Mapping cellular processes in the mesenchyme during palatal development in the absence of Tbx1 reveals complex proliferation changes and perturbed cell packing and polarity

The 22q11 deletion syndromes represent a spectrum of overlapping conditions including cardiac defects and craniofacial malformations. Amongst the craniofacial anomalies that are seen, cleft of the secondary palate is a common feature. Haploinsufficiency of TBX1 is believed to be a major contributor toward many of the developmental structural anomalies that occur in these syndromes, and targeted deletion of Tbx1 in the mouse reproduces many of these malformations, including cleft palate. However, the cellular basis of this defect is only poorly understood. Here, palatal development in the absence of Tbx1 has been analysed, focusing on cellular properties within the whole mesenchymal volume of the palatal shelves. Novel image analyses and data presentation tools were applied to quantify cell proliferation rates, including regions of elevated as well as reduced proliferation, and cell packing in the mesenchyme. Also, cell orientations (nucleus–Golgi axis) were mapped as a potential marker of directional cell movement. Proliferation differed only subtly between wild‐type and mutant until embryonic day (E)15.5 when proliferation in the mutant was significantly lower. Tbx1 (−/−) palatal shelves had slightly different cell packing than wild‐type, somewhat lower before elevation and higher at E15.5 when the wild‐type palate has elevated and fused. Cell orientation is biased towards the shelf distal edge in the mid‐palate of wild‐type embryos but is essentially random in the Tbx1 (−/−) mutant shelves, suggesting that polarised processes such as directed cell rearrangement might be causal for the cleft phenotype. The implications of these findings in the context of further understanding Tbx1 function during palatogenesis and of these methods for the more general analysis of genotype–phenotype functional relationships are discussed

Turing’s Genius – Defining an apt microcosm

Alan Turing (1912–1954) is widely acknowledged as a genius. As well as codebreaking during World War II and taking a pioneering role in computer hardware design and software after the War, he also wrote three important foundational papers in the fields of theoretical computer science, artificial intelligence, and mathematical biology. He has been called the father of computer science, but he also admired by mathematicians, philosophers, and perhaps more surprisingly biologists, for his wide-ranging ideas. His influence stretches from scientific to cultural and even political impact. For all these reasons, he was a true polymath. This paper considers the genius of Turing from various angles, both scientific and artistic. The four authors provide position statements on how Turing has influenced and inspired their work, together with short biographies, as a starting point for a panel session and visual music performance

A pp-Wave With 26 Supercharges

A pp-wave solution to 11-dimensional supergravity is given with precisely 26 supercharges. Its uniqueness and the absence of 11-dimensional pp-waves which preserve (precisely) 28 or 30 supercharges is discussed. Compactification on a spacelike circle gives a IIA configuration with all 26 of the supercharges. For this compactification, D0 brane charge does not appear in the supersymmetry algebra. Indeed, the 26 supercharge IIA background does not admit any supersymmetric D-branes. In an appendix, a 28 supercharge IIB pp-wave is presented along with its supersymmetry algebra.Comment: 18 pages REVTeX 4 and AMSLaTeX. v3: Equations (III.17) and (III.18) corrected. Reference added. v4: more typos corrected and references adde

The Influence of Different Light Angles During Standardized Patient Photographic Assessment on the Aesthetic Perception of the Face

BACKGROUND 2D baseline and follow-up clinical images are potentially subject to inconsistency due to alteration of imaging parameters. However, no study to date has attempted to quantify the magnitude by which such images can be influenced. OBJECTIVE The objective of the present study is to identify the magnitude by which images can be influenced by changing the imaging light angle. METHODS This study is based on the evaluation of 2D frontal images of the face and included a total of 51 subjects of which n = 14 were males and n = 37 were females. Faces were photographed at 0°, 30°, and 60° light angle under identical and standardized conditions. Images were randomized and rated by 27 blinded raters for age, facial attractiveness, body mass index (BMI), temporal hollowing, lower cheek fullness, nasolabial sulcus severity, and jawline contour. RESULTS Facial attractiveness decreased, facial unattractiveness increased and the evaluated BMI (based on facial assessment) increased statistically significantly at 60°. The assessment of regional facial scores, i.e., temporal hollowing, lower cheek fullness, and jawline contour, showed no statistically meaningful changes both at 30° and at 60° light angle. CONCLUSION The results indicate that there might be an observed blind range in light angle (0°-30°) which does not influence facial assessment. Increasing the light angle past the threshold value to 60° might result in a statistically significant impact on facial perception which should be accounted for when documenting and/or presenting facial 2D images. LEVEL OF EVIDENCE V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266

