Meeting report - New York Symposium on Quantitative Biology of the Cell.

In the city that never sleeps, great science never takes a break. On 15 January 2016, the 'New York Symposium on Quantitative Biology of the Cell', a one-day local meeting of the American Society for Cell Biology (ASCB), took place at Columbia University Medical Center in upper Manhattan. Focusing on the quantitative understanding of cellular and multicellular systems, this meeting created an otherwise rare opportunity for interaction among scientists at various career levels with differing but complementary backgrounds. Highlighting cutting-edge experimental measurements and theoretical modeling, the symposium broke the barrier between disciplines and ignited a hopefully continuing regional dialogue on the emergent topic of quantitative biology of the cell.

Effectiveness and Safety of Secukinumab in Latin American Patients with Moderate to Severe Plaque Psoriasis: PURE Registry 12-Month Data.

BACKGROUND:  The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce. OBJECTIVES: To evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America. METHODS: PURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12 months in a Latin American population. RESULTS: Overall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month 12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month 3 and 81.8% versus 66.7% at month 12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month 12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month 12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period. CONCLUSION: Secukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America. TRIAL REGISTRATION: PURE: NCT02786186.

A tension-independent mechanism reduces Aurora B-mediated phosphorylation upon microtubule capture by CENP-E at the kinetochore.

During mitosis, Aurora B kinase is required for forming proper bi-oriented kinetochore-microtubule attachments. Current models suggest that tension exerted between a pair of sister-kinetochores (inter-kinetochore stretch) produces a spatial separation of Aurora B kinase from kinetochore-associated microtubule binding substrates, such as the Knl1-Mis12-Ndc80 (KMN) network, resulting in a decrease of phosphorylation and, thus, an increase of affinity for microtubules. Using Single-Molecule High-Resolution Colocalization (SHREC) microscopy analysis of the kinetochore-associated motor CENP-E, we now show that CENP-E undergoes structural rearrangements prior to and after tension generation at the kinetochore, and displays a bi-modal Gaussian distribution on a pair of bi-oriented sister kinetochores. The conformational change of CENP-E depends on its microtubule-stimulated motor motility and the highly flexible coiled-coil between its motor and kinetochore-binding tail domains. Chemical inhibition of the motor motility or perturbations of the coiled-coil domain of CENP-E increases Aurora B-mediated Ndc80 phosphorylation in a tension-independent manner. Metaphase chromosome misalignment caused by CENP-E inhibition can be rescued by chemical inhibition of Aurora B kinase. Furthermore, a pair of monotelic sister-kinetochores shows asymmetric levels of Aurora B-mediated phosphorylation in mono-polar spindles depending on CENP-E motor activity. These results collectively suggest a tension-independent mechanism to reduce Aurora B-mediated phosphorylation of outer kinetochore components in response to microtubule capture by CENP-E.

Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding.

BACKGROUND: The aim of this study was to measure the circulating levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon in patients who had undergone adjustable gastric banding (BND) or Roux-en-Y gastric bypass (RYGB) to understand the differences in glucose and insulin regulation after these procedures. METHODS: This was a cross-sectional study of 3 groups of women matched for age and body mass index: group 1, overweight controls (n = 13); group 2, BND (n = 10); and group 3, RYGB (n = 13). Venous blood was drawn with the patient in the fasted state and throughout a 3-hour period after a liquid meal. RESULTS: The fasting glucose level was similar between the 2 surgery groups; however, the fasting insulin concentrations were greater in the BND (10.0 microU/mL) than in the RYGB (6.2 microU/mL; P <0.05) group. The glucose level at 60 minutes was significantly lower in the RYGB group (70 mg/dL, range 38-82) than in the BND group (83 mg/dL, range 63-98). The GLP-1 levels at 30 minutes were more than threefold greater in the RYGB group (96 pmol/L) compared with the BND and overweight control (28 pmol/L) groups. The GLP-1 and insulin concentrations correlated at 30 minutes only in the RYGB group (r = .66; P = .013). The glucose-dependent insulinotropic peptide levels at 30 minutes were lower in the RYGB group (20 pmol/L) than in the BND group (31 pmol/L) or overweight control group (33 pmol/L). The peak glucagon levels were similar among the 3 groups. CONCLUSION: Exaggerated postprandial GLP-1 and blunted glucose-dependent insulinotropic peptide secretion after RYGB might contribute to the greater weight loss and improved glucose homeostasis compared with BND.

Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels.

OBJECTIVE: To quantify plasma concentrations of hormones that regulate energy homeostasis in order to establish possible mechanisms for greater weight loss after Roux-en-Y gastric bypass (RYGBP) compared with gastric banding (BND). RESEARCH METHODS AND PROCEDURES: Four groups of women were studied: lean (n = 8; mean BMI, 21.6 kg/m2); BND (n = 9; BMI, 35.8; 25% weight loss), RYGBP (n = 9; BMI, 34.2; 36% weight loss), and controls matched for BMI to the surgical groups (n = 11; BMI, 34.4). RESULTS: Fasting total peptide YY (PYY) and PYY(3-36) immunoreactivity were similar among all groups, but the postprandial response in the RYGBP group was exaggerated, such that 30 minutes after the meal, total and PYY(3-36) levels were 2- to 4-fold greater compared with all other groups. Maximal postprandial suppression of total ghrelin was blunted in the BND group (13%) compared with RYGBP (27%). Postprandial suppression of octanoylated ghrelin was also less in BND (29%) compared with RYGBP (56%). Fasting insulin was lower in RYGBP (6.6 microU/mL) compared with BND (10.0 microU/mL). Compared with lean controls, leptin concentrations were significantly higher in BND but not in RYGBP. There was a greater increase in post-meal satiety in the RYGBP group compared with BND and overweight controls. DISCUSSION: The differences between RYGBP and BND subjects in postprandial concentrations of PYY and ghrelin would be expected to promote increased satiety and earlier meal termination in RYGBP and may aid in greater weight loss. The differences in insulin and leptin concentrations associated with these procedures may also reflect differences in insulin sensitivity and energy partitioning.

Ectopía renal pélvica con litiasis coraliforme / Renal pelvic ectopy with coraliform lithiasis

Presentamos un caso de ectopía renal pélvica con litiasis coraliforme en una paciente de 46 años, quien llega al HRUJMCB (Hospital Regional Universitario José María Cabral y Báez) por dolor lumbar y en cuadrante inferior izquierdo del abdomen. Al examen físico, dolor localizado en fosa ilíaca izquierda. La radiografía simple de abdomen, sonografía y urografía excretora mostraron un cálculo coraliforme en un riñón ectópico pélvico izquierdo. Después de la pielolitomía la paciente presentó una buena evolución post operatoria

Lesiones ungueales de psoriasis. Instituto Dermatológico de Santo Domingo; dicienbre, 1988-mayo, 1989

Con el objetivo de investigar las lesiones ungueales de psoriasis, se realizó un estudio prospectivo, análitico y descriptivo con 100 pacientes que asistieron al Instituto Dermatológico de Santo Domingo en el período diciembre 1988-mayo 1989 con diagnóstico clínico e histopatológico de psoriasis cutánea. De estos pacientes el 84% presentó lesiones de psoriasis ungueal; el punteado o pitting constituyó la lesion más frecuente, (90.4%). El sexo más afectado fue el masculino (53.6%) y la población más afectada estuvo comprendida entre los 20-40 y más años de edad (90.5%)