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Akira Minami, Masakazu Saito, Shou Mamada, Daisuke Ieno, Tomoya Hikita, Tadanobu Takahashi, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialic acid bound to glycans in glycolipids and glycoproteins is essential for synaptic plasticity and memory. Sialidase (EC, which has 4 isozymes including Neu1, Neu2, Neu3 and Neu4, regulates the sialylation level of glycans by removing sialic acid from sialylglycoconjugate. In the present study, we investigated the distribution of sialidase activity in rat hippocampus and the role of sialidase in hippocampal memory processing. We previously developed a highly sensitive histochemical imaging probe for sialidase activity, BTP3-Neu5Ac...
2016: PloS One
Carlo Bianca, Annie Lemarchand
In order to mimic the interactions between cancer and the immune system at cell scale, we propose a minimal model of cell interactions that is similar to a chemical mechanism including autocatalytic steps. The cells are supposed to bear a quantity called activity that may increase during the interactions. The fluctuations of cell activity are controlled by a so-called thermostat. We develop a kinetic Monte Carlo algorithm to simulate the cell interactions and thermalization of cell activity. The model is able to reproduce the well-known behavior of tumors treated by immunotherapy: the first apparent elimination of the tumor by the immune system is followed by a long equilibrium period and the final escape of cancer from immunosurveillance...
October 21, 2016: Journal of Chemical Physics
Berhane Ghebrehiwet, Allen P Kaplan, Kusumam Joseph, Ellinor I B Peerschke
The blood plasma contains four biologically important proteolytic cascades, which probably evolved from the same ancestral gene. This in part may explain why each cascade has very similar "initiating trigger" followed by sequential and cascade-like downstream enzymatic activation pattern. The four cascades are: the complement system, the blood clotting cascade, the fibrinolytic system, and the kallikrein-kinin system. Although much has been written about the interplay between all these enzymatic cascades, the cross-talk between the complement and the kinin generating systems has become particularly relevant as this interaction results in the generation of nascent molecules that have significant impact in various inflammatory diseases including angioedema and cancer...
November 2016: Immunological Reviews
T O Roy-Layinde, J A Laoye, O O Popoola, U E Vincent
The phenomenon of vibrational resonance (VR) is examined and analyzed in a bi-harmonically driven two-fluid plasma model with nonlinear dissipation. An equation for the slow oscillations of the system is analytically derived in terms of the parameters of the fast signal using the method of direct separation of motion. The presence of a high frequency externally applied electric field is found to significantly modify the system's dynamics, and consequently, induce VR. The origin of the VR in the plasma model has been identified, not only from the effective plasma potential but also from the contributions of the effective nonlinear dissipation...
September 2016: Chaos
Alexander O Vargas, Quirin Krabichler, Carlos Guerrero-Bosagna
Paul Kammerer was the most outstanding neo-Lamarckian experimentalist of the early 20th century. He reported spectacular results in the midwife toad, including crosses of environmentally modified toads with normal toads, where acquired traits were inherited in Mendelian fashion. Accusations of fraud generated a great scandal, ending with Kammerer's suicide. Controversy reignited in the 1970s, when journalist Arthur Koestler argued against these accusations. Since then, others have argued that Kammerer's results, even if real, were not groundbreaking and could be explained by somatic plasticity, inadvertent selection, or conventional genetics...
October 26, 2016: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Y-Q He, X-Q Lang, L Lin, L Ji, X-Y Yuan, Q Chen, Y-M Ran, H-S Chen, L Li, J-M Wang, Z-G Wang, H Gregersen, D-W Zou, H-P Liang, M Yang
BACKGROUND: Patients with posttraumatic stress disorder (PTSD) often share co-morbidity with chronic pain conditions. Recent studies suggest a role of P2X3 receptors and ATP signaling in pain conditions. However, the underlying mechanisms of visceral hyperalgesia following exposure to PTSD-like stress conditions remain unclarified. METHODS: The behavior and hormones relevant for PTSD were studied. Visceromotor responses (VMR) and the abdominal withdrawal reflexes (AWR) to colorectal distention (CRD) were recorded to determine P2X3-receptor-mediated alteration of hyperalgesia following single-prolonged stress (SPS) exposure...
