Habit nail tic disorder: onychotillomania involving thumbs and toes responding to fluoxetine

Habit nail tic disorder is a type of nail dystrophy caused by repetitive trauma to the nail matrix. It is a body-focused repetitive behavior that is commonly reported among adults and may or may not be associated with obsessive-compulsive behavior. In this report, we present a case of a 12-year-old adolescent girl who had a central furrow with longitudinal ridges running parallel from the proximal to the distal end of both her thumbnails and toenails, giving them a "washboard" appearance and diagnosed as habit nail tic disorder, and treatment involved fluoxetine 20 mg and the application of permeable adhesive tape to protect the nails from external trauma. There was a positive response observed two months after the beginning of the treatment and the nail matrix resolved spontaneously

Temporal gene expression of mesenchymal cells in the pediatric lung

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting their applicability to longitudinal pediatric lung development. Temporal analysis of gene expression aims to bridge this gap, and the most common analytical approach utilizes Short Time-series Expression Miner (STEM) (Ernst, J. & Bar-Joseph, Z. BMC Bioinformatics, 2006). STEM utilizes unique methods to cluster, compare, and visualize short time-series gene expression data. METHODS: Dissociation of lung cells, sorting into enriched populations, and RNA isolation was performed at the Human Tissue Core of the Molecular Atlas of Lung Development Program (Bandyopadhyay, G. et al. Am. J. Physiol. Lung Cell Mol. Physiol, 2018). RNA sequencing (RNAseq) was performed at the University of Rochester Genomics Research Center using the Ilumina NovaSeq6000, and reads were aligned using the Splice Transcript Alignment to a Reference algorithm (STaR). Reads were further normalized using counts per million (CPM) and variance-mean dependence calculated with DESeq as implemented in Bioconductor. Genes not detected in at least 3 time points or exhibiting a minimum fold change of at least 3 across the time series were excluded from further analysis. Time-series analysis was performed with STEM, and profiles were assigned significance by Fisher’s exact test (p\u3c0.05). Genes selected from profiles of interest were functionally enriched using ToppGene Functional Gene Enricher (Chen, J. et al. BMC Bioinformatics, 2007). RESULTS: RNAseq was performed using RNA obtained from pulmonary mesenchymal cells, (n=24, (\u3c1 d/o - 8 y/o, 17 m, 7 f) generating 24.3±5.5 million reads at depth of 10 million reads (48.3±4.6% of genome mapped). CPM normalized expression values for repeat donor time points were averaged and then separated into a younger (n=9, \u3c1 d/o - 1 y/o) and older (n=8, 1 y/o - 8 y/o) group. A total of 17,843 genes passed filtering criteria in the younger group and 17,840 passed in the older group. Using STEM, 16 and 20 profiles were found to be significant in the younger and older group, respectively. 7 profiles in the younger group and 8 profiles in the older group were selected for further functional analysis based on significance and directionality of gene expression changes. Multiple profiles in both groups demonstrated matrix fibroblast associated gene expression increasing in both groups, peaking at 2 years. Next, proliferative fibroblast and cell division associated gene expression decreased from birth to 1 year in the younger group. Detection of multiple mesenchymal- like profiles validates the purity of cells enriched. Additionally, gene expression associated with immune- like pathways increased in both groups. Finally, cell signatures in the older group associated with the Wnt pathway decreased from 1 year until 2 years and then increased from 4 years to 8 years. CONCLUSIONS: In summary, analysis of dynamic gene expression in isolated cells across a time series demonstrates the unique heterogeneity of pulmonary mesenchymal cells throughout adolescence. In addition, increased gene expression associated with immune signatures during pediatric lung development was noted. Further validation and exploration using this technique may advance understanding of the diversity of pulmonary cell types and pathophysiology of pediatric lung disease

Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice.

Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity

Catestatin induces glycogenesis by stimulating the phosphoinositide 3-kinase-AKT pathway

Aim: Defects in hepatic glycogen synthesis contribute to post-prandial hyperglycaemia in type 2 diabetic patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA 352-372) improves glucose tolerance in insulin-resistant mice. Here, we seek to determine whether CST induces hepatic glycogen synthesis. Methods: We determined liver glycogen, glucose-6-phosphate (G6P), uridine diphosphate glucose (UDPG) and glycogen synthase (GYS2) activities; plasma insulin, glucagon, noradrenaline and adrenaline levels in wild-type (WT) as well as in CST knockout (CST-KO) mice; glycogen synthesis and glycogenolysis in primary hepatocytes. We also analysed phosphorylation signals of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-dependent kinase-1 (PDK-1), GYS2, glycogen synthase kinase-3β (GSK-3β), AKT (a kinase in AKR mouse that produces Thymoma)/PKB (protein kinase B) and mammalian/mechanistic target of rapamycin (mTOR) by immunoblotting. Results: CST stimulated glycogen accumulation in fed and fasted liver and in primary hepatocytes. CST reduced plasma noradrenaline and adrenaline levels. CST also directly stimulated glycogenesis and inhibited noradrenaline and adrenaline-induced glycogenolysis in hepatocytes. In addition, CST elevated the levels of UDPG and increased GYS2 activity. CST-KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role of CST in hepatic glycogenesis. CST improved insulin signals downstream of IR and IRS-1 by enhancing phospho-AKT signals through the stimulation of PDK-1 and mTORC2 (mTOR Complex 2, rapamycin-insensitive complex) activities. Conclusions: CST directly promotes the glycogenic pathway by (a) reducing glucose production, (b) increasing glycogen synthesis from UDPG, (c) reducing glycogenolysis and (d) enhancing downstream insulin signalling

Diabetic Cardiomyopathy: An Immunometabolic Perspective.

The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) in cardiomyocytes, which is followed by apoptosis, changes in immune responses with a consequent increase in fibrosis, remodeling of cardiomyocytes, and the resultant decrease in cardiac function. The heart is an omnivore, metabolically flexible, and consumes the highest amount of ATP in the body. Altered myocardial substrate and energy metabolism initiate the development of DCM. Diabetic hearts shift away from the utilization of glucose, rely almost completely on fatty acids (FAs) as the energy source, and become metabolically inflexible. Oxidation of FAs is metabolically inefficient as it consumes more energy. In addition to metabolic inflexibility and energy inefficiency, the diabetic heart suffers from impaired calcium handling with consequent alteration of relaxation-contraction dynamics leading to diastolic and systolic dysfunction. Sarcoplasmic reticulum (SR) plays a key role in excitation-contraction coupling as Ca(2+) is transported into the SR by the SERCA2a (sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a) during cardiac relaxation. Diabetic cardiomyocytes display decreased SERCA2a activity and leaky Ca(2+) release channel resulting in reduced SR calcium load. The diabetic heart also suffers from marked downregulation of novel cardioprotective microRNAs (miRNAs) discovered recently. Since immune responses and substrate energy metabolism are critically altered in diabetes, the present review will focus on immunometabolism and miRNAs

Quantum Chaos: Reduced Density Matrix Fluctuations in Coupled Systems

Following a recent work (briefly reviewed below) we consider temporal fluctuations in the reduced density matrix elements for a coupled system involving a pair of kicked rotors as also one made up of a pair of Harper Hamiltonians. These dynamical fluctuations are found to constitute a reliable indicator of the degree of chaos in the quantum dynamics, and are related to stationary features like the eigenvalue and eigenvector distributions of the system under consideration. A brief comparison is made with the evolution of the reduced distribution function in the classical phase space.Comment: 19 pages, 13 figures, elsart styl

Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.

The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-α and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance

Implications of recent solar neutrino observations: an analysis of charged current data

We have analysed the recent results from the observation of charged current \nu_e d \to e^- p p events from solar neutrinos by the Sudbury Neutrino Observatory SNO assuming neutrino oscillations with three active flavours. The data seem to prefer a low mass-squared difference and large mixing angle solution (the so-called LOW solution) in (12) parameter space. However, when combined with the Gallium charged current interaction data from Gallex and GNO, distinct (1\sigma) allowed regions corresponding to the large mixing angle (LMA) and small mixing angle (SMA) appear while the LOW solution is disfavoured upto 3\sigma standard deviation. The physical electron neutrino survival probability corresponding to these best fit solutions are then determined and analysed for their energy dependence.Comment: 16 pages Latex file, with 5 epsf figures; one reference adde