Optimizing the accuracy and precision of the single-pulse Laue technique for synchrotron photo-crystallography.

The accuracy that can be achieved in single-pulse pump-probe Laue experiments is discussed. It is shown that with careful tuning of the experimental conditions a reproducibility of the intensity ratios of equivalent intensities obtained in different measurements of 3-4% can be achieved. The single-pulse experiments maximize the time resolution that can be achieved and, unlike stroboscopic techniques in which the pump-probe cycle is rapidly repeated, minimize the temperature increase due to the laser exposure of the sample.

Inactivated and subunit vaccines to prevent shigellosis.

Shigellosis remains a formidable disease globally, with children of the developing world bearing the greatest number of infections. The need for an affordable, safe and efficacious vaccine has persisted for decades. Vaccines to prevent shigellosis can be divided into living and nonliving approaches.

Virulence, inflammatory potential, and adaptive immunity induced by Shigella flexneri msbB mutants.

The ability of genetically detoxified lipopolysaccharide (LPS) to stimulate adaptive immune responses is an ongoing area of investigation with significant consequences for the development of safe and effective bacterial vaccines and adjuvants. One approach to genetic detoxification is the deletion of genes whose products modify LPS. The msbB1 and msbB2 genes, which encode late acyltransferases, were deleted in the Shigella flexneri 2a human challenge strain 2457T to evaluate the virulence, inflammatory potential, and acquired immunity induced by strains producing underacylated lipid A.

The effect of less-lethal weapons on injuries in police use-of-force events.

Objectives: We investigated the effect of the use of less-lethal weapons, conductive energy devices (CEDs), and oleoresin capsicum (OC) spray on the prevalence and incidence of injuries to police officers and civilians in encounters involving the use of force.

Methods: We analyzed data from 12 police departments that documented injuries to officers and civilians in 24,380 cases. We examined monthly injury rates for 2 police departments before and after their adoption of CEDs.

17beta-Nitro-5alpha-androstan-3alpha-ol and its 3beta-methyl derivative: neurosteroid analogs with potent anticonvulsant and anxiolytic activities.

Many 17-substituted androstan-3alpha-ol analogs act as positive allosteric modulators of GABA(A) receptors and exert anticonvulsant and anxiolytic-like activity actions in animal models. The endogenous neurosteroid allopregnanolone (17beta-acetyl; 1) is among the most potent of these. Here we demonstrate that 3alpha-hydroxy-17beta-nitro-5alpha-androstane (2b) and its 3beta-methyl analog (3alpha-hydroxy-3beta-methyl-17beta-nitro-5alpha-androstane; 2c) modulate GABA(A) receptors as assessed by [(35)S]t-butylbicyclo-phosphorothionate and [(3)H]flunitrazepam binding with potencies equivalent to or greater than 1.

Proepileptic phenotype of SV2A-deficient mice is associated with reduced anticonvulsant efficacy of levetiracetam.

Purpose: Synaptic vesicle protein 2A (SV2A) constitutes a distinct binding site for an antiepileptic drug levetiracetam (Keppra). In the present study we characterized SV2A (+/-) heterozygous mice in several seizure models and tested if the anticonvulsant efficacy of levetiracetam is reduced in these mice.

Methods: Seizure thresholds of male SV2A (+/-) mice and their wild-type littermates were assessed in pilocarpine (i.

Institutional responses to self-injurious behavior among inmates.

To date, little research has systematically investigated perceptions of mental health professionals regarding motivations for self-injury among prison inmates. To help fill this gap, the authors used descriptive techniques to examine self-injurious behavior among inmates from the perspective of correctional mental health professionals. A quantitative survey assessed perceptions of mental health staff regarding etiology, motivations, and manifestations of self-injury.

Evidence for modulation of BAG3 by polyomavirus JC early protein.

Polyomavirus JC (JCV) infects oligodendrocytes and astrocytes in the brain and is the cause of the demyelinating disease progressive multifocal leukoencephalopathy (PML). In cell culture, JCV infection is characterized by severe damage to cellular DNA, which begins early in infection, and a viral cytopathic effect, which is observed late in infection. Nevertheless, these JCV-infected cells show a low level of apoptosis, at both the early and late stages of infection.

