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https://www.readbyqxmd.com/read/28749476/the-wide-genetic-landscape-of-clinical-frontotemporal-dementia-systematic-combined-sequencing-of-121-consecutive-subjects
#1
Cornelis Blauwendraat, Carlo Wilke, Javier Simón-Sánchez, Iris E Jansen, Anika Reifschneider, Anja Capell, Christian Haass, Melissa Castillo-Lizardo, Saskia Biskup, Walter Maetzler, Patrizia Rizzu, Peter Heutink, Matthis Synofzik
PurposeTo define the genetic spectrum and relative gene frequencies underlying clinical frontotemporal dementia (FTD).MethodsWe investigated the frequencies and mutations in neurodegenerative disease genes in 121 consecutive FTD subjects using an unbiased, combined sequencing approach, complemented by cerebrospinal fluid Aβ1-42 and serum progranulin measurements. Subjects were screened for C9orf72 repeat expansions, GRN and MAPT mutations, and, if negative, mutations in other neurodegenerative disease genes, by whole-exome sequencing (WES) (n = 108), including WES-based copy-number variant (CNV) analysis...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28749468/wwox-sensitises-ovarian-cancer-cells-to-paclitaxel-via-modulation-of-the-er-stress-response
#2
Szymon Janczar, Jaya Nautiyal, Yi Xiao, Edward Curry, Mingjun Sun, Elisa Zanini, Adam Jw Paige, Hani Gabra
There are clear gaps in our understanding of genes and pathways through which cancer cells facilitate survival strategies as they become chemoresistant. Paclitaxel is used in the treatment of many cancers, but development of drug resistance is common. Along with being an antimitotic agent paclitaxel also activates endoplasmic reticulum (ER) stress. Here, we examine the role of WWOX (WW domain containing oxidoreductase), a gene frequently lost in several cancers, in mediating paclitaxel response. We examine the ER stress-mediated apoptotic response to paclitaxel in WWOX-transfected epithelial ovarian cancer (EOC) cells and following siRNA knockdown of WWOX...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749203/cb002-a-novel-p53-tumor-suppressor-pathway-restoring-small-molecule-induces-tumor-cell-death-through-the-pro-apoptotic-protein-noxa
#3
Liz J Hernandez-Borrero, Shengliang Zhang, Amriti Lulla, David T Dicker, Wafik S El-Deiry
P53 tumor suppressor gene mutations occur in the majority of human cancers and contribute to tumor development, progression and therapy resistance. Direct functional restoration of p53 as a transcription factor has been difficult to achieve in the clinic. We performed a functional screen using a bioluminescence-based transcriptional read-out to identify small molecules that restore the p53 pathway in mutant p53-bearing cancer cells. We identified CB002, as a candidate that restores p53 function in mutant p53-expressing colorectal cancer cells and without toxicity to normal human fibroblasts...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28749049/mineral-trioxide-aggregate-enhances-the-osteogenic-capacity-of-periodontal-ligament-stem-cells-via-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#4
Yanqiu Wang, Yixiang Zhou, Lin Jin, Xiyao Pang, Yadie Lu, Zilu Wang, Yan Yu, Jinhua Yu
INTRODUCTION: Mineral trioxide aggregate (MTA), as a bioactive material, has a widespread application in clinical practice. To date, the effects of MTA on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs) remain unclear. MATERIALS AND METHODS: hPDLSCs were isolated from human periodontal ligament tissues and cultured with MTA conditioned media. Cell counting kit-8 (CCK-8) assay was performed to assess the proliferation capacity of MTA-treated hPDLSCs...
July 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28749036/advantages-of-rna-seq-compared-to-rna-microarrays-for-transcriptome-profiling-of-anterior-cruciate-ligament-tears
#5
Muhammad Farooq Rai, Eric D Tycksen, Linda J Sandell, Robert H Brophy
Microarrays and RNA-seq are at the forefront of high throughput transcriptome analyses. Since these methodologies are based on different principles there are concerns about the concordance of data between the two techniques. The concordance of RNA-seq and microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed in clinically derived ligament tissues. To demonstrate the concordance between RNA-seq and microarrays and to assess potential benefits of RNA-seq over microarrays, we assessed differences in transcript expression in anterior cruciate ligament (ACL) tissues based on time-from-injury...
