Biology subjects

Fujiwara, H.

Publications and source records attributed to Fujiwara, H..

3 recordsLinked to original sources

bioRxiv2018

Hair Follicle Epidermal Stem Cells Define a Niche for Tactile Sensation

The heterogeneity and compartmentalization of stem cells is a common principle in many epithelia, and is known to function in epithelial maintenance, but its other physiological roles remain elusive. Here we show transcriptional and anatomical contributions of compartmentalized epidermal stem cells (EpSCs) in tactile sensory unit formation in the hair follicle (HF). EpSCs in the follicle upper-bulge, where mechanosensory lanceolate complexes (LCs) innervate, express a unique set of extracellular matrix (ECM) and neurogenesis-related genes. These EpSCs deposit an ECM protein EGFL6 into the collar matrix, a novel ECM that tightly ensheathes LCs. EGFL6 is required for the proper patterning, touch responses, and v integrin-enrichment of LCs. By maintaining a quiescent original EpSC niche, the old bulge, EpSCs provide anatomically stable HF-LC interfaces, irrespective of the stage of follicle regeneration cycle. Thus, compartmentalized EpSCs provide a niche linking the HF and the nervous system throughout the hair cycle.

developmental biology↗

bioRxiv2018

Comparative evaluation of the GeeniusTM HIV 1/2 Confirmatory Assay and the HIV-1 and HIV-2 Western blots in the Japanese population

Accurate diagnosis of earlier HIV infection is essential for treatment and prevention. Currently, confirmation tests of HIV infection in Japan are performed using Western blot (WB), but WB has several limitations including low sensitivity and cross-reactivity between HIV-1 and HIV-2 antibodies. To address these problems, a new HIV testing algorithm and a more reliable confirmation and HIV-1/2 differentiation assay are required. The Bio-Rad Geenius HIV-1/2 Confirmatory Assay (Geenius) has recently been approved and recommended for use in the revised guidelines for diagnosis of HIV infection by the Center for Disease Control and Prevention (USA). We made comprehensive comparison of the performance of Geenius and the Bio-Rad NEW LAV BLOT 1 and 2 (NLB 1 and 2) which are WB kits for HIV-1 and HIV-2, respectively, to examine if Geenius is a suitable alternative to these WB assays which are now being used in HIV testing in Japan. A total of 166 HIV-1 positive samples (146 from patients with established HIV-1 infection and 20 from patients with acute infection), five HIV-1 seroconversion panels containing 21 samples and 30 HIV-2 positive samples were used. In addition, a total of 140 HIV negative samples containing 10 false-positives on screening tests were examined. The sensitivity of Geenius and NLB 1 for HIV-1 positive samples was 99.3% and 98.6%, respectively. Geenius provided more positive results in the samples from acute infections and detected positivity 0 to 32 days earlier in seroconversion panels than NLB 1. NLB 2 gave positive results in 12.3% of HIV-1 positive samples. The sensitivity of both Geenius and NLB 2 for HIV-2 positive samples was 100%. The specificity of Geenius, NLB 1 and NLB 2 was 98.5%, 81.5% and 90.0%, respectively. Geenius is an attractive alternative to WB for confirmation and differentiation of HIV-1 and HIV-2 infections. The adaptation of Geenius to the HIV testing algorithm may be advantageous for rapid diagnosis and the reduction of testing costs.

molecular biology↗

bioRxiv2018

ALOXE3 is a hepatic fasting-responsive lipoxygenase that enhances insulin sensitivity via hepatic PPARγ

ABSTARCTThe hepatic glucose fasting response is gaining traction as a therapeutic pathway to enhance hepatic and whole-host metabolism. However, the mechanisms underlying these metabolic effects remain unclear. Here, we demonstrate the lipoxygenase, ALOXE3, is a novel effector of the thepatic fasting response. We show that ALOXE3 is activated during fasting, glucose withdrawal, and trehalose/trehalose analogue treatment. Hepatocyte-specific ALOXE3 expression reduced weight gain and hepatic steatosis in dietaryand genetically obese (db/db) models. ALOXE3 expression moreover enhanced basal thermogenesis and abrogated insulin resistance in db/db diabetic mice. Targeted metabolomics demonstrated accumulation of the PPAR{gamma} ligand, 12-KETE in hepatocytes overexpressing ALOXE3. Strikingly, PPAR{gamma} inhibition reversed hepatic ALOXE3-mediated insulin sensitization, suppression of hepatocellular ATP production and oxygen consumption, and gene induction of PPAR{gamma} coactivator-1a (PGC1) expression. Moreover, hepatocyte-specific PPAR{gamma} deletion reversed the therapeutic effect of hepatic ALOXE3 expression on diet-induced insulin intolerance. ALOXE3 is therefore a novel effector of the hepatocellular fasting response that leverages both PPAR{gamma}-mediated and pleiotropic effects to augment hepatic and whole-host metabolism, and is thus a promising target to ameliorate metabolic disease.

physiology↗