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https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#1
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28088067/tuning-neural-circuits-by-turning-the-interneuron-knob
#2
REVIEW
Nathalie Dehorter, Nicolás Marichal, Oscar Marín, Benedikt Berninger
Interneurons play a critical role in sculpting neuronal circuit activity and their dysfunction can result in neurological and neuropsychiatric disorders. To temporally structure and balance neuronal activity in the adult brain interneurons display a remarkable degree of subclass-specific plasticity, of which the underlying molecular mechanisms have recently begun to be elucidated. Grafting new interneurons to pre-existing neuronal networks allows for amelioration of circuit dysfunction in rodent models of neurological disease and can reopen critical windows for circuit plasticity...
January 11, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#3
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28087949/the-vaginal-microbiota-and-urinary-tract-infection
#4
Ann E Stapleton
The vagina is a key anatomical site in the pathogenesis of urinary tract infection (UTI) in women, serving as a potential reservoir for infecting bacteria and a site at which interventions may decrease the risk of UTI. The vaginal microbiota is a dynamic and often critical factor in this pathogenic interplay, because changes in the characteristics of the vaginal microbiota resulting in the loss of normally protective Lactobacillus spp. increase the risk of UTI. These alterations may result from the influence of estrogen deficiency, antimicrobial therapy, contraceptives, or other causes...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087944/laboratory-diagnosis-and-susceptibility-testing-for-mycobacterium-tuberculosis
#5
Gary W Procop
The laboratory, which utilizes some of the most sophisticated and rapidly changing technologies, plays a critical role in the diagnosis of tuberculosis. Some of these tools are being employed in resource-challenged countries for the rapid detection and characterization of Mycobacterium tuberculosis. Foremost, the laboratory defines appropriate specimen criteria for optimal test performance. The direct detection of mycobacteria in the clinical specimen, predominantly done by acid-fast staining, may eventually be replaced by rapid-cycle PCR...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087895/crohn-disease-risk-prediction-best-practices-and-pitfalls-with-exome-data
#6
Manuel Giollo, David T Jones, Marco Carraro, Emanuela Leonardi, Carlo Ferrari, Silvio C E Tosatto
The Critical Assessment of Genome Interpretation (CAGI) experiment is the first attempt to evaluate the state-of-the-art in genetic data interpretation. Among the proposed challenges, Crohn disease (CD) risk prediction has become the most classic problem spanning three editions. The scientific question is very hard: can anybody assess the risk to develop CD given the exome data alone? This is one of the ultimate goals of genetic analysis, which motivated most CAGI participants to look for powerful new methods...
January 13, 2017: Human Mutation
https://www.readbyqxmd.com/read/28087891/physical-activity-and-exercise-for-chronic-pain-in-adults-an-overview-of-cochrane-reviews
#7
REVIEW
Louise J Geneen, R Andrew Moore, Clare Clarke, Denis Martin, Lesley A Colvin, Blair H Smith
BACKGROUND: Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning...
January 14, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28087735/relationships-linking-emotional-motor-cognitive-and-gabaergic-dysfunctions-in-dystrophin-deficient-mdx-mice
#8
Cyrille Vaillend, Rémi Chaussenot
Alterations in the Duchenne muscular dystrophy (DMD) gene have been associated with enhanced stress reactivity in vertebrate species, suggesting a role for brain dystrophin in fear-related behavioral and cognitive processes. Because the loss of dystrophin (Dp427) reduces clustering of central GABAA receptors, it is suspected that local inhibitory tuning and modulation of neuronal excitability are perturbed in a distributed brain circuit that normally controls such critical behavioral functions. In this study we undertook a large-scale behavioral study to evaluate fear-related behavioral disturbances in dystrophin-deficient mdx mice...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087713/functional-genomics-reveals-that-tumors-with-activating-phosphoinositide-3-kinase-mutations-are-dependent-on-accelerated-protein-turnover
#9
Teresa Davoli, Kristen E Mengwasser, Jingjing Duan, Ting Chen, Camilla Christensen, Eric C Wooten, Anthony N Anselmo, Mamie Z Li, Kwok-Kin Wong, Kristopher T Kahle, Stephen J Elledge
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087669/the-role-of-the-p38-mnk-eif4e-signaling-axis-in-tnf-production-downstream-of-the-nod1-receptor
#10
Mikhail V Pashenkov, Lyudmila S Balyasova, Yulia A Dagil, Boris V Pinegin
Activation of nucleotide-binding oligomerization domain (NOD) 1 and NOD2 by muropeptides triggers a complex transcriptional program in innate immune cells. However, little is known about posttranscriptional regulation of NOD1- and NOD2-dependent responses. When stimulated with a prototypic NOD1 agonist, N-acetylglucosaminyl-N-acetylmuramyl-l-alanyl-d-isoglutamyl-meso-diaminopimelic acid (GM-triDAP), human monocyte-derived macrophages (MDM) produced an order of magnitude more TNF, IL-6, and pro-IL-1β than did monocyte-derived dendritic cells (MDDC), despite similar NOD1 expression, similar cytokine mRNA kinetics, and comparable responses to LPS...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087668/the-threshold-of-protection-from-liver-stage-malaria-relies-on-a-fine-balance-between-the-number-of-infected-hepatocytes-and-effector-cd8-t-cells-present-in-the-liver
#11
Alexandra J Spencer, Rhea J Longley, Anita Gola, Marta Ulaszewska, Teresa Lambe, Adrian V S Hill
Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8(+) T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8(+) T cell response in the liver following Plasmodium berghei sporozoite challenge...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087655/hagfish-houdinis-biomechanics-and-behavior-of-squeezing-through-small-openings
#12
Calli R Freedman, Douglas S Fudge
Hagfishes are able to squeeze through small openings to gain entry to crevices, burrows, hagfish traps, and carcasses, but little is known about how they do this, or what the limits of this ability are. The purpose of this study was to describe this ability, and to investigate possible mechanisms by which it is accomplished. We investigated the hypothesis that the passive movement of blood within a hagfish's flaccid subcutaneous sinus allows it to squeeze through narrow apertures that it would not be able to if it were turgid...
