Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone: a prospective, longitudinal study

Major depressive disorder (MDD) is frequently diagnosed in military personnel returning from deployment. Literature suggests that MDD is associated with a pro-inflammatory state. To the best of our knowledge, no prospective, longitudinal studies on the association between development of depressive symptomatology and cytokine production by peripheral blood leukocytes have been published. The aim of this study was to investigate whether the presence of depressive symptomatology six months after military deployment is associated with the capacity to produce cytokines, as assessed before and after deployment. 1023 military personnel were included before deployment. Depressive symptoms and LPS- and T-cell mitogen-induced production of 16 cytokines and chemokines in whole blood cultures were measured before (T0), 1 (T1), and 6 (T2) months after return from deployment. Exploratory structural equation modeling (ESEM) was used for data reduction into cytokine patterns. Multiple group latent growth modeling was used to investigate differences in the longitudinal course of cytokine production between individuals with (n = 68) and without (n = 665) depressive symptoms at T2. Individuals with depressive symptoms after deployment showed higher T-cell cytokine production before deployment. Moreover, pre-deployment T-cell cytokine production significantly predicted the presence of depressive symptomatology 6 months after return. There was an increase in T-cell cytokine production over time, but this increase was significantly smaller in individuals developing depressive symptoms. T-cell chemokine and LPS-induced innate cytokine production decreased over time and were not associated with depressive symptoms. These results indicate that increased T-cell mitogen-induced cytokine production before deployment may be a vulnerability factor for development of depressive symptomatology in response to deployment to a combat-zone. In addition, deployment to a combat-zone affects the capacity of T-cells and monocytes to produce cytokines and chemokines until at least 6 months after return.     

DNA barcoding of euryglossine bees and the description of new species of Euhesma Michener (Hymenoptera,Colletidae, Euryglossinae)

This paper launches an open access DNA barcoding project “AUSBS” under the Barcoding of Life Datasystems (BOLD). The aims of the project are to help scientists who lack the necessary morphological knowledge to identify known species using molecular markers, to aid native bee specialists with the recognition of species groups that morphologically are difficult to define, and, eventually, to assist with the recognition of new species among known species. Using integrative taxonomy, i.e. morphological comparison to type specimens in Australian museum collections combined with phylogenetic analysis of a fragment of the mitochondrial DNA cytochrome c oxidase subunit I (mtCOI) gene sequences led to the recognition of four new species of Euhesma Michener (Hymenoptera: Colletidae: Euryglossini) collected during intensive surveys in remote Australian conservation areas, which are described. The new species are Euhesma micans, Euhesma lyngouriae, and Euhesma aulaca in a species group associated with Eremophila flowers, and Euhesma albamala in the walkeriana species group.     

ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation

Upon damage of DNA in eukaryotic cells, several repair and checkpoint proteins undergo a dramatic intranuclear relocalization, translocating to nuclear foci thought to represent sites of DNA damage and repair. Examples of such proteins include the checkpoint kinase ATR (ATM and Rad3-related) as well as replication protein A (RPA), a single-stranded DNA binding protein required in DNA replication and repair. Here, we used a microscopy-based approach to investigate whether the damage-induced translocation of RPA is an active process regulated by ATR. Our data show that in undamaged cells, ATR and RPA are uniformly distributed in the nucleus or localized to promyelocytic leukemia protein (PML) nuclear bodies. In cells treated with ionizing radiation, both ATR and RPA translocate to punctate, abundant nuclear foci where they continue to colocalize. Surprisingly, an ATR mutant that lacks kinase activity fails to relocalize in response to DNA damage. Furthermore, this kinase-inactive mutant blocks the translocation of RPA in a cell cycle-dependent manner. These observations demonstrate that the kinase activity of ATR is essential for the irradiation-induced release of ATR and RPA from PML bodies and translocation of ATR and RPA to potential sites of DNA damage.     

The Challenge of Living On: Psychopathology and Its Mediating Influence on the Readjustment of Former Child Soldiers

