Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05). rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies

One Under Glass

Grand Central Station 5:10 I blend myself into the train which sits in the slip waiting to fill with faceless angels and threats colored post 50\u27s win well-aged wafts into the seat beside me..

Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy

BACKGROUND: Patients with Multiple Endocrine Neoplasia type 2 (MEN 2) are at high risk of developing aggressive medullary thyroid carcinoma (MTC) in childhood, with the highest risk in those with MEN type 2B (of whom >95% have an M918T RET proto-oncogene mutation). Metastatic MTC has been reported as young as 3 months of age. Current guidelines recommend prophylactic thyroidectomy within the first year of life for MEN 2B. PATIENT FINDINGS: We report a 9-week-old infant with MTC due to familial MEN 2B. A full-term male infant, born to a mother with known MEN 2B and metastatic MTC, had an M918T RET proto-oncogene mutation confirmed at 4 weeks of age. He underwent prophylactic total thyroidectomy at 9 weeks of age. Pathology showed a focal calcitonin-positive nodule (2.5 mm), consistent with microscopic MTC. SUMMARY: This case highlights the importance of early prophylactic thyroidectomy in MEN 2B. Although current guidelines recommend surgery up to a year of life, MTC may occur in the first few weeks of life, raising the question of how early we should intervene. In this report, we discuss the risks, benefits and barriers to performing earlier thyroidectomy, soon after the first month of life, and make suggestions to facilitate timely intervention. Prenatal anticipatory surgical scheduling could be considered in familial MEN 2B. Multidisciplinary collaboration between adult and pediatric specialists is key to the optimal management of the infant at risk

Uncovering Marginalized Topics Using WebQuests: From Atlanta to the Zoot Suit Riots

A critical part of social studies instruction is involving students in making sense of social issues in the past and present to help inform their decisions in the future. Through engaged inquiry students can tackle relevant topics associated with race, class, culture, gender, language, and nationality and explore how these challenging issues mitigate people’s experiences. Moreover, these issues reflect similar tensions that students encounter in their everyday lives. Although these social issues have historical and contemporary relevance, they often are marginalized in state standards and textbooks

Uncovering Marginalized Topics Using WebQuests: From Atlanta to the Zoot Suit Riots

A critical part of social studies instruction is involving students in making sense of social issues in the past and present to help inform their decisions in the future. Through engaged inquiry students can tackle relevant topics associated with race, class, culture, gender, language, and nationality and explore how these challenging issues mitigate people’s experiences. Moreover, these issues reflect similar tensions that students encounter in their everyday lives. Although these social issues have historical and contemporary relevance, they often are marginalized in state standards and textbooks

Optimal Sequential Selection of a Monotone Sequence From a Random Sample

The length of the longest monotone increasing subsequence of a random sample of size n is known to have expected value asymptotic to 2n1/2. We prove that it is possible to make sequential choices which give an increasing subsequence of expected length asymptotic to (2n)1/2. Moreover, this rate of increase is proved to be asymptotically best possible

State of Health in Northern Kentucky: How We Compare, Why it Matters to Business

County-level data is becoming increasingly important for rural health planning. This presentation analyzes the health of several northern Kentucky counties and the potential consequences for the region’s employers

Assessment of Physician Workforce Supply and Demand in the US

Rural community and migrant health centers face major problems in attracting and retaining physicians. This presentation addresses that issue by projecting health services demands, physician specialty distribution and physician supply, as well as suggesting methods for increasing physician supply and reducing consumer demand