Association of COL1A1 rs180012 SNP and Fibromyalgia Suggests the Implication of Collagen Structure in Musculoskeletal Pain

Fibromyalgia (FM) is a complex, chronic condition, which causes widespread musculoskeletal pain, fatigue and a variety of other symptoms. Many polymorphisms related to neuroendocrine system function as the ApoE isoforms, Val158Met polymorphism in COMT, as well as a 44 bp deletion located in 5-HTTLPR, have been studied. Other polymorphisms have been related to inflammatory response such as the 70 bp VNTR in IL-4 or to citokine levels. Furthermore, some studies focused on finding out new FM related SNPs, have been performed by genome wide association scan (GWAS). The target of this work was to study a possible linkage of a collagen type I polymorphism (COL1A1 rs180012 SNP) affecting bone mineralization, with fibromyalgia. Results obtained show a clear association of ss homozygous genotype with FM patients no dependent on bone mineralization.

Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution

AIM： To establish the most common vacA alleles in Helicobacter pylori （ H pylon） strains isolated from Chilean patients and its relationship with gastritis and gastroduodenal ulcers, METHODS： Two hundred and forty five Hpyloriclinical isolates were obtained from 79 biopsies from Chilean infected patients suffedng from gastrointestinal diseases. An average of 2-3 strains per patient was isolated and the vac4 genotype was analyzed by PCR and 3% agarose electrophoresis. Some genotypes were checked by DNA sequencing. RESULTS： The most prevalent vacA genotype in Chilean patients was slb ml （76%）, followed by sla ml （21%）. In oontrast, the s2 m2 genotype was scarcely represented （3%）. The slb ml genotype was found most frequently linked to gastropathies （P〈0.05） rather than ulcers. Ulcers were found more commonly in male and older patients. Curiously, patents IMng in dties located North and far South of Santiago, thecapital and largest Chilean city, carried almost exclusively strains with the slb ml genotype. In contrast, patients from Santiago and cities located South of Santiago carded strains with either one or both sla ml and slb ml genotypes. Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that Chilean s2 sequence was identical to those of Australian, American, and Colombian strains but quite different from those of Alaska and India. CONCLUSION： Differences in geographic distribution of the s and m vacA alleles in Chile and a relationship of slb ml genotype with gastritis were found. Sequence data in part support a hispanic origin for the vacA genotype. Asymmetric distribution of genotypes slb ml and s2 m2 recedes H Pyloristrain distribution in Spain and Portugal.

Role of Salmonella enterica exposure in Chilean Crohn's disease patients

AIM:To study the association between exposure toSalmonella enterica(SE)and Crohn’s disease(CD)and its clinical implications in Chilean patients.METHODS:Ninety-four unrelated Chilean CD patients from CAREI(Active Cohort Registry of Inflammatory Bowel Disease)presenting to a single inflammatory bowel disease(IBD)unit of a University Hospital were prospectively included in this study.A complete clinical evaluation,including smoking history,was performed at the initial visit,and all the important data of clinical evolution of CD were obtained.Blood samples from these CD patients and 88 healthy sex-and agematched control subjects were analyzed for exposure to SE and for their NOD2/CARD15 gene status using the presence of anti-Salmonella lipopolysaccharide antibodies[immunoglobulin-G type(IgG)]and polymerase chain reaction(PCR),respectively.We also evaluated exposure to SE in 90 sex-and age-matched patients without CD,but with known smoking status(30 smokers,30 non-smokers,and 30 former smokers).RESULTS:CD patients comprised 54 females and 40males,aged 35.5±15.2 years at diagnosis with a mean follow-up of 9.0±6.8 years.CD was inflammatory in 59 patients(62.7%),stricturing in 24(25.5%)and penetrating in 15(15.5%).Thirty cases(31.9%)had lesions in the ileum,29(30.8%)had ileocolonic lesions,32(34.0%)had colonic lesions and 23(24.4%)had perianal disease.Sixteen CD patients(17%)were exposed to SE compared to 15(17%)of 88 healthy control subjects(P=0.8).Thirty-one CD patients(32.9%)were smokers,and 7(7.4%)were former smokers at diagnosis.In the group exposed to SE,10 of 16 patients(62.5%)were active smokers compared to 21 of 78 patients(26.9%)in the unexposed group(P=0.01).On the other hand,10 of 31 smoking patients(32%)were exposed to SE compared to 5 of 56 nonsmoking patients(9%),and one of the seven former smokers(14%)(P=0.01).In the group of 90 patients without CD,but whose smoking status was known,there was no differ-ence in exposure to SE[3 of 30 smokers(10%),5 of30 non-smokers(16%),and 5 of 30 former smokers(16%);P=0.6].There were no differences in disease severity between CD patients with and those without anti-SE IgG antibodies,estimated as the appearance of stricturing[2(12.5%)vs 22(28.2%);P=0.2]or penetrating lesions[2(12.5%)vs 13(16.6%);P=1.0];or the need for immunosuppressants[11(68.7%)vs 55(70.5%);P=1.0],anti-tumor necrosis factor therapy[1(6.2%)vs 7(8.9%);P=1.0],hospitalization[13(81.2%)vs 58(74.3%);P=0.7],or surgery[3(18.7%)vs 12(15.3%);P=0.3),respectively].No other factors were associated with SE,including NOD2/CARD15 gene status.Seventeen CD patients(18%)had at least one mutation of the NOD2/CARD15 gene.CONCLUSION:Our study found no association between exposure to SE and CD.We observed a positive correlation between SE exposure and cigarette smoking in Chilean patients with CD,but not with disease severity.