Current civil wars are characterized by the increasing involvement of civilian populations and the systematic employment of child soldiers. An example of such wars was the conflict in Northern Uganda, where the war-affected population is still challenged by the reintegration of formerly abducted children and youths. A cross-sectional, population-based survey, using a multistage cluster sampling approach of 1,113 Northern Ugandans aged between 12 and 25 in camps for internally displaced persons and locally validated instruments was conducted to assess symptoms and diagnoses of Posttraumatic Stress Disorder (PTSD) and probable Depression in war-affected, as well as formerly abducted individuals. Further objectives were to determine predictors of psychopathology and to relate indicators of maladjustment (i.e., impairments in daily and community functioning, somatic complaints, suicidality, aggressiveness and discrimination) to abduction, level of exposure to violence and psychopathology. 43% of the sample reported abduction by the rebel army. Exposure to violence among this group was higher than for non-abducted youths (t = 28.05; p<.001). PTSD point prevalence rates were 25% among former child soldiers and 7% among the comparison group. High suicidal ideation was present in 16% and 6% respectively. A higher amount of experienced and witnessed event-types (β = . 32. p<.001), loss of first-degree relatives (β = .13. p<.001) and the number of event-types involving forced perpetration (β = .23. p<.001) were identified as risk factors of PTSD symptoms in former child soldiers. The associations between abductee-status and indicators of maladjustment were fully mediated by level of trauma exposure and psychopathology. Results show that child soldiering and its psychological sequelae affect a substantial proportion of children and youths. After release or flight, their readjustment depends at least partly on their level of mental traumatization.     

Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosoma cruzi infection in mice

In this study, we examined the tissue specificity of inflammatory and oxidative responses and mitochondrial dysfunction in mice infected by Trypanosoma cruzi. In acute mice, parasite burden and associated inflammatory infiltrate was detected in all tissues (skeletal muscle>heart>stomach>colon). The extent of oxidative damage and mitochondrial decay was in the order of heart>stomach>skeletal muscle>colon. In chronic mice, a low level of parasite burden and inflammation continued in all tissues; however, oxidant overload and mitochondrial inefficiency mainly persisted in the heart tissue (also detectable in stomach). Further, we noted an unvaryingly high degree of oxidative stress, compromised antioxidant status, and decreased mitochondrial respiratory complex activities in peripheral blood of infected mice. A pair-wise log analysis showed a strong positive correlation in the heart-versus-blood (but not other tissues) levels of oxidative stress markers (malonyldialdehyde, glutathione disulfide), antioxidants (superoxide dismutase, MnSOD, catalase), and mitochondrial inhibition of respiratory complexes (CI/CIII) in infected mice. T. cruzi-induced acute inflammatory and oxidative responses are widespread in different muscle tissues. Antioxidant/oxidant status and mitochondrial function are consistently attenuated in the heart, and reflected in the peripheral-blood of T. cruzi-infected mice. Our results provide an impetus to investigate the peripheral-blood oxidative responses in relation to clinical severity of heart disease in chagasic human patients.     

Poly(ethylene glycol) microparticles produced by precipitation polymerization in aqueous solution

Methods were developed to perform precipitation photopolymerization of PEG-diacrylate. Previously, comonomers have been added to PEG when precipitation polymerization was desired. In the present method, the LCST of the PEG itself was lowered by the addition of the kosmotropic salt sodium sulfate to an aqueous solution. Typical of a precipitation polymerization, small microparticles or microspheres (1-5 μm) resulted with relatively low polydispersity. However, aggregate formation was often severe, presumably because of a lack of stabilization of the phase-separated colloids. Microparticles were also produced by copoymerization of PEG-diacrylate with acrylic acid or aminoethylmethacrylate. The comonomers affected the zeta potential of the formed microparticles but not the size. The carboxyl groups of acrylic-acid-containing PEG microparticles were activated, and scaffolds were formed by mixing with amine-containing PEG microparticles. Although the scaffolds were relatively weak, human hepatoma cells showed excellent viability when present during microparticle cross-linking.     

Impaired activity of volume-sensitive Cl- channel is involved in cisplatin resistance of cancer cells

The platinum-based drug cisplatin is a widely used anticancer drug which acts by causing the induction of apoptosis. However, resistance to the drug is a major problem. In this study we show that the KCP-4 human epidermoid cancer cell line, which serves as a model of acquired resistance to cisplatin, has virtually no volume-sensitive, outwardly rectifying (VSOR) chloride channel activity. The VSOR chloride channel's molecular identity has not yet been determined, and semi-quantitative RT-PCR experiments in this study suggested that the channel corresponds to none of three candidate genes. However, because it is known that the channel current plays an essential role in apoptosis, we hypothesized that lack of the current contributes to cisplatin resistance in these cells and that its restoration would reduce resistance. To test this hypothesis, we attempted to restore VSOR chloride current in KCP-4 cells. It was found that treatment with trichostatin A (TSA), a histone deacetylase inhibitor, caused VSOR chloride channel function to be partially restored. Treatment of the cells with both TSA and cisplatin resulted in an increase in caspase-3 activity at 24 h and a decrease in cell viability at 48 h. These effects were blocked by simultaneous treatment of the cells with a VSOR chloride channel blocker. These results indicate that restoration of the channel's functional expression by TSA treatment leads to a decrease in the cisplatin resistance of KCP-4 cells. We thus conclude that impaired activity of the VSOR chloride channel is involved in the cisplatin resistance of KCP-4 cancer cells.