Effects of a timeout contingency on the development of resurgence: an exploratory study with rats.

This experiment assessed the effects of a timeout (TO) contingency for target responding during treatment, on the development of resurgence. Rats were exposed to a two-component multiple schedule (VI 30-s VI 30-s) across three phases. In the first phase, target lever presses were reinforced in both components.

Transporter excess and clustering facilitate adaptor protein shuttling for bacterial efflux.

Multidrug efflux pumps confer not only antibiotic resistance to bacteria but also cell proliferation. In gram-negative bacteria, the ATP-binding cassette (ABC)-family transporter MacB, the adaptor protein MacA, and the outer membrane protein TolC form the MacA:MacB:TolC assembly to extrude antibiotics and virulence factors. Here, using quantitative single-molecule single-cell imaging, we uncover that, in cells, there is a large excess of MacB (and TolC) driving the limiting adaptor protein MacA mostly into the MacAB-TolC assembly.

Bruton tyrosine kinase covalent inhibition shapes the immune microenvironment in chronic lymphocytic leukemia.

Continuous treatment with ibrutinib not only exerts tumor control but also enhances T cell function in patients with chronic lymphocytic leukemia (CLL). We conducted longitudinal multi-omics analyses in samples from CLL patients receiving ibrutinib upfront to identify potential adaptive mechanisms to Bruton tyrosine kinase (BTK) inhibition during the first 12 months of continuous therapy. We found that ibrutinib induced a decrease in the expression of exhaustion markers and the proportion of Tregs and Tfh cells normalized to levels observed in healthy donors.

Hepatic stellate cells control liver zonation, size and functions via R-spondin 3.

Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood. Here we demonstrate that genetic depletion of HSCs changes WNT activity and zonation of hepatocytes, leading to marked alterations in liver regeneration, cytochrome P450 metabolism and injury.

Borderline Disseminated (Intermediate) Cutaneous Leishmaniasis: A Case-Based Approach to Diagnosis and Clinical Management in Pediatric Population.

Background: Cutaneous leishmaniasis (CL) is a neglected tropical disease with diverse clinical manifestations, ranging from localized CL to severe forms such as diffuse CL and mucocutaneous leishmaniasis. Borderline disseminated CL (BDCL), an intermediate form, is characterized by multiple disseminated lesions and poses unique diagnostic and therapeutic challenges, especially in pediatric patients. This study explores pediatric BDCL to better understand its clinical presentation, diagnostic approaches and treatment outcomes.