Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

THETA-rhythm makes the world go round:dissociative effects of TMS theta versus alpha entrainment of right pTPJ on embodied perspective transformations

Being able to imagine another person's experience and perspective of the world is a crucial human ability and recent reports suggest that humans "embody" another's viewpoint by mentally rotating their own body representation into the other's orientation. Our recent Magnetoencephalography (MEG) data further confirmed this notion of embodied perspective transformations and pinpointed the right posterior temporo-parietal junction (pTPJ) as the crucial hub in a distributed network oscillating at theta frequency (3-7 Hz). In a subsequent transcranial magnetic stimulation (TMS) experiment we interfered with right pTPJ processing and observed a modulation of the embodied aspects of perspective transformations. While these results corroborated the role of right pTPJ, the notion of theta oscillations being the crucial neural code remained a correlational observation based on our MEG data. In the current study we therefore set out to confirm the importance of theta oscillations directly by means of TMS entrainment. We compared entrainment of right pTPJ at 6 Hz vs. 10 Hz and confirmed that only 6 Hz entrainment facilitated embodied perspective transformations (at 160° angular disparity) while 10 Hz slowed it down. The reverse was true at low angular disparity (60° between egocentric and target perspective) where a perspective transformation was not strictly necessary. Our results further corroborate right pTPJ involvement in embodied perspective transformations and highlight theta oscillations as a crucial neural code

Alteration assemblages in Martian meteorites: implications for near-surface processes

The SNC (Shergotty-Nakhla-Chassigny) meteorites have recorded interactions between martian crustal fluids and the parent igneous rocks. The resultant secondary minerals – which comprise up to 1 vol.% of the meteorites – provide information about the timing and nature of hydrous activity and atmospheric processes on Mars. We suggest that the most plausible models for secondary mineral formation involve the evaporation of low temperature (25 – 150 °C) brines. This is consistent with the simple mineralogy of these assemblages – Fe-Mg-Ca carbonates, anhydrite, gypsum, halite, clays – and the chemical fractionation of Ca-to Mg-rich carbonate in ALH84001 "rosettes". Longer-lived, and higher temperature, hydrothermal systems would have caused more silicate alteration than is seen and probably more complex mineral assemblages. Experimental and phase equilibria data on carbonate compositions similar to those present in the SNCs imply low temperatures of formation with cooling taking place over a short period of time (e.g. days). The ALH84001 carbonate also probably shows the effects of partial vapourisation and dehydration related to an impact event post-dating the initial precipitation. This shock event may have led to the formation of sulphide and some magnetite in the Fe-rich outer parts of the rosettes. Radiometric dating (K-Ar, Rb-Sr) of the secondary mineral assemblages in one of the nakhlites (Lafayette) suggests that they formed between 0 and 670 Myr, and certainly long after the crystallisation of the host igneous rocks. Crystallisation of ALH84001 carbonate took place 0.5 Gyr after the parent rock. These age ranges and the other research on these assemblages suggest that environmental conditions conducive to near-surface liquid water have been present on Mars periodically over the last 1 Gyr. This fluid activity cannot have been continuous over geological time because in that case much more silicate alteration would have taken place in the meteorite parent rocks and the soluble salts would probably not have been preserved. The secondary minerals could have been precipitated from brines with seawater-like composition, high bicarbonate contents and a weakly acidic nature. The co-existence of siderite (Fe-carbonate) and clays in the nakhlites suggests that the pCO2 level in equilibrium with the parent brine may have been 50 mbar or more. The brines could have originated as flood waters which percolated through the top few hundred meters of the crust, releasing cations from the surrounding parent rocks. The high sulphur and chlorine concentrations of the martian soil have most likely resulted from aeolian redistribution of such aqueously-deposited salts and from reaction of the martian surface with volcanic acid volatiles. The volume of carbonates in meteorites provides a minimum crustal abundance and is equivalent to 50–250 mbar of CO2 being trapped in the uppermost 200–1000 m of the martian crust. Large fractionations in 18O between igneous silicate in the meteorites and the secondary minerals (30) require formation of the latter below temperatures at which silicate-carbonate equilibration could have taken place (400°C) and have been taken to suggest low temperatures (e.g. 150°C) of precipitation from a hydrous fluid

Prescribing exercise and lifestyle training for high risk women in pregnancy and early post-partum—is it worth it?

