Paradoxical signaling regulates structural plasticity in dendritic spines

Transient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics

o-Mercaptoacetamidobenzoic Acid as a Gravimetric Reagent for Zr(IV)

994-99

Geometric principles of second messenger dynamics in dendritic spines.

Dendritic spines are small, bulbous protrusions along dendrites in neurons and play a critical role in synaptic transmission. Dendritic spines come in a variety of shapes that depend on their developmental state. Additionally, roughly 14-19% of mature spines have a specialized endoplasmic reticulum called the spine apparatus. How does the shape of a postsynaptic spine and its internal organization affect the spatio-temporal dynamics of short timescale signaling? Answers to this question are central to our understanding the initiation of synaptic transmission, learning, and memory formation. In this work, we investigated the effect of spine and spine apparatus size and shape on the spatio-temporal dynamics of second messengers using mathematical modeling using reaction-diffusion equations in idealized geometries (ellipsoids, spheres, and mushroom-shaped). Our analyses and simulations showed that in the short timescale, spine size and shape coupled with the spine apparatus geometries govern the spatiotemporal dynamics of second messengers. We show that the curvature of the geometries gives rise to pseudo-harmonic functions, which predict the locations of maximum and minimum concentrations along the spine head. Furthermore, we showed that the lifetime of the concentration gradient can be fine-tuned by localization of fluxes on the spine head and varying the relative curvatures and distances between the spine apparatus and the spine head. Thus, we have identified several key geometric determinants of how the spine head and spine apparatus may regulate the short timescale chemical dynamics of small molecules that control synaptic plasticity

STABILITY-INDICATING RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF SOFOSBUVIR, VELPATASVIR, AND VOXILAPREVIR IN BULK AND TABLET DOSAGE FORMS

Objective: The present study was aimed to develop a novel, simple, rapid accurate and precise, stability-indicating reversed-phase high-performance liquid chromatography method for the simultaneous estimation of sofosbuvir, velpatasvir, and voxilaprevir in bulk and tablet dosage forms. Methods: The chromatographic elution was achieved in isocratic mode using the combination of sofosbuvir, velpatasvir, and voxilaprevir in the ratio of acetonitrile and water (65:35%v/v) using a Phenomenex C18 column which has specification (150 × 4.6 mm, 5 μ particle size) and the flow rate of 1.0 ml/min and wavelength (ultraviolet) detection at 220 nm. Results: The retention time obtained for sofosbuvir, velpatasvir, and voxilaprevir was 2.213 min, 2.568 min, and 2.917 min, respectively. Sofosbuvir, velpatasvir, and voxilaprevir and their combination drug product were exposed to acidic, alkali, thermal, photolytic, and oxidative stress conditions. The current method was validated according to the ICH guidelines for accuracy, precision, linearity, specificity, and sensitivity. Conclusion: The method developed is more sensitive, accurate, precise, and robust then the methods reported earlier. Retention time and run time were decreased; hence, the method is economical simple and precise. Forced degradation studies indicated for the suitability of the method for stability studies of sofosbuvir, velpatasvir, and voxilaprevir. The proposed method can be used for routine quality control analysis test in pharmaceutical industries

A case of fibrolipomatous hamartoma of the median nerve with macrodactyly

Fibrolipomatous hamartoma of nerve is a tumor-like lipomatous process principally involving affecting young persons. The median nerve is most commonly affectedinvolved. The lesion is characterized by a soft slowly growing mass, surrounding and infiltrating major nerves and their branches. It may cause symptoms of compression neuropathy and is associated with macrodactyly in one third of cases. Here, we present a case of Fibrolipomatous hamartoma of nerve in the wrist of a young man arising from median nerve. Debulking of the tumour was performed

Report of Acoustic Test on PSLV IS.1/2L Structure

The results of acoustic conducted on PSLV IS.1/2L at Acoustic Test Facility are briefly given. It contains test set up, Instrumentation details and tables of spectral response

Role of serum LDH in preeclampsia as a prognostic factor – a cross sectional case control study in tertiary care hospital

Background: LDH is an intracellular cytoplasmic enzyme. It is ubiquitous to all the major organ systems. Cellular enzymes in extracellular space have no metabolic function, although they serve as indicators of disturbances in cellular integrity. Serum LDH is abnormal in many disorders, therefore total serum LDH is highly sensitive but nonspecific test. In preeclampsia also LDH may be elevated and can indicate the prognosis for both mother and fetus. We conducted this study to examine the relationship between lactate dehydrogenase concentration and the severity of the disease and the occurrence of its complications.Methods: 200 pre-eclamptic women (121 with mild and 79 with severe pre-eclampsia) and 200 healthy normotensive controls were studied prospectively at Government Kilpauk medical college and hospital between January and December 2015. Demographic, hemodynamic, and laboratory data were compared among the three groups. The symptoms and complications of severe pre-eclampsia along with fetal outcome were analyzed according to the levels of LDH.Results: Severely pre-eclamptic patients were significantly younger, with low gravidity and parity. On the other hand, they had significantly increased systolic and diastolic pressure and liver enzymes, uric acid, urine albumin, and LDH levels. The symptoms and complications of pre-eclampsia along with perinatal mortality were increased significantly in patients with LDH >800 IU/l compared with those who had lower levels.Conclusions:  Lactate dehydrogenase is a useful biochemical marker that reflects the severity of pre-eclampsia. In our study, LDH has been evaluated as a biochemical marker for preeclampsia and as a prognosticator of the disease severity. Detection of high-risk patients with increased levels of LDH mandate close monitoring and management to prevent maternal and fetal morbidity and mortality

The Need for Complementary Alternative Medicine Knowledge among Health-Related Majors in Higher Education

Recently, as more people have become dissatisfied with current methods of medical treatment, the use of complementary alternative medicine (CAM) has increased, possibly due to concerns regarding harmful side effects of pharmaceuticals. According to The National Health Interview Survey, 38% of individuals in America utilized unconventional treatments for diseases, and those with stronger educational backgrounds and higher incomes were more likely to use CAM due to an increased awareness of available treatments (NIH, 2007). As the use of CAM increases, medical students and medical professionals are becoming more receptive to using CAM for their patients. It is essential that these professionals receive the proper information regarding all of CAM’s benefits, perhaps through a modified curriculum beginning in undergraduate education. Thus, proper integration of CAM with the existing curriculum will have to be a concerted effort among aptly trained faculty members and appointed leaders within each institution (Sierpina, 2007). Such efforts must be made in order to expand upon the 15 educational programs funded by the NIH for medical schools (Gaylord & Mann, 2007). Given the many benefits and vast scope of CAM, it is imperative that healthcare majors be properly educated and trained to make well-informed decisions for their patients

Ant species richness and diversity in some selected localities of Western Ghats

We have sampled ants from twelve different localities in the Uttara Kannada district of Karnataka, India using both a package of standardized trapping methods as well as by intensive all-out-search. The relative efficacies of trapping versus all-out-search are compared. Different methods of trapping are also compared among themselves. A check list of all ants seen by all methods put together, identified up to the genus level is provided. Different localities are compared by the similarity and diversity 'of their ant fauna. A weak but statistically significant positive correlation between ant species diversity. and plant species diversity is demonstrated. This report provides the first estimates of the diversity and abundance of ants for any forest habitat of India