Comprehensive Glycomic and Proteomic Analysis of Mouse Striatum and Lateral Hypothalamus Following Repeated Exposures to Cocaine or Methamphetamine.

Substance use disorder is a major concern, with few therapeutic options. Heparan sulfate (HS) and chondroitin sulfate (CS) interact with a plethora of growth factors and their receptors and have profound effects on cellular signaling. Thus, targeting these dynamic interactions might represent a potential novel therapeutic modality. In the present study, we performed mass spectrometry-based glycomic and proteomic analysis to understand the effects of cocaine and methamphetamine (METH) on HS, CS, and the proteome of two brain regions critically involved in drug addiction: the lateral hypothalamus and the striatum. We observed that cocaine and METH significantly alter HS and CS abundances as well as sulfate contents and composition. In particular, repeated METH or cocaine treatments reduced CS 4-O-sulfation and increased CS 6-O-sulfation. Since C4S and C6S exercise differential effects on axon growth, regeneration, and plasticity, these changes likely contribute to drug-induced neural plasticity in these brain regions. Notably, we observed that restoring these alterations by increasing CS 4-0 levels in the lateral hypothalamus by adeno-associated virus delivery of an shRNA to arylsulfatase B (N-acetylgalactosamine-4-sulfatase) ameliorated anxiety and prevented the expression of preference for cocaine in a novelty induced conditioned place preference test during cocaine withdrawal. Finally, proteomics analyses revealed a number of aberrant proteins in METH- and cocaine-treated versus saline-treated mice, including myelin proteolipid protein, calcium/calmodulin-dependent protein kinase type II subunit alpha, synapsin-2, tenascin-R, calnexin, annexin A7, hepatoma-derived growth factor, neurocan, and CSPG5, and oxidative phosphorylation among the top perturbed pathway. Taken together, these data support the role of HS, CS, and associated proteins in stimulants abuse and suggest that manipulation of HSPGs can represent a novel therapeutic strategy.

Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma.

The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here, we present the first comprehensive single-cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple in vitro models of benign and malignant mesothelial cells, and characterise these through comparison with in vivo transcriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at the single-cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. It has already enabled us to shed light on the transdifferentiation of mesothelial cells, allowing us to develop a simple method for prolonging mesothelial cell differentiation in vitro.

Strongyloides stercoralis infection in solid organ transplant recipients.

PURPOSE OF REVIEW: Strongyloides stercoralis infection remains of concern due to its high associated morbidity among solid organ transplant recipients (SOTR) and the risk of donor-derived infection (DDI). We review key aspects of epidemiology to inform screening for and treatment of chronic infection among organ transplant candidates to reduce the risk of infectious complications in the posttransplant setting. RECENT FINDINGS: In this work, we offer guidance regarding the optimal management of Strongyloides hyperinfection syndrome and disseminated infection and offer recommendations regarding posttreatment surveillance and the potential need for repeat treatment during subsequent periods of augmented immunosuppression. This review also provides updated recommendations for screening of deceased and living donors as recently proposed by the Organ Procurement and Transplantation Network's Ad Hoc Disease Transmission Advisory Committee. SUMMARY: Risk reduction of Strongyloides infection in the SOTR population can be further enhanced by optimized treatment of infection, posttreatment surveillance during at-risk periods and recent proposed policy shifts to universal donor screening.

International Psychology: views from around the world

It is an exposition on the state of psychology as it exists today in a group of diverse countries around the world. Included are descriptions of theoretical emphases, practical applications, the state of licensure - in short, a whole series of remarks meant to characterize the development of psychology, both as a science and as a profession, in the country under consideration. The emphasis is on the period from 1960 to the present, although some authors have chosen to provide a more historical view.(AU)