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Regulation of FGF signaling: recent insights from studying positive and negative modulators. - Seminars in cell & developmental biology
Fibroblast growth factor (FGF) signaling is involved in a multitude of biological processes, while impairment of FGF signaling is implicated in a variety of human diseases including developmental disorders and cancer. Therefore, it is not surprising that FGF activity is regulated at multiple and distinct levels. This review focuses on positive and negative modulation of the FGF signal exemplified by recently identified protein modulators anosmin-1, fibronectin-leucine-rich transmembrane protein 3 (FLRT3) and similar expression to FGF (Sef). We examine how these proteins regulate FGF signaling at multiple levels and across species. Finally, we describe the role of these regulators in human disease.Copyright Â© 2016. Published by Elsevier Ltd.
Slippery when sticky: Lubricating properties of thin films of Taxus baccata aril mucilage. - Biointerphases
Mucilage is hydrogel produced from succulent plants and microorganisms displaying unique adhesiveness and slipperiness simultaneously. The objective of this study is to establish an understanding on the lubricating mechanisms of the mucilage from Taxus baccata aril as thin, viscous lubricant films. Oscillation and flow rheological studies revealed that T. baccata mucilage is shear-thinning, thixotropic, and weak hydrogel that is highly stretchable under shear stress due to its high density physical crosslinking characteristics. In addition, T. baccata mucilage showed a distinct Weissenberg effect, i.e., increasing normal force with increasing shear rate, and thus it contributes to deplete the lubricant from tribological interfaces. Lubrication studies with a number of tribopairs with varying mechanical properties and surface wettability have shown that the lubricity of T. baccata mucilage is most effectively manifested at soft, hydrophilic, and rolling tribological contacts. Based on tenacious spreading on highly wetting surfaces, slip plane can be formed within mucilage hydrogel network even when the lubricating films cannot completely separate the opposing surfaces. Moreover, highly stretchable characteristics of mucilage under high shear enhance smooth shearing of two opposing surfaces as lubricating film.
Analysis of mechanisms of bacterial (Serratia marcescens) attachment, migration and killing of fungal hyphae. - Applied and environmental microbiology
We have found a remarkable capacity of the ubiquitous gram negative rod bacterium Serratia marcescens to migrate along and kill the mycelium of zygomycete molds. This migration was restricted to zygomycete molds, and several Basidiomycete spp. No migration was seen on any mold of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well. S. marcescens did not exhibit growth tropism towards zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm covering and killing the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion since mutants defective in this adhesin migrated equally well or faster than the wild- type strain. Killing does not depend on the secretion of S. marcescens chitinases as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. Better understanding of the mechanisms by which S. marcescens binds, spreads and kills fungal hyphae could serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol.Copyright Â© 2016, American Society for Microbiology. All Rights Reserved.
Correlating behaviour and gene expression endpoints in the dopaminergic system after modafinil administration in mouse. - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
The mechanisms of action of modafinil continue to be poorly characterised and its potential for abuse in preclinical models remains controverted. The aim of this study was to further elucidate the mechanism of action of modafinil, through a potential behavioural and molecular association in the mouse. A conditioned place preference (CPP) paradigm was implemented to investigate the rewarding properties of modafinil. Whole genome expression and qRT-PCR analysis were performed on the ventral tegmental area (VTA), nucleus accumbens (NAC) and prefrontal cortex (PFC) of modafinil-treated and control animals. Modafinil administration (65mg/kg) induced an increase in locomotor activity, an increase in the change of preference for the drug paired side after a conditioning period as well as changes to gene expression profiles in the VTA (120 genes), NAC (23 genes) and PFC (19 genes). A molecular signature consisting of twelve up-regulated genes was identified as common to the three brain regions. Multiple linear correlation analysis showed a strong correlation (R(2)>0.70) between the behavioural and molecular endpoints in the three brain regions. We show that modafinil had a concomitant effect on CPP, locomotor activity, and up-regulation of interferon-Î³ (IFN-Î³) regulated genes (Gbp2, Gbp3, Gbp10, Cd274, Igtp), while correlating the latter set of genes with behaviour changes evaluated through the CPP. A potential association can be proposed based on the dysregulation of p47 family genes and Gbp family of IFN-Î³ induced GTPases. In conclusion, these findings suggest a link between the behavioural and molecular events in the context of modafinil administration.Copyright Â© 2016 Elsevier B.V. and ECNP. All rights reserved.
