Association of a de novo 16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes

<p>Abstract</p> <p>Background</p> <p>Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.</p> <p>Case Presentation</p> <p>The patient was subjected to clinical and molecular evaluation, including array CGH analysis. The clinical features included left clinical anophthalmia, right microphthalmia, anteriorly placed anus with fistula, chordee, ventriculoseptal defect, patent ductus arteriosus, posteriorly rotated ears, hypotonia, growth retardation with delayed bone age, and mental retardation. The patient was found to have an approximately 5.6 Mb deletion of 16q11.2q12.1 by microarray based-comparative genomic hybridization, which includes the <it>SALL1 </it>gene, which causes Townes-Brocks syndrome.</p> <p>Conclusions</p> <p>Deletions of 16q11.2q12.2 have been reported in several individuals, although those prior reports did not note microphthalmia or anophthalmia. This region includes <it>SALL1</it>, which causes Townes-Brocks syndrome. In retrospect, this child has a number of features that can be explained by the <it>SALL1 </it>deletion, although it is not clear if the microphthalmia is a rare feature of Townes-Brocks syndrome or caused by other mechanisms. These data suggest that rare copy number changes may be a cause of syndromic microphthalmia allowing a personalized genomic medicine approach to the care of patients with these aberrations.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Prevalence of dyslipidaemia and associated risk factors in a rural population in south-western Uganda : a community based survey

BACKGROUND: The burden of dyslipidaemia is rising in many low income countries. However, there are few data on the prevalence of, or risk factors for, dyslipidaemia in Africa. METHODS: In 2011, we used the WHO Stepwise approach to collect cardiovascular risk data within a general population cohort in rural south-western Uganda. Dyslipidaemia was defined by high total cholesterol (TC) ≥ 5.2 mmol/L or low high density lipoprotein cholesterol (HDL-C) 6% (men aOR=3.00, 95%CI=1.37-6.59; women aOR=2.74, 95%CI=1.77-4.27). The odds of high TC was also higher among married men, and women with higher education or high BMI. CONCLUSION: Low HDL-C prevalence in this relatively young rural population is high whereas high TC prevalence is low. The consequences of dyslipidaemia in African populations remain unclear and prospective follow-up is required

A LOV Protein Modulates the Physiological Attributes of Xanthomonas axonopodis pv. citri Relevant for Host Plant Colonization

Recent studies have demonstrated that an appropriate light environment is required for the establishment of efficient vegetal resistance responses in several plant-pathogen interactions. The photoreceptors implicated in such responses are mainly those belonging to the phytochrome family. Data obtained from bacterial genome sequences revealed the presence of photosensory proteins of the BLUF (Blue Light sensing Using FAD), LOV (Light, Oxygen, Voltage) and phytochrome families with no known functions. Xanthomonas axonopodis pv. citri is a Gram-negative bacterium responsible for citrus canker. The in silico analysis of the X. axonopodis pv. citri genome sequence revealed the presence of a gene encoding a putative LOV photoreceptor, in addition to two genes encoding BLUF proteins. This suggests that blue light sensing could play a role in X. axonopodis pv. citri physiology. We obtained the recombinant Xac-LOV protein by expression in Escherichia coli and performed a spectroscopic analysis of the purified protein, which demonstrated that it has a canonical LOV photochemistry. We also constructed a mutant strain of X. axonopodis pv. citri lacking the LOV protein and found that the loss of this protein altered bacterial motility, exopolysaccharide production and biofilm formation. Moreover, we observed that the adhesion of the mutant strain to abiotic and biotic surfaces was significantly diminished compared to the wild-type. Finally, inoculation of orange (Citrus sinensis) leaves with the mutant strain of X. axonopodis pv. citri resulted in marked differences in the development of symptoms in plant tissues relative to the wild-type, suggesting a role for the Xac-LOV protein in the pathogenic process. Altogether, these results suggest the novel involvement of a photosensory system in the regulation of physiological attributes of a phytopathogenic bacterium. A functional blue light receptor in Xanthomonas spp. has been described for the first time, showing an important role in virulence during citrus canker disease

Ecosystem development after mangrove wetland creation : plant–soil change across a 20-year chronosequence

