Therapeutic Effect of Targeting Branched-Chain Amino Acid Catabolic Flux in Pressure-Overload Induced Heart Failure.

Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods and Results BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), a small-molecule inhibitor of branched-chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle-treated mice, whereas the BT2-treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity. Conclusions Our data provide the first proof-of-concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure

Glucagon Receptor Antagonism Ameliorates Progression of Heart Failure.

Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at 4 weeks after myocardial infarction. In addition, REMD2.59 treatment at the onset of pressure overload significantly suppressed cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. Initiation of REMD2.59 treatment 2 weeks after pressure overload significantly blunted the progression of cardiac pathology. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to ameliorate both onset and progression of heart failure

Detection of Favorable QTL Alleles and Candidate Genes for Lint Percentage by GWAS in Chinese Upland Cotton

Improving cotton yield is a major breeding goal for Chinese upland cotton. Lint percentage is an important yield component and a critical economic index for cotton cultivars, and raising the lint percentage has a close relationship to improving cotton lint yield. To investigate the genetic architecture of lint percentage, a diversity panel consisting of 355 upland cotton accessions was grown, and the lint percentage was measured in four different environments. Genotyping was performed with specific-locus amplified fragment sequencing (SLAF-seq). Twelve single-nucleotide polymorphisms (SNPs) associated with lint percentage were detected via a genome-wide association study (GWAS), in which five SNP loci distributed on chromosomes At3 (A02) and At4 (A08) and contained two major-effect QTLs, which were detected in the best linear unbiased predictions (BLUPs) and in more than three environments simultaneously. Furthermore, favorable haplotypes (FHs) of two major-effect QTLs and 47 putative candidate genes in the two linkage disequilibrium (LD) blocks of these associated loci were identified. The expression levels of these putative candidate genes were estimated using RNA-seq data from ten upland cotton tissues. We found that Gh_A02G1268 was very highly expressed during the early fiber development stage, whereas the gene was poorly expressed in the seed. These results implied that Gh_A02G1268 may determine the lint percentage by regulating seed and fiber development. The favorable QTL alleles and candidate genes for lint percentage identified in this study will have high potential for improving lint yield in future Chinese cotton breeding programs

Experimental investigations of CO2 adsorption behavior in shales: Implication for CO2 geological storage

Injecting CO2 into shale reservoirs has dual benefits for enhancing gas recovery and CO2 geological sequestration, which is of great significance to ensuring energy security and achieving the “Carbon Neutrality” for China. The CO2 adsorption behavior in shales largely determined the geological sequestration potential but remained uncharted. In this study, the combination of isothermal adsorption measurement and basic petro-physical characterization methods were performed to investigate CO2 adsorption mechanism in shales. Results show that the CO2 sorption capacity increase gradually with injection pressure before reaching an asymptotic maximum magnitude, which can be described equally well by the Langmuir model. TOC content is the most significant control factor on CO2 sorption capacity, and the other secondary factors include vitrinite reflectance, clay content, and brittle mineral content. The pore structure parameter of BET-specific surface area is a more direct factor affecting CO2 adsorption of shale than BJH pore volume. Langmuir CO2 adsorption capacity positive correlated with the surface fractal dimension (D1), but a significant correlation is not found with pore structure fractal dimension (D2). By introducing the Carbon Sequestration Leaders Forum and Department of Energy methods, the research results presented in this study can be extended to the future application for CO2 geological storage potential evaluation in shales

Identification, Expression, and Functional Analysis of the Group IId WRKY Subfamily in Upland Cotton (Gossypium hirsutum L.)

WRKY transcription factors have diverse functions in regulating stress response, leaf senescence, and plant growth and development. However, knowledge of the group IId WRKY subfamily in cotton is largely absent. This study identified 34 group IId WRKY genes in the Gossypium hirsutum genome, and their genomic loci were investigated. Members clustered together in the phylogenetic tree had similar motif compositions and gene structural features, revealing similarity and conservation within group IId WRKY genes. During the evolutionary process, 14 duplicated genes appeared to undergo purification selection. Public RNA-seq data were used to examine the expression patterns of group IId WRKY genes in various tissues and under drought and salt stress conditions. Ten highly expressed genes were identified, and the ten candidate genes revealed distinct expression patterns under drought and salt treatments by qRT-PCR analysis. Among them, Gh_A11G1801 was used for functional characterization. GUS activity was differentially induced by various stresses in Gh_A11G1801p::GUS transgenic Arabidopsis plants. The virus-induced gene silencing (VIGS) of Gh_A11G1801 resulted in drought sensitivity in cotton plants, which was accompanied by elevated malondialdehyde (MDA) content and reduced catalase (CAT) content. Taken together, these findings obtained in this study provide valuable resources for further studying group IId WRKY genes in cotton. Our results also enrich the gene resources for the genetic improvements of cotton varieties that are suitable for growth in stressful conditions

