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https://www.readbyqxmd.com/read/28222538/vps35-the-retromer-complex-and-parkinson-s-disease
#1
Erin T Williams, Xi Chen, Darren J Moore
Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson's disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identified to cause PD in multiple individuals and families worldwide. The exact molecular mechanism(s) by which VPS35 mutations induce progressive neurodegeneration in PD are not yet known. Understanding these mechanisms, as well as the perturbed cellular pathways downstream of mutant VPS35, is important for the development of appropriate therapeutic strategies...
February 8, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28222508/chronic-lithium-treatment-in-a-rat-model-of-basal-forebrain-cholinergic-depletion-effects-on-memory-impairment-and-neurodegeneration
#2
Francesca Gelfo, Debora Cutuli, Annalisa Nobili, Paola De Bartolo, Marcello D'Amelio, Laura Petrosini, Carlo Caltagirone
Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222492/discovery-of-mieap-regulated-mitochondrial-quality-control-as-a-new-function-of-tumor-suppressor-p53
#3
REVIEW
Yasuyuki Nakamura, Hirofumi Arakawa
The tumor suppressor p53 gene is frequently mutated in human cancers, and the p53 protein suppresses cancer. However, the mechanism behind the p53-mediated tumor suppression is still unclear. Recently, Mieap (the mitochondria-eating protein) was identified as a p53-inducible protein. Mieap induces the accumulation of lysosomal proteins within mitochondria (MALM: Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage, and eliminates the oxidized mitochondrial proteins to repair unhealthy mitochondria...
February 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#4
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28221867/osimertinib-in-pretreated-t790m-positive-advanced-non-small-cell-lung-cancer-aura-study-phase-ii-extension-component
#5
James Chih-Hsin Yang, Myung-Ju Ahn, Dong-Wan Kim, Suresh S Ramalingam, Lecia V Sequist, Wu-Chou Su, Sang-We Kim, Joo-Hang Kim, David Planchard, Enriqueta Felip, Fiona Blackhall, Daniel Haggstrom, Kiyotaka Yoh, Silvia Novello, Kathryn Gold, Tomonori Hirashima, Chia-Chi Lin, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Pasi A Jänne
Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28221865/cost-effectiveness-of-immune-checkpoint-inhibition-in-braf-wild-type-advanced-melanoma
#6
Christine G Kohn, Simon B Zeichner, Qiushi Chen, Alberto J Montero, Daniel A Goldstein, Christopher R Flowers
Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28221732/facile-fabrication-of-aie-active-fluorescent-polymeric-nanoparticles-with-ultra-low-critical-micelle-concentration-based-on-ce-iv-redox-polymerization-for-biological-imaging-applications
#7
Qing Wan, Dazhuang Xu, Liucheng Mao, Ziyang He, Guangjian Zeng, Yingge Shi, Fengjie Deng, Meiying Liu, Xiaoyong Zhang, Yen Wei
Fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) property have received increasing attention and possess promising biomedical application potential in the recent years. Many efforts have been devoted to the fabrication methodologies of FPNs and significant advance has been achieved. In this contribution, a novel strategy for the fabrication of AIE-active amphiphilic copolymers is reported for the first time based on the Ce(IV) redox polymerization. As an example, ene group containing AIE-active dye (named as Phe-alc) is directly grafted onto a water soluble polymer polyethylene glycol (PEG) in H2 O/THF system under low temperature...
February 21, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28221724/novel-pieces-for-the-emerging-picture-of-sulfoximines-in-drug-discovery-synthesis-and-evaluation-of-sulfoximine-analogues-of-marketed-drugs-and-advanced-clinical-candidates
#8
Ulrich Lücking, Juan Alberto Sirvent
Sulfoximines have gained considerable recognition as an important structural motif in drug discovery of late. In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan-CDK inhibitor), BAY 1143572 (PTEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention. Whilst the interest in this underrepresented functional group in drug discovery is clearly on the rise, there remains an incomplete understanding of the medicinal chemistry relevant properties of sulfoximines...
