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Genomics Medicine

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https://read.qxmd.com/read/30785203/evolutionary-rate-correlation-between-mitochondrial-encoded-and-mitochondria-associated-nuclear-encoded-proteins-in-insects
#1
Zhichao Yan, Gongyin Ye, John H Werren
The mitochondrion is a pivotal organelle for energy production, and includes components encoded by both the mitochondrial and nuclear genomes. Functional and evolutionary interactions are expected between the nuclear and mitochondrial encoded components. The topic is of broad interest in biology, with implications to genetics, evolution, and medicine. Here we compare the evolutionary rates of mitochondrial proteins and ribosomal RNAs to rates of mitochondria-associated nuclear-encoded proteins, across the major orders of holometabolous insects...
February 20, 2019: Molecular Biology and Evolution
https://read.qxmd.com/read/30782707/a-prospective-cohort-for-the-investigation-of-alteration-in-temporal-transcriptional-and-microbiome-trajectories-preceding-preterm-birth-a-study-protocol
#2
Tobias Brummaier, Basirudeen Syed Ahamed Kabeer, Stephen Lindow, Justin C Konje, Sasithon Pukrittayaamee, Juerg Utzinger, Mohammed Toufiq, Antonios Antoniou, Alexandra K Marr, Sangrawee Suriyakan, Tomoshige Kino, Souhaila Al Khodor, Annalisa Terranegra, François Nosten, Daniel H Paris, Rose McGready, Damien Chaussabel
INTRODUCTION: Preterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period. METHODS AND ANALYSIS: Four hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period...
January 15, 2019: BMJ Open
https://read.qxmd.com/read/30779404/readiness-of-clinical-genetic-healthcare-professionals-to-provide-genomic-medicine-an-australian-census
#3
Amy Nisselle, Ivan Macciocca, Fiona McKenzie, Hannah Vuong, Kate Dunlop, Belinda McClaren, Sylvia Metcalfe, Clara Gaff
We aimed to determine capacity and readiness of Australian clinical genetic healthcare professionals to provide genomic medicine. An online survey was administered to individuals with genetic counseling or clinical genetics qualifications in Australia. Data collected included: education, certification, continuing professional development (CPD), employment, and genetic versus genomic clinical practice. Of the estimated 630 clinical genetic healthcare professionals in Australia, 354 completed the survey (56.2% response rate)...
February 19, 2019: Journal of Genetic Counseling
https://read.qxmd.com/read/30774085/-france-and-great-britain-at-the-age-of-genomic-medicine-new-ethical-challenges-in-reproductive-medicine
#4
Ruth Horn
The announcement of the French Plan 'France Médecine Génomique 2015' demonstrates the will of the public authorities to make genomic medicine one of the flagships of public health and scientific research. It is against this backdrop that France announced its cooperation with Great Britain, one of the global leaders in genomics. The cooperation at an international level requires a common normative framework that addresses the new ethical challenges presented by genomic medicine. In order for such a framework to be adapted to different national contexts, it is important to identify and analyse the emerging ethical questions in general as well as within their specific national contexts...
February 2019: Médecine Sciences: M/S
https://read.qxmd.com/read/30773767/opto-epigenetic-modulation-of-dna-methylation-with-a-photo-responsive-small-molecule-approach
#5
Ha Phuong Nguyen, Sabrina Stewart, Mikiembo N Kukwikila, Sioned Fôn Jones, Daniel Offenbartl-Stiegert, Shiqing Mao, Shankar Balasubramanian, Stephan Beck, Stefan Howorka
Controlling the functional dynamics of DNA within living cells is essential in biomedical research. Epigenetic modifications such as DNA methylation play a key role in this process. Controlled DNA methylation editing can be attained via genetic means. Yet there are few chemical tools available for the spatial and temporal modulation of this modification. Here we present a small-molecule approach to modulate DNA methylation with light. The strategy uses a photo-tuneable version of a clinically used drug (5-aza-2-deoxycytidine) to alter the catalytic activity of DNA methyltransferases, the enzymes that methylate DNA...
February 17, 2019: Angewandte Chemie
https://read.qxmd.com/read/30773478/dna-damage-repair-alterations-modulate-m2-polarization-of-microglia-to-remodel-the-tumor-microenvironment-via-the-p53-mediated-mdk-expression-in-glioma
#6
Xiangqi Meng, Chunbin Duan, Hengyuan Pang, Qun Chen, Bo Han, Caijun Zha, Magafurov Dinislam, Pengfei Wu, Ziwei Li, Shihong Zhao, Ruijia Wang, Lin Lin, Chuanlu Jiang, Jinquan Cai
BACKGROUND: DNA damage repair (DDR) alterations are important events in cancer initiation, progression, and therapeutic resistance. However, the involvement of DDR alterations in glioma malignancy needs further investigation. This study aims to characterize the clinical and molecular features of gliomas with DDR alterations and elucidate the biological process of DDR alterations that regulate the cross talk between gliomas and the tumor microenvironment. METHODS: Integrated transcriptomic and genomic analyses were undertaken to conduct a comprehensive investigation of the role of DDR alterations in glioma...
