Absence of Serotype-Specific Surface Antigen in Laboratory Variants of Epidemic-Associated Listeria monocytogenes Strains

Variants that lacked reactivity with the serotype 4b-specific monoclonal antibody c74.22 and that lost susceptibility to certain Listeria- or serotype 4b-specific phages were identified in the course of genetic studies with serotype 4b Listeria monocytogenes strains H7550 and F2381L (epidemic clones I and II, respectively). Our findings suggest that such variants can become inadvertently established under laboratory conditions and suggest caution in work involving serotype 4b strains and genetic constructs thereof.     

The effect of a daytime 60-min nap opportunity on postural control in highly active individuals

Although napping is commonly used as a strategy to improve numerous physical and cognitive performances, the efficacy of this strategy for improving postural balance has not yet been elucidated. Thus, the aim of this study was to conduct a comprehensive examination of the effect of a 60 min nap opportunity (N60) on different components of postural control. Ten highly active individuals (age = 27 ± 3.5 y, height = 1.75 ± 0.52 m, weight = 66.02 ± 8.63 kg) performed, in a randomized order, two afternoon test sessions following no nap (NN) and N60. Postural balance was assessed using the sensory organisation test (SOT), the unilateral stance test (UST), and the limits of Stability Test performed on NeuroCom^® Smart Balance Master. The subjective rating of sleepiness before and after the nap conditions was also assessed. Compared to NN, N60 improved the composite balance score (p < 0.05, ES = 0.75, Δ = 5.3%) and the average and maximum percentage balance in the most challenging postural conditions of the SOT (p < 0.05 for SOT-4 and 5 and p < 0.0005 for SOT-6; ES range between 0.58 and 1.1). This enhanced postural balance in N60 was accompanied with improved visual (p < 0.05; ES = 0.93; Δ = 8.9%) and vestibular (p < 0.05; ES = 0.81; Δ = 10.5%) ratios and a reduced level of sleepiness perception (p < 0.001, ES = 0.87). However, no significant differences were found in any of the UST and LOS components’ scores (p > 0.05). Overall, a 60 min post lunch nap opportunity may be viable for improving static balance, although further work, involving larger samples and more complex motor activities, is warranted.     

Neutrophil apoptosis: A target for enhancing the resolution of inflammation

Neutrophils are essential for host defense and their programmed cell death and removal are critical for the optimal expression as well as for efficient resolution of inflammation. Delayed neutrophil apoptosis or impaired clearance of apoptotic neutrophils by macrophages contributes to the progression of chronic inflammation. Under most conditions, neutrophils are exposed to multiple factors and their fate would ultimately depend on the balance between pro‐survival and pro‐apoptotic signals. Life or death decisions are tightly controlled by a complex network of intracellular signaling pathways. Accumulating data indicate that receptors, such as the formyl peptide receptor 2/lipoxin receptor or β₂‐integrins can generate contrasting cues in neutrophils in a ligand‐specific manner and suggest a hierarchy among these signals. In this article, we review recent advances on how pro‐apoptosis and pro‐survival signals interact to determine the fate of neutrophils and the inflammatory response, and highlight novel pharmacological strategies that could be used to enhance the resolution of inflammation by redirecting neutrophils to apoptosis. J. Cell. Biochem. 108: 1039–1046, 2009. © 2009 Wiley‐Liss, Inc.     

Immunoaffinity purification and characterization of glyceraldehyde-3-phosphate dehydrogenase from human erythrocytes

A new procedure utilizing immunoaffinity column chromatography has been used for the purification of glyceraldehyde-3-phosphate dehydrogenase （GAPDH, EC 1.2.1.12） from human erythrocytes. The comparison between this rapid method （one step） and the tra- ditional procedure including ammonium sulfate fractionation followed by Blue Sepharose CL-6B chromatography shows that the new method gives a highest specific activity with a highest yield in a short time. The characterization of the purified GAPDH reveals that the native enzyme is a homotetramer of -150 kDa with an absolute specificity for the oxidized form of nicotinamide adenine dinucleotide （NAD＋）. Western blot analysis using purified monospecific polyclonal antibodies raised against the purified GAPDH showed a single 36 kDa band corresponding to the enzyme subunit. Studies on the effect of temperature and pH on enzyme activity revealed optimal values of about 43℃ and 8.5, respectively. The kinetic parameters were also calculated： the Vmax was 4.3 U/mg and the Km values against G3P and NAD＋ were 20.7 and 17.8 μM, respectively. The new protocol described represents a simple, economic, and reproducible tool for the purification of GAPDH and can be used for other proteins.     

