The Role of Formyl Peptide Receptors in Permanent and Low-Grade Inflammation: Helicobacter pylori Infection as a Model

Formyl peptide receptors (FPRs) are cell surface pattern recognition receptors (PRRs), belonging to the chemoattractant G protein-coupled receptors (GPCRs) family. They play a key role in the innate immune system, regulating both the initiation and the resolution of the inflammatory response. FPRs were originally identified as receptors with high binding affinity for bacteria or mitochondria N-formylated peptides. However, they can also bind a variety of structurally different ligands. Among FPRs, formyl peptide receptor-like 1 (FPRL1) is the most versatile, recognizing N-formyl peptides, non-formylated peptides, and synthetic molecules. In addition, according to the ligand nature, FPRL1 can mediate either pro- or anti-inflammatory responses. Hp(2-20), a Helicobacter pylori-derived, non-formylated peptide, is a potent FPRL1 agonist, participating in Helicobacter pylori-induced gastric inflammation, thus contributing to the related site or not-site specific diseases. The aim of this review is to provide insights into the role of FPRs in H. pylori-associated chronic inflammation, which suggests this receptor as potential target to mitigate both microbial and sterile inflammatory diseases.     

Fibromyalgia: Pathogenesis,Mechanisms, Diagnosis and Treatment Options Update

Fibromyalgia is a syndrome characterized by chronic and widespread musculoskeletal pain, often accompanied by other symptoms, such as fatigue, intestinal disorders and alterations in sleep and mood. It is estimated that two to eight percent of the world population is affected by fibromyalgia. From a medical point of view, this pathology still presents inexplicable aspects. It is known that fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission and processing of afferent nociceptive stimuli, with the prevalent manifestation of pain at the level of the locomotor system. In recent years, the pathogenesis of fibromyalgia has also been linked to other factors, such as inflammatory, immune, endocrine, genetic and psychosocial factors. A rheumatologist typically makes a diagnosis of fibromyalgia when the patient describes a history of pain spreading in all quadrants of the body for at least three months and when pain is caused by digital pressure in at least 11 out of 18 allogenic points, called tender points. Fibromyalgia does not involve organic damage, and several diagnostic approaches have been developed in recent years, including the analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms.     

Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes

Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p = 0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.     

Analytical solution for the modeling of the natural time-dependent reduction of waterborne viruses injected into fractured aquifers

We propose an analytical solution in order to explain the processes that determine the fate and behavior of the viruses during transport in a fractured aquifer at Salento (Italy). The calculations yield the efficiency of filtration in fractures at a site near Nardo? (Southern Italy) in reducing the numbers of enteric viruses (i.e., Enteroviruses and Norovirus) in secondary municipal effluents that have been injected in the aquifer over the period 2006-2007. The model predicted, by a theoretical expression, the time-dependent rate of virus reduction, which was in good agreement with field data. The analytical solution yields the achievable "Log reduction credits" for virus reduction in wells located at the setback distances that are usually adopted in local drinking water regulations. The resulting new analytical formula for the time-dependent reduction of viruses during subsurface transport can easily be applied in health risk-based models used to forecast the spread of waterborne diseases and provides appropriate criteria (i.e., distances) needed to meet standards for the quality of drinking water derived from undisinfected groundwater.     

Biogenic amine content and microbiological profile of Pecorino di Farindola cheese

“Pecorino di Farindola” is a traditional ewes’ milk cheese produced in the Abruzzo region (Italy) and ripened for a minimum of 90 days. The main objective of this research was to characterize the microbiological and chemical composition of this cheese, manufactured in ten dairy farms during the winter cheese-making season (December through March). By using classical enumeration system on specific media variability was observed in the viable numbers of aerobic mesophilic bacteria, enterobacteria, coagulase-negative staphylococci, yeasts, enterococci, mesophilic and thermophilic lactobacilli, lactococci and thermophilic streptococci. Salmonella spp., Listeria monocytogenes and Escherichia coli O157:H7 resulted to be absent in all the samples. Among compounds possibly impacting on human health, the isomer cis-9, trans-11 conjugated linoleic acid (CLA), was determined in high levels in all samples, ranging from 9.2 to 12.7 mg/g fat. Great diversity was also found in biogenic amine contents with a relevant presence of tyramine in all the cheeses. This work represents the first study on Pecorino di Farindola cheese and could contribute to deepen the knowledge on its microbiological and biochemical features, focusing on hygiene and consumer health aspects.     

