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https://www.readbyqxmd.com/read/27936513/probing-the-structural-dynamics-of-the-crispr-cas9-rna-guided-dna-cleavage-system-by-coarse-grained-modeling
#1
Wenjun Zheng
In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936512/genome-editing-of-the-disease-susceptibility-gene-cslob1-in-citrus-confers-resistance-to-citrus-canker
#2
Hongge Jia, Yunzen Zhang, Vladimir Orbovic, Jin Xu, Frank White, Jeffrey Jones, Nian Wang
Citrus is a highly valued tree crop worldwide, while, at the same time, citrus production faces many biotic challenges, including bacterial canker and Huanglongbing (HLB). Breeding for disease resistant varieties is the most efficient and sustainable approach to control plant diseases. Traditional breeding of citrus varieties is challenging due to multiple limitations, including polyploidy, polyembryony, extended juvenility, and long crossing cycles. Targeted genome editing technology has the potential to shorten varietal development for some traits, including disease resistance...
December 9, 2016: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/27936181/in-vivo-modelling-of-atp1a3-g316s-induced-ataxia-in-c-elegans-using-crispr-cas9-mediated-homologous-recombination-reveals-dominant-loss-of-function-defects
#3
Altar Sorkaç, Ivan C Alcantara, Anne C Hart
The NIH Undiagnosed Diseases Program admitted a male patient with unclassifiable late-onset ataxia-like symptoms. Exome sequencing revealed a heterozygous de novo mutation converting glycine 316 to serine in ATP1A3, which might cause disease. ATP1A3 encodes the Na+/K+ ATPase pump α3-subunit. Using CRISPR/Cas9-mediated homologous recombination for genome editing, we modelled this putative disease-causing allele in Caenorhabditis elegans, recreating the patient amino acid change in eat-6, the orthologue of ATP1A3...
2016: PloS One
https://www.readbyqxmd.com/read/27936040/a-high-throughput-strategy-for-dissecting-mammalian-genetic-interactions
#4
Victoria B Stockman, Lila Ghamsari, Gorka Lasso, Barry Honig, Sagi D Shapira, Harris H Wang
Comprehensive delineation of complex cellular networks requires high-throughput interrogation of genetic interactions. To address this challenge, we describe the development of a multiplex combinatorial strategy to assess pairwise genetic interactions using CRISPR-Cas9 genome editing and next-generation sequencing. We characterize the performance of combinatorial genome editing and analysis using different promoter and gRNA designs and identified regions of the chimeric RNA that are compatible with next-generation sequencing preparation and quantification...
2016: PloS One
https://www.readbyqxmd.com/read/27934590/generation-of-an-isogenic-gene-corrected-ipsc-line-from-a-pre-symptomatic-28-year-old-woman-with-an-r406w-mutation-in-the-microtubule-associated-protein-tau-mapt-gene
#5
Natakarn Nimsanor, Ulla Poulsen, Mikkel A Rasmussen, Christian Clausen, Ulrike A Mau-Holzmann, Jørgen E Nielsen, Troels T Nielsen, Poul Hyttel, Bjørn Holst, Benjamin Schmid
Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934586/generation-of-an-isogenic-gene-corrected-ipsc-line-from-a-symptomatic-59-year-old-female-patient-with-frontotemporal-dementia-caused-by-an-r406w-mutation-in-the-microtubule-associated-protein-tau-mapt-gene
#6
Natakarn Nimsanor, Ulla Poulsen, Mikkel A Rasmussen, Christian Clausen, Ulrike A Mau-Holzmann, Jørgen E Nielsen, Troels T Nielsen, Poul Hyttel, Bjørn Holst, Benjamin Schmid
Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27933636/primary-headaches-in-an-elderly-population-seeking-medical-care-for-cognitive-decline
#7
Michele Feleppa, Silvia Fucci, Marcelo E Bigal
OBJECTIVES: To assess the prevalence of specific headache disorders in a population older than 65 years seeking consultation due to memory problems or cognitive impairment. METHODS: We verified the occurrence of headache symptoms and the impact of headaches on daily life. Headaches were classified as per the International Classification of Headache Disorders, 2nd edition (ICHD-2). All patients were screened with the Mini-Mental State Examination (MMSE), followed by the Selective Reminding Test and neuroimaging...
