Diversity of Actinobacterial community in saline sediments from Yunnan and Xinjiang, China

The diversity and community structures of actinobacteria in saline sediments collected from Yunnan and Xinjiang Provinces, China, were investigated with cultivation and 16S rRNA gene analysis. A total of 163 actinobacterial isolates were obtained, and they were affiliated with the order Actinomycetales (distributed into five suborders: Streptosporangineae, Micrococcineae, Streptomycineae, Pseudonocardineae, and Glycomycineae). A total of 748 actinobacterial 16S rRNA gene clones were examined, and they could be classified into Actinomycetales, Acidimicrobiales, and unclassified actinobacteria. The Actinomycetales sequences were distributed into nine suborders: Streptosporangineae, Glycomycineae, Micromonosporineae, Pseudonocardineae, Corynebacterineae, Frankineae, Propionibacterineae, Streptomycineae, and Micrococcineae. The unclassified actinobacteria contained three new clusters at the level of subclass or order. Our 16S rRNA gene phylogenetic data indicated that actinobacterial communities were very diverse in the investigated saline sediments (salinity 0.4–11.6%) and some actinobacterial members may be halotolerant or halophilic. The actinobacterial community structures in the saline sediments were different from those in marine and freshwater environments. Our data have implications for a better understanding of the distribution of Actinobacteria in saline environments. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Association of Two CETP Polymorphisms With HDL Levels in the Chinese Obese Population

The association of two cholesterol ester transfer protein (CETP) polymorphisms, D442G and TAQIB (B1→B2), with high‐density lipoprotein (HDL) levels in 932 Chinese obese individuals (BMI ≥ 27) was investigated in comparison with normal controls (BMI ≤ 24). Independent association was demonstrated for TAQIB minor allele B2 and CETP442 minor allele G with elevated HDL levels. The CETP D442G polymorphism was associated with a much greater increase in HDL levels in subjects with BMI exceeding 27 kg/m² (+5.42 mg/dl, P = 0.0007) compared to normal controls (+1.97 mg/dl, P = 0.275), and the increase in HDL reached the highest level among subjects with BMI exceeding 30 kg/m² (+6.80 mg/dl, P = 0.016). TAQIB showed significant association with HDL levels only in normal BMI subgroup (P = 0.0017). TAQIB significantly interacted with serum triglyceride (TG) on modulating HDL levels (P = 0.027). The TAQIB–TG interaction effect remained marginally significant after controlling for BMI (P = 0.057). We conclude that D442G polymorphism is associated with more HDL elevation in obesity. TAQIB interacts with serum TG on modulating HDL levels, and the interaction is partly independent of BMI.     

Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia

Sex-related brain injury was evaluated after unilateral hypoxia-ischaemia (HI) in C57/BL6 mice on postnatal day (P) 5, 9, 21 or 60, corresponding developmentally to premature, term, juvenile and adult human brains. There was no sex difference in brain injury when the insult was severe, as evaluated by pathological scoring or tissue loss, but when the insult was moderate, adult (P60) females displayed less injury. In the immature (P9) male brains, neurones displayed a more pronounced translocation of apoptosis-inducing factor (AIF) (loss of AIF from the mitochondrial fraction and increase in nuclear AIF) after HI, whereas the female brain neurones displayed a stronger activation of caspase 3 (more pronounced loss of pro-caspase 3, increase in cleaved caspase 3 and increase in caspase 3 enzymatic activity). Two other mechanisms of injury, peroxynitrite-induced formation of nitrotyrosine and autophagy, were no different between males and females at P9. These data show that the CNS is more resistant to HI in adult females compared with males, whereas no sex differences were found in the extent of injury in neonatal mice. However, critical sex-dependent differences were demonstrated in vivo with regard to cellular, apoptosis-related mechanisms.     

A three-dimensional collagen-fiber network model of the extracellular matrix for the simulation of the mechanical behaviors and micro structures

The extracellular matrix (ECM) provides structural and biochemical support to cells and tissues, which is a critical factor for modulating cell dynamic behavior and intercellular communication. In order to further understand the mechanisms of the interactive relationship between cell and the ECM, we developed a three-dimensional (3D) collagen-fiber network model to simulate the micro structure and mechanical behaviors of the ECM and studied the stress–strain relationship as well as the deformation of the ECM under tension. In the model, the collagen-fiber network consists of abundant random distributed collagen fibers and some crosslinks, in which each fiber is modeled as an elastic beam and a crosslink is modeled as a linear spring with tensile limit, it means crosslinks will fail while the tensile forces exceed the limit of spring. With the given parameters of the beam and the spring, the simulated tensile stress–strain relation of the ECM highly matches the experimental results including damaged and failed behaviors. Moreover, by applying the maximal inscribed sphere method, we measured the size distribution of pores in the fiber network and learned the variation of the distribution with deformation. We also defined the alignment of the collagen-fibers to depict the orientation of fibers in the ECM quantitatively. By the study of changes of the alignment and the damaged crosslinks against the tensile strain, this paper reveals the comprehensive mechanisms of four stages of ‘toe’, ‘linear’, ‘damage’ and ‘failure’ in the tensile stress–strain relation of the ECM which can provide further insight in the study of cell-ECM interaction.     

Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β

Homeostasis and wound healing rely on stem cells (SCs) whose activity and directed migration are often governed by Wnt signaling. In dissecting how this pathway integrates with the necessary downstream cytoskeletal dynamics, we discovered that GSK3β, a kinase inhibited by Wnt signaling, directly phosphorylates ACF7, a > 500 kDa microtubule-actin crosslinking protein abundant in hair follicle stem cells (HF-SCs). We map ACF7's GSK3β sites to the microtubule-binding domain and show that phosphorylation uncouples ACF7 from microtubules. Phosphorylation-refractile ACF7 rescues overall microtubule architecture, but phosphorylation-constitutive mutants do not. Neither mutant rescues polarized movement, revealing that phospho-regulation must be dynamic. This circuitry is physiologically relevant and depends upon polarized GSK3β inhibition at the migrating front of SCs/progeny streaming from HFs during wound repair. Moreover, only ACF7 and not GSKβ-refractile-ACF7 restore polarized microtubule-growth and SC-migration to ACF7 null skin. Our findings provide insights into how this conserved spectraplakin integrates signaling, cytoskeletal dynamics, and polarized locomotion of somatic SCs.     

Oxidative Stress in the Liver of Mice Caused by Intraperitoneal Injection with Lanthanoides

In order to study the mechanisms underlying the effects of lanthanoid (Ln) on the liver, ICR mice were injected with LaCl₃, CeCl₃, and NdCl₃ at a dose of 20 mg/kg BW into the abdominal cavity daily for 14 days. We then examined oxidative stress-mediated responses in the liver. The increase of lipid peroxide in the liver produced by Ln suggested an oxidative attack that was activated by a reduction of antioxidative defense mechanisms as measured by analyzing the activities of superoxide dismutase, catalase, and ascorbate peroxidase, as well as antioxidant levels such as glutathione and ascorbic acid, which were greatest in Ce³⁺ treatment, medium in Nd³⁺, and least in La³⁺. Our results also implied that the oxidative stress in the liver caused by Ln likely is Ce³⁺ > Nd³⁺ >La³⁺, but the mechanisms need to be further studied in future.     

Ca(V)1.2 channel N-terminal splice variants modulate functional surface expression in resistance size artery smooth muscle cells

Voltage-dependent Ca(2+) (Ca(V)1.2) channels are the primary Ca(2+) influx pathway in arterial smooth muscle cells and are essential for contractility regulation by a variety of stimuli, including intravascular pressure. Arterial smooth muscle cell Ca(V)1.2 mRNA is alternatively spliced at exon 1 (e1), generating e1b or e1c variants, with e1c exhibiting relatively smooth muscle-specific expression in the cardiovascular system. Here, we examined physiological functions of Ca(V)1.2e1 variants and tested the hypothesis that targeting Ca(V)1.2e1 modulates resistance size cerebral artery contractility. Custom antibodies that selectively recognize Ca(V)1.2 channel proteins containing sequences encoded by either e1b (Ca(V)1.2e1b) or e1c (Ca(V)1.2e1c) both detected Ca(V)1.2 in rat and human cerebral arteries. shRNA targeting e1b or e1c reduced expression of that Ca(V)1.2 variant, induced compensatory up-regulation of the other variant, decreased total Ca(V)1.2, and reduced intravascular pressure- and depolarization-induced vasoconstriction. Ca(V)1.2e1b and Ca(V)1.2e1c knockdown reduced whole cell Ca(V)1.2 currents, with Ca(V)1.2e1c knockdown most effectively reducing total Ca(V)1.2 and inducing the largest vasodilation. Knockdown of α(2)δ-1, a Ca(V)1.2 auxiliary subunit, reduced surface expression of both Ca(V)1.2e1 variants, inhibiting Ca(V)1.2e1c more than Ca(V)1.2e1b. e1b or e1c overexpression reduced Ca(V)1.2 surface expression and whole cell currents, leading to vasodilation, with e1c overexpression inducing the largest effect. In summary, data indicate that arterial smooth muscle cells express Ca(V)1.2 channels containing e1b or e1c-encoded N termini that contribute to Ca(V)1.2 surface expression, α(2)δ-1 preferentially traffics the Ca(V)1.2e1c variant to the plasma membrane, and targeting of Ca(V)1.2e1 message or the Ca(V)1.2 channel proximal N terminus induces vasodilation.     

Fluid-structure interaction based study on the physiological factors affecting the behaviors of stented and non-stented thoracic aortic aneurysms

Endovascular aneurysm repair (EVAR) is considered as a promising alternative technique for the treatment of aortic aneurysm. However, complications often occur after EVAR. In this paper, the influence of the physiological factors on the biomechanical behaviors of stented and non-stented thoracic aortic aneurysm (TAA) were presented. Representative TAA models with different intraluminal thrombus (ILT) volume before and after stent-graft (SG) implantation were built. Fluid-structure interaction effect was taken into account. The relative sliding between the SG wall and the aortic wall was allowed. Results showed that the cardiac cycle and ILT volume should be given much more consideration than previously thought in future investigations on TAA compliance. The time-averaged longitudinal displacement of SG necks were not uniformly distributed along circumferential direction of the aortic wall. Drag force increased with the increase of the cardiac cycle and decreased with the decrease of ILT volume. Computational results of TAA wall stress, sac and lumen pressure indicated that patient with faster heart rate might be at great risk of aneurysm rupture. The stress absorption effect of the SG was influenced by both ILT and cardiac cycle, which was also found to have strong impact on flow pattern. We believe that this study will bring new insights into further researches on the relevant issues and provide mechanics-based implications for clinical management of EVAR for TAA patient.     

NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation,invasion and cell cycle of gastric cancer cells

N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1–NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.