Fractional reaction-diffusion equations

In a series of papers, Saxena, Mathai, and Haubold (2002, 2004a, 2004b) derived solutions of a number of fractional kinetic equations in terms of generalized Mittag-Leffler functions which provide the extension of the work of Haubold and Mathai (1995, 2000). The subject of the present paper is to investigate the solution of a fractional reaction-diffusion equation. The results derived are of general nature and include the results reported earlier by many authors, notably by Jespersen, Metzler, and Fogedby (1999) for anomalous diffusion and del-Castillo-Negrete, Carreras, and Lynch (2003) for reaction-diffusion systems with L\'evy flights. The solution has been developed in terms of the H-function in a compact form with the help of Laplace and Fourier transforms. Most of the results obtained are in a form suitable for numerical computation.Comment: LaTeX, 17 pages, corrected typo

Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins

Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.Funding Agencies|Swedish Research Council (Vetenskapsradet)|2008-3356|Swedish Foundation for Swedish Research|FFL4|Swedish Healthcare System (ALF)||Region Skane||</p

The Carbohydrate-Binding Site in Galectin-3 Is Preorganized To Recognize a Sugarlike Framework of Oxygens: Ultra-High-Resolution Structures and Water Dynamics

The recognition of carbohydrates by proteins is a fundamental aspect of communication within and between living cells. Understanding the molecular basis of carbohydrate-protein interactions is a prerequisite for the rational design of synthetic ligands. Here we report the high- to ultrahigh-resolution crystal structures of the carbohydrate recognition domain of galectin-3 (Gal3C) in the ligand-free state (1.08 angstrom at 100 K, 1.25 angstrom at 298 K) and in complex with lactose (0.86 angstrom) or glycerol (0.9 angstrom). These structures reveal striking similarities in the positions of water and carbohydrate oxygen atoms in all three states, indicating that the binding site of Gal3C is preorganized to coordinate oxygen atoms in an arrangement that is nearly optimal for the recognition of beta-galactosides. Deuterium nuclear magnetic resonance (NMR) relaxation dispersion experiments and molecular dynamics simulations demonstrate that all water molecules in the lactose-binding site exchange with bulk water on a time scale of nanoseconds or shorter. Nevertheless, molecular dynamics simulations identify transient water binding at sites that agree well with those observed by crystallography, indicating that the energy landscape of the binding site is maintained in solution. All heavy atoms of glycerol are positioned like the corresponding atoms of lactose in the Gal3C complexes. However, binding of glycerol to Gal3C is insignificant in solution at room temperature, as monitored by NMR spectroscopy or isothermal titration calorimetry under conditions where lactose binding is readily detected. These observations make a case for protein cryo-crystallography as a valuable screening method in fragment-based drug discovery and further suggest that identification of water sites might inform inhibitor design

Mouse DRG Cell Line with Properties of Nociceptors

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons

The Case of the Fickle Fingers: How the PRDM9 Zinc Finger Protein Specifies Meiotic Recombination Hotspots in Humans

Recent discoveries have revealed the central role of PRDM9 in mammalian recombination. The precise function of this protein, however, remains poorly understood, as do the causes for its rapid evolution and its role in reproductive isolation

Search For Exotic Tau-decays

The Crystal Ball detector at the Doris II storage ring at DESY was used to search for the exotic decay processes tau -&gt; e gamma, tau -&gt; e pi0, tau -&gt; e eta. No signal was observed. We obtained the following 90% CL upper limits on the branching fractions:B(tau -&gt; e gamma)&lt; 2.0x10^(-4),B(tau -&gt; e pi0) &lt; 1.4x10^(-4),B(tau -&gt; e eta) &lt; 2.4x10^(-4)

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains

Background: Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Methods: Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. Results: 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). Conclusions: In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread

Multiple mechanisms mediating carbon monoxide inhibition of the voltage-gated K+ channel Kv1.5

The voltage-gated K+ channel plays key roles in the vasculature and in atrial excitability, and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1.5 expressed in HEK293 cells in a concentration-dependent manner which involved multiple signalling pathways. CO inhibition was partially reversed by superoxide dismutase mimetics, and by suppression of mitochondrial reactive oxygen species. CO also elevated intracellular nitric oxide (NO) levels. Prevention of NO formation also partially reversed CO inhibition of Kv1.5, as did inhibition of soluble guanylyl cyclase. CO also elevated intracellular peroxynitrite levels, and a peroxynitrite scavenger markedly attenuated the ability of CO to inhibit Kv1.5. CO caused nitrosylation of Kv1.5, an effect which was also observed in C331A and C346A mutant forms of the channel, which had previously been suggested as nitrosylation sites within Kv1.5. Augmentation of Kv1.5 via exposure to hydrogen peroxide was fully reversed by CO. Native Kv1.5 recorded in HL-1 murine atrial cells was also inhibited by CO. Action potentials recorded in HL-1 cells were increased in amplitude and duration by CO, an effect mimicked and occluded by pharmacological inhibition of Kv1.5. Our data indicate that Kv1.5 is a target for modulation by CO via multiple mechanisms. This regulation has important implications for diverse cellular functions, including excitability, contractility and apoptosis

Pasquale del Pezzo, Duke of Caianello, Neapolitan mathematician

This article is dedicated to a reconstruction of some events and achievements, both personal and scientific, in the life of the Neapolitan mathematician Pasquale del Pezzo, Duke of Caianello