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The vasculature plays an essential role in the development and maintenance of blood-tissue interface homeostasis. Knowledge on the morphological and functional nature of the blood vessels in every single tissue is, however, very poor, but it is becoming clear that each organ is characterized by the presence of endothelial barriers with different properties fundamental for the maintenance of tissue resident immune homeostasis and for the recruitment of blood-trafficking immune cells. The tissue specificity of the vascular unit is dependent on the presence of differentiated endothelial cells that form continues, fenestrated, or sinusoidal vessels with different grades of permeability and different immune receptors, according to how that particular tissue needs to be protected. The gut-brain axis highlights the prominent role that the vasculature plays in allowing a direct and prompt exchange of molecules between the gut, across the gut vascular barrier (GVB), and the brain. Recently, we identified a new choroid plexus vascular barrier (PVB) which receives and integrates information coming from the gut and is fundamental in the modulation of the gut-brain axis. Several pathologies are linked to functional dysregulation of either the gut or the choroid plexus vascular barriers. In this review, we unveil the structural and functional analogies between the GVB and PVB, comparing their peculiar features and highlighting the functional role of pitcher and catcher of the gut-brain axis, including their role in the establishment of immune homeostasis and response upon systemic stimuli. We propose that when the gut vascular barrier-the main protecting system of the body from the external world-is compromised, the choroid plexus gatekeeper becomes a second barrier that protects the central nervous system from systemic inflammation.

Through the analyses of recovered pottery, this study explores the social dimension of an ancestor cult developed at the Petit-Chasseur megalithic necropolis (Upper Rhône Valley, Switzerland) during the Early Bronze Age (2200–1600 BC). The jar votive offerings and domestic pottery from settlement sites were characterized using a range of spectroscopic and microscopic techniques. Acquired archaeometric data allowed identification of six ceramic fabrics and two types of clay substrate—illite- and muscovite-based—which were used in pottery production. The present article discusses the pottery composition in the light of natural resources available in the region, thus shedding light on raw material choices and paste preparation recipes. The Early Bronze Age people that lived in the Upper Rhône Valley seem to have shared a common ceramic tradition, partly inherited from the previous Bell Beaker populations. The compositional correspondence between the jar offerings and domestic pottery revealed that the majority of the known Early Bronze Age groups partook in cultic activities at the Petit-Chasseur megalithic necropolis.

Objectives The fungal pathogen Thecaphora frezii Carranza & Lindquist causes peanut smut, a severe disease currently endemic in Argentina. To study the ecology of T. frezii and to understand the mechanisms of smut resistance in peanut plants, it is crucial to know the genetics of this pathogen. The objective of this work was to isolate the pathogen and generate the first draft genome of T. frezii that will be the basis for analyzing its potential genetic diversity and its interaction with peanut cultivars. Our research group is working to identify peanut germplasm with smut resistance and to understand the genetics of the pathogen. Knowing the genome of T. frezii will help analyze potential variants of this pathogen and contribute to develop enhanced peanut germplasm with broader and long-lasting resistance. Data description Thecaphora frezii isolate IPAVE 0401 (here referred as T.f.B7) was obtained from a single hyphal-tip culture, its DNA was sequenced using Pacific Biosciences Sequel II (PacBio) and Illumina NovaSeq6000 (Nova). Data from both sequencing platforms were combined and the de novo assembling estimated a 29.3 Mb genome size. Completeness of the genome examined using Benchmarking Universal Single-Copy Orthologs (BUSCO) showed the assembly had 84.6% of the 758 genes in fungi_odb10.

Objectives To comparatively assess the sonographic spectrum of carpal tunnel syndrome (CTS) in patients with rheumatoid arthritis (RA) and in patients with idiopathic CTS. Methods Fifty-seven RA patients and 25 idiopathic CTS patients were consecutively enrolled. The diagnosis of CTS in RA patients was made according to clinical history and examination. The following sonographic findings were assessed at carpal tunnel level: median nerve cross-sectional area (CSA) at the carpal tunnel proximal inlet, finger flexor tendons tenosynovitis, radio-carpal synovitis and intraneural power Doppler (PD) signal. Results CTS was diagnosed in 15/57 RA patients (26.3%). Twenty-three RA wrists with CTS, 84 RA wrists without CTS and 34 idiopathic CTS wrists were evaluated. The average CSA of the median nerve was higher in idiopathic CTS than in RA wrists with CTS (17.7 mm2 vs 10.6 mm2, p p = 0.04) and idiopathic CTS (p = 0.02). Intraneural PD signal was more common in CTS (in both RA and idiopathic CTS) wrists compared with wrists without CTS (p Conclusion The sonographic spectrum of CTS in RA patients is characterized by an inflammatory pattern, defined by the presence of finger flexor tendons tenosynovitis and/or radio-carpal joint synovitis. Conversely, a marked median nerve swelling is the dominant feature in idiopathic CTS. Intraneural PD signal is a frequent finding in both conditions. Key Points• Carpal tunnel syndrome (CTS) associated with rheumatoid arthritis (RA) and idiopathic CTS have distinct ultrasound patterns.• The most characteristic sonographic features of CTS in RA patients are those indicative of synovial tissue inflammation at carpal tunnel level. Conversely, marked median nerve swelling is the dominant finding in idiopathic CTS.• Intraneural power Doppler signal is a frequent finding in both conditions.• In patients with CTS, differently from electrophysiology, US can provide clues prompting a rheumatology referral in case of prominent inflammatory findings at carpal tunnel level.

Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. In the absence of an ideal screening modality, HCC is usually diagnosed at an advanced stage. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. Here, we evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes. Results Our data show that the chr1q and chr8p are two hotspot regions for genomic amplifications and deletions respectively. Among the amplified genes, YY1AP1 (chr1q22) possessed the largest correlation between CNA and gene expression. Moreover, it showed a positive correlation between CNA and tumor grade. Regarding deleted genes, CHMP7 (chr8p21.3) possessed the largest correlation between CNA and gene expression. Protein products of both genes interact with other cellular proteins to carry out various functional roles. These include ASH1L, ZNF496, YY1, ZMYM4, CHMP4A, CHMP5, CHMP2A and CHMP3, some of which are well-known cancer-related genes. Conclusions Our in-silico analysis demonstrates the importance of copy number alterations in the pathology of HCC. These findings open a door for future studies that evaluate our results by performing additional experiments.

Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies., Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

We discuss the design for a discrete, immediate, simple relativistic positioning system (rPS) which is potentially able of self-positioning (up to isometries) and operating without calibration or ground control assistance. The design is discussed in dimension two on spacetime (i.e. one spatial dimension plus one time dimension), in Minkowski and Schwarzschild solutions, as well as in dimension three (i.e. two spatial dimensions plus one time dimension) in Minkowski. The system works without calibration, clock synchronizations, or a priori knowledge about the motion of clocks, it is able to self-diagnose hypotheses break down (for example, if one clock temporarily becomes not-freely falling, or the gravitational field changes) and it is automatically back and operational when the assumed conditions are restored. In the Schwarzschild case, we show that the system can also best fit the gravitational mass of the source of the gravitational field and stress that no weak field assumptions are made anywhere. In particular, the rPS we propose can work in a region close to the horizon since it does not use approximations or PPN expansions. More generally, the rPS can be adapted as detectors for the gravitational field and we shall briefly discuss their role in testing different theoretical settings for gravity. In fact, rPS is a natural candidate for a canonical method to extract observables out of a gravitational theory, an activity also known as designing experiments to test gravity., Comment: 24 pages, 6 figures

Background Eosinophilic lung diseases represent a heterogeneous group of disorders with prominent infiltrate of eosinophils in lung interstitium and alveolar spaces. Peripheral blood eosinophilia is often present. Infections, drugs, allergens, toxic agents have to be evaluated as possible causes of eosinophilic lung infiltrates. The category of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2 represents an uncommon cause of eosinophilic lung infiltrate. Case presentation We report the case of a 70-year old man complaining of dry cough and dyspnea. Ground glass-opacities were seen on imaging studies and peripheral blood eosinophilia was present. A thorough step-wise patient’s evaluation led to identify the clonal nature of eosinophilia and the diagnosis of myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA was made. Conclusions Correlation with clinical history, laboratory tests and imaging studies is essential to achieve the correct diagnosis when facing with eosinophilic lung infiltrates. A prolonged eosinophilia can cause life-threatening organ damage. Identification of PDGFRA rearrangement, as in the present case, is particularly critical given the sensitivity and excellent response to imatinib, which has completely changed the natural history of this neoplasm.

Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC50 values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy., The work was supported by the Amazonia Fitomedicamentos (FITO05/2012) Ltda. and Barretos Cancer Hospital, all from Brazil.

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). The assay combines specific DNA extraction by multiplex magnetic capture hybridization (mMCH) with multiplex real-time PCR. The amplification assay showed linearity in the range 106–10 genomic units (GU)/PCR for each co-amplified species. The sensitivity corresponded to 1 GU/PCR for E. coli O157 and L. monocytogenes, and 10 GU/PCR for Salmonella spp. The immobilization process and the hybrid capture of the MCH showed good efficiency and reproducibility for all targets, allowing the combination in equal amounts of the different nanoparticle types in mMCH. MCH and mMCH efficiencies were similar. The detection limit of the method was 10 CFU in samples with individual pathogens and 102 CFU in samples with combination of the three pathogens in unequal amounts (amount’s differences of 2 or 3 log). In conclusion, this multiplex molecular platform can be applied to determine the presence of target species in food samples after culture enrichment. In this way, this method could be a time-saving and sensitive tool to be used in routine diagnosis.

NEET proteins comprise a new class of [2Fe-2S] cluster proteins. In human, three genes encode for NEET proteins: cisd1 encodes mitoNEET (mNT), cisd2 encodes the Nutrient-deprivation autophagy factor-1 (NAF-1) and cisd3 encodes MiNT (Miner2). These recently discovered proteins play key roles in many processes related to normal metabolism and disease. Indeed, NEET proteins are involved in iron, Fe-S, and reactive oxygen homeostasis in cells and play an important role in regulating apoptosis and autophagy. mNT and NAF-1 are homodimeric and reside on the outer mitochondrial membrane. NAF-1 also resides in the membranes of the ER associated mitochondrial membranes (MAM) and the ER. MiNT is a monomer with distinct asymmetry in the molecular surfaces surrounding the clusters. Unlike its paralogs mNT and NAF-1, it resides within the mitochondria. NAF-1 and mNT share similar backbone folds to the plant homodimeric NEET protein (At-NEET), while MiNT’s backbone fold resembles a bacterial MiNT protein. Despite the variation of amino acid composition among these proteins, all NEET proteins retained their unique CDGSH domain harboring their unique 3Cys:1His [2Fe-2S] cluster coordination through evolution. The coordinating exposed His was shown to convey the lability to the NEET proteins’ [2Fe-2S] clusters. In this minireview, we discuss the NEET fold and its structural elements. Special attention is given to the unique lability of the NEETs’ [2Fe-2S] cluster and the implication of the latter to the NEET proteins’ cellular and systemic function in health and disease. Graphical abstract