February 14, 2019: EBioMedicine
https://read.qxmd.com/read/30773189/cancer-genetic-markers-according-to-radiotherapeutic-response-in-patients-with-primary-glioblastoma-radiogenomic-approach-for-precision-medicine
#7
Kyungmi Yang, Sang Won Jung, Hyemi Shin, Do Hoon Lim, Jung-Il Lee, Doo-Sik Kong, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam
BACKGROUND AND PURPOSE: To find genetic markers associated with response to radiotherapy (RT) in glioblastoma (GB) patients. MATERIALS AND METHODS: From Jan 2009 to Dec 2016, 161 patients with newly diagnosed IDH-wild type GB were treated with surgery and adjuvant concurrent chemoradiotherapy with the Stupp's regimen, and then genomic research proceeded with their surgical specimens. Among the 161 patients, 49 with clinically measurable disease on postoperative MRI were analyzed...
February 2019: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://read.qxmd.com/read/30772464/deep-resp-forest-a-deep-forest-model-to-predict-anti-cancer-drug-response
#8
Ran Su, Xinyi Liu, Leyi Wei, Quan Zou
The identification of therapeutic biomarkers predictive of drug response is crucial in personalized medicine. A number of computational models to predict response of anti-cancer drugs have been developed as the establishment of several pharmacogenomics screening databases. In our study, we proposed a deep cascaded forest model, Deep-Resp-Forest, to classify the anti-cancer drug response as "sensitive" or "resistant". We made three contributions in this study. Firstly, diverse molecular data could be effectively integrated to provide more information than single type of data for the classification...
February 14, 2019: Methods: a Companion to Methods in Enzymology
https://read.qxmd.com/read/30771135/proteomic-and-genomic-profiling-of-pancreatic-cancer
#9
REVIEW
Daniel Ansari, William Torén, Qimin Zhou, Dingyuan Hu, Roland Andersson
Pancreatic cancer remains the most fatal human tumor type. The aggressive tumor biology coupled with the lack of early detection strategies and effective treatment are major reasons for the poor survival rate. Collaborative research efforts have been devoted to understand pancreatic cancer at the molecular level. Large-scale genomic studies have generated important insights into the genetic drivers of pancreatic cancer. In the post-genomic era, protein sequencing of tumor tissue, cell lines, pancreatic juice, and blood from patients with pancreatic cancer has provided a fundament for the development of new diagnostic and prognostic biomarkers...
February 15, 2019: Cell Biology and Toxicology
https://read.qxmd.com/read/30769780/increased-cytotoxicity-of-herpes-simplex-virus-thymidine-kinase-expression-in-human-induced-pluripotent-stem-cells
#10
Chizuru Iwasawa, Ryota Tamura, Yuki Sugiura, Sadafumi Suzuki, Naoko Kuzumaki, Minoru Narita, Makoto Suematsu, Masaya Nakamura, Kazunari Yoshida, Masahiro Toda, Hideyuki Okano, Hiroyuki Miyoshi
Human induced pluripotent stem cells (iPSCs) hold enormous promise for regenerative medicine. The major safety concern is the tumorigenicity of transplanted cells derived from iPSCs. A potential solution would be to introduce a suicide gene into iPSCs as a safety switch. The herpes simplex virus type 1 thymidine kinase ( HSV-TK ) gene, in combination with ganciclovir, is the most widely used enzyme/prodrug suicide system from basic research to clinical applications. In the present study, we attempted to establish human iPSCs that stably expressed HSV-TK with either lentiviral vectors or CRISPR/Cas9-mediated genome editing...
February 14, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30768178/personalized-medicine-in-cardio-oncology-the-role-of-ipsc
#11
Nazish Sayed, Mohamed Ameen, Joseph C Wu
Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure...
February 15, 2019: Cardiovascular Research
https://read.qxmd.com/read/30767786/ten-years-of-genome-medicine
#12
EDITORIAL
Charles Auffray, Julian L Griffin, Muin J Khoury, James R Lupski, Matthias Schwab
No abstract text is available yet for this article.
February 15, 2019: Genome Medicine
https://read.qxmd.com/read/30767757/targeting-chromatin-remodeling-for-cancer-therapy
#13
Jasmine Kaur, Abdelkader Daoud, Scott T Eblen
BACKGROUND: Epigenetic alterations comprise key regulatory events that dynamically alter gene expression and their deregulation is commonly linked to the pathogenesis of various diseases, including cancer. Unlike DNA mutations, epigenetic alterations involve modifications to proteins and nucleic acids that regulate chromatin structure without affecting the underlying DNA sequence, altering the accessibility of the transcriptional machinery to the DNA, thus modulating gene expression. In cancer cells, this often involves the silencing of tumor suppressor genes or the increased expression of genes involved in oncogenesis...
