In silico predictions of variant deleteriousness in the genomes of pig species

Predicting the deleteriousness of observed genomic variants has taken a step forward with the development of the Combined Annotation Dependent Depletion (CADD) [1] methodology, as it allows for comparable evaluations of variants on a genome-wide scale for coding and non-coding variants respectively. ..

A photoelectron spectroscopy study of the electronic structure evolution in CuInSe2-related compounds at changing copper content

Evolution of the valence-band structure at gradually increasing copper content has been analysed by x-ray photoelectron spectroscopy (XPS) in In2Se3, CuIn5Se8, CuIn3Se5, and CuInSe2 single crystals. A comparison of these spectra with calculated total and angular-momentum resolved density-of-states (DOS) revealed the main trends of this evolution. The formation of the theoretically predicted gap between the bonding and non-bonding states has been observed in both experimental XPS spectra and theoretical DOS

Cavitation-induced force transition in confined viscous liquids under traction

We perform traction experiments on simple liquids highly confined between parallel plates. At small separation rates, we observe a simple response corresponding to a convergent Poiseuille flow. Dramatic changes in the force response occur at high separation rates, with the appearance of a force plateau followed by an abrupt drop. By direct observation in the course of the experiment, we show that cavitation accounts for these features which are reminiscent of the utmost complex behavior of adhesive films under traction. Surprisingly enough, this is observed here in purely viscous fluids.Comment: Submitted to Physical Review Letters on May 31, 2002. Related informations on http://www.crpp.u-bordeaux.fr/tack.htm

Emerging evidence for CHFR as a cancer biomarker : from tumor biology to precision medicine

Novel insights in the biology of cancer have switched the paradigm of a "one-size-fits-all" cancer treatment to an individualized biology-driven treatment approach. In recent years, a diversity of biomarkers and targeted therapies has been discovered. Although these examples accentuate the promise of personalized cancer treatment, for most cancers and cancer subgroups no biomarkers and effective targeted therapy are available. The great majority of patients still receive unselected standard therapies with no use of their individual molecular characteristics. Better knowledge about the underlying tumor biology will lead the way toward personalized cancer treatment. In this review, we summarize the evidence for a promising cancer biomarker: checkpoint with forkhead and ring finger domains (CHFR). CHFR is a mitotic checkpoint and tumor suppressor gene, which is inactivated in a diverse group of solid malignancies, mostly by promoter CpG island methylation. CHFR inactivation has shown to be an indicator of poor prognosis and sensitivity to taxane-based chemotherapy. Here we summarize the current knowledge of altered CHFR expression in cancer, the impact on tumor biology and implications for personalized cancer treatment

The influence of semantic top-down processing in auditory verbal hallucinations

AbstractBackgroundAuditory verbal hallucinations (AVH) are one of the most prominent symptoms of schizophrenia but have also been reported in the general population. Several cognitive models have tried to elucidate the mechanism behind auditory verbal hallucinations, among which a top-down model. According to this model, perception is biased towards top-down information (e.g., expectations), reducing the influence of bottom-up information coming from the sense organs. This bias predisposes to false perceptions, i.e., hallucinations.MethodsThe current study investigated this hypothesis in non-psychotic individuals with frequent AVH, psychotic patients with AVH and healthy control subjects by applying a semantic top-down task. In this task, top-down processes are manipulated through the semantic context of a sentence. In addition, the association between hallucination proneness and semantic top-down errors was investigated.ResultsNon-psychotic individuals with AVH made significantly more top-down errors compared to healthy controls, while overall accuracy was similar. The number of top-down errors, corrected for overall accuracy, in the patient group was in between those of the other two groups and did not differ significantly from either the non-psychotic individuals with AVH or the healthy controls. The severity of hallucination proneness correlated with the number of top-down errors.DiscussionThese findings confirm that non-psychotic individuals with AVH are stronger influenced by top-down processing (i.e., perceptual expectations) than healthy controls. In contrast, our data suggest that in psychotic patients semantic expectations do not play a role in the etiology of AVH. This finding may point towards different cognitive mechanisms for pathological and nonpathological hallucinations

Why more boys than girls with ADHD receive treatment: A study of Dutch twins.

