Single-cell transcriptomic profiling of the mouse cochlea: An atlas for targeted therapies.

Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. As a result, the search for curative treatments, which are sorely lacking in the hearing field, has become a potentially achievable objective, particularly via cochlear gene and cell therapies. To this end, a complete inventory of cochlear cell types, with an in-depth characterization of their gene expression profiles right up to their final differentiation, is indispensable. We therefore generated a single-cell transcriptomic atlas of the mouse cochlea based on an analysis of more than 120,000 cells on postnatal day 8 (P8), during the prehearing period, P12, corresponding to hearing onset, and P20, when cochlear maturation is almost complete. By combining whole-cell and nuclear transcript analyses with extensive in situ RNA hybridization assays, we characterized the transcriptomic signatures covering nearly all cochlear cell types and developed cell type-specific markers. Three cell types were discovered; two of them contribute to the modiolus which houses the primary auditory neurons and blood vessels, and the third one consists in cells lining the scala vestibuli. The results also shed light on the molecular basis of the tonotopic gradient of the biophysical characteristics of the basilar membrane that critically underlies cochlear passive sound frequency analysis. Finally, overlooked expression of deafness genes in several cochlear cell types was also unveiled. This atlas paves the way for the deciphering of the gene regulatory networks controlling cochlear cell differentiation and maturation, essential for the development of effective targeted treatments.

Cognitive and Brain Gray Matter Changes in Children with Obstructive Sleep Apnea: A Voxel-Based Morphological Study.

BACKGROUND: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and clinical severity indicator of children with OSA. METHODS: Twenty-seven children with OSA (7.6 ± 2.5 years, apnea hypopnea index [AHI]: 9.7 ± 5.3 events/h) and 30 healthy controls (7.8 ± 2.6 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent 3.0 T magnetic resonance imaging of the brain and cognitive testing evaluating. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry were performed. Pearson's correlation analysis was performed between these features of gray matter volume (GMV) and obstructive apnea index (OAI) among children with OSA. RESULTS: In the comparison of children's Wechsler test scores of full-scale intelligence quotient and verbal intelligence quotient, the OSA group was significantly lower than the control group (p < 0.05). Compared with the control group, the GMV of many brain regions in the OSA group was significantly decreased (p < 0.05). In the correlation analysis of GMV and OAI in OSA group, right inferior frontal gyrus volume was significantly negatively correlated with OAI (r = - 0.49, p = 0.02). CONCLUSION: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions. This finding suggests an association between the OSA and decreased GMV in children.

DNABarcodeCompatibility: an R-package for optimizing DNA-barcode combinations in multiplex sequencing experiments.

SUMMARY: Using adequate DNA barcodes is essential to unambiguously identify each DNA library within a multiplexed set of libraries sequenced using next-generation sequencers. We introduce DNABarcodeCompatibility, an R-package that allows one to design single or dual-barcoding multiplex experiments by imposing desired constraints on the barcodes (including sequencer chemistry, barcode pairwise minimal distance and nucleotide content), while optimizing barcode frequency usage, thereby allowing one to both facilitate the demultiplexing step and spare expensive library-preparation kits. The package comes with a user-friendly interface and a web app developed in Java and Shiny (https://dnabarcodecompatibility.pasteur.fr), respectively, with the aim to help bridge the expertise of core facilities with the experimental needs of non-experienced users. AVAILABILITY AND IMPLEMENTATION: DNABarcodeCompatibility can be easily extended to fulfil specific project needs. The source codes of the R-package and its user interfaces are publicly available along with documentation at [https://github.com/comoto-pasteur-fr] under the GPL-2 licence. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome-wide association links candidate genes to resistance to Plum Pox Virus in apricot (Prunus armeniaca).

In fruit tree species, many important traits have been characterized genetically by using single-family descent mapping in progenies segregating for the traits. However, most mapped loci have not been sufficiently resolved to the individual genes due to insufficient progeny sizes for high resolution mapping and the previous lack of whole-genome sequence resources of the study species. To address this problem for Plum Pox Virus (PPV) candidate resistance gene identification in Prunus species, we implemented a genome-wide association (GWA) approach in apricot. This study exploited the broad genetic diversity of the apricot (Prunus armeniaca) germplasm containing resistance to PPV, next-generation sequence-based genotyping, and the high-quality peach (Prunus persica) genome reference sequence for single nucleotide polymorphism (SNP) identification. The results of this GWA study validated previously reported PPV resistance quantitative trait loci (QTL) intervals, highlighted other potential resistance loci, and resolved each to a limited set of candidate genes for further study. This work substantiates the association genetics approach for resolution of QTL to candidate genes in apricot and suggests that this approach could simplify identification of other candidate genes for other marked trait intervals in this germplasm.

