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https://www.readbyqxmd.com/read/28324299/fatal-familial-insomnia-clinical-aspects-and-molecular-alterations
#1
REVIEW
Franc Llorens, Juan-José Zarranz, Andre Fischer, Inga Zerr, Isidro Ferrer
PURPOSE OF REVIEW: Fatal familiar insomnia (FFI) is an autosomal dominant inherited prion disease caused by D178N mutation in the prion protein gene (PRNP D178N) accompanied by the presence of a methionine at the codon 129 polymorphic site on the mutated allele. FFI is characterized by severe sleep disorder, dysautonomia, motor signs and abnormal behaviour together with primary atrophy of selected thalamic nuclei and inferior olives, and expansion to other brain regions with disease progression...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28323974/phenotypic-spectrum-in-osteogenesis-imperfecta-due-to-mutations-in-tmem38b-unravelling-a-complex-cellular-defect
#2
Emma A Webb, Meena Balasubramanian, Nadja Fratzl-Zelman, Wayne A Cabral, Hannah Titheradge, Atif Alsaedi, Vrinda Saraff, Julie Vogt, Trevor Cole, Susan Stewart, Nicola J Crabtree, Brandi M Sargent, Sonja Gamsjaeger, Eleftherios P Paschalis, Paul Roschger, Klaus Klaushofer, Nick J Shaw, Joan C Marini, Wolfgang Högler
Context: Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Objectives: Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting: Natural history study in paediatric research centres. Patients: Eight patients with type XIV OI. Main Outcome Measures: Clinical examinations included: bone mineral density, radiographs, echocardiography and muscle biopsy...
March 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323756/tdf-associated-renal-tubular-dysfunction-non-invasive-assessment-of-mitochondrial-injury
#3
Ryan Samuels, Carla Roca Bayerri, John A Sayer, D Ashley Price, Brendan Ai Payne
OBJECTIVE: To determine whether TDF-associated renal tubular dysfunction is associated with evidence of mitochondrial injury in urine. DESIGN: Single centre cross-sectional observational study of HIV positive outpatients. METHODS: Biochemistry was performed on paired serum and urine samples. Mitochondrial DNA (mtDNA) was studied by real-time PCR and long-range PCR on cellular fractions of urine. RESULTS: 48 subjects were enrolled of whom half were TDF-treated...
March 18, 2017: AIDS
https://www.readbyqxmd.com/read/28320095/dt-13-a-saponin-monomer-13-of-the-dwarf-lilyturf-tuber-synergized-with-vinorelbine-to-induce-mitotic-arrest-via-activation-of-erk-signaling-pathway-in-nci-h1299-cells
#4
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319565/bone-marrow-graft-versus-host-disease-in-major-histocompatibility-complex-matched-murine-reduced-intensity-allogeneic-hemopoietic-cell-transplantation
#5
Kifah Shahin, Zamil Mattar, Pablo Silveira, Wei-Hsun Hsu, Linda Bendall, Derek Hart, Kenneth F Bradstock
BACKGROUND: Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced intensity conditioning (RIC) instead of myeloablative (MAC) conditioning, however, the biology underlying this treatment remains incompletely understood. METHODS: We investigated a murine model of major histocompatibility complex (MHC)-matched multiple minor histocompatibility antigen mismatched alloHCT, using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28319473/precision-medicine-in-asthma-the-role-of-bronchial-thermoplasty
#6
Amber J Oberle, Praveen Mathur
PURPOSE OF REVIEW: The inflammatory makeup of severe asthma is heterogeneous. Identification of the predominant cellular endotype via biomarkers can aid in the selection of more advanced therapies. This review is clinically focused on how to use these biomarkers to help select between biologic agents and/or bronchial thermoplasty. RECENT FINDINGS: Several Th2 biomarkers exist for the detection of eosinophilic disease; however, the best biomarker for clinical practice is debatable depending upon local resources...
