A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family

Hearing loss is a complex disorder caused by both genetic and environmental factors. Previously, mutations in CIB2 have been identified as a common cause of genetic hearing loss in Pakistani and Turkish populations. Here we report a novel (c.556C\u3eT; p.(Arg186Trp)) transition mutation in the CIB2 gene identified through whole exome sequencing (WES) in a Caribbean Hispanic family with non-syndromic hearing loss. CIB2 belongs to the family of calcium-and integrin-binding (CIB) proteins. The carboxy-termini of CIB proteins are associated with calcium binding and intracellular signaling. The p.(Arg186Trp) mutation is localized within predicted type II PDZ binding ligand at the carboxy terminus. Our ex vivo studies revealed that the mutation did not alter the interactions of CIB2 with Whirlin, nor its targeting to the tips of hair cell stereocilia. However, we found that the mutation disrupts inhibition of ATP-induced Ca2+ responses by CIB2 in a heterologous expression system. Our findings support p.(Arg186Trp) mutation as a cause for hearing loss in this Hispanic family. In addition, it further highlights the necessity of the calcium binding property of CIB2 for normal hearing

The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, of which 174 were highly enriched, including all known markers of these cells. Analysis of common variants near the corresponding genes in the AGRE collection implicated the RNA binding protein CELF6 in autism risk. Screening for rare variants in CELF6 identified an inherited premature stop codon in one of the probands. Subsequent disruption of Celf6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. This work provides a reproducible and accurate method to profile serotonergic neurons under a variety of conditions and suggests a novel paradigm for gaining information on the etiology of psychiatric disorders

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

Coex-Rank: An approach incorporating co-expression information for combined analysis of microarray data

Microarrays have been widely used to study differential gene expression at the genomic level. They can also provide genome-wide co-expression information. Biologically related datasets from independent studies are publicly available, which requires robust combined approaches for integration and validation. Previously, meta-analysis has been adopted to solve this problem

Anti-IgE therapy for IgE-mediated allergic diseases: from neutralizing IgE antibodies to eliminating IgE+ B cells

Abstract Allergic diseases are inflammatory disorders that involve many types of cells and factors, including allergens, immunoglobulin (Ig)E, mast cells, basophils, cytokines and soluble mediators. Among them, IgE plays a vital role in the development of acute allergic reactions and chronic inflammatory allergic diseases, making its control particularly important in the treatment of IgE-mediated allergic diseases. This review provides an overview of the current state of IgE targeted therapy development, focusing on three areas of translational research: IgE neutralization in blood; IgE-effector cell elimination; and IgE+ B cell reduction. IgE-targeted medicines such as FDA approved drug Xolair (Omalizumab) represent a promising avenue for treating IgE-mediated allergic diseases given the pernicious role of IgE in disease progression. Additionally, targeted therapy for IgE-mediated allergic diseases may be advanced through cellular treatments, including the modification of effector cells

Whole-Genome Sequencing and iPLEX MassARRAY Genotyping Map an EMS-Induced Mutation Affecting Cell Competition in Drosophila melanogaster

Cell competition, the conditional loss of viable genotypes only when surrounded by other cells, is a phenomenon observed in certain genetic mosaic conditions. We conducted a chemical mutagenesis and screen to recover new mutations that affect cell competition between wild-type and RpS3 heterozygous cells. Mutations were identified by whole-genome sequencing, making use of software tools that greatly facilitate the distinction between newly induced mutations and other sources of apparent sequence polymorphism, thereby reducing false-positive and false-negative identification rates. In addition, we utilized iPLEX MassARRAY for genotyping recombinant chromosomes. These approaches permitted the mapping of a new mutation affecting cell competition when only a single allele existed, with a phenotype assessed only in genetic mosaics, without the benefit of complementation with existing mutations, deletions, or duplications. These techniques expand the utility of chemical mutagenesis and whole-genome sequencing for mutant identification. We discuss mutations in the Atm and Xrp1 genes identified in this screen

Qal'at Sem'am. IV : Rapport final, 3 : Les objets métalliques

UV radiation of sunlight is one of harmful factors for earth organisms, especially for photoautotrophs because they require light for energy and biomass production. A number of works have already been done regarding the effects of UV-B radiation at biochemical and molecular level, which showed that UV-B radiation could inhibit photosynthesis activity and reduce photosynthetic electron transport. However quite limited information can accurately make out inhibition site of UV-B radiation on photosynthetic electron transport. In this study, this issue was investigated through measuring oxygen evolution activity, chlorophyll a fluorescence and gene expression in a model unicellular green alga Chlamydomonas reinhardtii. Our results indicated that UV-B radiation could evidently decrease photosynthesis activity and inhibit electron transport by blocking electron transfer process from the first plastoquinone electron acceptors Q(A) to second plastoquinone electron acceptors Q(B), but not impair electron transfer from the water oxidizing complex to Q(A). The psbA gene expression was also altered by UV-B radiation, where up-regulation occurred at 2, 4 and 6h after exposure and down-regulation happened at 12 and 24 h after exposure. These results suggested that UV-B could affects D1 protein normal turnover, so there was not enough D1 for binding with Q(B), which may affect photosynthetic electron transport and photosynthesis activity

MicroRNAs modulate adaption to multiple abiotic stresses in Chlamydomonas reinhardtii

MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were downregulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively. Q-PCR data indicated that ATP4, which was expressed inversely in relation to Cre-miR906-3p under stress conditions. Overexpressing of Cre-miR906-3p enhanced resistance to multiple stresses; conversely, overexpressing of ATP4 produced the opposite effect. These data of Q-PCR, degradome sequencing and adaptation of overexpressing lines indicated that Cre-miR906-3p and its target ATP4 were a part of the same pathway for stress adaptation. We found that Cre-miR910 and its target NCR2 were also a part of this pathway. Overexpressing of Cre-miR910 decreased, whereas that of NCR2 increased the adaption to multiple stresses. Our findings suggest that the two classes of miRNAs synergistically mediate stress adaptation in algae.</p