Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain.

Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2alpha (eukaryotic translation initiation factor 2 subunit alpha) dephosphorylation, significantly reduced KA-induced ER stress and neuronal death in vivo and in vitro. KA-induced rise in intracellular calcium was not affected by Salubrinal. The results show that ER responses are essential parts of excitotoxicity mediated by glutamate receptor activation and that Salubrinal decreases neuronal death in vivo. Inhibition of ER stress by small molecular compounds may be beneficial for treatment of various neuronal injuries and brain disorders

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

Filicide in Austria and Finland - A register-based study on all filicide cases in Austria and Finland 1995-2005

<p>Abstract</p> <p>Background</p> <p>Filicide is the tragic crime of murdering one's own child. Previous research has found that the offending parents are commonly depressed and that suicide is often associated as an actual act or an intention. Yet, filicide is an underreported crime and previous studies have been strained with methodological problems. No comprehensive international studies on filicide have been presented in the literature until now.</p> <p>Methods</p> <p>This was a descriptive, comprehensive, register-based study of all filicides in Austria and Finland during 1995-2005. Filicide-suicide cases were also included.</p> <p>Results</p> <p>Most of the perpetrators were the biological mothers; in Austria 72%, in Finland 52%. Suicide followed filicide either as an attempt or a fulfilled act in 32% and 54% of the cases in Austria and Finland, respectively. Psychotic mood disorders were diagnosed for 10% of the living perpetrators in Austria, and 12% in Finland. Non-psychotic depression was diagnosed in 9% of surviving perpetrators in Austria, 35% in Finland.</p> <p>Conclusion</p> <p>The data from the two countries demonstrated that filicide is such a multifaceted and rare phenomenon that national data from individual countries seldom offer sufficient scope for its thorough study. Further analyses are needed to produce a complete picture of filicide.</p

Time-Dependent Behavior of Cation Transport through Cellulose Acetate-Cationic Polyelectrolyte Membranes

Cation transport through a cellulose acetate-poly(N,N-dimethylaminoethyl methacrylate) membrane (CA:PDMAEMA) was studied with scanning electrochemical microscope (SECM) and the thickness increase of the membrane was monitored with ellipsometry. Upon addition of the polyelectrolyte PDMAEMA, the permeability of the probe cation (ferrocenium methanol, FcMeOH) was increased as much as 40-fold. Soaking membranes in an electrolyte solution doubled the permeability in plain CA membranes, whereas for PDMAEMA containing membranes the opposite was observed and the permeability was reduced by 20–40%. This time-dependent behavior is shown to be a result of the presence of PDMAEMA within the membrane matrix, thus providing an interesting platform for controllable membrane permeability

Comparison of three methods of DNA extraction from human bones with different degrees of degradation

There is a necessity for deceased identification as a result of many accidents and sometimes bones are the only accessible source of DNA. So far, a universal method that allows for extraction of DNA from materials at different stages of degradation does not exist. The aims of this study were: the comparison of three methods of DNA extraction from bones with different degree of degradation and an evaluation of the usefulness of these methods in forensic genetics. The efficiency of DNA extraction, the degree of extract contamination by polymerase chain reaction (PCR) inhibitors and the possibility of determining the STR loci profile were especially being compared. Nuclear DNA from bones at different states of degradation was isolated using three methods: classical, organic phenol–chloroform extraction, DNA extraction from crystal aggregates and extraction by total demineralisation. Total demineralisation is the best method for most cases of DNA extraction from bones, although it does not provide pure DNA. DNA extraction from aggregates removes inhibitors much better and is also a good method of choice when identity determination of exhumed remains is necessary. In the case of not buried bones (remains found outside) total demineralisation or phenol–chloroform protocols are more efficient for successful DNA extraction