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Paulina R Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M Royer, Tina L Beckett, M Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L Sudduth, Wenjie Lou, Erin Abner, Richard Kryscio, Donna M Wilcock, Edward G Barrett, Elizabeth Head
Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer's disease. Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1-42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11-12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); and (4) ENR/VAC (E/V) and treated for 20 months...
September 26, 2016: Neurobiology of Aging
Jingchuan Guo, Akira Fujiyoshi, Kamal Masaki, Abhisek Vishnu, Aya Kadota, Emma J M Barinas-Mitchell, Takashi Hisamatsu, Vasudha Ahuja, Naoyuki Takashima, Rhobert W Evans, Bradley J Willcox, Katsuyuki Miura, Beatriz Rodriguez, Hirotsugu Ueshima, Lewis H Kuller, Akira Sekikawa
OBJECTIVE: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV). METHOD: Study participants (n = 656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan)...
October 20, 2016: Journal of Hypertension
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
Alexander Leithner, Alexander Eichner, Jan Müller, Anne Reversat, Markus Brown, Jan Schwarz, Jack Merrin, David J J de Gorter, Florian Schur, Jonathan Bayerl, Ingrid de Vries, Stefan Wieser, Robert Hauschild, Frank P L Lai, Markus Moser, Dontscho Kerjaschki, Klemens Rottner, J Victor Small, Theresia E B Stradal, Michael Sixt
Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation...
October 24, 2016: Nature Cell Biology
Vera Pader, Sanika Hakim, Kimberley L Painter, Sivaramesh Wigneshweraraj, Thomas B Clarke, Andrew M Edwards
Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA)(1,2). Although resistance is rare, treatment failure can occur in more than 20% of cases(3,4) and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S...
October 24, 2016: Nature Microbiology
Nuno Basílio, Sheiraz Al Bittar, Nathalie Mora, Olivier Dangles, Fernando Pina
3-Deoxyanthocyanidins and their O-β-d-glucosides are natural pigments abundant in black sorghum. O-glycosidation can perturb the acid-base properties of the chromophore and lower its electron density with a large impact on the distribution of colored and colorless forms in aqueous solution. In this work, the influence of O-glycosidation on color is systematically studied from a series of 3-deoxyanthocyanin analogs. The pH- and light-dependent reversible reactions of 7-β-d-glucopyranosyloxy-4'-hydroxyflavylium (P3) and 4'-β-d-glucopyranosyloxy-7-hydroxyflavylium (P5) were completely characterized in mildly acidic solution and compared with the parent aglycone 4',7-dihydroxyflavylium ion and the O-methylethers of P3 and P5...
October 20, 2016: International Journal of Molecular Sciences
M Kvandová, M Majzúnová, I Dovinová
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways...
October 24, 2016: Physiological Research
Andreas Widder, Christian Kuehn
In this paper, we focus on the influence of heterogeneity and stochasticity of the population on the dynamical structure of a basic susceptible-infected-susceptible (SIS) model. First we prove that, upon a suitable mathematical reformulation of the basic reproduction number, the homogeneous system and the heterogeneous system exhibit a completely analogous global behaviour. Then we consider noise terms to incorporate the fluctuation effects and the random import of the disease into the population and analyse the influence of heterogeneity on warning signs for critical transitions (or tipping points)...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
Beata Jackowska-Zduniak, Urszula Forys
A proposed model consisting of two coupled models (Hodgkin-Huxley and Yanagihara-Noma-Irisawa model) is considered as a description of the heart's action potential. System of ordinary differential equations is used to recreate pathological behaviour in the conducting heart's system such as double fire and the most common tachycardia: atrioventricular nodal reentrant tachycardia (AVNRT). Part of the population has an abnormal accessory pathways: fast and slow (Fujiki, 2008). These pathways in the atrioventricular node (AV node) are anatomical and functional contributions of supraventricular tachycardia...
December 1, 2016: Mathematical Biosciences and Engineering: MBE
Heinrich Krobath, Tao Chen, Hue Sun Chan
Volumetric properties of proteins bear directly on their biological functions in hyperbaric environments and are useful in general as a biophysical probe. To gain insight into conformation-dependent protein volume, we developed an implicit-solvent atomic chain model that transparently embodies two physical origins of volume. First, a fundamental geometric term capturing the van der Waals volume of the protein and the particulate, finite-size nature of the water molecules, modeled together by the volume encased by the protein's molecular surface...
October 24, 2016: Biochemistry
Bharathkumar Inturi, Gurubasavaraj V Pujar, Madhusudhan N Purohit
Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug-resistant TB (MDR-TB)...
October 24, 2016: Archiv der Pharmazie
Matthew Osmond, Sarah M Bernier, Mina B Pantcheva, Melissa D Krebs
Glaucoma is a disease in which damage to the optic nerve leads to progressive, irreversible vision loss. The intraocular pressure (IOP) is the only modifiable risk factor for glaucoma and its lowering is considered a useful strategy for preventing or slowing down the progression of glaucomatous neuropathy. Elevated intraocular pressure associated with glaucoma is due to increased aqueous humor outflow resistance, primarily through the trabecular meshwork (TM) of the eye. Current in vitro models of the trabecular meshwork are oversimplified and do not capture the organized and complex three-dimensional nature of this tissue that consists primarily of collagen and glycoasaminoglycans...