July 27, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28748988/-characterization-of-patients-with-sporadic-colorectal-cancer-following-the-new-consensus-molecular-subtypes-cms
#6
Ana María Wielandt, Cynthia Villarroel, Claudia Hurtado, Daniela Simian, Diego Zamorano, Maripaz Martínez, Magdalena Castro, María Teresa Vial, Udo Kronberg, Francisco López-Kostner
BACKGROUND: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. AIM: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways...
April 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/28748860/current-nondopaminergic-therapeutic-options-for-motor-symptoms-of-parkinson-s-disease
#7
REVIEW
Juan-Juan Du, Sheng-Di Chen
OBJECTIVE: The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD). DATA SOURCES: Papers in English published in PubMed, Cochrane, and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords: PD, nondopaminergic therapy, adenosine, glutamatergic, adrenergic, serotoninergic, histaminic, and iron chelator. We also reviewed the ongoing clinical trials in the website of clinicaltrials...
August 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28748774/exposure-to-parental-psychopathology-and-offspring-s-risk-of-suicide-related-thoughts-and-behaviours-a-systematic-review
#8
S M Goodday, J Shuldiner, S Bondy, A E Rhodes
AIMS: The primary objective of this systematic review was to identify and synthesise analytic studies examining the association between exposure to parental psychopathology in childhood and the nature of subsequent suicide-related thoughts (SRT) and suicide-related behaviour (SRB) (severity of ideation, planned/unplanned attempts/lethality) and to describe the direction, and magnitude of associations. The secondary objective was to determine if the associations from the primary objective differ by the type(s) and timing of parental psychopathology, sex/gender of the parent and child and is mediated by child psychiatric symptoms and family functioning...
July 27, 2017: Epidemiology and Psychiatric Sciences
https://www.readbyqxmd.com/read/28748642/noonan-syndrome-in-diverse-populations
#9
Paul Kruszka, Antonio R Porras, Yonit A Addissie, Angélica Moresco, Sofia Medrano, Gary T K Mok, Gordon K C Leung, Cedrik Tekendo-Ngongang, Annette Uwineza, Meow-Keong Thong, Premala Muthukumarasamy, Engela Honey, Ekanem N Ekure, Ogochukwu J Sokunbi, Nnenna Kalu, Kelly L Jones, Julie D Kaplan, Omar A Abdul-Rahman, Lisa M Vincent, Amber Love, Khadija Belhassan, Karim Ouldim, Ihssane El Bouchikhi, Anju Shukla, Katta M Girisha, Siddaramappa J Patil, Nirmala D Sirisena, Vajira H W Dissanayake, C Sampath Paththinige, Rupesh Mishra, Eva Klein-Zighelboim, Bertha E Gallardo Jugo, Miguel Chávez Pastor, Hugo H Abarca-Barriga, Steven A Skinner, Eloise J Prijoles, Eben Badoe, Ashleigh D Gill, Vorasuk Shotelersuk, Patroula Smpokou, Monisha S Kisling, Carlos R Ferreira, Leon Mutesa, Andre Megarbane, Antonie D Kline, Amy Kimball, Emmy Okello, Peter Lwabi, Twalib Aliku, Emmanuel Tenywa, Nonglak Boonchooduang, Pranoot Tanpaiboon, Antonio Richieri-Costa, Ambroise Wonkam, Brian H Y Chung, Roger E Stevenson, Marshall Summar, Kausik Mandal, Shubha R Phadke, María G Obregon, Marius G Linguraru, Maximilian Muenke
Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%...
July 27, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28748534/mir-130b-directly-targets-arhgap1-to-drive-activation-of-a-metastatic-cdc42-pak1-ap1-positive-feedback-loop-in-ewing-sarcoma
#10
Laura Satterfield, Ryan Shuck, Lyazat Kurenbekova, Wendy Allen-Rhoades, Dean Edwards, Shixia Huang, Kimal Rajapakshe, Cristian Coarfa, Lawrence A Donehower, Jason T Yustein
Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing towards sarcoma metastasis...
