A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy.

Introduction: Transplant vasculopathy (TV) is a major complication after solid organ transplantation, distinguished by an arterial intimal thickening that obstructs the vascular lumen and leads to organ rejection. To date, TV remains largely untreatable, mainly because the processes involved in its development remain unclear. Aortic transplantation in mice, used to mimic TV, relies on highly variable experimental protocols, particularly regarding the type of anastomosis used to connect the donor aorta to the recipient.

Integration of Partner Notification Services at a Sexually Transmitted Infections Clinic.

Objectives: PNS is critical to prevent the spread of STIs. We evaluated the feasibility of integrating PNS into an STI clinic focused on MSM.

Design/methods: The RI STI Clinic, in partnership with the RIDOH, implemented a PNS program in 2019.

Pre-Exposure Prophylaxis Care Cascade Among Men Who Have Sex with Men Engaging in Partner Notification Services at a Sexually Transmitted Infections Clinic.

Partner notification services (PNS) offers opportunities to discuss HIV pre-exposure prophylaxis (PrEP) and provide referrals. We evaluated the PrEP care cascade among men who have sex with men (MSM) engaging in PNS within a sexually transmitted infections clinic. Among 121 MSM eligible for PrEP during PNS, 21% subsequently initiated PrEP.

The hepatokine FGL1 regulates hepcidin and iron metabolism during anemia in mice by antagonizing BMP signaling.

As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure the adequate supply of iron to the bone marrow for red blood cell production.

The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice.

Unlabelled: As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure adequate supply of iron to the bone marrow for red blood cells production.

ERK2 Mutations Affect Interactions, Localization, and Dimerization.

The most frequent ERK2 (MAPK1) mutation in cancers, E322K, lies in the common docking (CD) site, which binds short motifs made up of basic and hydrophobic residues present in the activators MEK1 (MAP2K1) and MEK2 (MAP2K2), in dual specificity phosphatases (DUSPs) that inactivate the kinases, and in many of their substrates. Also, part of the CD site, but mutated less often in cancers, is the preceding aspartate (D321N). These mutants were categorized as gain of function in a sensitized melanoma system.

Interactomes of Glycogen Synthase Kinase-3 Isoforms.

Functional differentiation of the two isoforms of the protein-serine/threonine kinase, glycogen synthase kinase-3 (GSK-3), is an unsettled area of research. The isoforms are highly similar in structure and are largely redundant, though there is also evidence for specific roles. Identification of isoform-specific protein interactors may elucidate the differences in function and provide insight into isoform-selective regulation.

A Randomized Trial of a Brief Behavioral Intervention for PrEP Uptake Among Men Who Have Sex With Men at Increased Risk for HIV Infection.

Background: The aim of this study was to evaluate the efficacy of a novel, brief 2-session behavioral intervention to promote HIV pre-exposure prophylaxis (PrEP) uptake among men who have sex with men (MSM) who are behaviorally at risk for HIV.

Setting: A pilot randomized controlled trial was conducted at a sexually transmitted infection (STI) clinic to compare a brief motivational interviewing intervention with passive referral only for PrEP uptake.

Methods: MSM who scored as "high risk" on the HIV Incidence Risk index for MSM was offered a brief (15-20 minutes) motivational interviewing-based intervention at the time of STI testing to address barriers to PrEP uptake, including low risk perception, stigma, side effects, and cost.

Impact of the COVID-19 Pandemic on Sexually Transmitted Infection Clinic Visits.

Coronavirus disease 2019 is responsible for a global pandemic and has impacted health care accessibility and delivery. Clinic data were reviewed for an STI clinic from September 2019 to May 2020. A significant decrease in rates of STI visits and treatments during the coronavirus disease 2019 pandemic was observed.

Considerations for STI Clinics During the COVID-19 Pandemic.

Coronavirus disease (COVID-19) is responsible for a global pandemic. It is important to balance the need for access to healthcare services, including testing and treatment for sexually transmitted infections. Sexually transmitted infection programs must consider how to use limited resources and implement novel approaches to provide continued access to care.

Targeting lysosome function causes selective cytotoxicity in VHL-inactivated renal cell carcinomas.

The inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), has been identified as the earliest event in renal cell carcinoma (RCC) development. The loss of heterogeneity by chromosome 3p deletion followed by inactivating mutations on the second VHL copy are events present in close to 90% of patients. Our study illustrates a lysosomal vulnerability in VHL-inactivated RCC in vitro.

