ALBERT

Description: Background: Polymyositis is an immune-mediated myopathy with clinical features of proximal muscle weakness. Dysphagia and neck flexor weakness can develop along with respiratory muscle weakness as the disease progresses. Kennedy disease or X-linked spinobulbar muscular atrophy is a rare X-linked recessive disorder with clinical features of slowly progressive atrophy and weakness of limb and bulbar muscles. These two disorders may have overlapping clinical manifestations.Case presentationWe present the case of a 52-year-old Filipino man with chronic weakness involving his proximal muscle groups who carried the diagnosis of polymyositis and was refractory to multiple immunomodulatory therapies. Further neurologic examination and history taking along with selective serologic and electrodiagnostic studies instead confirmed the diagnosis of Kennedy disease. Conclusions: Distinction between polymyositis and Kennedy disease may be difficult given the potential overlapping clinical manifestations. However, with careful neurological history taking, examination, and selective serologic plus electrodiagnostic investigations the correct diagnosis may be made, thus sparing the patient ineffective therapy. One must always be sure of the diagnosis of polymyositis before it's classified as refractory.

Description: Background: Double-stranded (ds) RNA fungal viruses are typically isometric single-shelled particles that are classified into three families, Totiviridae, Partitiviridae and Chrysoviridae, the members of which possess monopartite, bipartite and quadripartite genomes, respectively. Recent findings revealed that mycovirus-related dsRNA viruses are more diverse than previously recognized. Although an increasing number of viral complete genomic sequences have become available, the evolution of these diverse dsRNA viruses remains to be clarified. This is particularly so since there is little evidence for horizontal gene transfer (HGT) among dsRNA viruses. Results: In this study, we report the molecular properties of two novel dsRNA mycoviruses that were isolated from a field strain of Sclerotinia sclerotiorum, Sunf-M: one is a large monopartite virus representing a distinct evolutionary lineage of dsRNA viruses; the other is a new member of the family Partitiviridae. Comprehensive phylogenetic analysis and genome comparison revealed that there are at least ten monopartite, three bipartite, one tripartite and three quadripartite lineages in the known dsRNA mycoviruses and that the multipartite lineages have possibly evolved from different monopartite dsRNA viruses. Moreover, we found that homologs of the S7 Domain, characteristic of members of the genus phytoreovirus in family Reoviridae are widely distributed in diverse dsRNA viral lineages, including chrysoviruses, endornaviruses and some unclassified dsRNA mycoviruses. We further provided evidence that multiple HGT events may have occurred among these dsRNA viruses from different families. Conclusions: Our study provides an insight into the phylogeny and evolution of mycovirus-related dsRNA viruses and reveals that the occurrence of HGT between different virus species and the development of multipartite genomes during evolution are important macroevolutionary mechanisms in dsRNA viruses.

Description: Background: Identifying modifiable factors that influence the epidemiology of colorectal cancer incidence among multiethnic groups might be informative for the development of public health strategies targeting the disease. Minimal data exists describing the impact of physical activity on colorectal polyp risk in United States minority populations. The aim of this study is to evaluate the relationship of exercise on the prevalence of polyps in a multiethnic colorectal cancer screening population. Results: We enrolled 982 patients: 558 Hispanic, 202 Asian ,149 Black, and 69 White. Patients who reported exercising one or more hours weekly had a lower prevalence of any polyps (25.3% vs 33.2%, P = 0.008) as well as adenomas (13.8 vs. 18.9%, P = 0.03) compared to those who did not exercise. Black and Hispanic patients and those who were overweight or obese also had lower prevalence of polyps if they led an active lifestyle. Multivariate analysis revealed that age 〉55, male sex, and Black race/ethnicity were positively associated with the presence of adenomas, while a history of exercising one hour or more weekly was an independent negative predictor for the presence of adenomas anywhere in the colon (OR 0.67; 95% CI 0.4 - 0.9, P = 0.03). Conclusions: Exercising one hour per week was associated with a lower prevalence of polyps and adenomas when compared to those who exercised less or not at all. An active lifestyle provides benefits to groups who are at risk for colorectal cancer, such as Blacks. It also provides significant protection to overweight and obese individuals. Public health initiatives should promote physical activity as a cancer prevention tool in multiethnic populations.

Description: Background: Obesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels. Methods: Two groups of adult non-diabetic human subjects consisting of lean and obese (n = 47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP-40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRT-PCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects. Results: Obese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P 〈 0.05). No differential expression was observed for HSP-27 between the two groups. Higher levels of HSP-72 and GRP-94 proteins correlated positively with the indices of obesity (body mass index and percent body fat) and circulating levels of IFN-gamma-inducible protein 10 (IP-10) and RANTES chemokines. This expression pattern was concomitant with increased inflammatory response in the adipose tissue as monitored by increased levels of Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-alpha), and RANTES (P 〈 0.05). Physical exercise reduced the expression of various HSPs in obese to normal levels observed in lean subjects with a parallel decrease in the endogenous levels of IL-6, TNF-alpha, and RANTES. Conclusion: Taken together, these data indicate that obesity triggers differential regulation of various components of the HSR in non-diabetic subjects and a 3-month physical moderate exercise was sufficient to restore the normal expression of HSPs in the adipose tissue with concomitant attenuation in the inflammatory response.

