Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

<p>Abstract</p> <p>Background</p> <p>Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells.</p> <p>Methods</p> <p>Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr⁷⁰¹-phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR.</p> <p>Results</p> <p>SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr⁷⁰¹-phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation.</p> <p>Conclusions</p> <p>These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ.</p

The Burden of Trachoma in Ayod County of Southern Sudan

Trachoma, a neglected tropical disease, is the leading cause of infectious blindness and is targeted for global elimination by the year 2020. We conducted a survey in Ayod County of Jonglei State, Southern Sudan, to determine whether blinding trachoma was a public health problem and to plan interventions to control this disease. We found the burden of trachoma in Ayod to be one of the most severe ever documented. Not only were adults affected by the advanced manifestations of the disease as is typical for older age groups, but young children were also affected. At least one person with clinical signs of trachoma was found in nearly every household, and 1 in 3 households had a person with severe blinding trachoma. Characteristics previously identified as risk factors were ubiquitous among surveyed households, but we were unable to identify why trachoma is so severe in this location. Surgical interventions are needed urgently to improve vision and prevent irreversible blindness in children and adults. Mass antibiotic distribution may alleviate current infections and transmission of trachoma may be reduced if communities adopt the behavior of face washing and safe disposal of human waste. Increasing access to improved water sources may not only improve hygiene but also reduce the spread of guinea worm and other water-borne diseases

A catastrophic tropical drought kills hydraulically vulnerable tree species.

Drought-related tree mortality is now a widespread phenomenon predicted to increase in magnitude with climate change. However, the patterns of which species and trees are most vulnerable to drought, and the underlying mechanisms have remained elusive, in part due to the lack of relevant data and difficulty of predicting the location of catastrophic drought years in advance. We used long-term demographic records and extensive databases of functional traits and distribution patterns to understand the responses of 20 to 53 species to an extreme drought in a seasonally dry tropical forest in Costa Rica, which occurred during the 2015 El Niño Southern Oscillation event. Overall, species-specific mortality rates during the drought ranged from 0% to 34%, and varied little as a function of tree size. By contrast, hydraulic safety margins correlated well with probability of mortality among species, while morphological or leaf economics spectrum traits did not. This firmly suggests hydraulic traits as targets for future research

TRATAMIENTO SINDROMICO DE FLUJO VAGINAL EN GESTANTES ATENDIDAS EN EL CENTRO DE SALUD CHACAPUNCO ENERO A JUNIO 2017

TesisObjetivo: Determinar las características del tratamiento sindrómico de flujo vaginal. Metodología: El tipo de investigación es sustantiva, nivel descriptivo y diseño descriptivo simple. Se trabajó con una muestra censal de 30 gestantes que desarrollaron síndrome de flujo vaginal resultados: Las características encontradas en la edad fue edad mínima 17 años y la máxima 40 años, la mayoría presentó 23 años., el 53% son convivientes. Según el grado de instrucción, el 60% de las gestantes tienen primaria, el 47% son amas de casa, el 87% procede del área rural. Dentro de las características clínicas el 67% de las gestantes tienen abundante secreción, las características de las secreciones vaginales son el 67% presentan aspecto leche cortada, el 33% mal olor. Y los síntomas identificados fueron 60% disuria y prurito vulvar. Se encontró que el 60% de las gestantes atendidas tienen como diagnostico presuntivo trichomona y cándida. Las complicaciones encontradas fueron: amenaza de parto prematuro 60%, amenaza de aborto 27%. La respuesta al tratamiento sindrómico de flujo vaginal en gestantes el 73% de las gestantes se suministró el Metronidazol y al 87% con Clotrimazol. Conclusión: El tratamiento sindrómico de flujo vaginal con medicamentos resulto que el 83% de las gestantes fue efectivo y el 17% de las gestantes no fue efectivo. Palabras claves: Síndrome de flujo vaginal, tratamiento y gestantes