DYX1C1 is required for axonemal dynein assembly and ciliary motility

DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2–4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start-codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary motility defects. In humans, we identified recessive loss-of-function DYX1C1 mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4)

Mathematical modelling and validation of the drying process in a chimney-dependent solar crop dryer

A simulation procedure describing the drying process within a Chimney-Dependent Solar Crop Dryer (CDSCD) has been developed. The simulation follows the authors’ experimental work on the effect of varying drying chamber roof inclination on the ventilation and drying processes, and their work on the development of simulation code to help optimise ventilation in such dryers. The current paper presents the modelling and subsequent validation of the drying process inside the dryer, to come out with a design tool for the CDSCD. The work considers the height of the crop shelf above the drying-chamber base, crop resistance to airflow and the shading on the drying-chamber base and their effects on the drying process. The under-load condition temperatures and velocities are predicted to within a relative difference of 1.5% and 10%, respectively of the observed values. Even though the heat inertia of the physical model causes deviation between the predicted drying path and the observed drying path, the two paths tend to converge at the end of each drying cycle, with a general prediction to within 10% relative difference of the observed crop moisture content. The validation results show that the simulation code can serve as an effective tool for comparing and refining the designs of the CDSCD for optimum drying performanc

Carbonic anhydrase inhibitors : 2-substituted-1,3,4-thiadiazole-5sulfamides act as powerful and selective inhibitors of the microchondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrase I, II and IV.

International audienc

Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Background: Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA. Patients and Methods: A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle–Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures. Results: After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0–39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively. Conclusion: HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials