Study of the ecological gas for MRPCs

The Multigap Resistive Plate Chamber (MRPC) is a gaseous detector; the performance depends very much on the gas mixture as well as the design. MRPCs are used as a timing device in several collider experiments and cosmic ray experiments thanks to the excellent timing performance. The typical gas mixtures of RPC-type detectors at current experiments are based on the gases $\rm C_2F_4H_2$ and $\rm SF_6$. These gases have very high Global Warming Potential (GWP) values of 1430 and 23900 respectively. The present contribution has been performed as a part of efforts to reduce the amount of greenhouse gases used in high energy experiments. The performance of MRPC has been measured with two different gas mixtures; $\rm C_2F_4H_2$ based gas mixtures and the ecological $\rm C_3F_4H_2$ (HFO-1234ze). A small MRPC was used for the tests. It has an sensitive area of 20 $\times$ 20 $\rm cm^2$; it was been built with 6 gaps of 220 $\mu$m. In normal operation, the strong space charge created within the gas avalanche limits the avalanche's growth. $\rm SF_6$ plays an important part in the process due to its high attachment coefficient at low electric fields. It is thus necessary to find another gas that has a similar attachment coefficient. $\rm CF_{3}I$ is a possible candidate. Tests were performed with this gas added to $\rm C_3F_4H_2$

AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates.

OBJECTIVES: To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates. METHODS: Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target. RESULTS: Genomes of four multiply antibiotic-resistant A. baumannii clinical strains, from a US hospital system, belonging to prevalent MLST ST2 (Pasteur scheme) and ST281 (Oxford scheme) clade F isolates were sequenced to completion. A class 1 integron carrying aadB (tobramycin resistance) and aadA2 (streptomycin/spectinomycin resistance) was identified. The class 1 integron was 6.8 kb, bounded by IS26 at both ends, and embedded in a new target location between an α/β-hydrolase and a reductase. Due to its novel insertion site and unique RI composition, we suggest naming this novel RI AbGRI4. Molecular analysis of global A. baumannii isolates identified multiple AbGRI4 RI variants in non-ST2 clonal lineages, including variations in the resistance gene cassettes, integron backbone and insertion breakpoints at the hydrolase gene. CONCLUSIONS: A novel RI insertion target harbouring a class 1 integron was identified in a subgroup of ST2/ST281 clinical isolates. Variants of the RI suggested evolution and horizontal transfer of the RI across clonal lineages. Long- and short-read hybrid assembly technology completely resolved the genomic context of IS-bounded RIs, which was not possible using short reads alone

Identification of microRNAs and their targets in four Gossypium species using RNA sequencing

MicroRNAs (miRNAs) are small non-coding endogenous riboregulators that play significant roles in plant growth, development, metabolism, defense, and stress responses. Upland cotton is best known for its economic value as natural fiber and oil. It is also an important model for genome evolution, polyploidy effects, cell growth, and cell wall biosynthesis. The polyploid species, Gossypium hirsutum L. (2n = 52), evolved from two progenitors (2n = 26), one contributing an ancestral genome similar to A genomes of G. herbaceum and G. arboreum, and the other like the D genome of G. raimondii. There is much to be learned about Gossypium miRNAs and their gene targets, about the effects of polyploidy and their practical ramifications. In this study, small-RNA (sRNA) libraries from four Gossypium species and three tissue libraries (seed, seedling, and leaf) from G. hirsutum were constructed and analyzed using high-throughput sequencing with Illumina/MiSeq then computational prediction by MIREAP. Results showed 245 known miRNAs belonging to 67 miRNA families and 149 novel (non-redundant and redundant) miRNAs derived from 394 genomic loci. This unified study identified 21 and 33 conserved miRNA families across four Gossypium species and three tissue libraries, respectively. Similar to canonical miRNAs, the 5′ of novel miRNAs had the higher preference for U and A residues. In this study, 551 potential target genes were predicted in 45 conserved miRNA families, while 439 targets were associated with 113 novel miRNAs. The majority of the conserved (34%) and novel (22%) miRNA targets identified belonged to cellular processes and signaling. However, the functional diversity of novel miRNA targets is attributed to the tissue and species bias. Most of the identified targets were regulated by mRNA cleavage than by translational repression. These results provide a basis for better understanding regulatory networks in upland cotton (G. hirsutum) and its closest progenitors. Keywords: Cotton, Progenitor, Sequencing, Prediction, MIREAP, sRNA, miRNA, Family, Known, Novel, Gene regulation, Targe

SVEP1 as a Genetic Modifier of TEK-Related Primary Congenital Glaucoma

PURPOSE. Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss by the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploinsufficiency accounts for 5% of PCG in diverse populations, with low penetrance explained by variable dysgenesis of Schlemm’s canal (SC) in mice. We report eight families with TEK-related PCG, and provide evidence for SVEP1 as a disease modifier in family 8 with a higher penetrance and severity. METHODS. Exome sequencing identified coding/splice site variants with an allele frequency less than 0.0001 (gnomAD). TEK variant effects were assayed in constructtransfected HEK293 cells via detection of autophosphorylated (active) TEK protein. An enucleated eye from an affected member of family 8 was examined via histology. SVEP1 expression in developing outflow tissues was detected by immunofluorescent staining of 7-day mouse anterior segments. SVEP1 stimulation of TEK expression in human umbilical vascular endothelial cells (HUVECs) was measured by TaqMan quantitative PCR. RESULTS. Heterozygous TEK loss-of-function alleles were identified in eight PCG families, with parent–child disease transmission observed in two pedigrees. Family 8 exhibited greater disease penetrance and severity, histology revealed absence of SC in one eye, and SVEP1:p.R997C was identified in four of the five affected individuals. During SC development, SVEP1 is secreted by surrounding tissues. SVEP1:p.R997C abrogates stimulation of TEK expression by HUVECs. CONCLUSIONS. We provide further evidence for PCG caused by TEK haploinsufficiency, affirm autosomal dominant inheritance in two pedigrees, and propose SVEP1 as a modifier of TEK expression during SC development, affecting disease penetrance and severity.Supported by the National Institutes of Health [R01EY014685 to T.Y., R01HL124120, T32DK108738, R01EY025799, and P30DK114857 to S.Q.]; the Research to Prevent Blindness Inc. [Lew R. Wasserman Award to T.Y.]; a University of Wisconsin Centennial Scholars Award [to T.Y.]; the Flinders Foundation and the National Health and Medical Research Council of Australia [APP1116360, APP1107098, and fellowship APP1154824 to J.C.]; the Foundation for Science and Technology, Human Potential Operational Program/European Social Fund [fellowship SFRH/BD/90445/2012 to S.C.]; the Agency for Science Technology and Research, under the Industry Alignment Fund - Pre-Positioning Programme, as part of the Innovations in Food & Chemical Safety Programme [H18/01/a0/b14 to V.L.]; the Ophthalmic Research Center of Shahid Beheshti University of Medical Sciences and the Iran National Science Foundation [940012 to E.E.]; a Core Grant for Vision Research from the National Eye Institute/National Institutes of Health to the University of Wisconsin-Madison [P30EY016665]; and an Unrestricted Grant from Research to Prevent Blindness, Inc. to the UW-Madison Department of Ophthalmology and Visual Sciences. The authors are grateful to the Vanderbilt clinical site of the Undiagnosed Diseases Network for contribution of one individual for this manuscript: John A Phillips III, John H. Newman, Joy Cogan, and Rizwan Hamid; supported in part by the National Institutes of Health Common Fund [UO1HG007674]