July 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28748356/pd-l1-induced-by-ifn-%C3%AE-from-tumor-associated-macrophages-via-the-jak-stat3-and-pi3k-akt-signaling-pathways-promoted-progression-of-lung-cancer
#11
Xiaohui Zhang, Yuanyuan Zeng, Qiuxia Qu, Jianjie Zhu, Zeyi Liu, Weiwei Ning, Hui Zeng, Nan Zhang, Wenwen Du, Cheng Chen, Jian-An Huang
BACKGROUND: Interferon-γ (IFN-γ) is conventionally regarded as an inflammatory cytokine that has a pivotal role in anti-infection and tumor immune surveillance. It has been used clinically to treat a variety of malignancies. However, increased evidence has suggested IFN-γ can act to induce tumor progression. The role of IFN-γ in regulating antitumor immunity appears to be complex and paradoxical. The mechanism underlying the dual aspects of IFN-γ function in antitumor immunity is not clear...
July 26, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28748184/complement-in-non-antibody-mediated-kidney-diseases
#12
REVIEW
Andrea Angeletti, Joselyn Reyes-Bahamonde, Paolo Cravedi, Kirk N Campbell
The complement system is part of the innate immune response that plays important roles in protecting the host from foreign pathogens. The complement components and relative fragment deposition have long been recognized to be strongly involved also in the pathogenesis of autoantibody-related kidney glomerulopathies, leading to direct glomerular injury and recruitment of infiltrating inflammation pathways. More recently, unregulated complement activation has been shown to be associated with progression of non-antibody-mediated kidney diseases, including focal segmental glomerulosclerosis, C3 glomerular disease, thrombotic microangiopathies, or general fibrosis generation in progressive chronic kidney diseases...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28747873/mitochondria-bioenergetics-and-excitotoxicity-new-therapeutic-targets-in-perinatal-brain-injury
#13
REVIEW
Bryan Leaw, Syam Nair, Rebecca Lim, Claire Thornton, Carina Mallard, Henrik Hagberg
Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28747872/l-3-n-butylphthalide-protects-hspb8-k141n-mutation-induced-oxidative-stress-by-modulating-the-mitochondrial-apoptotic-and-nrf2-pathways
#14
Xiao-Dong Yang, Zhi-Dong Cen, Hai-Peng Cheng, Kai Shi, Jie Bai, Fei Xie, Hong-Wei Wu, Bei-Bei Li, Wei Luo
Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is the most common inherited peripheral nerve disorder. Missense mutations, such as K141N, in the small heat shock protein HSPB8 are known to cause distal hereditary motor neuropathy 2A (dHMN2A) or Charcot-Marie-Tooth neuropathy type 2L (CMT2L). However, of critical clinical significance, very few specific therapies for this disease exist. In the present study, we investigated the impact of mutant K141N HSPB8 on mitochondrial distribution and function in a cellular model of CMT2L...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28747747/involvement-of-monocyte-subsets-in-the-immunopathology-of-giant-cell-arteritis
#15
Yannick van Sleen, Qi Wang, Kornelis S M van der Geest, Johanna Westra, Wayel H Abdulahad, Peter Heeringa, Annemieke M H Boots, Elisabeth Brouwer
Monocytes/macrophages are critical in systemic and local inflammation in giant cell arteritis (GCA) and possibly in clinically overlapping polymyalgia rheumatica (PMR). Therefore, we aimed to understand the contribution of monocyte subsets and the CX3CR1-CX3CL1 and CCR2-CCL2 migratory pathways, to the pathology of GCA. Peripheral blood monocytes were enumerated in samples from newly-diagnosed, untreated GCA and PMR patients and after prednisone-induced remission. The distribution of classical (CD14(bright)CD16(neg)) and the more pro-inflammatory, intermediate (CD14(bright)CD16+) and non-classical (CD14(dim)CD16+) monocyte subsets was analysed by flow cytometry...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747716/burn-induced-muscle-metabolic-derangements-and-mitochondrial-dysfunction-are-associated-with-activation-of-hif-1%C3%AE-and-mtorc1-role-of-protein-farnesylation
#16
Harumasa Nakazawa, Kazuhiro Ikeda, Shohei Shinozaki, Masayuki Kobayashi, Yuichi Ikegami, Ming Fu, Tomoyuki Nakamura, Shingo Yasuhara, Yong-Ming Yu, J A Jeevendra Martyn, Ronald G Tompkins, Kentaro Shimokado, Tomoko Yorozu, Hideki Ito, Satoshi Inoue, Masao Kaneki
