Quantitative prenatal growth of the cervical sympathetic trunk components in sheep (Ovis arise) during the foetal period

Background: Six liner measurements of constant cranial cervical ganglion (CCG), three inconstant main, first, second middle cervical ganglia (MG, MG1, MG2), and interganglionic branch (IGB) were taken to determine normal foetal growth rates and patterns of cervical sympathetic trunk (CST) components in different gestational ages. Materials and methods: Forty sheep foetuses of both sexes aged from 60 to 140 days were divided into four groups and 80 sides of foetuses were examined under a stereomicroscope using a digital calliper. Results: Following findings were obtained: 1) There was no significant difference for the values between sex and body side among all age groups, although sex and laterality differences in CST length and laterality differences in IGB total length and MG1 width were found regardless of age groups. 2) Correlations between dimensions of CST components and crown-rump length (CRL) were always positive during foetal period and decreased with increasing foetal age. 3) The highest growth rate in CST components in foetal sheep took place in the youngest age group because of rapid growth rates in lengths of IGB and CCG. Conclusions: Based on these detailed findings, comparative prenatal growth rates and patterns of animal organs and body, embryological and histological data as well as neurovertebral relationships among cervical parts of sympathetic trunk, spinal cord, and vertebral column were discussed and compared with previous studies. Although allometric growth of CST in relation to CRL was constant between foetal sheep and pig, there were specific characteristics in prenatal growth of CST components in foetal sheep which were different from those of foetal pig. It seems that only growth pattern in length of CST in sheep during foetal period follows the same growth pattern of CRL, body weight, and length of cervical parts of spinal cord and vertebral column

A comparison of He and Ne FIB imaging of cracks in microindented silicon nitride

Helium ion microscopy (HIM) offers potential as a high spatial resolution technique for imaging insulating samples that are susceptible to charging artifacts. In this study helium and neon ion microscopy are used to image cracking in microindented samples of the non-conductive ceramic silicon nitride. The crack morphology of radial cracks emanating from the microindentations has been characterized for two different compositions of silicon nitride, with and without conductive coatings. Gold coating enhances crack edge contrast, but masks grain contrast for both He and Ne ion-induced secondary electron (ISE) imaging. Carbon coating enables the crystalline and glassy phases to be distinguished, more clearly with Ne-ISE, and the cracking pathway is found to be primarily intergranular. Zones of < 100 nm diameter depleted ion-induced secondary electron emission along the crack paths are identified, consistent with charging ‘hotspots’

An Efficient Implementation of the Finite-volume Method For the Solution of Radiation Transport in Circuit Breakers

In this paper, we propose to revisit the method to solve the radiation transport equation in circuit breakers to reduce the computation time. It is based on an explicit approach using a space marching algorithm. The method can further be accelerated using a Cartesian grid and using the axisymmetric assumption. Comparisons performed in terms of accuracy and efficiency between the P1 model, the implicit finite-volume discrete ordinate method and the space-marching finite-volume discrete ordinate method show that the explicit approach is more that an order of magnitude faster than the implicit approach, for the same accuracy

Finite elements based approaches for the modelling of radial crack formation upon Vickers indentation in silicon nitride ceramics

© 2019 By having superior properties silicon nitride ceramics can be considered as the state-of-the-art material in the bearing industry. Vickers indentation of this material is typically accompanied by formation of cracks visible on surface. Two Finite Elements models are developed in the current work: the first model is based on fracture mechanics and the second on cleavage stress criterion. Plastic behavior of silicon nitride is included in the modeling, and since little is known on the plasticity of this material, the Drucker-Prager model (used for non-metallic materials)along with the classical J2-plasticity are explored. The results of the fracture mechanics based model correlate well with experimental results in terms of surface crack length. The numerical results in terms of the morphology of the indented zone (including cracks and plastic zone)are provided by the stress criterion based model, and these results correlate well too, with the experimental data

Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy.

