Conformational stability and differential structural analysis of LcrV, PcrV, BipD, and SipD from type III secretion systems.

Diverse Gram-negative bacteria use type III secretion systems (T3SS) to translocate effector proteins into the cytoplasm of eukaryotic cells. The type III secretion apparatus (T3SA) consists of a basal body spanning both bacterial membranes and an external needle. A sensor protein lies at the needle tip to detect environmental signals that trigger type III secretion.

Experimental sleep fragmentation impairs attentional set-shifting in rats.

Study Objective: To evaluate the effect of experimental sleep fragmentation (sleep interruption; SI) on complex learning in an intradimensional-extradimensional (ID/ED) set-shifting task in rats.

Design: A sleep fragmentation paradigm of intermittent forced locomotion was validated in adult rats by examining electrographic effects. Discrimination task performances were assessed in rats following sleep fragmentation or 2 control conditions.

Selective cholinergic depletion of the hippocampus spares both behaviorally induced Arc transcription and spatial learning and memory.

We demonstrated previously that when hippocampal-dependent learning and plasticity are compromised by fornix lesions, behaviorally induced expression of the immediate early gene, Arc, is correspondingly low. The medial septum and the vertical diagonal band are major sources of subcortical afferents that innervate the hippocampus via the fornix. Here we assessed the specific contribution of cholinergic afferents from these regions to the impairments in spatial learning and behavioral induction of Arc transcription produced by fornix lesions.

Asymmetry of attentional set in rhesus monkeys learning colour and shape discriminations.

We trained rhesus monkeys on six visual discrimination problems using stimuli that varied in both shape and colour. For one group of animals shape was always relevant in these six problems, and colour always irrelevant, and for the other animals vice versa. During these "intradimensional shifts" (ID) the problems were learned at equal rates by the two groups, shape-relevant and colour-relevant.

Diminished response to recombinant factor VIIa in a patient with idiopathic thrombocytopenic purpura.

Objective: To describe the hypotheses that may explain a diminished hemostatic response in a patient receiving multiple doses of recombinant coagulation factor VIIa (rFVIIa) for off-label treatment of bleeding events.

Case Summary: A 70-year-old female with a significant history of idiopathic thrombocytopenic purpura (ITP) was admitted for coronary artery bypass grafting surgery. The patient developed thrombocytopenia and persistent hemorrhage postoperatively that was refractory to conventional therapy for ITP.

Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence.

Illicit use of drugs frequently begins and escalates during adolescence, with long-term adverse consequences. Because it is increasingly accepted that neural development continues through adolescence, addiction research has become more invested in understanding the behavioral and molecular consequences of early exposure to drugs of abuse. In a novel binge administration paradigm designed to model the pattern of human adolescent drug use, we administered ascending doses of cocaine or saline during a 12-d developmental period [postnatal day 35 (P35) to P46] corresponding to human adolescence.

Early discrimination reversal learning impairment and preserved spatial learning in a longitudinal study of Tg2576 APPsw mice.

To understand the relationship between amyloid-beta and cognitive decline in Alzheimer's disease, we evaluated cortical and hippocampal function in a transgenic mouse model of amyloid over-expression in Alzheimer's disease, the Tg2576 mouse. Tg2576 mice and their non-transgenic littermates were assessed at both 6 and 14 months of age in a battery of cognitive tests: attentional set-shifting, water maze spatial reference memory and T-maze working memory. Spatial reference memory was not affected by Tg status at either age.

Preclinical pharmacologic evaluation of MST-997, an orally active taxane with superior in vitro and in vivo efficacy in paclitaxel- and docetaxel-resistant tumor models.

Purpose: Because resistance to paclitaxel and docetaxel is frequently observed in the clinic, new anti-microtubule agents have been sought. The aim of this study was to evaluate the efficacy and oral activity of a novel taxane (MST-997) in paclitaxel- and docetaxel-resistant tumor models in vitro and in vivo.

Experimental Design: Tubulin polymerization assays, immunohistochemistry, and cell cycle analysis was used to evaluate mechanism of action of MST-997.

Sleep deprivation in rats produces attentional impairments on a 5-choice serial reaction time task.

Study Objectives: To develop a rodent model of the attentional dysfunction caused by sleep loss.

Design: The attentional performance of rats was assessed after 4, 7, and 10 hours of total sleep deprivation on a 5-choice serial reaction time task, in which rats detect and respond to brief visual stimuli.

Setting: The rats were housed, sleep deprived, and behaviorally tested in a controlled laboratory setting.

Multi-element survey of wild edible fungi and blackberries in the UK.

A survey of 12 metals including lead (Pb), copper (Cu), cadmium (Cd), mercury (Hg), arsenic (As) and platinum (Pt) was carried out using ICP-MS in 34 samples of wild fungi and 48 samples of wild blackberries collected from sites across the UK. On a fresh weight basis (mg/kg) levels of Pb were in the range 0.003-5.

Marrow stromal cells from patients affected by MPS I differentially support haematopoietic progenitor cell development.

Bone marrow transplantation is the therapy of choice in patients affected by MPS I (Hurler syndrome), but a high incidence of rejection limits the success of this treatment. The deficiency of alpha-L-iduronidase (EC 1.2.

Purkinje cell loss accompanies motor impairment in rats developing at altered gravity.

We have previously reported that the developmental exposure of rats to altered gravity (1.65 g) from gestational day 8 to postnatal day 21 impacts motor functions and cerebellar structure. The present study examined whether the decrease in cerebellar mass accompanied by impaired performance on a rotorod in hypergravity-exposed rats was related to a decrease in Purkinje cell number.

Spatial memory performance 2 weeks after general anesthesia in adult rats.

We have previously demonstrated that general anesthesia with 1.2% isoflurane-70% nitrous oxide impairs acquisition of a radial arm maze task in both young and aged rats when testing begins 2 days after anesthesia and in aged rats when testing begins 2 wk later. We designed this study to examine whether postanesthesia learning impairment is persistent in young rats.

Perinatal exposure to polychlorinated biphenyls differentially affects cerebellar development and motor functions in male and female rat neonates.

Perinatal exposure to polychlorinated biphenyls (PCBs) interacts with genetics and impacts the course of the central nervous system (CNS) development in both humans and animals. To test the hypothesis that the neurobehavioral impairments, and specifically motor dysfunctions following perinatal PCB exposure in rats are associated with changes in a specific brain region, the cerebellum, we compared neurodevelopment, motor behavior, cerebellar structure, and protein expression in rat neonates exposed to the PCB mixture Aroclor 1254 (A1254, 10.0 mg/kg/day) from gestational day 11 until postnatal day (P) 21 with that of controls.

Absorption of selenium from wheat, garlic, and cod intrinsically labeled with Se-77 and Se-82 stable isotopes.

There is limited information on the absorption of selenium from different foods in humans because of technical difficulties associated with isotopic labeling of dietary selenium. Wheat, garlic, and cod fish were intrinsically labeled with Se-77 or Se-82 stable isotopes. Labeled meals were fed in random order to 14 adults, with a minimum washout period of six weeks between each test meal.

Impaired motor learning in mice expressing torsinA with the DYT1 dystonia mutation.

Primary early-onset generalized dystonia is an autosomal dominant disorder caused by a deletion (DeltaGAG) in the DYT1 gene encoding torsinA. The gene defect has incomplete penetrance, with approximately 30% of carriers developing clinically evident dystonia. We describe lines of transgenic mice that express either human mutant torsinA (hMT) or human wild-type (hWT) torsinA.

Changes in the chemical form of selenium observed during the manufacture of a selenium-enriched sourdough bread for use in a human nutrition study.

High-performance liquid chromatography interfaced with inductively coupled plasma mass spectrometry, and hydride generation-inductively coupled plasma mass spectrometry were used, respectively, to investigate changes in both the chemical form and the concentration of selenium during its bio-incorporation and bio-accumulation into rye seedlings. A 60-fold increase in the total level of selenium in the seedlings ('control' biomass = 0.99 mg kg(-1), 'enriched' biomass = 55.

The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4.

The papillomavirus transcriptional activator, E2, is involved in key functions of the viral life cycle. These include transcriptional regulation, viral DNA replication, and viral genome segregation. The transactivation domain of E2 is required for each of these functions.

PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in rats.

Persistent suppression of N-methyl-d-aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions in a pattern similar to changes reported in schizophrenia. This similarity suggests that chronic NMDA receptor antagonism in animals may represent a useful model of neurobiological and related cognitive deficits in schizophrenia. Schizophrenia is associated with impairments in frontal lobe-dependent cognitive functions, including working memory and attentional shifting.

IpaD of Shigella flexneri is independently required for regulation of Ipa protein secretion and efficient insertion of IpaB and IpaC into host membranes.

Shigella flexneri causes human dysentery after invading the cells of the colonic epithelium. The best-studied effectors of Shigella entry into colonocytes are the invasion plasmid antigens IpaC and IpaB. These proteins are exported via a type III secretion system (TTSS) to form a pore in the host membrane that may allow the translocation of other effectors into the host cytoplasm.

The fimYZ genes regulate Salmonella enterica Serovar Typhimurium invasion in addition to type 1 fimbrial expression and bacterial motility.

An important step in Salmonella enterica serovar Typhimurium virulence is the ability to invade the intestinal epithelium. The invasion process requires a large number of genes encoded on Salmonella pathogenicity island 1 (SPI-1) at centisome 63 as well as genes located in other positions throughout the chromosome. Expression of the invasive phenotype is tightly regulated by environmental cues that are processed by a complex regulatory scheme.

Sexual dimorphism in cerebellar structure, function, and response to environmental perturbations.

Sexual dimorphism of CNS structure and function has been observed in humans and animals, but remains relatively unrecognized in the context of the cerebellum. Recent research in our laboratory has examined whether these gender differences extend to cerebellar structure and function, as well as the impact of environmental factors on the developing cerebellum. Perinatal exposure to both chemical and physical perturbations in the environment (in our experiments, PCBs or hypergravity) affects growth, neurodevelopment, and motor coordination differently in males and females.

An acidic amphipathic helix in the Bovine Papillomavirus E2 protein is critical for DNA replication and interaction with the E1 protein.

The papillomavirus E2 proteins function in viral transcriptional regulation, and genome replication and episomal maintenance. The transactivation domain is essential for these activities. To identify functional regions, a structural model of the BPV1 E2 transactivation domain was used to target surface residues for mutation.