Description: Background: Transcript profiling of differentiating secondary xylem has allowed us to draw a generalpicture of the genes involved in wood formation. However, our knowledge is still limitedabout the regulatory mechanisms that coordinate and modulate the different pathwaysproviding substrates during xylogenesis. The development of compression wood in conifersconstitutes an exceptional model for these studies. Although differential expression of a fewgenes in differentiating compression wood compared to normal or opposite wood has beenreported, the broad range of features that distinguish this reaction wood suggest that theexpression of a larger set of genes would be modified. Results: By combining the construction of different cDNA libraries with microarray analyses we haveidentified a total of 496 genes in maritime pine (Pinus pinaster, Ait.) that change inexpression during differentiation of compression wood (331 up-regulated and 165 downregulatedcompared to opposite wood). Samples from different provenances collected indifferent years and geographic locations were integrated into the analyses to mitigate theeffects of multiple sources of variability. This strategy allowed us to define a group of genesthat are consistently associated with compression wood formation. Correlating with thedeposition of a thicker secondary cell wall that characterizes compression wood development,the expression of a number of genes involved in synthesis of cellulose, hemicellulose, ligninand lignans was up-regulated. Further analysis of a set of these genes involved in Sadenosylmethioninemetabolism, ammonium recycling, and lignin and lignans biosynthesisshowed changes in expression levels in parallel to the levels of lignin accumulation in cellsundergoing xylogenesis in vivo and in vitro. Conclusions: The comparative transcriptomic analysis reported here have revealed a broad spectrum ofcoordinated transcriptional modulation of genes involved in biosynthesis of different cell wallpolymers associated with within-tree variations in pine wood structure and composition. Inparticular, we demonstrate the coordinated modulation at transcriptional level of a gene setinvolved in S-adenosylmethionine synthesis and ammonium assimilation with increased demand for coniferyl alcohol for lignin and lignan synthesis, enabling a better understandingof the metabolic requirement in cells undergoing lignification.

Description: Background: Although numerous candidate gene and genome-wide association studies have been performed on blood pressure, a small number of regulating genetic variants having a limited effect have been identified. This phenomenon can partially be explained by possible gene-gene/epistasis interactions that were little investigated so far. Methods: We performed a pre-planned two-phase investigation: in phase 1, one hundred single nucleotide polymorphisms (SNPs) in 65 candidate genes were genotyped in 1,912 French unrelated adults in order to study their two-locus combined effects on blood pressure (BP) levels. In phase 2, the significant epistatic interactions observed in phase 1 were tested in an independent population gathering 1,755 unrelated European adults. Results: Among the 9 genetic variants significantly associated with systolic and diastolic BP in phase 1, some may act through altering the corresponding protein levels: SNPs rs5742910 (Padjusted

Description: Background: The study of quantitative trait loci (QTL) in cotton (Gossypium spp.) is focused on traits of agricultural significance. Previous studies have identified a plethora of QTL attributed to fiber quality, disease and pest resistance, branch number, seed quality and yield and yield related traits, drought tolerance, and morphological traits. However, results among these studies differed due to the use of different genetic populations, markers and marker densities, and testing environments. Since two previous meta-QTL analyses were performed on fiber traits, a number of papers on QTL mapping of fiber quality, yield traits, morphological traits, and disease resistance have been published. To obtain a better insight into the genome-wide distribution of QTL and to identify consistent QTL for marker assisted breeding in cotton, an updated comparative QTL analysis is needed. Results: In this study, a total of 1,223 QTL from 42 different QTL studies in Gossypium were surveyed and mapped using Biomercator V3 based on the Gossypium consensus map from the Cotton Marker Database. A meta-analysis was first performed using manual inference and confirmed by Biomercator V3 to identify possible QTL clusters and hotspots. QTL clusters are composed of QTL of various traits which are concentrated in a specific region on a chromosome, whereas hotspots are composed of only one trait type. QTL were not evenly distributed along the cotton genome and were concentrated in specific regions on each chromosome. QTL hotspots for fiber quality traits were found in the same regions as the clusters, indicating that clusters may also form hotspots. Conclusions: Putative QTL clusters were identified via meta-analysis and will be useful for breeding programs and future studies involving Gossypium QTL. The presence of QTL clusters and hotspots indicates consensus regions across cultivated tetraploid Gossypium species, environments, and populations which contain large numbers of QTL, and in some cases multiple QTL associated with the same trait termed a hotspot. This study combines two previous meta-analysis studies and adds all other currently available QTL studies, making it the most comprehensive meta-analysis study in cotton to date.

Description: Background: Cocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine.Case presentationA 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly. Conclusion: The exact incidence of cocaine related cardiomyopathy is unknown and likely underreported. The clinical course is abrupt and comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however β-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response.

Description: Background: Cocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine.Case presentationA 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly. Conclusion: The incidence of probable cocaine related cardiomyopathy is unknown and likely underreported. The clinical course occurs abruptly and is comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however Ss-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response.