31 research outputs found
A Molecular Dynamics study
Prozessive Enzyme bilden eine spezielle Klasse von Enzymen, die vermutlich während vieler katalytischer Durchläufe an ihrem Substrat haften bleiben. Hierdurch gleitet das Substrat am Enzym entlang und die Zeit bis zu einem zufälligen diffusiven Aufeinandertreffen von Enzym und Substrat wird reduziert, was die Effizienz der Enzyme um ein Vielfaches erhöht. Obwohl Informationen über die Struktur vieler prozessiver Enzyme zur Verfügung stehen, ist die Gleitphase, die inhärent dynamisch ist, weitgehend unbekannt. Wir unternehmen erste Schritte, um den Gleitprozess zu verstehen, indem wir einen Prototyp für ein Prozessives Enzym untersuchen, nämlich Streptococcus Pneumoniae Hyaluronate lyase, ein bakterielles Enzym, das das Polysaccharidsubstrat Hyaluronsäure abbaut. Wir haben den Zusammenhang zwischen der Flexibilität des Enzyms, wie sie in Essential Dynamics Molekulardynamik Simulationen beobachtet wurde, mit Enzym-Substrat Interaktionen untersucht, indem wir etliche freie Simulationen und erzwungene Molekulardynamiksimulationen angewandt haben. Auf diese Art haben wir eine Kopplung von Domänenbewegungen des Enzyms mit der Prozessivität oder der Gleitphase des Substrates aufgezeigt. Bei dem vermuteten Mechanismus der Substrattranslokation haben wir eine Energiebarriere entlang der Prozessionsrichtung beobachtet und es ist zu vermuten, dass diese sich aus der Reorientierung des Zuckers innerhalb der Proteinspalte ergibt. Diese Sichtweise wurde unterstützt durch Force Probe Molekulardynamiksimulationen und Umbrella Sampling Simulationen, die angewandt wurden, um vorläufige freie Energie Profile zu erhalten, die dem Mechanismus zu Grunde liegen. Die beobachtete freie Energie Barriere ist niedrig genug, um leicht durch thermische Fluktuationen überwunden zu werden, so dass essentielle langsame kollektive Reorganisationen der Domains als wahrscheinliche Raten bestimmende Faktoren für den prozessiven Zyklus in Frage kommen. Experimentelle Bestätigung zusammen mit weiteren rechnergestützten Studien wird von großem Nutzen für das Verständnis dieses komplexen Mechanismus sein
Coral bleaching due to increased sea surface temperature in Gulf of Kachchh Region, India, during June 2016
327-332The 2015-2016 E1 Niño Southern Oscillation event was one of the extreme climate events which elevated the sea surface temperature (SST) of tropical oceans, which in turn increased the level of thermal stress on corals. Coral bleaching event is mainly caused due to high positive SST anomaly, i.e., when SST exceeds its normal summer maxima. Corals in the Gulf of Kachchh region of Gujarat earlier experienced coral bleaching events during 1988, 2010 and 2014. For this study, SST was derived from NOAA OISST data set which is available daily at 0.25° global grids from 1982 to present. The climatologically warmest month for the Gulf of Kachchh region is June when the maximum monthly mean temperature is 29.31°C, as observed from NOAA OISST. The present study focuses on monitoring daily SST anomalies during summer 2016 for the Gulf of Kachchh reefs and field observations on early responses of coral bleaching from Laku Point reef, a site known for high coral diversity. It was found that in summer 2016, SST rose to 30.62 °C and recorded a maximum positive anomaly of 1.31°C in the month of June. A total of 72 days out of 122-day monitoring period showed positive SST anomaly, including 28 days of continuous positive thermal stress in June 2016.To validate coral bleaching forecast at the end of the regional warmest quarter, a field visit was carried out at Laku Point reef near Poshitra village in the southern coast of the Gulf of Kachchh. A total of 13 coral species and a sea anemone were found bleached in various proportions during the field sampling after two months of prolonged thermal stress. The field data showed an average of 3.9% bleaching of corals at colony scale. The maximum proportion of colony scale bleaching was observed in Porites lutea species
Polycythemia: a mystery solved by history
Testosterone is responsible for increased muscle mass. Leaner body mass helps control weight and increases energy. High levels of testosterone help build muscles and also stimulate growth in strength. Androgenic-anabolic steroids (AAS) are drugs that are structurally related to the cyclic steroid rings system and have similar effects to testosterone in the body. Athletes who abuse steroids do so for muscle growth and quick recovery. Testosterone - whether it's injected, applied via a patch or cream, or taken orally - allows athletes to rapidly increase muscle mass beyond their usual capacity, and also reduces their recovery time which allows them to train continuously with little need to rest their bodies in between workouts. Physiologically, erythrocytosis is defined by an erythrocyte mass that exceeds 125% of that predicted for sex and body mass. Much of the concern with the use of testosterone involves increase in blood viscosity, resulting from increased red blood cell mass causing a potential increased risk for venous thromboembolism (VTE), myocardial infarction (MI), and cerebrovascular accidents (CVA). We report a case of secondary polycythemia related to testosterone therapy
A rare case of cranial metastasis from an initial presentation of hepatocellular carcinoma
Cranial metastases from hepatocellular carcinoma (HCC) has been seldom reported. Reported herein is the case of a painless parietal bone mass as an initial presentation of HCC in a 63-year-old female patient who was subsequently diagnosed to have HCV related cirrhosis. The biopsy from cranial lesion was confirmatory of HCC on immunohistochemistry. The patient had no known history of chronic liver disease. The presented diagnosis was made through detailed history, laboratory parameters and cross sectional imaging
Anti-Proliferative Role of Recombinant Lethal Toxin of Bacillus Anthracis on Primary Mammary Ductal Carcinoma Cells Revealing Its Therapeutic Potential
Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p \u3c 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ±1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96), followed by nerve growth factor receptor (NGFR) and human epidermal growth factor receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic molecule against primary mammary ductal carcinoma cells and also the c-Met as potential alternative receptor for LF to mediate and modulate PA independent signal transduction