Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency.

A rare neurodevelopmental disorder has been linked to a well-conserved splice site variant in the TRAPPC4 gene (c.454 + 3A > G), which causes mis-splicing of TRAPPC4 transcripts and reduced levels of TRAPPC4 protein. Patients present with severe progressive neurological symptoms including seizures, microcephaly, intellectual disability and facial dysmorphism.

Spectroscopic and Computational Insights into the Mechanism of Cofactor Cobalt-Carbon Bond Homolysis by the Adenosylcobalamin-Dependent Enzyme Ethanolamine Ammonia-Lyase.

The adenosylcobalamin (AdoCbl)-dependent enzyme ethanolamine ammonia-lyase (EAL) catalyzes the conversion of ethanolamine to acetaldehyde and ammonia. As is the case for all AdoCbl-dependent isomerases, the catalytic cycle of EAL is initiated by homolytic cleavage of the cofactor's Co-C bond, producing Cocobalamin (CoCbl) and an adenosyl radical that serves to abstract a hydrogen atom from the substrate. Remarkably, in the presence of substrate, the rate of Co-C bond homolysis of enzyme-bound AdoCbl is increased by 12 orders of magnitude.

Separating Infectious Proctitis from Inflammatory Bowel Disease-A Common Clinical Conundrum.

Proctitis refers to inflammation in the rectum and may result in rectal bleeding, discharge, urgency, tenesmus, and lower abdominal pain. It is a common presentation, particularly in genitourinary medicine and gastroenterology, as the two most common causes are sexually transmitted infections and inflammatory bowel disease. The incidence of infective proctitis is rising, particularly amongst high-risk groups, including men who have sex with men, those with HIV seropositive status, and those participating in high-risk sexual behaviours.

TRAPPopathies: Severe Multisystem Disorders Caused by Variants in Genes of the Transport Protein Particle (TRAPP) Complexes.

The TRAPP (TRAnsport Protein Particle) protein complex is a multi-subunit complex involved in vesicular transport between intracellular compartments. The TRAPP complex plays an important role in endoplasmic reticulum-to-Golgi and Golgi-to-plasma membrane transport, as well as autophagy. TRAPP complexes comprise a core complex, TRAPPI, and the association of peripheral protein subunits to make two complexes, known as TRAPPII and TRAPPIII, which act as Guanine Nucleotide Exchange Factors (GEFs) of Rab11 and Rab1, respectively.

Transcatheter aortic valve implantation complexity score.

Background: Increasing demand for transcatheter aortic valve implantation (TAVI) places greater emphasis on the efficiency of pathways and services. A significant limitation to increasing TAVI capacity is the availability of cardiac catheterisation laboratory time. We have developed a novel complexity scoring system (TAVI ComplEXity; TEX score) which can aid in planning lists with appropriate case selection.