Search results for " Pathways"

Long-Term Potentiation in the Neonatal Rat Barrel Cortex In Vivo

2012

Long-term potentiation (LTP) is important for the activity-dependent formation of early cortical circuits. In the neonatal rodent barrel cortex, LTP has been studied only in vitro . We combined voltage-sensitive dye imaging with extracellular multielectrode recordings to study whisker stimulation-induced LTP in the whisker-to-barrel cortex pathway of the neonatal rat barrel cortex in vivo . Single whisker stimulation at 2 Hz for 10 min induced an age-dependent expression of LTP in postnatal day (P) 0 to P14 rats, with the strongest expression of LTP at P3–P5. The magnitude of LTP was largest in the activated barrel-related column, smaller in the surrounding septal region, and no LTP could b…

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

2022

We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, an…

Evolution of vertebrate survival circuits

2018

Evolution selects those adaptive features that increase reproductive probabilities and facilitate survival. Analysing the brain circuits mediating risk-avoidance (e.g. defense) and those allowing reward-seeking (motivated) behaviours in different vertebrates leads to several main conclusions. First, circuits mediating risk-avoidance are similar in all studied vertebrates, where they include amygdala homologues located in the posterior half of the cerebral hemispheres, in close relationship with the chemosensory systems. Second, in all vertebrates, reward-seeking behaviours involve the activity of tegmento-striatal dopaminergic pathways, plus other inputs to the ventral striatum, including a…

Promoter Activation in Dhfq Mutants as an Efficient Tool for Specialized Metabolite Production Enabling Direct Bioactivity Testing

2019

Abstract Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene‐sequence‐similarity‐based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseud…

Environmental noise is a cardiovascular risk factor – mechanistic insights on oxidative stress, inflammatory pathways and endothelial dysfunction and…

2020

Systems Biology, Bioinformatics and Medicine Approaches to Cancer Progression Outcomes

2011

Because of the complexity of carcinogenesis and tumour development, it is critical to understand the underlying organizing principles. In this chapter a possible approach is illustrated, starting with a description of breast cancer prognosis as a function of three powerful biological motifs derived from gene expression profiling. A proliferation metagene describing the transition from slow to fast proliferation leads to the most dramatic aggravation of prognosis. A second immune cell metagene represents an opponent of tumour evolution, whereby only fast-proliferating tumours that are not recognized and eliminated by immune cells can progress. In the absence of endocrine treatment, a third m…

HER2 Signaling and Breast Cancer Stem Cells: The Bridge behind HER2-Positive Breast Cancer Aggressiveness and Therapy Refractoriness

2021

Simple Summary Breast cancer (BC) is not a single disease, but a group of different tumors, and altered HER2 expression defines a particularly aggressive subtype. Although HER2 pharmacological inhibition has dramatically improved the prognosis of HER2-positive BC patients, there is still an urgent need for improved knowledge of HER2 biology and mechanisms underlying HER2-driven aggressiveness and drug susceptibility. Emerging data suggest that the clinical efficacy of molecularly targeted therapies is related to their ability to target breast cancer stem cells (BCSCs), a population that is not only self-sustaining and able to differentiate into distinct lineages, but also contributes to tum…

Raising Awareness on the Clinical and Social Relevance of Adequate Chronic Pain Care.

2022

Appropriate pain care should be regarded as a right and effectively guaranteed to people with chronic pain (CP). Law 38, enacted in Italy in 2010, establishes the citizen’s right not to suffer. Twelve years later, such right appears still disregarded in Italy and the current access to adequate pain care reveals significant shortcomings. In addition, a mismatch between CP-associated burden and the available healthcare resources in the framework of our national health system has been observed. This article gathers the perspectives of a Board of Italian anesthesiologists on the state of the art of CP management in Italy and aims at strengthening the scientific rationale and clinical relevance …

Tryptophan catabolism via kynurenine production in Streptomyces coelicolor: identification of three genes coding for the enzymes of tryptophan to ant…

2011

Most enzymes involved in tryptophan catabolism via kynurenine formation are highly conserved in Prokaryotes and Eukaryotes. In humans, alterations of this pathway have been related to different pathologies mainly involving the central nervous system. In Bacteria, tryptophan and some of its derivates are important antibiotic precursors. Tryptophan degradation via kynurenine formation involves two different pathways: the eukaryotic kynurenine pathway, also recently found in some bacteria, and the tryptophan-to-anthranilate pathway, which is widespread in microorganisms. The latter produces anthranilate using three enzymes also involved in the kynurenine pathway: tryptophan 2,3-dioxygenase (TD…

Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus

2020

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini&ndash