Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans

Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response (UPRmt), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of C. elegans are usually conserved across phyla. Thus, understanding the mechanisms of mitochondria-mediated defense responses in C. elegans may provide insights into similar mechanisms in complex organisms, including mammals.110Ysciescopuskc

Dendritic Cell Migration Is Tuned by Mechanical Stiffness of the Confining Space

The coordination of cell migration of immune cells is a critical aspect of the immune response to pathogens. Dendritic cells (DCs), the sentinels of the immune system, are exposed to complex tissue microenvironments with a wide range of stiffnesses. Recent studies have revealed the importance of mechanical cues in immune cell trafficking in confined 3D environments. However, the mechanism by which stiffness modulates the intrinsic motility of immature DCs remains poorly understood. Here, immature DCs were found to navigate confined spaces in a rapid and persistent manner, surveying a wide range when covered with compliant gels mimicking soft tissues. However, the speed and persistence time of random motility were both decreased by confinement in gels with higher stiffness, mimicking skin or diseased, fibrotic tissue. The impact of stiffness of surrounding tissue is crucial because most in vitro studies to date have been based on cellular locomotion when confined by microfabricated polydimethylsiloxane structures. Our study provides evidence for a role for environmental mechanical stiffness in the surveillance strategy of immature DCs in tissues

Conformal and Ultra Shallow Junction Formation Achieved Using a Pulsed-Laser Annealing Process Integrated With a Modified Plasma Assisted Doping Method

Recently, a shallow and conformal doping profile is required for promising 3D structured devices. In this study, we deposited the dopant phosphorus (P) using modified plasma assisted doping (PaD) followed by an annealing process to electrically activate the dopants. A rapid thermal annealing process (RTP) was the first approach tested for activation but it resulted in a deep junction ( > 35 nm). To reduce the junction depth, we tried the fiash lamp annealing process (FLP) to shorten the annealing time. We also predicted the annealing temperature by numerical thermal analysis, which reached 1,020 degrees C. However, the FLP resulted in a deep junction (similar to 30 nm), which was not shallow enough to suppress short channel effects. Since an even shorter annealing process was required to form a ultra-shallow junction, we tried the laser annealing process (LAP) as a promising alternative. The LAP, which had a power density of 0.3 J/cm(2), increased the surface temperature up to 1,100 degrees C with a shallow isothermal layer. Using the LAP, we achieved a USJ with an activated surface dopant concentration of 3.86 x 10(19) cm(-3) and a junction depth of 10 nm, which will allow further scaling-down of devices.1

Improved Surgical Technique for Heterotopic Aortic Transplantation in Mice

Transplant arteriosclerosis is the main limitation for long-term survival of solid organ transplant recipients. Animal models would provide invaluable tools to investigate the cellular and molecular mechanisms underlying the pathogenesis of transplant arteriosclerosis, as well as for studies with novel drugs and other reagents for the prevention of the disease. We have therefore developed a modified technique for aortic transplantation in mice. The central suture ligation of the recipient abdominal aorta allowed a simpler end-to-side anastomosis of a segment of the donor thoracic aorta into the infrarenal portion of the recipient abdominal aorta. Using this technique, the overall survival rate was 94%. We also observed typical aspects of chronic rejection of the aortic allografts not observed with isografts. Our new technique is relatively easy to perform and has a low incidence of thrombosis, thus being useful for studying various aspects of transplant arteriosclerosis

Clinical Efficacy of Primary Tumor Volume Measurements: Comparison of Different Primary Sites

ObjectivesThe purpose of study was to determine the clinical efficacy of primary tumor volume measurements of different primary sites in the oropharynx compared to the oral cavity.MethodsA retrospective analysis of 85 patients with oral cavity or oropharynx cancer. The tumor area was manually outlined from axial magnetic resonance (MR) series. The software calculated the tumor volumes, automatically. The values of the primary tumor volumes were then subdivided into separate groups (≤3,500 mm3, >3,500 mm3).ResultsThe prognostic indicators were the cT and cN (oral cavity); age, primary site, cT, cN, and primary tumor volume (oropharynx) on the univariate analysis. There was no significant prognostic factor for oral cavity cancer on the multivariate analysis. Primary site, cN, and primary tumor volume were independent prognostic indicators for oropharynx cancer by multivariate analysis.ConclusionPrimary tumor volume measurement is a reliable way to stratify outcome, and make up for the weak points in the American Joint Committee on Cancer staging system with oropharynx cancer

An mRNA-specific tRNAi carrier eIF2A plays a pivotal role in cell proliferation under stress conditions: Stress-resistant translation of c-Src mRNA is mediated by eIF2A

c-Src, a non-receptor protein tyrosine kinase, activates NF-��B and STAT3, which in turn triggers the transcription of anti-apoptosis- and cell cycle-related genes. c-Src protein regulates cell proliferation, cell motility and programmed cell death. And the elevated level of activated c-Src protein is related with solid tumor generation. Translation of c-Src mRNA is directed by an IRES element which mediates persistent translation under stress conditions when translation of most mRNAs is inhibited by a phosphorylation of the alpha subunit of eIF2 carrying the initiator tRNA (tRNAi) to 40S ribosomal subunit under normal conditions. The molecular basis of the stress-resistant translation of c-Src mRNA remained to be elucidated. Here, we report that eIF2A, an alternative tRNAi carrier, is responsible for the stress-resistant translation of c-Src mRNA. eIF2A facilitates tRNAi loading onto the 40S ribosomal subunit in a c-Src mRNAdependent manner. And a direct interaction between eIF2A and a stem-loop structure (SL I) in the c-Src IRES is required for the c-Src IRES-dependent translation under stress conditions but not under normal conditions. Finally, we showed that the eIF2Adependent translation of c-Src mRNA plays a pivotal role in cell proliferation under stress conditions. ? The Author(s) 2016.115sciescopu

The role of Qa-2, the functional homolog of HLA-G, in a Behcet's disease-like mouse model induced by the herpes virus simplex

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the HLA-G molecule is a genetic risk factor for Behcet's disease (BD). In this study, we evaluated the level of Qa-2, a murine nonclassical class I MHC molecule and possible functional homolog of HLA-G, to determine if it was associated with various symptoms of BD-like mice. In addition, we investigated siRNA (small interfering RNA) treatment to determine if it inhibited Qa-2 expression, thereby changing the symptoms of mice.</p> <p>Methods</p> <p>RNA interference (RNAi) and vector transfection were employed to manipulate gene expression <it>in vivo </it>in mice. siRNA (small interfering RNA) or Qa-2 expression vector was applied to inhibit or up-regulate Qa-2 expression, respectively.</p> <p>Results</p> <p>The Qa-2 levels in granulocytes were lower in BD-like mice than in normal controls. The silencing of Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times at 3-day intervals) specifically reduced the Qa-2 levels and worsened the BD-like symptoms.</p> <p>Conclusions</p> <p>Silencing Qa-2 by injecting siRNA into mice resulted in deterioration of symptoms in BD-like mice.</p

Isolation and characterization of differentially expressed genes in the mycelium and fruit body of Pleurotus ostreatus

The fruiting body of one of the most widely cultivated mushrooms, the oyster mushroom (Pleurotus ostreatus) is highly interesting, both commercially and scientifically. In the present study, we performed comparative proteomic profiling of P. ostreatus at two unique developmental stages; mycelium and fruit body, using two-dimensional gel electrophoresis (2-DE). Seven hundred fourteen (714) spots were detected and 29 spots (showing a high level of difference in their expressions) were identified by tandem mass spectrometry and basic local alignment search tool (BLAST) searching of an expressed sequence tag (EST) database of P. ostreatus. Among them, six proteins (putative fatty acid oxygenase, heat shock sks2, PriA homologue, Ap-1 like transcription factor YAP7, mung bean seed albumin, and C2H2 Zinc finger domain protein) and one protein (peroxisomal biogenesis factor 6) showed increased expression levels at the fruiting process and the mycelial stage, respectively. Through reverse transcriptase-polymerase chain reaction analysis, priA homologue and AP-1 like transcription factor yap7 showed gradually increased expression from mycelia to fruit body, whereas putative fatty acid oxygenase and heat shock protein sks2 were expressed only in the fruit body. These results provide useful information for future studies of mushroom development of P. ostreatus.Keywords: Developmental stage, mushroom fruiting, Pleurotus ostreatus, protein, two-dimensional gel electrophoresisAfrican Journal of Biotechnology Vol. 12(24), pp. 3790-379