This paper is not subject to U.S. copyright. The definitive version was published in Ecosystems 15 (2012): 848-866, doi:10.1007/s10021-012-9551-1.Mangrove wetland restoration and creation efforts are increasingly proposed as mechanisms to compensate for mangrove wetland losses. However, ecosystem development and functional equivalence in restored and created mangrove wetlands are poorly understood. We compared a 20-year chronosequence of created tidal wetland sites in Tampa Bay, Florida (USA) to natural reference mangrove wetlands. Across the chronosequence, our sites represent the succession from salt marsh to mangrove forest communities. Our results identify important soil and plant structural differences between the created and natural reference wetland sites; however, they also depict a positive developmental trajectory for the created wetland sites that reflects tightly coupled plant-soil development. Because upland soils and/or dredge spoils were used to create the new mangrove habitats, the soils at younger created sites and at lower depths (10–30 cm) had higher bulk densities, higher sand content, lower soil organic matter (SOM), lower total carbon (TC), and lower total nitrogen (TN) than did natural reference wetland soils. However, in the upper soil layer (0–10 cm), SOM, TC, and TN increased with created wetland site age simultaneously with mangrove forest growth. The rate of created wetland soil C accumulation was comparable to literature values for natural mangrove wetlands. Notably, the time to equivalence for the upper soil layer of created mangrove wetlands appears to be faster than for many other wetland ecosystem types. Collectively, our findings characterize the rate and trajectory of above- and below-ground changes associated with ecosystem development in created mangrove wetlands; this is valuable information for environmental managers planning to sustain existing mangrove wetlands or mitigate for mangrove wetland losses

The RNA Helicase Rm62 Cooperates with SU(VAR)3-9 to Re-Silence Active Transcription in Drosophila melanogaster

Gene expression is highly dynamic and many genes show a wide range in expression over several orders of magnitude. This regulation is often mediated by sequence specific transcription factors. In addition, the tight packaging of DNA into chromatin can provide an additional layer of control resulting in a dynamic range of gene expression covering several orders of magnitude. During transcriptional activation, chromatin barriers have to be eliminated to allow an efficient progression of the RNA polymerase. This repressive chromatin structure has to be re-established quickly after it has been activated in order to tightly regulate gene activity. We show that the DExD/H box containing RNA helicase Rm62 is targeted to a site of rapid induction of transcription where it is responsible for an increased degree of methylation at H3K9 at the heat shock locus after removal of the heat shock stimulus. The RNA helicase interacts with the well-characterized histone methyltransferase SU(VAR)3-9 via its N-terminus, which provides a potential mechanism for the targeting of H3K9 methylation to highly regulated genes. The recruitment of SU(VAR)3-9 through interaction with a RNA helicase to a site of active transcription might be a general mechanism that allows an efficient silencing of highly regulated genes thereby enabling a cell to fine tune its gene activity over a wide range

Socioeconomic Inequalities in the Prevalence of Nine Established Cardiovascular Risk Factors in a Southern European Population

The evaluation of the gender-specific prevalence of cardiovascular risk factors across socioeconomic position (SEP) categories may unravel mechanisms involved in the development of coronary heart disease. Using a sample of 1704 community dwellers of a Portuguese urban center aged 40 years or older, assessed in 1999–2003, we quantified the age-standardized prevalence of nine established cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, smoking, sedentariness, abdominal obesity, poor diet, excessive alcohol intake and depression) across SEP and gender categories. Data on individual education and occupation were collected by questionnaire and used to characterize SEP. The prevalence of seven out of nine well-established risk factors was higher in men. Among women, the prevalence of most of the studied risk factors was higher in lower SEP groups. The main exception was smoking, which increased with education and occupation levels. Among men, socioeconomic gradients were less clear, but lower SEP was associated with a higher prevalence of diabetes, excessive alcohol intake and depression in a graded mode. The historical cultural beliefs and practices captured throughout the lifecourse frame the wide socioeconomic gradients discernible in our study conducted in an unequal European developed population. While men were more exposed to most risk factors, the clearer associations between SEP and risk factors among women support that their adoption of particular healthy behaviors is more dependent on material and symbolic conditions. To fully address the issue of health inequalities, interventions within the health systems should be complemented with population-based policies specifically designed to reduce socioeconomic gradients

Tremor in multiple sclerosis

Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide some relief, but published evidence of effectiveness is very limited. Most trials were of small size and of short duration. Cannabinoids appear ineffective. Tremor reduction can be obtained with stereotactic thalamotomy or thalamic stimulation. However, the studies were small and information on long-term functional outcome is scarce. Physiotherapy, tremor reducing orthoses, and limb cooling can achieve some functional improvement. Tremor in MS remains a significant challenge and unmet need, requiring further basic and clinical research