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Early gene

Yan Zhou, Jialei Zhu, Yang Lv, Chenghuan Song, Jianhua Ding, Ming Xiao, Ming Lu, Gang Hu
The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major feature in the pathology of Parkinson's disease (PD). Using neural stem or progenitor cells (NSC/NPCs), the prospect of replacing the missing or damaged DA neurons is very attractive for PD therapy. However, little is known about the endogenous mechanisms and molecular pathways regulating the NSC/NPC proliferation and differentiation in the development of PD. Herein, using Kir6.2 knockout (Kir6.2-/- ) mice, we observed that genetic deficiency of Kir6...
March 21, 2018: Molecular Neurobiology
Karina Jácome-López, Mayra Furlan-Magaril
The spatial organization of the chromatinized genome inside the cell nucleus impacts genomic function. In transcription, the hierarchical genome structure creates spatial regulatory landscapes, in which modulating elements like enhancers can contact their target genes and activate their expression, as a result of restricting their exploration to a specific topological neighbourhood. Here we describe exciting recent findings obtained through "C" technologies in pluripotent cells and early embryogenesis and emphasize some of the key unanswered questions arising from them...
2018: Methods in Molecular Biology
Estela G García-González, Bladimir Roque-Ramirez, Carlos Palma-Flores, J Manuel Hernández-Hernández
Epigenetic regulation is achieved at many levels by different factors such as tissue-specific transcription factors, members of the basal transcriptional apparatus, chromatin-binding proteins, and noncoding RNAs. Importantly, chromatin structure dictates the availability of a specific genomic locus for transcriptional activation as well as the efficiency with which transcription can occur. Chromatin immunoprecipitation (ChIP) is a method that allows elucidating gene regulation at the molecular level by assessing if chromatin modifications or proteins are present at a specific locus...
2018: Methods in Molecular Biology
Andrew L Lopez, Irina V Larina
The heart is a dynamic organ that quickly undergoes morphological and mechanical changes through early embryonic development. Characterizing these early moments is important for our understanding of proper embryonic development and the treatment of heart disease. Traditionally, tomographic imaging modalities and fluorescence-based microscopy are excellent approaches to visualize structural features and gene expression patterns, respectively, and connect aberrant gene programs to pathological phenotypes. However, these approaches usually require static samples or fluorescent markers, which can limit how much information we can derive from the dynamic and mechanical changes that regulate heart development...
2018: Methods in Molecular Biology
Giulia F Del Gobbo, E Magda Price, Courtney W Hanna, Wendy P Robinson
Background: 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon metabolism that ensures the availability of methyl groups for methylation reactions. Two single-nucleotide polymorphisms (SNPs) in the MTHFR gene, 677C>T and 1298A>C, result in a thermolabile enzyme with reduced function. These variants, in both the maternal and/or fetal genes, have been associated with pregnancy complications including miscarriage, neural tube defects (NTDs), and preeclampsia (PE), perhaps due to altered capacity for DNA methylation (DNAm)...
2018: Clinical Epigenetics
Maria K Paulmann, Grit Kunert, Matthias R Zimmermann, Nina Theis, Anatoli Ludwig, Doreen Meichsner, Ralf Oelmüller, Jonathan Gershenzon, Antje Habekuss, Frank Ordon, Alexandra C U Furch, Torsten Will
Barley yellow dwarf virus (BYDV) is a phloem limited virus that is persistently transmitted by aphids. Due to huge yield losses in agriculture, the virus is of high economic relevance. Since the control of the virus itself is not possible, tolerant barley genotypes are considered as the most effective approach to avoid yield losses. Although several genes and quantitative trait loci are known and used in barley breeding for virus tolerance, little is known about molecular and physiological backgrounds of this trait...
2018: Frontiers in Plant Science
Johan Tolö, Grit Taschenberger, Kristian Leite, Markus A Stahlberg, Gesche Spehlbrink, Janina Kues, Francesca Munari, Stefano Capaldi, Stefan Becker, Markus Zweckstetter, Camin Dean, Mathias Bähr, Sebastian Kügler
α-Synuclein (α-Syn) is intimately linked to the etiology of Parkinson's Disease, as mutations and even subtle increases in gene dosage result in early onset of the disease. However, how this protein causes neuronal dysfunction and neurodegeneration is incompletely understood. We thus examined a comprehensive range of physiological parameters in cultured rat primary neurons overexpressing α-Syn at levels causing a slowly progressive neurodegeneration. In contradiction to earlier reports from non-neuronal assay systems we demonstrate that α-Syn does not interfere with essential ion handling capacities, mitochondrial capability of ATP production or basic electro-physiological properties like resting membrane potential or the general ability to generate action potentials...
