Declined frontal white matter integrity in Alzheimer’s disease: a diffusion tensor imaging study

INTRODUCTION: Previous studies on structural changes of Alzheimer’s disease (AD) have been focused on grey matter atrophy. There is a resurgence of interests on white matter integrity in this prominently increasing patient population. Diffusion tensor imaging (DTI) provides key information on the microstructural changes beyond macroscopic anatomical imaging by in-vivo tracing molecular diffusion in the brain, and the measured fractional anisotrophy (FA) value may represent axonal integrity of neuronal networks. Data of DTI from AD patients are limited, and the literature is controversial regarding whether the AD process has a greater impact on anterior versus posterior cerebral white matter. METHODS: Eighteen patients with mild AD and 16 age-matched healthy adults were recruited into the study. Demographic features of the two groups were comparable. Data of DTI were collected using a Philips 3.0T MRI scanner. Scan parameters were as follows: B0=800 s/mm2, FOV=224*224*140 mm, resolution=1.75*1.75*2 mm, non-collinear 15 directions was acquired. 3D T1 anatomy was also collected. We processed DTI data with DTI toolbox, and anatomical T1 data with VBM5 toolbox in SPM. Voxel-by-voxel analysis was applied to compare the difference in FA value, and volume of white matter of the normalised brain between the elderly and AD groups. RESULTS: Voxel-based analysis showed no significant difference in white matter volume between the two groups, but FA value was reduced greatly in the left anterior cingulate (−10,37,−3), right anterior cingulate (12,0,28), and left medial frontal lobe (−18,32,−12). Minor reduction was found in other brain regions such as body of the corpus callosum, right midbrain (12,−12,−6), right posterior corpus callosum (8,−44,2), and bilateral, especially right temporal lobe (36,−8,−20), upon right hippocampus. Coordinates (x,y,z) were labelled according to Talairach atlas. CONCLUSION: DTI could be valid and more sensitive than traditional T1 anatomy in detecting microscopic white matter lesions. Our data showed a greater decrement in FA value over the anterior than posterior brain regions, and this decrement was not due to white matter atrophy. Our findings are in line with the retrogenesis hypothesis which predicts reversed demyelination during the process of AD, as the frontal lobe fibres are myelinated relatively late during brain development. These results also support previous findings of our behavioural study that frontal lobe abnormality might be the neural basis for cognitive deficit in AD patients.published_or_final_versionThe 15th Medical Research Conference; Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 suppl 1, p. 21, abstract no. 2

Antigenic cross-reactivity between severe acute respiratory syndrome-associated coronavirus and human coronaviruses 229E and OC43

Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a ≥4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

A patient with asymptomatic severe acute respiratory syndrome (SARS) and antigenemia from the 2003-2004 community outbreak of SARS in Guangzhou, China.

An asymptomatic case of severe acute respiratory syndrome (SARS) occurred early in 2004, during a community outbreak of SARS in Guangzhou, China. This was the first time that a case of asymptomatic SARS was noted in an individual with antigenemia and seroconversion. The asymptomatic case patient and the second index case patient with SARS in the 2003-2004 outbreak both worked in the same restaurant, where they served palm civets, which were found to carry SARS-associated coronaviruses. Epidemiological information and laboratory findings suggested that the findings for the patient with asymptomatic infection, together with the findings from previously reported serological analyses of handlers of wild animals and the 4 index case patients from the 2004 community outbreak, reflected a likely intermediate phase of animal-to-human transmission of infection, rather than a case of human-to-human transmission. This intermediate phase may be a critical stage for virus evolution and disease prevention.published_or_final_versio

Immunoassays Based on Penicillium marneffei Mp1p Derived from Pichia pastoris Expression System for Diagnosis of Penicilliosis

BACKGROUND: Penicillium marneffei is a dimorphic fungus endemic in Southeast Asia. It can cause fatal penicilliosis in humans, particularly in HIV-infected people. Diagnosis of this infection is difficult because its clinical manifestations are not distinctive. Specialized laboratory tests are necessary to establish a definitive diagnosis for successful management. We have demonstrated previously that a cell wall mannoprotein Mp1p, abundant in P. marneffei, is a potential biomarker for diagnosis of P. marneffei infections. In the present study, we describe immunoassays based on Mp1p derived from the yeast Pichia pastoris expression system. METHODOLOGY/PRINCIPAL FINDINGS: We generated monoclonal antibodies (MAbs) and rabbit polyclonal antibodies (PAbs) against Mp1p expressed in P. pastoris. Subsequently, we developed two Mp1p antigen capture ELISAs which employed MAbs for both the capture and detecting antibodies (MAb-MAb pair) or PAbs and MAbs as the capture and detecting antibodies (PAbs-MAb pair) respectively. The two Mp1p antigen ELISAs detected Mp1p specifically in cultures of P. marneffei yeast phase at 37-40 degrees C and had no cross-reaction with other tested pathogenic fungi. The sensitivities and specificities of the two antigen assays were found to be 55% (11/20) and 99.6% (538/540) for MAb-MAb Mp1p ELISA, and 75% (15/20) and 99.4% (537/540) for PAbs-MAb Mp1p ELISA performed using 20 sera with culture-confirmed penicilliosis, and 540 control sera from 15 other mycosis patients and 525 healthy donors. Meanwhile, we also developed an anti-Mp1p IgG antibody ELISA with an evaluated sensitivity of 30% (6/20) and a specificity of 98.5% (532/540) using the same sera. Furthermore, combining the results of Mp1p antigen and antibody detection improved the sensitivity of diagnosis to 100% (20/20). CONCLUSIONS/SIGNIFICANCE: Simultaneous detection of antigen and antibody using the immunoassays based on Mp1p derived from P. pastoris greatly improves detection sensitivity. The procedures should be useful for the routine diagnosis of penicilliosis.published_or_final_versio

Female Resistance to Invading Males Increases Infanticide in Langurs

BACKGROUND: Infanticide by adult male occurs in many mammalian species under natural conditions, and it is often assumed to be a goal-directed action and explained predominately by sexual selection. Motivation of this behavior in mammals is limitedly involved. METHODOLOGY AND PRINCIPAL FINDINGS: We used long-term reproductive records and direct observation in captivity and in the field of two snub-nosed langur species on the basis of individual identification to investigate how infanticide happened and to be avoided in nonhuman primates. Our observations suggested that infanticide by invading males might be more accidental than goal-directed. The invading male seemed to monopolize all the females including lactating mothers during takeovers. Multiparous mothers who accepted the invading male shortly after takeovers avoided infanticide in most cases. Our results conjectured primiparous mothers would decrease infanticidal possibility if they sexually accepted the invading male during or immediately after takeovers. In the studied langur species, voluntary abortion or mating with the invading male was evidently adopted by females to limit or avoid infanticide by takeover males. CONCLUSIONS AND SIGNIFICANCE: The objective of the invading male was to monopolize all adult females after his takeover. It appeared that the mother's resistance to accepting the new male as a mating partner was the primary incentive for infanticide. Motivation analysis might be helpful to further understand why infanticide occurs in primate species

Time series analysis of dengue fever and weather in Guangzhou, China

<p>Abstract</p> <p>Background</p> <p>Monitoring and predicting dengue incidence facilitates early public health responses to minimize morbidity and mortality. Weather variables are potential predictors of dengue incidence. This study explored the impact of weather variability on the transmission of dengue fever in the subtropical city of Guangzhou, China.</p> <p>Methods</p> <p>Time series Poisson regression analysis was performed using data on monthly weather variables and monthly notified cases of dengue fever in Guangzhou, China for the period of 2001-2006. Estimates of the Poisson model parameters was implemented using the Generalized Estimating Equation (GEE) approach; the quasi-likelihood based information criterion (QICu) was used to select the most parsimonious model.</p> <p>Results</p> <p>Two best fitting models, with the smallest QICu values, are selected to characterize the relationship between monthly dengue incidence and weather variables. Minimum temperature and wind velocity are significant predictors of dengue incidence. Further inclusion of minimum humidity in the model provides a better fit.</p> <p>Conclusion</p> <p>Minimum temperature and minimum humidity, at a lag of one month, are positively associated with dengue incidence in the subtropical city of Guangzhou, China. Wind velocity is inversely associated with dengue incidence of the same month. These findings should be considered in the prediction of future patterns of dengue transmission.</p

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic

Seroepidemiology of coxsackievirus A6, coxsackievirus A16, and Enterovirus 71 infections among children and adolescents in Singapore, 2008-2010

10.1371/journal.pone.0127999PLoS ONE105e012799

Species Used for Drug Testing Reveal Different Inhibition Susceptibility for 17beta-Hydroxysteroid Dehydrogenase Type 1

Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD 1) for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17β-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17β-HSD types 1, 2, 4, 5 and 7 but also against 17β-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17β-HSDs analyzed were observed. Especially, the rodent 17β-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17β-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution