Complete genome sequence of avian bornavirus genotype 1 from a Macaw with proventricular dilatation disease

Avian bornaviruses (ABV) were first detected and described in 2008. They are the etiologic agents of proventricular dilatation disease (PDD), a frequently fatal neurologic disease of captive parrots. Seven ABV genogroups have been identified worldwide from a variety of sources, and that number may increase as surveillance for novel bornaviruses continues. Here, we report the first complete sequence of a genogroup 1 avian bornavirus (ABV1).     

A diagnostic expert system

The introduction of new technologies in the field of electronics has influenced the development of technical equipment over the last few years. The progressive miniaturization of integrated circuits makes possible an expansion of the spectrum of functions offered by this equipment. This also applies to medical technology. These more complex units call for new methods of fault detection and diagnosis. In addition to analytical redundancy, tools developed by the artificial intelligence research community, such as expert systems, are becoming more and more important for fault diagnosis. On the basis of a realized diagnosis expert system the possibilities as well as the limits of such system are discussed. Also, possible future developments of artificial intelligence, like machine learning, are considered.     

An anatomically based patient-specific finite element model of patella articulation: towards a diagnostic tool

A 3D anatomically based patient-specific finite element (FE) model of patello-femoral (PF) articulation is presented to analyse the main features of patella biomechanics, namely, patella tracking (kinematics), quadriceps extensor forces, surface contact and internal patella stresses. The generic geometries are a subset from the model database of the International Union of Physiological Sciences (IUPS) (http://www.physiome.org.nz) Physiome Project with soft tissue derived from the widely used visible human dataset, and the bones digitised from an anatomically accurate physical model with muscle attachment information. The models are customised to patient magnetic resonance images using a variant of free-form deformation, called 'host-mesh' fitting. The continuum was solved using the governing equation of finite elasticity, with the multibody problem coupled through contact mechanics. Additional constraints such as tissue incompressibility are also imposed. Passive material properties are taken from the literature and implemented for deformable tissue with a non-linear micro-structurally based constitutive law. Bone and cartilage are implemented using a 'St-Venant Kirchoff' model suitable for rigid body rotations. The surface fibre directions have been estimated from anatomy images of cadaver muscle dissections and active muscle contraction was based on a steady-state calcium-tension relation. The 3D continuum model of muscle, tendon and bone is compared with experimental results from the literature, and surgical simulations performed to illustrate its clinical assessment capabilities (a Maquet procedure for reducing patella stresses and a vastus lateralis release for a bipartite patella). Finally, the model limitations, issues and future improvements are discussed.     

Development of a diagnostic system for Burkholderia pseudomallei infections

Monoclonal antibodies were generated against whole cell lysate of Burkholderia pseudomallei. Two out of 6 monoclonal antibodies were found specific and exhibited high affinity against B. pseudomallei, one of which, was utilized to develop sandwich ELISA for detection of specific B. pseudomallei antigen. Immunoassays were found to be specific as no reaction was observed with closely related Burkholderia and Pseudomonas species. Blood samples from experimentally infected mice were found positive for isolation till 4 days post infection (DPI) and ELISA till 10 DPI. One out of 40 sick animal serum samples tested in Thailand was found positive by sandwich ELISA that was earlier confirmed by isolation of B. pseudomallei. The results indicate the potentiality of the assay for its applicability in specific diagnosis of septicaemic melioidosis.     

SIDD: A Semantically Integrated Database towards a Global View of Human Disease

Background

A number of databases have been developed to collect disease-related molecular, phenotypic and environmental features (DR-MPEs), such as genes, non-coding RNAs, genetic variations, drugs, phenotypes and environmental factors. However, each of current databases focused on only one or two DR-MPEs. There is an urgent demand to develop an integrated database, which can establish semantic associations among disease-related databases and link them to provide a global view of human disease at the biological level. This database, once developed, will facilitate researchers to query various DR-MPEs through disease, and investigate disease mechanisms from different types of data.

Methodology

To establish an integrated disease-associated database, disease vocabularies used in different databases are mapped to Disease Ontology (DO) through semantic match. 4,284 and 4,186 disease terms from Medical Subject Headings (MeSH) and Online Mendelian Inheritance in Man (OMIM) respectively are mapped to DO. Then, the relationships between DR-MPEs and diseases are extracted and merged from different source databases for reducing the data redundancy.

Conclusions

A semantically integrated disease-associated database (SIDD) is developed, which integrates 18 disease-associated databases, for researchers to browse multiple types of DR-MPEs in a view. A web interface allows easy navigation for querying information through browsing a disease ontology tree or searching a disease term. Furthermore, a network visualization tool using Cytoscape Web plugin has been implemented in SIDD. It enhances the SIDD usage when viewing the relationships between diseases and DR-MPEs. The current version of SIDD (Jul 2013) documents 4,465,131 entries relating to 139,365 DR-MPEs, and to 3,824 human diseases. The database can be freely accessed from: http://mlg.hit.edu.cn/SIDD.     

Gene discovery in cervical cancer : towards diagnostic and therapeutic biomarkers

Cervical cancer is a potentially preventable disease; however, it remains the second most common malignancy in women worldwide. The human papillomavirus (HPV) is the single most important etiological agent in cervical cancer. HPV contributes to neoplastic progression through the action of two viral oncoproteins E6 and E7, which interfere with critical cell cycle pathways, tumor protein p53, and retinoblastoma protein. However, evidence suggests that HPV infection alone is insufficient to induce malignant changes, and other host genetic variations are important in the development of cervical cancer. Advances in molecular biology and high throughput technologies have heralded a new era in biomarker discovery and identification of molecular targets related to carcinogenesis. These advancements have improved our understanding of carcinogenesis and will facilitate screening, early detection, management, and personalized targeted therapy. A number of these developments and molecular targets associated with cervical cancer will be addressed in this review.     

Raman spectroscopic analysis of skin as a diagnostic tool for Human African Trypanosomiasis

Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control has significantly reduced new cases and motivated a target for the elimination of Trypanosoma brucei gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests to detect Trypanosoma brucei infection by interrogating the skin are therefore needed. Recent advances have improved the cost, sensitivity and portability of Raman spectroscopy technology for non-invasive medical diagnostics, making it an attractive tool for gambiense-HAT detection. The aim of this work was to assess and develop a new non-invasive diagnostic method for T. brucei through Raman spectroscopy of the skin. Infections were performed in an established murine disease model using the animal-infective Trypanosoma brucei brucei subspecies. The skin of infected and matched control mice was scrutinized ex vivo using a confocal Raman microscope with 532 nm excitation and in situ at 785 nm excitation with a portable field-compatible instrument. Spectral evaluation and Principal Component Analysis confirmed discrimination of T. brucei-infected from uninfected tissue, and a characterisation of biochemical changes in lipids and proteins in parasite-infected skin indicated by prominent Raman peak intensities was performed. This study is the first to demonstrate the application of Raman spectroscopy for the detection of T. brucei by targeting the skin of the host. The technique has significant potential to discriminate between infected and non-infected tissue and could represent a unique, non-invasive diagnostic tool in the goal for elimination of gambiense-HAT as well as for Animal African Trypanosomiasis (AAT).     

Differentiated HL-60 cells are a valid model system for the analysis of human neutrophil migration and chemotaxis

We have carried out a detailed comparison of the motile properties of differentiated HL-60 cells and human peripheral blood neutrophils. We compared the effects of chemotactic stimuli and of inhibitors of signalling proteins on morphology, chemokinesis and chemotaxis of neutrophils and differentiated HL-60 cells using videomicroscopy and a filter assay for chemotaxis. We also assessed expression of signalling and cytoskeletal proteins using Western blotting.Chemotactic peptide induced a front-tail polarity in HL-60 cells comparable to that of neutrophils. Chemokinetic and chemotactic responses to chemotactic peptide were also very similar for both cell types, concerning mean speed of migration, the fraction of migrated cells and the concentration of stimulus optimal for activation. The cytokine interleukin-8 was in contrast clearly less effective in activating motile responses of differentiated HL-60 cells as compared to neutrophils.An important functional role of Rho-activated kinases and phosphatidylinositol 3-kinase in motile responses of HL-60 cells, consistent with their upregulation during differentiation, could be confirmed using inhibitors with specificity for the corresponding enzymes. The only difference observed here between HL-60 cells and neutrophils concerned the differential effects of a protein kinase C inhibitor.In summary, the results presented here show that differentiated HL-60 cells, stimulated with chemotactic peptide, are a valid model system to study molecular mechanisms of neutrophil emigration.     

A new cancer diagnostic system based on a CDK profiling technology

A series of molecular pathological investigations of the molecules that stimulate the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous accumulation of knowledge of the clinical significance of these molecules for cancer diagnosis. However, the molecules have yet to be applied to clinical cancer diagnosis, as there is no available technology for application of the knowledge in a clinical setting. We hypothesized that the direct measurement of CDK activities and expressions (CDK profiling) might produce clinically relevant values for the diagnosis. This study investigated the clinical relevance of CDK profiling in gastrointestinal carcinoma tissues by using originally developed expression and activity analysis methods. We have established novel methods and an apparatus for analyzing the expression and activities of the CDK molecules in lysate of tumor tissue in a clinical setting, and examined 30 surgically dissected gastrointestinal carcinomas and corresponding normal mucosal specimens. We demonstrate here that remarkably elevated CDK2 activity is evident in more than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately mirrored the differences in proliferation between tumor and normal colonic tissues. Our results suggest that CDK profiling is a potent molecular-clinical approach to complement the conventional pathological diagnosis, and to further assist in the individualized medications.     

Low Gestational Weight Gain Skews Human Sex Ratios towards Females

Background

Human males are more vulnerable to adverse conditions than females starting early in gestation and continuing throughout life, and previous studies show that severe food restriction can influence the sex ratios of human births. It remains unclear, however, whether subtle differences in caloric intake during gestation alter survival of fetuses in a sex-specific way. I hypothesized that the ratio of male to female babies born should vary with the amount of weight gained during gestation. I predicted that women who gain low amounts of weight during gestation should produce significantly more females, and that, if gestational weight gain directly influences sex ratios, fetal losses would be more likely to be male when women gain inadequate amounts of weight during pregnancy.

Methods

I analyzed data collected from over 68 million births over 23 years to test for a relationship between gestational weight gain and natal sex ratios, as well as between gestational weight gain and sex ratios of fetal deaths at five gestational ages.

Results

Gestational weight gain and the proportion of male births were positively correlated; a lower proportion of males was produced by women who gained less weight and this strong pattern was exhibited in four human races. Further, sex ratios of fetal losses at 6 months of gestation were significantly male-biased when mothers had gained low amounts of weight during pregnancy, suggesting that low caloric intake during early fetal development can stimulate the loss of male fetuses.

Conclusion

My data indicate that human sex ratios change in response to resource availability via sex-specific fetal loss, and that a pivotal time for influences on male survival is early in fetal development, at 6 months of gestation.