Functional divergence caused by mutations in an energetic hotspot in ERK2.

The most frequent extracellular signal-regulated kinase 2 (ERK2) mutation occurring in cancers is E322K (E-K). ERK2 E-K reverses a buried charge in the ERK2 common docking (CD) site, a region that binds activators, inhibitors, and substrates. Little is known about the cellular consequences associated with this mutation, other than apparent increases in tumor resistance to pathway inhibitors.

STF-62247 accumulates in lysosomes and blocks late stages of autophagy to selectively target von Hippel-Lindau-inactivated cells.

Autophagy is a highly conserved, homeostatic process by which cytosolic components reach lysosomes for degradation. The roles played by different autophagic processes in cancer are complex and remain cancer type and stage dependent. Renal cell carcinoma (RCC) is the most common subtype of kidney cancer and is characterized by the inactivation of the von Hippel-Lindau (VHL) tumor suppressor.

Quantitative proteomics to study a small molecule targeting the loss of von Hippel-Lindau in renal cell carcinomas.

Inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), is known to play an important role in the development of sporadic clear cell renal cell carcinomas (ccRCCs). Even if available targeted therapies for metastatic RCCs (mRCCs) have helped to improve progression-free survival rates, they have no durable clinical response. We have previously shown the feasibility of specifically targeting the loss of VHL with the identification of a small molecule, STF-62247.

Recent advances in understanding the cellular roles of GSK-3.

Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed protein kinase that sits at the nexus of multiple signaling pathways. Its deep integration into cellular control circuits is consummate to its implication in diseases ranging from mood disorders to diabetes to neurodegenerative diseases and cancers. The selectivity and insulation of such a promiscuous kinase from unwanted crosstalk between pathways, while orchestrating a multifaceted response to cellular stimuli, offer key insights into more general mechanisms of cell regulation.

(1)H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity.

Autophagy and cell death to target cancer cells: exploiting synthetic lethality as cancer therapies.

Since 1940 chemotherapy has been one of the major therapies used to kill cancer cells. However, conventional standard cytotoxic agents have a low therapeutic index and often show toxicity in healthy cells. Over the past decade, progress in molecular biology and genomics has identified signaling pathways and mutations driving different types of cancer.

Intracellular expression of inflammatory proteins S100A8 and S100A9 leads to epithelial-mesenchymal transition and attenuated aggressivity of breast cancer cells.

S100 inflammatory proteins have been previously shown to modulate breast cancer processes. More specifically, genome-wide transcriptome studies associate S100A8 and S100A9 members to breast cancer progression and malignancy. Findings have shown that S100A8 and S100A9 can signal and regulate cancer cell behavior through both extracellular and intracellular-initiated cascades.

A biomimetic route for construction of the [4+2] and [3+2] core skeletons of dimeric pyrrole-imidazole alkaloids and asymmetric synthesis of ageliferins.

The pyrrole-imidazole alkaloids have fascinated chemists for decades because of their unique structures. The high nitrogen and halogen contents and the densely functionalized skeletons make their laboratory synthesis challenging. We describe herein an oxidative method for accessing the core skeletons of two classes of pyrrole-imidazole dimers.

A Highly Selective Vanadium Catalyst for Benzylic C-H Oxidation.

Vanadium complexes have been used extensively to catalyze olefin and alcohol oxidation. However, their application in C-H oxidation has not been well-studied. We report herein that commercially available Cp(2)VCl(2) catalyzes benzylic C-H oxidation selectively and effectively, giving no aromatic oxidation products.

The quadrupole moment of substituted cyclopentadienyl anions.

Previous work in our group on the cation binding of substituted cyclopentadienyl anions (Cp) showed the curious result that Cp traceless electric quadrupole moments (Θ(zz)) are almost all positive. Probing this issue further here we show that substituted Cp Θ(zz) values are always significantly more positive than the analogous substituted benzenes. Given the nature of aromatic Θ(zz) values, this is the opposite of what would be predicted.

Preference for Na+-pi binding over Na+-dipole binding in Na+-arene interactions.

The cation binding of dipolar aromatics was investigated employing computational techniques. In most cases, cation binding at the pi region of the aromatic (the cation-pi interaction), which can be thought of as a cation-quadrupole interaction, is preferred over cation binding at the negative end of the dipole moment. Surprisingly, in some cases, the cation-dipole complex is not even a minimum on the potential energy surface.