January 13, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28087636/r-spondin-1-is-required-for-specification-of-hematopoietic-stem-cells-through-wnt16-and-vegfa-signaling-pathways
#13
Jamie R Genthe, Wilson K Clements
Hematopoietic stem cells (HSCs) are the therapeutic component of bone marrow transplants, but finding immune-compatible donors limits treatment availability and efficacy. Recapitulation of endogenous specification during development is a promising approach to directing HSC specification in vitro, but current protocols are not capable of generating authentic HSCs with high efficiency. Across phyla, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta concurrent with arteriovenous specification and intersegmental vessel (ISV) sprouting, processes regulated by Notch and Wnt...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#14
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28087598/bayesian-network-inference-modeling-identifies-trib1-as-a-novel-regulator-of-cell-cycle-progression-and-survival-in-cancer-cells
#15
Rina Gendelman, Heming Xing, Olga K Mirzoeva, Preeti Sarde, Christina Curtis, Heidi Feiler, Paul McDonagh, Joe W Gray, Iya Khalil, W Michael Korn
Molecular networks governing cellular responses to targeted therapies are complex dynamic systems with non-intuitive behaviors. Here we applied a novel computational strategy to infer probabilistic causal relationships between network components based on gene expression. We constructed a model comprised of an ensemble of networks using multidimensional data from cell line models of cell cycle arrest caused by inhibition of MEK1/2. Through simulation of reverse-engineered Bayesian network modeling, we generated predictions of G1-S transition...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087544/children-s-experiences-of-chronic-fatigue-syndrome-myalgic-encephalomyelitis-cfs-me-a-systematic-review-and-meta-ethnography-of-qualitative-studies
#16
Roxanne M Parslow, Sarah Harris, Jessica Broughton, Adla Alattas, Esther Crawley, Kirstie Haywood, Alison Shaw
OBJECTIVE: To synthesis the qualitative studies of children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). DESIGN: Systematic review and meta-ethnography. BACKGROUND: CFS/ME is an important disabling illness, with uncertain cause and prognosis. As a result, children with CFS/ME can find themselves living with greater uncertainty and stigma, exacerbating the impact of the condition. There is a growing body of qualitative research in CFS/ME, yet there has been no attempt to systematically synthesis the studies involving children...
January 13, 2017: BMJ Open
https://www.readbyqxmd.com/read/28087511/invited-commentary-ambient-environment-and-the-risk-of-preterm-birth
#17
Sandie Ha, Pauline Mendola
Preterm birth is a common adverse birth outcome known to be associated with increased infant mortality, and it often results in a higher burden of offspring morbidity in both the short and long terms. The potential for environmental factors, particularly air pollution and meteorological parameters, to increase preterm birth risk has received significant attention worldwide, but the findings are generally inconsistent, with variations in study designs and methods across populations and geographic locations. In the current issue of the Journal, Giorgis-Allemand et al...
January 13, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28087483/cell-number-per-spheroid-and-electrical-conductivity-of-nanowires-influence-the-function-of-silicon-nanowired-human-cardiac-spheroids
#18
Yu Tan, Dylan Richards, Robert C Coyle, Jenny Yao, Ruoyu Xu, Wenyu Gou, Hongjun Wang, Donald R Menick, Bozhi Tian, Ying Mei
: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide an unlimited cell source to treat cardiovascular diseases, the leading cause of death worldwide. However, current hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087402/accuracy-is-in-the-eyes-of-the-pathologist-the-visual-interpretive-process-and-diagnostic-accuracy-with-digital-whole-slide-images
#19
Tad T Brunyé, Ezgi Mercan, Donald L Weaver, Joann G Elmore
Digital whole slide imaging is an increasingly common medium in pathology, with application to education, telemedicine, and rendering second opinions. It has also made it possible to use eye tracking devices to explore the dynamic visual inspection and interpretation of histopathological features of tissue while pathologists review cases. Using whole slide images, the present study examined how a pathologist's diagnosis is influenced by fixed case-level factors, their prior clinical experience, and their patterns of visual inspection...
January 10, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28087238/lymphocyte-circadian-clocks-control-lymph-node-trafficking-and-adaptive-immune-responses
#20
David Druzd, Olga Matveeva, Louise Ince, Ute Harrison, Wenyan He, Christoph Schmal, Hanspeter Herzel, Anthony H Tsang, Naoto Kawakami, Alexei Leliavski, Olaf Uhl, Ling Yao, Leif Erik Sander, Chien-Sin Chen, Kerstin Kraus, Alba de Juan, Sophia Martina Hergenhan, Marc Ehlers, Berthold Koletzko, Rainer Haas, Werner Solbach, Henrik Oster, Christoph Scheiermann
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes...
January 6, 2017: Immunity
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