Serodiagnosis of bovine trypanosomosis caused by non-tsetse transmitted Trypanosoma (Duttonella) vivax parasites using the soluble form of a Trypanozoon variant surface glycoprotein antigen. - Veterinary parasitology
Previous studies have shown that a 64-kDa antigen (p64) that was purified from the Venezuelan TeAp-N/D1 isolate of Trypanosoma (Trypanozoon) equiperdum corresponds to the soluble form of its predominant variant surface glycoprotein (VSG), and exhibited cross-reactivity with Trypanosoma (Duttonella) vivax. The course of experimental acute infections of bovines with T. vivax were followed by measuring whole anti-p64 antibodies and specific anti-p64 IgG and IgM antibodies in animal sera by indirect enzyme-linked immunosorbent assay (ELISA). The value of p64 to diagnose bovine trypanosomosis was also examined using 350 sera from healthy and T. vivax-infected cows living in a trypanosomosis-endemic and enzootic stable area, and 48 sera obtained during a trypanosomosis outbreak. Serological assays showed that âˆ¼70-80% of the infected sera contained anti-p64 antibodies, based on the comparative immunodetection of the T. equiperdum clarified antigenic fraction used as a reference test. In the absence of a gold standard, Bayesian analysis for multiple testing estimated a sensitivity and specificity of 71.6% and 98.8%, respectively, for the indirect ELISA using p64â€‰as antigen. An apparent prevalence of 37.7% for bovine trypanosomosis infection was also estimated with a Bayesian approach when the p64 ELISA test was used. Employing blood from acute infected cows, the indirect ELISA response against p64 was contrasted with the microhematocrit centrifuge method and analyses by polymerase chain reaction (PCR) using specific primers targeting the inter-specific length variation of the internal transcribed spacer 1 region of the 18S ribosomal gene. The efficiency of p64 for the detection of anti-trypanosome antibodies in acute infected bovines was also corroborated serologically by comparing its response to that of the Indonesian Trypanosoma evansi Rode Trypanozoon antigen type (RoTat) 1.2 VSG, which possesses high specificity and sensitivity. As expected, PCR was the best method to detect parasites and diagnose bovine trypanosomosis; however, a substantial level of concordance (Cohen's Îº=0.667) was obtained when serological tests using p64 and RoTat 1.2 VSG were compared. Additionally, an agglutination assay was designed using p64 covalently coupled to carboxylate-modified latex microparticles, which was proven here to be suitable for a fast qualitative diagnosis of bovine trypanosomosis.Copyright Â© 2016 Elsevier B.V. All rights reserved.
The First Alcohol Drink Triggers mTORC1-Dependent Synaptic Plasticity in Nucleus Accumbens Dopamine D1 Receptor Neurons. - The Journal of neuroscience : the official journal of the Society for Neuroscience
Early binge-like alcohol drinking may promote the development of hazardous intake. However, the enduring cellular alterations following the first experience with alcohol consumption are not fully understood. We found that the first binge-drinking alcohol session produced enduring enhancement of excitatory synaptic transmission onto dopamine D1 receptor-expressing neurons (D1+ neurons) in the nucleus accumbens (NAc) shell but not the core in mice, which required D1 receptors (D1Rs) and mechanistic target of rapamycin complex 1 (mTORC1). Furthermore, inhibition of mTORC1 activity during the first alcohol drinking session reduced alcohol consumption and preference of a subsequent drinking session. mTORC1 is critically involved in RNA-to-protein translation, and we found that the first alcohol session rapidly activated mTORC1 in NAc shell D1+ neurons and increased synaptic expression of the AMPAR subunit GluA1 and the scaffolding protein Homer. Finally, D1R stimulation alone was sufficient to activate mTORC1 in the NAc to promote mTORC1-dependent translation of the synaptic proteins GluA1 and Homer. Together, our results indicate that the first alcohol drinking session induces synaptic plasticity in NAc D1+ neurons via enhanced mTORC1-dependent translation of proteins involved in excitatory synaptic transmission that in turn drives the reinforcement learning associated with the first alcohol experience. Thus, the alcohol-dependent D1R/mTORC1-mediated increase in synaptic function in the NAc may reflect a neural imprint of alcohol's reinforcing properties, which could promote subsequent alcohol intake.Consuming alcohol for the first time is a learning event that drives further drinking. Here, we identified a mechanism that may underlie the reinforcing learning associated with the initial alcohol experience. We show that the first alcohol experience induces a persistent enhancement of excitatory synaptic transmission on NAc shell D1+ neurons, which is dependent on D1R and mTORC1. We also find that mTORC1 is necessary for the sustained alcohol consumption and preference across the initial drinking sessions. The first alcohol binge activates mTORC1 in NAc D1+ neurons and increases levels of synaptic proteins involved in glutamatergic signaling. Thus, the D1R/mTORC1-dependent plasticity following the first alcohol exposure may be a critical cellular component of reinforcement learning.Copyright Â© 2016 the authors 0270-6474/16/360701-13$15.00/0.
