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https://www.readbyqxmd.com/read/27914038/serotonin-5-ht6-receptor-antagonists-in-alzheimer-s-disease-therapeutic-rationale-and-current-development-status
#1
Hilda Ferrero, Maite Solas, Paul T Francis, Maria J Ramirez
Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Because of the lack of effective treatments for this illness, research focused on identifying compounds that restore cognition and functional impairments in patients with AD is a very active field. Since its discovery in 1993, the serotonin 5-HT6 receptor has received increasing attention, and a growing number of studies supported 5-HT6 receptor antagonism as a target for improving cognitive dysfunction in AD. This article reviews the rationale behind investigations into the targeting of 5-HT6 receptors as a symptomatic treatment for cognitive and/or behavioral symptoms of AD...
December 3, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27914000/from-transformation-to-metastasis-deconstructing-the-extracellular-matrix-in-breast-cancer
#2
Shelly Kaushik, Michael W Pickup, Valerie M Weaver
The extracellular matrix (ECM) is a guiding force that regulates various developmental stages of the breast. In addition to providing structural support for the cells, it mediates epithelial-stromal communication and provides cues for cell survival, proliferation, and differentiation. Perturbations in ECM architecture profoundly influence breast tumor progression and metastasis. Understanding how a dysregulated ECM can facilitate malignant transformation is crucial to designing treatments to effectively target the tumor microenvironment...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913798/generalizability-of-the-maximum-proportional-recovery-rule-to-visuospatial-neglect-early-poststroke
#3
Caroline Winters, Erwin E H van Wegen, Andreas Daffertshofer, Gert Kwakkel
Background and objective Proportional recovery of upper-extremity motor function and aphasia after stroke may suggest common mechanisms for spontaneous neurobiological recovery. This study aimed to investigate if the proportional recovery rule also applies to visuospatial neglect (VSN) in right-hemispheric first-ever ischemic stroke patients and explored the possible common underlying mechanisms. Methods Patients with upper-limb paresis and VSN were included. Recovery defined as the change in Letter Cancellation Test (LCT) score at ~8 days and 6 months poststroke...
December 2, 2016: Neurorehabilitation and Neural Repair
https://www.readbyqxmd.com/read/27913797/promoting-gait-recovery-and-limiting-neuropathic-pain-after-spinal-cord-injury-two-sides-of-the-same-coin
#4
Catherine Mercier, Meyke Roosink, Jason Bouffard, Laurent J Bouyer
Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems...
December 2, 2016: Neurorehabilitation and Neural Repair
https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#5
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913591/temporal-expectations-guide-dynamic-prioritization-in-visual-working-memory-through-attenuated-alpha-oscillations
#6
Freek van Ede, Marcel Niklaus, Anna C Nobre
: While working memory is generally considered a highly dynamic mnemonic store, popular laboratory tasks employed to understand its psychological and neural mechanisms (such as change detection and continuous reproduction) often remain relatively "static", involving the retention of a set number of items throughout a shared delay interval. In the current study, we investigated visual working memory in a more dynamic setting, and assessed: 1) whether internally guided temporal expectations can dynamically and reversibly prioritize individual mnemonic items at specific times at which they are deemed most relevant and 2) the neural substrates that support such dynamic prioritization...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913518/treatment-options-for-patients-with-myelodysplastic-syndromes-after-hypomethylating-agent-failure
#7
Hetty E Carraway
The treatment of patients with myelodysplastic syndromes (MDSs) has hinged primarily on supportive care (ie, blood transfusions, colony stimulating agents, iron chelation, etc.) and the US Food and Drug Administration-approved agents, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For patients no longer benefitting from these agents, there is a paucity of effective therapies. The challenges at this time include our limited understanding of the mechanisms of resistance to these therapies and the variables employed to select next best therapies for patients based on: (1) their performance status and medical comorbidities; (2) the molecular feature(s) of their MDS; (3) the prior treatments they have received; and (4) the long-term goal(s)/possibilities for their future treatment (ie, transplant vs no transplant)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913439/retinitis-pigmentosa-associated-cystoid-macular-oedema-pathogenesis-and-avenues-of-intervention
#8
REVIEW
S Strong, G Liew, M Michaelides
Hereditary retinal diseases are now the leading cause of blindness certification in the working age population (age 16-64 years) in England and Wales, of which retinitis pigmentosa (RP) is the most common disorder. RP may be complicated by cystoid macular oedema (CMO), causing a reduction of central vision. The underlying pathogenesis of RP-associated CMO (RP-CMO) remains uncertain, however, several mechanisms have been proposed, including: (1) breakdown of the blood-retinal barrier, (2) failure (or dysfunction) of the pumping mechanism in the retinal pigment epithelial, (3) Müller cell oedema and dysfunction, (4) antiretinal antibodies and (5) vitreous traction...
