North Atlantic ocean circulation and abrupt climate change during the last glaciation.

The most recent ice age was characterized by rapid and hemispherically asynchronous climate oscillations, whose origin remains unresolved. Variations in oceanic meridional heat transport may contribute to these repeated climate changes, which were most pronounced during marine isotope stage 3, the glacial interval 25 thousand to 60 thousand years ago. We examined climate and ocean circulation proxies throughout this interval at high resolution in a deep North Atlantic sediment core, combining the kinematic tracer protactinium/thorium (Pa/Th) with the deep water-mass tracer, epibenthic δ(13)C. These indicators suggest reduced Atlantic overturning circulation during every cool northern stadial, with the greatest reductions during episodic Hudson Strait iceberg discharges, while sharp northern warming followed reinvigorated overturning. These results provide direct evidence for the ocean's persistent, central role in abrupt glacial climate change

Predictors of Segmented School Day Physical Activity and Sedentary Time in Children from A Northwest England Low-income Community

Background: Schools have been identified as important settings for health promotion through physical activity participation, particularly as children are insufficiently active for health. The aim of this study was to investigate the child and school-level influences on children′s physical activity levels and sedentary time during school hours in a sample of children from a low-income community; Methods: One hundred and eighty-six children (110 boys) aged 9–10 years wore accelerometers for 7 days, with 169 meeting the inclusion criteria of 16 h∙day−1 for a minimum of three week days. Multilevel prediction models were constructed to identify significant predictors of sedentary time, light, and moderate to vigorous physical activity during school hour segments. Child-level predictors(sex, weight status, maturity offset, cardiorespiratory fitness, physical activity self-efficacy, physical activity enjoyment) and school-level predictors (number on roll, playground area, provision score) were entered into the models; Results: Maturity offset, fitness, weight status, waist circumference-to-height ratio, sedentary time, moderate to vigorous physical activity, number of children on roll and playground area significantly predicted physical activity and sedentary time; Conclusions: Research should move towards considering context-specific physical activity and its correlates to better inform intervention strategies

Evaluation of wrist and hip sedentary behaviour and moderate-to-vigorous physical activity raw acceleration cutpoints in older adults

Wrist-based accelerometers are now common in assessing physical activity (PA) and sedentary behaviour (SB) in population-based studies, but there is a scarcity of raw acceleration cutpoints in older adults. The study aimed to determine and evaluate wrist-based GENEActiv (GA) and hip-based ActiGraph GT3X+ (AG) raw acceleration cutpoints for SB and moderate-to-vigorous PA (MVPA) in older adults ≥60 years of age. A laboratory-based calibration analyses of 34 healthy older adults involved receiver operator characteristic (ROC) curves to determine raw acceleration cutpoints for SB and MVPA. ROC analysis revealed an area under the curve (AUC) of 0.88 for GA SB and MVPA, and 0.90 for AG SB and 0.94 for AG MVPA. Sensitivity optimised SB and specificity optimised MVPA GA cutpoints of 57 mg and 104 mg, and AG cutpoints of 15 mg and 69 mg were also generated, respectively. Cross-validation analysis revealed moderate agreement for GA and AG SB cutpoints, and fair to substantial agreement for GA and AG MVPA cutpoints, respectively. The resultant cutpoints can classify older adults as engaging in SB or not engaging in MVPA but the sensitivity optimised SB cutpoints should be interpreted with a degree of caution due to their modest cross-validation results

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

A recurrent mosaic mutation of SMO, encoding the hedgehog signal transducer smoothened, is the major cause of Curry-Jones syndrome

Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single affected individual; in another, biopsy of skin lesions showed features of trichoblastoma. The combination of asymmetric clinical features, patchy skin manifestations, and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving hedgehog (Hh) signaling. Here, we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO (c.1234C>T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that transduces Hh signaling. We identified eight mutation-positive individuals (two of whom had not been reported previously) with highly similar phenotypes and demonstrated varying amounts of the mutant allele in different tissues. We present detailed findings from brain MRI in three mutation-positive individuals. Somatic SMO mutations that result in constitutive activation have been described in several tumors, including medulloblastoma, ameloblastoma, and basal cell carcinoma. Strikingly, the most common of these mutations is the identical nonsynonymous variant encoding p.Leu412Phe. Furthermore, this substitution has been shown to activate SMO in the absence of Hh signaling, providing an explanation for tumor development in CJS. This raises therapeutic possibilities for using recently generated Hh-pathway inhibitors. In summary, our work uncovers the major genetic cause of CJS and illustrates strategies for gene discovery in the context of low-level tissue-specific somatic mosaicism

An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.Medical Research CouncilNewlife Foundation for disabled childre

Reversed flow of Atlantic deep water during the Last Glacial Maximum

The meridional overturning circulation (MOC) of the Atlantic Ocean is considered to be one of the most important components of the climate system. This is because its warm surface currents, such as the Gulf Stream, redistribute huge amounts of energy from tropical to high latitudes and influence regional weather and climate patterns, whereas its lower limb ventilates the deep ocean and affects the storage of carbon in the abyss, away from the atmosphere. Despite its significance for future climate, the operation of the MOC under contrasting climates of the past remains controversial. Nutrient-based proxies1, 2 and recent model simulations3 indicate that during the Last Glacial Maximum the convective activity in the North Atlantic Ocean was much weaker than at present. In contrast, rate-sensitive radiogenic 231Pa/230Th isotope ratios from the North Atlantic have been interpreted to indicate only minor changes in MOC strength4, 5, 6. Here we show that the basin-scale abyssal circulation of the Atlantic Ocean was probably reversed during the Last Glacial Maximum and was dominated by northward water flow from the Southern Ocean. These conclusions are based on new high-resolution data from the South Atlantic Ocean that establish the basin-scale north to south gradient in 231Pa/230Th, and thus the direction of the deep ocean circulation. Our findings are consistent with nutrient-based proxies and argue that further analysis of 231Pa/230Th outside the North Atlantic basin will enhance our understanding of past ocean circulation, provided that spatial gradients are carefully considered. This broader perspective suggests that the modern pattern of the Atlantic MOC—with a prominent southerly flow of deep waters originating in the North Atlantic—arose only during the Holocene epoch

The learning styles neuromyth:when the same term means different things to different teachers

Alexia Barrable - ORCID: 0000-0002-5352-8330 https://orcid.org/0000-0002-5352-8330Although learning styles (LS) have been recognised as a neuromyth, they remain a virtual truism within education. A point of concern is that the term LS has been used within theories that describe them using completely different notions and categorisations. This is the first empirical study to investigate education professionals’ conceptualisation, as well as means of identifying and implementing LS in their classroom. A sample of 123 education professionals were administered a questionnaire consisting both closed- and open-ended questions. Responses were analysed using thematic analysis. LS were found to be mainly conceptualised within the Visual-Auditory-(Reading)-Kinaesthetic (VAK/VARK) framework, as well as Gardner’s multiple intelligences. Moreover, a lot of education professionals confused theories of learning (e.g., behavioural or cognitive theories) with LS. In terms of identifying LS, educators reported using a variety of methods, spanning from observation and everyday contact to the use of tests. The ways LS were implemented in the classroom were numerous, comprising various teaching aids, participatory techniques and motor activities. Overall, we argue that the extended use of the term LS gives the illusion of a consensus amongst educators, when a closer examination reveals that the term LS is conceptualised, identified and implemented idiosyncratically by different individuals. This study aims to be of use to pre-service and in-service teacher educators in their effort to debunk the neuromyth of LS and replace it with evidence-based practices.https://doi.org/10.1007/s10212-020-00485-236pubpub

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations