The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes.

Biomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the biology, contributing to the overall chronic nature of desmopathy. A major challenge has been the lack of representative two-dimensional (2D) models mimicking inflammatory processes in the presence of dynamic mechanical strain, both being crucial for ligament homeostasis. Physiological levels of strain exert anti-inflammatory effects, while excessive strain can facilitate inflammatory mechanisms.

Transcriptional memory drives accelerated re-activation of several biosynthetic gene clusters in Aspergillus nidulans.

Organisms are repeatedly exposed to fluctuating environmental and nutritional conditions. Transcriptional memory has been shown to be a mechanism to cope with these fluctuations because it increases the speed and the magnitude of the cellular response to a certain re-occurring condition and therefore optimizes adaptation and fitness in a given environment. We found that genes coding for sterigmatocystin (ST) production in Aspergillus nidulans are activated stronger when cells are repeatedly exposed to nutrient starvation, compared to cells that experience this condition for the first time.

Iron transport pathways in the human malaria parasite revealed by RNA-sequencing.

Host iron deficiency is protective against severe malaria as the human malaria parasite depends on bioavailable iron from its host to proliferate. The essential pathways of iron acquisition, storage, export, and detoxification in the parasite differ from those in humans, as orthologs of the mammalian transferrin receptor, ferritin, or ferroportin, and a functional heme oxygenase are absent in . Thus, the proteins involved in these processes may be excellent targets for therapeutic development, yet remain largely unknown.

A free-living, walking-based, exercise programme, with exercise timed relative to breakfast, to improve metabolic health in people living with overweight and obesity: A feasibility study.

Optimising the timing of food intake relative to exercise may maximise the effectiveness of free-living exercise programmes on improvements in glycaemic control and cardio-metabolic health. This study aimed to assess the feasibility of a free-living, walking-based exercise programme and determine whether undertaking each exercise session before or after breakfast would most benefit longer-term metabolic health. Thirty-four people living with obesity (43±12 y, BMI 35.

Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1).

Background: Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8 T cells and natural killer cells, with minimal expansion of regulatory T cells, thereby mitigating the risk of toxicities associated with high-affinity interleukin-2 receptor activation. Clinical outcomes with nemvaleukin are unknown. ARTISTRY-1 investigated the safety, recommended phase 2 dose (RP2D), and antitumor activity of nemvaleukin in patients with advanced solid tumors.