February 21, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28221708/improved-management-of-small-pelagic-fisheries-through-seasonal-climate-prediction
#9
Désirée Tommasi, Charles A Stock, Kathleen Pegion, Gabriel A Vecchi, Richard D Methot, Michael A Alexander, David M Checkley
Populations of small pelagic fish are strongly influenced by climate. The inability of managers to anticipate environment-driven fluctuations in stock productivity or distribution can lead to overfishing and stock collapses, inflexible management regulations inducing shifts in the functional response to human predators, lost opportunities to harvest populations, bankruptcies in the fishing industry, and loss of resilience in the human food supply. Recent advances in dynamical global climate prediction systems allow for sea surface temperature (SST) anomaly predictions at a seasonal scale over many shelf ecosystems...
October 12, 2016: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28221385/ir-spectroscopic-investigations-of-chemical-and-photochemical-reactions-on-metal-oxides-bridging-the-materials-gap
#10
REVIEW
Yuemin Wang, Christof Wöll
In this review, we highlight recent progress (2008-2016) in infrared reflection absorption spectroscopy (IRRAS) studies on oxide powders achieved by using different types of metal oxide single crystals as reference systems. Precise polarization- and azimuth-dependent IRRAS data recorded for single crystal substrates has allowed for fundamental insights into the surface chemistry and photochemistry of numerous probe molecules on various surfaces exposed by three very important metal oxides (ZnO, TiO2, and CeO2)...
February 21, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28221262/recent-advances-in-computed-tomographic-technology-cardiopulmonary-imaging-applications
#11
Azadeh Tabari, Roberto Lo Gullo, Venkatesh Murugan, Alexi Otrakji, Subba Digumarthy, Mannudeep Kalra
Cardiothoracic diseases result in substantial morbidity and mortality. Chest computed tomography (CT) has been an imaging modality of choice for assessing a host of chest diseases, and technologic advances have enabled the emergence of coronary CT angiography as a robust noninvasive test for cardiac imaging. Technologic developments in CT have also enabled the application of dual-energy CT scanning for assessing pulmonary vascular and neoplastic processes. Concerns over increasing radiation dose from CT scanning are being addressed with introduction of more dose-efficient wide-area detector arrays and iterative reconstruction techniques...
March 2017: Journal of Thoracic Imaging
https://www.readbyqxmd.com/read/28221219/improving-the-evaluation-and-diagnosis-of-clinically-significant-prostate-cancer-in-2017
#12
Sigrid V Carlsson, Monique J Roobol
PURPOSE OF REVIEW: To provide an overview of the current state of the evidence and highlight recent advances in the evaluation and diagnosis of clinically significant prostate cancer, focusing on biomarkers, risk calculators and multiparametric MRI (mpMRI). RECENT FINDINGS: In 2017 there are numerous options to improve early detection as compared to a purely prostate-specific antigen (PSA)-based approach. All have strengths and drawbacks. In addition to repeating the PSA and performing clinical work-up (digital rectal examination and estimation of prostate volume), additional tests investigated in the initial biopsy setting are: %free PSA, Prostate Health Index, 4-kallikrein score, SelectMDx, and Michigan Prostate Score and in the repeat setting: %free PSA, Prostate Health Index, 4-kallikrein score, Prostate Cancer Antigen 3, and ConfirmMDx...
February 17, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28221171/pathogenesis-of-severe-pneumonia-advances-and-knowledge-gaps
#13
Joseph P Mizgerd
PURPOSE OF REVIEW: Pneumonia is a common disease that becomes severe in a subset of patients, dependent on host biology including mechanisms of immune resistance and tissue resilience. This review emphasizes discoveries in pneumonia biology from 2016, highlighting questions and directions that are especially pressing or newly emerging. RECENT FINDINGS: Novel cell-cell interactions mediating innate immune responses against microbes in the lung have been elucidated, between distinct leukocyte subtypes as well as between leukocytes and the structural cells of the lung...
February 17, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28221157/minimally-invasive-pcnl-mip
#14
Stefano Paolo Zanetti, Luca Boeri, Andrea Gallioli, Michele Talso, Emanuele Montanari
Miniaturized percutaneous nephrolithotomy (mini-PCNL) has increased in popularity in recent years and is now widely used to overcome the therapeutic gap between conventional PCNL and less-invasive procedures such as shock wave lithotripsy (SWL) or flexible ureterorenoscopy (URS) for the treatment of renal stones. However, despite its minimally invasive nature, the superiority in terms of safety, as well as the similar efficacy of mini-PCNL compared to conventional procedures, is still under debate. The aim of this chapter is to present one of the most recent advancements in terms of mini-PCNL: the Karl Storz "minimally invasive PCNL" (MIP)...
