Protein cellular localization prediction with Support Vector Machines and Decision Trees

Many cellular functions are carried out in specific compartments of the cell. The prediction of the cellular localization of a protein is thus related to its function identification. This paper uses two Machine Learning techniques, Support Vector Machines (SVMs) and Decision Trees, in the prediction of the localization of proteins from three categories of organisms: gram-positive and gram-negative bacteria and fungi. For all categories considered, the localization task has multiple classes, which correspond to the possible protein locations. Since SVMs are originally designed for the solution of two-class problems, this paper also investigates and compares several strategies to extend this technique to perform multiclass predictions.     

Evolutionary conservation of biotinidase: implications for the enzyme's structure and subcellular localization

Biotinidases from various species ranging from fungi and insects to human have specific amino acids, and regions that are evolutionarily conserved. These specific amino acids and regions are further supported by their homology to a variety of amidases and nitrilases and by the location of missense mutations that cause biotinidase deficiency in humans. Glu-Lys-Cys residues from three of these regions are considered the catalytic triad involved in the catalysis of the amide linkage. The last one-third of the biotinidase sequence is lacking in nitrilases-amidases, which do not bind biocytin or biotin, therefore, it is likely that the biocytin-biotin-binding site of biotinidase is within this portion of the molecule. Although there are many missense mutations at the far C-terminus of the enzyme, the function of this region is still unclear. Biotinidase may have different functions in different cells or in different subcellular compartments. Using computer programs that predict the subcellular localization of proteins based on their N-terminal signal peptides, microsomal localization resulting in secretion was predicted for biotinidase from all species, whereas there is little consistent support for mitochondrial or nuclear localization of the enzymes. Additional immunohistochemical studies of various human tissues at different stages of development are necessary to resolve the ambiguity of subcellular localization of biotinidase.     

BCL-2--general considerations

BCL-2 protein is a oncoprotein considered to have an important role in the regulation of programmed cell death--apoptosis. The intracellular localization, the relation with other oncoproteins, the antioxidant function and the pathological implications are discussed.     

Regulatory T cells after organ transplantation: where does their action take place?

Regulatory T cells are considered to be pivotal for the induction of tolerance to donor antigens. In the past decades, several regulatory T-cell subsets have been identified, such as CD4(+)CD25(+) regulatory T cells and the CD8(+)CD28(-) suppressor T cells. Although many studies have investigated the role of these regulators in transplant tolerance, relatively little attention has focused on the exact place where these cells suppress immune responses directed to donor antigens. The localization of regulatory T cells may influence their effect on allogeneic immune responses. More insight into the localization and migration of regulatory T cells in transplant recipients is therefore important, especially when these cells are to be used for monitoring purposes and for cellular immune therapy. In the present review we summarize current knowledge about the presence of functional donor-directed regulatory T cells in the secondary lymphoid organs, peripheral blood, and the transplanted organ itself. In addition, we discuss the importance of the appropriate localization for the control of anti-donor immune reactivity.     

Involvement of aquaporin 5 in Sjögren’s syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune disease with the pathological hallmark of lymphoplasmacytic infiltration of exocrine glands - more specifically salivary and lacrimal glands - resulting in a diminished production of tears and saliva (sicca syndrome). The pathophysiology underscoring the mechanisms of the sicca symptoms in SS has still yet to be unraveled but recent advances have identified a cardinal role of aquaporin-5 (AQP5) as a key player in saliva secretion as well as salivary gland epithelial cell dysregulation. AQP5 expression and localization are significantly altered in salivary glands from patients and mice models of the disease, shedding light on a putative mechanism accounting for diminished salivary flow.Furthermore, aberrant expression and localization of AQP5 protein partners, such as prolactin-inducible protein and ezrin, may account for altered AQP5 localization in salivary glands from patients suffering from SS and are considered as new players in SS development. This review provides an overview of the role of AQP5 in SS salivary gland epithelial cell dysregulation, focusing on its trafficking and protein-protein interactions.     

Nuclear Localization of Immunoglobulins in Renal Biopsies of Patients with Lupus Nephritis

Immunofluorescent evaluation of renal biopsies from 19 patients with lupus nephritis revealed nuclear localization of immunoglobulins (IgG and IgM) in 6 patients. Homogeneous, nuclear rim and speckled patterns of nuclear localization were observed. The extent of localization varied, with only occasional nuclei fluorescing in 1 case, whereas approximately 50% of the nuclei exhibited fluorescence in the most extreme case. The phenomenon of nuclear localization of immunoglobulins was not observed in immunofluorescent studies of 225 renal biopsies from patients with conditions other than lupus nephritis. The possibility that nuclear localization of immunoglobulins occurred artifactually in the 6 patients was considered and was discounted by determining antinuclear antibody titers on serum obtained concurrently with the renal biopsy Nuclear localization was not confined to areas of histologically evident parenchymal destruction, indicating that antinuclear antibodies do not react only with nuclear antigens after tissue breakdown, but may gain access to intracellular antigens prior to cell dissolution.     

