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https://www.readbyqxmd.com/read/28815464/inherited-nonsyndromic-ichthyoses-an-update-on-pathophysiology-diagnosis-and-treatment
#1
REVIEW
Anders Vahlquist, Judith Fischer, Hans Törmä
Hereditary ichthyoses are due to mutations on one or both alleles of more than 30 different genes, mainly expressed in the upper epidermis. Syndromic as well as nonsyndromic forms of ichthyosis exist. Irrespective of etiology, virtually all types of ichthyosis exhibit a defective epidermal barrier that constitutes the driving force for hyperkeratosis, skin scaling, and inflammation. In nonsyndromic forms, these features are most evident in severe autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis, but to some extent also occur in the common type of non-congenital ichthyosis...
August 16, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28797108/natural-disease-history-of-mouse-models-for-limb-girdle-muscular-dystrophy-types-2d-and-2f
#2
S Pasteuning-Vuhman, K Putker, C L Tanganyika-de Winter, J W Boertje-van der Meulen, L van Vliet, M Overzier, J J Plomp, A Aartsma-Rus, M van Putten
Limb-girdle muscular dystrophy types 2D and 2F (LGMD 2D and 2F) are autosomal recessive disorders caused by mutations in the alpha- and delta sarcoglycan genes, respectively, leading to severe muscle weakness and degeneration. The cause of the disease has been well characterized and a number of animal models are available for pre-clinical studies to test potential therapeutic interventions. To facilitate transition from drug discovery to clinical trials, standardized procedures and natural disease history data were collected for these mouse models...
2017: PloS One
https://www.readbyqxmd.com/read/28793217/mutation-in-the-core-structure-of-desmin-intermediate-filaments-affects-myoblast-elasticity
#3
Catherine Even, Gilles Abramovici, Florence Delort, Anna F Rigato, Virginie Bailleux, Abel de Sousa Moreira, Patrick Vicart, Felix Rico, Sabrina Batonnet-Pichon, Fatma Briki
Elastic properties of cells are mainly derived from the actin cytoskeleton. However, intermediate filaments are emerging as major contributors to the mechanical properties of cells. Using atomic force microscopy, we studied the elasticity of mouse myoblasts expressing a mutant form of the gene encoding for desmin intermediate filaments, p.D399Y. This variant produces desmin aggregates, the main pathological symptom of myofibrillar myopathies. Here we show that desmin-mutated cells display a 39% increased median elastic modulus compared to wild-type cells...
August 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28790313/evolution-of-new-regulatory-functions-on-biophysically-realistic-fitness-landscapes
#4
Tamar Friedlander, Roshan Prizak, Nicholas H Barton, Gašper Tkačik
Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge...
August 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28779874/brief-report-met-exon-14-alterations-and-new-resistance-mutations-to-tyrosine-kinase-inhibitors-risk-of-inadequate-detection-with-current-amplicon-based-ngs-panels
#5
Brigitte Poirot, Ludovic Doucet, Shirine Benhenda, Jérôme Champ, Véronique Meignin, Jacqueline Lehmann-Che
INTRODUCTION: Targeted therapies, as tyrosine kinase inhibitors (TKI), have dramatically improved the treatment of lung adenocarcinoma and detection of activating mutations of genes like EGFR or ALK is now mandatory in clinical setting. However, additional targetable alterations are continuously described and force us to adapt our detection methods. We evaluate here the ability of 8 amplicon-based next generation sequencing (NGS) panels to detect the recently described MET exon 14 alterations or new resistance-mutations to TKI...
August 2, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28747543/mutation-profile-based-methods-for-understanding-selection-forces-in-cancer-somatic-mutations-a-comparative-analysis
#6
Zhan Zhou, Yangyun Zou, Gangbiao Liu, Jingqi Zhou, Jingcheng Wu, Shimin Zhao, Zhixi Su, Xun Gu
Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes (CN/CS) and normal populations (pN/pS). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743260/molecular-evolution-of-two-asymptomatic-echovirus-6-strains-that-constitute-a-novel-branch-of-recently-epidemic-echovirus-6-in-china
#7
Hao Sun, Xiaoqin Huang, Keqin Lin, Kai Huang, Jiayou Chu, Zhaoqing Yang, Shaohui Ma
BACKGROUND: Echovirus 6 (E6) infections are associated with aseptic meningitis and acute flaccid paralysis (AFP). But some infections, sometimes most of them, are asymptomatic. The mechanism of E6 virulence is unknown. Analyses of the molecular evolution of asymptomatic E6 may help understand why the infections show different manifestations. METHODS: Ninety-six stool samples of healthy children in Yunnan, China were collected and two E6 strains were isolated from them...