Rapid selection of phage-resistant mutants in Streptococcus thermophilus by immunoselection and cell sorting

Immunoselection and flow cytometry allowed the isolation from Streptococcus thermophilus strain Str31 of double mutants displaying resistance to the phage phi31 and good acid production. Strain Str31 is very sensitive to phage phi31. This phage-host system seemed therefore particularly suitable to test the validity of the selection method adopted in this study. Mutants were stable with respect to both characters. The isolation of the double mutants required 4 to 5 days. The approach does not involve genetic manipulations and can therefore be an alternative to genetic engineering when this technology cannot be applied.     

Lactobacillus pentosus dominates spontaneous fermentation of Italian table olives

Culture-dependent and -independent approaches were applied to identify the bacterial species involved in Italian table olive fermentation. Bacterial identification showed that Lactobacillus pentosus was the dominant species although the presence of Lactobacillus plantarum, Lactobacillus casei, Enterococcus durans, Lactobacillus fermentum and Lactobacillus helveticus was observed. Rep-PCR allowed to obtain strain-specific profiles and to establish a correlation with table olive environment. PCR-DGGE (Denaturing Gradient Gel Electrophoresis) confirmed the heterogeneity of bacterial community structure in fermented table olives as well as the prevalence of L. pentosus. The strains were characterized on the basis of technological properties (NaCl tolerance, β-glucosidase activity and the ability to grow in synthetic brine and in presence of 1 g/100 mL oleuropein). L. pentosus showed a high capacity of adaptation to the different conditions characterizing the olive ecosystem. This species showed the highest percentage of strains able to grow in presence of 10 g/100 mL NaCl, oleuropein and in the synthetic brine. Moreover, all the strains belonging to L. pentosus and L. plantarum species showed a β-glucosidase activity. This study allowed both to identify the main species and strains associated to Italian table olives and to obtain a lactic acid bacteria collection to apply as starter culture in the process of olive fermentation.     

Alginate-based coatings charged with hydroxyapatite and quercetin for fresh-cut papaya shelf life

In this study, the effect of alginate-based coatings charged with quercetin glycoside compounds and hydroxyapatite/quercetin glycoside compounds (HA/QUE) on the microbiological quality, and on bioactive compounds of fresh-cut papaya, was evaluated for 14 days at 6 °C. Alginate coatings with hydroxyapatite/quercetin showed a high capability to slow down the growth of all microbiological parameters investigated. At the end of cold storage, the total bacteria count in papaya samples covered with HA/QUE alginate coating was 4.8 log CFU g⁻¹ which is significantly lower (P < 0.05) than 8.3 log CFU g⁻¹ for uncoated samples. Total carotenoids’ percentage decrease, at the end of storage, was about 20% in papaya with active coatings, with respect to the losses of 39 and 35%, registered in uncoated and alginate-coated samples respectively. Vitamin C content and the antioxidant activity measured in papaya coated with HA/QUE alginate showed significantly higher values (P < 0.05) for each storage day than those detected for control- and alginate-coated samples. Based on the sensory evaluation, active-coated fresh-cut papaya reached, at the end of the storage period, suitable values for commercial purposes.     

Programming robots by example

This article presents a prototypical machine learning system (ETAR) that acquir programs for robot tasks. the long-term goal of this project is to discover how to make computer technology, in particular robots, more useful to (and controllable by) people in general. Rather than require programming expertise, the idea is to build a system that learns robot programs from users' examples. Thus the ETAR learning algorithm begins by sampling the robot path while a user physically leads it through the task. A general procedure, possibly containing loops, branches, and variables, is induced from these examples. the ETAR algorithm is novel because an implicit focus mechaism is used to control the entire generalization process. the focus forces ETAR to concentrate on the important domain objects, thus eliminating useless steps and translat the sampled sequence into a series of robot primitive motions. Loops and branches are introduced as the focus objects repeat or differ. Finally, robot positional variables are introduced as functions of the common characteristics of the objects in the focus. the programs that ETAR generates for three tasks-block stacking, obtaining an object with a certain characteristic, and sorting-are shown to provide an intuitive feel for the types of tasks that ETAR can learn. the article concludes with a general discussion of the current issues in programming by example and describes how this new learner is related to previous systems in this area. ETAR has been implemented on an Excalibur robot © 1993 John Wiley & Sons, Inc.