Improvement of transfection with reprogramming factors in urine-derived cells

Human-induced pluripotent stem cells(iPSCs)are an accessible source of adult-derived,patient-specific pluripotent stem cells for use in basic research,drug discovery,disease modeling,and stem cell therapy.Improving the accessibility of methods to obtain iPSCs regardless of the cell source can enhance their clinical application.Therefore,our purpose is to report a simple protocol to obtain iPS-like cells from urine-derived renal epithelial cells(RECs)using different extracellular matrices and transfection reagents.In this study,we began by culturing urine-derived cells from healthy donors to establish a primary culture of renal epithelial cells,followed by their characterization.Subsequently,we generated iPS-like cells by transfecting renal epithelial cells(RECs)with vectors expressing Oct4,Sox2,L-Myc,Lin-28,and Klf4,and we compared the efficacy of different extracellular matrices and transfection reagents.The resultant iPS-like cells showed a human embryonic stem cell-like morphology and expressed the specific pluripotency markers Oct3/4,Nanog,Lin28,and Klf4.We concluded that Lipofectamine Stem Cell transfection reagent is more effective than FuGENE in obtaining iPS-like cells under the conditions tested.Moreover,the three matrices are similar in their efficiency of obtaining iPS-like cells.This report provides an experimental protocol for obtaining and generating iPS-like cells from urine samples for further cell therapy research on different human diseases.

Insights on the crosstalk between dendritic cells and helper T cells in novel genetic etiology for mendelian susceptible mycobacterial disease

Mendelian susceptibility to mycobacterial disease(MSMD)is an inherited predisposition to infections by Bacille-Calmette Guérin(BCG)vaccine or by environmental mycobacteria.The etiology of MSMD has been associated with up to nineteen different genetic mutations in interferon(IFN)-γ-related genes.1 Although mycobacteria susceptibility-associated genetic mutations are rare in the population,their diagnosis is crucial for an efficient and timely treatment.Kong et al.2 have recently described an autosomal recessive deficiency in the signal peptidase-like 2 A(SPPL2-a)as a new genetic etiology for MSMD in three patients that had suffered BCG dissemination disease.

The transcriptional regulator JAZ8 interacts with the C2 protein from geminiviruses and limits the geminiviral infection in Arabidopsis

Jasmonates(JAs) are phytohormones that finely regulate critical biological processes, including plant development and defense. JASMONATE ZIM-DOMAIN(JAZ) proteins are crucial transcriptional regulators that keep JA-responsive genes in a repressed state. In the presence of JA-Ile, JAZ repressors are ubiquitinated and targeted for degradation by the ubiquitin/proteasome system,allowing the activation of downstream transcription factors and, consequently, the induction of JA-responsive genes. A growing body of evidence has shown that JA signaling is crucial in defending against plant viruses and their insect vectors. Here, we describe the interaction of C2proteins from two tomato-infecting geminiviruses from the genus Begomovirus, tomato yellow leaf curl virus(TYLCV) and tomato yellow curl Sardinia virus(TYLCSaV), with the transcriptional repressor JAZ8 from Arabidopsis thaliana and its closest orthologue in tomato, SlJAZ9. Both JAZ and C2proteins colocalize in the nucleus, forming discrete nuclear speckles. Overexpression of JAZ8did not lead to altered responses to TYLCV infection in Arabidopsis;however, knock-down of JAZ8 favors geminiviral infection. Low levels of JAZ8 likely affect the viral infection specifically,since JAZ8-silenced plants neither display obvious developmental phenotypes nor present differences in their interaction with the viral insect vector. In summary, our results show that the geminivirus-encoded C2 interacts with JAZ8 in the nucleus, and suggest that this plant protein exerts an anti-geminiviral effect.

Response to lipopolysaccharide in Octodon degus pups produces age-related sickness behavior but does not have effects in juveniles

During vertebrate development,the immune function is inefficient and is mainly controlled by innate defense.While there have been detailed studies of various aspects of innate immune function,the effects of this func­tion in the growth of vertebrates is still not well known.Similarly,there is little information regarding how ear­ly endotoxin exposure would affect juvenile phenotypes,specifically in a non-model mammal like a precocial rodent.We evaluated the response to an antigen and its cost in offspring of the rodent Octodon degus.We in­oculated pups at 4 different ages(8,15,22 and 30 days after birth)with an antigen to determine the ontogeny and costs of the response to an endotoxin.We assessed changes in body mass,body temperature,sickness be­havior and the levels of a key mediator of the inflammatory response,the cytokine interleukin-1β.We also de­termined the effects of early endotoxin exposure on the resting metabolic rate of juvenile animals(i.e.90 days after birth).The cytokine levels,body mass and body temperature were unaffected by time of inoculation and treatment.However,pups subjected to inoculation at 22 days after birth with the antigen showed reduced loco­motion.Juvenile resting metabolic rate was not affected by early endotoxin exposure.These results suggest that the magnitude of O.degus responses would not change with age.We discuss whether the lack of effect of the response on body mass or body condition is caused by environmental variables or by the precocial characteris­tics of O.degus.

THEMIS,the new kid on the block for T-cell development

Understanding T-cell development is a major goal of the immunology field and is crucial for the elucidation of the mechanisms behind self-tolerance and the occurrence of autoimmune disorders.T-cell development is a complex process that begins in the bone marrow or fetal liver,where lymphoid progenitors arise.