Perinatal/Neonatal case presentation: pulmonary artery sling associated with respiratory distress. - SpringerPlus
Pulmonary artery sling is a very rare cause of pediatric respiratory distress. The estimated prevalence of the disease was first determined by Yu et al. in 2008 as 59 per million school-aged children. Associated symptoms are cough, wheezing, and feeding difficulty, all of which are common in routine outpatient pediatric clinical encounters. We report a case of a premature male neonate twin who was admitted to the neonatal intensive care unit with respiratory distress and pneumothorax. His presentation, as well as the etiology of his pulmonary disease, was felt to be consistent with those of numerous other premature infants. Akin to this was his delayed discharge on account of his slow progress with oral feeding. Parents gave a history of tachypnea and feeding difficulty to his doctors. He presented twice to the emergency room in respiratory distress. At 4Â months of age, while in hospital for a pulmonary infection, he had an echocardiogram that revealed a pulmonary artery sling. We review the literature on this vascular anomaly, discuss its diagnosis and management, and critique the clinical thinking that determined this child's course from the perspective of availability heuristics.
White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis. - Multiple sclerosis (Houndmills, Basingstoke, England)
While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind.The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients.Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS).A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance (R(2)â€‰=â€‰0.48, pâ€‰=â€‰0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major.Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.Â© The Author(s), 2016.
AMPylation matches BiP activity to client protein load in the endoplasmic reticulum. - eLife
The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP affects protein folding homeostasis and the response to ER stress. Reversible inactivating covalent modification of BiP is believed to contribute to the balance between chaperones and unfolded ER proteins, but the nature of this modification has so far been hinted at indirectly. We report that deletion of FICD, a gene encoding an ER-localized AMPylating enzyme, abolished detectable modification of endogenous BiP enhancing ER buffering of unfolded protein stress in mammalian cells, whilst deregulated FICD activity had the opposite effect. In vitro, FICD AMPylated BiP to completion on a single residue, Thr(518). AMPylation increased, in a strictly FICD-dependent manner, as the flux of proteins entering the ER was attenuated in vivo. In vitro, Thr(518) AMPylation enhanced peptide dissociation from BiP 6-fold and abolished stimulation of ATP hydrolysis by J-domain cofactor. These findings expose the molecular basis for covalent inactivation of BiP.
Measurement of the differential cross section for top quark pair production in pp collisions at [Formula: see text]. - The European physical journal. C, Particles and fields
The normalized differential cross section for top quark pair ([Formula: see text]) production is measured in pp collisions at a centre-of-mass energy of 8[Formula: see text] at the CERN LHC using the CMS detector in data corresponding to an integrated luminosity of 19.7[Formula: see text]. The measurements are performed in the lepton[Formula: see text]jets ([Formula: see text][Formula: see text]jets) and in the dilepton ([Formula: see text], [Formula: see text], and [Formula: see text]) decay channels. The [Formula: see text] cross section is measured as a function of the kinematic properties of the charged leptons, the jets associated to b quarks, the top quarks, and the [Formula: see text] system. The data are compared with several predictions from perturbative quantum chromodynamic up to approximate next-to-next-to-leading-order precision. No significant deviations are observed relative to the standard model predictions.
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133 Littleton Rd Suite 202
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