December 9, 2016: Headache
https://www.readbyqxmd.com/read/27933285/developmental-profile-and-diagnoses-in-children-presenting-with-motor-stereotypies
#8
Francesco Cardona, Francesca Valente, Daniela Miraglia, Caterina D'Ardia, Valentina Baglioni, Flavia Chiarotti
INTRODUCTION: Motor stereotypies represent a typical example of the difficulty in distinguishing non-clinical behaviors (physiological and transient) from symptoms or among different disorders ["primary stereotypies," associated with autistic spectrum disorder (ASD), intellectual disabilities, genetic syndromes, and sensory impairment]. The aim of this study was to obtain an accurate assessment on the relationship between stereotypies and neurodevelopmental disorders. METHODS: We studied 23 children (3 girls), aged 36-95 months, who requested a consultation due to the persistence or increased severity of motor stereotypies...
2016: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/27933251/robust-image-hashing-using-ring-partition-pgnmf-and-local-features
#9
Ram Kumar Karsh, R H Laskar, Bhanu Bhai Richhariya
BACKGROUND: Image authentication is one of the challenging research areas in the multimedia technology due to the availability of image editing tools. Image hash may be used for image authentication which should be invariant to perceptually similar image and sensitive to content changes. The challenging issue in image hashing is to design a system which simultaneously provides rotation robustness, desirable discrimination, sensitivity and localization of forged area with minimum hash length...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27933223/epigenetic-editing-on-the-verge-of-reprogramming-gene-expression-at-will
#10
REVIEW
David Cano-Rodriguez, Marianne G Rots
Genome targeting has quickly developed as one of the most promising fields in science. By using programmable DNA-binding platforms and nucleases, scientists are now able to accurately edit the genome. These DNA-binding tools have recently also been applied to engineer the epigenome for gene expression modulation. Such epigenetic editing constructs have firmly demonstrated the causal role of epigenetics in instructing gene expression. Another focus of epigenome engineering is to understand the order of events of chromatin remodeling in gene expression regulation...
2016: Current Genetic Medicine Reports
https://www.readbyqxmd.com/read/27933209/prevalence-and-incidence-of-gout-in-southern-sweden-from-the-socioeconomic-perspective
#11
Meliha C Kapetanovic, Mohaned Hameed, Aleksandra Turkiewicz, Tuhina Neogi, Tore Saxne, Lennart Jacobsson, Martin Englund
OBJECTIVES: To estimate the prevalence and cumulative incidence of gout in southern Sweden with respect to socioeconomic status. METHODS: Among residents of Skåne region in the year 2013 (total population 1.3 million), adult persons (age 18 years +) who between 1998 and 2013 received a diagnosis of gout (International Classification of Disease 10th Edition (ICD-10) code M10) by any physician were identified using the Skåne Healthcare Register. We calculated the point prevalence by end of 2013 and annual cumulative incidence in 2013 standardised to the whole Skåne population according to sex, individual information on occupation (white collar/blue collar), income (low/middle/high) and level of education (primary school/high school/university)...
2016: RMD Open
https://www.readbyqxmd.com/read/27932948/rna-editing-systemic-relevance-and-clue-to-disease-mechanisms
#12
REVIEW
Jochen C Meier, Svenja Kankowski, Heinz Krestel, Florian Hetsch
Recent advances in sequencing technologies led to the identification of a plethora of different genes and several hundreds of amino acid recoding edited positions. Changes in editing rates of some of these positions were associated with diseases such as atherosclerosis, myopathy, epilepsy, major depression disorder, schizophrenia and other mental disorders as well as cancer and brain tumors. This review article summarizes our current knowledge on that front and presents glycine receptor C-to-U RNA editing as a first example of disease-associated increased RNA editing that includes assessment of disease mechanisms of the corresponding gene product in an animal model...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27932772/-modification-and-evaluation-of-assessment-of-%C3%A2-medication-literacy
#13
Feng Zheng, Zhuqing Zhong, Siqing Ding, Aijing Luo, Zina Liu
To translate and revise the Medication Literacy Assessment in English (MedLitRxSE-English) and evaluate its validity and reliability.
