Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: a preliminary study

AIM: To evaluate the ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition. METHODS: Twenty healthy Italian volunteers, eight males and twelve females, participated in the study. Ten subjects took a sachet containing 4 × 109 colony-forming units (CFU) of Bifidobacterium longum BB536 and 109 CFU of Lactobacillus rhamnosus HN001, 30 min before breakfast (pre-prandial administration), while ten subjects took a sachet of probiotic product 30 min after breakfast (post-prandial administration). The ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize human gut microbiota was assessed by means of quantitative real-time PCR, while changes in gut microbiota composition were detected by using Ion Torrent Personal Genome Machine. RESULTS: Immediately after 1-mo of probiotic administration, B. longum BB536 and L. rhamnosus HN001 load was increased in the majority of subjects in both pre-prandial and post-prandial groups. This increase was found also 1 mo after the end of probiotic oral intake in both groups, if compared to samples collected before probiotic consumption. At phyla level a significant decrease in Firmicutes abundance was detected immediately after 1-mo of B. longum BB536 and L. rhamnosus HN001 oral intake. This reduction persisted up to 1 mo after the end of probiotic oral intake together with a significant decrease of Proteobacteria abundance if compared to samples collected before probiotic administration. Whereas, at species level, a higher abundance of Blautia producta, Blautia wexlerae and Haemophilus ducrey was observed, together with a reduction of Holdemania filiformis, Escherichia vulneris, Gemmiger formicilis and Streptococcus sinensis abundance. In addition, during follow-up period we observed a further reduction in Escherichia vulneris and Gemmiger formicilis, together with a decrease in Roseburia faecis and Ruminococcus gnavus abundance. Conversely, the abundance of Akkermansia muciniphila was increased if compared to samples collected at the beginning of the experimental time course. CONCLUSION: B. longum BB536 and L. rhamnosus HN001 showed the ability to modulate the gut microbiota composition, leading to a significant reduction of potentially harmful bacteria and an increase of beneficial ones. Further studies are needed to better understand the specific mechanisms involved in gut microbiota modulation

On the coherent rotation of diffuse matter in numerical simulations of galaxy clusters

We present a study on the coherent rotation of the intracluster medium and dark matter components of simulated galaxy clusters extracted from a volume-limited sample of the MUSIC project. The set is re-simulated with three different recipes for the gas physics: $(i)$ non-radiative, $(ii)$ radiative without AGN feedback, and $(iii)$ radiative with AGN feedback. Our analysis is based on the 146 most massive clusters identified as relaxed, 57 per cent of the total sample. We classify these objects as rotating and non-rotating according to the gas spin parameter, a quantity that can be related to cluster observations. We find that 4 per cent of the relaxed sample is rotating according to our criterion. By looking at the radial profiles of their specific angular momentum vector, we find that the solid body model is not a suitable description of rotational motions. The radial profiles of the velocity of the dark matter show a prevalence of the random velocity dispersion. Instead, the intracluster medium profiles are characterized by a comparable contribution from the tangential velocity and the dispersion. In general, the dark matter component dominates the dynamics of the clusters, as suggested by the correlation between its angular momentum and the gas one, and by the lack of relevant differences among the three sets of simulations.Comment: 12 pages, updated to match the MNRAS versio

A novel method to titrate Herpes simplex virus-1 (HSV-1) using laser-based scanning of near-infrared fluorophores conjugated antibodies

Among several strategies used for Herpes simplex virus (HSV) detection in biological specimens, standard plaque assay (SPA) remains the most reliable method to evaluate virus infectivity and quantify viral replication. However, it is a manual procedure, thereby affected by operator subjectivity, and it may be particularly laborious for multiple sample analysis. Here we describe an innovative method to perform the titration of HSV type 1 (HSV-1) in different samples, using the “In-Cell WesternTM” Assay (ICW) from LI-COR, a quantitative immunofluorescence assay that exploits laser-based scanning of near infrared (NIR). In particular, we employed NIR-immunodetection of viral proteins to monitor foci of HSV-1 infection in cell monolayers, and exploited an automated detection of their fluorescence intensity to evaluate virus titre. This innovative method produced similar and superimposable values compared to SPA, but it is faster and can be performed in 96 well plate, thus allowing to easily and quickly analyze and quantify many samples in parallel. These features make our method particularly suitable for the screening and characterization of antiviral compounds, as we demonstrated by testing acyclovir (ACV), the main anti-HSV-1 drug. Moreover, we developed a new data analysis system that allowed to overcome potential bias due to unspecific florescence signals, thus improving data reproducibility. Overall, our method may represents a useful tool for both clinical and research purposes

The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression

The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from the initiation to the malignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a "physiological" response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progressi

Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism

Phenylketonuria (PKU) is the most common genetic metabolic disease with a well-documented association with autism spectrum disorders. It is characterized by the deficiency of the phenylalanine hydroxylase activity, causing plasmatic hyperphenylalaninemia and variable neurological and cognitive impairments. Among the potential pathophysiological mechanisms implicated in autism spectrum disorders is the excitation/inhibition (E/I) imbalance which might result from alterations in excitatory/inhibitory synapse development, synaptic transmission and plasticity, downstream signalling pathways, and intrinsic neuronal excitability. Here, we investigated functional and molecular alterations in the prefrontal cortex (pFC) of BTBR-Pah(enu2) (ENU2) mice, the animal model of PKU. Our data show higher frequency of inhibitory transmissions and significant reduced frequency of excitatory transmissions in the PKU-affected mice in comparison to wild type. Moreover, in the pFC of ENU2 mice, we reported higher levels of the post-synaptic cell-adhesion proteins neuroligin1 and 2. Altogether, our data point toward an imbalance in the E/I neurotransmission favouring inhibition in the pFC of ENU2 mice, along with alterations of the molecular components involved in the organization of cortical synapse. In addition to being the first evidence of E/I imbalance within cortical areas of a mouse model of PKU, our study provides further evidence of E/I imbalance in animal models of pathology associated with autism spectrum disorders

Empirical insights on the nature of synergies among HRM policies - an analysis of an ethics-oriented HRM system

In the last years, several HRM scholars have theoretically support the idea that the policies bundled in an HRM system present synergistic effects. Surprisingly, empirical studies about those synergistic effects are scarce, and their results unstable. As a result, some critical voices in the HR field are questioning the idea of synergies among HR policies, and calling for more research which does not take them for granted. Addressing this gap, this study tests the existence and nature of synergies in HRM systems targeted at improving the employees' perception of benevolent and principled ethical climates. Results from a probabilistic sample of 6000 employees from 6 European countries highlight that synergies occur both for benevolent and principled ethical climates, even if the specific components of the HRM system presenting synergistic effects are different in the two cases. Implications of the findings for HRM practice are presented and discussed

Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment

Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy bloc