Nucleic acid vaccines

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.     

On the mechanism of action of adjuvants.

Evidence is presented that one a way which adjuvants exert their effect is by initiating an enduring increase in the localization of labelled cells in draining lymphoid tissues. Agents not generally considered to be adjuvants (carbon, latex, sheep erythrocytes) but capable of altering lymphocyte recirculation are shown to prevent the induction of tolerance by soluble bovine gamma globulin (BGG). These properties fulfil the criteria for adjuvanticity as defined by Dresser (1968) and link the expression of adjuvanticity to alterations in lymphocyte circulation.     

Immune privilege and inflammation of the testis – lessons from the infertile male

Immune cells are regular components of the testis and likely to participate in the complex local regulation of testicular function. Studies in experimental animals indicate that the testis is an immunologically privileged site where germ cell antigens are protected from autoimmune attack and foreign tissue grafts may survive for extended periods. However, the testicular environment does not preclude immune activation resulting in inflammatory reactions. Active immunization with testicular tissue or adoptive transfer of specific T lymphocytes causes autoimmune orchitis. Whereas symptomatic orchitis due to viral or bacterial infections is considered to be rare in man, recent studies among infertile males revealed a high prevalence of asymptomatic testicular inflammatory reactions associated with impaired spermatogenesis. Notably, the infiltration of T lymphocytes into the testis reflects disturbance of the delicate local immunoregulation. Both predominant peritubular localization of lymphocytes and characteristic morphological changes of the seminiferous tubules support the concept that activation of autoreactive T cells inducible by various etiological factors including noninfectious agents is involved. With regard to localization and functional polarization of T lymphocytes, adhesion molecules as well as chemokines and their receptors have to be considered as crucial components. In conclusion, immunopathological reactions in the testis should not be neglected as underlying reason or cofactor of male infertility. Further investigation of the mechanisms that regulate testicular immune functions in health and disease may encourage the search for appropriate therapeutic strategies such as specific immunomodulation.     

Epithelial-myoepitheliales Karzinom der Trachea

The tracheobronchial glands are considered to be counterparts of the minor salivary glands in the respiratory tract and can develop similar tumors (tumors of salivary gland type). Within this group of neoplasia epithelial-myoepithelial carcinoma of the respiratory tract is very rare and the diagnosis is often difficult. The first case of this tumor entity in the trachea is reported and a review of the literature on these tumors is presented. The exact histological classification as well as the localization and the endoscopic findings of these lesions are crucial for therapeutic decision-making.     

Features and distribution of intracerebrally injected peritoneal macrophages.

Radioactively labeled macrophages were injected intracerebrally in order to acquire additional criteria for the identity of certain intracerebral cell types with cells of the monocyte-macrophage series. The intracerebral distribution of the labeled cells, their reactive ability following silver impregnation, and the formation of processes were considered as indications for ameboid motility. The localization, reactive ability, and structure of the cells were similar to that found in cells inside the brain which are considered to be monocyte derivatives, i.e., intraventricular cells such as epiplexus cells and supraependymal cells, progressive microglia, free subarachnoidal cells, and perivascular cells of intracerebral vessels. A survival time of 2 months was assumed for the cells since isolated, intracerebrally administered, peritoneal macrophages can still be demonstrated inside the subarachnoid space 2 months after the injection.     

Lymphocyte Recirculation: the Need for Site-Specific Receptors to Dictate T-Lymphocyte Localization into Different Tissue Sites

This paper addresses the need for receptors involved in recirculation of T lymphocytes both during development and during an immune response or inflammation. Some known receptors present on T lymphocytes which are important in maintaining normal T-cell localization and function, i.e. the integrins, LECAMs, LPAM-1 and H-CAM (CD44) are considered in terms of the specificity which they confer on lymphocyte recirculation. A clear understanding of lymphocyte trafficking patterns and of the receptors involved may provide, for example, novel therapies for treatment of malignant cancer, alleviation of damage caused by lymphocytes during inflammatory responses, and targeting of cells to sites of infection.     

Current aspects of the problem of thesaurismoses

The main changes occuring in the theory of thesaurismoses are presented briefly. Main groups of thesaurismoses characterized by disorders of one or another kind of metabolism are dealt with. Most frequently occuring forms of thesaurismoses are described and by their examples it is shown how new nosological entities are distinguished by the nature of metabolic disorders, by the defect of the enzyme, and by the degree of severity of the enzymatic block. The main criteria for morphological diagnosis of thesaurismoses are presented including the presence of accumulation cell, their localization in different organs, histochemical analysis of accumulation products and electron microscopic findings. Biochemical examinations are considered to be essential for diagnosis.     

