The neuropeptide galanin extensively coexists with norepinephrine in locus coeruleus (LC) neurons. Previous research in this laboratory has demonstrated that unlimited access to activity wheels in the home cage increases mRNA for galanin (GAL) in the LC, and that GAL mediates some of the beneficial effects of exercise on brain function. To assess whether capacity for aerobic exercise modulates this upregulation in galanin mRNA, three heterogeneous rat models were tested: rats selectively bred for (1) high intrinsic (untrained) aerobic capacity (High Capacity Runners, HCR) and (2) low intrinsic aerobic capacity (Low Capacity Runners, LCR) and (3) unselected Sprague-Dawley (SD) rats with and without free access to running wheels for 3 weeks.
View Article and Find Full Text PDFWe report a manganese porphyrin mediated aliphatic C-H bond chlorination using sodium hypochlorite as the chlorine source. In the presence of catalytic amounts of phase transfer catalyst and manganese porphyrin Mn(TPP)Cl 1, reaction of sodium hypochlorite with different unactivated alkanes afforded alkyl chlorides as the major products with only trace amounts of oxygenation products. Substrates with strong C-H bonds, such as neopentane (BDE =∼100 kcal/mol) can be also chlorinated with moderate yield.
View Article and Find Full Text PDFAntigen recognition by T cells involves large scale spatial reorganization of numerous receptor, adhesion, and costimulatory proteins within the T cell-antigen presenting cell (APC) junction. The resulting patterns can be distinctive, and are collectively known as the immunological synapse. Dynamical assembly of cytoskeletal network is believed to play an important role in driving these assembly processes.
View Article and Find Full Text PDFOxygenated heme proteins are known to react rapidly with nitric oxide (NO) to produce peroxynitrite (PN) at the heme site. This process could lead either to attenuation of the effects of NO or to nitrosative protein damage. PN is a powerful nitrating and oxidizing agent that has been implicated in a variety of cell injuries.
View Article and Find Full Text PDFCrystallisation of yttrium and other trivalent metal cations of similar radius with racemic N,N'-2-methylpiperazinebis(methylene phosphonic acid) gives a small pore bisphosphonate metal-organic framework solid displaying coordinative and hydrogen bonding and permanent porosity.
View Article and Find Full Text PDFCell membranes exhibit multiple layers of complexity, ranging from their specific molecular content to their emergent mechanical properties and dynamic spatial organization. Both compositional and geometrical organizations of membrane components are known to play important roles in life processes, including signal transduction. Supported membranes, comprised of a bilayer assembly of phospholipids on the solid substrate, have been productively served as model systems to study wide range problems in cell biology.
View Article and Find Full Text PDFSignal transduction originates at the membrane, where the clustering of signaling proteins is a key step in transmitting a message. Membranes are difficult to study, and their influence on signaling is still only understood at the most rudimentary level. Recent advances in the biophysics of membranes, surveyed in this review, have highlighted a variety of phenomena that are likely to influence signaling activity, such as local composition heterogeneities and long-range mechanical effects.
View Article and Find Full Text PDFNat Rev Mol Cell Biol
May 2010
The coordinated organization of cell membrane receptors into diverse micrometre-scale spatial patterns is emerging as an important theme of intercellular signalling, as exemplified by immunological synapses. Key characteristics of these patterns are that they transcend direct protein-protein interactions, emerge transiently and modulate signal transduction. Such cooperativity over multiple length scales presents new and intriguing challenges for the study and ultimate understanding of cellular signalling.
View Article and Find Full Text PDFRiverbank filtration has been shown to be effective for removing viable Cryptosporidium parvum oocysts. Drinking water systems that employ riverbank filtration may receive additional treatment credits beyond that which they can obtain using traditional engineering approaches. In order to develop guidance for removal effectiveness, screening level predictive modeling by colloid filtration theory combined with advection and dispersion modeling is potentially useful.
View Article and Find Full Text PDFVirtual worlds offer the potential for friendship, compassionate listening and support, and even love for 15 million users worldwide. But virtual analogs of crimes such as rape, murder, and pedophilia also exist within these worlds. The writings of Freud and Winnicott provide one model for understanding what may motivate these virtual crimes and how to think about them clinically.
View Article and Find Full Text PDFActivation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed.
View Article and Find Full Text PDFThe organization and dynamics of receptors and other molecules in the plasma membrane are not well understood. Here we analyzed the spatio-temporal dynamics of T cell antigen receptor (TCR) complexes and linker for activation of T cells (Lat), a key adaptor molecule in the TCR signaling pathway, in T cell membranes using high-speed photoactivated localization microscopy, dual-color fluorescence cross-correlation spectroscopy and transmission electron microscopy. In quiescent T cells, both molecules existed in separate membrane domains (protein islands), and these domains concatenated after T cell activation.
View Article and Find Full Text PDFLipid bilayers supported by substrates with nanometer-scale surface corrugations hold interest in understanding both nanoparticle-membrane interactions and the challenges of constructing models of cell membranes on surfaces with desirable properties, e.g., porosity.
View Article and Find Full Text PDFOxygenated hemoproteins are known to react rapidly with nitric oxide (NO) to produce peroxynitrite (PN) at the heme site. This process could lead either to attenuation of the effects of NO or to nitrosative protein damage. Peroxynitrite is a powerful nitrating and oxidizing agent that has been implicated in a variety of cell injuries.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2009
During antigen recognition by T cells, signaling molecules on the T cell engage ligands on the antigen-presenting cell and organize into spatially distinctive patterns. These are collectively known as the immunological synapse (IS). Causal relationships between large-scale spatial organization and signal transduction have previously been established.
View Article and Find Full Text PDFThe detection and kinetic characterization of a cytochrome P450 model compound I, [OFe(IV)-4-TMPyP](+) (1), in aqueous solution shows extraordinary reaction rates for C-H hydroxylations. Stopped-flow spectrophotometric monitoring of the oxidation of Fe(III)-4-TMPyP with mCPBA revealed the intermediate 1, which displays a weak, blue-shifted Soret band at 402 nm and an absorbance at 673 nm, typical of a porphyrin pi-radical cation. This intermediate was subsequently transformed into the well-characterized OFe(IV)-4-TMPyP.
View Article and Find Full Text PDFTwo-dimensional dispersions of colloidal particles with a range of surface chemistries and electrostatic potentials are characterized under a series of solution ionic strengths. A combination of optical imaging techniques are employed to monitor both the colloid structure and the electrostatic surface potential of individual particles . We find that like-charge multiparticle interactions can be tuned from exclusively repulsive to long-range attractive by changing the particle surface composition.
View Article and Find Full Text PDFBoth the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort-related cost-benefit decision-making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed-ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)].
View Article and Find Full Text PDFDetection and characterization of molecular interactions on membrane surfaces is important to biological and pharmacological research. Here, silver nanocubes interfaced with glass-supported model membranes form a label-free sensor that measures protein binding to the membrane. The technique utilizes plasmon resonance scattering of nanocubes, which are chemically coupled to the membrane.
View Article and Find Full Text PDFIntroduction: Decisions about the intensity of treatment for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are influenced by predictions about survival and quality of life. Evidence suggests that these predictions are poorly calibrated and tend to be pessimistic.
Aim: The aim of this study was to develop an outcome prediction model for COPD patients to support treatment decisions.
Background: Palliative care programs assist with prognostication, symptom control, and communication with patient and family. Hospitals often require financial justification for new programs Objective: Study the financial impact of the palliative care consultation (PCc) service in a public hospital.
Setting/subjects: From January to December 2005, 258 deaths occurred on the medicine service.