Deletion of Carboxypeptidase E in ß-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice.

Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesity and hyperglycemia. We aimed to determine whether loss of Cpe in pancreatic ß-cells disrupts proinsulin processing and accelerates development of diabetes and obesity in mice. Pancreatic ß-cell-specific Cpe knockout mice (ßCpeKO; Cpefl/fl x Ins1Cre/+) lack mature insulin granules and have elevated proinsulin in plasma; however, glucose-and KCl-stimulated insulin secretion in ßCpeKO islets remained intact. High-fat diet-fed ßCpeKO mice showed weight gain and glucose tolerance comparable with those of Wt littermates. Notably, ß-cell area was increased in chow-fed ßCpeKO mice and ß-cell replication was elevated in ßCpeKO islets. Transcriptomic analysis of ßCpeKO ß-cells revealed elevated glycolysis and Hif1α-target gene expression. On high glucose challenge, ß-cells from ßCpeKO mice showed reduced mitochondrial membrane potential, increased reactive oxygen species, reduced MafA, and elevated Aldh1a3 transcript levels. Following multiple low-dose streptozotocin injections, ßCpeKO mice had accelerated development of hyperglycemia with reduced ß-cell insulin and Glut2 expression. These findings suggest that Cpe and proper proinsulin processing are critical in maintaining ß-cell function during the development of hyperglycemia. ARTICLE HIGHLIGHTS: Carboxypeptidase E (Cpe) is an enzyme that removes the carboxy-terminal arginine and lysine residues from peptide precursors. Mutations in CPE lead to obesity and type 2 diabetes in humans, and whole-body Cpe knockout or mutant mice are obese and hyperglycemic and fail to convert proinsulin to insulin. We show that ß-cell-specific Cpe deletion in mice (ßCpeKO) does not lead to the development of obesity or hyperglycemia, even after prolonged high-fat diet treatment. However, ß-cell proliferation rate and ß-cell area are increased, and the development of hyperglycemia induced by multiple low-dose streptozotocin injections is accelerated in ßCpeKO mice.

Substantial Decline in Invasive Pneumococcal Disease During Coronavirus Disease 2019 Pandemic in Hong Kong.

Compared with other countries, a more substantial decrease in the incidence of invasive pneumococcal disease was observed in Hong Kong, which is most likely attributable to the proactive mass adoption of face masks by the public. Human behavioral changes, particularly mask wearing, should be considered as an additional preventive strategy against invasive pneumococcal disease.

Tsukamurella asaccharolytica sp. nov., Tsukamurella conjunctivitidis sp. nov. and Tsukamurella sputi sp. nov., isolated from patients with bacteraemia, conjunctivitis and respiratory infection in Hong Kong.

Three bacterial strains, HKU70T, HKU71T and HKU72T, were isolated from the conjunctival swab, blood and sputum samples of three patients with conjunctivitis, bacteraemia and respiratory infection, respectively, in Hong Kong. The three strains were aerobic, Gram-stain positive, catalase-positive, non-sporulating and non-motile bacilli and exhibited unique biochemical profiles distinguishable from currently recognized Tsukamurella species. 16S rRNA, secA, rpoB and groEL gene sequence analyses revealed that the three strains shared 99.6-99.9, 94.5-96.8, 95.7-97.8 and 97.7-98.9 % nucleotide identities with their corresponding closest Tsukamurella species respectively. DNA-DNA hybridization confirmed that they were distinct from other known species of the genus Tsukamurella (26.2±2.4 to 36.8±1.2 % DNA-DNA relatedness), in line with results of in silico genome-to-genome comparison (32.2-40.9 % Genome-to-Genome Distance Calculator and 86.3-88.9 % average nucleotide identity values]. Fatty acids, mycolic acids, cell-wall sugars and peptidoglycan analyses showed that they were typical of members of Tsukamurella. The G+C content determined based on the genome sequence of strains HKU70T, HKU71T and HKU72T were 69.9, 70.2 and 70.5 mol%, respectively. Taken together, our results supported the proposition and description of three new species, i.e. Tsukamurella sputi HKU70T (=JCM 33387T=DSM 109106T) sp. nov., Tsukamurella asaccharolytica HKU71T (=JCM 33388T=DSM 109107T) sp. nov. and Tsukamurella conjunctivitidis HKU72T (=JCM 33389T=DSM 109108T) sp. nov.