October 24, 2016: Biotechnology and Bioengineering
Andrés Palacio Chaverra
OBJECTIVE(S): Colombia has the third largest black population in the Americas after Brazil and the USA. In 2005 mortality rate under 5 in Colombia was 21.5 per 1000, with a reduction of 82% between 2005 and 1955. That rate is not in line with rates for Cuba (6.8), Chile (9.1) or Costa Rica (10.4). Here we aim to provide evidence that a further reduction of child mortality relates to the unspoken racial gap in a pioneering country in family planning and praised in the 2000 WHO report as having the world's fairest health care reform in terms of coverage and financial access...
October 24, 2016: Ethnicity & Health
Ashley Page, David Perry, Philip Young, Daniel A Mitchell, Bruno G Frenguelli, Patrick R Unwin
A vast range of interfacial systems exhibit charge heterogeneities on the nanoscale. These differences in local surface charge density are challenging to visualize, but recent work has shown the scanning ion conductance microscope (SICM) to be a very promising tool to spatially resolve and map surface charge and topography via a hopping potential sweep technique with a single nanopipette probe, with harmonic modulation of a bias applied between quasi-reference counter electrodes in the nanopipette and bulk solution, coupled with lock-in detection...
October 24, 2016: Analytical Chemistry
Yoonbae Oh, Cheonho Park, Do Hyoung Kim, Hojin Shin, Yu Min Kang, Mark DeWaele, Jeyeon Lee, Hoon-Ki Min, Charles D Blaha, Kevin Bennet, In Young Kim, Kendall H Lee, Dong Pyo Jang
Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, to-date, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods...
October 24, 2016: Analytical Chemistry
N Almenara, L Ibarlucea, C Mendicute-Fierro, J M Seco, A Rodríguez-Diéguez, M A Garralda, M A Huertos
[RhCl(NCO)(nbyl)(PR3)] (nbyl = σ-norbornenyl; NCO = quinoline-8-acyl; R = p-F-C6H4) (1) has been synthesized by the reaction of [Rh(nbd)Cl]2 (nbd = norbornadiene) with 2 equivalents of NCHO (quinoline-8-carbaldehyde) and 2 equivalents of PR3. Compound 1 has been fully characterized in solution and also in the solid state by X-ray diffraction. Compound 1 shows low stability in solution and undergoes slow ring closure isomerization to [RhCl(NCO)(ntyl)(PR3)] (ntyl = σ-nortricyclyl) (2) after 12 hours. Reaction of 1 with an extra equivalent of aldehyde (NCHO) and PR3 led to the formation of [RhCl(H)(NCO)(PR3)2] (3) and an equivalent of ketone, which is a hydroacylation product...
October 24, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Federica Lo Verso, José A Pomposo, Juan Colmenero, Angel J Moreno
By means of extensive simulations, we investigate concentrated solutions of globular single-chain nanoparticles (SCNPs), an emergent class of synthetic soft nano-objects. By increasing the concentration, the SCNPs show flattening, and even reentrant behaviour, in the density dependence of their structural and dynamic correlations, as well as a soft caging regime and weak dynamic heterogeneity. The latter is confirmed by validation of the Stokes-Einstein relation up to concentrations far beyond the overlap density...
October 24, 2016: Soft Matter
Jaehoon Jeong, Jooyeok Seo, Sungho Nam, Hyemi Han, Hwajeong Kim, Thomas D Anthopoulos, Donal D C Bradley, Youngkyoo Kim
Achievement of extremely high stability for inverted-type polymer:fullerene solar cells is reported, which have bulk heterojunction (BHJ) layers consisting of poly[4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene-alt-3-fluorothieno[3,4-b]thiophene-2-carboxylate] (PTB7-Th) and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM), by employing UV-cut filter (UCF) that is mounted on the front of glass substrates. The UCF can block most of UV photons below 403 nm at the expense of ≈20% reduction in the total intensity of solar light...
April 2016: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Matthew S Yorek, Lawrence J Coppey, Hanna Shevalye, Alexander Obrosov, Randy H Kardon, Mark A Yorek
Aims. In this study a streptozotocin induced type 1 diabetes mouse model was used to assess the effectiveness of salsalate, menhaden oil, the combination of salsalate and menhaden oil, or resolvin D1 on neuropathic endpoints. Materials and Methods. Changes in body weight, blood glucose, serum markers for triglycerides, free fatty acids, cholesterol, and resolvin D1, motor and sensory nerve conduction velocities and thermal sensitivity were assessed, as well as performing in vivo confocal microscopy of subepithelial corneal nerves and immunohistochemistry of nerves in the cornea and foot pad...
2016: Journal of Nutrition and Metabolism
Anatoliy I Yashin, Konstantin G Arbeev, Deqing Wu, Liubov Arbeeva, Alexander Kulminski, Irina Kulminskaya, Igor Akushevich, Svetlana V Ukraintseva
BACKGROUND AND OBJECTIVE: To clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet expectations of the researchers. Most detected genetic associations have not reached a genome-wide level of statistical significance, and suffered from the lack of replication in the studies of independent populations. The reasons for slow progress in this research area include low efficiency of statistical methods used in data analyses, genetic heterogeneity of aging and longevity related traits, possibility of pleiotropic (e...
2016: North American Actuarial Journal: NAAJ
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