2018: Frontiers in Molecular Neuroscience
Yi-Fan Tong, Ning Meng, Miao-Qin Chen, Han-Ning Ying, Ming Xu, Billy Lu, Jun-Jie Hong, Yi-Fan Wang, Xiu-Jun Cai
AIM: To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). METHODS: In the present study, ALPPS, partial hepatecotmy (PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified...
March 14, 2018: World Journal of Gastroenterology: WJG
Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, James S Blachly, Christopher J Walker, Deedra Nicolet, Shelley Orwick, Sophia E Maharry, Andrew J Carroll, Richard M Stone, Albert de la Chapelle, Eunice S Wang, Jonathan E Kolitz, Bayard L Powell, John C Byrd, Clara D Bloomfield
Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Yuxuan Wang, Lu Li, Christopher Douville, Joshua D Cohen, Ting-Tai Yen, Isaac Kinde, Karin Sundfelt, Susanne K Kjær, Ralph H Hruban, Ie-Ming Shih, Tian-Li Wang, Robert J Kurman, Simeon Springer, Janine Ptak, Maria Popoli, Joy Schaefer, Natalie Silliman, Lisa Dobbyn, Edward J Tanner, Ana Angarita, Maria Lycke, Kirsten Jochumsen, Bahman Afsari, Ludmila Danilova, Douglas A Levine, Kris Jardon, Xing Zeng, Jocelyne Arseneau, Lili Fu, Luis A Diaz, Rachel Karchin, Cristian Tomasetti, Kenneth W Kinzler, Bert Vogelstein, Amanda N Fader, Lucy Gilbert, Nickolas Papadopoulos
We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease...
March 21, 2018: Science Translational Medicine
Yuxia Gao, Wenqiang Wang, Tian Zhang, Zhen Gong, Huayao Zhao, Guan-Zhu Han
During plant-pathogen interactions, plants use intracellular proteins with nucleotide-binding site and leucine-rich repeat (NBS-LRR) domains to detect pathogens. NBS-LRR proteins represent a major class of plant disease resistance genes (R-genes). Whereas R-genes have been well characterized in angiosperms, little is known about their origin and early diversification. Here we perform comprehensive evolutionary analyses of R-genes in plants and report the identification of R-genes in basal-branching streptophytes, including charophytes, liverworts, and mosses...
March 21, 2018: Plant Physiology
Huachun Cui, Sami Banerjee, Sijia Guo, Na Xie, Gang Liu
Rapid initiation and timely resolution of inflammatory response in macrophages are synergistic events that are known to be equally critical to optimal host defense against pathogen infections. However, the regulation of these processes, in particular by a specific cellular metabolic program, has not been well understood. In this study, we found that IFN regulatory factor 2 (IRF2) underwent an early degradation in a proteasome-mediated pathway in LPS-treated mouse macrophages, followed by a later recovery of the expression via transactivation...
March 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiaogai Hou, Qi Guo, Weiqiang Wei, Lili Guo, Dalong Guo, Lin Zhang
Tree peony ( Paeonia suffruticosa Andrews) is a perennial woody shrub bearing large and colorful flowers. However, the flowering period is short and relatively uniform, which to an important extent hinders the cultivation and exploitation of ornamental peonies. In this study, the segregation of an F₁ population derived from P. ostti 'Feng Dan' (an early-flowering cultivar) × P. suffruticosa 'Xin Riyuejin' (a late-flowering cultivar) was used to screen and analyze candidate genes associated with flowering period of the two parents...
March 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xue Cao, Qiuqiong Tang, Tim Holland-Letz, Melanie Gündert, Katarina Cuk, Sarah Schott, Jörg Heil, Michael Golatta, Christof Sohn, Andreas Schneeweiss, Barbara Burwinkel
Breast cancer (BC) is the most common cancer among women and has high mortality rates. Early detection is supposed to be critical for the patient's prognosis. In recent years, several studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop putative screening markers for cancer. However, most of the studies have not yet been validated. In our study, we analyzed the promoter methylation of RASSF1A and ATM in peripheral blood DNA of 229 sporadic patients and 151 healthy controls by the MassARRAY EpiTYPER assay...