 Methods: We introduced MedLitRxSE-English from abroad. According to the principles of Brislin and culture adjustment, we revised it as a Chinese edition. Using random sampling method, from Oct, 2014 to Jan, 2015, 461 non-hospitalized patients from the outpatient departments of the top three hospitals in Changsha city were investigated. The reliability and validity of the scale was tested...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27932771/-analysis-of-the-status-and-influential-factors-for-prenatal-care-and-postpartum-visit-among-pregnant-women-based-on-the-first-health-service-survey-in-hunan-province
#14
Wei Zhang, Xunjie Cheng, Lin Zhang, Peishan Ning, Li Li, Xin Deng, Jing Deng, Guoqing Hu
To evaluate the status and influential factors for prenatal care and postpartum visit among pregnant women in Hunan Province from 2008 to 2013 based on the data from the First Health Service Survey in Hunan Province.
 Methods: Based on the data of prenatal care and postpartum visit among pregnant women from the First Health Service Survey of Hunan Province in 2013, proportion of pregnant women, who didn't meet the criteria for prenatal care and postpartum visit, were calculated (≥5 times for prenatal care and ≥2 times for postpartum visit, according to the National Basic Public Health Service program, 2009 Edition)...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27932568/targeting-hif2-in-clear-cell-renal-cell-carcinoma
#15
Hyejin Cho, William G Kaelin
Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1...
December 8, 2016: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/27930735/gene-editing-approaches-against-viral-infections-and-strategy-to-prevent-occurrence-of-viral-escape
#16
Martyn K White, Wenhui Hu, Kamel Khalili
No abstract text is available yet for this article.
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27930369/measuring-moral-distress-among-critical-care-clinicians-validation-and-psychometric-properties-of-the-italian-moral-distress-scale-revised
#17
Giulia Lamiani, Ilaria Setti, Luca Barlascini, Elena Vegni, Piergiorgio Argentero
OBJECTIVES: Moral distress is a common experience among critical care professionals, leading to frustration, withdrawal from patient care, and job abandonment. Most of the studies on moral distress have used the Moral Distress Scale or its revised version (Moral Distress Scale-Revised). However, these scales have never been validated through factor analysis. This article aims to explore the factorial structure of the Moral Distress Scale-Revised and develop a valid and reliable scale through factor analysis...
December 7, 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27930336/resistance-mutation-conserved-between-insects-and-mites-unravels-the-benzoylurea-insecticide-mode-of-action-on-chitin-biosynthesis
#18
Vassilis Douris, Denise Steinbach, Rafaela Panteleri, Ioannis Livadaras, John Anthony Pickett, Thomas Van Leeuwen, Ralf Nauen, John Vontas
Despite the major role of chitin biosynthesis inhibitors such as benzoylureas (BPUs) in the control of pests in agricultural and public health for almost four decades, their molecular mode of action (MoA) has in most cases remained elusive. BPUs interfere with chitin biosynthesis and were thought to interact with sulfonylurea receptors that mediate chitin vesicle transport. Here, we uncover a mutation (I1042M) in the chitin synthase 1 (CHS1) gene of BPU-resistant Plutella xylostella at the same position as the I1017F mutation reported in spider mites that confers etoxazole resistance...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929612/effects-of-cumulative-herpesviridae-and-toxoplasma-gondii-infections-on-cognitive-function-in-healthy-bipolar-and-schizophrenia-subjects
#19
Nora Hamdani, Claire Daban-Huard, Ophelia Godin, Hakim Laouamri, Stéphane Jamain, Dodji Attiba, Marine Delavest, Jean-Pierre Lépine, Philippe Le Corvoisier, Josselin Houenou, Jean-Romain Richard, Robert H Yolken, Rajagopal Krishnamoorthy, Ryad Tamouza, Marion Leboyer, Faith B Dickerson
OBJECTIVE: Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls. METHODS: Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test)...
December 6, 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27929521/efficient-footprint-free-human-ipsc-genome-editing-by-consolidation-of-cas9-crispr-and-piggybac-technologies
#20
Gang Wang, Luhan Yang, Dennis Grishin, Xavier Rios, Lillian Y Ye, Yong Hu, Kai Li, Donghui Zhang, George M Church, William T Pu
Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations...
January 2017: Nature Protocols
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