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Anand Pandey, Vipin Gupta, Shailendra P Singh, Vijendra Kumar, Rajesh Verma
A trophic ulcer is a pressure ulcer caused by external trauma to a part of the body that is compromised due to disease, vascular insufficiency, or loss of afferent nerve fibers. Spinal dysraphism (ie, neural tube defects [NTD]) such as meningomyelocele is a risk factor for developing these ulcers in adults and pediatric patients. Information regarding the occurrence of trophic ulcers in pediatric patients with NTD is lacking. A review of the English-language literature on skin/neuropathic ulcers in patients with NTDs, irrespective of study design, published between 1975 and 2014, was undertaken using the PubMed database...
December 2015: Ostomy/wound Management
Anne Rochtus, Raf Winand, Griet Laenen, Elise Vangeel, Benedetta Izzi, Christine Wittevrongel, Yves Moreau, Carla Verpoorten, Katrien Jansen, Chris Van Geet, Kathleen Freson
BACKGROUND: Neural tube defects (NTDs) are severe congenital malformations that arise from failure of neurulation during early embryonic development. The molecular basis underlying most human NTDs still remains largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, DNA methylation changes could play a role in NTDs. We performed a methylome analysis for patients with myelomeningocele (MMC). Using a candidate CpG analysis for HOX genes, a significant association between HOXB7 hypomethylation and MMC was found...
2016: Clinical Epigenetics
Xiaojing Qiao, Yahui Liu, Peiqiang Li, Zhongzhong Chen, Huili Li, Xueyan Yang, Richard H Finnell, Zhangmin Yang, Ting Zhang, Bin Qiao, Yufang Zheng, Hongyan Wang
The planar cell polarity (PCP) pathway is critical for proper embryonic development of the neural tube and heart. Mutations in these genes have previously been implicated in the pathogenesis of neural tube defects (NTDs), but not in congenital heart defects (CHDs) in humans. We systematically identified the mutation patterns of CELSR1-3 , one family of the core PCP genes, in human cohorts composed of 352 NTD cases, 412 CHD cases, and matched controls. A total of 72 disease-specific rare novel coding mutations were identified, of which 37 were identified in CHD cases, and 36 were identified in NTD patients...
October 18, 2016: Clinical Science (1979-)
M G Basáñez, M Walker, H C Turner, L E Coffeng, S J de Vlas, W A Stolk
Human onchocerciasis (river blindness) is one of the few neglected tropical diseases (NTDs) whose control strategies have been informed by mathematical modelling. With the change in focus from elimination of the disease burden to elimination of Onchocerca volvulus, much remains to be done to refine, calibrate and validate existing models. Under the impetus of the NTD Modelling Consortium, the teams that developed EPIONCHO and ONCHOSIM have joined forces to compare and improve these frameworks to better assist ongoing elimination efforts...
2016: Advances in Parasitology
Issei S Shimada, Saikat Mukhopadhyay
Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets...
October 12, 2016: Birth Defects Research. Part A, Clinical and Molecular Teratology
Meilin Tian, Shixin Ye
Allostery is essential to neuronal receptor function, but its transient nature poses a challenge for characterization. The N-terminal domains (NTDs) distinct from ligand binding domains are a major locus for allosteric regulation of NMDA receptors (NMDARs), where different modulatory binding sites have been observed. The inhibitor ifenprodil, and related phenylethanoamine compounds specifically targeting GluN1/GluN2B NMDARs have neuroprotective activity. However, whether they use differential structural pathways than the endogenous inhibitor Zn(2+) for regulation is unknown...
October 7, 2016: Scientific Reports
Mohan Zhao, Heng Zhang, Guangfeng Liu, Li Wang, Jian Wang, Zengqiang Gao, Yuhui Dong, Linbo Zhang, Yong Gong
RsmI and RsmH are conserved S-Adenosylmethionine (AdoMet)-dependent methyltransferases (MTases) that are responsible for the 2'-O-methylation and N4-methylation of C1402 in bacterial 16S rRNA, respectively. Methylation of m4Cm1402 plays a role in fine-tuning the shape and functions of the P-site to increase the decoding fidelity, and was recently found to contribute to the virulence of Staphylococcus aureus in host animals. Here we report the 2.20-Å crystal structure of homodimeric RsmI from Escherichia coli in complex with the cofactor AdoMet...
2016: PloS One
Jean Frantz Lemoine, Anne Marie Desormeaux, Franck Monestime, Carl Renad Fayette, Luccene Desir, Abdel Nasser Direny, Sarah Carciunoiu, Lior Miller, Alaine Knipes, Patrick Lammie, Penelope Smith, Melissa Stockton, Lily Trofimovich, Kalpana Bhandari, Richard Reithinger, Kathryn Crowley, Eric Ottesen, Margaret Baker
Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented...
October 2016: PLoS Neglected Tropical Diseases
Yan Qin, Yingming Pang, Zhihong Cheng
INTRODUCTION: The needle trap device (NTD) technique is a new microextraction method for sampling and preconcentration of volatile organic compounds (VOCs). Previous NTD studies predominantly focused on analysis of environmental volatile compounds in the gaseous and liquid phases. Little work has been done on its potential application in biological samples and no work has been reported on analysis of bioactive compounds in essential oils from herbal medicines. OBJECTIVE: The main purpose of the present study is to develop a NTD sampling method for profiling VOCs in biological samples using herbal medicines as a case study...
September 30, 2016: Phytochemical Analysis: PCA
Bing Li, Hong Sun, Changfeng Chen
Recently synthesized nanotwinned diamond (NTD) exhibits unprecedented Vickers hardness exceeding 200 GPa [Q. Huang et al., Nature (London) 510, 250 (2014)]. This extraordinary finding challenges the prevailing understanding of material deformation and stress response under extreme loading conditions. Here we unveil by first-principles calculations a novel indenter-deformation generated stress confinement mechanism that suppresses the graphitization or bond collapse failure modes commonly known in strong covalent solids, leading to greatly enhanced peak stress and strain range in the indented diamond lattice...
September 9, 2016: Physical Review Letters
Amit Pathania, Arvind Kumar Gupta, Swati Dubey, Balasubramanian Gopal, Abhijit A Sardesai
: ArgO and LysE are members of the LysE family of exporter proteins and ordinarily mediate export of L-arginine (Arg) in Escherichia coli and L-lysine (Lys) and Arg in Corynebacterium glutamicum respectively. Under certain conditions ArgO also mediates Lys export. To delineate the arrangement of ArgO in the cytoplasmic membrane of E. coli we have employed a combination of cysteine accessibility in situ, alkaline phosphatase fusion reporters and protein modelling, to arrive at a topological model for ArgO...
September 19, 2016: Journal of Bacteriology
Emmanuel S Antonarakis, Chandtip Chandhasin, Erica Osbourne, Jun Luo, Marianne D Sadar, Frank Perabo
: : Despite the recent approval and widespread use of abiraterone acetate and enzalutamide for the treatment of castration-resistant prostate cancer (CRPC), this disease still poses significant management challenges because of various tumor escape mechanisms, including those that allow androgen receptor (AR) signaling to remain active. These AR-related resistance mechanisms include AR gene amplification or overexpression, constitutively active ligand-independent AR splice variants, and gain-of-function mutations involving the AR ligand-binding domain (LBD), among others...
September 14, 2016: Oncologist
Catharina von Nicolai, Åsa Ehlén, Charlotte Martin, Xiaodong Zhang, Aura Carreira
BRCA2 tumour-suppressor protein is well known for its role in DNA repair by homologous recombination (HR); assisting the loading of RAD51 recombinase at DNA double-strand breaks. This function is executed by the C-terminal DNA binding domain (CTD) which binds single-stranded (ss)DNA, and the BRC repeats, which bind RAD51 and modulate its assembly onto ssDNA. Paradoxically, analysis of cells resistant to DNA damaging agents missing the CTD restore HR proficiency, suggesting another domain may take over its function...
2016: Nature Communications
Jun Kyu Mun, Jinyoung Youn, Jin Whan Cho, Eung-Seok Oh, Ji Sun Kim, Suyeon Park, Wooyoung Jang, Jin Se Park, Seong-Beom Koh, Jae Hyeok Lee, Hee Kyung Park, Han-Joon Kim, Beom S Jeon, Hae-Won Shin, Sun-Ah Choi, Sang Jin Kim, Seong-Min Choi, Ji-Yun Park, Ji Young Kim, Sun Ju Chung, Chong Sik Lee, Tae-Beom Ahn, Won Chan Kim, Hyun Sook Kim, Sang Myung Cheon, Jae Woo Kim, Hee-Tae Kim, Jee-Young Lee, Ji Sun Kim, Eun-Joo Kim, Jong-Min Kim, Kwang Soo Lee, Joong-Seok Kim, Min-Jeong Kim, Jong Sam Baik, Ki-Jong Park, Hee Jin Kim, Mee Young Park, Ji Hoon Kang, Sook Kun Song, Yong Duk Kim, Ji Young Yun, Ho-Won Lee, In-Uk Song, Young H Sohn, Phil Hyu Lee, Jeong-Ho Park, Hyung Geun Oh, Kun Woo Park, Do-Young Kwon
Despite the clinical impact of non-motor symptoms (NMS) in Parkinson's disease (PD), the characteristic NMS in relation to the motor subtypes of PD is not well elucidated. In this study, we enrolled drug-naïve PD patients and compared NMS between PD subtypes. We enrolled 136 drug-naïve, early PD patients and 50 normal controls. All the enrolled PD patients were divided into tremor dominant (TD) and non-tremor dominant (NTD) subtypes. The Non-Motor Symptom Scale and scales for each NMS were completed. We compared NMS and the relationship of NMS with quality of life between normal controls and PD patients, and between the PD subtypes...
2016: PloS One
Julia Asencio-Hernández, Bruno Kieffer, Marc-André Delsuc
There is growing evidence that bisphenol A (BPA), a molecule largely released in the environment, has detrimental effects on ecosystems and on human health. It acts as an endocrine disruptor targeting steroid hormone receptors, such as the estrogen receptor (ER), estrogen-related receptor (ERR) and androgen receptor (AR). BPA-derived molecules have recently been shown to interact with the AR N-terminal domain (AR-NTD), which is known to be largely intrinsically disordered. This N-terminal domain contains an 11 residue conserved domain that forms amyloid fibers upon oxidative dimerisation through its strictly conserved Cys240 residue...
2016: PloS One
Carmen A Banuelos, Iran Tavakoli, Amy H Tien, Daniel P Caley, Nasrin R Mawji, Zhenzhen Li, Jun Wang, Yu Chi Yang, Yusuke Imamura, Luping Yan, Jian Guo Wen, Raymond J Andersen, Marianne D Sadar
Androgen receptor (AR) is a validated drug target for all stages of prostate cancer including metastatic castration-resistant prostate cancer (CRPC). All current hormone therapies for CRPC target the C-terminal ligand-binding domain of AR and ultimately all fail with resumed AR transcriptional activity. Within the AR N-terminal domain (NTD) is activation function-1 (AF-1) that is essential for AR transcriptional activity. Inhibitors of AR AF-1 would potentially block most AR mechanisms of resistance including constitutively active AR splice variants that lack the ligand-binding domain...
October 14, 2016: Journal of Biological Chemistry
Phurpa Wangchuk, Paul R Giacomin, Mark S Pearson, Michael J Smout, Alex Loukas
Schistosomiasis and trichuriasis are two of the most common neglected tropical diseases (NTD) that affect almost a billion people worldwide. There is only a limited number of effective drugs to combat these NTD. Medicinal plants are a viable source of parasiticides. In this study, we have investigated six of the 19 phytochemicals isolated from two Bhutanese medicinal plants, Corydalis crispa and Pleurospermum amabile, for their anthelmintic properties. We used the xWORM technique and Scanning Electron Microscope-based imaging to determine the activity of the compounds...
2016: Scientific Reports
S A Gray, R N Coler, D Carter, A A Siddiqui
There is an urgent need to develop new vaccines for tuberculosis, HIV/AIDS, and malaria, as well as for chronic and debilitating infections known as neglected tropical diseases (NTDs). The term "NTD" emerged at the beginning of the new millennium to describe a set of diseases that are characterized as (1) poverty related, (2) endemic to the tropics and subtropics, (3) lacking public health attention and inadequate industrial investment, (4) having poor research funding and a weak research and development (R&D) pipeline, (5) usually associated with high morbidity but low mortality, and (6) often having no safe and long-lasting treatment available...
2016: Progress in Molecular Biology and Translational Science
Priyanka Mehta, Peter J Hotez
No abstract text is available yet for this article.
August 2016: PLoS Neglected Tropical Diseases
Xiaojiao Chen, Min Zhu, Lei Jiang, Wenyang Zhao, Jia Li, Jianyan Wu, Chun Li, Baohui Bai, Gang Lu, Hongyu Chen, Peter Moffett, Xiaorong Tao
The tomato resistance protein Sw-5b differs from the classical coiled-coil nucleotide-binding leucine-rich repeat (CC-NB-LRR) resistance proteins by having an extra N-terminal domain (NTD). To understand how NTD, CC and NB-LRR regulate autoinhibition and activation of Sw-5b, we dissected the function(s) of each domain. When viral elicitor was absent, Sw-5b LRR suppressed the central NB-ARC to maintain autoinhibition of the NB-LRR segment. The CC and NTD domains independently and additively enhanced the autoinhibition of NB-LRR...
October 2016: New Phytologist
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