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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
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
Brooke N Wolford, Cristen J Willer, Ida Surakka
The combination of Electronic Health Records (EHRs) with genetic data has ushered in the next wave of complex disease genetics. Population-based biobanks and other large cohorts provide sufficient sample sizes to identify novel genetic associations across the hundreds to thousands of phenotypes gleaned from EHRs. In this review we summarize the current state of these EHR-linked biobanks, explore ongoing methods development in the field, and highlight recent discoveries of genetic associations. We enumerate the many existing biobanks with EHRs linked to genetic data, many of which are available to researchers via application and contain sample sizes > 50,000...
March 14, 2018: Human Molecular Genetics
Jiawei Wang, Bingjiao Yang, André Leier, Tatiana T Marquez-Lago, Morihiro Hayashida, Andrea Rocker, Zhang Yanju, Tatsuya Akutsu, Kuo-Chen Chou, Richard A Strugnell, Jiangning Song, Trevor Lithgow
Motivation: Many Gram-negative bacteria use type VI secretion systems (T6SS) to export effector proteins into adjacent target cells. These secreted effectors (T6SEs) play vital roles in the competitive survival in bacterial populations, as well as pathogenesis of bacteria. Although various computational analyses have been previously applied to identify effectors secreted by certain bacterial species, there is no universal method available to accurately predict T6SS effector proteins from the growing tide of bacterial genome sequence data...
March 14, 2018: Bioinformatics
Julia K Nussbacher, Gene W Yeo
RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced UV crosslinking followed by immunoprecipitation (eCLIP) datasets for 126 RBPs to discover miR-encoding genomic loci that are statistically enriched for RBP binding. We find that 92% of RBPs interact directly with at least one miR locus, and that some interactions are cell line specific despite expression of the miR locus in both cell lines evaluated...
March 15, 2018: Molecular Cell
Jared T Hammill, Deepak Bhasin, Daniel C Scott, Jaeki Min, Yizhe Chen, Yan Lu, Lei Yang, Ho Shin Kim, Michele C Connelly, Courtney Hammill, Gloria Holbrook, Cynthia Jeffries, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg)...
March 16, 2018: Journal of Medicinal Chemistry
Christopher Nicolai Roterman, Won-Kyung Lee, Xinming Liu, Rongcheng Lin, Xinzheng Li, Yong-Jin Won
The recent discovery of two new species of kiwaid squat lobsters on hydrothermal vents in the Pacific Ocean and in the Pacific sector of the Southern Ocean has prompted a re-analysis of Kiwaid biogeographical history. Using a larger alignment with more fossil calibrated nodes than previously, we consider the precise relationship between Kiwaidae, Chirostylidae and Eumunididae within Chirostyloidea (Decapoda: Anomura) to be still unresolved at present. Additionally, the placement of both new species within a new "Bristly" clade along with the seep-associated Kiwa puravida is most parsimoniously interpreted as supporting a vent origin for the family, rather than a seep-to-vent progression...
2018: PloS One
Ya Chen, Yong Tang, Beibei Mao, Wenchao Li, Hongwei Jin, Liangren Zhang, Zhenming Liu
Any type of breast cancer not expressing genes of the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) is referred to as triple-negative breast cancer (TNBC). Accordingly, TNBCs do not respond to hormonal therapies or medicines targeting the ER, PR, or HER2. Systemic chemotherapy is therefore the only treatment option available today and prognoses remain poor. We report the discovery and characterization of N-(naphtho[1,2-b]furan-5-yl)benzenesulfonamides as selective inhibitors of TNBCs...
March 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Andrew R Tee
Mammalian target of rapamycin (mTOR, now referred to as mechanistic target of rapamycin) is considered as the master regulator of cell growth. A definition of cell growth is a build-up of cellular mass through the biosynthesis of macromolecules. mTOR regulation of cell growth and cell size is complex, involving tight regulation of both anabolic and catabolic processes. Upon a growth signal input, mTOR enhances a range of anabolic processes that coordinate the biosynthesis of macromolecules to build cellular biomass, while restricting catabolic processes such as autophagy...
March 16, 2018: International Journal of Molecular Sciences
Steve Peigneur, Jan Tytgat
Venoms from marine and terrestrial animals (cone snails, scorpions, spiders, snakes, centipedes, cnidarian, etc.) can be seen as an untapped cocktail of biologically active compounds, being increasingly recognized as a new emerging source of peptide-based therapeutics.
March 16, 2018: Toxins
Daniel M P Ardisson-Araújo, Ana Maria Rodrigues da Silva, Fernando L Melo, Ethiane Rozo Dos Santos, Daniel R Sosa-Gómez, Bergmann M Ribeiro
In this report, we described the genome of a novel baculovirus isolated from the monocot insect pest Mocis latipes , the striped grass looper. The genome has 134,272 bp in length with a G + C content of 38.3%. Based on the concatenated sequence of the 38 baculovirus core genes, we found that the virus is a betabaculovirus closely related to the noctuid-infecting betabaculoviruses including Pseudaletia unipuncta granulovirus (PsunGV), Trichoplusia ni granulovirus (TnGV), Helicoverpa armigera granulovirus (HearGV), and Xestia c-nigrum granulovirus (XecnGV)...
