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https://www.readbyqxmd.com/read/28339911/a-null-variant-in-the-apolipoprotein-l3-gene-is-associated-with-non-diabetic-nephropathy
#1
Karl L Skorecki, Jessica H Lee, Carl D Langefeld, Saharon Rosset, Shay Tzur, Walter G Wasser, Revital Shemer, Gregory A Hawkins, Jasmin Divers, Rulan S Parekh, Man Li, Matthew G Sampson, Matthias Kretzler, Martin R Pollak, Shrijal Shah, Daniel Blackler, Brendan Nichols, Michael Wilmot, Seth L Alper, Barry I Freedman, David J Friedman
Background.: Inheritance of apolipoprotein L1 gene ( APOL1 ) renal-risk variants in a recessive pattern strongly associates with non-diabetic end-stage kidney disease (ESKD). Further evidence supports risk modifiers in APOL1 -associated nephropathy; some studies demonstrate that heterozygotes possess excess risk for ESKD or show earlier age at ESKD, relative to those with zero risk alleles. Nearby loci are also associated with ESKD in non-African Americans. Methods.: We assessed the role of the APOL3 null allele rs11089781 on risk of non-diabetic ESKD...
February 20, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28335551/molecular-basis-for-modulation-of-metabotropic-glutamate-receptors-and-their-drug-actions-by-extracellular-ca-2
#2
REVIEW
Juan Zou, Jason Y Jiang, Jenny J Yang
Metabotropic glutamate receptors (mGluRs) associated with the slow phase of the glutamatergic signaling pathway in neurons of the central nervous system have gained importance as drug targets for chronic neurodegenerative diseases. While extracellular Ca(2+) was reported to exhibit direct activation and modulation via an allosteric site, the identification of those binding sites was challenged by weak binding. Herein, we review the discovery of extracellular Ca(2+) in regulation of mGluRs, summarize the recent developments in probing Ca(2+) binding and its co-regulation of the receptor based on structural and biochemical analysis, and discuss the molecular basis for Ca(2+) to regulate various classes of drug action as well as its importance as an allosteric modulator in mGluRs...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335496/quantitative-analysis-of-the-kshv-transcriptome-following-primary-infection-of-blood-and-lymphatic-endothelial-cells
#3
A Gregory Bruce, Serge Barcy, Terri DiMaio, Emilia Gan, H Jacques Garrigues, Michael Lagunoff, Timothy M Rose
The transcriptome of the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) after primary latent infection of human blood (BEC), lymphatic (LEC) and immortalized (TIME) endothelial cells was analyzed using RNAseq, and compared to long-term latency in BCBL-1 lymphoma cells. Naturally expressed transcripts were obtained without artificial induction, and a comprehensive annotation of the KSHV genome was determined. A set of unique coding sequence (UCDS) features and a process to resolve overlapping transcripts were developed to accurately quantitate transcript levels from specific promoters...
March 19, 2017: Pathogens
https://www.readbyqxmd.com/read/28334947/protocadherin-19-pcdh19-interacts-with-paraspeckle-protein-nono-to-co-regulate-gene-expression-with-estrogen-receptor-alpha-er%C3%AE
#4
Duyen H Pham, Chuan Tan, Claire C Homan, Kristy Kolc, Mark Corbett, Dale McAninch, Archa Fox, Paul Thomas, Raman Kumar, Jozef Gecz
De novo and inherited mutations of X-chromosome cell adhesion molecule protocadherin 19 (PCDH19) cause frequent, highly variable epilepsy, autism, cognitive decline and behavioural problems syndrome. Intriguingly, hemizygous null males are not affected while heterozygous females are, contradicting established X-chromosome inheritance. The disease mechanism is not known. Cellular mosaicism is the likely driver. We have identified p54nrb/NONO, a multifunctional nuclear paraspeckle protein with known roles in nuclear hormone receptor gene regulation, as a PCDH19 protein interacting partner...
March 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333931/differential-gene-expression-in-patients-with-subsyndromal-symptomatic-depression-and-major-depressive-disorder
#5
Chengqing Yang, Guoqin Hu, Zezhi Li, Qingzhong Wang, Xuemei Wang, Chengmei Yuan, Zuowei Wang, Wu Hong, Weihong Lu, Lan Cao, Jun Chen, Yong Wang, Shunying Yu, Yimin Zhou, Zhenghui Yi, Yiru Fang
BACKGROUND: Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures...
2017: PloS One
https://www.readbyqxmd.com/read/28324900/infant-guided-co-regulated-feeding-in-the-neonatal-intensive-care-unit-part-ii-interventions-to-promote-neuroprotection-and-safety
#6
Catherine S Shaker
Feeding skills of preterm neonates in a neonatal intensive care unit are in an emergent phase of development and require careful support to minimize stress. The underpinnings that influence and enhance both neuroprotection and safety were discussed in Part I. An infant-guided, co-regulated approach to feeding can protect the vulnerable neonate's neurologic development, support the parent-infant relationship, and prevent feeding problems that may endure. Contingent interventions are used to maintain subsystem stability and enhance self-regulation, development, and coping skills...
April 2017: Seminars in Speech and Language
https://www.readbyqxmd.com/read/28324899/infant-guided-co-regulated-feeding-in-the-neonatal-intensive-care-unit-part-i-theoretical-underpinnings-for-neuroprotection-and-safety
#7
Catherine S Shaker
The rapid progress in medical and technical innovations in the neonatal intensive care unit (NICU) has been accompanied by concern for outcomes of NICU graduates. Although advances in neonatal care have led to significant changes in survival rates of very small and extremely preterm neonates, early feeding difficulties with the transition from tube feeding to oral feeding are prominent and often persist beyond discharge to home. Progress in learning to feed in the NICU and continued growth in feeding skills after the NICU may be closely tied to fostering neuroprotection and safety...
April 2017: Seminars in Speech and Language
https://www.readbyqxmd.com/read/28316142/evolutionary-ecology-of-beta-lactam-gene-clusters-in-animals
#8
Wouter Suring, Karen Meusemann, Alexander Blanke, Janine Mariën, Tim Schol, Valeria Agamennone, Anna Faddeeva-Vakhrusheva, Matty P Berg, Bram Brouwer, Nico M van Straalen, Dick Roelofs
Beta-lactam biosynthesis was thought to occur only in fungi and bacteria, but we recently reported the presence of isopenicillin N synthase in a soil-dwelling animal, Folsomia candida. However, it has remained unclear whether this gene is part of a larger beta-lactam biosynthesis pathway and how widespread the occurrence of penicillin biosynthesis is among animals. Here, we analyzed the distribution of beta-lactam biosynthesis genes throughout the animal kingdom and identified a beta-lactam gene cluster in the genome of F...
March 18, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28303318/bone-alkaline-phosphatase-and-tartrate-resistant-acid-phosphatase-potential-co-regulators-of-bone-mineralization
#9
Cecilia Halling Linder, Barbro Ek-Rylander, Michael Krumpel, Maria Norgård, Sonoko Narisawa, José Luis Millán, Göran Andersson, Per Magnusson
Phosphorylated osteopontin (OPN) inhibits hydroxyapatite crystal formation and growth, and bone alkaline phosphatase (BALP) promotes extracellular mineralization via the release of inorganic phosphate from the mineralization inhibitor inorganic pyrophosphate (PPi). Tartrate-resistant acid phosphatase (TRAP), produced by osteoclasts, osteoblasts, and osteocytes, exhibits potent phosphatase activity towards OPN; however, its potential capacity as a regulator of mineralization has not previously been addressed...
