Lentivirus-mediated gene therapy for Fabry disease: 5-year End-of-Study results from the Canadian FACTs trial.

Background: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of α-galactosidase A (α-gal A) activity. Our goal was to correct the enzyme deficiency in Fabry patients by transferring the cDNA for α-gal A into their CD34+ hematopoietic stem/progenitor cells (HSPCs). Overexpression of α-gal A leads to secretion of the hydrolase; which can be taken up and used by uncorrected bystander cells.

Functional reconstruction following bilateral amputation of the manus and pes in a cat with frostbite injury.

This case report describes metacarpophalangeal (MCP)- and metatarsophalangeal (MTP)-level amputation and reconstruction of all 4 paws of a young female domestic shorthair cat. All 4 paws, the ears, and the distal portion of the tail underwent severe frostbite injury resulting in tissue death. Following MCP and MTP amputation, weight-bearing surface reconstruction was achieved using metacarpal and metatarsal paw-pad advancement flaps.

Changing patterns of global nitrogen deposition driven by socio-economic development.

Advances in manufacturing and trade have reshaped global nitrogen deposition patterns, yet their dynamics and drivers remain unclear. Here, we compile a comprehensive global nitrogen deposition database spanning 1977-2021, aggregating 52,671 site-years of data from observation networks and published articles. This database show that global nitrogen deposition to land is 92.

Consultation informs strategies to improve functional evidence use in variant classification.

To determine if a variant identified by diagnostic genetic testing is causal for disease, applied genetics professionals evaluate all available evidence to assign a clinical classification. Experimental assay data can provide strong functional evidence for or against pathogenicity in variant classification, but appears to be underutilised. We surveyed genetic diagnostic professionals in Australasia to assess their application of functional evidence in clinical practice.

A missense variant effect map for the human tumor-suppressor protein CHK2.

The tumor suppressor CHEK2 encodes the serine/threonine protein kinase CHK2 which, upon DNA damage, is important for pausing the cell cycle, initiating DNA repair, and inducing apoptosis. CHK2 phosphorylation of the tumor suppressor BRCA1 is also important for mitotic spindle assembly and chromosomal stability. Consistent with its cell-cycle checkpoint role, both germline and somatic variants in CHEK2 have been linked to breast and other cancers.