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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27906046/chromatin-landscapes-and-genetic-risk-in-systemic-lupus
#2
Joyce S Hui-Yuen, Lisha Zhu, Lai Ping Wong, Kaiyu Jiang, Yanmin Chen, Tao Liu, James N Jarvis
BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27905473/carcinogenic-human-papillomavirus-infection
#3
Mark Schiffman, John Doorbar, Nicolas Wentzensen, Silvia de Sanjosé, Carole Fakhry, Bradley J Monk, Margaret A Stanley, Silvia Franceschi
Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways...
December 1, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27903783/uncovering-the-mechanisms-of-caenorhabditis-elegans-ageing-from-global-quantification-of-the-underlying-landscape
#4
Lei Zhao, Jin Wang
Recent studies on Caenorhabditis elegans reveal that gene manipulations can extend its lifespan several fold. However, how the genes work together to determine longevity is still an open question. Here we construct a gene regulatory network for worm ageing and quantify its underlying potential and flux landscape. We found ageing and rejuvenation states can emerge as basins of attraction at certain gene expression levels. The system state can switch from one attractor to another driven by the intrinsic or external perturbations through genetics or the environment...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/27899610/malacards-an-amalgamated-human-disease-compendium-with-diverse-clinical-and-genetic-annotation-and-structured-search
#5
Noa Rappaport, Michal Twik, Inbar Plaschkes, Ron Nudel, Tsippi Iny Stein, Jacob Levitt, Moran Gershoni, C Paul Morrey, Marilyn Safran, Doron Lancet
The MalaCards human disease database (http://www.malacards.org/) is an integrated compendium of annotated diseases mined from 68 data sources. MalaCards has a web card for each of ∼20 000 disease entries, in six global categories. It portrays a broad array of annotation topics in 15 sections, including Summaries, Symptoms, Anatomical Context, Drugs, Genetic Tests, Variations and Publications. The Aliases and Classifications section reflects an algorithm for disease name integration across often-conflicting sources, providing effective annotation consolidation...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27898704/genetic-structure-and-potential-environmental-determinants-of-local-genetic-diversity-in-japanese-honeybees-apis-cerana-japonica
#6
Teruyoshi Nagamitsu, Mika Yasuda, Fuki Saito-Morooka, Maki N Inoue, Mio Nishiyama, Koichi Goka, Shinji Sugiura, Kaoru Maeto, Kimiko Okabe, Hisatomo Taki
Declines in honeybee populations have been a recent concern. Although causes of the declines remain unclear, environmental factors may be responsible. We focused on the potential environmental determinants of local populations of wild honeybees, Apis cerana japonica, in Japan. This subspecies has little genetic variation in terms of its mitochondrial DNA sequences, and genetic variations at nuclear loci are as yet unknown. We estimated the genetic structure and environmental determinants of local genetic diversity in nuclear microsatellite genotypes of fathers and mothers, inferred from workers collected at 139 sites...
2016: PloS One
https://www.readbyqxmd.com/read/27898685/high-resolution-phenotypic-landscape-of-the-rna-polymerase-ii-trigger-loop
#7
Chenxi Qiu, Olivia C Erinne, Jui M Dave, Ping Cui, Huiyan Jin, Nandhini Muthukrishnan, Leung K Tang, Sabareesh Ganesh Babu, Kenny C Lam, Paul J Vandeventer, Ralf Strohner, Jan Van den Brulle, Sing-Hoi Sze, Craig D Kaplan
The active sites of multisubunit RNA polymerases have a "trigger loop" (TL) that multitasks in substrate selection, catalysis, and translocation. To dissect the Saccharomyces cerevisiae RNA polymerase II TL at individual-residue resolution, we quantitatively phenotyped nearly all TL single variants en masse. Three mutant classes, revealed by phenotypes linked to transcription defects or various stresses, have distinct distributions among TL residues. We find that mutations disrupting an intra-TL hydrophobic pocket, proposed to provide a mechanism for substrate-triggered TL folding through destabilization of a catalytically inactive TL state, confer phenotypes consistent with pocket disruption and increased catalysis...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27896605/personalized-medicine-in-a-new-genomic-era-ethical-and-legal-aspects
#8
Maria Shoaib, Mansoor Ali Merchant Rameez, Syed Ather Hussain, Mohammed Madadin, Ritesh G Menezes
The genome of two completely unrelated individuals is quite similar apart from minor variations called single nucleotide polymorphisms which contribute to the uniqueness of each and every person. These single nucleotide polymorphisms are of great interest clinically as they are useful in figuring out the susceptibility of certain individuals to particular diseases and for recognizing varied responses to pharmacological interventions. This gives rise to the idea of 'personalized medicine' as an exciting new therapeutic science in this genomic era...
November 28, 2016: Science and Engineering Ethics
https://www.readbyqxmd.com/read/27895058/diagnosis-and-management-of-aml-in-adults-2017-eln-recommendations-from-an-international-expert-panel
#9
Hartmut Döhner, Elihu Estey, David Grimwade, Sergio Amadori, Frederick R Appelbaum, Thomas Büchner, Hervé Dombret, Benjamin L Ebert, Pierre Fenaux, Richard A Larson, Ross L Levine, Francesco Lo-Coco, Tomoki Naoe, Dietger Niederwieser, Gert J Ossenkoppele, Miguel Sanz, Jorge Sierra, Martin S Tallman, Hwei-Fang Tien, Andrew H Wei, Bob Löwenberg, Clara D Bloomfield
The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults published in 2010 has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease, as well as in the development of novel anti-leukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations...
November 28, 2016: Blood
https://www.readbyqxmd.com/read/27891219/environmental-selection-is-a-main-driver-of-divergence-in-house-sparrows-passer-domesticus-in-romania-and-bulgaria
#10
Julia C Geue, Csongor I Vágási, Mona Schweizer, Péter L Pap, Henri A Thomassen
Both neutral and adaptive evolutionary processes can cause population divergence, but their relative contributions remain unclear. We investigated the roles of these processes in population divergence in house sparrows (Passer domesticus) from Romania and Bulgaria, regions characterized by high landscape heterogeneity compared to Western Europe. We asked whether morphological divergence, complemented with genetic data in this human commensal species, was best explained by environmental variation, geographic distance, or landscape resistance-the effort it takes for an individual to disperse from one location to the other-caused by either natural or anthropogenic barriers...
November 2016: Ecology and Evolution
https://www.readbyqxmd.com/read/27890672/epigenetics-of-cell-fate-reprogramming-and-its-implications-for-neurological-disorders-modelling
#11
REVIEW
Maciej Grzybek, Aleksandra Golonko, Marta Walczak, Pawel Lisowski
The reprogramming of human induced pluripotent stem cells (hiPSCs) proceeds in a stepwise manner with reprogramming factors binding and epigenetic composition changes during transition to maintain the epigenetic landscape, important for pluripotency. There arises a question as to whether the aberrant epigenetic state after reprogramming leads to epigenetic defects in induced stem cells causing unpredictable long term effects in differentiated cells. In this review, we present a comprehensive view of epigenetic alterations accompanying reprogramming, cell maintenance and differentiation as factors that influence applications of hiPSCs in stem cell based technologies...
November 23, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27890425/the-changing-landscape-in-radiotherapy-for-breast-cancer-lessons-from-long-term-follow-up-in-some-european-breast-cancer-trials
#12
REVIEW
Harry Bartelink
This review describes the developments in the radiation treatment of breast cancer based on some randomized European trials during the past decades. It will focus on the relevance of long term follow-up in breast cancer patients, starting with the surprising and important change in treatment results during follow-up shown in a locally advanced breast cancer trial. Breast conserving therapy (BCT) in stage I and II breast cancer was explored and tested in a randomized trial to prove equivalence between BCT and mastectomy...
November 24, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27889871/genetic-relationships-and-spatial-genetic-structure-among-populations-of-rhodnius-prolixus-hemiptera-reduviidae-in-colombia-and-venezuela-based-on-mitochondrial-cytochrome-b-sequences
#13
K P Luna-Marín, V M Angulo-Silva, J Hernández-Torres, M Ruiz-García
One hundred twenty Rhodnius prolixus (Stal) (Hemiptera: Reduviidae) specimens from 6 Colombian Departments and 1 Venezuelan State had 594-bp of the mitochondrial cytochrome-b gene sequenced to improve the understanding of evolutionary processes that shape the main vector of Chagas disease. The levels of genetic diversity for this species were low-medium with reference to other bugs. The genetic heterogeneity among the populations was very limited which means there has been extensive gene flow and/or very recent split processes...