July 25, 2017: Virology Journal
https://www.readbyqxmd.com/read/28742865/a-novel-mitochondrial-genome-of-arborophila-and-new-insight-into-arborophila-evolutionary-history
#8
Chaochao Yan, Biqin Mou, Yang Meng, Feiyun Tu, Zhenxin Fan, Megan Price, Bisong Yue, Xiuyue Zhang
The lineage of the Bar-backed Partridge (Arborophila brunneopectus) was investigated to determine the phylogenetic relationships within Arborophila as the species is centrally distributed within an area covered by the distributions of 22 South-east Asian hill partridge species. The complete mitochondrial genome (mitogenome) of A. brunneopectus was determined and compared with four other hill partridge species mitogenomes. NADH subunit genes are radical in hill partridge mitogenomes and contain the most potential positive selective sites around where variable sites are abundant...
2017: PloS One
https://www.readbyqxmd.com/read/28733602/distinct-selective-forces-and-neanderthal-introgression-shaped-genetic-diversity-at-genes-involved-in-neurodevelopmental-disorders
#9
Alessandra Mozzi, Diego Forni, Rachele Cagliani, Uberto Pozzoli, Mario Clerici, Manuela Sironi
In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728823/piezo1-channels-in-vascular-development-and-the-sensing-of-shear-stress
#10
A J Hyman, S Tumova, D J Beech
A critical point in mammalian development occurs before mid-embryogenesis when the heart starts to beat, pushing blood into the nascent endothelial lattice. This pushing force is a signal, detected by endothelial cells as a frictional force (shear stress) to trigger cellular changes that underlie the essential processes of vascular remodeling and expansion required for embryonic growth. The processes are complex and multifactorial and Piezo1 became a recognized player only 2years ago, 4years after Piezo1's initial discovery as a functional membrane protein...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28720700/hitchhiking-and-epistasis-give-rise-to-cohort-dynamics-in-adapting-populations
#11
Sean W Buskirk, Ryan Emily Peace, Gregory I Lang
Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28714588/cellular-force-assay-detects-altered-contractility-caused-by-a-nephritis-associated-mutation-in-nonmuscle-myosin-iia
#12
Shota P Fukuda, Tsubasa S Matsui, Takafumi Ichikawa, Taichi Furukawa, Noriyuki Kioka, Shuichiro Fukushima, Shinji Deguchi
Recent progress in understanding the essential roles of mechanical forces in regulating various cellular processes expands the field of biology to one where interdisciplinary approaches with engineering techniques become indispensable. Contractile forces or contractility-inherently present in proliferative cells due to the activity of ubiquitous nonmuscle myosin II (NMII)-are one of such mechano-regulators, but because NMII works downstream of diverse signaling pathways, it is often difficult to predict how the inherent cellular forces change upon perturbations to particular molecules...
July 17, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28701314/cux1-promotes-cell-proliferation-and-polycystic-kidney-disease-progression-in-an-adpkd-mouse-model
#13
Binu Porath, Safia Livingston, Erica L Andres, Alexandra M Petrie, Joshua C Wright, Anna E Woo, Carol G Carlton, Richard Baybutt, Gregory B Vanden Heuvel
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common monogenic hereditary disorders in humans characterized by fluid-filled cysts, primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant mice, and in human ADPKD cells. However, forced expression of Cux1 is insufficient to induce cystic disease in transgenic mice, or to induce rapid cyst formation after cilia disruption in the kidneys of adult mice...
July 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28699086/estimating-direct-cost-of-cystic-fibrosis-care-using-irish-registry-healthcare-resource-utilisation-data-2008-2012
#14
Abaigeal D Jackson, Andrew L Jackson, Godfrey Fletcher, Gerardine Doyle, Mary Harrington, Shijun Zhou, Fiona Cullinane, Charles Gallagher, Edward McKone
BACKGROUND: Understanding the determinants of cost of cystic fibrosis (CF) care and health outcomes may be useful for financial planning for the delivery of CF services. Registries contain information otherwise unavailable to healthcare activity/cost monitoring systems. We estimated the direct medical cost of CF care using registry data and examined how cost was affected by patient characteristics and CF gene (CF Transmembrane Conductance Regulator [CFTR]) mutation. METHODS: Healthcare resource utilisation data (2008-2012) were obtained for CF patients enrolled with the Irish CF Registry by 2013 from linked registry and national hospitalisation database records...