January 2017: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/28221138/-epidemiology-of-urinary-lithiasis-in-spain-new-scenarios
#15
Julia Carrasco Valiente, Enrique Gómez Gómez, María José Requena Tapia
Renal lithiasis is one of the most common disorders in modern society, constituting an important health problem that associates a great economic burden. The nature of stone disease varies according to age and sex, being also influenced by dietary and lifestyle factors, and climatic variations among others. In spite of the advances made in the management of this pathology, it continues being a disease with a high recurrence rate. In recent years, several studies have pointed out that its prevalence is rising especially in developed countries...
January 2017: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/28221067/ethical-concerns-for-telemental-health-therapy-amidst-governmental-surveillance
#16
Samuel D Lustgarten, Alexander J Colbow
Technology, infrastructure, governmental support, and interest in mental health accessibility have led to a burgeoning field of telemental health therapy (TMHT). Psychologists can now provide therapy via computers at great distances and little cost for parties involved. Growth of TMHT within the U.S. Department of Veterans Affairs and among psychologists surveyed by the American Psychological Association (APA) suggests optimism in this provision of services (Godleski, Darkins, & Peters, 2012; Jacobsen & Kohout, 2010)...
February 2017: American Psychologist
https://www.readbyqxmd.com/read/28220995/development-of-hydrogels-for-regenerative-engineering
#17
REVIEW
Xiaofei Guan, Meltem Avci-Adali, Emine Alarçin, Hao Cheng, Sara Saheb Kashaf, Yuxiao Li, Aditya Chawla, Hae Lin Jang, Ali Khademhosseini
The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale...
February 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28220904/recent-advances-in-occupational-and-environmental-health-hazards-of-workers-exposed-to-gasoline-compounds
#18
REVIEW
Christopher E Ekpenyong, Asuquo E Asuquo
The impact of health and environmental hazards, associated with the constituents of gasoline, on occupationally exposed workers has been recorded over the past few decades. However, the scientific literature on their pathogenic potential remains incomplete, which could affect the current understanding of the associated health risks. This review provides current information based on recently improved research techniques to evaluate gasoline toxicity profiles for humans. Our current knowledge provides insight into the intricate mechanism of gasoline-induced adverse effects, including the formation of reactive metabolites via bio-activation and subsequent generation of reactive oxygen species (ROS) and oxidative stress, which are involved in multiple mechanisms that are central to the aetiology of gasoline-induced toxicity...
February 21, 2017: International Journal of Occupational Medicine and Environmental Health
https://www.readbyqxmd.com/read/28220810/dengue-virus-ns1-protein-activates-immune-cells-via-tlr4-but-not-tlr2-or-tlr6
#19
Naphak Modhiran, Daniel Watterson, Antje Blumenthal, Alan G Baxter, Paul R Young, Katryn J Stacey
The secreted hexameric form of the dengue virus (DENV) non-structural protein 1 (NS1) has recently been shown to elicit inflammatory cytokine release and disrupt endothelial cell monolayer integrity. This suggests that circulating NS1 contributes to the vascular leak that plays a major role in the pathology of dengue haemorrhagic fever and shock. Pathways activated by NS1 are thus of great interest as potential therapeutic targets. Recent works have separately implicated both toll-like receptor 4 (TLR4) and the TLR2/6 heterodimer in immune cell activation by NS1...
February 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28220803/tcf7-is-suppressed-by-the-androgen-receptor-via-microrna-1-mediated-downregulation-and-is-involved-in-the-development-of-resistance-to-androgen-deprivation-in-prostate-cancer
#20
M K Siu, W-Y Chen, H-Y Tsai, H-Y Chen, J J Yin, C-L Chen, Y-C Tsai, Y-N Liu
BACKGROUND: Resistance to androgen deprivation therapy (ADT) represents a key step in the malignant progression of prostate cancer, and mutation to androgen receptor (AR) is one major driver to an androgen-independent phenotype. However, alternative oncogenic pathways that bypass AR signaling have emerged as an important mechanism promoting resistance to ADT. It is known that AR activation can prevent the interaction between β-catenin and T cell factor/lymphoid enhancer-binding factor (TCF/LEF) family, inhibiting the Wnt signaling pathway...
February 21, 2017: Prostate Cancer and Prostatic Diseases
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