December 2, 2016: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/27913431/pro-brain-derived-neurotrophic-factor-probdnf-mediated-p75ntr-activation-promotes-depolarizing-actions-of-gaba-and-increases-susceptibility-to-epileptic-seizures
#9
Baptiste Riffault, Nazim Kourdougli, Camille Dumon, Nadine Ferrand, Emmanuelle Buhler, Fabienne Schaller, Caroline Chambon, Claudio Rivera, Jean-Luc Gaiarsa, Christophe Porcher
The brain-derived neurotrophic factor (BDNF) is synthesized as a precursor, namely proBDNF, which can be processed into mature BDNF (mBDNF). Evidences suggest that proBDNF signaling through p75(NTR) may account for the emergence of neurological disorders. These findings support the view that the relative availability of mBDNF and proBDNF forms is an important mechanism underlying brain circuit formation and cognitive functions. Here we describe novel insights into the proBDNF/p75(NTR) mechanisms and function in vivo in modulating neuronal circuit and synaptic plasticity during the first postnatal weeks in rats...
December 1, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27913418/a-novel-rhamnose-rich-hetero-exopolysaccharide-isolated-from-lactobacillus-paracasei-dg-activates-thp-1-human-monocytic-cells
#10
Silvia Balzaretti, Valentina Taverniti, Simone Guglielmetti, Walter Fiore, Mario Minuzzo, Hansel N Ngo, Judith B Ngere, Sohaib Sadiq, Paul N Humphreys, Andrew P Laws
: Lactobacillus paracasei DG is a bacterial strain with recognized probiotic properties and is used in commercial probiotic products. However, the mechanisms underlying its probiotic properties are mainly unknown. In this study, we tested the hypothesis that the capability of strain DG to interact with the host is, at least partly, associated with its ability to synthesize a surface-associated exopolysaccharide (EPS). Comparative genomics revealed the presence of putative EPS gene clusters in DG genome; accordingly, EPS was isolated from the surface of the bacterium...
December 2, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27913395/metabolomic-characterization-of-hepatocellular-carcinoma-in-patients-with-liver-cirrhosis-for-biomarker-discovery
#11
Cristina Di Poto, Alessia Ferrarini, Yi Zhao, Rency S Varghese, Chao Tu, Yiming Zuo, Minkun Wang, Mohammad R Nezami Ranjbar, Yue Luo, Chi Zhang, Chirag S Desai, Kirti Shetty, Mahlet G Tadesse, Habtom W Ressom
BACKGROUND: Metabolomics plays an important role in providing insight into the etiology and mechanisms of hepatocellular carcinoma (HCC). This is accomplished by a comprehensive analysis of patterns involved in metabolic alterations in human specimens. This study compares the levels of plasma metabolites in HCC cases versus cirrhotic patients and evaluates the ability of candidate metabolites in distinguishing the two groups. Also, it investigates the combined use of metabolites and clinical covariates for detection of HCC in patients with liver cirrhosis...