March 17, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28319113/combinatorial-crispr-cas9-screens-for-de-novo-mapping-of-genetic-interactions
#7
John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih-Chung Kuo, Dan Du, Assen Roguev, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies...
March 20, 2017: Nature Methods
https://www.readbyqxmd.com/read/28319015/collection-storage-inspection-and-quality-control-of-platelet-concentrates-obtained-by-apheresis-the-situation-in-spain
#8
Azucena Castrillo, Teresa Jimenez-Marco, José L Arroyo, María L Jurado, Luis Larrea, Rosa M Maymo, Jorge Monge, Carmen Muñoz, Ángel Pajares, Marta Yáñez
BACKGROUND: Diverse variables are involved in apheresis platelet collection, processing and storage. This survey shows how these are realized in Spain. METHOD: An analysis of collected data was performed in a questionnaire completed by ten Transfusion Centers (TC) which perform between 50 and 520 apheresis procedures per month. This information comprises the procedures used to collect, inspect and store apheresis platelet concentrates (PC), and quality control data...
February 22, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28318914/systemic-and-network-functions-of-the-microtubule-associated-protein-tau-implications-for-tau-based-therapies
#9
REVIEW
Lidia Bakota, Abdala Ussif, Gunnar Jeserich, Roland Brandt
Tau is a microtubule-associated neuronal protein, whose primary role was long thought to regulate axonal microtubule assembly. Tau is subject to many posttranslational modifications and can aggregate into neurofibrillary tangles, which are considered to be a hallmark of several neurodegenerative diseases collectively called "tauopathies". The most common tauopathy is Alzheimer's disease, where tau pathology correlates with sites of neurodegeneration. Tau belongs to the class of intrinsically disordered proteins, which are known to interact with many partners and are considered to be involved in various signaling, regulation and recognition processes...
March 16, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28317394/an-update-on-the-pathophysiology-and-management-of-polycystic-liver-disease
#10
May Yw Wong, Geoffrey W McCaughan, Simone I Strasser
Polycystic liver disease (PLD) is characterized by the presence of multiple cholangiocyte-derived hepatic cysts that progressively replace liver tissue. They are classified as an inherited ciliopathy /cholangiopathy as pathology exists at the level of the primary cilia of cholangiocytes. Aberrant expression of the proteins in primary cilia can impair their structures and functions, thereby promoting cystogenesis. Areas covered: This review begins by looking at the epidemiology of PLD and its natural history...
March 18, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28317340/production-of-pancreatic-progenitor-cells-from-human-induced-pluripotent-stem-cells-using-a-three-dimensional-suspension-bioreactor-system
#11
Yuichiro Mihara, Katsuhisa Matsuura, Yoshihiro Sakamoto, Teruo Okano, Norihiro Kokudo, Tatsuya Shimizu
Islet replacement is a promising strategy for the treatment of patients with type 1 diabetes and patients who have undergone total pancreatectomy. Recent progress in cellular reprogramming technology may allow the transplantation of a patient's own pancreatic cells. Although many studies have reported the differentiation of pancreatic progenitor cells from mouse and human pluripotent stem cells (PSCs), obtaining sufficient cell numbers for clinical applications remains problematic. Here, we describe the mass production of human pancreatic progenitor cells from human induced (i)PSCs using a three-dimensional suspension bioreactor system...
March 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28316878/report-on-the-national-eye-institute-audacious-goals-initiative-replacement-of-retinal-ganglion-cells-from-endogenous-cell-sources
#12
Monica L Vetter, Peter F Hitchcock
This report emerges from a workshop convened by the National Eye Institute (NEI) as part of the "Audacious Goals Initiative" (AGI). The workshop addressed the replacement of retinal ganglion cells (RGCs) from exogenous and endogenous sources, and sought to identify the gaps in our knowledge and barriers to progress in devising cellular replacement therapies for diseases where RGCs die. Here, we briefly review relevant literature regarding common diseases associated with RGC death, the genesis of RGCs in vivo, strategies for generating transplantable RGCs in vitro, and potential endogenous cellular sources to regenerate these cells...
