RAGE gene three polymorphisms with Crohn's disease susceptibility in Chinese Han population

AIM: To investigate the association of three polymorphisms in the receptor for advanced glycation end product (RAGE) gene with Crohn’s disease (CD) risk in a Chinese population.

Designer TAL Effectors Induce Disease Susceptibility and Resistance to Xanthomonas oryzae pv. Oryzae in Rice

TAL （transcription activator-like） effectors from Xanthomonas bacteria activate the cognate host genes, leading to disease susceptibility or resistance dependent on the genetic context of host target genes. The modular nature and DNA recognition code of TAL effectors enable custom-engineering of designer TAL effectors （dTALE） for gene activation. However, the feasibility of dTALEs as transcription activators for gene functional analysis has not been demonstrated. Here, we report the use of dTALEs, as expressed and delivered by the pathogenic Xanthomonas oryzae pv. oryzae （Xoo）, in revealing the new function of two previously identified disease-related genes and the potential of one developmental gene for disease susceptibility in rice/Xoo interactions. The dTALE gene dTALE-xa27, designed to target the susceptible allele of the resistance gene Xa27, elicited a resistant reaction in the otherwise susceptible rice cultivar IR24. Four dTALE genes were made to induce the four annotated Xa27 homologous genes in rice cultivar Nipponbare, but none of the four induced Xa27-1ike genes conferred resistance to the dTALE-containing Xoo strains. A dTALE gene was also generated to activate the recessive resistance gene xa13, an allele of the disease-susceptibility gene Os8N3 （also named Xa13 or OsSWEETll, a member of sucrose efflux transporter SWEET gene family）. The induction of xa13 by the dTALE rendered the resistant rice IRBB13 （xa13/xa13） susceptible to Xoo. Finally, OsSWEET12, an as-yet uncharacterized SWEET gene with no corresponding naturally occurring TAL effector identified, conferred susceptibility to the Xoo strains expressing the corresponding dTALE genes. Our results demonstrate that dTALEs can be delivered through the bacterial secretion system to activate genes of interest for functional analysis in plants.

Inflammatory bowel disease and celiac disease:Overlaps and differences

Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.

Are women more susceptible to ischemic heart disease compared to men? A literature overview

Ischemic heart disease(IHD) is known as the leading cause of death in both genders. Moreover, significant sex differences were found in cardiac structure, function, pathophysiology, presentation, treatment, and outcome of IHD. The presence of unique risk factors such as exposure to menarche and pregnancy, more anemia, hypertension, and autoimmune disorders in women have recently received attention. Ischemic symptoms are more indefinite and vague in women compared to men as well as a delay in diagnosis, treatment, and worse outcomes compared to men. Women usually receive less evidence-based treatment and intervention, with less concern on preventive health care. Clinical trials primarily recruit male patients and women are underrepresented. Without any correct diagnosis, treatment, and prevention, these problems are accumulated and continue up to older age. Accordingly, with the belief of longer life in women and the increased prevalence of IHD with aging, it will become an important public health problem and concern in the future. This narrative review aimed to provide an overview of some of the differences between the two genders in terms of IHD with paying more attention to practical points.

Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pyloriassociated gastric low-grade marginal zone B-cell lymphoma of MALT type

AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.

Polymorphisms of some cytokines and chronic hepatitis B and C virus infection

AIM： To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus （HBV） and hepatitis C virus （HCV） infection. METHODS： Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked imrnunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction （PCR）. Hepatocellular injury, as revealed by alanine aminotransferase （ALT） and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-γ＋874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR.RESULTS： Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele. CONCLUSION： These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage.

Genetic counseling in post-genomic era: Don't pretend to know the meaning of a gene mutation if you don't know

In this post-genomic era, more and more susceptibility loci of many possible genetic diseases are published. As our knowledge about these susceptibility loci is limited and partial, we should be very careful and responsible when patients seek genetic counseling about these possible genetic diseases. We should apply Confucius' s principle about knowledge and information to genetic conseling, and tell the truth to our patients about what we know and what we do not know. Like many other cancers, breast cancer is a very complicated, multifactorial disease; genetic factors, lifestyles and eating habits, environmental factors, and viral infections might be involved in breast cancer; hence, it is difficult to figure out the real etiology of breast cancer. It is not crystal clear that a person who carries mutations of the breast cancer 1, early onset and/or breast cancer 2, early onset genes would eventually get breast cancer in her/his lifetime. No person should undergo a preventive double mastectomy, unless we know the etiology of breast cancer someday.

Bright artificial light at night is associated with increased body mass,poor reproductive success and compromised disease tolerance in Australian budgerigars(Melopsittacus undulatus)

Artificial light at night(ALAN)can cause circadian disruption and result in adverse behavioral and ecologi­cal effects in free-living birds,but studies on captive pet birds as companion animals have been infrequent.We studied the effects of exposure to bright ALAN on body mass,melatonin sulfate levels,reproduction and dis­ease severity in Australian budgerigars(Melopsittacus undulatus)kept in captivity.During the experiment,birds were kept under outdoor temperature,humidity and natural photoperiod from September to December.A total of 48 birds were equally split into 4 groups(6 mating pairs each)and concurrently exposed to ALAN of 200 lux with different duration(0,30,60 and 90 min).Monthly observations were recorded for all dependent parame­ters.ALAN exposure increased mass gain and suppressed melatonin levels in a dose-dependent manner,espe­cially during December.In addition,ALAN exposure in all duration groups decreased egg production and re­duced hatchability from 61%±14%in the ALAN-unexposed control group to 0%in the ALAN-exposed birds.Disease severity was also found to increase in line with the duration of ALAN exposure.In captive M.undu­latus,ALAN exposure was demonstrated to affect photoperiodic regulation with subsequent excess mass gain and reproduction impairment,and increased susceptibility to infections plausibly through duration dose-depen­dent suppression of melatonin.To the best of our knowledge,this is the first study to demonstrate a possible as­sociation between acute bright ALAN of increasing duration and both natural development of infections as well as reproductive cessation in captive birds.Our findings could be used to improve breeding conditions of captive birds.

An Overview of Genome-Wide Association Studies in Alzheimer＇s Disease

Genome-wide association studies（GWASs）have revealed a plethora of putative susceptibility genes for Alzheimer＇s disease（AD）. With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD.

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.

Correlation of pulmonary functions of COPD patients to those of their first-degree children

Objective To assess the risk factors correlating to the likelihood for airflow obstruction among first degree children of chronic obstructive pulmonary disease (COPD) patients and whether familial aggregation of pulmonary function abnormality exists Methods Fifty nine smokers with COPD and 28 smokers without COPD as control and all their children available were recruited into the study Their history was recorded and a binary logistic regression analysis was carried out to ascertain the effects of their relationship to a proband with COPD, when other potential risk factors were controlled Results Children with COPD probands showed increased risk of FEV1 below the 70% predicted (OR=1 987) after accounting for the effects of smoking, sex and clinical symptoms The lower the pulmonary function of the COPD proband, the higher the risk to their children for FEV1 below the 70% predicted Conclusions Our finding demonstrates the presence of a household aggregation inclination of COPD and pulmonary function impairment Genetic factors might act as the basis of the familial aggregation

Opposing roles of plant laticifer cells in the resistance to insect herbivores and fungal pathogens

More than 12,000 plant species(ca.10%of flowering plants)exude latex when their tissues are injured.Latex is produced and stored in specialized cells named“laticifers”.Laticifers form a tubing system composed of rows of elongated cells that branch and create an internal network encompassing the entire plant.Laticifers constitute a recent evolutionary achievement in ecophysiological adaptation to specific natural environments;however,their fitness benefit to the plant still remains to be proven.The identification of Euphorbia lathyris mutants(pil mutants)deficient in laticifer cells or latex metabolism,and therefore compromised in latex production,allowed us to test the importance of laticifers in pest resistance.We provided genetic evidence indicating that laticifers represent a cellular adaptation for an essential defense strategy to fend off arthropod herbivores with different feeding habits,such as Spodoptera exigua and Tetranychus urticae.In marked contrast,we also discovered that a lack of laticifer cells causes complete resistance to the fungal pathogen Botrytis cinerea.Thereafter,a latex-derived factor required for conidia germination on the leaf surface was identified.This factor promoted disease susceptibility enhancement even in the non-latex-bearing plant Arabidopsis.We speculate on the role of laticifers in the coevolutionary arms race between plants and their enemies.

Impact of mycotoxin on immune response and consequences for pig health

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities, especially cereals. Due to their high consumption of cereals, pigs are exposed to these toxins. In the European Union, regulations and/or recommendations exist in pig feed for aflatoxins, ochratoxin A, fumonisins,zearalenone, and trichothecenes, deoxynivalenol and T-2 toxin. These mycotoxins have different toxic effects, but they all target the immune system. They have immunostimulatory or immunosuppressive effects depending on the toxin, the concentration and the parameter investigated. The immune system is primarily responsible for defense against invading organisms. The consequences of the ingestion of mycotoxin-contaminated feed are an increased susceptibility to infectious diseases, a reactivation of chronic infection and a decreased vaccine efficacy. In this review we summarized the data available on the effect of mycotoxins on the immune system and the consequences for pig health.