IMPORTANCE Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects. OBJECTIVE To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine. DESIGN In silico predictions, in vitro, and case-control investigations. SETTING Academic and clinical facilities. PARTICIPANTS The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. EXPOSURES Patients received olanzapine monotherapy for 8 weeks. MAIN OUTCOMES AND MEASURES In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia. RESULTS Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment. CONCLUSIONS AND RELEVANCE Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and functionally contributes to genetic modulation of known endophenotypes of schizophrenia-like higher-level cognitive behaviors and related prefrontal activity, as well as response to treatment with olanzapine.

Novel alternatively spliced variants of the human mitochondrial transcription factor A predicted by the computational tool ASPic were experimentally validated in different normal and tumoral human tissues by RT-PCR and DNA sequencing. The comparison between the 5′UTR length and the distribution of the different transcripts showed that the transcripts with the shortest 5′UTR are present in all the investigated tissues, while the longest 5′UTR seems to be related to tissue-specificity. Studies about the localization and function of the most widely diffuse alternative isoform Tr6 were carried out.

Salmonella enterica subsp. enterica serovar Gallinarum (S. Gallinarum) is the causative agent of fowl typhoid, a major threat in poultry which causes mortality and high morbidity. The standard method for detection of S. Gallinarum relies on culture isolation and it requires more than five days for final confirmation. Recently, molecular methods have been developed, but they are not considered as golden standards, also because they do not allow pathogen quantification. Therefore, we developed a real time quantitative PCR (qPCR) which may represent a fast and accurate method that reduce drastically the extent of the analytical process, while being sensitive and specific. In order to grant specificity, a specific probe has been designed to detect the amplification products. The method has been tested in vitro and it has been proved to be effective for detection and absolute quantification of S. Gallinarum. In particular we found high sensitivity and specificity, with accuracy higher than 98%. Therefore, we find that the method may be suitable for diagnostic and other application, such as environmental monitoring.