July 11, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28698407/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#15
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696257/transient-and-dynamic-dna-supercoiling-potently-stimulates-the-leu-500-promoter-in-escherichia-coli
#16
Xiaoduo Zhi, Samantha Dages, Kelley Dages, Yingting Liu, Zi-Chun Hua, John Makemson, Fenfei Leng
The inactive prokaryotic leu-500 promoter (Pleu-500) contains a single A-to-G point mutation in the -10 region of the leucine operon promoter, which causes leucine auxotrophy. This promoter can be activated by (-) DNA supercoiling in Escherichia coli topA strains. However, whether this activation arises from global, permanent or transient, dynamic supercoiling is still not fully understood. In this article, using a newly established in vivo system carrying a pair of divergently coupled promoters, i.e., an IPTG-inducible promoter and Pleu-500 that control the expression of lacZ and luc (the firefly luciferase gene) respectively, we demonstrate that transient, dynamic (-) DNA supercoiling provided by divergent transcription in both wild-type and topA strains can potently activate Pleu-500...
July 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28690787/the-effects-of-historical-fragmentation-on-major-histocompatibility-complex-class-ii-%C3%AE-and-microsatellite-variation-in-the-aegean-island-reptile-podarcis-erhardii
#17
Trent Santonastaso, Jackie Lighten, Cock van Oosterhout, Kenneth L Jones, Johannes Foufopoulos, Nicola M Anthony
The major histocompatibility complex (MHC) plays a key role in disease resistance and is the most polymorphic gene region in vertebrates. Although habitat fragmentation is predicted to lead to a loss in MHC variation through drift, the impact of other evolutionary forces may counter this effect. Here we assess the impact of selection, drift, migration, and recombination on MHC class II and microsatellite variability in 14 island populations of the Aegean wall lizard Podarcis erhardii. Lizards were sampled from islands within the Cyclades (Greece) formed by rising sea levels as the last glacial maximum approximately 20,000 before present...
July 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28689197/nkl-homeobox-gene-msx1-acts-like-a-tumor-suppressor-in-nk-cell-leukemia
#18
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox gene MSX1 is physiologically expressed in lymphoid progenitors and subsequently downregulated in developing T- and B-cells. In contrast, elevated expression levels of MSX1 persist in mature natural killer (NK)-cells, indicating a functional role in this compartment. While T-cell acute lymphoblastic leukemia (T-ALL) subsets exhibit aberrant overexpression of MSX1, we show here that in malignant NK-cells the level of MSX1 transcripts is aberrantly downregulated. Chromosomal deletions at 4p16 hosting the MSX1 locus have been described in NK-cell leukemia patients...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28659438/linker-proteins-restore-basement-membrane-and-correct-lama2-related-muscular-dystrophy-in-mice
#19
Judith R Reinhard, Shuo Lin, Karen K McKee, Sarina Meinen, Stephanie C Crosson, Maurizio Sury, Samantha Hobbs, Geraldine Maier, Peter D Yurchenco, Markus A Rüegg
LAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is the most frequent form of early-onset, fatal congenital muscular dystrophies. It is caused by mutations in LAMA2, the gene encoding laminin-α2, the long arm of the heterotrimeric (α2, β1, and γ1) basement membrane protein laminin-211 (Lm-211). We establish that despite compensatory expression of laminin-α4, giving rise to Lm-411 (α4, β1, and γ1), muscle basement membrane is labile in LAMA2 MD biopsies. Consistent with this deficit, recombinant Lm-411 polymerized and bound to cultured myotubes only weakly...
June 28, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28652603/skeletal-dysplasia-mutations-effect-on-human-filamins-structure-and-mechanosensing
#20
Jonne Seppälä, Rafael C Bernardi, Tatu J K Haataja, Maarit Hellman, Olli T Pentikäinen, Klaus Schulten, Perttu Permi, Jari Ylänne, Ulla Pentikäinen
Cells' ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B...
June 26, 2017: Scientific Reports
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