More boys than girls with attention deficit hyperactivity disorder (ADHD) receive treatment. One explanation for this bias may be that boys score higher on disruptive behavior scales than girls. Although this was supported by findings in clinical samples, recent studies in nonreferred samples showed that boys and girls with ADHD are similar with respect to their levels of disruptive behavior as reported by their mother. In this report, we investigate whether the difference in treatment rate is associated with higher teacher problem scores in boys with ADHD than in girls with ADHD. Data were obtained from mothers and teachers in a nonreferred sample of 283 boys and 291 girls with and without ADHD. Children were selected when they scored either low (controls) or high (probands) on attention problems. Mothers completed DSM-IV interviews, Child Behavior Checklists (CBCL) and the Conners Rating Scale (CRS). Teachers filled in the Teacher Report Form (TRF), and the CRS. Boys and girls with ADHD had similar levels of psychiatric illness and school impairment (such as being held back, special class placement and learning problems) by mother report. Mothers reported similar levels of aggression and attention problems in boys and girls with ADHD. In contrast, teachers consistently rated boys with ADHD as having higher scores on reports of attention problems and aggression than girls with ADHD. Gender differences vary across settings: boys and girls with ADHD are rated as behaving differently at school, but not at home. The higher level of teacher reported problem behavior at school may explain the high male-female ratio for ADHD in clinical settings. These findings have implications for the results of genetic studies that rely on referred samples, as these studies may give a distorted view of sex differences in the population

Synchronization of organ pipes: experimental observations and modeling

We report measurements on the synchronization properties of organ pipes. First, we investigate influence of an external acoustical signal from a loudspeaker on the sound of an organ pipe. Second, the mutual influence of two pipes with different pitch is analyzed. In analogy to the externally driven, or mutually coupled self-sustained oscillators, one observes a frequency locking, which can be explained by synchronization theory. Further, we measure the dependence of the frequency of the signals emitted by two mutually detuned pipes with varying distance between the pipes. The spectrum shows a broad ``hump'' structure, not found for coupled oscillators. This indicates a complex coupling of the two organ pipes leading to nonlinear beat phenomena.Comment: 24 pages, 10 Figures, fully revised, 4 big figures separate in jpeg format. accepted for Journal of the Acoustical Society of Americ

Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

Bioelectronic interfaces employing arrays of sensors and bioactuators are promising tools for the study, repair and engineering of cardiac tissues. They are typically constructed from rigid and brittle materials processed in a cleanroom environment. An outstanding technological challenge is the integration of soft materials enabling a closer match to the mechanical properties of biological cells and tissues. Here we present an algorithm for direct writing of elastic membranes with embedded electrodes, optical waveguides and microfluidics using a commercial 3D printing system and a palette of silicone elastomers. As proof of principle, we demonstrate interfacing of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs), which are engineered to express Channelrhodopsin-2. We demonstrate electrical recording of cardiomyocyte field potentials and their concomitant modulation by optical and pharmacological stimulation delivered via the membrane. Our work contributes a simple prototyping strategy with potential applications in organ-on-chip or implantable systems that are multi-modal and mechanically soft

The need for additional care in patients with classical galactosaemia

Purpose: Classical galactosaemia is an inborn error of galactose metabolism which may lead to impairments in body functions and accordingly, need for additional care. The primary aim of this study was to establish the type and intensity of this additional care. Materials and methods: Patients with classical galactosaemia aged >/=2 years were evaluated with the Capacity Profile, a standardised method to classify additional care needs according to type and intensity. Based on a semi-structured interview, current impairments in five domains of body functions were determined. The intensity of additional care was assessed (from 0, usual care, to 5, total dependence). Results: Forty-four patients with classical galactosaemia, 18 males and 26 females (median age 15 years, range 2-49 years), were included. There was a wide spectrum of impairments in mental functions. Motor function impairments were present in four patients, and mild speech impairments in eight patients. Additional care for sensory functions was uncommon. All patients needed a diet, which care is scored in the physical health domain. Conclusions: Apart from the diet all patients need, classical galactosaemia leads to the need for additional care mainly in the domains of mental functions and speech and voice functions. Implications for rehabilitation The Capacity Profile is a useful tool to demonstrate additional care needs in classical galactosaemia. In classical galactosaemia additional care is mostly indicated by mental impairments and speech and voice functions. One-fifth of patients have impairment of speech and voice functions at time of the study, and half of all patients had received speech therapy in childhood. Over 70% of patients need additional care/help due to impairment of mental functions, ranging from coaching due to social vulnerability to full day care

Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67:a unique subtype

INTRODUCTION: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (PI) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up. METHODS: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1). RESULTS: All patients had N0 or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was ≤40%. OS was longer for Ki-67 ≤40% compared to >40% (17 months (95% CI 11-23 months) vs. 5 months (95% CI 0.7-9 months), p=0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67 ≤40%. 8/11 patients could be subclassified and both SCLC-like (n=6) and NSCLC-like (n=2) subtype were present. No MEN1 mutation was found. CONCLUSION: Stage IV LCNEC with a solitary brain metastasis and N0/N1 disease show in the majority of cases Ki-67 PI ≤40% and prolonged survival, distinguishing them from general LCNEC. This unique subgroup can be both of the SCLC-like and NSCLC-like subtype