March 16, 2018: Viruses
Carlos Fernández-Hernando, Yajaira Suárez
PURPOSE OF REVIEW: Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with several aspects of vascular dysfunction. RECENT FINDINGS: MiRNAs have been found to be critical modulators of endothelial homeostasis. The dysregulation of miRNAs has been linked to endothelial dysfunction and the development and progression of vascular disease which and open new opportunities of using miRNAs as potential therapeutic targets for vascular disease...
March 14, 2018: Current Opinion in Hematology
Hanrui Zhang
PURPOSE OF REVIEW: Lysosomal acid lipase (LAL), encoded by the LIPA gene, is an essential lysosomal enzyme that hydrolyzes cholesteryl ester and triglyceride delivered to the lysosome. This review highlights the novel pathophysiological role of LAL, the functional genomic discoveries of LIPA as a risk locus for coronary heart diseases (CHD), and the clinical advance in therapies for LAL deficiency. RECENT FINDINGS: The essential role of LAL in lipid metabolism has been confirmed in human and mice with LAL deficiency...
March 15, 2018: Current Opinion in Lipidology
Cleverson Carlos Matiolli, Maeli Melotto
Yeast-two-hybrid (Y2H) cDNA library screening is a valuable tool to uncover protein-protein interactions and represents a widely used method to investigate protein function. However, cDNA libraries with low transcript representation limits the depth of the screening. We have developed a Y2H library with cDNA made from Arabidopsis leaves exposed to several stressors as well as untreated leaves. The library was built using pooled mRNA extracted from plants challenged with plant and human bacterial pathogens, the flg22 elicitor, the phytotoxin coronatine, and several hormones associated with environmental stress responses...
March 16, 2018: Molecular Plant-microbe Interactions: MPMI
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
Guy G Marcus, Dae-Jeong Kim, Jacob A Tutmaher, Jose A Rodriguez-Rivera, Jonas Okkels Birk, Christof Niedermeyer, Hannoh Lee, Zachary Fisk, Collin L Broholm
We report the discovery of a field driven transition from a single-q to multi-q spin density wave (SDW) in the tetragonal heavy fermion compound CeAuSb_{2}. Polarized along c, the sinusoidal SDW amplitude is 1.8(2)μ_{B}/Ce for T≪T_{N}=6.25(10)  K with a wave vector q_{1}=(η,η,1/2) [η=0.136(2)]. For H∥c, harmonics appearing at 2q_{1} evidence a striped magnetic texture below μ_{∘}H_{1}=2.78(1)  T. Above H_{1}, these are replaced by coupled harmonics at q_{1}+q_{2}=(2η,0,0)+c^{*} until μ_{∘}H_{2}=5...
March 2, 2018: Physical Review Letters
Luis Bering, Felix M Paulussen, Andrey P Antonchick
The nitrosonium ion-catalyzed dehydrogenative coupling of heteroarenes under mild reaction conditions is reported. The developed method utilizes ambient molecular oxygen as a terminal oxidant, and only water is produced as byproduct. Dehydrogenative coupling of heteroarenes translated into the rapid discovery of novel hedgehog signaling pathway inhibitors, emphasizing the importance of the developed methodology.
March 16, 2018: Organic Letters
Fan Sun, Zhongnan Guo, Ning Liu, Dan Wu, Jiawei Lin, Erjian Cheng, Tianping Ying, Shiyan Li, Wenxia Yuan
In this work, we report the discovery of a new Ni-based quasi-one-dimensional selenide: Cs0.9 Ni3.1 Se3 . This compound adopts the TlFe3 Te3 -type structure with space group P63 / m, which consists of infinite [Ni3 Se3 ] chains with face-sharing Ni6 octahedra along the c direction. The lattice parameters are calculated as a = 9.26301(4) Å and c = 4.34272(2) Å, with the Ni-Ni distance in the ab plane as 2.582(3) Å, suggesting the formation of a Ni-Ni metallic bond in this compound. Interestingly, it has been found that Cs0...
March 16, 2018: Inorganic Chemistry
Susana R Cerqueira, Yee-Shuan Lee, Mary Bartlett Bunge
In vitro models using Schwann cell and astrocyte co-cultures have been used to understand the mechanisms underlying the formation of boundaries between these cells in vivo. Schwann cell/astrocyte co-cultures also mimic the in vivo scenario of a transplant in a spinal cord injury site, thereby allowing testing of therapeutic approaches. In this chapter, we describe a triple cell culture system with Schwann cells, astrocytes, and neurons that replicates axon growth from a Schwann cell graft into an astrocyte-rich region...
2018: Methods in Molecular Biology
Paula V Monje
This chapter describes protocols to establish simplified in vitro assays of Schwann cell (SC) differentiation in the absence of neurons. The assays are based on the capacity of isolated primary SCs to increase or decrease the expression of myelination-associated genes in response to the presence or absence of cell permeable analogs of cyclic adenosine monophosphate (cAMP). No special conditions of media or substrates beyond the administration or removal of cAMP analogs are required to obtain a synchronous response on differentiation and dedifferentiation...
2018: Methods in Molecular Biology
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