Genetic analysis of muscle development in Drosophila melanogaster

The different thoracic muscles of Drosophila are affected specifically in the mutants: stripe (sr), erect wing (ewg), vertical wings (vtw), and nonjumper (nj). We have tested the extent of this specificity by means of a genetic analysis of these loci, multiple mutant combinations, and gene dosage experiments. A quantitative, rather than a qualitative, specificity is found in the mutant phenotypes. All muscles are altered by mutations in any given gene, but the severity of these alterations is muscle specific. The locus stripe seems to have a polar organization where different allelic combinations show quantitative specificity in the muscle affected. In addition to the muscle phenotypes, neural alterations are detected in these mutants. The synergism found between ewg, vtw and ewg, sr as well as the dosage effect of the distal end of the X chromosome upon the expression of ewg and sr suggests the existence of functional relationships among the loci analyzed.Peer Reviewe

Merging biomass and CO2 utilization; process design and assessment on simultaneous production of lactic acid and formic acid from glycerol and CO2

Biomass and CO2 conversion is receiving great attention to address climate change and energy crisis. Bio-based lactic acid (LA) appeals industries, however, current technologies suffer from low productivity and waste pro-duction. The transfer hydrogenation of glycerol and CO2 to LA and formic acid (FA) has been proposed as an alternative pathway, but further development and process design are required. This study proposes the inte-grated process for conversion of glycerol and CO2 to LA and FA derivatives. A two-pot/two-step transfer hy-drogenation was demonstrated to achieve high products yield, catalyst reusability, and product separation. The esterification of lactate and formate salts to corresponding esters utilizing CO2 was also developed, which re-duces H2SO4 consumption and K2SO4 waste. Techno-economic and life cycle assessments reveal that CO2 uti-lization is crucial for high economic benefit and low climate change impact. This study shows integrating biomass and CO2 could have synergies to design greener process

Computational Fluid Dynamics Based Optimal Design of Guiding Channel Geometry in U‑Type Coolant Layer Manifold of Large-Scale Microchannel Fischer–Tropsch Reactor

A microchannel Fischer–Tropsch reactor retaining high heat and mass transfer performance requires uniform flow distribution on the coolant side to induce isothermal condition for controllable and sustainable operation. The present work improved the flow performance of a large-scale layer of over 100 channels by introducing an extremely simple guiding fin in the inlet and outlet rectangular manifolds. Case studies with three-dimensional computational fluid dynamics (CFD) were carried out where the upper and bottom lengths of the guiding fin were the main geometric variables. Then the optimization work was conducted to estimate the performance of the optimal design. The robustness for the proposed geometry was tested with varying the flow rate, fluid type, and temperature. The result showed that the proposed design can retain uniform distribution over a wide operation range (500 ≤ <i>Re</i>_GF ≤ 10800)

CRISPR screens identify a novel combination treatment targeting BCL-X L and WNT signaling for KRAS/BRAF-mutated colorectal cancers

Metastatic or recurrent colorectal cancer (CRC) patients require systemic chemotherapy, but the therapeutic options of targeted agents remain limited. CRC patients with KRAS or BRAF gene mutations exhibit a worse prognosis and are resistant to anti-EGFR treatment. Previous studies have shown that the expression of anti-apoptotic protein BCL-XL is increased in CRC patients with KRAS/BRAF mutations, suggesting BCL-XL as a therapeutic target for this subgroup. Here, we performed genome-wide CRISPR/Cas9 screens of cell lines with KRAS mutations to investigate the factors required for sensitivity to BCL-XL inhibitor ABT-263 using single-guide RNAs (sgRNAs) that induce loss-of-function mutations. In the presence of ABT-263, sgRNAs targeting negative regulators of WNT signaling (resulting in WNT activation) were enriched, whereas sgRNAs targeting positive regulators of WNT signaling (resulting in WNT inhibition) were depleted in ABT-263-resistant cells. The activation of WNT signaling was highly associated with an increased expression ratio of anti- to pro-apoptotic BCL-2 family genes in CRC samples. Genetic and pharmacologic inhibition of WNT signaling using β-catenin short hairpin RNA or TNIK inhibitor NCB-0846, respectively, augmented ABT-263-induced cell death in KRAS/BRAF-mutated cells. Inhibition of WNT signaling resulted in transcriptional repression of the anti-apoptotic BCL-2 family member, MCL1, via the functional inhibition of the β-catenin-containing complex at the MCL1 promoter. In addition, the combination of ABT-263 and NCB-0846 exhibited synergistic effects in in vivo patient-derived xenograft (PDX) models with KRAS mutations. Our data provide a novel targeted combination treatment strategy for the CRC patient subgroup with KRAS or BRAF mutations