Dimensional evolution between one- and two-dimensional topological phases

published_or_final_versio

Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons

Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal neuropathies characterized by a phenotype that is more severe in the upper extremities. We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. GARS is a member of the family of aminoacyl-tRNA synthetases responsible for charging tRNA with cognate amino acids; GARS ligates glycine to tRNAGly. Here, we present functional analyses of disease-associated GARS mutations and show that there are not any significant mutation-associated changes in GARS expression levels; that the majority of identified GARS mutations modeled in yeast severely impair viability; and that, in most cases, mutant GARS protein mislocalizes in neuronal cells. Indeed, four of the five mutations studied show loss-of-function features in at least one assay, suggesting that tRNA-charging deficits play a role in disease pathogenesis. Finally, we detected endogenous GARS-associated granules in the neurite projections of cultured neurons and in the peripheral nerve axons of normal human tissue. These data are particularly important in light of the recent identification of CMT-associated mutations in another tRNA synthetase gene [YARS(tyrosyl-tRNA synthetase gene)]. Together, these findings suggest that tRNA-charging enzymes play a key role in maintaining peripheral axons

In vivo and in vitro studies of Th17 response to specific immunotherapy in house dust mite-induced allergic rhinitis patients

10.1371/journal.pone.0091950PLoS ONE93-POLN

Optogenetic control of Drosophila using a red-shifted channelrhodopsin reveals experience-dependent influences on courtship

Optogenetics allows the manipulation of neural activity in freely moving animals with millisecond precision, but its application in Drosophila melanogaster has been limited. Here we show that a recently described red activatable channelrhodopsin (ReaChR) permits control of complex behavior in freely moving adult flies, at wavelengths that are not thought to interfere with normal visual function. This tool affords the opportunity to control neural activity over a broad dynamic range of stimulation intensities. Using time-resolved activation, we show that the neural control of male courtship song can be separated into (i) probabilistic, persistent and (ii) deterministic, command-like components. The former, but not the latter, neurons are subject to functional modulation by social experience, which supports the idea that they constitute a locus of state-dependent influence. This separation is not evident using thermogenetic tools, a result underscoring the importance of temporally precise control of neuronal activation in the functional dissection of neural circuits in Drosophila

Taxonomic notes on the armored spiders of the families Pacullidae and Tetrablemmidae (Arachnida, Araneae) from Singapore

Eight species of armored spiders belonging to two families, Pacullidae Simon, 1894 and Tetrablemmidae O. Pickard-Cambridge, 1873, are reported from Singapore. Five species are documented as new to science: Paculla bukittimahensis Lin & Li, sp. n. (male and female), P. globosa Lin & Li, sp. n. (male and female), Ablemma malacca Lin & Li, sp. n. (male and female), Singaporemma lenachanae Lin & Li, sp. n. (male and female), and Sulaimania brevis Lin & Li, sp. n. (male). The three known species are Brignoliella besutensis Lin, Li & Jager, 2012, B. michaeli Lehtinen, 1981, and Singaporemma singulare Shear, 1978, of which the female of B. besutensis is described for the first time. For comparison, types of Singaporemma adjacens Lehtinen, 1981 from Vietnam, Singaporemma halongense Lehtinen, 1981 from Vietnam, Singaporemma singulare from Singapore and Sulaimania vigelandi Lehtinen, 1981 from Malaysia are studied and photographed

Sparse, decorrelated odor coding in the mushroom body enhances learned odor discrimination

Sparse coding may be a general strategy of neural systems for augmenting memory capacity. In Drosophila melanogaster, sparse odor coding by the Kenyon cells of the mushroom body is thought to generate a large number of precisely addressable locations for the storage of odor-specific memories. However, it remains untested how sparse coding relates to behavioral performance. Here we demonstrate that sparseness is controlled by a negative feedback circuit between Kenyon cells and the GABAergic anterior paired lateral (APL) neuron. Systematic activation and blockade of each leg of this feedback circuit showed that Kenyon cells activated APL and APL inhibited Kenyon cells. Disrupting the Kenyon cell–APL feedback loop decreased the sparseness of Kenyon cell odor responses, increased inter-odor correlations and prevented flies from learning to discriminate similar, but not dissimilar, odors. These results suggest that feedback inhibition suppresses Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the odor specificity of memories

Stiffness evaluation of a novel ankle rehabilitation exoskeleton with a type-variable constraint

This paper presents a novel ankle rehabilitation exoskeleton with two rotational degrees of freedom, which is suitable for dynamical rehabilitation for patients with neurological impairments. Its stiffness performance is assessed in consideration that the interaction between the footplate and the ground may deflect the mechanism away from the desired/predefined motion patterns. The novel design employs a universal-prismatic-universal (U-P-U) joint link, whose constraint type changes between a couple and a line vector during manipulation of the exoskeleton. To conduct a stiffness analysis of such a mechanism with a type-variable constraint – for the first time – a modified screw-based method (SBM) is proposed. Comparisons with the results obtained from finite element analysis verified that, the modified SBM provides reliable estimates of the exoskeleton's stiffness within the complete workspace (covering the constraint-type transition configurations). The stiffness of the exoskeleton is further evaluated by acquiring the minimum/maximum stiffness values, after computing the distribution of the most crucial linear and angular stiffness parameters within the workspace. Moreover, the influence of the architectural parameters on the stiffness properties is considered for further design optimization

Exome Sequencing Analysis and Clinical Features of a Chinese Patient with 3M Syndrome and A Review of Literature

Xiao-Li Chen,1,2 Dai-Shan Zheng,3 Yi-Fan Shen,3 Zhen-Lang Lin,1,2 Shang-Qin Chen,4,* Xiu-Man Xiao4,* 1Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Clinical Research Center for Pediatric Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Key Laboratory of Perinatal Medicine of Wenzhou, Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shang-Qin Chen, Key Laboratory of Perinatal Medicine of Wenzhou, Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email [email protected] Xiu-Man Xiao, Key Laboratory of Perinatal Medicine of Wenzhou, Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email [email protected]: 3M syndrome is a rare autosomal recessive genetic disorder characterized by significant intrauterine and postnatal growth restriction. There is limited research on its genetic basis within the Chinese population.Methods: We performed trio-based whole-exome sequencing to identify the pathogenic gene in the affected child and collected and organized clinical and imaging data. Relevant information was reviewed through a literature search.Results: In this study, we present a case involving prenatal diagnostic abnormalities and postnatal confirmation of 3M syndrome, including detailed documentation of clinical features and associated genetic variants. Notably, during prenatal ultrasound examination, the fetus exhibited increased nuchal translucency (NT) and delayed limb development. Postnatally, whole-exome sequencing revealed the compound heterozygous mutations in the CUL7 gene: c.3646– 2A>G and c.3355+5G>A. The splicing mutation c.3646– 2A>G is a novel pathogenic mutation, while the c.3355+5G>A mutation has been previously reported. In-silico analysis predicted strong pathogenicity for both splicing mutations. Through follow-up, we observed that the patient’s height and weight are below the first percentile, with abnormal skeletal development and distinctive facial features. Based on literature review of reported cases, these mutations disrupt the normal function of CUL7-OBSL1-CCDC8 complex in the ubiquitin-proteasome pathway, leading to impaired growth regulation.Discussion: This study identified a novel splicing mutation in the CUL7 gene in a patient with 3M syndrome, expanding the genetic spectrum of this disorder and contributing novel insights for clinical diagnosis and management.Keywords: 3M syndrome, CUL7, whole-exome sequencin

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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