geneCBR: a translational tool for multiple-microarray analysis and integrative information retrieval for aiding diagnosis in cancer research

Background  

Bioinformatics and medical informatics are two research fields that serve the needs of different but related communities. Both domains share the common goal of providing new algorithms, methods and technological solutions to biomedical research, and contributing to the treatment and cure of diseases. Although different microarray techniques have been successfully used to investigate useful information for cancer diagnosis at the gene expression level, the true integration of existing methods into day-to-day clinical practice is still a long way off. Within this context, case-based reasoning emerges as a suitable paradigm specially intended for the development of biomedical informatics applications and decision support systems, given the support and collaboration involved in such a translational development. With the goals of removing barriers against multi-disciplinary collaboration and facilitating the dissemination and transfer of knowledge to real practice, case-based reasoning systems have the potential to be applied to translational research mainly because their computational reasoning paradigm is similar to the way clinicians gather, analyze and process information in their own practice of clinical medicine.     

A novel nucleocytoplasmic traffic GTPase identified as a functional target of the bipartite geminivirus nuclear shuttle protein

In contrast to the accumulated data on nuclear transport mechanisms of macromolecules, little is known concerning the regulated release of nuclear-exported complexes and their subsequent trans-cytoplasmic movement. The bipartite begomovirus nuclear shuttle protein (NSP) facilitates the nuclear export of viral DNA and cooperates with the movement protein (MP) to transport viral DNA across the plant cell wall. Here, we identified a cellular NSP-interacting GTPase (NIG) with biochemical properties consistent with a nucleocytoplasmic transport role. We show that NIG is a cytosolic GTP-binding protein that accumulates around the nuclear envelope and possesses intrinsic GTPase activity. NIG interacts with NSP in vitro and in vivo (under transient expression), and redirects the viral protein from the nucleus to the cytoplasm. We propose that NIG acts as a positive contributor to geminivirus infection by modulating NSP nucleocytoplasmic shuttling and hence facilitating MP–NSP interaction in the cortical cytoplasm. In support of this, overexpression of NIG in Arabidopsis enhances susceptibility to geminivirus infection. In addition to highlighting the relevance of NIG as a cellular co-factor for NSP function, our findings also have implications for general nucleocytoplasmic trafficking of cellular macromolecules.     

Underutilization of social insurance among the poor: evidence from the Philippines

Background

Many developing countries promote social health insurance as a means to eliminate unmet health needs. However, this strategy may be ineffective if there are barriers to fully utilizing insurance.

Methods

We analyzed the utilization of social health insurance in 30 hospital districts in the central regions of the Philippines between 2003 and 2007. Data for the study came from the Quality Improvement Demonstration Study (QIDS) and included detailed patient information from exit interviews of children under 5 years of age conducted in seven waves among public hospital districts located in the four central regions of the Philippines. These data were used to estimate and identify predictors of underutilization of insurance benefits - defined as the likelihood of not filing claims despite having legitimate insurance coverage - using logistic regression.

Results

Multivariate analyses using QIDS data from 2004 to 2007 reveal that underutilization averaged about 15% throughout the study period. Underutilization, however, declined over time. Among insured hospitalized children, increasing length of stay in the hospital and mother''s education, were associated with less underutilization. Being in a QIDS intervention site was also associated with less underutilization and partially accounts for the downward trend in underutilization over time.

Discussion

The surprisingly high level of insurance underutilization by insured patients in the QIDS sites undermines the potentially positive impact of social health insurance on the health of the marginalized. In the Philippines, where the largest burden of health care spending falls on households, underutilization suggests ineffective distribution of public funds, failing to reach a significant proportion of households which are by and large poor. Interventions that improve benefit awareness may combat the problem of underutilization and should be the focus of further research in this area.     

Cyclooxygenase-2 and Prostaglandin E2 Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute Trypanosoma cruzi Infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68⁺ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b⁺Ly6G^- cells purified from infected heart tissue express COX-2 and produce prostaglandin E₂ (PGE₂) ex vivo. T. cruzi infections in COX-2 or PGE₂-dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.     

Intraseasonal variation in immune defence,body mass and hematocrit in adult house martins Delichon urbica

The intensity of parasite infections often increases during the reproductive season of the host as a result of parasite reproduction, increased parasite transmission and increased host susceptibility. We report within‐individual variation in immune parameters, hematocrit and body mass in adult house martins Delichon urbica rearing nestlings in nests experimentally infested with house martin bugs Oeciacus hirundinis and birds rearing nestlings in initially parasite‐free nests. From first to second broods body mass and hematocrit of breeding adult house martins decreased. In contrast leucocytes and immunoglobulins became more abundant. When their nests were infested with ectoparasites adults lost more weight compared with birds raising nestlings in nests treated with pyrethrin, whereas the decrease in hematocrit was more pronounced during infection with blood parasites. Neither experimental infestation with house martin bugs nor blood parasites had a significant effect on the amount of immune defences.     

Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool.     

Use of cloned populations of mouse lymphocytes to analyze cellular differentiation

We describe a method for generation of homogeneous cell populations that each arise from clonal expansion of cells at a discrete stage of differentiation within a single lineage. We have used this to produce continuously propagatable lymphocyte clones. Each clone represents a cell at a progressive stage of thymus-dependent cellular differentiation. These cloned cells bear stable surface membrane glycoproteins characteristic of precursor cells and mature progeny; conditions allowing maximal cloning efficiencies for each cell type (10–85%) have been established. Mature lymphocyte clones continue to express specialized function and provide material for biochemical analysis of T lymphocyte functions; one fully differentiated clone from the “inducer” lymphocyte set synthesizes a molecule that activates other lymphocytes to secrete immunoglobulin. This activity is associated with a highly purified molecule having a molecular weight of 45,000 daltons and an isoelectric point of approximately 6.0. This molecule, together with clones of precursor and mature T lymphocytes, may provide a system to further study the mechanisms of gene activation during cellular differentiation.     

Communication via sex pheromones within and among Arrenurus spp. mites (Acari: Hydrachnida; Arrenuridae)

We present direct experimental evidence of pheromone use in six species of Arrenurus and indirect evidence for four species, including members of the subgenera Megaluracarus, Truncaturus, and Arrenurus. Water in which females were housed elicited arrestant behaviour in males, males oriented to the source, and at least some individuals in each species assumed the male readiness posture, a precursor to coupling. Most species responded to water treated with conspecific females, but there was also interspecific sex pheromone responsiveness. Arrenurus manubriator and A. megalurus demonstrated reciprocal pheromone cross-attractancy. Males of A. major, A. marshallae, and A. birgei responded to water from females of related species from within their subgenera. Arrenurus apetiolatus males failed to respond to conspecific female-treated water, but the same water elicited arrestant behaviour and orientation in A. manubriator. Heterospecific reactions to female-conditioned water were limited to cases involving members of the same species group and were not seen between species representing different species groups or different subgenera. The species for which cross-attractancy has been demonstrated commonly co-occur in nature, so apparently these pheromones are of limited value for species recognition. Shared reaction to sex pheromones provides additional evidence for inferring close phylogenetic relationship among species, and thus far, corresponds with morphological evidence based on adult males and larvae.