The nematode degenerin UNC-105 forms ion channels that are activated by degeneration- or hypercontraction-causing mutations

Nematode degenerins have been implicated in touch sensitivity and other forms of mechanosensation. Certain mutations in several degenerin genes cause the swelling, vacuolation, and death of neurons, and other mutations in the muscle degenerin gene unc-105 cause hypercontraction. Here, we confirm that unc-105 encodes an ion channel and show that it is constitutively active when mutated. These mutations disrupt different regions of the channel and have different effects on its gating. The UNC-105 channels are permeable to small monovalent cations but show voltage-dependent block by Ca2+ and Mg2+. Amiloride also produces voltage-dependent block, consistent with a single binding site 65% into the electric field. Mammalian cells expressing the mutant channels accumulate membranous whorls and multicompartment vacuoles, hallmarks of degenerin-induced cell death across species.     

Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group

Two patients with the Kennedy's disease (KD) mutation have been identified in the Newcastle Brain Tissue Bank. One of these patients had presenile dementia as a prominent clinical feature, previously undescribed in KD. The pathologic substrate underlying the cognitive changes in this patient included neuronal depletion and gliosis in the hippocampus and subcortical gliosis in the prefrontal region. Immunostaining for macrophage markers showed evidence for subtle corticospinal tract pathology in both cases. In contrast to the molecular pathologic features found in ALS, surviving motor neurons in the two KD cases showed no evidence of ubiquitinated inclusions or alterations in neurofilament phosphorylation.     

Predicting forage indigestible NDF from lignin concentration

We used chemical composition and in vitro digestibility data from temperate and tropical forages to develop relationships between indices of lignification and forage indigestible NDF. Neutral detergent fiber indigestibility increased nonlinearly as the lignin concentration of the NDF increased. Differences in estimated indigestible NDF using equations developed for a specific forage class (C3 and C4 grasses and legumes) were small and are probably not biologically significant when compared to those estimated from a common equation. Selected equations were compared with the Cornell Net Carbohydrate and Protein System (CNCPS) for the prediction of ADG. The linear equation (2.4 times NDF lignin content) used by the CNCPS and the Beef NRC had some of the largest errors due to mean bias. A log-log model [4.37 x (lignin/NDF)(.84)] provided the best combination of low total prediction error, low mean bias, and minimal error due to regression bias when permanganate lignin was used. A similar equation based on sulfuric acid lignin [6.17 x (lignin/NDF)(.77)] also met the above criteria. These equations then were evaluated with the CNCPS model against animal growth data from diets ranging in forage quality. Regardless of the equation used for predicting unavailable fiber, the CNCPS underpredicted daily gain, with mean biases ranging from -.10 to -.22 kg/d. Regression bias ranged from .13 to .14 kg/d and the coefficients differed from unity (P = .0001). The new equations gave numerically lower energy allowable ADG by steers compared to the linear equation currently used by the CNCPS model. The estimates were lower due to a higher predicted indigestible NDF, which resulted in a lower estimated forage energy value.     

Sclerosing stromal tumour of the ovary

Two cases of sclerosing stromal tumour of the ovary in young Melanesian females are described and the differential diagnosis is discussed. Sclerosing stromal tumour of the ovary is a rare benign tumour of ovarian stromal origin which is associated with endocrine activity in a few cases. One of the patients presented with signs of precocious puberty and the tumour in this patient was considered as a functioning lesion.     

Genomic characterization of the coding region of the human type II 5''-deiodinase gene

The conserved residue Asp477 in yeast transketolase is located in the substrate channel of the enzyme and forms a hydrogen bond with the C2-hydroxyl group of the acceptor substrate. The significance of this interaction for the recognition of the preferred acceptor substrates, D-alpha-hydroxyaldehydes was investigated by site-directed mutagenesis. In the wild-type enzyme the kcat/KM values are by three to four orders of magnitude lower for 2-deoxyaldoses or substrates with L-configuration at the C2-atom. In the Asp477 Ala mutant, the kcat/KM values for D-alpha-hydroxyaldehydes are decreased by a thousandfold, while the kcat/KM values for substrates with L-configuration or 2-deoxyaldoses are similar to wild-type enzyme. These results indicate that Asp477 is involved in determining the enantioselectivity of transketolase.