Correlation between a single nucleotide polymorphism (G/T at nt –88) in the Mx1 gene promoter and the response to interferon therapy for hepatitis C virus in Egyptian patients

Interferon used in the treatment of hepatitis C virus (HCV) patients stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene- 1 (Mx1). Mx1 gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promotor region that affect the expression of Mx 1 protein and was suggested to be associated with the response of HCV. In this study, we assessed the relation between the SNP in the Mx1 gene and the responsiveness of Egyptian HCV patients to pegylated interferon and ribavirin treatment along with other host-related and virus-related predictors of treatment outcome. We genotyped the biallelic G/T SNP in the promoter region of Mx1 gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 42 interferon treatment-naïve Egyptian patients that were treated with pegylated interferon and ribavirin. We found that Mx1 nt-88 SNP is not significantly correlated to achieving sustained virological response (SVR) after pegylated interferon alpha and ribavirin combined treatment. We conclude that Mx1 gene polymorphism at codon nt-88 cannot be considered as biological marker to potentially identify responders and non-responders of HCV patients to achieve a sustained virological response to treatment with interferon (IFN) in combination with ribavirin.Key words: Hepatitis C virus (HCV), interferon (IFN), myxovirus resistance protein (Mx1 protein), myxovirus resistance gene-1 (Mx1 gene), single nucleotide polymorphism (SNP)

Severe vitamin D deficiency in 6 Canadian First Nation formula-fed infants

Background. Rickets was first described in the 17th century and vitamin D deficiency was recognized as the underlying cause in the early 1900s. Despite this long history, vitamin D deficiency remains a significant health concern. Currently, vitamin D supplementation is recommended in Canada for breast fed infants. There are no recommendations for supplementation in formula-fed infants. Objective. The objective of this report is to bring attention to the risk of severe vitamin D deficiency in high risk, formula fed infants. Design. A retrospective chart review was used to create this clinical case series. Results. Severe vitamin D deficiency was diagnosed in six formula-fed infants over a two-and-a-half year period. All six infants presented with seizures and they resided in First Nation communities located at latitude 54 in the province of Manitoba. While these infants had several risk factors for vitamin D deficiency, they were all receiving cow's milk based formula supplemented with 400 IU/L of vitamin D. Conclusion. This report suggests that current practice with regards to vitamin D supplementation may be inadequate, especially for high-risk infants. Health care professionals providing service to infants in a similar situation should be aware of this preventable condition. Hopefully this would contribute to its prevention, diagnosis and management

The risk of subjective symptoms in mobile phone users in Poland – An epidemiological study

Objectives: To assess the type and incidence of subjective symptoms related to the use of mobile phones in Polish users. Material and Methods: The study was conducted in 2005 using a questionnaire survey. Although it has been quite a long time, up to now, no such data have been published for Poland. The questionnaire consisted of 53 questions concerning sex, age, education, general health, characteristics of a mobile phone (hand-held, loud-speaking unit) as well as the habits associated with its use (frequency and duration of calls, text messages, etc.) and complaints associated with using a mobile phone. Results: As many as 1800 questionnaires were sent. The response was obtained from 587 subjects aged 32.6±11.3 (48.9% women, 51.1% men); the age did not differ significantly between men and women. The subjects owned a cell phone for an average of 3 years. Majority of the respondents used the phone intensively, i.e. daily (74%) or almost daily (20%). Headaches were reported significantly more often by the people who talked frequently and long in comparison with other users (63.2% of the subjects, p = 0.0029), just like the symptoms of fatigue (45%, p = 0.013). Also, the feeling of warmth around the ear and directly to the auricle was reported significantly more frequently by the intensive mobile phone users, compared with other mobile phone users (47.3%, p = 0.00004 vs. 44.6%, p = 0.00063, respectively). Most symptoms appeared during or immediately after a call and disappeared within 2 h after the call. Continuous headache, persisting for longer than 6 h since the end of a call, was reported by 26% of the subjects. Conclusions: Our results show that the mobile phone users may experience subjective symptoms, the intensity of which depends on the intensity of use of mobile phones

The Future of Biologic Agents in the Treatment of Sjögren’s Syndrome

The gain in knowledge regarding the cellular mechanisms of T and B lymphocyte activity in the pathogenesis of Sjögren’s syndrome (SS) and the current availability of various biological agents (anti-TNF-α, IFN- α, anti-CD20, and anti-CD22) have resulted in new strategies for therapeutic intervention. In SS, various phase I and II studies have been performed to evaluate these new strategies. Currently, B cell-directed therapies seem to be more promising than T cell-related therapies. However, large, randomized, placebo-controlled clinical trials are needed to confirm the promising results of these early studies. When performing these trials, special attention has to be paid to prevent the occasional occurrence of the severe side effects

Estrogen-like activity of seafood related to environmental chemical contaminants

BACKGROUND: A wide variety of environmental pollutants occur in surface waters, including estuarine and marine waters. Many of these contaminants are recognised as endocrine disrupting chemicals (EDCs) which can adversely affect the male and female reproductive system by binding the estrogen receptor and exhibiting hormone-like activities. In this study the estrogenic activity of extracts of edible marine organisms for human consumption from the Mediterranean Sea was assayed. METHODS: Marine organisms were collected in two different areas of the Mediterranean Sea. The estrogenic activity of tissues was assessed using an in vitro yeast reporter gene assay (S. cerevisiae RMY 326 ER-ERE). Concentrations of polychlorinated biphenyls (PCBs) (congeners 28, 52, 101, 118, 138, 153, 180) in fish tissue was also evaluated. RESULTS: Thirty-eight percent of extracts showed a hormone-like activity higher than 10% of the activity elicited by 10 nM 17b-estradiol (E2) used as control. Total PCB concentrations ranged from 0.002 up to 1.785 ng/g wet weight. Chemical analyses detected different levels of contamination among the species collected in the two areas, with the ones collected in the Adriatic Sea showing concentrations significantly higher than those collected in the Tyrrhenian Sea (p < 0.01). CONCLUSION: The more frequent combination of chemicals in the samples that showed higher estrogenic activity was PCB 28, PCB 101, PCB 153, PCB 180. The content of PCBs and estrogenic activity did not reveal any significant correlation

Genomic Sequence Analysis of Granulovirus Isolated from the Tobacco Cutworm, Spodoptera litura

Background: Spodoptera litura is a noctuid moth that is considered an agricultural pest. The larvae feed on a wide range of plants and have been recorded on plants from 40 plant families (mostly dicotyledons). It is a major pest of many crops. To better understand Spodoptera litura granulovirus (SpliGV), the nucleotide sequence of the SpliGV DNA genome was determined and analyzed. Methodology/Principal Findings: The genome of the SpliGV was completely sequenced. The nucleotide sequence of the SpliGV genome was 124,121 bp long with 61.2 % A+T content and contained 133 putative open reading frames (ORFs) of 150 or more nucleotides. The 133 putative ORFs covered 86.3 % of the genome. Among these, 31 ORFs were conserved in most completely sequenced baculovirus genomes, 38 were granulovirus (GV)-specific, and 64 were present in some nucleopolyhedroviruses (NPVs) and/or GVs. We proved that 9 of the ORFs were SpliGV specific. Conclusions/Significance: The genome of SpliGV is 124,121 bp in size. One hundred thirty-three ORFs that putatively encode proteins of 50 or more amino acid residues with minimal overlap were determined. No chitinase or cathepsin genes, which are involved in the liquefaction of the infected host, were found in the SpliGV genome, explaining why SpliGVinfected insects do not degrade in a typical manner. The DNA photolyase gene was first found in the genus Granulovirus. When phylogenic relationships were analyzed, the SpliGV was most closely related to Trichoplusia ni granulovirus (TnGV

Large-scale proteomic identification of S100 proteins in breast cancer tissues

<p>Abstract</p> <p>Background</p> <p>Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression.</p> <p>Methods</p> <p>Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing.</p> <p>Results</p> <p>The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group.</p> <p>Conclusions</p> <p>This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis that a significant deregulation of multiple S100 protein members is associated with breast cancer progression, and suggest that these proteins might act as potential prognostic factors for patient stratification. We propose that this may offer a significant contribution to the knowledge and clinical applications of the S100 protein family to breast cancer.</p

Formin1 Mediates the Induction of Dendritogenesis and Synaptogenesis by Neurogenin3 in Mouse Hippocampal Neurons

Neurogenin3, a proneural transcription factor controlled by Notch receptor, has been recently shown to regulate dendritogenesis and synaptogenesis in mouse hippocampal neurons. However, little is known about the molecular mechanisms involved in these actions of Ngn3. We have used a microarray analysis to identify Ngn3 regulated genes related with cytoskeleton dynamics. One of such genes is Fmn1, whose protein, Formin1, is associated with actin and microtubule cytoskeleton. Overexpression of the Fmn1 isoform-Ib in cultured mouse hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs at 4 days in vitro. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritogenesis and synaptogenesis and indicate that this protein is a key component of the Ngn3 signaling pathway that controls neuronal differentiation

A review of African horse sickness and its implications for Ireland

African horse sickness is an economically highly important non-contagious but infectious Orbivirus disease that is transmitted by various species of Culicoides midges. The equids most severely affected by the virus are horses, ponies, and European donkeys; mules are somewhat less susceptible, and African donkeys and zebra are refractory to the devastating consequences of infection. In recent years, Bluetongue virus, an Orbivirus similar to African horse sickness, which also utilises Culicoides spp. as its vector, has drastically increased its range into previously unaffected regions in northern Europe, utilising indigenous vector species, and causing widespread economic damage to the agricultural sector. Considering these events, the current review outlines the history of African horse sickness, including information concerning virus structure, transmission, viraemia, overwintering ability, and the potential implications that an outbreak would have for Ireland. While the current risk for the introduction of African horse sickness to Ireland is considered at worst ‘very low’, it is important to note that prior to the 2006 outbreak of Bluetongue in northern Europe, both diseases were considered to be of equal risk to the United Kingdom (‘medium-risk’). It is therefore likely that any outbreak of this disease would have serious socio-economic consequences for Ireland due to the high density of vulnerable equids and the prevalence of Culicoides species, potentially capable of vectoring the virus

A two-step target binding and selectivity support vector machines approach for virtual screening of dopamine receptor subtype-selective ligands

10.1371/journal.pone.0039076PLoS ONE76