Mucosal adjuvanticity of a Shigella invasin complex with dna-based vaccines.

Protection against many infectious diseases may require the induction of cell-mediated and mucosal immunity. Immunization with plasmid DNA-based vaccines has successfully induced cell-mediated immune responses in small animals but is less potent in humans. Therefore, several methods are under investigation to augment DNA vaccine immunogenicity.

Kinetic isotope effects on dehalogenations at an aromatic carbon.

In order to interpret the observed isotopic fractionation it is necessaryto understand its relationship with the isotope effect(s) on steps that occur during the conversion of the initial reactant to the final product. We examine this relationship from the biochemical point of view and elaborate on the consequences of the assumptions that it is based on. We illustrate the discrepancies between theoretical and experimental interpretation of kinetic isotope effects on examples of dehalogenation reactions that occur at an aromatic carbon atom.

Protective role of Puralpha to cisplatin.

Background: The nucleic acid-binding protein Puralpha is involved at stalled DNA replication forks, in double-strand break (DSB) DNA repair and the cellular response to DNA replication stress. Puralpha also regulates homologous recombination-directed DNA repair (HRR).

Results: Cells lacking Puralpha showed enhanced sensitivity to cisplatin as evaluated by assays for cell viability and cell clonogenicity.

Influence of the solvent description on the predicted mechanism of SN2 reactions.

The influence of the implicit solvent model on transition state structures of two S N2 reactions of biochemical importance is presented. In the considered methyl transfer reaction, we show experimentally that the rate constant in blood serum is about 60% slower than in the aqueous solution and that the implicit solvent model with slightly modified parameters for water captures correctly the energetics of this reaction. With the example of the reaction between 4-methyl-1,2,4-triazol-3-thione and ethyl bromoacetate, we show that relative stabilities of the conformationally different transition states depend upon the solvent inclusion strategy.

Effects of chronic treatment with levetiracetam on hippocampal field responses after pilocarpine-induced status epilepticus in rats.

Levetiracetam (Keppra) is a new generation antiepileptic drug characterized by a unique profile of activity in experimental models of epilepsy. It also has a distinct binding site in the brain, i.e.

Role of Puralpha in the modulation of homologous recombination-directed DNA repair by HIV-1 Tat.

Background: The nucleic acid-binding protein Puralpha is involved at stalled DNA replication forks, in double-strand break (DSB) DNA repair and the cellular response to DNA replication stress. Puralpha interacts with HIV-1 Tat, which regulates homologous recombination-directed DNA repair (HRR).

Materials And Methods: We investigated Rad51 and HRR regulation in mouse embryo fibroblasts (MEFs) from PURA -/- knockout mice that lack Puralpha.

Benefit of combination therapy in epilepsy: a review of the preclinical evidence with levetiracetam.

Levetiracetam (Keppra) is an antiepileptic drug (AED) characterized by a novel mechanism of action, unique profile of activity in seizure models, and broad-spectrum clinical efficacy. The present report critically reviews several preclinical studies focused on combination therapy with levetiracetam and other anticonvulsants in various seizure and epilepsy models. Administration of levetiracetam together with many different clinically used AEDs or other anticonvulsants generally enhances their protective activity and, among existing AEDs, this was particularly prevalent with valproate.

Modulation of AMP deaminase in rat hearts subjected to ischemia and reperfusion by purine riboside.

Changes in AMP deaminase (AMPD) activity influence heart function and progression of heart disease, but the underlying mechanism is unknown. We evaluated the effect of purine riboside (Purr) on the activity of AMPD in perfused rat hearts and in isolated rat cardiomyocytes. Brief perfusion of the pre-ischemic heart with 200 micro M Purr resulted in activation of AMPD, more pronounced degradation of the adenine nucleotides, and reduced recovery of the adenine nucleotide pool during reperfusion.

The dopamine D3/D2 agonist (+)-PD-128,907 [(R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol)] protects against acute and cocaine-kindled seizures in mice: further evidence for the involvement of D3 receptors.

Previous findings have demonstrated a protective role for dopamine D(3)/D(2) receptor agonists in the convulsant and lethal effects of acutely administered cocaine. Data are provided here to establish that the protection occurs through a D(3)-linked mechanism and that protection is extended to seizure kindling. The D(3) antagonist SB-277011-A [4-quinolinecarboxamide,N-[trans-4-[2-(6-cyano-3,4-dihydro-2(1H)-isoquinolinyl)ethyl]-cyclohexyl]-(9CI)] prevented the anticonvulsant effect of the D(3)/D(2) receptor agonist (+)-PD-128,907 [(R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol)] on cocaine-induced seizures.

Encircling reperfusion pattern on the stress-minus-delay bull's-eye map improves sensitivity of myocardial perfusion scans.

Background: Myocardial perfusion imaging is subject to considerable noise due to re-registration and attenuation artifact.

Methods: On a retrospective review, we identified 51 studies that showed encircling reperfusion pattern on a stress-minus-delay bull's-eye map with concurrent cardiac catheterization within 4 months. Encircling reperfusion was defined as a band of reversibility > or =2.

Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella flexneri 2a.

Development of a subunit vaccine for shigellosis requires identification of protective antigens and delivering these antigens in a manner that stimulates immunity comparable to that induced by natural infection. The Shigella invasin complex (Invaplex) vaccine is an ion-exchange-purified extract from virulent Shigella that consists of LPS and several other proteins, including the invasins IpaB and IpaC. Intranasal delivery of Invaplex stimulates protective immunity in small animal models for shigellosis.

SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy.

SV2A, a synaptic vesicle protein, has been recently identified as a binding target for levetiracetam (Keppra). The specific mechanism by which SV2A binding leads to seizure protection has not yet been fully elucidated. However, a functional correlation between SV2A binding affinity and anticonvulsant potency has been observed in the mouse audiogenic seizure model.

The initial zones of the atrioventricular node: really neglected anatomical features of potential clinical significance?

The constant evolution of medical knowledge and accompanying development of diagnostic and treatment possibilities for arrhythmias and conduction disturbances has reawakened interest in the structure and function of the conduction system of the human heart, especially in the region of the atrioventricular (AV) junction and within the junction itself. Of the large number of studies dealing with the AV junction few focus on the initial zones of the AV node. These were described for the first time by Tawara in 1906.

Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks.

The purpose of the present study was to examine the effects of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a selective inhibitor of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II), an enzyme catalyzing the cleavage of glutamate from the neuropeptide N-acetyl-aspartyl-glutamate (NAAG), on memory processes in mice. Long-term memory was evaluated in step-through passive avoidance task while alternation behavior, as a measure involving spatial working memory, was assessed in Y-maze task. Additionally, horizontal activity was evaluated by means of electronically monitored locomotor activity system.

JC virus agnoprotein inhibits in vitro differentiation of oligodendrocytes and promotes apoptosis.

Productive infection of oligodendrocytes, which are responsible for the formation of myelin sheath in the central nervous system, with the human neurotropic virus JC virus (JCV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition to encoding T antigen and the capsid proteins, which are produced at the early and late phases of the infection cycle, respectively, JCV encodes a small regulatory protein named agnoprotein that is important for successful completion of the virus life cycle. Here we used bipotential CG-4 cells to examine the impact of agnoprotein on oligodendrocyte differentiation and survival in the absence of JCV lytic infection.

Puralpha as a cellular co-factor of Rev/RRE-mediated expression of HIV-1 intron-containing mRNA.

To ensure successful replication, HIV-1 has developed a Rev-mediated RNA transport system that promotes the export of unspliced genomic RNA from nuclei to cytoplasm. This process requires the Rev responsive element (RRE) that is positioned in the viral transcript encoding Env protein, as well as in unspliced and singly spliced viral transcripts. We identified Puralpha, a single-stranded nucleic acid binding protein as a cellular partner for Rev that augments the appearance of unspliced viral RNAs in the cytoplasm.

NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice.

Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.