Nuclear GAPDH in cortical microglia mediates cellular stress-induced cognitive inflexibility.

We report a mechanism that underlies stress-induced cognitive inflexibility at the molecular level. In a mouse model under subacute cellular stress in which deficits in rule shifting tasks were elicited, the nuclear glyceraldehyde dehydrogenase (N-GAPDH) cascade was activated specifically in microglia in the prelimbic cortex. The cognitive deficits were normalized with a pharmacological intervention with a compound (the RR compound) that selectively blocked the initiation of N-GAPDH cascade without affecting glycolytic activity.

A longitudinal characterization of the adaptive and behavioral profile in Sotos syndrome.

Delineation of a developmental and behavioral trajectory is a key-topic in the context of a genetic syndrome. Short- and long-term implications concerning school outcome, independent living, and working opportunities are strictly linked to the cognitive and behavioral profile of an individual. For the first time, we present a longitudinal characterization of the adaptive and behavioral profile of a pediatric sample of 32 individuals with Sotos Syndrome (SoS) (18 males, 14 females; mean age 9.

Maternal Multiple Sclerosis and Offspring's Cognitive and Behavioral Development: What Do We Know until Now?

Multiple Sclerosis (MS) is a chronic pathological condition representing one of the main causes of neurological disability in the female young population. MS, as an immune disorder, could impact fetus development, and, considering the need for and the possibility of pharmacological treatment during pregnancy, the possible influence of medication on developmental trajectories represents a topic of great interest. We provide an overview of the available literature on the influence of maternal Multiple Sclerosis on offspring cognitive and behavioral development.

Prenatal immune stress blunts microglia reactivity, impairing neurocircuitry.

Recent studies suggested that microglia, the primary brain immune cells, can affect circuit connectivity and neuronal function. Microglia infiltrate the neuroepithelium early in embryonic development and are maintained in the brain throughout adulthood. Several maternal environmental factors-such as an aberrant microbiome, immune activation and poor nutrition-can influence prenatal brain development.

Maternal Perinatal Depression and Risk of Neurodevelopmental Disorders in Offspring: Preliminary Results from the SOS MOOD Project.

The latest research is attempting to define whether there may be an association between maternal Perinatal Depression (PD), the use of psychotropic medications during pregnancy, and a higher risk of neurodevelopmental disorders in children, including Autism Spectrum Disorder (ASD). A better understanding of the relation between PD and ASD is a key element to develop early interventions. This study has been developed in the context of the SOS MOOD project.

Developmental Stressors Induce Innate Immune Memory in Microglia and Contribute to Disease Risk.

Many types of stressors have an impact on brain development, function, and disease susceptibility including immune stressors, psychosocial stressors, and exposure to drugs of abuse. We propose that these diverse developmental stressors may utilize a common mechanism that underlies impaired cognitive function and neurodevelopmental disorders such as schizophrenia, autism, and mood disorders that can develop in later life as a result of developmental stressors. While these stressors are directed at critical developmental windows, their impacts are long-lasting.

Carriage of Carbapenem-Resistant Enterobacterales in Adult Patients Admitted to a University Hospital in Italy.

The emerging spread of carbapenemase-producing Enterobacterales (CPE) strains, in particular, and , has become a significant threat to hospitalized patients. Carbapenemase genes are frequently located on plasmids than can be exchanged among clonal strains, increasing the antibiotic resistance rate. The aim of this study was to determine the prevalence of CPE in patients upon their admission and to analyze selected associated factors.

Plasmid Replicon Typing of Antibiotic-Resistant From Clams and Marine Sediments.

Unlike human isolates, environmental isolates have not been thoroughly investigated for the diversity and transferability of antibiotic-resistant plasmids. In this study, antibiotic-resistant strains from marine sediment ( = 50) and clams ( = 53) were analyzed (i) for their plasmid content using a PCR-based plasmid replicon typing (PBRT) kit and (ii) for the transferability of plasmid-associated antibiotic resistance (AR) traits by mating experiments. Fifteen of the thirty replicons targeted by the PBRT kit were detected in the isolates; 8/15 were identified in both sediment and clam isolates, although at different frequencies.

A negative feedback mechanism links UBC gene expression to ubiquitin levels by affecting RNA splicing rather than transcription.

UBC gene plays a critical role in maintaining ubiquitin (Ub) homeostasis. It is upregulated under stress conditions, and herein we report that it is downregulated upon Ub overexpression. Downregulation occurs in a dose-dependent manner, suggesting the existence of a fine-tuned Ub sensing mechanism.