February 14, 2019: Current Molecular Pharmacology
https://read.qxmd.com/read/30767736/3d-printing-in-personalized-drug-delivery
#14
Afsana, Vineet Jain, Nafis Haider, Keerti Jain
BACKGROUND: Personalized medicines are becoming more popular as they enables the use of patient's genomics and hence help in better drug design with fewer side effects. In fact several doses can be combined into one dosage form which suits the patient's demography. 3 Dimensional (3D) printing technology for personalized medicine is a modern day treatment method based on genomics of patient. METHODS: 3D printing technology uses digitally controlled devices for formulating API and excipients in a layer by layer pattern for developing a suitable personalized drug delivery system as per the need of patient...
February 15, 2019: Current Pharmaceutical Design
https://read.qxmd.com/read/30767728/epigenomics-guided-drug-development-recent-advances-in-solving-the-cancer-treatment-jigsaw-puzzle
#15
Kevin Dzobo
The human epigenome plays a key role in determining cellular identity and eventually function. Drug discovery undertakings have focused mainly on the role of genomics in carcinogenesis, with the focus turning to the epigenome recently. Drugs targeting DNA and histone modifications are under development with some such as 5-azacytidine, decitabine, vorinostat, and panobinostat already approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This expert review offers a critical analysis of the epigenomics-guided drug discovery and development and the opportunities and challenges for the next decade...
February 2019: Omics: a Journal of Integrative Biology
https://read.qxmd.com/read/30766616/pathway-based-classification-of-genetic-diseases
#16
Ivan Y Iourov, Svetlana G Vorsanova, Yuri B Yurov
Background: In medical genetics, diseases are classified according to the nature (hypothetical nature) of the underlying genetic defect. The classification is "gene-centric" and "factor-centric"; a disease may be, thereby, designated as monogenic, oligogenic or polygenic/multifactorial. Chromosomal diseases/syndromes and abnormalities are generally considered apart from these designations due to distinctly different formation mechanisms and simultaneous encompassing from several to several hundreds of co-localized genes...
2019: Molecular Cytogenetics
https://read.qxmd.com/read/30764760/ads-hcspark-a-scalable-haplotypecaller-leveraging-adaptive-data-segmentation-to-accelerate-variant-calling-on-spark
#17
Anghong Xiao, Zongze Wu, Shoubin Dong
BACKGROUND: The advance of next generation sequencing enables higher throughput with lower price, and as the basic of high-throughput sequencing data analysis, variant calling is widely used in disease research, clinical treatment and medicine research. However, current mainstream variant caller tools have a serious problem of computation bottlenecks, resulting in some long tail tasks when performing on large datasets. This prevents high scalability on clusters of multi-node and multi-core, and leads to long runtime and inefficient usage of computing resources...
February 14, 2019: BMC Bioinformatics
https://read.qxmd.com/read/30763338/tailored-neoadjuvant-epirubicin-cyclophosphamide-and-nanoparticle-albumin-bound-paclitaxel-for-breast-cancer-the-phase-ii-neonab-trial-clinical-outcomes-and-molecular-determinants-of-response
#18
Caitlin Murphy, Andrea Muscat, David Ashley, Violet Mukaro, Linda West, Yang Liao, David Chisanga, Wei Shi, Ian Collins, Sally Baron-Hay, Sujata Patil, Geoffrey Lindeman, Mustafa Khasraw
BACKGROUND: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. PATIENTS AND OUTCOME MEASURES: Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25...
2019: PloS One
https://read.qxmd.com/read/30762612/genetic-profiling-for-disease-stratification-in-chronic-obstructive-pulmonary-disease-and-asthma
#19
Senani N H Rathnayake, Maarten Van den Berge, Alen Faiz
PURPOSE OF REVIEW: In asthma and chronic obstructive pulmonary disease (COPD), the movement towards genetic profiling with a push towards 'personalized medicine' has been hindered by complex environment--gene interactions and lack of tools to identify clear causal genetic traits. In this review, we will discuss the need for genetic profiling in asthma and COPD, what methods are currently used in the clinics and the recent finding using new sequencing methods. RECENT FINDINGS: Over the past 10-15 years, genome-wide association studies analysis of common variants has provide little in the way of new genetic profiling markers for asthma and COPD...
February 11, 2019: Current Opinion in Pulmonary Medicine
https://read.qxmd.com/read/30759475/-genome-editing-with-crispr-cas9-first-steps-towards-a-new-era-in-medicine
#20
Bernhard Schermer, Thomas Benzing
The emergence of genome editing technologies can be regarded as one of the most groundbreaking revolutions in the history of science. Modern genome editing allows the introduction of precise mutations into the genome of virtually all cells and organisms without leaving any additional trace. Undoubtedly, genome editing with CRISPR/Cas9, often casually referred to as "genetic scissors", will revolutionize medical research and development. However, at the same time it creates a great need for ethical considerations as it might hold risks for both people and the environment that cannot yet be fully assessed...
February 2019: Deutsche Medizinische Wochenschrift
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