March 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28315704/interleukin-6-and-prostate-cancer-current-developments-and-unsolved-questions
#13
Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models...
March 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28315669/cell-survival-interplay-between-hypoxia-and-pre-mrna-splicing
#14
Arvydas Kanopka
RNA splicing takes place in the nucleus and occurs either coor post-transcriptionally. Noncoding sequences (introns) in nuclear mRNA precursors (pre-mRNA) are removed by dedicated splicing machinery. The coding sequences (exons) are joined to generate the mature mRNA that is exported to the cytoplasm and translated into protein. Splicing events are tissue-specific. This process plays an important role in cellular differentiation and organism development. The splicing machinery heavily contributes to biological complexity and especially to the ability of cells to adapt to different developmental stages and altered cellular conditions...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28315483/functional-proteomic-analysis-of-corticosteroid-pharmacodynamics-in-rat-liver-relationship-to-hepatic-stress-signaling-energy-regulation-and-drug-metabolism
#15
Vivaswath S Ayyar, Richard R Almon, Debra C DuBois, Siddharth Sukumaran, Jun Qu, William J Jusko
Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL)...
March 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28315304/sphingosine-1-phosphate-a-double-edged-sword-in-the-brain
#16
REVIEW
Indulekha Karunakaran, Gerhild van Echten-Deckert
The physiological functions of sphingosine 1-phosphate (S1P) and its pathological roles in various diseases are increasingly being elucidated. Particularly, a growing body of literature has implicated S1P in the pathogenesis of brain related disorders. With the deciphering of more intricate aspects of S1P signalling, there is also a need to reconsider the notion of S1P only as a determinant of cell survival and proliferation. Further the concept of 'S1P-ceramide' balance as the controlling switch of cellular fate and functions needs to be refined...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315228/clinical-value-of-monoclonal-antibodies-and-tyrosine-kinase-inhibitors-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#17
REVIEW
Wiktoria Blaszczak, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28315121/untangling-the-biology-of-genetic-cardiomyopathies-with-pluripotent-stem-cell-disease-models
#18
REVIEW
Jan W Buikema, Sean M Wu
PURPOSE OF REVIEW: Recently, the discovery of strategies to reprogram somatic cells into induced pluripotent stem (iPS) cells has led to a major paradigm change in developmental and stem cell biology. The application of iPS cells and their cardiac progeny has opened novel directions to study cardiomyopathies at a cellular and molecular level. This review discusses approaches currently undertaken to unravel known inherited cardiomyopathies in a dish. RECENT FINDINGS: With improved efficiency for mutation correction by genome editing, human iPS cells have now provided a platform to untangle the biology of cardiomyopathies...
April 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28314989/inhibition-of-got1-sensitizes-colorectal-cancer-cells-to-5-fluorouracil
#19
Chengyu Hong, Jian Zheng, Xiaoling Li
PURPOSE: Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined. METHODS: HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28314835/endocrine-therapy-in-the-current-management-of-postmenopausal-estrogen-receptor-positive-metastatic-breast-cancer
#20
Virginia G Kaklamani, William J Gradishar
Metastatic breast cancer (MBC) results in substantial morbidity and mortality for women afflicted with this disease. A majority of MBCs are hormone-responsive and estrogen receptor-positive, making endocrine therapy (ET) an integral component of systemic therapy. With a primary goal of minimizing the effects of estrogen on hormone-responsive MBC, ETs are among the first targeted treatments that aim to inhibit the influence of estrogen receptor activation on tumor proliferation. Several biochemical mechanisms have been the focus of drug development for treatment, including selective estrogen-receptor modulation, aromatase inhibition, and selective estrogen-receptor degradation...
March 17, 2017: Oncologist
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