P-selectin glycoprotein ligand 1 promotes T cell lymphoma development and dissemination

P-selectin glycoprotein ligand-1 (PSGL-1) is a membrane-bound glycoprotein expressed in lymphoid and myeloid cells. It is a ligand of P-, E- and L-selectin and is involved in T cell trafficking and homing to lymphoid tissues, among other functions. PSGL-1 expression has been implicated in different lymphoid malignancies, so here we aimed to evaluate the involvement of PSGL-1 in T cell lymphomagenesis and dissemination. PSGL-1 was highly expressed at the surface of human and mouse T cell leukemia and lymphoma cell lines. To assess its impact on T cell malignancies, we stably expressed human PSGL-1 (hPSGL-1) in a mouse thymic lymphoma cell line, which expresses low levels of endogenous PSGL-1 at the cell surface. hPSGL-1-expressing lymphoma cells developed subcutaneous tumors in athymic nude mice recipients faster than control empty vector or parental cells. Moreover, the kidneys, lungs and liver of tumor-bearing mice were infiltrated by hPSGL-1-expressing malignant T cells. To evaluate the role of PSGL-1 in lymphoma cell dissemination, we injected intravenously control and hPSGL-1-expressing lymphoma cells in athymic mice. Strikingly, PSGL-1 expression facilitated disease infiltration of the kidneys, as determined by histological analysis and anti-CD3 immunohistochemistry. Together, these results indicate that PSGL-1 expression promotes T cell lymphoma development and dissemination to different organs.We thank Roger McEver, José M Almendral, Hind Medyouf, João T Barata and Neil D Perkins for providing reagents and cells, André Mozes (CBMR Flow Cytometry Unit) for technical assistance and Sara Miranda and Nuno Bastos for immunohistochemistry technical assistance. This work was supported by Fundação para a Ciência e a Tecnologia (Portugal), European Social Fund , European Regional Development Fund ( PTDC/SAU-OBD/103336/2008 , PTDC/MED-ONC/32592/2017 , UID/BIM/04773/2013 , NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-007274 grants, IF/00056/2012 contract to NRdS and SFRH/BD/147979/2019 fellowship to JLP), and Gilead Sciences Portugal (Programa Gilead GÉNESE PGG/038/2017 grant). The authors acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy , member of the national infrastructure PPBI - Portuguese Platform of Bioimaging ( PPBI-POCI-01-0145-FEDER-022122 ). We thank Roger McEver, Jos? M Almendral, Hind Medyouf, Jo?o T Barata and Neil D Perkins for providing reagents and cells, Andr? Mozes (CBMR Flow Cytometry Unit) for technical assistance and Sara Miranda and Nuno Bastos for immunohistochemistry technical assistance. This work was supported by Funda??o para a Ci?ncia e a Tecnologia (Portugal), European Social Fund, European Regional Development Fund (PTDC/SAU-OBD/103336/2008, PTDC/MED-ONC/32592/2017, UID/BIM/04773/2013, NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-007274 grants, IF/00056/2012 contract to NRdS and SFRH/BD/147979/2019 fellowship to JLP), and Gilead Sciences Portugal (Programa Gilead G?NESE PGG/038/2017 grant). The authors acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122)

Symmetric Biomechanically Guided Prone-to-Supine Breast Image Registration

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration. The breast tissue is modelled as a neo-Hookean material and gravity is considered as the main source of deformation in the original images. In addition to gravity, our framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme avoids an explicit meshing step and enables simulations to be performed directly in the image space. The explicit time integration scheme allows the motion at the interface between chest and breast to be constrained along the chest wall. The feasibility and accuracy of the approach presented here was assessed by measuring the target registration error (TRE) using a numerical phantom with known ground truth deformations, nine clinical prone MRI and supine CT image pairs, one clinical prone-supine CT image pair and four prone-supine MRI image pairs. The registration reduced the mean TRE for the numerical phantom experiment from initially 19.3 to 0.9 mm and the combined mean TRE for all fourteen clinical data sets from 69.7 to 5.6 mm

Osteoinduction in human fat derived stem cells by recombinant human bone morphogenetic protein-2 produced in Escherichia coli

Bioactive recombinant human bone morphogenetic protein-2 (rhBMP-2) was obtained using Escherichia coli pET-25b expression system: 55 mg purified rhBMP-2 were achieved per g cell dry wt, with up to 95% purity. In murine C2C12 cell line, rhBMP-2 induced an increase in the transcription of Smads and of osteogenic markers Runx2/Cbfa1 and Osterix, measured by semi-quantitative RT-PCR. Bioassays performed in human fat-derived stem cells showed an increased activity of the early osteogenic marker, alkaline phosphatase, and the absence of cytotoxicity

Dynamics of early establishment of SARS-CoV-2 VOC Omicron lineages in Minas Gerais, Brazil

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for the public health of Brazil. In this study, we examined the effects of the Omicron introduction in Minas Gerais (MG), the second-most populous state of Brazil. A total of 430 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples from November 2021 to June 2022 from Belo Horizonte (BH) city were sequenced. These newly sequenced genomes comprise 72% of all previously available SARS-CoV-2 genomes for the city. Evolutionary analysis of novel viral genomes reveals that a great diversity of Omicron sublineages have circulated in BH, a pattern in-keeping with observations across Brazil more generally. Bayesian phylogeographic reconstructions indicate that this diversity is a product of a large number of international and national importations. As observed previously, São Paulo state is shown as a significant hub for viral spread throughout the country, contributing to around 70% of all viral Omicron introductions detected in MG

New Insights into the Genetic Regulation of Homologue Disjunction in Mammalian Oocytes

Mammalian oocytes execute a unique meiotic programme involving 2 arrest stages and an unusually protracted preamble to chromosome segregation during the first meiotic division (meiosis I). How mammalian oocytes successfully navigate their exceptional meiotic journey has long been a question of immense interest. Understanding the minutiae of female mammalian meiosis I is not merely of academic interest as 80–90% of human aneuploidy is the consequence of errors arising at this particular stage of oocyte maturation, a stage with a peculiar vulnerability to aging. Recent evidence indicates that oocytes employ many of the same cast of proteins during meiosis I as somatic cells do during mitosis, often to execute similar tasks, but intriguingly, occasionally delegate them to unexpected and unprecedented roles. This is epitomised by the master cell-cycle regulon, the anaphase-promoting complex or cyclosome (APC/C), acting in concert with a critical APC/C-targeted surveillance mechanism, the spindle assembly checkpoint (SAC). Together, the APC/C and the SAC are among the most influential entities overseeing the fidelity of cell-cycle progression and the precision of chromosome segregation. Here I review the current status of pivotal elements underpinning homologue disjunction in mammalian oocytes including spindle assembly, critical biochemical anaphase-initiating events, APC/C activity and SAC signalling along with contemporary findings relevant to progressive oocyte SAC dysfunction as a model for age-related human aneuploidy