Cell line derived xenograft mouse models are a suitable in vivo model for studying tumor budding in colorectal cancer

Tumor budding (TB) is an important prognostic parameter in colorectal cancer (CRC) and associated with metastasis. However, the mechanisms of TB have not been fully elucidated and a major limitation is the absence of in vivo models. Here, we determine the suitability of human cell line derived xenografts (CDX) as models of TB in CRC. Pan-cytokeratin (CK)-stained next-generation Tissue Microarrays (ngTMA) of two CDX models (HT-29, n = 12 and HCT-8, n = 8) and human CRC (n = 27 high-grade and 25 low-grade budding tumors, each) were evaluated for TB. Immunohistochemistry for E-cadherin, β-catenin, Ki-67, ZEB1, and TWIST1 was performed. HT-29 and HCT-8 were predominantly high-grade and no/low-grade TB tumors, respectively. TB counts in the tumor center (intratumoral budding, ITB) were significantly higher in HT-29 CDX tumors compared to human CRC (p = 0.0099). No difference was found in TB counts at the invasion front (peritumoral budding, PTB; p=0.07). ITB and PTB were strongly correlated (r = 0.438 and r = 0.62 in CDX and human CRC, respectively). Immunohistochemistry profiles were comparable in CDX and human CRC tissues. TB in the CDX mouse models is phenotypically similar to human CRCs and highlights comparable protein profiles. The HT-29 CDX could be a suitable model for the in vivo assessment of TB.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Alice in wonderland: experimental jurisprudence on the internal point of view

Humans have this extraordinary cognitive ability: They imagine inexistent objects, they treat them as if they were real, and by doing so they make them real. They thus give rise to a shared institutional reality that enables them to cooperate in ways that would be impossible otherwise. In this paper, we would like to revisit the account that HLA Hart gives of the practice of collective acceptance that makes a legal system possible. We try to provide an explanation of what Hart calls the 'internal point of view', on the basis of experiments on institutional concepts, drawing on the paradigm known as 'embodied cognition'. Experts and non-experts in law rated the role of several cognitive dimensions for a list of words referring to two kinds of abstract concepts (institutional and theoretical/scientific) and two kinds of concrete ones (food and artifact). Institutional concepts were distinguished into pure-institutional (e.g., 'contract', 'state', 'property') and meta-institutional (e.g., 'norm', 'duty', 'justice'). The results provide an empirical account of how our way of thinking about institutions changes as we acquire expertise in the legal field, thus shading light on the cognitive underpinnings of the 'internal point of view'

Insights on the origin of vitrified rocks from serravuda, acri (Italy): Rock fulgurite or anthropogenic activity?

In this study, twenty five partially vitrified rocks and four samples of vitrified rocks collected on the top hill called Serravuda (Acri, Calabria, Italy) are analyzed. The goal is to shed light on the origin of these enigmatic vitrified materials. The analyzed vitrified rocks are a breccia of cemented rock fragments (gneiss, granitoid, and amphibolite fragments) which extends for more than 10 m, forming a continuous mass along the northern and north-west border of the flat top hill. Surrounded by the vitrified accumulation, exposed Paleozoic granitoid substrate rocks show limited melting or heat-alteration processes. By mapping minerals embedded in the glass matrix via X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM), an interpretation of source rock material, reactions, and thermometric indications to form vitrified materials on the top hill of Serravuda, Acri (Italy), is provided. The mineralogical composition of heated or partially vitrified samples is heterogeneous owing to the effects of heating events, but it mostly recalls the parent rock composition (gneiss, granitoid, and amphibolite). The presence of quartz, cristobalite, tridymite, mullite, plagioclase, hercynite, cordierite, and olivine in Serravuda partially vitrified rocks and glasses suggests that samples were subjected to pyrometamorphism and the temperature range at which the glass formed was about 1000–1100◦C in the presence of hydrous gas, burning organic material (e.g., wood), and assuming thermodynamic equilibrium. Lithologies of the heated or partially vitrified rock fragments are a mixture of parent rocks not outcropping on the top of the hill such as gneiss and amphibolite. Data suggest that Serravuda vitrified rocks are most likely the result of anthropic activities and could represent remnants of vitrified fort walls. The mineral assemblage of partially vitrified rocks and glasses suggests that the fort walls were made of slabs derived from the local metamorphic rocks with the addition of Serravuda substrate Paleozoic granitoid rocks to improve the strength and insulation of the fort walls