November 26, 2016: Neotropical Entomology
https://www.readbyqxmd.com/read/27889536/compact-integration-of-multi-network-topology-for-functional-analysis-of-genes
#14
Hyunghoon Cho, Bonnie Berger, Jian Peng
The topological landscape of molecular or functional interaction networks provides a rich source of information for inferring functional patterns of genes or proteins. However, a pressing yet-unsolved challenge is how to combine multiple heterogeneous networks, each having different connectivity patterns, to achieve more accurate inference. Here, we describe the Mashup framework for scalable and robust network integration. In Mashup, the diffusion in each network is first analyzed to characterize the topological context of each node...
November 22, 2016: Cell Systems
https://www.readbyqxmd.com/read/27886423/an-approach-for-identifying-cryptic-barriers-to-gene-flow-that-limit-species-geographic-ranges
#15
Steven J Micheletti, Andrew Storfer
Species' geographic range limits are most often not demarcated by obvious dispersal barriers. Poor quality habitat at the edge of a species' range can prevent range expansion by preventing outward migration or through reducing adaptive potential resulting from decreased genetic diversity. We identified habitat variables that constrain gene flow across the entire geographic range of an endemic salamander (Ambystoma barbouri) in the eastern United States, and we tested whether increased resistance resulting from these variables provides cryptic dispersal barriers at the range edges...
November 25, 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27886331/effect-of-fragmentation-on-the-natural-genetic-diversity-of-theobroma-speciosum-willd-ex-spreng-populations
#16
T L Varella, A A B Rossi, J F E Dardengo, G F Silveira, M D A Souza, M L S Carvalho
Forest fragmentation reduces the effective size of natural populations, isolates individuals in the landscape, and, consequently, changes species' mating systems by increasing the degree of relatedness between individuals and inbreeding. Investigating the impact of habitat degradation on forest fragments helps to assess the genetic and ecological consequences of these changes, and allows the development of effective and sustainable conservation strategies to manage the genetic resources of species living in degraded landscapes...
November 21, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27883087/inter-annual-maintenance-of-the-fine-scale-genetic-structure-in-a-biennial-plant
#17
Javier Valverde, José María Gómez, Cristina García, Timothy F Sharbel, María Noelia Jiménez, Francisco Perfectti
Within plant populations, space-restricted gene movement, together with environmental heterogeneity, can result in a spatial variation in gene frequencies. In biennial plants, inter-annual flowering migrants can homogenize gene frequencies between consecutive cohorts. However, the actual impact of these migrants on spatial genetic variation remains unexplored. Here, we used 10 nuclear microsatellite and one plastid genetic marker to characterize the spatial genetic structure within two consecutive cohorts in a population of the biennial plant Erysimum mediohispanicum (Brassicaceae)...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881744/directional-selection-effects-on-patterns-of-phenotypic-co-variation-in-wild-populations
#18
A P A Assis, J L Patton, A Hubbe, G Marroig
Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory...
November 30, 2016: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/27881664/lipid-disequilibrium-disrupts-er-proteostasis-by-impairing-erad-substrate-glycan-trimming-and-dislocation
#19
Milton To, Clark W H Peterson, Melissa A Roberts, Jessica L Counihan, Tiffany T Wu, Mercedes S Forster, Daniel K Nomura, James A Olzmann
The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analog, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27881471/selection-limits-to-adaptive-walks-on-correlated-landscapes
#20
Jorge Pérez Heredia, Barbora Trubenová, Dirk Sudholt, Tiago Paixão
Adaptation depends critically on the effects of new mutations and their dependency on the genetic background they occur in. These two factors can be summarized by the fitness landscape. However, it would require testing all mutations in all backgrounds, making the definition and analysis of fitness landscapes mostly inaccessible. Instead of postulating a particular fitness landscape, we address this problem by considering general classes of landscapes and calculating an upper limit for the time it takes for a population to reach a fitness peak, circumventing the need to have full knowledge about the fitness landscape...
November 23, 2016: Genetics
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