Multifunctional Cd-CP for fluorescence sensing of Cr(VI), MnO4-, acetylacetone and ascorbic acid in aqueous solutions.

The development of multifunctional fluorescent chemosensors for the detection of multiple targets remains challenging but of great importance. In this paper, one novel coordination polymer (CP), denoted as [Cd2(edda)(phen)2]∙H2O (compound 1, H4edda = 5,5' (ethane-1,2-diylbis(oxy)) diisophthalic acid, phen = 1,10-phenanthroline) is successfully designed and prepared under hydrothermal conditions. Structural analysis indicates that compound 1 possesses a one-dimensional (1D) double chain structure, then self-assembles into a three-dimensional (3D) supramolecular framework via π…π interactions between phen molecules. Interestingly, compound 1 is found to be tolerant in wide range of acidic to alkaline aqueous solutions (pH = 2-13). Fluorescent spectral investigations reveal that compound 1 exhibits highly selective and sensitive fluorescence responses toward MnO4-, Cr(VI) ions, acetylacetone (acac) and ascorbic acid (AA) by fluorescence quenching in the aqueous phase. The detection limits are in the very low range, reaching µM level for the detection of MnO4-, Cr(VI) ions, nM for AA and ppm for acac detection. The distinguished multi-responsive performance suggests compound 1 to be a potential multifunctional probe. Furthermore, the possible quenching mechanisms have also been systematically investigated in this work.

3D ZnII-Based coordination polymer: Synthesis, structure and fluorescent sensing property for nitroaromatic compounds.

A water-stable ZnII-based coordination polymer (CP) with excellent photophysical behavior, namely [Zn2L(atez)(H2O)2] (compound 1; H3L = 4-(2',3'-dicarboxylphenoxy); atez = 5-aminotetrazole), was successfully prepared by the solvothermal reaction of Zn ions with a π-conjugated and semi-rigid multicarboxylate ligand H3L in the presence of N-containing linker atez. Compound 1 displays a hierarchically pillared three-dimensional (3D) (3,4,5)-connected (4·62) (42·64) (43·64·83) net which is based on two-dimensional (2D) multicarboxylate- ZnII layers strutted by the atez ligands. Sensing investigations of compound 1 reveal that this material can selectively and sensitively detect nitroaromatic compounds in water suspension through fluorescence quenching effect. In particular, it is worth noting that it shows highly specific detection of nitrobenzene (NB) and 2,4,6-trinitrophenol (TNP) with remarkable quenching constants (KSV = 7.5 × 104 M-1 for NB and KSV = 1.9 × 105 M-1 for TNP) and low limit of detection (LOD = 0.93 µM for NB and LOD = 0.36 µM for TNP). Investigations reveal that the probable mechanisms for such sensing processes are the concurrent presence of fluorescence resonance energy transfer (FRET) as well as photoinduced electron transfer (PET) between the CP and nitroaromatic molecules. This work not only offers an effective route to improve the application of fluorescent CPs but also provide one novel probable fluorescence probe for nitroaromatic compounds.

[Characteristics of Industrial Volatile Organic Compounds(VOCs) Emission in China from 2011 to 2019].

In order to better understand the industrial volatile organic compounds(VOCs) emissions in China in recent years, an industrial VOCs emission inventory was developed from 2011 to 2019, based on the dynamic emission factors method and the comprehensive source classification system. The results showed that VOCs emissions increased first from 11122.7 kt in 2011 to 13397.9 kt in 2017, and then decreased to 13247.0 kt in 2019. The emission structure of the four source categories changed. The contribution from basic organic chemical industries, gasoline storage and transportation, manufacturing(i.e., coatings, inks, pigments, and similar products), and industrial protective coatings continued to increase. On the contrary, the contributions of oil and natural gas processing, automobile, and container manufacturing industries declined over the study period. Among the industrial emissions in China in 2019, industrial coating, printing, and basic organic chemical industries emitted large amounts of VOCs(accounting for 39.2% of the total emission), and because their contribution became increasingly prominent since 2011, these sectors will be the key emission sources in the future. With respect to the spatial distribution in 2019, East China and South China had the largest VOCs emissions. Shandong, Guangdong, Jiangsu, and Zhejiang were the four provinces that contributed the most, accounting for 40.6% of the total VOCs emissions.