Evaluation of multiple-sphere head models for MEG source localization

Magnetoencephalography (MEG) source analysis has largely relied on spherical conductor models of the head to simplify forward calculations of the brain's magnetic field. Multiple- (or overlapping, local) sphere models, where an optimal sphere is selected for each sensor, are considered an improvement over single-sphere models and are computationally simpler than realistic models. However, there is limited information available regarding the different methods used to generate these models and their relative accuracy. We describe a variety of single- and multiple-sphere fitting approaches, including a novel method that attempts to minimize the field error. An accurate boundary element method simulation was used to evaluate the relative field measurement error (12% on average) and dipole fit localization bias (3.5 mm) of each model over the entire brain. All spherical models can contribute in the order of 1 cm to the localization bias in regions of the head that depart significantly from a sphere (inferior frontal and temporal). These spherical approximation errors can give rise to larger localization differences when all modeling effects are taken into account and with more complex source configurations or other inverse techniques, as shown with a beamformer example. Results differed noticeably depending on the source location, making it difficult to recommend a fitting method that performs best in general. Given these limitations, it may be advisable to expand the use of realistic head models.     

Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system

Bax and Bcl-2 proteins are identified as regulating molecules for programmed cell death. In the central nervous system, programmed cell death or apoptosis is considered to be an important phenomenon that is related to neuron vulnerability to a variety of toxic effects, including ischaemic insult. In this study, localization of Bax and Bcl-2 proteins was investigated in the human central nervous system using autopsy cases without any neurological disorder. Results were compared with findings in the rat. Most neurons in human cerebral cortex, basal ganglia and brain stem were positive for both Bax and Bcl-2 proteins, whereas Purkinje cells in cerebellum and neurons in hippocampal CA1, CA2 and CA3 regions were positive for Bax but negative or weakly positive for Bcl-2. Glial cells examined in all sections were negative for both proteins. Choroid plexus, ependymal cells and arachnoid villi showed positive reactivity for both proteins. A possible relationship between the localization of Bax or Bcl-2 proteins and the cell vulnerability in central nervous system is discussed.     

On the classification of dissecting aortic aneurysms

Aortic dissections are most commonly categorized into types A and B depending on the involvement of ascending or descending aorta based on the Stanford system and into types I, II and III using DeBakey classification. The latest classification was proposed by the European Society of Cardiology in 2001. The authors present their own classification of distal aortic dissecting aneurysms that takes into account antegrade and retrograde dissection of the aorta, besides localization of proximal fenestration. Surgical strategies for the treatment of different variants of aortic dissecting aneurysms are considered.     

Pulmonary localization of Enterocytozoon bieneusi in an AIDS patient: case report and review

Enterocytozoon bieneusi is an agent of intestinal microsporidiosis leading to malabsorption syndrome and diarrhea in AIDS patients. Respiratory tract microsporidiosis due to Encephalitozoon spp. has been reported. To date, however, only two cases of pulmonary involvement of E. bieneusi have been documented for patients with intestinal microsporidiosis. We report here another pulmonary localization of E. bieneusi in a human immunodeficiency virus-infected patient. Clinical features of these three cases are reviewed. E. bieneusi can colonize the respiratory tract but could be considered a simple carriage associated with an intestinal infection.     

一种基于独立成分分析的功能磁共振数据处理方法

独立成分分析（ICA）是统计信号处理中的一项新技术，用来从混合信号的多维观测中提取具有统计独立性的成分。我们针对功能磁共振数据处理，采用先对相邻的两体元信号作ICA分离，然后与参考信号进行相关，把相关系数大于一定阈值的体元作为刺激引起兴奋的体元，从而实现刺激的功能定位。经实际脑功能磁共振数据试验，初步证明了方法的有效性。     

Magnetic targeting after femoral artery administration and biocompatibility assessment of superparamagnetic iron oxide nanoparticles

Ferrofluids are attractive candidates for magnetic targeting system because of their fluidity and magnetism. The magnetic nanoparticles in ferrofluids should have combined properties of superparamagnetic behavior, target localization, and biocompatibility. The magnetic targeting and biocompatibility of superparamagnetic iron oxide nanoparticles stabilized by alginate (SPION-alginate) was investigated in vitro and in vivo. The localization of SPION-alginate by an external magnetic field in vitro was quantitatively evaluated by determining the iron content, and the results revealed that the localization ratio of SPION-alginate was 56%. Magnetic targeting of the SPION-alginate after femoral artery administration with the magnetic field in rats was quantitatively investigated by iron content and qualitatively confirmed by histological evaluation and magnetic resonance imaging. The ratio of iron content between the target site and the nontarget site were 8.88 at 0.5 h and 7.50 at 2 h, respectively. The viability of RAW264.7 cells and L929 cells was apparently unaltered upon exposure to SPION-alginate. The incubation with erythrocytes indicated that the SPION-alginate did not induce erythrocytes hemolysis and aggregation. In conclusions, the SPION-alginate had magnetic targeting with an external magnetic field and did not be detained at the injection site without the magnetic field. The SPION-alginate was generally considered to be biocompatible in cytotoxicity and hemolysis aspects.