The Messinian "Calcare di Base" (Sicily, Italy) revisited

Three different types of carbonate deposits are included within the "Calcare di Base",commonly envisaged to record the Messinian salinity crisis onset: type 1 consists of sulphur-bearinglimestones, representing the biogenic product of bacterial sulphate reduction after original gypsum;type 2 comprises dm-thick laminated dolomitic limestones interbedded with diatomites, sapropels andmarls found at the top the Tripoli Formation; type 3, the most common variety, consists of m-thickbrecciated limestones interbedded with shales and clastic gypsum.Type 3 shows sedimentary features suggesting a clastic origin and deposition from high- to lowdensitygravity flows; thus, these deposits can be regarded as an end-member of a large variety ofevaporite-bearing gravity flow deposits, with a dominant carbonate component.The genetic and stratigraphic characterization of these carbonates has strong implications for a bettercomprehension of Messinian events; the three types of Calcare di Base seem to have formed duringdifferent stages of the Messinian salinity crisis (MSC). Type 2 formed in the first stage (5.96-5.60 Ma),and is the only type that can be regarded as the Lower Gypsum time-equivalent. Type 3 was depositedin the second stage (5.60-5.55 Ma) and its base is associated with a regional-scale hiatus and erosion(Messinian erosional surface). Type 1 formed even later, likely in post-Messinian time, throughdiagenetic processes affecting resedimented gypsum deposited during the second stage of the MSC.It follows that not all the Calcare di Base deposits record the onset of the Messinian salinity crisis, ascommonly thought. Thus, a detailed facies characterization of these carbonate deposits is fundamental for both stratigraphic reconstructions and a better comprehension of Messinian events

Assessing the Genomic Variability of Gardnerella vaginalis through Comparative Genomic Analyses: Evolutionary and Ecological Implications

Gardnerella vaginalis is described as a common anaerobic vaginal bacterium whose presence may correlate with vaginal dysbiotic conditions. In the current study, we performed phylogenomic analyses of 72 G. vaginalis genome sequences, revealing noteworthy genome differences underlying a polyphyletic organization of this taxon. Particularly, the genomic survey revealed that this species may actually include nine distinct genotypes (GGtype1 to GGtype9). Furthermore, the observed link between sialidase and phylogenomic grouping provided clues of a connection between virulence potential and the evolutionary history of this microbial taxon. Specifically, based on the outcomes of these in silico analyses, GGtype3, GGtype7, GGtype8, and GGtype9 appear to have virulence potential since they exhibited the sialidase gene in their genomes. Notably, the analysis of 34 publicly available vaginal metagenomic samples allowed us to trace the distribution of the nine G. vaginalis genotypes identified in this study among the human population, highlighting how differences in genetic makeup could be related to specific ecological properties. Furthermore, comparative genomic analyses provided details about the G. vaginalis pan- and core genome contents, including putative genetic elements involved in the adaptation to the ecological niche as well as many putative virulence factors. Among these putative virulence factors, particularly noteworthy genes identified were the gene encoding cholesterol dependent cytolysin (CDC) toxin vaginolysin and genes related to microbial biofilm formation, iron uptake, adhesion to the vaginal epithelium, as well as macrolide antibiotic resistance. IMPORTANCE The identification of nine different genotypes among members of G. vaginalis allowed us to distinguish an uneven distribution of virulence-associated genetic traits within this taxon and thus suggest the potential occurrence of putative pathogen and commensal G. vaginalis strains. These findings, coupled with metagenomics microbial profiling of human vaginal microbiota, permitted us to get insights into the distribution of the genotypes among the human population, highlighting the presence of different structural communities in terms of G. vaginalis genotypes

Glycaemic control in the perioperative period

The prevalence of type 2 diabetes mellitus and the potential for perioperative dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or glucose variability) continue to increase dramatically. The majority of investigations on perioperative glycaemic control focused on critically ill patients and concentrated on goals of therapy, level of intensity of insulin infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of recent guidelines calling for less strict glucose control. Areas of perioperative glycaemic control that deserve further investigation include preoperative identification of patients with undiagnosed type 2 diabetes and other forms of dysglycaemia, determination of appropriate intraoperative glucose goals, and establishment of the impact and natural history of perioperative abnormalities in glucose homeostasis. In the heterogeneous adult perioperative population, it is unlikely that one standard of perioperative glycaemic control is appropriate for all patients. This review presents recent evidence and expert guidance to aid preoperative assessment, intraoperative management, and postoperative care of the dysglycaemic adult patien

Phonons in thin GaAs quantum wires

Phonon frequencies and potentials for an array of thin rectangular GaAs wires embedded in AlAs are calculated within a microscopic scheme. The confined and interface character of optical modes are clearly evident from their dispersion and from the spatial profiles. Our results allow us to conclude that macroscopic models based on the dielectric continuum scheme are adequate to describe confined phonon profiles at wave vectors relevant to el-ph scattering, in contrast with approaches based on mechanical boundary conditions, which yield modes with the wrong symmetry sequence. The implications for electron-phonon scattering rates are discussed