Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity,Cognition and Antipsychotic Medication

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.     

Improving wastewater effluent filtration by changing flow regimes—Investigations in two cold climate pilot scale systems

Two pilot-scale experimental filter systems (FSs) filled with light-weight aggregates (LWA) or crushed limestone (CL) and operated under different flow regimes were established during the summer of 2005. The main objective of the study was to compare continuous-flow hybrid CL and LWA filters and batch-operated LWA filters in order to determine optimal loading, design parameters, management schemes and operational regimes for LWA-based FSs in cold climate conditions for the secondary treatment of domestic wastewater. With higher re-circulation rates of treated water, purification efficiency increased in terms of most water quality indicators in both types of filter systems. In the batch-operated FS the highest purification efficiencies of 96% and 51% for BOD₇ and N_tot, respectively, were achieved when the re-circulation rate of 200% was applied. In the continuous-flow FS the highest purification efficiencies of 99% and 81% for BOD₇ and N_tot, respectively, were achieved when the re-circulation rate up to 300% was applied. In order to achieve effective organic matter removal, nitrification/denitrification and TSS removal, the re-circulation rate must be from 100% to 300% of the inflowing wastewater. Both FS designs, the continuous-flow hybrid systems and the batch-operated filters, are suitable for the secondary treatment of domestic wastewater in cold climate conditions.     

Common growth signal and spatial synchrony of the chronologies of tree-rings from pines in the Baltic Sea region over the last nine centuries

The common growth signal and spatial synchrony of nine chronologies of tree rings (Pinus sylvestris L.) from the Baltic Sea region were studied using moving correlations with time windows of 50 and 100 years. Drifts from synchrony to asynchrony and again back to synchrony across several centuries were observed. The chronologies showed higher (or lower) coefficients of correlations and correspondingly gentler (or steeper) declines in spatial synchrony in certain periods. In accordance with research into other ecological phenomena, the origin of the spatial synchrony was found to relate to the intensity of the westerly circulation over the Atlantic and Europe as described by the North Atlantic Oscillation (NAO) index. The tree rings from all of the analysed subregions were found to be wider, identifying faster periods of growth, when there was a positive NAO during the extended winter season from December to March that preceded the period of growth. Previous studies showed that the NAO index can be linked with the growth of tree rings because of factors in the local climate that affect growth, such as temperature and precipitation. Moreover, the spatial synchrony showed multidecadal fluctuations that were correlated with variations of a similar scale in the reconstructed NAO index. However, a high degree of spatial synchrony was observed during the 20^th century in the presence of values of NAO index that were strongly negative. A more detailed view was provided by maps of the correlations in which spatial changes were demonstrated in the growth of pines between the 12^th and the 20^th century. These results could be used as background information in the development of improved proxy-based reconstructions of the NAO index (or other similar meteorological variables), which could also be inferred from tree ring data relating to earlier centuries.     

Gap junction-mediated bystander effect in primary cultures of human malignant gliomas with recombinant expression of the HSVtk gene

The ability of herpes simplex virus type 1 thymidine kinase (HSV-tk)-expressing cells incubated with ganciclovir (GCV) to induce cytotoxicity in neighboring HSV-tk-negative (bystander) cells has been well documented. Although it has been suggested that this bystander cell killing occurs via the transfer of phosphorylated GCV, the mechanism(s) of this bystander effect and the importance of gap junctions for the effect of prodrug/suicide gene therapy in primary human glioblastoma cells remains elusive. Surgical biopsies of malignant gliomas were used to establish explant primary cultures. Proliferating tumor cells were characterized immunohistochemically and found to express glial tumor markers including nestin, vimentin, glial fibrillary acidic protein (GFAP), S-100, and gap junction protein connexin 43 (Cx43). Western blot analysis revealed the presence of phosphorylated isoforms of Cx43 and Calcein/DiI fluorescent dye transfer showed evidence of efficient gap junction communication (GJC). In order to study the effect(s) of prodrug/suicide gene therapy in these cultures, human glioblastoma cell cultures were transfected with the HSVtk gene for transient or stable expression. Ganciclovir treatment of these cultures led to >90% of cells dead within 1 week. Eradication of cells could be inhibited by the addition of α-glycyrrhetinic acid (AGA), a GJC inhibitor. In parallel experiments, AGA decreased the immunodetection of phosphorylated Cx43 as analyzed by Western blot and inhibited fluorescent dye transfer. In conclusion, these observations are consistent with GJC as the mediator of the bystander effect in primary cultures of human glioblastoma cells by the transfer of phosphorylated GCV from HSVtk gene transfected cells to untransfected ones.     

Expression of ric-8 (synembryn) gene in the nervous system of developing and adult mouse

Recent biochemical studies revealed that ric-8A encodes a guanine nucleotide exchange factor for a subset of Galpha proteins. Ric-8 is a key component of a signaling network in C. elegans that regulates neurotransmitter secretion and also plays a role in centrosome-mediated events during early embryogenesis. Here we show that during the early development in mice (E9.5-E12.0) ric-8 (synembryn) is expressed in the developing nervous system such as the cranial ganglia, neural tube, sympathetic chain and dorsal root ganglia. Ric-8 is also found in the lens, vomeronasal organ, and endolymphatic sac. In adult brain, it is expressed in the neocortex, hippocampus, and cerebellum as well as in the pineal gland and ependymal layer.     

Epitope of titin A-band-specific monoclonal antibody Tit1 5 H1.1 is highly conserved in several Fn3 domains of the titin molecule. Centriole staining in human,mouse and zebrafish cells

Background

Previously we have reported on the development of a new mouse anti-titin monoclonal antibody, named MAb Titl 5 H1.1, using the synthetic peptide N-AVNKYGIGEPLESDSVVAK-C which corresponds to an amino acid sequence in the A-region of the titin molecule as immunogen. In the human skeletal muscles, MAb Titl 5 H1.1 reacts specifically with titin in the A-band of the sarcomere and in different non-muscle cell types with nucleus and cytoplasm, including centrioles. In this report we have studied the evolutionary aspects of the binding of MAb Tit1 5 H1.1 with its target antigen (titin).

Results

We have specified the epitope area of MAb Tit1 5 H1.1 by subpeptide mapping to the hexapeptide N-AVNKYG-C. According to protein databases this amino acid sequence is located in the COOH-terminus of several different Fn3 domains of the A-region of titin molecule in many organisms, such as human being, mouse, rabbit, zebrafish (Danio rerio), and even in sea squirt (Ciona intestinalis). Our immunohisto- and cytochemical studies with MAb Tit1 5 H1.1 in human, mouse and zebrafish tissues and cell cultures showed a striated staining pattern in muscle cells and also staining of centrioles, cytoplasm and nuclei in non-muscle cells.

Conclusions

The data confirm that titin can play, in addition to the known roles in striated muscle cells also an important role in non-muscle cells as a centriole associated protein. This phenomenon is highly conserved in the evolution and is related to Fn3 domains of the titin molecule. Using titin A-band-specific monoclonal antibody MAb Tit1 5 H1.1 it was possible to locate titin in the sarcomeres of skeletal muscle cells and in the centrioles, cytoplasm and nuclei of non-muscle cells in phylogenetically so distant organisms as Homo sapiens, Mus musculus and zebrafish (Danio rerio).

     

生物毒素的应用研究

概述了生物毒素对人类以及农业、畜牧业和海洋渔业的危害,并阐述了生物毒素在生物学、药学、医学及军事科学中的应用研究现状及最新进展;同时对生物毒素研究的发展趋势进行了分析,这将为生物毒素的合理开发利用奠定基础。