Central Sleep Apnea Alters Neuronal Excitability and Increases the Randomness in Sleep-Wake Transitions.

OBJECTIVE: While most studies on Central Sleep Apnea (CSA) have focused on breathing and metabolic disorders, the neuronal dysfunction that causes CSA remains largely unknown. Here, we investigate the underlying neuronal mechanism of CSA by studying the sleep-wake dynamics as derived from hypnograms. METHODS: We analyze sleep data of seven groups of subjects: healthy adults (n = 48), adults with obstructive sleep apnea (OSA) (n = 29), adults with CSA (n = 25), healthy children (n = 40), children with OSA (n = 18), children with CSA (n = 73) and CSA children treated with CPAP (n = 10). We calculate sleep-wake parameters based on the probability distributions of wake-bout durations and sleep-bout durations. We compare these parameters with results obtained from a neuronal model that simulates the interplay between sleep- and wake-promoting neurons. RESULTS: We find that sleep arousals of CSA patients show a characteristic time scale (i.e., exponential distribution) in contrast to the scale-invariant (i.e., power-law) distribution that has been reported for arousals in healthy sleep. Furthermore, we show that this change in arousal statistics is caused by triggering more arousals of similar durations, which through our model can be related to a higher excitability threshold in sleep-promoting neurons in CSA patients. CONCLUSIONS: We propose a neuronal mechanism to shed light on CSA pathophysiology and a method to discriminate between CSA and OSA. We show that higher neuronal excitability thresholds can lead to complex reorganization of sleep-wake dynamics. SIGNIFICANCE: The derived sleep parameters enable a more specific evaluation of CSA severity and can be used for CSA diagnosis and monitor CSA treatment.

Genetic heterogeneity of congenital hearing impairment in Algerians from the Ghardaïa province.

BACKGROUND: Consanguinity rate is high in Algeria, and the population is thus at high risk for genetic diseases transmitted on an autosomal recessive mode. Inherited congenital hearing impairment (HI) is a highly heterogeneous disorder, which affects approximately 1 in 800 Algerian newborns. Several hundreds of genes responsible for deafness have been reported among which more than one hundred are responsible for isolated deafness, of which 19 have already been reported to be involved in the Algerian population. This study focuses on patients from the Ghardaïa province, an ethnically and geographically isolated region of Southern Algeria that has the highest consanguinity rate in the country (56%). METHODS: Eleven families, with at least two related members experiencing moderate to profound congenital HI, were recruited and screened for mutations in known HI genes. RESULTS: A preliminary screening for common mutations in GJB2 and GJB6 identified the prevalent GJB2:c.35delG mutation in four families. Targeted exome sequencing further identified the causal mutations in the remaining seven families: CIB2:c.97C > T; p.(Arg33*), MYO7A:c.470+1G > A; p.(?), and SLC26A4:c.410C > T; p.(Ser137Leu) biallelic mutations in two families each, and a TECTA:c.2743 A > G; p.(Ile915Val) monoallelic mutation in the only family with autosomal dominant transmission of the HI. Of note, the missense mutations of SLC26A4 and TECTA had not been previously reported. CONCLUSION: These results further substantiate the genetic heterogeneity of HI, even in reportedly isolated populations. However, several families may harbor the same mutations as a result of a long history of marriages between relatives. This study has important implications for the HI molecular diagnosis strategy, and to develop genetic counseling for families originating from the Ghardaïa province of Algeria.

[Study of dental caries and the influence of social-behavioral risk factors on dental caries of 1,080 15-year-old adolescents].

OBJECTIVE: To describe the dental caries of 15-year-old adolescents in Hubei province, and to determine the influence of various social-behavioral risk factors on dental caries in the population. METHODS: The survey employed a multistage, stratified, non-geometric proportional randomized sampling, representing adolescents aged 15-year-old in Hubei province. The epidemiological investigation of dental caries was made by clinical oral health examination. Oral health knowledge, attitude and behavior investigated by questionnaire. RESULTS: The prevalence and mean DMFT in 1,080 15-year-old adolescents in Hubei province was 24.4% and 0.45, respectively. 11.4% of the adolescents brushed their teeth at least twice a day, 33.1% of the adolescents ever visited the dentists. A significant higher prevalence of dental caries was observed in girls (OR = 1.70). In addition, those who visit dentists and those who the scores of the consumption of sugar drink were high tended to have a higher prevalence of dental caries. CONCLUSION: The dental caries prevalence of adolescents in Hubei province is low, but oral health habit of adolescents seems poor. Gender and consumption of sugar drink may be risk factors of dental caries.