March 16, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28300292/hdac1-and-hdac3-underlie-dynamic-h3k9-acetylation-during-embryonic-neurogenesis-and-in-schizophrenia-like-animals
#10
Josef Večeřa, Eva Bártová, Jana Krejčí, Soňa Legartová, Denisa Komůrková, Jana Rudá-Kučerová, Tibor Štark, Eva Dražanová, Tomáš Kašpárek, Alexandra Šulcová, Frank J Dekker, Wiktor Szymanski, Christian Seiser, Georg Weitzer, Raphael Mechoulam, Vincenzo Micale, Stanislav Kozubek
Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes...
March 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28298358/identification-of-%C3%AE-catenin-interacting-proteins-in-nuclear-fractions-of-native-rat-collecting-duct-cells
#11
Jacqueline R Hwang, Chung-Lin Chou, Barbara Medvar, Mark A Knepper, Hyun Jun Jung
The gene encoding the aquaporin-2 water channel is regulated transcriptionally in response to vasopressin. In the renal collecting duct, vasopressin stimulates the nuclear translocation and phosphorylation (at Ser552) of β-catenin, a multifunctional protein that acts as a transcriptional co-regulator in the nucleus. The purpose of this study was to identify β-catenin interacting proteins that may be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells using both experimental and computational approaches...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28289476/dna-methylation-at-modifier-genes-of-lung-disease-severity-is-altered-in-cystic-fibrosis
#12
Milena Magalhães, Isabelle Rivals, Mireille Claustres, Jessica Varilh, Mélodie Thomasset, Anne Bergougnoux, Laurent Mely, Sylvie Leroy, Harriet Corvol, Loïc Guillot, Marlène Murris, Emmanuelle Beyne, Davide Caimmi, Isabelle Vachier, Raphaël Chiron, Albertina De Sario
BACKGROUND: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28286748/the-importance-of-rest-for-development-and-function-of-beta-cells
#13
REVIEW
David Martin, Anne Grapin-Botton
Beta cells are defined by the genes they express, many of which are specific to this cell type, and ensure a specific set of functions. Beta cells are also defined by a set of genes they should not express (in order to function properly), and these genes have been called forbidden genes. Among these, the transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. In the cell types where it is expressed, REST represses the expression of hundreds of genes that are crucial for both neuronal and pancreatic endocrine function, through the recruitment of multiple transcriptional and epigenetic co-regulators...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28285767/large-scale-trans-eqtls-affect-hundreds-of-transcripts-and-mediate-patterns-of-transcriptional-co-regulation
#14
Boel Brynedal, JinMyung Choi, Towfique Raj, Robert Bjornson, Barbara E Stranger, Benjamin M Neale, Benjamin F Voight, Chris Cotsapas
Efforts to decipher the causal relationships between differences in gene regulation and corresponding differences in phenotype have been stymied by several basic technical challenges. Although detecting local, cis-eQTLs is now routine, trans-eQTLs, which are distant from the genes of origin, are far more difficult to find because millions of SNPs must currently be compared to thousands of transcripts. Here, we demonstrate an alternative approach: we looked for SNPs associated with the expression of many genes simultaneously and found that hundreds of trans-eQTLs each affect hundreds of transcripts in lymphoblastoid cell lines across three African populations...
March 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28282643/nab2-maintains-thymus-cellularity-with-aging-and-stress
#15
K Taraszka Hastings, Diana Elizalde, Leela Muppana, Sarah Levine, Christy M Kamel, Wendy M Ingram, Jennifer T Kirkpatrick, Chengcheng Hu, Matthew P Rausch, Amelia L Gallitano
Thymic cellularity is influenced by a variety of biological and environmental factors, such as age and stress; however, little is known about the molecular genetic mechanisms that regulate this process. Immediate early genes of the Early growth response (Egr) family have critical roles in immune function and response to environmental stress. The transcription factors, Egr1, Egr2 and Egr3, play roles in the thymus and in peripheral T-cell activation. Nab2, which binds Egrs 1, 2, and 3 as a co-regulator of transcription, also regulates peripheral T-cell activation...
March 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28282383/shared-regulatory-sites-are-abundant-in-the-human-genome-and-shed-light-on-genome-evolution-and-disease-pleiotropy
#16
Pin Tong, Jack Monahan, James G D Prendergast
Large-scale gene expression datasets are providing an increasing understanding of the location of cis-eQTLs in the human genome and their role in disease. However, little is currently known regarding the extent of regulatory site-sharing between genes. This is despite it having potentially wide-ranging implications, from the determination of the way in which genetic variants may shape multiple phenotypes to the understanding of the evolution of human gene order. By first identifying the location of non-redundant cis-eQTLs, we show that regulatory site-sharing is a relatively common phenomenon in the human genome, with over 10% of non-redundant regulatory variants linked to the expression of multiple nearby genes...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28277935/the-pre-mrna-retention-and-splicing-complex-controls-expression-of-the-mediator-subunit-med20
#17
Yang Zhou, Marcus J O Johansson
The heterotrimeric pre-mRNA retention and splicing (RES) complex, consisting of Bud13p, Snu17p and Pml1p, promotes splicing and nuclear retention of a subset of intron-containing pre-mRNAs. Yeast cells deleted for individual RES genes show growth defects that are exacerbated at elevated temperatures. Although the growth phenotypes correlate to the splicing defects in the individual mutants, the underlying mechanism is unknown. Here, we show that the temperature sensitive (Ts) growth phenotype of bud13Δ and snu17Δ cells is a consequence of inefficient splicing of MED20 pre-mRNA, which codes for a subunit of the Mediator complex; a co-regulator of RNA polymerase II transcription...
February 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28273483/ceramide-is-metabolized-to-acylceramide-and-stored-in-lipid-droplets
#18
Can E Senkal, Mohamed F Salama, Ashley J Snider, Janet J Allopenna, Nadia A Rana, Antonius Koller, Yusuf A Hannun, Lina M Obeid
In an approach aimed at defining interacting partners of ceramide synthases (CerSs), we found that fatty acyl-CoA synthase ACSL5 interacts with all CerSs. We demonstrate that ACSL5-generated FA-CoA was utilized with de novo ceramide for the generation of acylceramides, poorly studied ceramide metabolites. Functionally, inhibition of ceramide channeling to acylceramide enhanced accumulation of de novo ceramide and resulted in augmentation of ceramide-mediated apoptosis. Mechanistically, we show that acylceramide generation is catalyzed by diacylglycerol acyltransferase 2 (DGAT2) on lipid droplets...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28273452/enhancer-mediated-oncogenic-function-of-the-menin-tumor-suppressor-in-breast-cancer
#19
Koen M A Dreijerink, Anna C Groner, Erica S M Vos, Alba Font-Tello, Lei Gu, David Chi, Jaime Reyes, Jennifer Cook, Elgene Lim, Charles Y Lin, Wouter de Laat, Prakash K Rao, Henry W Long, Myles Brown
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER(+) cells...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28272414/defined-chromosome-structure-in-the-genome-reduced-bacterium-mycoplasma-pneumoniae
#20
Marie Trussart, Eva Yus, Sira Martinez, Davide Baù, Yuhei O Tahara, Thomas Pengo, Michael Widjaja, Simon Kretschmer, Jim Swoger, Steven Djordjevic, Lynne Turnbull, Cynthia Whitchurch, Makoto Miyata, Marc A Marti-Renom, Maria Lluch-Senar, Luís Serrano
DNA-binding proteins are central regulators of chromosome organization; however, in genome-reduced bacteria their diversity is largely diminished. Whether the chromosomes of such bacteria adopt defined three-dimensional structures remains unexplored. Here we combine Hi-C and super-resolution microscopy to determine the structure of the Mycoplasma pneumoniae chromosome at a 10 kb resolution. We find a defined structure, with a global symmetry between two arms that connect opposite poles, one bearing the chromosomal Ori and the other the midpoint...
March 8, 2017: Nature Communications
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