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Despite continuous updates of the human reference genome, there are still hundreds of unresolved gaps which account for ~5% of the total sequence length. Given the availability of whole genome de novo assemblies, especially those derived from long-read sequencing data, gap-closing sequences can be determined. By comparing 17 de novo long-read sequencing assemblies with the human reference genome, we identified a total of 1,125 gap-closing sequences for 132 (16.9% of 783) gaps and added up to 2.2 Mbp novel sequences to the human reference genome. More than 90% non-redundant sequences could be verified by unmapped reads from the Simons Genome Diversity Project (279 human samples) dataset. In addition, 15.6% of the non-reference sequences were found in at least one of four non-human primate genomes. We further demonstrated that the non-redundant sequences had high content of tandem repeats and potential biology function. [https://www.selleckchem.com/products/DMXAA(ASA404).html NSC 640488 chemical structure] Moreover, 40 (30.5%) of the 132 closed gaps were shown to be polymorphic; such sequences may play an important biological role and can be useful in the investigation of human genetic diversity.Tilapia are amongst the most important farmed fish species worldwide, and are fundamental for the food security of many developing countries. Several genetically improved Nile tilapia (Oreochromis niloticus) strains exist, such as the iconic Genetically Improved Farmed Tilapia (GIFT), and breeding programmes typically follow classical pedigree-based selection. The use of genome-wide single-nucleotide polymorphism (SNP) data can enable an understanding of the genetic architecture of economically important traits and the acceleration of genetic gain via genomic selection. Due to the global importance and diversity of Nile tilapia, an open access SNP array with known utility across multiple tilapia strains would be beneficial for aquaculture research and production. In the current study, a ~65K SNP array was designed based on SNPs discovered from whole-genome sequence data from a GIFT breeding nucleus population and the overlap with SNP datasets from several other farmed and wild Nile tilapia strains. The SNP array was applied to clearly distinguish between different tilapia populations across Asia and Africa, with at least ~30,000 SNPs segregating in each of the diverse population samples tested. It is anticipated that this SNP array will be an enabling tool for population genetics and tilapia breeding research, facilitating consistency and comparison of results across studies.Background African-Americans are historically under-represented in SLE studies and engaging them in behavioural interventions is challenging. The Women Empowered to Live with Lupus (WELL) study is a trial conducted to examine the effectiveness of the Chronic Disease Self-Management Program (CDSMP) among African-American women with SLE. We describe enrolment and retention challenges and successful strategies of the WELL study. Methods The Georgians Organized Against Lupus (GOAL) cohort, a population-based cohort established in Atlanta, Georgia, was used to enrol a sample of 168 African-American women with SLE into the CDSMP. The CDSMP is a 6-week, group-based programme led by peers to enhance self-management skills in people with chronic conditions. Study performance standards were predefined and close monitoring of recruitment and retention progress was conducted by culturally competent staff members. Continuous contact with participants, research coordinators' notes and regular research team meetings served ing successful strategies and achieving the desired recruitment and retention outcomes of a behavioural trial involving African-American women with SLE. Trial registration number NCT02988661.In the peripheral nerve, mechanosensitive axons are insulated by myelin, a multilamellar membrane formed by Schwann cells. Here, we offer first evidence that a myelin degradation product induces mechanical hypersensitivity and global transcriptomics changes in a sex-specific manner. Focusing on downstream signaling events of the functionally active 84-104 myelin basic protein (MBP84-104) fragment released after nerve injury, we demonstrate that exposing the sciatic nerve to MBP84-104 via endoneurial injection produces robust mechanical hypersensitivity in female, but not in male, mice. RNA-Seq and systems biology analyses revealed a striking sexual dimorphism in molecular signatures of the dorsal root ganglia (DRG) and spinal cord response, not observed at the nerve injection site. Mechanistically, intra-sciatic MBP84-104 induced phospholipase C (PLC)-driven (females) and phosphoinositide 3-kinase-driven (males) phospholipid metabolism (tier 1). PLC/inositol trisphosphate receptor (IP3R) and estrogen receptor co-regulation in spinal cord yielded Ca2+-dependent nociceptive signaling induction in females that was suppressed in males (tier 2). IP3R inactivation by intrathecal xestospongin C attenuated the female-specific hypersensitivity induced by MBP84-104. According to sustained sensitization in tiers 1-2, T cell-related signaling spreads to the DRG and spinal cord in females, but remains localized to the sciatic nerve in males (tier 3). These results are consistent with our previous finding that MBP84-104-induced pain is T cell-dependent. In summary, an autoantigenic peptide endogenously released in nerve injury triggers multi-site, sex-specific transcriptome changes, leading to neuropathic pain only in female mice. MBP84-104 acts through sustained co-activation of metabolic, estrogen receptor-mediated nociceptive and autoimmune signaling programs.Objectives Children hospitalized with infections are commonly transitioned from intravenous (IV) to enteral (per os [PO]) antibiotics before discharge, after which they may be observed in the hospital to ensure tolerance of PO therapy and continued clinical improvement. We sought to describe the frequency and predictors of in-hospital observation after transition from IV to PO antibiotics in children admitted for skin and soft tissue infections (SSTIs). Methods We conducted a retrospective cohort study of children with SSTIs discharged between January 1, 2016, and June 30, 2018, using the Pediatric Health Information System database. Children were classified as observed if hospitalized ≥1 day after transitioning from IV to PO antibiotics. We calculated the proportion of observed patients and used logistic regression with random intercepts to identify predictors of in-hospital observation. Results Overall, 15% (558 of 3704) of hospitalizations for SSTIs included observation for ≥1 hospital day after the transition from IV to PO antibiotics.