December 2, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27913196/nf-kb-regulated-exosomal-mir-155-promotes-the-inflammation-associated-with-arsenite-carcinogenesis
#12
Chao Chen, Fei Luo, Xinlu Liu, Lu Lu, Hui Xu, Qianlei Yang, Junchao Xue, Le Shi, Jun Li, Aihua Zhang, Qizhan Liu
In the cancer microenvironment, extracellular communication allows various types of cells to coordinate and execute biological functions. Emerging evidence indicates that exosomes, as mediators of cell communication, are involved in tumor progression. Little is known, however, about the mechanism by which exosomal miRNAs regulate inflammatory infiltration in arsenite-induced liver cancer. The present research aimed to determine if miRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 and THLE-3 cells, which are functionally active in the recipient cells...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913184/tolerance-of-hyperammonemia-in-brain-of-heteropneustes-fossilis-is-supported-by-glutamate-glutamine-cycle
#13
Suman Mishra, Rajnikant Mishra
This report presents analysis of molecular switches associated with tolerance to hyperammonemia in Heteropneustes fossilis because it tolerates about 100-fold more ammonia than mammals. Brains of Heteropneustes fossilis exposed to 100mM ammonium chloride were dissected after Zero hour as control, 16hrs and 20hrs exposure. The status of neuron and glia were analysed by Golgi staining, Luxol Fast Blue, and Nissl's staining. The expression patterns of genes associated to homeostasis of neuron and glia, management of oxidative stress and inflammation, ammonia metabolism and brain derived neurotrophic factor were analysed through reverse-transcriptase-polymerase chain reaction...
November 29, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27913118/forces-controlling-organ-growth-and-size
#14
REVIEW
Dominik Eder, Christof Aegerter, Konrad Basler
One of the fundamental questions in developmental biology is what determines the final size and shape of an organ. Recent research strongly emphasizes that besides cell-cell communication, biophysical principals govern organ development. The architecture and mechanics of a tissue guide cellular processes such as movement, growth or differentiation. Furthermore, mechanical cues do not only regulate processes at a cellular level but also provide constant feedback about size and shape on a tissue scale. Here we review several models and experimental systems which are contributing to our understanding of the roles mechanical forces play during organ development...
November 29, 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#15
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
November 29, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27912773/china-s-health-assistance-to-africa-opportunism-or-altruism
#16
REVIEW
Shuang Lin, Liangmin Gao, Melissa Reyes, Feng Cheng, Joan Kaufman, Wafaa M El-Sadr
China has made substantial health commitments to Africa in the past several decades. However, while much has been written regarding China-Africa aid overall, relatively little attention has been given to China's health aid. To better understand these investments, we provide an overview of the current framework and characteristics of China's health aid to Africa. China's health assistance has been perceived by some as opportunistic, largely as a demonstration of China's engagement in "soft power" and an attempt to enhance its access to natural resources and political favors by African countries...
December 3, 2016: Globalization and Health
https://www.readbyqxmd.com/read/27912202/bioresorbable-stents-current-and-upcoming-bioresorbable-technologies
#17
REVIEW
Hui Ying Ang, Heerajnarain Bulluck, Philip Wong, Subbu S Venkatraman, Yingying Huang, Nicolas Foin
Bioresorbable scaffolds (BRS) represent a novel horizon in interventional cardiology for the treatment of coronary artery disease. The technology was introduced to overcome limitations of current metallic drug-eluting stents such as late in-stent restenosis and permanently caging the vessel. The concept of the BRS is to provide temporal support to the vessel during healing before being degraded and resorbed by the body, promoting restoration of the vessel vasomotion. Currently, there are several BRS that are under development or already commercially available...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27911843/impact-of-the-gut-microbiota-on-enhancer-accessibility-in-gut-intraepithelial-lymphocytes
#18
Nicholas P Semenkovich, Joseph D Planer, Philip P Ahern, Nicholas W Griffin, Charles Y Lin, Jeffrey I Gordon
The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to define chromatin accessibility in predicted enhancer regions of intestinal αβ(+) and γδ(+) intraepithelial lymphocytes purified from germ-free mice, their conventionally raised (CONV-R) counterparts, and mice reared germ free and then colonized with CONV-R gut microbiota at the end of the suckling-weaning transition...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#19
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911807/enhanced-limonene-production-in-cyanobacteria-reveals-photosynthesis-limitations
#20
Xin Wang, Wei Liu, Changpeng Xin, Yi Zheng, Yanbing Cheng, Su Sun, Runze Li, Xin-Guang Zhu, Susie Y Dai, Peter M Rentzepis, Joshua S Yuan
Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
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