Functional characterization of endogenous siRNA target genes in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>Small interfering RNA (siRNA) molecules mediate sequence specific silencing in RNA interference (RNAi), a gene regulatory phenomenon observed in almost all organisms. Large scale sequencing of small RNA libraries obtained from <it>C. elegans </it>has revealed that a broad spectrum of siRNAs is endogenously transcribed from genomic sequences. The biological role and molecular diversity of <it>C. elegans </it>endogenous siRNA (endo-siRNA) molecules, nonetheless, remain poorly understood. In order to gain insight into their biological function, we annotated two large libraries of endo-siRNA sequences, identified their cognate targets, and performed gene ontology analysis to identify enriched functional categories.</p> <p>Results</p> <p>Systematic trends in categorization of target genes according to the specific length of siRNA sequences were observed: 18- to 22-mer siRNAs were associated with genes required for embryonic development; 23-mers were associated uniquely with post-embryonic development; 24–26-mers were associated with phosphorus metabolism or protein modification. Moreover, we observe that some argonaute related genes associate with siRNAs with multiple reads. Sequence frequency graphs suggest that different lengths of siRNAs share similarities in overall sequence structure: the 5' end begins with G, while the body predominates with U and C.</p> <p>Conclusion</p> <p>These results suggest that the lengths of endogenous siRNA molecules are consequential to their biological functions since the gene ontology categories for their cognate mRNA targets vary depending upon their lengths.</p

Increased [H-3] quisqualic acid binding density in the dorsal striatum and anterior insula of alcoholics : A post-mortem whole-hemisphere autoradiography study

The function of group I metabotropic glutamate receptors mGluR1 and mGluR5 is involved in the hyperglutamatergic state caused by chronic alcohol. Preclinical studies suggest that group I mGluR modulation could serve as a novel treatment of alcoholism. Considering the wide role of glutamatergic neurochemistry in addiction, group I mGluR binding was studied in brain areas involved in decision-making, learning and memory. Post-mortem whole hemisphere autoradiography was used to study the binding density of [H-3] quisqualic acid, a potent group I mGluR agonist, in 9 Cloninger type 1 alcoholics, 8 Cloninger type 2 alcoholics and 10 controls. Binding was studied in the dorsal striatum, hippocampus and cortex. Alcoholics displayed a trend towards increased [ H-3] quisqualic acid binding in all brain areas. The most robust findings were in the putamen (p = 0.006) and anterior insula (p = 0.005), where both alcoholic subtypes displayed increased binding compared to the controls. These findings suggest altered group I mGluR function in alcoholic subjects in the dorsal striatum, which is involved in habitual learning, and in the anterior insula, which has a pivotal role in the perception of bodily sensations. Increased [H-3] quisqualic acid binding might suggest a beneficial impact of mGluR1/5 modulators in the treatment of alcoholism.Peer reviewe

The Association of Ambient Temperature and Violent Crime

It is controversial if global warming will result into increased crime and conflict rate, and no causal neurobiological mechanisms have been proposed for the putative association between ambient temperature and aggressive behavior. This study shows that during 1996-2013, ambient temperature explained 10% of variance in the violent crime rate in Finland, corresponding to a 1.7% increase/degree centigrade. Ambient temperature also correlated with a one month delay in circannual changes in peripheral serotonin transporter density among both offenders and healthy control subjects, which itself correlated strongly with the monthly violent crime rate. This suggests that rise in temperature modulates serotonergic transmission which may increase impulsivity and general human activity level, resulting into increase in social interaction and risk of violent incidents. Together, these results suggest that the effect of ambient temperature on occurrence of violent crime is partly mediated through the serotonergic system, and that a 2 degrees C increase in average temperatures would increase violent crime rates by more than 3% in non-tropical and non-subtropical areas, if other contributing factors remained constant.Peer reviewe

TAFFEL: Independent Enrichment Analysis of gene sets

<p>Abstract</p> <p>Background</p> <p>A major challenge in genomic research is identifying significant biological processes and generating new hypotheses from large gene sets. Gene sets often consist of multiple separate biological pathways, controlled by distinct regulatory mechanisms. Many of these pathways and the associated regulatory mechanisms might be obscured by a large number of other significant processes and thus not identified as significant by standard gene set enrichment analysis tools.</p> <p>Results</p> <p>We present a novel method called Independent Enrichment Analysis (IEA) and software TAFFEL that eases the task by clustering genes to subgroups using Gene Ontology categories and transcription regulators. IEA indicates transcriptional regulators putatively controlling biological functions in studied condition.</p> <p>Conclusions</p> <p>We demonstrate that the developed method and TAFFEL tool give new insight to the analysis of differentially expressed genes and can generate novel hypotheses. Our comparison to other popular methods showed that the IEA method implemented in TAFFEL can find important biological phenomena, which are not reported by other methods.</p

Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics

Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of alcoholics (N = 14) and non-alcoholic controls (N = 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior cingulate cortex (ACC), and anterior insula (AINS). DHEA levels were increased in most alcoholic subjects compared to controls. However, only a subgroup of alcoholics showed increased PREGN levels. Negative Spearman correlations between tissue levels of PREGN and previous reports of [H-3]naloxone binding to mu-opioid receptors were observed in the AINS, ACC, NAC, and frontal cortex (R values between -0.6 and -.8; p valuesPeer reviewe