Machado-Joseph disease in a Sudanese family links East Africa to Portuguese families and allows reestimation of ancestral age of the Machado lineage.

Machado-Joseph disease (MJD/SCA3) is the most frequent dominant ataxia worldwide. It is caused by a (CAG) expansion. MJD has two major ancestral backgrounds: the Machado lineage, found mainly in Portuguese families; and the Joseph lineage, present in all five continents, probably originating in Asia.

Fasting influences aquaporin expression, water transport and adipocyte metabolism in the peritoneal membrane.

Background: The water channels aquaporin-1 (AQP1) and AQP7 are abundantly expressed in the peritoneal membrane. While AQP1 facilitates water transport during peritoneal dialysis (PD), the role of AQP7, which mediates glycerol transport during fasting, remains unknown.

Methods: We investigated the distribution of AQP7 and AQP1 and used a mouse model of PD to investigate the role of AQP7 in the peritoneal membrane at baseline and after fasting.

Yemenite-Jewish families with Machado-Joseph disease (MJD/SCA3) share a recent common ancestor.

In 1994, a kindred from Yemen was described as the first Jewish family with Machado-Joseph disease (MJD/SCA3), a dominant ataxia caused by the expansion of a (CAG) above 61 repeats, in ATXN3. MJD is spread worldwide due to an ancient variant of Asian origin (the Joseph lineage). A second, more recent, independent expansion arose in a distinct haplotype (Machado lineage); other possible origins are still under study.

A Pipeline to Assess Disease-Associated Haplotypes in Repeat Expansion Disorders: The Example of MJD/SCA3 .

At least 40 human diseases are associated with repeat expansions; yet, the mutational origin and instability mechanisms remain unknown for most of them. Previously, genetic epidemiology and predisposing backgrounds for the instability of some expanding have been studied in different populations through the analysis of diversity flanking the respective pathogenic repeats. Here, we aimed at developing a pipeline to assess disease-associated haplotypes at oligonucleotide repeat , combining analysis of single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs).

Properties that rank protein:protein docking poses with high accuracy.

The development of docking algorithms to predict near-native structures of protein:protein complexes from the structure of the isolated monomers is of paramount importance for molecular biology and drug discovery. In this study, we assessed the capacity of the interfacial area of protein:protein complexes and of Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA)-derived properties, to rank docking poses. We used a set of 48 protein:protein complexes, and a total of 67 docking experiments distributed among bound:bound, bound:unbound, and unbound:unbound test cases.

New Parameters for Higher Accuracy in the Computation of Binding Free Energy Differences upon Alanine Scanning Mutagenesis on Protein-Protein Interfaces.

Knowing how proteins make stable complexes enables the development of inhibitors to preclude protein-protein (P:P) binding. The identification of the specific interfacial residues that mostly contribute to protein binding, denominated as hot spots, is thus critical. Here, we refine an in silico alanine scanning mutagenesis protocol, based on a residue-dependent dielectric constant version of the Molecular Mechanics/Poisson-Boltzmann Surface Area method.