Stability and turbulent transport in Taylor–Couette flow from analysis of experimental data

International audienceThis paper provides a prescription for the turbulent viscosity in rotating shear flows for use e.g. in geophysical and astrophysical contexts. This prescription is the result of the detailed analysis of the experimental data obtained in several studies of the transition to turbulence and turbulent transport in Taylor-Couette flow. We first introduce a new set of control parameters, based on dynamical rather than geometrical considerations, so that the analysis applies more naturally to rotating shear flows in general and not only to Taylor-Couette flow. We then investigate the transition thresholds in the supercritical and the subcritical regime in order to extract their general dependencies on the control parameters. The inspection of the mean profiles provides us with some general hints on the mean to laminar shear ratio. Then the examination of the torque data allows us to propose a decomposition of the torque dependence on the control parameters in two terms, one completely given by measurements in the case where the outer cylinder is at rest, the other one being a universal function provided here from experimental fits. As a result, we obtain a general expression for the turbulent viscosity and compare it to existing prescription in the literature. Finally, throughout all the paper we discuss the influence of additional effects such as stratification or magnetic fields

ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations

Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESCs), including a knockout and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR) and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-sequencing analyses in Zscan10−/− mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10

Deficient sustained attention to response task and P300 characteristics in early Huntington’s disease

Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington’s disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (p < 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (p < 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Morphology of howler monkeys: a review and quantitative analyses.

44 pagesInternational audienceRecognition of a particularly derived eco-behavioral strategy for thegenus Alouatta has been crucial for studying and understanding its equally derivedcranial and postcranial morphology. The unique architecture of the skull and mandiblehas very likely evolved in relation to both masticatory correlates associatedwith an increasingly folivorous diet as well as the use of vocal communication associatedwith social behavior and an energy-minimizing strategy. Comparisons of cranialmorphology using three-dimensional geometric morphometrics havehighlighted signifi cant interspecifi c shape differences. Alouatta seniculus is themost divergent in both cranial and hyoid morphology and exhibits the most pronouncedlevels of sexual dimorphism in those areas. Cranial variability is expressedin facial prognathism and airorhynchy, basicranial fl exure, and zygomatic height.Inter- and intraspecifi c differences based on these axes of variation are very likelylinked to interspecifi c variations in diet, behavior, and life history. This is furtherevident in the dental anatomy of the genus, indicating adaptations to a shift to amore folivorous diet. In addition, recent studies provide further evidence for signifi -cant inter- and intraspecifi c variations in hyoid size and shape. Alouatta seniculuspossesses the largest and most infl ated hyoid bulla, and the species that occupy distributionalextremes ( A. palliata , A. caraya ) are differentiated by highly distinct hyoidshapes. These data indicate a complex relationship between morphology and behavior,with possible biogeographic implications. In terms of postcranial morphology, the forelimb bears a mixture of features that favor quadrupedalism with restrictedabduction and overhead extension, providing stable contact and support alongbranches. In contrast, the hind limb appears to allow for a wider range of movementin all joints, with an emphasis on thigh extension and abduction, leg rotation, andpowerful grasping with a habitually inverted foot. Interspecifi c variation revealstraits that can be ultimately related to subtle differences in the frequency of use ofdifferent positional modes, associated with variable eco-social factors. Theseresults, deriving from different anatomical regions, provide evidence for understandingmorphological variation across howler species in terms of morphofunctionaladaptations, environmental pressure, and niche partitioning

Physiological and pharmacological insights into the role of ionic channels in cardiac pacemaker activity

The generation of cardiac pacemaker activity is a complex phenomenon which requires the coordinated activity of different membrane ionic channels, as well as intracellular signalling factors including Ca(2+) and second messengers. The precise mechanism initiating automaticity in primary pacemaker cells is still matter of debate and certain aspects of how channels cooperate in the regulation of pacemaking by the autonomic nervous system have not been entirely elucidated. Research in the physiopathology of cardiac automaticity has also gained a considerable interest in the domain of cardiovascular pharmacology, since accumulating clinical and epidemiological evidence indicate a link between an increase in heart rate and the risk of cardiac mortality and morbidity. Lowering the heart rate by specific bradycardic agents in patients with heart disease constitutes a promising way to increase cardioprotection and improve survival. Thus, the elucidation of the mechanisms underlying the generation of pacemaker activity is necessary for the development of new therapeutic molecules for controlling the heart rate. Recent work on genetically modified mouse models provided new and intriguing evidence linking the activity of ionic channels genes to the generation and regulation of pacemaking. Importantly, results obtained on genetically engineered mouse strains have demonstrated that some channels are specifically involved in the generation of cardiac automaticity and conduction, but have no functional impact on the contractile activity of the heart. In this article, we will outline the current knowledge on the role of ionic channels in cardiac pacemaker activity and suggest new potential pharmacological targets for controlling the heart rate without concomitant negative inotropism