Cumulative Risk Effects in the Bullying of Children and Young People with Autism Spectrum Conditions

Students with autism are more likely to be bullied than their typically developing peers. However, several studies have shown that their likelihood of being bullied increases in the context of exposure to certain risk factors (e.g. behaviour difficulties, poor peer relationships). This study explores vulnerability to bullying from a cumulative risk perspective, where the number of risks rather than their nature is considered. 722 teachers and 119 parents of young people with ASC participated in the study. Established risk factors were summed to form a cumulative risk score in teacher and parent models. There was evidence of a cumulative risk effect in both models, suggesting that as the number of risks increased, so did exposure to bullying. A quadratic effect was found in the teacher model, indicating that there was a disproportionate increase in the likelihood of being bullied in relation to the number of risk factors to which a young person was exposed. In light of these findings, it is proposed that more attention needs to be given to the number of risks to which children and young people with ASC are exposed when planning interventions and providing a suitable educational environment

Stretched Strings in Noncommutative Field Theory

Motivated by recent discussions of IR/UV mixing in noncommutative field theories, we perform a detailed analysis of the non-planar amplitudes of the bosonic open string in the presence of an external B-field at the one-loop level. We carefully isolate, at the string theory level, the contribution which is responsible for the IR/UV behavior in the field theory limit. We show that it is a pure open string effect by deriving it from the factorization of the one-loop amplitude into the disk amplitudes of intermediate open string insertions. We suggest that it is natural to understand IR/UV mixing as the creation of intermediate ``stretched strings''.Comment: 20 pages AMSLaTeX using JHEP.cls, 6 eps figures. Typos corrected and references adde

Psychiatric disorders in children with 16p11.2 deletion and duplication

Deletion and duplication of 16p11.2 (BP4–BP5) have been associated with an increased risk of intellectual disability and psychiatric disorder. This is the first study to compare the frequency of a broad spectrum of psychiatric disorders in children with 16p11.2 deletion and duplication. We aimed to evaluate (1) the nature and prevalence of psychopathology associated with copy number variation (CNV) in children with 16p11.2 by comparing deletion and duplication carriers with family controls; (2) whether deletion and duplication carriers differ in frequency of psychopathology. 217 deletion carriers, 77 deletion family controls, 114 duplication carriers, and 32 duplication family controls participated in the study. Measures included standardized research diagnostic instruments. Deletion carriers had a higher frequency of any psychiatric disorder (OR = 8.9, p < 0.001), attention deficit hyperactivity disorder (ADHD) (OR = 4.0, p = 0.01), and autism spectrum disorder (ASD) (OR = 39.9, p = 0.01) than controls. Duplication carriers had a higher frequency of any psychiatric diagnosis (OR = 5.3, p = 0.01) and ADHD (OR = 7.0, p = 0.02) than controls. The prevalence of ASD in child carriers of deletions and duplications was similar (22% versus 26%). Comparison of the two CNV groups indicated a higher frequency of ADHD in children with the duplication than deletion (OR = 2.7, p = 0.04) as well as a higher frequency of overall psychiatric disorders (OR = 2.8, p = 0.02) and psychotic symptoms (OR = 4.7, p = 0.02). However, no differences between deletion and duplications carriers in the prevalence of ASD were found. Both deletion and duplication are associated with an increased risk of psychiatric disorder, supporting the importance of early recognition, diagnosis, and intervention in these groups

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella