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Molecular biology

Mariella G Filbin, Dominik Sturm
Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features...
February 2018: Seminars in Neurology
Elizabeth R Gerstner, Kristian W Pajtler
Ependymoma can arise throughout the whole neuraxis. In children, tumors predominantly occur intracranially, whereas the spine is the most prevalent location in adults. Significant variance in the grade II versus grade III distinction of ependymomas has led to the acknowledgment that the clinical utility of histopathological classification is limited. Epigenomic profiling efforts have identified molecularly distinct groups of ependymomas that adequately reflect the biological, clinical, and histopathological heterogeneities across anatomical compartments, age groups, and grades...
February 2018: Seminars in Neurology
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Philipp Kickingereder, Ovidiu Cristian Andronesi
Magnetic resonance imaging plays a key role in diagnosis and treatment monitoring of brain tumors. Novel imaging techniques that specifically interrogate aspects of underlying tumor biology and biochemical pathways have great potential in neuro-oncology. This review focuses on the emerging role of 2-hydroxyglutarate-targeted magnetic resonance spectroscopy, as well as radiomics and radiogenomics in establishing diagnosis for isocitrate dehydrogenase mutant gliomas, and for monitoring treatment response and predicting prognosis of this group of brain tumor patients...
February 2018: Seminars in Neurology
Silvia Salerno, Aída Nelly García-Argáez, Elisabetta Barresi, Sabrina Taliani, Francesca Simorini, Concettina La Motta, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
Inhibition of angiogenesis via blocking vascular endothelial growth factor receptor (VEGFR) signaling pathway emerged as an established approach in anticancer therapy. So far, many monoclonal antibodies and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1-21 featuring different substitution patterns on the pendant phenyl moiety, combined with H, OCH3 , or Cl at 8-position...
March 7, 2018: European Journal of Medicinal Chemistry
Hendrik Göddeke, M Hadi Timachi, Cedric A Hutter, Laura Galazzo, Markus A Seeger, Mikko Karttunen, Enrica Bordignon, Lars V Schäfer
ATP-binding cassette (ABC) transporters are ATP-driven molecular machines, in which ATP binding and hydrolysis in the nucleotide-binding domains (NBDs) is chemo-mechanically coupled to large-scale, alternating access conformational changes in the transmembrane domains (TMDs), ultimately leading to the translocation of substrates across biological membranes. The precise nature of the structural dynamics behind the large-scale conformational transition as well as the coupling of NBD and TMD motions is still unresolved...
March 16, 2018: Journal of the American Chemical Society
Shushan He, Lutz Maibaum
Understanding the (de)mixing behavior of multicomponent lipid bilayers is an important step towards unraveling the nature of spatial composition heterogeneities in cellular membranes and their role in biological function. We use coarse-grained molecular dynamics simulations to study the composition phase diagram of a quaternary mixture of phospholipids and cholesterol. This mixture is known to exhibit both uniform and coexisting phases. We compare and combine different statistical measures of membrane structure to identify the onset of phase coexistence in composition space...
March 16, 2018: Journal of Physical Chemistry. B
Charles Hellec, Maxime Delos, Mathieu Carpentier, Agnès Denys, Fabrice Allain
Heparan sulfate 3-O-sulfotransferases (HS3STs) catalyze the final maturation step of heparan sulfates. Although seven HS3ST isozymes have been described in human, 3-O-sulfation is a relatively rare modification, and only a few biological processes have been described to be influenced by 3-O-sulfated motifs. A conflicting literature has recently reported that HS3ST2, 3A, 3B and 4 may exhibit either tumor-promoting or anti-oncogenic properties, depending on the model used and cancer cell phenotype. Hence, we decided to compare the consequences of the overexpression of each of these HS3STs in the same cellular model...
2018: PloS One
Yimin Wang, Fang Ye, Chanyan Huang, Faling Xue, Yingyuan Li, Shaowei Gao, Zeting Qiu, Si Li, Qinchang Chen, Huaqiang Zhou, Yiyan Song, Wenqi Huang, Wulin Tan, Zhongxing Wang
BACKGROUND: Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. METHODS: Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected...
March 15, 2018: Clinical Journal of Pain
Caleb J Bashor, James J Collins
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function...
March 16, 2018: Annual Review of Biophysics
Jejoong Yoo, Aleksei Aksimentiev
In contrast to ordinary polymers, the vast majority of biological macromolecules adopt highly ordered three-dimensional structures that define their functions. The key to folding of a biopolymer into a unique 3D structure or to an assembly of several biopolymers into a functional unit is a delicate balance between the attractive and repulsive forces that also makes such self-assembly reversible under physiological conditions. The all-atom molecular dynamics (MD) method has emerged as a powerful tool for studies of individual biomolecules and their functional assemblies, encompassing systems of ever increasing complexity...