Metabolic derangements are a clinically significant complication of major trauma (e.g., burn injury) and include various aspects of metabolism, such as insulin resistance, muscle wasting, mitochondrial dysfunction and hyperlactatemia. Nonetheless, the molecular pathogenesis and the relation between these diverse metabolic alterations are poorly understood. We have previously shown that burn increases farnesyltransferase (FTase) expression and protein farnesylation and that FTase inhibitor (FTI) prevents burn-induced hyperlactatemia, insulin resistance, and increased proteolysis in mouse skeletal muscle...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747714/transcriptomic-biomarkers-to-discriminate-bacterial-from-nonbacterial-infection-in-adults-hospitalized-with-respiratory-illness
#17
Soumyaroop Bhattacharya, Alex F Rosenberg, Derick R Peterson, Katherine Grzesik, Andrea M Baran, John M Ashton, Steven R Gill, Anthony M Corbett, Jeanne Holden-Wiltse, David J Topham, Edward E Walsh, Thomas J Mariani, Ann R Falsey
Lower respiratory tract infection (LRTI) commonly causes hospitalization in adults. Because bacterial diagnostic tests are not accurate, antibiotics are frequently prescribed. Peripheral blood gene expression to identify subjects with bacterial infection is a promising strategy. We evaluated whole blood profiling using RNASeq to discriminate infectious agents in adults with microbiologically defined LRTI. Hospitalized adults with LRTI symptoms were recruited. Clinical data and blood was collected, and comprehensive microbiologic testing performed...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747516/redundant-and-diverse-intranodal-pacemakers-and-conduction-pathways-protect-the-human-sinoatrial-node-from-failure
#18
Ning Li, Brian J Hansen, Thomas A Csepe, Jichao Zhao, Anthony J Ignozzi, Lidiya V Sul, Stanislav O Zakharkin, Anuradha Kalyanasundaram, Jonathan P Davis, Brandon J Biesiadecki, Ahmet Kilic, Paul M L Janssen, Peter J Mohler, Raul Weiss, John D Hummel, Vadim V Fedorov
The human sinoatrial node (SAN) efficiently maintains heart rhythm even under adverse conditions. However, the specific mechanisms involved in the human SAN's ability to prevent rhythm failure, also referred to as its robustness, are unknown. Challenges exist because the three-dimensional (3D) intramural structure of the human SAN differs from well-studied animal models, and clinical electrode recordings are limited to only surface atrial activation. Hence, to innovate the translational study of human SAN structural and functional robustness, we integrated intramural optical mapping, 3D histology reconstruction, and molecular mapping of the ex vivo human heart...
July 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28747205/detection-of-antibiotic-resistance-is-essential-for-gonorrhoea-point-of-care-testing-a-mathematical-modelling-study
#19
Stephanie M Fingerhuth, Nicola Low, Sebastian Bonhoeffer, Christian L Althaus
BACKGROUND: Antibiotic resistance is threatening to make gonorrhoea untreatable. Point-of-care (POC) tests that detect resistance promise individually tailored treatment, but might lead to more treatment and higher levels of resistance. We investigate the impact of POC tests on antibiotic-resistant gonorrhoea. METHODS: We used data about the prevalence and incidence of gonorrhoea in men who have sex with men (MSM) and heterosexual men and women (HMW) to calibrate a mathematical gonorrhoea transmission model...
July 26, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28746957/-need-for-information-about-medical-rehabilitation-of-persons-with-german-pension-insurance-a-written-survey
#20
Anna Lena Walther, Johannes Falk, Ruth Deck
Aim In order to acquire target group-specific information on rehabilitation for members of the German pension insurance, they were asked about their ideas about medical rehabilitation and desired information regarding subjects and kind of information transfer. Method The core of the project was a written survey of members of the German pension insurance. N=600 insured people were invited to participate in the study. The questionnaire was developed in a qualitative pre-study. Results N=196 questionnaires were evaluated...
July 26, 2017: Das Gesundheitswesen
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