Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish

A Retrospective Review of Microbiological Methods Applied in Studies Following the Deepwater Horizon Oil Spill

The Deepwater Horizon (DWH) oil spill in the Gulf of Mexico in 2010 resulted in serious damage to local marine and coastal environments. In addition to the physical removal and chemical dispersion of spilled oil, biodegradation by indigenous microorganisms was regarded as the most effective way for cleaning up residual oil. Different microbiological methods were applied to investigate the changes and responses of bacterial communities after the DWH oil spills. By summarizing and analyzing these microbiological methods, giving recommendations and proposing some methods that have not been used, this review aims to provide constructive guidelines for microbiological studies after environmental disasters, especially those involving organic pollutants

Acclimation of Culturable Bacterial Communities under the Stresses of Different Organic Compounds

The phylogenetic diversity of bacterial communities in response to environmental disturbances such as organic pollution has been well studied, but little is known about the way in which organic contaminants influence the acclimation of functional bacteria. In the present study, tolerance assays for bacterial communities from the sediment in the Pearl River Estuary were conducted with the isolation of functional bacteria using pyrene and different estrogens as environmental stressors. Molecular ecological networks and phylogenetic trees were constructed using both 16S rRNA gene sequences of cultured bacterial strains and 16S rRNA gene-based pyrosequencing data to illustrate the successions of bacterial communities and their acclimations to the different organic compounds. A total of 111 bacterial strains exhibiting degradation and endurance capabilities in response to the pyrene estrogen-induced stress were successfully isolated and were mainly affiliated with three orders, Pseudomonadales, Vibrionales, and Rhodobacterales. Molecular ecological networks and phylogenetic trees showed various adaptive abilities of bacteria to the different organic compounds. For instance, some bacterial OTUs could be found only in particular organic compound-treated groups while some other OTUs could tolerate stresses from different organic compounds. Furthermore, the results indicated that some new phylotypes were emerged under stresses of different organic pollutions and these new phylotypes could adapt to the contaminated environments and contribute significantly to the microbial community shifts. Overall, this study demonstrated a crucial role of the community succession and the acclimation of functional bacteria in the adaptive responses to various environmental disturbances

A Preliminary Genetic Analysis of Complement 3 Gene and Schizophrenia

<div><p>Complement pathway activation was found to occur frequently in schizophrenia, and complement 3 (C3) plays a major role in this process. Previous studies have provided evidence for the possible role of C3 in the development of schizophrenia. In this study, we hypothesized that the gene encoding C3 (C3) may confer susceptibility to schizophrenia in Han Chinese. We analyzed 7 common single nucleotide polymorphisms (SNPs) of C3 in 647 schizophrenia patients and 687 healthy controls. Peripheral <i>C3</i> mRNA expression level was measured in 23 drug-naïve patients with schizophrenia and 24 controls. Two SNPs (rs1047286 and rs2250656) that deviated from Hardy-Weinberg equilibrium were excluded for further analysis. Among the remaining 5 SNPs, there was no significant difference in allele and genotype frequencies between the patient and control groups. Logistic regression analysis showed no significant SNP-gender interaction in either dominant model or recessive model. There was no significant difference in the level of peripheral <i>C3</i> expression between the drug-naïve schizophrenia patients and healthy controls. In conclusion, the results of this study do not support <i>C3</i> as a major genetic susceptibility factor in schizophrenia. Other factors in AP may have critical roles in schizophrenia and be worthy of further investigation.</p></div

Factors Correlating to the Development of Hepatitis C Virus Infection in Hemodialysis Patients—Findings Mainly from Asiatic Populations: A Systematic Review and Meta-Analysis

Hemodialysis is an effective replacement therapy for chronic renal failure patients. In recent decades, the number of hemodialysis patients has grown rapidly and some measures for preventing blood-borne diseases have been implemented, but hepatitis C virus (HCV) infection remains a significant problem. The meta-analysis published in 2009 on HCV infection-related factors was based on localized study objects, and some additional studies have been published since 2009; however, the contribution of these factors remains under dispute. Our study pooled the odds ratios (ORs) or mean standard deviations (MDs) with 95% confidence intervals (CIs) and analyzed sensitivity using Review Manager 5.1 software (5.1 version Copenhagen: The Nordic Cochrane Centre; 2011) by searching data in the PubMed, Elsevier, Springer, Wiley, and EBSCO databases. Spearman correlation analysis was performed using the SPSS package. In our meta-analysis, 1715 HCV-infected hemodialysis patients and 7093 non-HCV-infected hemodialysis patients from 44 studies were analyzed. The pooled ORs with 95% CIs were: histories of blood transfusion, 4.30 (3.11, 5.96); weekly hemodialysis times &gt; 2, 6.00 (3.25, 11.06); kidney transplantation, 5.80 (3.95, 8.52); hemodialysis units &gt; 2, 6.90 (2.42, 19.68); shared hemodialysis devices, 5.00 (2.35, 10.65); and drug addiction, 4.73 (1.54, 14.47). The pooled MDs with 95% CIs were duration of hemodialysis (months) 27.48 (21.67, 33.30). There was a positive correlation between duration of hemodialysis and the HCV infection rate (p &lt; 0.01). Hemodialysis patients, especially from Asia, with shared hemodialysis devices, hemodialysis units &gt; 2, blood transfusion, kidney transplantation, and drug addiction were at increased risk of HCV infection. The HCV infection rate increased with the duration of hemodialysis. High-risk hemodialysis patients should be monitored and receive timely screening

Comparison of genotype and allele frequencies of 5 <i>C3</i> SNPs in 647 schizophrenia patients and 687 healthy controls.

<p>^a<i>P</i> values were not adjusted by Bonferroni correction</p><p>^b<i>P</i> values were calculated for Hardy-Weinberg equilibrium</p><p>^c<i>P</i> values were adjusted by Bonferroni correction.</p><p>Comparison of genotype and allele frequencies of 5 <i>C3</i> SNPs in 647 schizophrenia patients and 687 healthy controls.</p

Logistic regression analysis of <i>C3</i> SNPs×gender interaction in dominant model.

<p>^a<i>P</i> values were not adjusted by Bonferroni correction</p><p>^b<i>P</i> values were adjusted by Bonferroni correction.</p><p>Logistic regression analysis of <i>C3</i> SNPs×gender interaction in dominant model.</p