Turkey’s Gallipoli centenary events are set to become the latest focal point in the Armenian genocide dispute

On 24 April, events will be held in Turkey to commemorate the First World War campaign in Gallipoli, which took place in 1915. Hayk Hovhannisyan writes, however, that the commemoration has generated controversy because it risks overshadowing another centenary: that of the mass killing of Armenians, which is traditionally marked on the same day. He argues that Turkey’s decision to bring the date forward one day from the usual date of 25 April was made for political reasons and that the international community should be more willing to criticise Turkey’s President Recep Tayyip Erdoğan over the issue

As Armenia moves closer to the EU, Russia is taking advantage of the country’s economic and geopolitical vulnerabilities to maintain its influence.

Like many former Soviet-states, Armenia has recently pursued closer relations with the EU, much to Russia’s displeasure. Hayk Hovhannisyan looks at Russia’s increasingly punitive stance towards Armenia, such as increasing gas prices and greater arms sales to Armenia’s rival, Azerbaijan. Armenia has been trying to walk a fine line not to infuriate the ‘bear’ to the north, but now, without further support from the West, its European integration is likely to become more complicated

As the global economic landscape undergoes significant transformation, Russia must reform its domestic and foreign policies to meet new challenges

Russia’s vast energy resources have long given the country substantial influence in the international arena. As Hayk Hovhannisyan notes, however, a number of current developments present a threat to Russia’s economic and global position. New energy supply routes and the shale gas extraction ‘boom’ may reduce demand for Russian energy resources; while a slowdown in the BRIC economies, allied with negotiations over the Transatlantic Trade and Investment Partnership (TTIP) and the Trans-Pacific Partnership (TPP), could have profound implications for the country’s economy

High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism

Functional characterization of a human histone gene cluster duplication

Histones are the major protein component of nucleosomes, and de novo histone synthesis is essential for packaging newly replicated DNA into chromatin. As a result, histone gene expression is exquisitely and functionally coupled with DNA replication. Vastly divergent organisms such as yeast, fly and human all demonstrate the phylogenetically conserved propensity to maintain clustering of histone genes at one or more genomic loci. Although specific mechanisms are unclear, clustering is presumed to be important for common stringent transcriptional control of these genes at the G1/S phase transition. In this study, we describe a genomic duplication of the human histone gene cluster located at chromosome 1q21, which effectively doubles the previously known size and gene number of that cluster. The duplication persists in all examined tissues and cell lines, and the duplicated genes are transcriptionally active. Levels of messenger RNAs for duplicated histone H4 genes are high relative to those for non-duplicated H4 genes. Our data suggest that transcriptionally robust histone H4 genes may have been preferentially duplicated during evolution

Six-Coordinate Nitrato Complexes of Iron Porphyrins with Trans S-Donor Ligands.

The reaction of dimethyl sulfide (DMS) and tetrahydrothiophene (THT) with thin, amorphous layers of the nitrato complexes Fe(Por)(η2-O2NO) (Por = meso-tetraphenylporphyrinato dianion or meso-tetra- p-tolylporphyrinato dianion) at low temperature leads to formation of the corresponding six-coordinate complexes Fe(Por)(L)(η1-ONO2) (L = DMS, THT) as characterized by Fourier transform infrared and optical spectroscopy measurements. Adduct formation was accompanied by bidentate-to-monodentate linkage isomerization of the nitrato ligand, with the FeIII center remaining in a high-spin electronic state. These adducts are thermally unstable; warming to room temperature restores the initial Fe(Por)(η2-O2NO) species

Maintenance of Open Chromatin and Selective Genomic Occupancy at the Cell Cycle-Regulated Histone H4 Promoter during Differentiation of HL-60 Promyelocytic Leukemia Cells

