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Sanhita Sinharay, Dianne Lee, Swati Shah, Siva Muthusamy, Georgios Z Papadakis, Xiang Zhang, Dragan Maric, William C Reid, Dima A Hammoud
INTRODUCTION: In vivo imaging biomarkers of various HIV neuropathologies, including dopaminergic dysfunction, are still lacking. Towards developing dopaminergic biomarkers of brain involvement in HIV, we assessed the pre and postsynaptic components of the dopaminergic system in the HIV-1 transgenic rat (Tg), a well-characterized model of treated HIV+ patients, using small-animal PET imaging. METHODS: Fifteen to 18 month-old Tg and wild type (WT) rats were imaged with both [18F]-FP-CMT, a dopamine transporter (DAT) ligand (n=16), and [18F]-Fallypride, a D2/D3 dopamine receptor (D2/D3DR) ligand (n=16)...
August 31, 2017: Nuclear Medicine and Biology
Rishi Sharma, Soo-Young Kim, Anjali Sharma, Zhi Zhang, Siva Pramodh Kambhampati, Sujatha Kannan, Rangaramanujam M Kannan
Brain related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood brain barrier (BBB), and potency. Despite its potential in the clinic, and in preclinical models, the high doses needed to affect a positive therapeutic response has led to side effects...
October 13, 2017: Bioconjugate Chemistry
David J Vance, Jacqueline M Tremblay, Yinghui Rong, Siva Krishna Angalakurthi, David B Volkin, C Russell Middaugh, David D Weis, Charles B Shoemaker, Nicholas J Mantis
We previously produced a heavy chain-only antibody VH domain (VHH)-displayed phage library from two alpacas that had been immunized with ricin toxoid and non-toxic mixtures of ricin's enzymatic (RTA) and binding (RTB) subunits (Vance et al J. Biol. Chem. 288:36538-47. doi: 10.1074/jbc.M113.519207). Initial and subsequent screens of that library by direct ELISA yielded more than two dozen unique RTA- and RTB-specific VHHs, including 10 whose structures were subsequently solved in complex with RTA. To generate a more complete antigenic map of ricin toxin and define the epitopes associated with toxin-neutralizing activity, we subjected the VHH-displayed phage library to additional pannings on both receptor bound and antibody-captured ricin...
October 11, 2017: Clinical and Vaccine Immunology: CVI
Venkata Siva Sai Sujith Sajja, Anna Jablonska, Norman J Haughey, Jeff W M Bulte, Robert D Stevens, Joseph Long, Piotr Walczak, Miroslaw Janowski
At present, accurate and reliable biomarkers to ascertain the presence, severity, or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an urgent need to establish accurate and reliable biomarkers capable of mbTBI detection. Currently, there are no studies that identify changes in miRNA and lipids at varied severities of bTBI. Various biological components such as lipids, circulating mRNA, and miRNA, could potentially be detected using advanced techniques such as next-generation sequencing and mass spectroscopy...
October 12, 2017: Journal of Neurotrauma
Pierre-Yves Le Roux, Shankar Siva, Jason Callahan, Yannis Claudic, David Bourhis, Daniel P Steinfort, Rodney J Hicks, Michael S Hofman
BACKGROUND: Functional volumes computed from (68)Ga-ventilation/perfusion (V/Q) PET/CT, which we have shown to correlate with pulmonary function test parameters (PFTs), have potential diagnostic utility in a variety of clinical applications, including radiotherapy planning. An automatic segmentation method would facilitate delineation of such volumes. The aim of this study was to develop an automated threshold-based approach to delineate functional volumes that best correlates with manual delineation...
October 10, 2017: EJNMMI Research
Chen-Chu Wang, Kundan Sivashanmugan, Chung-Ku Chen, Jian-Ren Hong, Wei-I Sung, Jiunn-Der Liao, Yuh-Shyong Yang
Protein tyrosine sulfation (PTS) is a key modulator of extracellular protein-protein interaction (PPI), which regulates principal biological processes. For example, the capsid protein VP1 of enterovirus 71 (EV71) specifically interacts with sulfated P-selectin glycoprotein ligand-1 (PSGL-1) to facilitate virus invasion. Currently available methods cannot be used to directly observe PTS-induced PPI. In this study, atomic force microscopy was used to measure the interaction between sulfated or mutated PSGL-1 and VP1...
October 13, 2017: Journal of Physical Chemistry Letters
M Sankari, H Hridya, P Sneha, C George Priya Doss, Siva Ramamoorthy
The current study was undertaken to analyse the effect of short-term UV-B and UV-C radiations in provoking carotenoid biosynthesis in Bixa orellana. Seeds of B. orellana were germinated and exposed to the short term UV pre-treatment under controlled environmental condition for 5days. The UV treated young seedlings response in pigment contents; antioxidant enzyme activity and mRNA gene expression level were analysed. The pigment content such as chlorophyll was increased in both UV-B and UV-C treated seedlings, but the total carotenoid level was decreased when compared to the control seedlings this can be attributed to the plant adaptability to survive in a stressed condition...
October 2, 2017: Journal of Photochemistry and Photobiology. B, Biology
Michael S Hofman, Peter Eu, Price Jackson, Emily Hong, David Binns, Amir Iravani, Declan Murphy, Catherine Mitchell, Shankar Siva, Rodney J Hicks, Jennifer D Young, Philip Blower, Gregory E Mullen
Objectives: Ga-68 labelled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as (68)Ga-HBED-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical (68)Ga-THP-PSMA has a simplified design for one-step kit-based radiolabelling. It features the tris(hydroxypyridinone) (THP) ligand, which complexes (68)Ga3+ rapidly at low concentration, room temperature and over a wide pH range, enabling direct elution from a (68)Ge/(68)Ga generator into a lyophilized kit in one-step without manipulation...
October 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Nirmal R Gopinathan, Balaji Saibaba, Siva S Santhanam, Kevin Syam
We report a unique case of post-traumatic avascular necrosis of tibia in a 12-year-old boy following a Salter-Harris type II physeal injury of the proximal tibia. The diagnosis was made on the basis of classical radiological findings. The only clinical symptom was diffuse shin pain. The patient was managed conservatively. At our 2-year follow-up, there was clinical and radiological evidence of spontaneous resolution of avascular necrosis, but with sequelae. The child developed a limb-length discrepancy and genu valgum...
October 3, 2017: Journal of Pediatric Orthopedics. Part B
Yongsheng Bai, Jeff Kinne, Lizhong Ding, Ethan C Rath, Aaron Cox, Siva Dharman Naidu
BACKGROUND: It is generally thought that most canonical or non-canonical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs. However, the question of whether at least some U12-type splicing occurs in the cytoplasm is still unclear. In recent years next-generation sequencing technologies have revolutionized the field. The "Read-Split-Walk" (RSW) and "Read-Split-Run" (RSR) methods were developed to identify genome-wide non-canonical spliced regions including special events occurring in cytoplasm...
October 3, 2017: BMC Bioinformatics
Akihito Uji, Siva Balasubramanian, Jianqin Lei, Elmira Baghdasaryan, Mayss Al-Sheikh, SriniVas R Sadda
Importance: Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging. Objective: To investigate multiple en face image averaging on OCTA images of the choriocapillaris. Design, Setting, and Participants: Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study...
October 5, 2017: JAMA Ophthalmology
Charles Shepherd, Matthias Koepp, Melissa Myland, Keyur Patel, Cristiana Miglio, Vathani Siva, Elizabeth Gray, Maureen Neary
INTRODUCTION: Epilepsy is highly prevalent in tuberous sclerosis complex (TSC), a multi-system genetic disorder. The clinical and economic burden of this condition is expected to be substantial due to treatment challenges, debilitating co-morbidities and the relationship between TSC-related manifestations. This study estimated healthcare resource utilisation (HCRU) and costs for patients with TSC with epilepsy (TSC+E) in the UK. METHODS: Patients with TSC+E in the Clinical Practice Research Datalink (CPRD) linked to Hospital Episodes Statistics were identified from April 1997 to March 2012...
October 5, 2017: BMJ Open
Chuanbin Yang, Cui-Zan Cai, Ju-Xian Song, Jie-Qiong Tan, Siva Sundara Kumar Durairajan, Ashok Iyaswamy, Ming-Yue Wu, Lei-Lei Chen, Zhenyu Yue, Min Li, Jia-Hong Lu
Alzheimer disease (AD) is the most common neurodegenerative disease characterized by the deposition of amyloid plaque in the brain. The autophagy-associated PIK3C3-containing phosphatidylinositol 3-kinase (PtdIns3K) complex has been shown to interfere with APP metabolism and amyloid beta peptide (Aβ) homeostasis via poorly understood mechanisms. Here we report that NRBF2 (nuclear receptor binding factor 2), a key component and regulator of the PtdIns3K, is involved in APP-CTFs homeostasis in AD cell models...
October 5, 2017: Autophagy
Irla Siva Kumar, Sandeep Kumar
Self-assembled supramolecular structures formed by disc-shaped molecules, commonly known as discotic liquid crystals (DLCs), have attracted tremendous interest during the past decade due to their potential applications in wide-viewing liquid crystal displays, sensors, photovoltaic solar cells, light emitting diodes, thin film transistors, etc. Since the discovery, only about sixty different core molecules have been explored to prepare about 3500 DLCs. We have realised a new heterocyclic aromatic molecular motif, s-heptazine, which functions as a core fragment for the synthesis of discotic liquid crystals on appropriate functionalization...
October 5, 2017: Chemical Communications: Chem Comm
Litty Babu, Siva R Uppalapati, Murali H Sripathy, Prakash N Reddy
Safety and protective efficacy of recombinant multi-epitope subunit vaccine (r-AK36) was evaluated in a mouse model. Recombinant AK36 protein comprised of immunodominant antigens from outer membrane proteins (Omp's) of Klebsiella pneumoniae namely OmpA and OmpK36. r-AK36 was highly immunogenic and the hyperimmune sera reacted strongly with native OmpA and OmpK36 proteins from different K. pneumoniae strains. Hyperimmune sera showed cross-reactivity with Omp's of other Gram-negative organisms. Humoral responses showed a Th2-type polarized immune response with IgG1 being the predominant antibody isotype...
2017: Frontiers in Microbiology
Dhavala Suri, Siva Vantari, Shalikram Joshi, Kartik Senapati, Pratap Kumar Sahoo, Shikha Varma, Ram Shanker Patel
We present a detailed study of thermal and electrical transport behavior of single crystal Titanium disulphide flakes, which belongs to the two dimensional, transition metal dichalcogenide class of materials. In-plane Seebeck effect measurements revealed a typical metal-like linear temperature dependence in the range of 85 - 285 K. Electrical transport measurements with in-plane current geometry exhibited a nearly T<sup>2</sup> dependence of resistivity in the range of 42 - 300 K. However, transport measurements along the out-of-plane current geometry showed a transition in temperature dependence of resistivity from T<sup>2</sup> to T<sup>5</sup> beyond 200 K...
October 4, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
Enrico Borrelli, Jianqin Lei, Siva Balasubramanian, Akihito Uji, Mariano Cozzi, Valentina Sarao, Paolo Lanzetta, Giovanni Staurenghi, SriniVas R Sadda
BACKGROUND/AIMS: To investigate the presence of short-wave fluorophores within regions of age-related macular degeneration (AMD)-associated macular atrophy (MA) area. METHODS: This is a prospective, observational, cross-sectional case series. 25 eyes (18 patients) with late AMD and clinically identified MA were enrolled. Eyes were imaged using a confocal light-emitting diode blue-light fundus autofluorescence (FAF) device (EIDON, CenterVue, Padua, Italy) with 450 nm excitation wavelength and the capability for 'colour' FAF imaging, including both the individual red and green components of the emission spectrum...
September 25, 2017: British Journal of Ophthalmology
Yoshio Nakatani, Helen K Opel-Reading, Matthias Merker, Diana Machado, Sönke Andres, S Siva Kumar, Danesh Moradigaravand, Francesc Coll, João Perdigão, Isabel Portugal, Thomas Schön, Dina Nair, K R Uma Devi, Thomas A Kohl, Patrick Beckert, Taane G Clark, Gugu Maphalala, Derrick Khumalo, Roland Diel, Kadri Klaos, Htin Lin Aung, Gregory M Cook, Julian Parkhill, Sharon J Peacock, Soumya Swaminathan, Miguel Viveiros, Stefan Niemann, Kurt L Krause, Claudio U Köser
Screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine.
October 2, 2017: Antimicrobial Agents and Chemotherapy
Siva Arumugam Saravanaperumal, Simon J Gibbons, John Malysz, Lei Sha, David R Linden, Joseph H Szurszewski, Gianrico Farrugia
Intracellular Cl(-) homeostasis is regulated by anion-permeable channels and transporters and contributes to excitability of many cell types including smooth muscle and interstitial cells of Cajal (ICC) . Our aims were to investigate the effects on electrical activity in mouse jejunal muscle strips, of substituting extracellular Cl(-) (Cl(-)o ) with the impermeant anions, gluconate and isethionate. On reducing Cl(-)o , effects were observed on electrical slow waves with small effects on smooth muscle membrane voltage (Em )...
October 3, 2017: Experimental Physiology
Ramana R Mittapalli, Siva S R Namashivaya, Aleksandr S Oshchepkov, Tatiana A Shumilova, Tobias Rüffer, Heinrich Lang, Evgeny A Kataev
Bicyclic receptors bearing anthracene as a strap were designed for selective oxalate binding in a buffered aqueous solution. The receptors were found to possess two mechanisms of fluorescence response depending on the pH of a buffered solution. Receptor 2 binds oxalate at pH 6.2 showing a 10-fold fluorescence enhancement and a two orders of magnitude selectivity over other anions.
October 12, 2017: Chemical Communications: Chem Comm
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