E. coli F1 -ATPase: Site-directed mutagenesis of the β-subunit

AbstractResidues βGlu-181 and βGlu-192 of E. coli F1-ATPase (the DCCD-reactive residues) were mutated to Gln. Purified βGln-181 F1 showed 7-fold impairment of ‘unisite’ Pi formation from ATP and a large decrease in affinity for ATP. Thus the β-181 carboxyl group in normal F1 significantly contributes to catalytic site properties. Also, positive catalytic site cooperativity was attenuated from 5 × 104- to 548-fold in βGln-181 F1. In contrast, purified βGln-192 F1 showed only 6-fold reduction in ‘multisite’ ATPase activity. Residues βGly-149 and βGly-154 were mutated to Ile singly and in combination. These mutations, affecting residues which are strongly conserved in nucleotide-binding proteins, were chosen to hinder conformational motion in a putative ‘flexible loop’ in β-subunit. Impairment of purified F1-ATPase ranged from 5 to 61%, with the double mutant F1 less impaired than either single mutant. F1 preparations containing βIle-154 showed 2-fold activation after release from membranes, suggesting association with F0 restrained turnover on F1 in these mutants

Mantra: an open method for object and movement tracking

Mantra is a free and open-source software package for object tracking. It is specifically designed to be used as a tool for response collection in psychological experiments and requires only a computer and a camera (a webcam is sufficient). Mantra is compatible with widely used software for creating psychological experiments. In Experiments 1 and 2, we validated the spatial and temporal precision of Mantra in realistic experimental settings. In Experiments 3 and 4, we validated the spatial precision and accuracy of Mantra more rigorously by tracking a computer controlled physical stimulus and stimuli presented on a computer screen

Estimating Foodborne Gastroenteritis, Australia

An estimated 4.0–6.9 million episodes of foodborne gastroenteritis occur in Australia each year

Nipah Virus-associated Encephalitis Outbreak, Siliguri, India

Nipah virus, not previously detected in India, caused an outbreak of febrile encephalitis in West Bengal

Discovery and implementation of transcriptional biomarkers of synthetic LXR agonists in peripheral blood cells

<p>Abstract</p> <p>Background</p> <p>LXRs (Liver X Receptor α and β) are nuclear receptors that act as ligand-activated transcription factors. LXR activation causes upregulation of genes involved in reverse cholesterol transport (RCT), including ABCA1 and ABCG1 transporters, in macrophage and intestine. Anti-atherosclerotic effects of synthetic LXR agonists in murine models suggest clinical utility for such compounds.</p> <p>Objective</p> <p>Blood markers of LXR agonist exposure/activity were sought to support clinical development of novel synthetic LXR modulators.</p> <p>Methods</p> <p>Transcript levels of LXR target genes ABCA1 and ABCG1 were measured using quantitative reverse transcriptase/polymerase chain reaction assays (qRT-PCR) in peripheral blood from mice and rats (following a single oral dose) and monkeys (following 7 daily oral doses) of synthetic LXR agonists. LXRα, LXRβ, ABCA1, and ABCG1 mRNA were measured by qRT-PCR in human peripheral blood mononuclear cells (PBMC), monocytes, T- and B-cells treated <it>ex vivo </it>with WAY-252623 (LXR-623), and protein levels in human PBMC were measured by Western blotting. ABCA1/G1 transcript levels in whole-blood RNA were measured using analytically validated assays in human subjects participating in a Phase 1 SAD (Single Ascending Dose) clinical study of LXR-623.</p> <p>Results</p> <p>A single oral dose of LXR agonists induced ABCA1 and ABCG1 transcription in rodent peripheral blood in a dose- and time-dependent manner. Induction of gene expression in rat peripheral blood correlated with spleen expression, suggesting LXR gene regulation in blood has the potential to function as a marker of tissue gene regulation. Transcriptional response to LXR agonist was confirmed in primates, where peripheral blood ABCA1 and ABCG1 levels increased in a dose-dependent manner following oral treatment with LXR-623. Human PBMC, monocytes, T- and B cells all expressed both LXRα and LXRβ, and all cell types significantly increased ABCA1 and ABCG1 expression upon <it>ex vivo </it>LXR-623 treatment. Peripheral blood from a representative human subject receiving a single oral dose of LXR-623 showed significant time-dependent increases in ABCA1 and ABCG1 transcription.</p> <p>Conclusion</p> <p>Peripheral blood cells express LXRα and LXRβ, and respond to LXR agonist treatment by time- and dose-dependently inducing LXR target genes. Transcript levels of LXR target genes in peripheral blood are relevant and useful biological indicators for clinical development of synthetic LXR modulators.</p

Risk Factors for Nipah Virus Encephalitis in Bangladesh1

Patients in Goalando were likely infected by direct contact with fruit bats or their secretions, rather than through contact with an intermediate host

Shared Agency with Parents for Educational Goals: Ethnic Differences and Implications for College Adjustment

This study proposed and confirmed three ways in which college students can perceive shared agency and two ways in which they can perceive non-shared agency with parents when pursuing educational goals in college. Differences and similarities were examined among participants from four ethnic backgrounds (N = 515; 67% female): East Asian American, Southeast Asian American, Filipino/Pacific Islander American, and European American. Results indicated that Asian American youth reported higher levels of non-shared agency with parents (i.e., parental directing and noninvolvement), lower levels of shared agency (i.e., parental accommodation, support, or collaboration), and poorer college adjustment compared to European Americans. However, ethnic similarities were found whereby perceived shared agency in education with parents was associated with college adjustment. Multiple mediation analyses also indicated that our model of shared and non-shared agency with parents explained differences in college adjustment between Asian and European Americans, though more strongly for comparisons between European and East Asian Americans. Our results suggest that parents continue to be important in the education of older youth but that continued directing of youth’s education in college can be maladaptive

Modelling Visual Search with the Selective Attention for Identification Model (VS-SAIM): A Novel Explanation for Visual Search Asymmetries

In earlier work, we developed the Selective Attention for Identification Model (SAIM [16]). SAIM models the human ability to perform translation-invariant object identification in multiple object scenes. SAIM suggests that central for this ability is an interaction between parallel competitive processes in a selection stage and a object identification stage. In this paper, we applied the model to visual search experiments involving simple lines and letters. We presented successful simulation results for asymmetric and symmetric searches and for the influence of background line orientations. Search asymmetry refers to changes in search performance when the roles of target item and non-target item (distractor) are swapped. In line with other models of visual search, the results suggest that a large part of the empirical evidence can be explained by competitive processes in the brain, which are modulated by the similarity between target and distractor. The simulations also suggest that another important factor is the feature properties of distractors. Finally, the simulations indicate that search asymmetries can be the outcome of interactions between top-down (knowledge about search items) and bottom-up (feature of search items) processing. This interaction in VS-SAIM is dominated by a novel mechanism, the knowledge-based on-centre-off-surround receptive field. This receptive field is reminiscent of the classical receptive fields but the exact shape is modulated by both, top-down and bottom-up processes. The paper discusses supporting evidence for the existence of this novel concept

Recurrent Zoonotic Transmission of Nipah Virus into Humans, Bangladesh, 2001–2007

More than half of identified cases result from person-to-person transmission

Age of Child, More than HPV Type, Is Associated with Clinical Course in Recurrent Respiratory Papillomatosis

Background: RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV), 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Methodology/Principal Findings: Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with a least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher that that of patients with HPV 6 (Fisher's exact p=0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p=0.014). Both by multiple linear regression and by multiple logistics regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. Conclusions/Significance Abstract: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course. © 2008 Buchinsky et al