In a Perspective, Jane Norman and Rebecca Reynolds discuss two randomized controlled trials aimed at testing behavioral interventions for women at risk of gestational diabetes

Recovery of ζ-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer

Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent ζ-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including ζ-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for ζ-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower ζ-chain expression in circulating CD3+ cells and a higher percentage of ζ-chain negative CD3+ and CD4+ cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of ζ-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer

Preparation of Group I Introns for Biochemical Studies and Crystallization Assays by Native Affinity Purification

The study of functional RNAs of various sizes and structures requires efficient methods for their synthesis and purification. Here, 23 group I intron variants ranging in length from 246 to 341 nucleotides—some containing exons—were subjected to a native purification technique previously applied only to shorter RNAs (<160 nucleotides). For the RNAs containing both exons, we adjusted the original purification protocol to allow for purification of radiolabeled molecules. The resulting RNAs were used in folding assays on native gel electrophoresis and in self-splicing assays. The intron-only RNAs were subjected to the regular native purification scheme, assayed for folding and employed in crystallization screens. All RNAs that contained a 3′ overhang of one nucleotide were efficiently cleaved off from the support and were at least 90% pure after the non-denaturing purification. A representative subset of these RNAs was shown to be folded and self-splicing after purification. Additionally, crystals were grown for a 286 nucleotide long variant of the Clostridium botulinum intron. These results demonstrate the suitability of the native affinity purification method for the preparation of group I introns. We hope these findings will stimulate a broader application of this strategy to the preparation of other large RNA molecules

Patterns of genetic diversity and differentiation in the tsetse fly Glossina morsitans morsitans Westwood populations in East and southern Africa

Genetic diversity and differentiation within and among nine G. morsitans morsitanspopulations from East and southern Africa was assessed by examining variation at seven microsatellite loci and a mitochondrial locus, cytochrome oxidase (COI). Mean COI diversity within populations was 0.63 ± 0.33 and 0.81 taken over all populations. Diversities averaged over microsatellite loci were high (mean number of alleles/locus ≥7.4; mean H E ≥ 65%) in all populations. Diversities averaged across populations were greater in East Africa (mean number of alleles = 22 ± 2.6; mean h e = 0.773 ± 0.033) than in southern Africa (mean number of alleles = 18.7 ± 4.0; mean h e = 0.713 ± 0.072). Differentiation among all populations was highly significant (R ST = 0.25, F ST = 0.132). Nei’s G ij statistics were 0.09 and 0.19 within regions for microsatellites and mitochondria, respectively; between regions, G ij was 0.14 for microsatellites and 0.23 for mitochondria. G ST among populations was 0.23 for microsatellite loci and 0.40 for mitochondria. The F, G and R statistics indicate highly restricted gene flow among G. m. morsitans populations separated over geographic scales of 12–917 km

Impaired working speed and executive functions as frontal lobe dysfunctions in young first-degree relatives of schizophrenic patients

The aim of the investigation was to detect neuropsychological markers, such as sustained and selective attention and executive functions, which contribute to the vulnerability to schizophrenia especially in young persons. Performance was assessed in 32 siblings and children of schizophrenic patients and 32 matched controls using Wisconsin Card Sorting Test, Colour-Word-Interference-Test, Trail Making Test, and d2-Concentration-Test. The first-degree relatives showed certain impairments on all four tests, in particular, slower times on all time-limited tests. These results suggest the need for more time when completing neuropsychological tasks involving selected and focused attention, as well as cognitive flexibility, as a possible indicator of genetic vulnerability to schizophrenia