During the shutdown of proliferation and onset of differentiation of HL-60 promyelocytic leukemia cells, expression of the cell cycle-dependent histone genes is downregulated at the level of transcription. To address the mechanism by which this regulation occurs, we examined the chromatin structure of the histone H4/n (FO108, H4FN) gene locus. Micrococcal nuclease, DNase I, and restriction enzymes show similar cleavage sites and levels of sensitivity at the H4/n locus in both proliferating and differentiated HL-60 cells. In contrast, differentiation-related activation of the cyclin-dependent kinase inhibitor p21(cip1/WAF1) gene is accompanied by increased nuclease hypersensitivity. Chromatin immunoprecipitation assays of the H4/n gene reveal that acetylated histones H3 and H4 are maintained at the same levels in proliferating and postproliferative cells. Thus, the chromatin of the H4/n locus remains in an open state even after transcription ceases. Using ligation-mediated PCR to visualize genomic DNase I footprints at single-nucleotide resolution, we find that protein occupancy at the site II cell cycle element is selectively diminished in differentiated cells while the site I element remains occupied. Decreased occupancy of site II is reflected by loss of the site II binding protein HiNF-P. We conclude that H4 gene transcription during differentiation is downregulated by modulating protein interaction at the site II cell cycle element and that retention of an open chromatin conformation may be associated with site I occupancy

Transcriptional induction of the osteocalcin gene during osteoblast differentiation involves acetylation of histones h3 and h4

The remodeling of chromatin is required for tissue-specific gene activation to permit interactions of transcription factors and coregulators with their cognate elements. Here, we investigate the chromatin-mediated mechanisms by which the bone-specific osteocalcin (OC) gene is transcriptionally activated during cessation of cell growth in ROS 17/2.8 osteosarcoma cells and during normal osteoblast differentiation. Acetylation of histones H3 and H4 at the OC gene promoter was assayed during the proliferative and postproliferative stages of cell growth by using chromatin immunoprecipitation assays with antibodies that recognize different acetylated forms of histones H3 or H4. The results show that the promoter and coding regions of the OC gene contain very low levels of acetylated histones H3 and H4 during the proliferative period of osteoblast differentiation when the OC gene is inactive. Active expression of the OC gene in mature osteoblasts and confluent ROS 17/2.8 cells is functionally linked to preferential acetylation of histone H4 and, to a lesser extent, to acetylation of histone H3. Histone acetylation at the loci for RUNX2 (CBFA1), alkaline phosphatase, bone sialoprotein, osteopontin, and the cell growth regulator p21, which are expressed throughout osteoblast differentiation, is not altered postproliferatively. We conclude that acetylation of histones H3 and H4 is functionally coupled to the chromatin remodeling events that mediate the developmental induction of OC gene transcription in bone cells

Study of neuroprotective activity of new acetylcholinesterase inhibitors TVA and TVS in experimental model of Alzheimer’s disease

Introduction: Alzheimer’s disease (AD) is a severe neurodegenerative disease characterized by loss of synaptic connection between neurons of the cortex and subcortical regions. The cholinergic deficit is a consistent and early finding in AD, hence acetylcholinesterase inhibitors (AChEIs) are used for symptomatic improvement of AD. Most of these therapeutic agents are hepatotoxic, leading to liver failure and other complications. Therefore, the study of new AChEIs with less toxic impact and better effectivity is a topical challenge. In view of this, we synthesized novel chemical compounds: TVA and TVS that possess AChEI activity and studied their neuroprotective effect in an experimental AD model. Materials and methods: Studies were performed on white rats. Acute toxicity studies were performed by Karber’s method. AD was induced via bilateral intracerebroventricular administration of Aβ 25–35. Histopathological examinations were performed in the hippocampus and the entorhinal cortex. Liver tissue was additionally examined to monitor the hepatotoxicity of these compounds. Results: Studies of the hippocampus showed that compared to control and TVA-treated groups, under the influence of TVS there were few morphological alterations. Experimental groups showed an increase in the glial cell count, compared to the intact animals. In comparison to the AD group, the increase in microglia was not that prominent under the action of the novel compounds. Under the influence of TVA and TVS, the entorhinal cortex was more susceptible to neuronal injury, although TVS protected pyramidal neurons. Also, the group treated with TVA had signs of acute liver damage, while under the influence of TVS there were no signs of liver changes. Discussion: Histopathological examination showed that the neurodegenerative processes in the hippocampus, as well as in the entorhinal cortex, were significantly reduced under the influence of TVS, compared with the control group. At the same time, TVA had no significant effect on the protection of neuronal cells. Also, TVS was less toxic, and there was no sign of hepatotoxicity during the experiments. Conclusion: These studies demonstrated that TVS possesses neuroprotective activity and reduces neuronal damage induced by Aβ. Graphical abstract