Genomic comparison of carbapenem-resistant Enterobacteriaceae from humans and gulls in Alaska.

Objectives: Wildlife may harbour clinically important antimicrobial-resistant bacteria, but the role of wildlife in the epidemiology of antimicrobial-resistant bacterial infections in humans is largely unknown. In this study, we aimed to assess dissemination of the bla carbapenemase gene among humans and gulls in Alaska.

Methods: We performed whole-genome sequencing to determine the genetic context of bla in bacterial isolates from all four human carbapenemase-producing Enterobacteriaceae (CPE) infections reported in Alaska between 2013-2018 and to compare the sequences with seven previously reported CPE isolates from gull faeces within the same region and time period.

A tissue-specific screen of ceramide expression in aged mice identifies ceramide synthase-1 and ceramide synthase-5 as potential regulators of fiber size and strength in skeletal muscle.

Loss of skeletal muscle mass is one of the most widespread and deleterious processes in aging humans. However, the mechanistic metabolic principles remain poorly understood. In the framework of a multi-organ investigation of age-associated changes of ceramide species, a unique and distinctive change pattern of C and C ceramide species was detected in aged skeletal muscle.

Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6.

Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study, we show that the specific alteration of the cytochrome c oxidase (COX), representing a common defect found in mitochondrial diseases, facilitates mitochondrial apoptosis in response to oxidative stress. Our data identified an increased ceramide synthase 6 (CerS6) activity as an important pro-apoptotic response to COX dysfunction induced either by chemical or genetic approaches.

TNF-receptor-1 adaptor protein FAN mediates TNF-induced B16 melanoma motility and invasion.

Background: Locomotion of cancer cells can be induced by TNF and other motogenic factors secreted by cells of the tumour microenvironment such as macrophages. Based on our recent findings that the TNF receptor adaptor protein FAN mediates TNF-induced actin reorganisation and regulates the directed migration of immune cells responding to chemotactic cues, we addressed the role of FAN in cancer cell motility and the formation of invadopodia, a crucial feature in tumour invasion.

Methods: In B16 mouse melanoma cells, FAN was downregulated and the impact on FAN on cell motility and invasion was determined using in vitro assays and in vivo animal models.

Selection of potent non-toxic inhibitory sequences from a randomized HIV-1 specific lentiviral short hairpin RNA library.

RNA interference (RNAi) has been considered as an efficient therapeutic approach against the human immunodeficiency virus type 1 (HIV-1). However, to establish a durable inhibition of HIV-1, multiple effective short hairpin RNAs (shRNAs) need to be stably expressed to prevent the emergence of viral escape variants. In this study, we engineered a randomized lentiviral H1-promoter driven shRNA-library against the viral genome.