October 25, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Jeymohan Joseph, Paola Cinque, Deborah Colosi, Ameet Dravid, Luminita Ene, Howard Fox, Dana Gabuzda, Magnus Gisslen, Sarah Beth Joseph, Scott Letendre, Shibani S Mukerji, Avindra Nath, Ignacio Perez-Valero, Deborah Persaud, Richard W Price, Vasudev R Rao, Ned Sacktor, Ronald Swanstrom, Alan Winston, Valerie Wojna, Edwina Wright, Serena Spudich
CSF HIV escape is a recently recognised phenomenon that suggests that despite suppressive treatment, HIV RNA may be detected in the CNS compartment in some individuals. In rare cases this is associated with clinical neurological disease, while in most cases, neurological consequences are not apparent. Attempts at characterising the biological substrates of CSF escape and further investigating the neurological consequences need to be made to better understand the implications of this condition for the HIV cure agenda as well as for clinical outcomes...
October 5, 2016: Journal of Virus Eradication
Raul G Nogueira, Osama O Zaidat, Alicia C Castonguay, Diogo C Haussen, Coleman O Martin, William E Holloway, Nils Mueller-Kronast, Joey English, Italo Linfante, Guilherme Dabus, Tim W Malisch, Franklin A Marden, Hormozd Bozorgchami, Andrew Xavier, Ansaar T Rai, Michael T Froehler, Aamir Badruddin, Thanh N Nguyen, M Asif Taqi, Michael G Abraham, Vallabh Janardhan, Albert J Yoo, Hashem Shaltoni, Alex Abou-Chebl, Peng R Chen, Gavin W Britz, Roberta Novakovic, Ashish Nanda, Ritesh Kaushal, Mohammad A Issa, Michael R Frankel, Rishi Gupta
BACKGROUND: The Interventional Management of Stroke III (IMS-III) trial demonstrated no benefit for intravenous recombinant tissue plasminogen activator (IV rt-PA) followed by endovascular therapy versus IV rt-PA alone. However, IMS-III mostly included earlier generation devices. The recent thrombectomy trials have incorporated the stent-retriever technology, but their generalizability remains unknown. METHODS: The North American Solitaire Acute Stroke (NASA) registry recruited patients treated with the Solitaire FR™ device between March 2012 and February 2013...
September 2016: Interventional Neurology
Meng Wang, Ying Li, Mingyi HuangFu, Yi Xiao, Tianyuan Zhang, Min Han, Donghang Xu, Fangyuan Li, Daishun Ling, Yi Jin, Jianqing Gao
AIM: To design pluronic F68 (PF68)-conjugated polyamidoamine (PAMAM) dendrimer conjugates for doxorubicin (DOX) delivery for overcoming multidrug resistance, and clarify the reversal mechanism. MATERIALS & METHODS: A series of PAMAM-PF68 conjugates were designed. The antitumor activity of the DOX-loaded conjugates was evaluated against MCF-7/ADR cells, tumor spheroids and tumors. Several bioinformatics were detected to characterize the reversal mechanism. RESULTS: Increased antitumor activity of the DOX-loaded conjugates was achieved in vitro and in vivo...
October 26, 2016: Nanomedicine
Gizem Ölmezer, Maryna Levikova, Dominique Klein, Benoît Falquet, Gabriele Alessandro Fontana, Petr Cejka, Ulrich Rass
Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2...
October 25, 2016: Nature Communications
Akihiro Nishio, Ryo Horita, Tadahiro Sado, Seiko Mizutani, Takahiro Watanabe, Ryosuke Uehara, Mayumi Yamamoto
AIMS: Many studies have reported that the prevalence of mental illness and cognitive disability is higher among homeless individuals compared to the general population, and the rates of mental illness among the homeless population have recently increased. This study compared causes of homelessness or barriers to escaping homelessness for people with/without mental illness/cognitive disability, revealed problems with the Japanese homeless policy, and proposed an effective and necessary support system...