Junctophilin-2 (JPH2) is a part of the junctional membrane complex that facilitates calcium-handling in the cardiomyocyte. Previously, missense variants in JPH2 have been linked to hypertrophic cardiomyopathy; however, pathogenic "loss of function" (LOF) variants have not been described. Family-based genetic analysis of GME individuals with cardiomyopathic disease identified an Iranian patient with dilated cardiomyopathy (DCM) as a carrier of a novel, homozygous single nucleotide insertion in JPH2 resulting in a stop codon (JPH2-p.E641*). A second Iranian family with consanguineous parents hosting an identical heterozygous variant had 2 children die in childhood from cardiac failure. To characterize ethnicity-dependent genetic variability in JPH2 and to identify homozygous JPH2 variants associated with cardiac disease, we identified variants in JPH2 in a worldwide control cohort (gnomAD) and 2 similar cohorts from the Greater Middle East (GME Variome, Iranome). These were compared against ethnicity-matched clinical whole exome sequencing (WES) referral tests and a case cohort of individuals with hypertrophic cardiomyopathy (HCM) based on comprehensive review of the literature. Worldwide, 1.45% of healthy individuals hosted a rare JPH2 variant with a significantly higher proportion among GME individuals (4.45%); LOF variants were rare overall (0.04%) yet were most prevalent in GME (0.21%). The increased prevalence of LOF variants in GME individuals was corroborated among region-specific, clinical WES cohorts. In conclusion, we report ethnic-specific differences in JPH2 rare variants, with GME individuals being at higher risk of hosting homozygous LOF variants. This conclusion is supported by the identification of a novel JPH2 LOF variant confirmed by segregation analysis resulting in autosomal recessive pediatric DCM due to presumptive JPH2 truncation

Pre-Stimulus Activity Predicts the Winner of Top-Down vs. Bottom-Up Attentional Selection

Our ability to process visual information is fundamentally limited. This leads to competition between sensory information that is relevant for top-down goals and sensory information that is perceptually salient, but task-irrelevant. The aim of the present study was to identify, from EEG recordings, pre-stimulus and pre-saccadic neural activity that could predict whether top-down or bottom-up processes would win the competition for attention on a trial-by-trial basis. We employed a visual search paradigm in which a lateralized low contrast target appeared alone, or with a low (i.e., non-salient) or high contrast (i.e., salient) distractor. Trials with a salient distractor were of primary interest due to the strong competition between top-down knowledge and bottom-up attentional capture. Our results demonstrated that 1) in the 1-sec pre-stimulus interval, frontal alpha (8–12 Hz) activity was higher on trials where the salient distractor captured attention and the first saccade (bottom-up win); and 2) there was a transient pre-saccadic increase in posterior-parietal alpha (7–8 Hz) activity on trials where the first saccade went to the target (top-down win). We propose that the high frontal alpha reflects a disengagement of attentional control whereas the transient posterior alpha time-locked to the saccade indicates sensory inhibition of the salient distractor and suppression of bottom-up oculomotor capture

NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease

A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized protein quality control pathway—Ribosome-associated Quality Control (RQC)—by mediating proteolytic targeting of incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to neurodegeneration in mice. Whether neurodegeneration results from defective RQC and whether defective RQC contributes to human disease have remained unknown. Here we show that three independently-generated mouse models with mutations in a different component of the RQC complex, NEMF/Rqc2, develop progressive motor neuron degeneration. Equivalent mutations in yeast Rqc2 selectively interfere with its ability to modify aberrant translation products with C-terminal tails which assist with RQC-mediated protein degradation, suggesting a pathomechanism. Finally, we identify NEMF mutations expected to interfere with function in patients from seven families presenting juvenile neuromuscular disease. These uncover NEMF’s role in translational homeostasis in the nervous system and implicate RQC dysfunction in causing neurodegeneration

Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration.

OBJECTIVE: To characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families. METHODS: We used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model. RESULTS: We identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years. CONCLUSIONS: This study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy

Spontaneous Prediction Error Generation in Schizophrenia

Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks