Main features of natural focality of ixodid tick-borne borreliosis in Russia

In a general form the "key" data on natural focality of ixodid tick-borne borrelioses and ecology of their agents--B. burgdorferi s. 1. in Russia, which have been accumulated by now, are presented. Vectors and reservoir hosts of different species of Borrelia, as well as a landscape preference of natural foci and ecological factors, determining risk of human infection, are characterized.     

Methodological aspects in the study of the natural foci of zoonoses

Conceptions of different authors on the natural focus of zoonosis infections are analysed and an improved definition of this phenomenon is proposed. The natural focus of disease is the antropoecosystem of certain hierarchic level (biosocial system), where the existence and appearance of the infection agent is supported and the disease is realized in people at certain infection rate.     

Fumonisins: current research trends in developmental toxicology

Fumonisin B₁ (FB₁) is a mycotoxin produced byFusarium verticillioides that is found in maize and maize-based foods. Reproductive studies in CD1 mice, rats and rabbits initially found no evidence that fumonisins are teratogenic. However, more recent findings suggest that they might increase the risk of neural tube defects (NTDs) in populations consuming large amounts of fumonisin-contaminated corn. When ≥15 mg/kg body weight fumonisin B₁ (FB₁) was given to pregnant LM/Bc mice by intraperitoneal (ip) injection, all litters were positive for NTDs. To determine if NTD induction is unique to the inbred LM/Bc mouse strain, NTD induction in LM/Bc and CD1 mice was compared: (a) in a study in whichF. verticillioides culture material providing ≤150 ppm FB₁ was fed to female mice before and during gestation, and (b) in a study in which FB₁ was given by ip injection to CD1 dams on gestation days 7 and 8, the critical time for NTD development. In the feeding study, one of five LM/Bc litters from dams fed the 150 ppm FB₁ diet was positive for NTDs whereas no NTDs were found in the CD1 litters. In the ip injection study, 40% of the litters at the highest dose tested, 45 mg/kg body weight, were positive for NTDs and one of nine low-dose (15 mg/kg body weight) litters was also positive. Thus, FB₁ induced NTDs in both LM/Bc and CD1 mice although the latter strain appears less sensitive. Comparative investigations using these strains will be useful for elucidating the mechanisms underlying fumonisin-induced NTDs in mice and determining the suitability of mouse models for studying the relationships between fumonisins and NTDs in humans.     

Bio-ontologies: current trends and future directions

In recent years, as a knowledge-based discipline, bioinformatics has been made more computationally amenable. After its beginnings as a technology advocated by computer scientists to overcome problems of heterogeneity, ontology has been taken up by biologists themselves as a means to consistently annotate features from genotype to phenotype. In medical informatics, artifacts called ontologies have been used for a longer period of time to produce controlled lexicons for coding schemes. In this article, we review the current position in ontologies and how they have become institutionalized within biomedicine. As the field has matured, the much older philosophical aspects of ontology have come into play. With this and the institutionalization of ontology has come greater formality. We review this trend and what benefits it might bring to ontologies and their use within biomedicine.     

Super-SILAC: current trends and future perspectives

Stable isotope labeling with amino acids in cell culture (SILAC) has risen as a powerful quantification technique in mass spectrometry (MS)–based proteomics in classical and modified forms. Previously, SILAC was limited to cultured cells because of the requirement of active protein synthesis; however, in recent years, it was expanded to model organisms and tissue samples. Specifically, the super-SILAC technique uses a mixture of SILAC-labeled cells as a spike-in standard for accurate quantification of unlabeled samples, thereby enabling quantification of human tissue samples. Here, we highlight the recent developments in super-SILAC and its application to the study of clinical samples, secretomes, post-translational modifications and organelle proteomes. Finally, we propose super-SILAC as a robust and accurate method that can be commercialized and applied to basic and clinical research.     

Oncoproteomics: current trends and future perspectives

Oncoproteomics is the application of proteomics technologies in oncology. Functional proteomics is a promising technique for the rational identification of biomarkers and novel therapeutic targets for cancers. Recent progress in proteomics has opened new avenues for tumor-associated biomarker discovery. With the advent of new and improved proteomics technologies, such as the development of quantitative proteomic methods, high-resolution, -speed and -sensitivity mass spectrometry and protein arrays, as well as advanced bioinformatics for data handling and interpretation, it is now possible to discover biomarkers that can reliably and accurately predict outcomes during cancer management and treatment. However, there are several difficulties in the study of proteins/peptides that are not inherent in the study of nucleic acids. New challenges arise in large-scale proteomic profiling when dealing with complex biological mixtures. Nevertheless, oncoproteomics offers great promise for unveiling the complex molecular events of tumorigenesis, as well as those that control clinically important tumor behaviors, such as metastasis, invasion and resistance to therapy. In this review, the development and advancement of oncoproteomics technologies for cancer research in recent years are expounded.     

Functional organization of natural tick-borne encephalitis foci and prognosis of their epidemic manifestation: analysis of one-dimensional temporal series of infection

Temporal extrapolation prognosis of tick-borne encephalitis diseases in the Primorye territory and its certain regions is made by means of autoregression models. The results obtained shows good prospects of used methods and models.     

An assessment of natural and human disturbance effects on Mexican ecosystems: current trends and research gaps

Mexico harbors more than 10% of the planet’s endemic species. However, the integrity and biodiversity of many ecosystems is experiencing rapid transformation under the influence of a wide array of human and natural disturbances. In order to disentangle the effects of human and natural disturbance regimes at different spatial and temporal scales, we selected six terrestrial (temperate montane forests, montane cloud forests, tropical rain forests, tropical semi-deciduous forests, tropical dry forests, and deserts) and four aquatic (coral reefs, mangrove forests, kelp forests and saline lakes) ecosystems. We used semi-quantitative statistical methods to assess (1) the most important agents of disturbance affecting the ecosystems, (2) the vulnerability of each ecosystem to anthropogenic and natural disturbance, and (3) the differences in ecosystem disturbance regimes and their resilience. Our analysis indicates a significant variation in ecological responses, recovery capacity, and resilience among ecosystems. The constant and widespread presence of human impacts on both terrestrial and aquatic ecosystems is reflected either in reduced area coverage for most systems, or reduced productivity and biodiversity, particularly in the case of fragile ecosystems (e.g., rain forests, coral reefs). In all cases, the interaction between historical human impacts and episodic high intensity natural disturbance (e.g., hurricanes, fires) has triggered a reduction in species diversity and induced significant changes in habitat distribution or species dominance. The lack of monitoring programs assessing before/after effects of major disturbances in Mexico is one of the major limitations to quantifying the commonalities and differences of disturbance effects on ecosystem properties.     

Congenital hyperinsulinism: current trends in diagnosis and therapy

Background

To investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects.

Methods

Purified GAD65-Ab from neurological patients and monoclonal GAD65-Ab with distinct epitope specificities (b78 and b96.11) were administered in vivo to rat cerebellum. Effects of intra-cerebellar administration of GAD65-Ab were determined using neurophysiological and neurochemical methods.

Results

Intra-cerebellar administration of GAD65-Ab from a SPS patient (Ab SPS) impaired the NMDA-mediated turnover of glutamate, but had no effect on NMDA-mediated turnover of glycerol. By contrast, GAD65-Ab from a patient with cerebellar ataxia (Ab CA) markedly decreased the NMDA-mediated turnover of glycerol. Both GAD65-Ab increased the excitability of the spinal cord, as assessed by the F wave/M wave ratios. The administration of BFA, an inhibitor of the recycling of vesicles, followed by high-frequency stimulation of the cerebellum, severely impaired the cerebello-cortical inhibition only when Ab CA was used. Moreover, administration of transcranial direct current stimulation (tDCS) of the motor cortex revealed a strong disinhibition of the motor cortex with Ab CA. Monoclonal antibodies b78 and b96.11 showed distinct effects, with greater effects of b78 in terms of increase of glutamate concentrations, impairment of the adaptation of the motor cortex to repetitive peripheral stimulation, disinhibition of the motor cortex following tDCS, and increase of the F/M ratios. Ab SPS shared antibody characteristics with b78, both in epitope recognition and ability to inhibit enzyme activity, while Ab CA had no effect on GAD65 enzyme activity.

Conclusions

These results suggest that, in vivo, neurological impairments caused by GAD65-Ab could vary according to epitope specificities. These results could explain the different neurological syndromes observed in patients with GAD65-Ab.     

Unfoldment and manifestation: The natural philosphy of evolution

A study is made of the general principles and theories pertaining to evolution, among which the definition, the evidences, the philosophical roots (the origin of life, the scale of nature, the morphogenetic potentialities), the three models (the Lamarckian, the Darwinistic and an alterative), and a further development of the last-mentioned model.     

Tumor vaccine: current trends in antigen specific immunotherapy

Effective cancer treatment to prevent the tumor growth as well as to stop its recurrence is the dream of oncologists. Currently available therapeutic measures like, radiotherapy and chemotherapy, often suffer from severe toxicity and lack of specificity of the drug towards tumor cells. Another promising approach is the 'immunotherapy', in which either the immune system is activated by tumor vaccine to combat the tumor growth or antitumor antibodies can be used. Vaccination can stimulate humoral, cellular and innate immune systems to generate various effector molecules, like antibody, cytotoxic T cells, cytokines etc. In antigen specific immunotherapy, the immune system can be stimulated actively by antigen based tumor vaccine to kill only those tumor cells, having expression of the particular tumor associated antigen. Different experimental, preclinical and clinical studies have proved that generated immune responses are effective to restrict the tumor growth. Useful strategies of antigen specific immunotherapy and outcome of various laboratory and clinic based studies are discussed.     

Vaccine adjuvants: current state and future trends

The problem with pure recombinant or synthetic antigens used in modern day vaccines is that they are generally far less immunogenic than older style live or killed whole organism vaccines. This has created a major need for improved and more powerful adjuvants for use in these vaccines. With few exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce a good antibody (Th2) response, it has little capacity to stimulate cellular (Th1) immune responses which are so important for protection against many pathogens. In addition, alum has the potential to cause severe local and systemic side-effects including sterile abscesses, eosinophilia and myofascitis, although fortunately most of the more serious side-effects are relatively rare. There is also community concern regarding the possible role of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet need for safer and more effective adjuvants suitable for human use. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. Each of these areas are highly specialized with their own unique needs in respect of suitable adjuvant technology. This paper reviews the state of the art in the adjuvant field, explores future directions of adjuvant development and finally examines some of the impediments and barriers to development and registration of new human adjuvants.     

Bacterial otitis media: current vaccine development strategies

Otitis media is the most common reason for children less than 5 years of age to visit a medical practitioner. Whilst the disease rarely results in death, there is significant associated morbidity. The most common complication is loss of hearing at a critical stage of the development of speech, language and cognitive abilities in children. The cause and pathogenesis of otitis media is multifactorial. Among the contributing factors, the single most important are viral and bacterial infections. Infection with respiratory syncytial virus, influenza viruses, para-influenza viruses, enteroviruses and adenovirus are most commonly associated with acute and chronic otitis media. Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis are the most commonly isolated bacteria from the middle ears of children with otitis media. Treatment of otitis media has largely relied on the administration of antimicrobials and surgical intervention. However, attention has recently focused on the development of a vaccine. For a vaccine to be effective against bacterial otitis media, it must, at the very least, contain antigens that induce a protective immune response in the middle ear against the three most common infecting bacteria. Whilst over the past decade there has been significant progress in the development of vaccines against invasive S. pneumoniae disease, these vaccines are less efficacious for otitis media. The search for candidate vaccine antigens for non-typeable H. influenzae are well advanced whilst less progress has been made for M. catarrhalis. No human studies have been conducted for non-typeable H. influenzae or M. catarrhalis and the concept of a tribacterial vaccine remains to be tested in animal models. Only when vaccine antigens are determined and an understanding of the immune responses induced in the middle ear by infection and immunization is gained will the formulation of a tribacterial vaccine against otitis media be possible.     

Three-dimensional tissue cultures: current trends and beyond

Life science research focuses on deciphering the biochemical mechanisms that regulate cell proliferation and function and largely depends on the use of tissue culture methods in which cells are grown on two-dimensional hard plastic or glass surfaces. However, the flat surface of the tissue culture plate represents a poor topological approximation of the complex three-dimensional (3D) architecture of a tissue or organ composed of various cell types, extracellular matrix (ECM) and interstitial fluids. Moreover, if we consider a cell as a perfectly defined volume, flattened cells have full access to the environment and limited cell-to-cell contact. However if the cell is a cube in a simple cuboidal epithelium, then its access to the lumen is limited to one face, with the opposite face facing the basal membrane and the remaining four faces lying in close contact with neighbouring cells. This is of great importance when considering the access of viruses and bacteria to the cell surface, the excretion of soluble factors or proteins or the signalling within or between cells. This short review discusses various cell culture approaches to improve the simulation of the 3D environment of cells.