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Paween Mahinthichaichan, Robert B Gennis, Emad Tajkhorshid
Cytochrome aa3 is the terminal respiratory enzyme of all eukaryotes and many bacteria and archaea, reducing O2 to water and harnessing the free energy from the reaction to generate the transmembrane electrochemical potential. The diffusion of O2 to the heme-copper catalytic site, which is buried deep inside the enzyme, is the initiation step of the reaction chemistry. Our previous molecular dynamics (MD) study with cytochrome ba3 , a homologous enzyme of cytochrome aa3 in Thermus thermophilus, demonstrated that O2 diffuses from the lipid bilayer to its reduction site through a 25-Å long tunnel inferred by Xe-binding sites detected by X-ray crystallography$ ...
March 16, 2018: Biochemistry
Taishi Nakamura, Guangshuo Zhu, Mark J Ranek, Kristen Kokkonen-Simon, Manling Zhang, Grace E Kim, Kenichi Tsujita, David A Kass
BACKGROUND: Stimulation of sGC (soluble guanylate cyclase) or inhibition of PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression of pathological cardiac stress. Because PDE5 and sGC reside in separate microdomains, we speculated that PKG1α oxidation might also differentially influence the effects from their pharmacological modulation...
March 2018: Circulation. Heart Failure
Michael J Diamond
Manifestations of failures in both symbolic and actual flesh-and-blood fathering reveal the inescapable role played by the father's unconscious transmissions in the ever present triadic matrix. Perelberg's crucial distinction between the murdered narcissistic father and the dead symbolic father suggests the problematic internalizations that fail to uphold the paternal law required for oedipal resolution. Three father-child narratives derived from classical literature and mythology are presented in order to elucidate significant unconscious paternal fantasies pertaining to lethal rivalry and neglect of the child's otherness...
February 2018: Journal of the American Psychoanalytic Association
P Marega, E A Liberti, J J S Freitas, K S Kietzer
BACKGROUND: Gastrointestinal (GI) dysmotility is common in patients with cancer. There are a few studies about the myenteric plexus in the presence of anatomically remote tumors. METHODS: Forty-eight male Wistar rats were divided into a control (CT) or Walker-256 (TW) group. Tumor cells were subcutaneously injected and saline was injected in the CT group. After 14 days, the small and large intestines were removed for histochemical analysis. The macroscopic morphology of the intestines and the fecal excretion were also observed...
March 15, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Patrice Rassam, Kathleen R Long, Renata Kaminska, David J Williams, Grigorios Papadakos, Christoph G Baumann, Colin Kleanthous
Gram-negative bacteria depend on energised protein complexes that connect the two membranes of the cell envelope. However, β-barrel outer-membrane proteins (OMPs) and α-helical inner-membrane proteins (IMPs) display quite different organisation. OMPs cluster into islands that restrict their lateral mobility, while IMPs generally diffuse throughout the cell. Here, using live cell imaging of Escherichia coli, we demonstrate that when transient, energy-dependent transmembrane connections are formed, IMPs become subjugated by the inherent organisation of OMPs and that such connections impact IMP function...
March 14, 2018: Nature Communications
Krzysztof Kucharz, Martin Lauritzen
Cortical spreading depolarization waves, the cause underlying migraine aura, are also the markers and mechanism of pathology in the acutely injured human brain. Propagation of spreading depolarization wave uniquely depends on the interaction between presynaptic and postsynaptic glutamate N-methyl-d-aspartate receptors (NMDARs). In the normally perfused brain, even a single wave causes a massive depolarization of neurons and glia, which results in transient loss of neuronal function and depression of the ongoing electrocorticographic activity...
March 12, 2018: Brain: a Journal of Neurology
Sachiko Udagawa, Shinji Ohkubo, Aiko Iwase, Yuto Susuki, Shiho Kunimatsu-Sanuki, Takeo Fukuchi, Chota Matsumoto, Yuko Ohno, Hiroshi Ono, Kazuhisa Sugiyama, Makoto Araie
PURPOSE: Traffic accidents are associated with the visual function of drivers, as well as many other factors. Driving simulator systems have the advantage of controlling for traffic- and automobile-related conditions, and using pinhole glasses can control the degree of concentric concentration of the visual field. We evaluated the effect of concentric constriction of the visual field on automobile driving, using driving simulator tests. METHODS: Subjects meeting criteria for normal eyesight were included in the study...
2018: PloS One
Jose Angel Fernandez-Roldan, Rafael Perez Del Real, Cristina Bran, Manuel Vazquez, Oksana Chubykalo-Fesenko
Diameter-modulated nanowires offer an important paradigm to design the magnetization response of 3D magnetic nanostructures by engineering the domain wall pinning. With the aim to understand its nature and to control the process, we analyze the magnetization response in FeCo periodically modulated polycrystalline nanowires varying the minor segment diameter. Our modelling indicates a very complex behavior with a strong dependence on the disorder distribution and an important role of topologically non-trivial magnetization structures...
March 14, 2018: Nanoscale
Jeremie Maire, Roman Anufriev, Takuma Hori, Junichiro Shiomi, Sebastian Volz, Masahiro Nomura
Semiconductor nanowires are potential building blocks for future thermoelectrics because of their low thermal conductivity. Recent theoretical works suggest that thermal conductivity of nanowires can be further reduced by additional constrictions, pillars or wings. Here, we experimentally study heat conduction in silicon nanowires with periodic wings, called fishbone nanowires. We find that like in pristine nanowires, the nanowire cross-section controls thermal conductivity of fishbone nanowires. However, the periodic wings further reduce the thermal conductivity...
