A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

<p>Abstract</p> <p>Background</p> <p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis caused by more than 500 different mutations in the <it>COL7A1 </it>gene and characterized by blistering of the skin following a minimal friction or mechanical trauma.</p> <p>The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation.</p> <p>Methods</p> <p>Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs) throughout the <it>COL7A1 </it>gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin.</p> <p>Results</p> <p>Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation.</p> <p>Conclusion</p> <p>Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (<b><it>CCGCTCAAA_6527insC</it></b>), thus suggesting the presence of a common ancestor.</p

Nitrogen forms affect root structure and water uptake in the hybrid poplar

The study analyses the effects of two different forms of nitrogen fertilisation (nitrate and ammonium) on root structure and water uptake of two hybrid poplar (Populus maximowiczii x P. balsamifera) clones in a field experiment. Water uptake was studied using sap flow gauges on individual proximal roots and coarse root structure was examined by excavating 18 whole-root systems. Finer roots were scanned and analyzed for architecture. Nitrogen forms did not affect coarse-root system development, but had a significant effect on fine-root development. Nitrate-treated trees presented higher fine:coarse root ratios and higher specific root lengths than control or ammonium treated trees. These allocation differences affected the water uptake capacity of the plants as reflected by the higher sapflow rate in the nitrate treatment. The diameter of proximal roots at the tree base predicted well the total root biomass and length. The diameter of smaller lateral roots also predicted the lateral root mass, length, surface area and the number of tips. The effect of nitrogen fertilisation on the fine root structure translated into an effect on the functioning of the fine roots forming a link between form (architecture) and function (water uptake)

A COL7A1 Mutation Causes Dystrophic Epidermolysis Bullosa in Rotes Höhenvieh Cattle

We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to the severity, extent and progression of the skin and oral lesions. Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction, leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa. The pedigree was consistent with monogenic autosomal recessive inheritance. We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping. The COL7A1 gene encoding collagen type VII alpha 1 is located within this interval and COL7A1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB) in humans. A SNP in the bovine COL7A1 exon 49 (c.4756C>T) was perfectly associated with the observed disease. The homozygous mutant T/T genotype was exclusively present in affected calves and their parents were heterozygous C/T confirming the assumed recessive mode of inheritance. All known cases and genotyped carriers were related to a single cow, which is supposed to be the founder animal. The mutant T allele was absent in 63 animals from 24 cattle breeds. The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL7A1 function (p.R1586*). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis. Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed

DAYENU: a simple filter of smooth foregrounds for intensity mapping power spectra

We introduce DPSS Approximate lazY filtEriNg of foregroUnds (DAYENU), a linear, spectral filter for H I intensity mapping that achieves the desirable foreground mitigation and error minimization properties of inverse co-variance weighting with minimal modelling of the underlying data. Beyond 21-cm power-spectrum estimation, our filter is suitable for any analysis where high dynamic-range removal of spectrally smooth foregrounds in irregularly (or regularly) sampled data is required, something required by many other intensity mapping techniques. Our filtering matrix is diagonalized by Discrete Prolate Spheroidal Sequences which are an optimal basis to model band-limited foregrounds in 21-cm intensity mapping experiments in the sense that they maximally concentrate power within a finite region of Fourier space. We show that DAYENU enables the access of large-scale line-of-sight modes that are inaccessible to tapered discrete Fourier transform estimators. Since these modes have the largest SNRs,DAYENU significantly increases the sensitivity of 21-cm analyses over tapered Fourier transforms. Slight modifications allow us to use DAYENU as a linear replacement for iterative delay CLEAN ing (DAYENUREST). We refer readers to the Code section at the end of this paper for links to examples and code

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

An unexpected evolution of symptomatic mild middle cerebral artery (MCA) stenosis: asymptomatic occlusion

<p>Abstract</p> <p>Background</p> <p>The intracranial localization of large artery disease is recognized as the main cause of ischemic stroke in the world, considering all countries, although its global burden is widely underestimated. Indeed it has been reported more frequently in Asians and African-American people, but the finding of intracranial stenosis as a cause of ischemic stroke is relatively common also in Caucasians. The prognosis of patients with stroke due to intracranial steno-occlusion is strictly dependent on the time of recanalization. Moreover, the course of the vessel involvement is highly dynamic in both directions, improvement or worsening, although several data are derived from the atherosclerotic subtype, compared to other causes.</p> <p>Case description</p> <p>We report the clinical, neurosonological and neuroradiological findings of a young woman, who came to our Stroke Unit because of the abrupt onset of aphasia during her work. An urgent neurosonological examination showed a left M1 MCA stenosis, congruent with the presenting symptoms; magnetic resonance imaging confirmed this finding and identified an acute ischemic lesion on the left MCA territory. The past history of the patient was significant only for a hyperinsulinemic condition, treated with metformine, and a mild overweight. At this time a selective cerebral angiography was not performed because of the patient refusal and she was discharged on antiplatelet and lipid-lowering therapy, having failed to identify autoimmune or inflammatory diseases. Within 1 month, she went back to our attention because of the recurrence of aphasia, lasting about ten minutes. Neuroimaging findings were unchanged, but the patient accepted to undergo a selective cerebral angiography, which showed a mild left distal M1 MCA stenosis.</p> <p>During the follow-up the patient did not experienced any recurrence, but a routine neurosonological examination found an unexpected evolution of the known MCA stenosis, i.e. left M1 MCA occlusion. Neuroradiological imaging did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the left M1 MCA occlusion.</p> <p>Conclusions</p> <p>Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at our knowledge.</p

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire

BACKGROUND: Doppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo. METHODS: We perfused glass pipes of defined inner diameters (1.5 – 5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes. RESULTS: In vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r(2 )> 0.85). Above a critical Reynolds number of 500 – indicating turbulent flow – the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 ± 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments. CONCLUSION: Doppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making

Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification

Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility of these signatures to the confounding effects of ITH using gene expression microarray data obtained from multiple tumour regions of a cohort of 24 patients, including central tumour, the tumour invasive front and lymph node metastasis. Sample clustering alongside correlative assessment revealed variation in the ability of each signature to cluster samples according to patient-of-origin rather than region-of-origin within the multi-region dataset. Signatures focused on cancer-cell intrinsic gene expression were found to produce more clinically useful, patient-centred classifiers, as exemplified by the CRC intrinsic signature (CRIS), which robustly clustered samples by patient-of-origin rather than region-of-origin. These findings highlight the potential of cancer-cell intrinsic signatures to reliably stratify CRC patients by minimising the confounding effects of stromal-derived ITH

Conscientiousness, Career Success, and Longevity: A Lifespan Analysis

Markers of executive functioning, such as prudent planning for the future and impulse control, are related to conscientiousness and may be central to both occupational success and health outcomes. The aim of the study was to examine relations among conscientiousness, career success, and mortality risk across a 65-year period. Using data derived from 693 male participants in the Terman Life Cycle Study, we examined associations among childhood personality, midlife objective career success, and lifelong mortality risk through 2006. Conscientiousness and career success each predicted lower mortality risk (N = 693, relative hazard (rh) = 0.82 [95% confidence interval = 0.74, 0.91] and rh = 0.80 [0.71, 0.91], respectively), with both shared and unique variance. Importantly, childhood personality moderated the success–longevity link; conscientiousness was most relevant for least successful individuals. Conscientiousness and career success predicted longevity, but not in a straightforward manner. Findings highlight the importance of lifespan processes