Evaluation of PCR-based methods for the identification of enteroaggregative hemorrhagic Escherichia coli in sprouts.

In this study real-time PCR assays were evaluated for the detection of enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104:H4 in artificially contaminated mung bean and/alfalfa sprouts inoculated with 1, 10, and 100 CFU of EAHEC O104:H4 per 25 g sample (20, 10, and 2 replicates respectively). After selective culture enrichment the samples were tested using commercial real-time PCR kits detecting aggR/aaiC, stx/eae, and wzx. Using the commercial real-time PCR kits, the artificially contaminated samples were detected in the range of 75-80% positive results when contaminated with approximately 1 CFU, and 100% at 10 and 100 CFU.

Rapid and simultaneous detection of Salmonella spp., Escherichia coli O157, and Listeria monocytogenes by magnetic capture hybridization and multiplex real-time PCR.

The application of rapid, specific, and sensitive methods for pathogen detection and quantification is very advantageous in diagnosis of human pathogens in several applications, including food analysis. The aim of this study was the evaluation of a method for the multiplexed detection and quantification of three significant foodborne pathogenic species (Escherichia coli O157, Salmonella spp., and Listeria monocytogenes).

Detection of Shiga toxin-producing Escherichia coli (STEC) in ground beef and bean sprouts: Evaluation of culture enrichment conditions.

The main purpose of this work was to evaluate culture enrichment conditions, with particular regard to those reported in ISO/TS 13136:2012, for STEC detection in food. The culture media evaluated included mTSB with novobiocin 0-16mg/l (mTSB+N) or acriflavin 12mg/l (mTSB+A); BPW; mBPWp with acriflavin 10mg/l, cefsulodin 10mg/l, vancomycin 8mg/l (mBPWp+ACV); and mBPWp with cefsulodin 10mg/l, vancomycin 8mg/l (mBPWp+CV). They were used for the growth of STEC O157, O26, O103, O111, O145 and O104 in pure cultures or in artificially contaminated food matrices (ground beef, mung bean sprouts).

Prevalence and antibiotic resistance of Pseudomonas aeruginosa in water samples in central Italy and molecular characterization of oprD in imipenem resistant isolates.

Scope: This study aimed to analyse the prevalence, antibiotic resistance and genetic relatedness of P. aeruginosa isolates obtained from potable and recreational water samples (n. 8,351) collected from different settings (swimming pools, n.

Validation and application of a quantitative real-time PCR assay to detect common wheat adulteration of durum wheat for pasta production.

Pasta is the Italian product par excellence and it is now popular worldwide. Pasta of a superior quality is made with pure durum wheat. In Italy, addition of Triticum aestivum (common wheat) during manufacturing is not allowed and, without adequate labeling, its presence is considered an adulteration.

Comparative analysis of the standard PCR-Based Replicon Typing (PBRT) with the commercial PBRT-KIT.

Plasmids are the main vectors of resistance and virulence genes in Enterobacteriaceae and plasmid typing is essential for the analysis of evolution, epidemiology and spread of antibacterial resistance. The PCR-Based Replicon Typing (PBRT), developed by Carattoli et al. in 2005, was an efficient method for plasmid identification and typing in Enterobacteriaceae.

Presence of Escherichia coli O157, Salmonella spp., and Listeria monocytogenes in Raw Ovine Milk Destined for Cheese Production and Evaluation of the Equivalence Between the Analytical Methods Applied.

Italy is one of the main producers and exporters of cheese made from unpasteurized sheep milk. Since raw milk and its derived products are known sources of human infections, cheese produced from raw sheep milk could pose a microbiological threat to public health. Hence, the objectives of the study were: to characterize the potential risk of the presence of pathogens Escherichia coli O157, Listeria monocytogenes, and Salmonella in raw ovine milk destined for cheese production obtained from all the sheep farms (n = 24) in the Marches region (Central Italy) that directly transform raw milk into cheeses and to evaluate the equivalence between the analytical methods applied.

Molecular Dissection of the Human Ubiquitin C Promoter Reveals Heat Shock Element Architectures with Activating and Repressive Functions.

The promoter of the polyubiquitin C gene (UBC) contains putative heat shock elements (HSEs) which are thought to mediate UBC induction upon stress. However, the mapping and the functional characterization of the cis-acting determinants for its up-regulation have not yet been addressed. In this study, the sequence encompassing 916 nucleotides upstream of the transcription start site of the human UBC gene has been dissected by in silico, in vitro and in vivo approaches.

