Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study.

Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention.     

Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages

TLRs, including TLR4, play a crucial role in inflammatory-based diseases, and TLR4 has been identified as a therapeutic target for pharmacological intervention. In previous studies, we investigated the potential of FP7, a novel synthetic glycolipid active as a TLR4 antagonist, to inhibit haematopoietic and non-haematopoietic MyD88-dependent TLR4 pro-inflammatory signalling. The main aim of this study was to investigate the action of FP7 and its derivative FP12 on MyD88-independent TLR4 signalling in THP-1 derived macrophages. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 and FP12 on TRIF-dependent TLR4 functional activity in response to LPS and other endogenous TLR4 ligands in THP-1 macrophages. A different kinetic in the inhibition of endotoxin-driven TBK1, IRF3 and STAT1 phosphorylation was observed using different LPS chemotypes. Following activation of TLR4 by LPS, data revealed that FP7 and FP12 inhibited TBK1, IRF3 and STAT1 phosphorylation which was associated with down-regulation IFN-β and IP-10. Specific blockage of the IFN type one receptor showed that these novel molecules inhibited TRIF-dependent TLR4 signalling via IFN-β pathways. These results add novel information on the mechanism of action of monosaccharide FP derivatives. The inhibition of the TRIF-dependent pathway in human macrophages suggests potential therapeutic uses for these novel TLR4 antagonists in pharmacological interventions on inflammatory diseases.     

Integrated Phenotypic-Genotypic Analysis of Candidate Probiotic Weissella Cibaria Strains Isolated from Dairy Cows in Kuwait

Probiotics and Antimicrobial Proteins - Probiotics represent a possible strategy for controlling intestinal infections in livestock. Members of the Weissella genus are increasingly being studied...     

P2X7: a receptor with a split personality that raises new hopes for anti-cancer therapy

Purinergic Signalling -     

A phylogenetic analysis of rissooidean and cingulopsoidean families (Gastropoda: Caenogastropoda)

The Rissooidea is one of the largest and most diverse molluscan superfamilies, with 23 recognized Recent families including marine, freshwater and terrestrial members. The Cingulopsoidea are a group of three marine families previously included within the Rissooidea. A previous molecular analysis including two rissooideans and one cingulopsoidean, indicated the possibility that the Rissooidea is at least diphyletic. We use new molecular data to investigate the polyphyly of Rissooidea and test the monophyly of Cingulopsoidea with a greatly increased taxon set. This study includes the greatest sampling to date with 43 species of 14 families of Rissooidea and all families of Cingulopsoidea. Bayesian and maximum likelihood analyses of 16S and 28S show that there are two major clades encompassing taxa previously included in Rissooidea. These are the Rissooidea s.s. containing Rissoidae and Barleeiidae and the Truncatelloidea containing Anabathridae, Assimineidae, Falsicingulidae, Truncatellidae, Pomatiopsidae, Hydrobiidae s.l., Hydrococcidae, Stenothyridae, Calopiidae, Clenchiellidae, Caecidae, Tornidae, and Iravadiidae. Rissoidae is not monophyletic, with Lironoba grouping with Emblanda (Emblandidae) and Rissoina forming a separate clade with Barleeiidae. Iravadiidae is not monophyletic, with Nozeba being sister to the Tornidae. Tatea, usually included within Hydrobiidae, is distinct from that family and Nodulus, previously included in Anabathridae, groups with the hydrobiids.     

Effects of 90 min of manual repetitive work on skin temperature and median and ulnar nerve conduction parameters: A pilot study in normal subjects

To test whether the influence of manual activity should be considered when interpreting the results of nerve conduction study (NCS) of the upper limbs performed during work shifts, we evaluated the short-term effect of 90-min repetitive manual work on NCS parameters. Twenty-eight healthy volunteers underwent NCS of the dominant limb at the end of an interview (T₀), after a 30-min rest in sitting position (T₁) and after performing a standardized 90-min manual task (T₂). The task was designed to simulate typical assembly and packing activities. No significant differences were observed for skin temperature (Ts) and NCS parameters between T₀ and T₁. Significantly (p < 0.001) higher Ts mean values were found at T₂ as compared to the previous tests for both females and males. The regression analysis showed an association between temperature variation and nerve conduction velocity values for the median and ulnar nerve at T₂ as compared to T₁. In females, a reduction of the mean sensory nerve action potential (SNAP) amplitude at T₂ was recorded, whereas an opposite trend was observed among males. Manual work is able to influence hand Ts and to modify NCS parameters. SNAP amplitudes changes suggest gender differences in peripheral nerve characteristics that deserve further investigation.     

Do habitat shifts drive diversification in teleost fishes? An example from the pufferfishes (Tetraodontidae)

Habitat shifts are implicated as the cause of many vertebrate radiations, yet relatively few empirical studies quantify patterns of diversification following colonization of new habitats in fishes. The pufferfishes (family Tetraodon‐tidae) occur in several habitats, including coral reefs and freshwater, which are thought to provide ecological opportunity for adaptive radiation, and thus provide a unique system for testing the hypothesis that shifts to new habitats alter diversification rates. To test this hypothesis, we sequenced eight genes for 96 species of pufferfishes and closely related porcupine fishes, and added 19 species from sequences available in GenBank. We time‐calibrated the molecular phylogeny using three fossils, and performed several comparative analyses to test whether colonization of novel habitats led to shifts in the rate of speciation and body size evolution, central predictions of clades experiencing ecological adaptive radiation. Colonization of freshwater is associated with lower rates of cladogenesis in pufferfishes, although these lineages also exhibit accelerated rates of body size evolution. Increased rates of cladogenesis are associated with transitions to coral reefs, but reef lineages surprisingly exhibit significantly lower rates of body size evolution. These results suggest that ecological opportunity afforded by novel habitats may be limited for pufferfishes due to competition with other species, constraints relating to pufferfish life history and trophic ecology, and other factors.     

3D strain map of axially loaded mouse tibia: a numerical analysis validated by experimental measurements

A combined experimental/numerical study was performed to calculate the 3D octahedral shear strain map in a mouse tibia loaded axially. This study is motivated by the fact that the bone remodelling analysis, in this in vivo mouse model should be performed at the zone of highest mechanical stimulus to maximise the measured effects. Accordingly, it is proposed that quantification of bone remodelling should be performed at the tibial crest and at the distal diaphysis. The numerical model could also be used to furnish a more subtle analysis as a precise correlation between local strain and local biological response can be obtained with the experimentally validated numerical model.