Publication

Long noncoding RNAs (lncRNAs) are functionally associated with cancer development and progression. Although gene copy number variation (CNV) is common in hepatocellular carcinoma (HCC), it is not known how CNV in lncRNAs affects HCC progression and recurrence. We aimed to identify a CNV-related lncRNA involved in HCC progression and recurrence and illustrate its underlying mechanisms and prognostic value. We analyzed the whole genome sequencing (WGS) data of matched cancerous and noncancerous liver samples from 49 patients with HCC to identify lncRNAs with CNV.

Bile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3-8.

Although stressful events predispose individuals to psychiatric disorders, such as depression, not all people who undergo a stressful life experience become depressed, suggesting that gene-environment interactions (GxE) determine depression risk. The ventral hippocampus (vHPC) plays key roles in motivation, sociability, anhedonia, despair-like behaviors, anxiety, sleep, and feeding, pointing to the involvement of this brain region in depression.

Autopsies of patients who have died from COVID-19 have been crucial in delineating patterns of injury associated with SARS-CoV-2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections.

Background PTSD is a multigenic and multifactorial disorder occurring in the aftermath of significant trauma exposure. Recent GWAS have identified many high confidence loci as risk factors for PTSD, which have shed some light on impaired mechanisms. However, there are still fundamental gaps in our understanding of how these risk genes and pathways are interrelated in causing PTSD but are likely reflected in cell type-specific transcriptomic and epigenetic changes in the brain. Therefore, it is necessary to uncover the individual cell type contribution to the molecular pathology of PTSD.

Background Aberrant prefrontal cortex (PFC) activity occurs in patients with neuropsychiatric disorders during sustained attention tasks, suggesting that PFC dysfunction underlies attention deficits in these patients. However, the mechanisms by which the PFC regulates sustained attention remain unclear. Methods Behavioral testing and c-Fos immunohistochemistry during performance of a touchscreen sustained attention task (rCPT) in mice. In vivo calcium and norepinephrine imaging to assess patterns of activity during the rCPT.

Background Bulk tissue RNA-sequencing studies in human post-mortem brains have reported differentially expressed genes between patients with Schizophrenia (SCZ) and controls. Single-nucleus RNA-sequencing data indicate that genes downregulated in SCZ were particularly enriched in a sub-population of excitatory neurons (Ex21) indexed by SMYD1 gene. POSTN and NR4A2 are two genes highly specific to Ex21 and significantly downregulated in SCZ. We hypothesized that either the number of Ex21 cells or the expression of POSTN and NR4A2 within them would be reduced in SCZ vs. controls.

Background: The NIH Helping to End Addiction Long-term (HEAL) Initiative aims to focus efforts on advancing scientific solutions to stem the opioid crisis, improving prevention and treatment of opioid misuse/addiction, and enhancing pain management. Goal: NINDS is charged with accelerating the discovery and development of new non-addictive pharmacologic and non-pharmacologic pain therapeutics as part of the HEAL Initiative. NINDS established the Preclinical Screening Platform for Pain (PSPP) to accelerate and enhance testing of novel, non-addictive pain therapeutics.

Painful diabetic neuropathy (PDN) is an intractable and debilitating disease characterized by neuropathic pain and small-fiber degeneration. Given the prevalence of the disease, there is a dire need to identify new targets for the development of disease-modifying therapeutics for PDN. In patients with PDN, dorsal root ganglion (DRG) nociceptors become hyperexcitable and eventually degenerate, but the molecular mechanism underlying the phenomenon is unknown.

Chronic low back pain (cLBP) prevalence increases with advancing age and is a leading contributor to mobility disability among older adults. Opioids are commonly prescribed treatments to reduce pain related symptoms. The rise in opioid use and misuse can enhance a variety of issues in the adult population; such as, lack of mobility and decrease in overall health and wellbeing. Few studies have examined the impact of opioid use on mobility in older adults with cLBP. Therefore, we sought to examine the relationship between self-reported opioid use and self-reported mobility.