and glucose intolerance due to reduced insulin secretion, but normal peripheral insulin sensitivity. In vitro, islets of Hv1-de[fi]cient and heterozygous mice, INS-1 (832/13) cells with siRNA-mediated knockdown of Hv1 exhibit a marked defect in glucose- and K+-induced insulin secretion. Hv1 de[fi]ciency decreases both insulin and proinsulin contents, and limits glucose-induced Ca2+ entry and membrane depolarization. Furthermore, loss of Hv1 increases insulin-containing granular pH and decreases cytosolic pH. In addition, histologic studies show a decrease in {beta} cell mass in islets of Hv1-deficient mice. Collectively, our results indicate that Hv1 supports insulin secretion in the {beta} cell by calcium entry, membrane depolarization and intracellular pH regulation.

cell biology↗