Distribution and biological role of the oligopeptide-binding protein (OppA) in Xanthomonas species

In this study we investigated the prevalence of the oppA gene, encoding the oligopeptide binding protein (OppA) of the major bacterial oligopeptide uptake system (Opp), in different species of the genus Xanthomonas. The oppA gene was detected in two Xanthomonas axonopodis strains among eight tested Xanthomonas species. The generation of an isogenic oppA-knockout derivative of the Xac 306 strain, showed that the OppA protein neither plays a relevant role in oligopeptide uptake nor contributes to the infectivity and multiplication of the bacterial strain in leaves of sweet orange (Citrus sinensis) and Rangpur lime (Citrus limonia). Taken together these results suggest that the oppA gene has a recent evolutionary history in the genus and does not contribute in the physiology or pathogenesis of X. axonopodis

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Measurement of the inclusive and differential Higgs boson production cross sections in the decay mode to a pair of τ Leptons in pp collisions at sqrt[s]=13 TeV

Measurements of the inclusive and differential fiducial cross sections of the Higgs boson are presented, using the τ lepton decay channel. The differential cross sections are measured as functions of the Higgs boson transverse momentum, jet multiplicity, and transverse momentum of the leading jet in the event, if any. The analysis is performed using proton-proton collision data collected with the CMS detector at the LHC at a center-of-mass energy of 13  TeV and corresponding to an integrated luminosity of 138  fb^{-1}. These are the first differential measurements of the Higgs boson cross section in the final state of two τ leptons. In final states with a large jet multiplicity or with a Lorentz-boosted Higgs boson, these measurements constitute a significant improvement over measurements performed in other final states

Sandfly fauna (Diptera: Psychodidae) in an urban area, Central-West of Brazil

ABSTRACT Biological and ecological relations among vectors and their pathogens are important to understand the epidemiology of vector-borne diseases. Camapuã is an endemic area for visceral and tegumentary leishmaniasis. The aim of this study was to characterize the sandfly fauna present in Camapuã , MS, Brazil. Sand flies were collected every fortnight from May 2014 to April 2015 using automatic light traps in the domicile and peridomicile of twelve neighborhoods and forest. The collected specimens were identified based on morphology according to the valid identification keys. In total, 2005 sandflies of five genera and nine species were collected. Nyssomyia whitmani and Lutzomyia cruzi were the most abundant species. Males were more abundant, with a male-to-female ratio of 2.14. The highest diversity was observed in peripheral neighborhood, with abundant plant cover. The peridomicile presented greater abundance of sandflies, with the predominance of Ny. whitmani . No significant correlation between the absolute frequencies of the most abundant species and the precipitation variable was observed; however, there was a predominance of Lu. cruzi in the rainy season. We observed a high frequency of sandflies in urban area, especially vector species. The presence of Nyssomyia whitmani and Lutzomyia cruzi indicate the necessity for health surveillance in the municipality. Additional method of collection such as sticky trap is also recommended for appropriate faunestic study

Observation of triple J/ψ meson production in proton-proton collisions

Data availability: Tabulated results are provided in the HEPData record for this analysis71. Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in CMS data preservation, re-use and open access policy.Code availability: The CMS core software is publically available at https://github.com/cms-sw/cmssw.Copyright . Protons consist of three valence quarks, two up-quarks and one down-quark, held together by gluons and a sea of quark-antiquark pairs. Collectively, quarks and gluons are referred to as partons. In a proton-proton collision, typically only one parton of each proton undergoes a hard scattering – referred to as single-parton scattering – leaving the remainder of each proton only slightly disturbed. Here, we report the study of double- and triple-parton scatterings through the simultaneous production of three J/ψ mesons, which consist of a charm quark-antiquark pair, in proton-proton collisions recorded with the CMS experiment at the Large Hadron Collider. We observed this process – reconstructed through the decays of J/ψ mesons into pairs of oppositely charged muons – with a statistical significance above five standard deviations. We measured the inclusive fiducial cross-section to be 272+141−104(stat)±17(syst)fb, and compared it to theoretical expectations for triple-J/ψ meson production in single-, double- and triple-parton scattering scenarios. Assuming factorization of multiple hard-scattering probabilities in terms of single-parton scattering cross-sections, double- and triple-parton scattering are the dominant contributions for the measured process.SCOAP3.Change history: 27 February 2023A Correction to this paper has been published: https://doi.org/10.1038/s41567-023-01992-