October 24, 2016: Psychiatry and Clinical Neurosciences
Armando Arias, Lucy Thorne, Elsa Ghurburrun, Dalan Bailey, Ian Goodfellow
Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase fidelity can also impact virus transmission between susceptible hosts...
September 2016: MSphere
Shaw D Bamber, Stig Westerlund
Sub-sea geological storage of carbon dioxide (CO2) provides a viable option for the Carbon Capture and Storage (CCS) approach for reducing atmospheric emissions of this greenhouse gas. Although generally considered to offer a low risk of major leakage, it remains relevant to establish the possible consequences for marine organisms that live in or on sediments overlying these storage areas if such an event may occur. The present study has used a series of laboratory exposures and behavioral bioassays to establish the sensitivity of Arctica islandica to simulated leakages of CO2...
October 11, 2016: Aquatic Toxicology
Matthias Kohl, Andreas Härtel, Michael Schmiedeberg
The slow dynamics in a glassy hard-sphere system is dominated by cage breaking events, i.e. rearrangements where a particle escapes from the cage formed by its neighboring particles. We study such events for an overdamped colloidal system by the means of Brownian dynamics simulations. While it is difficult to relate cage breaking events to structural mean field results in bulk, we show that the microscopic dynamics of particles close to a wall can be related to the anisotropic two-particle density. In particular, we study cage-breaking trajectories, mean forces on a tracked particle, and the impact of the history of trajectories...
October 24, 2016: Journal of Physics. Condensed Matter: An Institute of Physics Journal
Theresa L Whiteside
Tumor-derived exosomes (TEX) are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions...
October 20, 2016: Vaccines
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Hagop S Akiskal
What I uttered in Athens moved with apparent emotion [that seem to have not escaped Jules Angst's concern] was spontaneous, except for what is printed in the program book, which has somehow vanished from my office, unlike him with his larger than life figure whose memory will live for as long as he lives in the minds and hearts of all those who were privileged to be his family, colleagues, patients, friends, and… countless others, plus those whose email addresses I cannot locate right now sitting in the sunshine of La Jolla-far away from my loved ones-and wondering what ethnic, genetic and environmental factors-perhaps even several Greek gods combined-to produce the original mind and heart of our Athenian friend who, nonetheless, lived in Rome-and now resting not in the 'atheist' cemetery [it took me 5 minutes to spell this word]-but in our hearts for as long as they will beat-perhaps eventually in another realm, 'from whose bourn'-according to Hamlet-no one has ever returned-that's the promise of the Eternal City-where Athanasios is lying...
October 21, 2016: Current Neuropharmacology
Marta Canuti, Kimberly E O'Leary, Bruce D Hunter, Grant Spearman, Davor Ojkic, Hugh G Whitney, Andrew S Lang
Aleutian mink disease virus (AMDV) causes plasmacytosis, an immune complex-associated syndrome that affects wild and farmed mink. The virus can also infect other small mammals (e.g., ferrets, skunks, ermines, and raccoons), but the disease in these hosts has been studied less. In 2007, a mink plasmacytosis outbreak began on the Island of Newfoundland, and the virus has been endemic in farms since then. In this study, we evaluated the molecular epidemiology of AMDV in farmed and wild animals of Newfoundland since before the beginning of the outbreak and investigated the epidemic in a global context by studying AMDV worldwide, thereby examining its diffusion and phylogeography...
January 2016: Virus Evolution
Jean-Pierre Routy, Bertrand Routy, Gina M Graziani, Vikram Mehraj
The term "immune privilege" was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege...
2016: International Journal of Tryptophan Research: IJTR
Lou-Yan Ma, Ya-Li Lv, Kang Huo, Jie Liu, Su-Hang Shang, Yu-Lang Fei, Yan-Bo Li, Bei-Yu Zhao, Meng Wei, Yong-Ning Deng, Qiu-Min Qu
β-Amyloid (Aβ) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aβ deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aβ1-42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p<0...
October 20, 2016: Behavioural Brain Research
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