Effect of farm characteristics and practices on hygienic quality of ovine raw milk used for artisan cheese production in central Italy.

A survey on ovine dairy farms directly transforming own-produced milk, in the Italian Marche region, was carried out to assess flock and milking practices that may influence milk hygienic-sanitary conditions. A census survey established that 24 dairy farms were located in this region. Bulk milk samples were collected throughout the milking period in each dairy farm in 2013.

Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants.

Ubiquitin (Ub) is a small 76-amino acid protein that is engaged in many different pathways within the cell, including protein turnover. During proteotoxic stress, when the demand of clearing damaged/misfolded proteins strongly increases, cells activate Ub gene transcription to face the need of extra ubiquitin. This paper shows the contribution of the four ubiquitin coding genes (UBB, UBC, UBA52, RPS27A) to the ubiquitin RNA pool under basal and stressful conditions.

Inhibition of Testosterone Aromatization by the Indole-3-carbinol Derivative CTet in CYP19A1-overexpressing MCF-7 Breast Cancer Cells.

Natural products such as aromatase inhibitors have been the object of growing attention in recent years because of their potential to inhibit aromatase with fewer side effects and the possible translation of their current use as chemotherapeutic agents to future clinical applications in breast cancer chemoprevention. We have previously investigated CTet, a novel anticancer agent obtained from the broccoli-derived compound indole-3- carbinol (I3C), that shows great anticancer potential in both in vitro and in vivo studies. Here we evaluated the potential of CTet as a chemopreventive agent in aromatase expressing MCF-7/AROM-1 breast cancer cells.

Yin Yang 1 intronic binding sequences and splicing elicit intron-mediated enhancement of ubiquitin C gene expression.

In a number of organisms, introns affect expression of the gene in which they are contained. Our previous studies revealed that the 5'-UTR intron of human ubiquitin C (UbC) gene is responsible for the boost of reporter gene expression and is able to bind, in vitro, Yin Yang 1 (YY1) trans-acting factor. In this work, we demonstrate that intact YY1 binding sequences are required for maximal promoter activity and YY1 silencing causes downregulation of luciferase mRNA levels.

Molecules altering the intracellular thiol content modulate NF-kB and STAT-1/IRF-1 signalling pathways and IL-12 p40 and IL-27 p28 production in murine macrophages.

Background: The aim of this study was to investigate the molecular mechanisms involved in the production of Th1 cytokines, namely IL-12 and IL-27, when the intra-macrophage redox state was altered by different chemical entities such as GSH-C4, which is reduced glutathione carrying an aliphatic chain, or I-152, a pro-drug of N-acetyl-cysteine (NAC) and beta-mercaptoethylamine. We had already demonstrated that GSH-C4 and I-152 could shift the immune response towards Th1 in Ovalbumin-immunized mice as well as enhance Th1 response in HIV-1 Tat-immunized mice.

Methodology/principal Findings: By a new high performance liquid chromatography method, we found that 20 mM GSH-C4 provided a number of thiol species in the form of GSH, while 20 mM I-152 decreased GSH and increased the thiols in the form of NAC and I-152.

Palytoxin and an Ostreopsis toxin extract increase the levels of mRNAs encoding inflammation-related proteins in human macrophages via p38 MAPK and NF-κB.

Background: Palytoxin and, likely, its analogues produced by the dinoflagellate genus Ostreopsis, represent a class of non-proteinaceous compounds displaying high toxicity in animals. Owing to the wide distribution and the poisonous effects of these toxins in humans, their chemistry and mechanism of action have generated a growing scientific interest. Depending on the exposure route, palytoxin and its Ostreopsis analogues may cause several adverse effects on human health, including acute inflammatory reactions which seem more typical of cutaneous and inhalation contact.

Unique toxin profile of a Mediterranean Ostreopsis cf. ovata strain: HR LC-MS(n) characterization of ovatoxin-f, a new palytoxin congener.

Currently, the benthic dinoflagellate Ostreopsis cf. ovata represents a serious concern to human health in the whole Mediterranean basin due to the production of palytoxin congeners, a putative palytoxin and ovatoxins (ovatoxin-a, -b, -c, -d/-e), listed among the most potent marine toxins. High resolution liquid chromatography-mass spectrometry (HR LC-MS) based investigation of a North Western Adriatic strain of Ostreopsis cf.