Highlights d T cells of exposed donors or vaccinees effectively recognize SARS-CoV-2 variants d Effective recognition in AIM and FluoroSPOT assays, for spike and other proteins d 93% and 97% of CD4 and CD8 epitopes are 100% conserved across variants

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The widespread distribution of the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the adult brain suggests its role in a broad range of brain functions. Here we show evidence supporting a physical interaction of PTEN with a region in the third intracellular loop (3L4F) of the serotonin 5-HT2C receptor (5-HT2cR, formerly 5-HT1c receptor) in cell cultures. PTEN limits agonist-induced phosphorylation of 5-HT2cR through its protein phosphatase activity. We showed the probable existence of PTEN:5-HT2cR complexes in putative dopaminergic neurons in the rat ventral tegmental area (VTA), a brain region in which virtually all abused drugs exert rewarding effects by activating its dopamine neurons. We synthesized the interfering peptide Tat-3L4F, which is able to disrupt PTEN coupling with 5-HT2cR. Systemic application of Tat-3L4F or the 5-HT2cR agonist Ro600175 suppressed the increased firing rate of VTA dopaminergic neurons induced by delta9-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana. Using behavioral tests, we found that Tat-3L4F or Ro600175 blocks conditioned place preference of THC or nicotine, and that Ro600175, but not Tat-3L4F, produces anxiogenic effects, penile erection, hypophagia and motor functional suppression. These results suggest a potential strategy for treating drug addiction with the Tat-3L4F peptide.

Chronic hepatitis B (CHB) is characterized by functionally impaired virus-specific CD8+ T-cell responses. However, the mechanism underlying this dysfunction has not been fully clarified. We examined the role of a newly identified protein, T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), in regulating the antiviral CD8 + T-cell response in CHB patients. Tim-3 expression on peripheral virus-specific

Objective-The purpose of this study was to test the hypothesis that ACE2 overexpression may enhance atherosclerotic plaque stability by antagonizing ACE activity and converting angiotensin II to angiotensin 1-7. Methods and Results-Atherosclerotic plaques were induced in the abdominal aorta of 114 rabbits by endothelial injury and atherogenic diet. Gene therapy was performed in group A at week 4 and in group B at week 12, respectively. Each group of rabbits were randomly divided into 3 subgroups which received, respectively, a recombinant ACE2 expressing vector (AdACE2), a control vector AdEGFP and AdACE2ϩA779, an antagonist of angiotensin 1-7 receptor. Local ACE2 overexpression attenuated the progression of lesions from week 4 to week 8, but not progression of plaque size from week 12 to week 16. In group B rabbits, local ACE2 overexpression resulted in stable plaque compositions, ie, fewer macrophages, less lipid deposition and more collagen contents, higher plaque stability scores, decreased angiotensin II levels, and increased angiotensin 1-7 levels in plaque tissues in the AdACE2 subgroup compared with those in the AdEGFP subgroup. Conclusions-Overexpression of ACE2 results in stabilized atherosclerotic plaques and the mechanism is probably the conversion of vasoconstrictive angiotensin II to vessel protective angiotensin 1-7. (Arterioscler Thromb Vasc Biol. 2008;28:1270-1276)Key Words: atherosclerosis Ⅲ angiotensin converting enzyme 2 Ⅲ angiotensin Ⅲ inflammation Ⅲ plaque stability R ecent studies have shown that the endogenous levels of angiotensin II (Ang II) are regulated by the opposing action of 2 carboxypeptidases, angiotensin-converting enzyme (ACE) and ACE2. The latter is a more recently discovered homologue of ACE and is thought to counterbalance ACE by cleaving Ang I and Ang II into inactive Ang 1-9 and vasodilating and antiproliferative Ang-(1-7), respectively. ACE2 is thus considered a potential therapeutic target of the rennin-angiotensin system (RAS) for treatment of cardiovascular diseases owing to its key role in the formation of vessel protective peptides from Ang II. 1,2 Both ACE and ACE2 are considered key regulators of many cardiovascular pathological processes. Although Ang II and its receptor angiotensin subtype 1 receptor (AT 1 R) have been reported by many studies to be expressed in atherosclerotic lesions, ACE2 was reported only recently to be expressed in vascular endothelial cells, macrophages, and smooth muscle cells (SMCs). 3 More recently, ACE2 gene transfer was reported to result in a significant regression of left ventricular hypertrophy in spontaneously hypertensive rats. 4 However, little is known about the exact role of ACE2 in the formation and stabilization of atherosclerotic plaques. Because local RAS plays an important role in the pathogenesis of atherosclerosis, 5 it is reasonable to assume that imbalance of the activities of these 2 enzymes, ACE and ACE2, may have paramount importance in the pathogenesis of atherosclerosis. Therefore, we hypothesize that overexpress...

ROSTATE CANCER IS A COMMONand expensive disease in the United States. 1,2 In part because of the untoward morbidity of traditional radiation and surgical therapies, advances in the treatment of localized disease have evolved over the last decade. Chief among these are the development of intensitymodulated radiotherapy (IMRT) and robotic prostatectomy. Although the evidence underlying these technologies is mixed, 3,4 both are generally perceived as being more targeted and less toxic than prior therapies. During a period of increasing population-based rates of prostate cancer treatment, 5,6

Matrix metalloproteinases (MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial-mesenchymal transition (EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition (EndoMT) and pericyte-myofibroblast transdifferentiation.

The present work describes the targeting of an EGFR antisense gene to human brain cancer cells, which results in a 70-80% inhibition in cancer cell growth. PILs provide a new approach to gene targeting that is effective in vivo following intravenous administration without viral vectors.