Genome sequence of the cultivated cotton <i>Gossypium arboreum</i>

The complex allotetraploid nature of the cotton genome (AADD; 2n = 52) makes genetic, genomic and functional analyses extremely challenging. Here we sequenced and assembled the Gossypium arboreum (AA; 2n = 26) genome, a putative contributor of the A subgenome. A total of 193.6 Gb of clean sequence covering the genome by 112.6-fold was obtained by paired-end sequencing. We further anchored and oriented 90.4% of the assembly on 13 pseudochromosomes and found that 68.5% of the genome is occupied by repetitive DNA sequences. We predicted 41,330 protein-coding genes in G. arboreum. Two whole-genome duplications were shared by G. arboreum and Gossypium raimondii before speciation. Insertions of long terminal repeats in the past 5 million years are responsible for the twofold difference in the sizes of these genomes. Comparative transcriptome studies showed the key role of the nucleotide binding site (NBS)-encoding gene family in resistance to Verticillium dahliae and the involvement of ethylene in the development of cotton fiber cells.Genetics &amp; HereditySCI(E)[email protected]; [email protected]; [email protected]

Untersuchungen uber das Schicksal der in rohes und gekochtes Brunnenwasser gemischten pathogenen Bakterien

Der Verfasser hat Untersuchungen uber die Lebensdauer von pathogenen Darmbakterien, die in rohes und gekochtes Brunnenwasser gemischt wurden, durchgefuhrt. Er hat 5 Brunnenwasser untersucht mit B. typhosus, B. paratyphosus A u. B, B. dysenteriae Komagome A u. B, B. dysenteriae Shiga; die Stamme erhielt Verf. aus dem Staatlichen Institut fur Infektionskrankheiten und aus dem bakteriologischen Institut zu Chiba. Die Ergebnisse sind folgende: 1) war die Menge der verwandten Bakterien klein (ca. 1/3000 Ose in 10 cc.), lebten alle Bakterien in rohem Wasser langer als in gekochtem Wasser. 2) war die Bakterienmenge relativ gross (1 Ose in 10 cc.), lebten die Bakterien zwar langer als bei geringer Menge, verschwanden aber in rohem Wasser schneller als in gekochtem. 3) Unter beiden Versuchsanordnungen lebten die Bakterien im Brunnenwasser langer als in Aq. dest. oder in physiologischer Kochsalzlosung. 4) Die Tabellen zeigen kurz die Ergebnisse: (Autoreferat

Generation of ESTs for Flowering Gene Discovery and SSR Marker Development in Upland Cotton

BACKGROUND: Upland cotton, Gossypium hirsutum L., is one of the world's most important economic crops. In the absence of the entire genomic sequence, a large number of expressed sequence tag (EST) resources of upland cotton have been generated and used in several studies. However, information about the flower development of this species is rare. METHODOLOGY/PRINCIPAL FINDINGS: To clarify the molecular mechanism of flower development in upland cotton, 22,915 high-quality ESTs were generated and assembled into 14,373 unique sequences consisting of 4,563 contigs and 9,810 singletons from a normalized and full-length cDNA library constructed from pooled RNA isolated from shoot apexes, squares, and flowers. Comparative analysis indicated that 5,352 unique sequences had no high-degree matches to the cotton public database. Functional annotation showed that several upland cotton homologs with flowering-related genes were identified in our library. The majority of these genes were specifically expressed in flowering-related tissues. Three GhSEP (G. hirsutum L. SEPALLATA) genes determining floral organ development were cloned, and quantitative real-time PCR (qRT-PCR) revealed that these genes were expressed preferentially in squares or flowers. Furthermore, 670 new putative microsatellites with flanking sequences sufficient for primer design were identified from the 645 unigenes. Twenty-five EST-simple sequence repeats were randomly selected for validation and transferability testing in 17 Gossypium species. Of these, 23 were identified as true-to-type simple sequence repeat loci and were highly transferable among Gossypium species. CONCLUSIONS/SIGNIFICANCE: A high-quality, normalized, full-length cDNA library with a total of 14,373 unique ESTs was generated to provide sequence information for gene discovery and marker development related to upland cotton flower development. These EST resources form a valuable foundation for gene expression profiling analysis, functional analysis of newly discovered genes, genetic linkage, and quantitative trait loci analysis