March 19, 2018: International Journal of Molecular Sciences
Eveline Hoebe, Coral Wille, Stacy Hagemeier, Shannon Kenney, Astrid Greijer, Jaap Middeldorp
Epstein-Barr Virus (EBV) BamHI-A rightward frame 1 (BARF1) protein is considered a viral oncogene in epithelial cells and has immune-modulating properties. During viral lytic replication BARF1 is expressed as an early gene, regulated by the immediate early EBV protein R. However, in viral latency BARF1 is exclusively expressed in epithelial tumors such as nasopharyngeal (NPC) and gastric carcinoma (GC) but not in lymphomas, indicating that activation of the BARF1 promoter is cell type specific. Undifferentiated NPC is characterized by high expression of ΔNp63 isoforms of the epithelial differentiation marker p63, a member of the p53 family of transcription factors...
March 17, 2018: Cancers
Patrizia Mecocci, Marta Baroni, Umberto Senin, Virginia Boccardi
Alzheimer's disease (AD) represents the most common form of dementia in old age subjects, and despite decades of studies, the underlying etiopathogenetic mechanisms remain unsolved. The definition of AD has changed over the past years, offering an ever more detailed definition of pre-morbid and pre-clinical status, but without a similar strong emphasis on the role of aging as the main risk factor. In fact, while early-onset AD is a clear consequence of gene mutations, late-onset AD is more likely due to a gradual accumulation of age-related damages...
March 16, 2018: Journal of Alzheimer's Disease: JAD
Grażyna Janikowska, Tomasz Janikowski, Alina Pyka-Paj K, Urszula Mazurek, Marcin Janikowski, Maciej Gonciarz, Zbigniew Lorenc
BACKGROUNDS: Colorectal cancer is the third most common cancer in economically developed countries. Molecular studies and, in particular, gene expression have contributed to advances in the diagnosis and treatment of many cancers. Genes can be molecular and therapeutic markers, but because of the large molecular diversity in colorectal cancer the knowledge is not yet fully established. Probably one of the most crucial processes during early cancer development is inflammation. The inflammatory response in the tumor is an important indicator of molecular etiology and later of cancer progression...
March 2, 2018: Cancer Biomarkers: Section A of Disease Markers
Xiaolei Zhang, Michelle B Trevino, Miao Wang, Stephen J Gardell, Julio E Ayala, Xianlin Han, Daniel P Kelly, Bret H Goodpaster, Rick B Vega, Paul M Coen
The progression of age-related sarcopenia can be accelerated by impaired recovery of muscle mass following periods of disuse due to illness or immobilization. However, the mechanisms underlying poor recovery of aged muscle following disuse remain to be delineated. Recent evidence suggests that mitochondrial energetics play an important role in regulation of muscle mass. Here, we report that 22-24 month old mice with low muscle mass and low glucose clearance rate also display poor early recovery of muscle mass following 10 days of hind limb unloading...
March 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Wei Zhang, Guihai Feng, Libin Wang, Fei Teng, Liu Wang, Wei Li, Ying Zhang, Qi Zhou
The generation of induced pluripotent stem cells (iPSCs) offers a great opportunity in research and regenerative medicine. The current poor efficiency and incomplete mechanistic understanding of the reprogramming process hampers the clinical application of iPSCs. MeCP2 connects histone modification and DNA methylation, which are key changes of somatic cell reprogramming. However, the role of MeCP2 in cell reprogramming has not been examined. In this study, we found that MeCP2 deficiency enhanced reprogramming efficiency and stimulated cell proliferation through regulating cell cycle protein expression in the early stage of reprogramming...
March 19, 2018: Journal of Molecular Cell Biology
Mateja Hajdinjak, Qiaomei Fu, Alexander Hübner, Martin Petr, Fabrizio Mafessoni, Steffi Grote, Pontus Skoglund, Vagheesh Narasimham, Hélène Rougier, Isabelle Crevecoeur, Patrick Semal, Marie Soressi, Sahra Talamo, Jean-Jacques Hublin, Ivan Gušić, Željko Kućan, Pavao Rudan, Liubov V Golovanova, Vladimir B Doronichev, Cosimo Posth, Johannes Krause, Petra Korlević, Sarah Nagel, Birgit Nickel, Montgomery Slatkin, Nick Patterson, David Reich, Kay Prüfer, Matthias Meyer, Svante Pääbo, Janet Kelso
Although it has previously been shown that Neanderthals contributed DNA to modern humans, not much is known about the genetic diversity of Neanderthals or the relationship between late Neanderthal populations at the time at which their last interactions with early modern humans occurred and before they eventually disappeared. Our ability to retrieve DNA from a larger number of Neanderthal individuals has been limited by poor preservation of endogenous DNA and contamination of Neanderthal skeletal remains by large amounts of microbial and present-day human DNA...
March 21, 2018: Nature
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