March 13, 2018: Scientific Reports
Charlotte A Hall, Robert P Chilcott
The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light as a result of the antagonistic actions of the iris sphincter and dilator muscles. Since these muscles are innervated by the parasympathetic and sympathetic nervous systems, respectively, different parameters of the PLR can be used as indicators for either sympathetic or parasympathetic modulation. Thus, the PLR provides an important metric of autonomic nervous system function that has been exploited for a wide range of clinical applications...
March 13, 2018: Diagnostics
Stephen Shinsky, David W Christianson
Polyamines such as putrescine, spermidine, and spermine are small aliphatic cations that serve myriad biological functions in all forms of life. While polyamine biosynthesis and cellular trafficking pathways are generally well defined, it is only recently that the molecular basis of reversible polyamine acetylation has been established. In particular, enzymes that catalyze polyamine deacetylation reactions have been identified and structurally characterized: histone deacetylase 10 (HDAC10) from Homo sapiens and Danio rerio (zebrafish) is a highly specific N8-acetylspermidine deacetylase, and its prokaryotic counterpart, acetylpolyamine amidohydrolase (APAH) from Mycoplana ramosa, is a broad-specificity polyamine deacetylase...
March 13, 2018: Biochemistry
Juan Xu, Haiqing Wu, Songwen Chen, Baozhen Qi, Genqing Zhou, Lidong Cai, Liqun Zhao, Yong Wei, Shaowen Liu
Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA-30c (miR-30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR-30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR-30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR-30c is significantly down-regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor-β1 (TGF-β1)...
March 13, 2018: Journal of Cellular and Molecular Medicine
Silvia G V Alvarez, Angela McBrien
The ductus arteriosus (DA) is a crucial part of the fetal circulation, both in the normal fetus and in critical congenital heart disease (CHD). It allows shunting between the pulmonary and systemic circulations. In physiological prenatal conditions, the DA lets the majority of right ventricular output bypass the fluid-filled, high-resistance lungs. The DA can cause hemodynamic compromise in the fetus and neonate when constricted or absent (in isolation or in patients with CHD) and may lead to pre- or postnatal sequelae within other systems when forming part of a vascular ring...
March 7, 2018: Seminars in Fetal & Neonatal Medicine
Peter M Grace, Xiaohui Wang, Keith A Strand, Michael V Baratta, Yingning Zhang, Erika L Galer, Hang Yin, Steven F Maier, Linda R Watkins
The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq - and Gi -coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which was abolished by intrathecal interleukin-1 receptor antagonist...
March 9, 2018: Experimental Neurology
Dennis Küster
Small pupils elicit empathic socioemotional responses comparable to those found for emotional tears. This might be understood in an evolutionary context. Intense emotional tearing increases tear film volume and disturbs tear layer uniformity, resulting in blurry vision. A constriction of the pupils may help to mitigate this handicap, which in turn may have resulted in a perceptual association of both signals. However, direct empirical evidence for a role of pupil size in tearful emotional crying is still lacking...
January 2018: Evolutionary Psychology: An International Journal of Evolutionary Approaches to Psychology and Behavior
Edith Jottrand, Thomas Serste, Jean-Pierre Mulkay, Charlotte Vandueren, Philippe Unger
No abstract text is available yet for this article.
February 23, 2018: European Heart Journal Cardiovascular Imaging
João Cavaleiro Rufo, Inês Paciência, Diana Silva, Carla Martins, Joana Madureira, Eduardo de Oliveira Fernandes, Patrícia Padrão, Pedro Moreira, Luís Delgado, André Moreira
BACKGROUND: Endurance swimming exercises coupled to disinfection by-products exposure has been associated with increased airways dysfunction and neurogenic inflammation in elite swimmers. However, the impact of swimming pool exposure at a recreational level on autonomic activity has never been explored. Therefore, this study aimed to investigate how swimming pool attendance is influencing lung and autonomic function in school-aged children. METHODS: A total of 858 children enrolled a cross sectional survey...
2018: PloS One
Jenny L Wilkerson, Zachary A Curry, Pamela D Kinlow, Brittany L Mason, Ku-Lung Hsu, Mario van der Stelt, Benjamin F Cravatt, Aron H Lichtman
A great need exists for the identification of new effective analgesics to treat sustained pain. However, most preclinical nociceptive assays measure behavioral responses evoked by noxious stimuli (i.e., pain-stimulated behavior), which presents a challenge to distinguish between motor impairing and antinociceptive effects of drugs. Here, we demonstrate that chronic constriction injury of the sciatic nerve (CCI) elicits common pain-stimulated responses (i.e., mechanical allodynia and thermal hyperalgesia) as well as reduces marble burying/digging behaviors that occur during the early stages of the neuropathy and resolve within one week...
March 8, 2018: Pain
Pablo J Sáez, Lucie Barbier, Rafaele Attia, Hawa-Racine Thiam, Matthieu Piel, Pablo Vargas
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21...
2018: Methods in Molecular Biology
Meritxell Llorca-Torralba, Juan A Mico, Esther Berrocoso
The persistent activation of N-methyl-d-aspartate acid receptors (NMDARs) seems to be responsible for a series of changes in neurons associated with neuropathic pain, including the failure of opioids that act through mu-opioid receptors (MORs) to provide efficacious pain relief. As the noradrenergic locus coeruleus (LC) forms part of the endogenous analgesic system, we explored how intra-LC administration of morphine, a MORs agonist, alone or in combination with MK-801, a NMDARs antagonist, affects the sensorial and affective dimension of pain in a rat model of neuropathic pain; chronic constriction injury (CCI)...
March 7, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
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