March 16, 2018: Physical Chemistry Chemical Physics: PCCP
Guido Kobbe, Thomas Schroeder, Rainer Haas, Ulrich Germing
Allogeneic blood stem cell transplantation (aBSCT) still is the only curative therapy for patients with myelodysplastic syndromes. While it carries the hope for cure for some patients, it may result in severe toxicity and death from complications or recurrent disease in others. Recent developments have improved patient and donor selection as well as technical aspects of the transplant procedure and post-transplant care, including early detection and treatment of relapse. Areas covered: This review will discuss current stratification tools to identify suitable patients, donors and transplant techniques...
March 16, 2018: Expert Review of Hematology
Michael B Ranke, Jan M Wit
Growth hormone (GH) research and its clinical application for the treatment of growth disorders span more than a century. During the first half of the 20th century, clinical observations and anatomical and biochemical studies formed the basis of the understanding of the structure of GH and its various metabolic effects in animals. The following period (1958-1985), during which pituitary-derived human GH was used, generated a wealth of information on the regulation and physiological role of GH - in conjunction with insulin-like growth factors (IGFs) - and its use in children with GH deficiency (GHD)...
March 16, 2018: Nature Reviews. Endocrinology
Mario A Saporta, Renata de Moraes Maciel
The human skin is richly innervated by nerve fibers of different calibers and functions, including thickly myelinated large fibers that act as afferents for mechanoreceptors in the dermal papillae. Skin biopsies offer minimally invasive access to these myelinated fibers, in which each internode represents an individual myelinating Schwann cell. Using this approach, human myelinated nerve fibers can be analyzed by several methods, including immunostaining, morphometric and ultrastructural analysis, and molecular biology techniques...
2018: Methods in Molecular Biology
Hironori Aoki, Eiichiro Yamamoto, Hiro-O Yamano, Tamotsu Sugai, Tomoaki Kimura, Yoshihito Tanaka, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Taku Harada, Gota Sudo, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Takeshi Niinuma, Masahiro Kai, Masanori Nojima, Hiromu Suzuki, Hiroshi Nakase
BACKGROUND: Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. AIMS: We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. METHODS: A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L)...
March 15, 2018: Digestive Diseases and Sciences
Xiaohui Zhao, Fuqiang Fan, Huaidong Zhou, Panwei Zhang, Gaofeng Zhao
In-depth understanding of indigenous microbial assemblages resulted from aged contamination by polycyclic aromatic hydrocarbons (PAHs) is of vital importance in successful in situ bioremediation treatments. Soil samples of three boreholes were collected at 12 different vertical depths. Overall, the dominating three-ring PAHs (76.2%) were closely related to distribution patterns of soil dehydrogenase activity, microbial cell numbers, and Shannon biodiversity index (H') of indigenous microorganisms. High-molecular-weight PAHs tend to yield more diverse communities...
March 15, 2018: Bioprocess and Biosystems Engineering
Junxiang Wang, Guifang Lin, Khadija Batool, Shuaiqi Zhang, Mingfeng Chen, Jin Xu, Juan Wu, Liang Jin, Ivan Gelbic, Lei Xu, Lingling Zhang, Xiong Guan
Ectropis oblique Prout (Lepidoptera: Geometridae) is one of the main pests that damages the tea crop in Southeast Asia. To understand the molecular mechanisms of its feeding biology, transcriptomes of the alimentary tract (AT) and of the body minus the AT of E. oblique were successfully sequenced and analyzed in this study. A total of 36,950 unigenes from de novo sequences were assembled. After analysis using six annotation databases (e.g., Gene Ontology, Kyoto Encyclopedia of Genes and Genome, and NCBI nr), a series of putative genes were found for this insect species that were related to digestion, detoxification, the immune system, and Bacillus thuringiensis (Bt) receptors...
March 12, 2018: Journal of Economic Entomology
Harriet C Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Webb, Luk J R Rombauts, Beverley J Vollenhoven, Lois A Salamonsen, Tracey A Edgell
The regenerative, proliferative phase of a woman's menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined. We hypothesized that alterations in the secreted proteome of the endometrium of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration...
March 13, 2018: Biology of Reproduction
Abinaya Manivannan, Jin-Hee Kim, Eun-Young Yang, Yul-Kyun Ahn, Eun-Su Lee, Sena Choi, Do-Sun Kim
Pepper is an economically important horticultural plant that has been widely used for its pungency and spicy taste in worldwide cuisines. Therefore, the domestication of pepper has been carried out since antiquity. Owing to meet the growing demand for pepper with high quality, organoleptic property, nutraceutical contents, and disease tolerance, genomics assisted breeding techniques can be incorporated to develop novel pepper varieties with desired traits. The application of next-generation sequencing (NGS) approaches has reformed the plant breeding technology especially in the area of molecular marker assisted breeding...
2018: BioMed Research International
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