Anti-tubercular activity of ruthenium (II) complexes with polypyridines

A series of nine polypyridyl-ruthenium (II) complexes (N-ligands = 2,2'-bipyridines; 2,2'-6',2'-terpyridines, di-alkyloxy-2,2'-6,2-bipyridine-3,3'-di-carboxylates), were tested against Mycobacterium tuberculosis (MBT). The complex (11) showed remarkable activity against MBT as compared to other complexes, (1-10). The aquo ligand of complex (11), as opposed to other chloro and acetonitrile derivatives, appears to play a key role in the antitubercular potency of this new class of metal-based compounds.     

The design and synthesis of a tricyclic single-nitrogen scaffold that serves as a 5-HT2C receptor agonist

5-HT2C agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT2C agonists. SAR was developed around this chemotype and compounds were identified that were potent (Ki<15 nM) and selective relative to other 5-HT2 receptors. The most promising compound displayed a good pharmacokinetic profile in multiple animal species, and was efficacious in an acute feeding study in rats.     

Very High Surface Capacity Observed Using Si Negative Electrodes Embedded in Copper Foam as 3D Current Collectors

Cu foam is evaluated as a replacement for metal foil current collectors to create 3D composite electrodes with the objective to produce Si‐based anodes with high loadings. The electrodes are prepared by casting the slurry into the porosity of the foam. With such a design, the loading and the surface capacity can reach values as high as 10 mg cm^?2 and 10 mAh cm^?2. Compared to the common 2D design, the 3D copper framework shows a great advantage in the cycle life (more than 400 cycles at a Si loading of 10 mg cm^?2 with commercial micrometric particles) and power performance. The thinness of the composite coating on the foam walls favors a better preservation of the electronic wiring upon cycling and fast lithium ion diffusion. A higher coulombic efficiency in half cells with lithium metal as the counter electrode is achieved by using carbon nanofibers (CNF) rather than carbon black (CB). The possibility to reach, in practice, higher surface capacity could allow a significant increase in both the volumetric and gravimetric energy densities by 23% and 19%, respectively, for the Cu foam‐silicon//LiFePO₄ stack compared to the graphite/LiFePO₄ stack of traditional design.     

Borrelia crocidurae in Ornithodoros ticks from northwestern Morocco: a range extension in relation to climatic change?

Tick‐borne relapsing fever (TBRF) is caused by Borrelia spirochetes transmitted to humans by Argasid soft ticks of the genus Ornithodoros. We investigated the presence of Ornithodoros ticks in rodent burrows in nine sites of the Gharb region of northwestern Morocco where we recently documented a high incidence of TBRF in humans. We assessed the Borrelia infection rate by nested PCR and sequencing. All sites investigated were colonized by ticks of the Ornithodoros marocanus complex and a high proportion of burrows (38.4%) were found to be infested. Borrelia infections were observed in 6.8% of the ticks tested. Two Borrelia species were identified by sequencing: B. hispanica and B. crocidurae. The discovery in northwestern Morocco of Ornithodoros ticks infected by B. crocidurae represents a 350 km range extension of this Sahelo‐Saharan spirochete in North Africa. The spread of B. crocidurae may be related to the increasing aridity of northwestern Morocco in relation to climate change.     

Exploring the Structural Mechanism of Covalently Bound E3 Ubiquitin Ligase: Catalytic or Allosteric Inhibition?

Covalent inhibition has recently gained a resurgence of interest in several drug discovery areas. The expansion of this approach is based on evidence elucidating the selectivity and potency of covalent inhibitors when bound to particular amino acids of a biological target. The Nedd4-1, an E3 ubiquitin ligase, is characterized by two covalent binding sites, of which catalytic Cys^cat and allosteric Cys^allo are enclosed. This enzyme has demonstrated inhibition at both the above-mentioned binding sites; however, a detailed molecular understanding of the structural mechanism of inhibition upon Cys^cat and Cys^allo binding remains vague. This prompted us to provide the first account of investigating the preferential covalent binding mode and the underlying structural and molecular dynamic implications. Based on the molecular dynamic analyses, it was evident that although both catalytic and allosteric covalent binding led to greater stability of the enzyme, a preferential covalent mechanism of inhibition was seen in the allosteric-targeted system. This was supported by a more favorable binding energy in the allosteric site compared to the catalytic site, in addition to the larger number of residue interactions and stabilizing hydrogen bonds occurring in the allosteric covalent bound complex. The fundamental dynamic analysis presented in this report compliments, as well as adds to previous experimental findings, thus leading to a crucial understanding of the structural mechanism by which Nedd4-1 is inhibited. The findings from this study may assist in the design of more target-specific Nedd4-1 covalent inhibitors exploring the surface-exposed cysteine residues.