Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.     

In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model

There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM). Bisphenol-A (BPA) and tributyltin (TBT) were used as controls while four other chemicals, namely perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS) and dichlorodiphenyldichloroethylene (DDE), were used as “unknowns”. Regarding cell viability, BPA and TBT increased cell death as previously observed. Their mode of action involved the activation of estrogen receptors and PPARγ, respectively. ROS production was a consistent key event in BPA-and TBT-treated cells. None of the other MDCs tested modified viability or ROS production. Concerning GSIS, TBT increased insulin secretion while BPA produced no effects. PFOA decreased GSIS, suggesting that this chemical could be a “new” diabetogenic agent. Our results indicate that the EndoC-βH1 cell line is a suitable human β-cell model for testing diabetogenic MDCs. Optimization of the test methods proposed here could be incorporated into a set of protocols for the identification of MDCs.     

Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation

Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1β and IL-10 in human skin explants stimulated with rCAMP1 and C. acnes. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as IL6, TNF, CXCL1, CXCL2, CXCL3, CXCL8, IL-1β, chemokine ligand (CCL)2, CCL4 and colony stimulating factor (CSF)2. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.     

Characterizing landscape changes in central Rondonia using Landsat TM imagery

An analysis of landscape changes in a region of pioneer settlements in central Rondonia, western Brazilian Amazon, was derived from Landsat TM data. Total deforested area increased from 206 x 103 ha in 1977, to 565 x 103 ha in 1985 and to 1210 x 103 ha, or 35.5% of the region, in 1995. Eighty-one per cent of the total 1995 deforestation had occurred in regions within 12.5km from areas of pioneer colonization deforested by 1977. Deforested area exceeded 79% in regions within 12.5km from the region's first road.     

家具与衣服

Couch Sleeper、Home Traveller、Lingerie Locker是Anne Lorenz在Karlsruhe艺术设计学院时毕业作品的一部分。可能因为女性天生对衣服就有很高的敏锐度,Anne Lorenz一直着迷于研究家具与衣物之间的关系,并不断探讨它们之间的形式与功能。     

Effects of exercising before versus after eating on dieting and exercise evaluations: A preliminary investigation.

Psychological processes may play a role in the evaluation of the effectiveness of exercise and subsequent food intake. In order to further investigate this phenomenon, the effects of the timing of exercise relative to an eating opportunity were evaluated. Female undergraduate participants who were of average weight and did not exercise regularly were randomly assigned to one of three conditions (exercise before eating [n = 10], exercise after eating [n = 11], or no exercise [n = 12]). Expectations of the effectiveness of the exercise, value of dieting, and intake were assessed. Participants who exercised after eating had higher expectations of the effectiveness of the exercise than those who exercised before eating, while those who exercised before eating reported valuing dieting more than controls. No effects on intake emerged; therefore, there appears to be a disconnect between dieting appraisals and actual eating behaviour. The results are discussed in relation to theories on conflicting goals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cell design in bacteria as a convex optimization problem

In this paper, we investigate the prediction of the cell composition of bacteria with respect to their medium. By modeling the bacterium as an interconnection of subsystems, the problem is written as a non-smooth convex optimization problem equivalent to a Linear Programming feasibility problem. We then obtain a new method, called Resource Balance Analysis (RBA), predicting the distribution of the available resources in the medium among the various cellular subsystems. Beyond its predictive capability, the proposed approach grasps some fundamental aspects of the bacterium physiology by including a refined model. This method reveals the existence of an intrinsic bottleneck in the system resource distribution of the bacterium, leading to the existence of a structural limitation of its growth rate which can be predicted. RBA is also able to predict the configuration of the metabolic network for a given medium at steady-state regimen which nicely fits the available experimental results for the gram-positive model bacterium Bacillus subtilis.     

Finite element model updating and structural damage identification using OMAX data

The main limitations in the finite element (FE) model updating technique lie in the ability of the FE model to represent the true behavior of the structure (modelling problem), and in the ability to identify enough modal parameters with sufficient accuracy, especially for large structures that are tested in operational conditions (identification problem). In this paper, the identification problem is solved with an OMAX approach, where an artificial force is used in operational conditions and a structural model is identified that takes both the forced and the ambient excitation into account. From an extensive case study on a real three-span bridge, it is observed that, while updating the FE model using the experimental output-only data yields a good fit, discrepancies show up when the more extensive set of OMAX data is used for validation, or even for updating. It can be concluded that an OMAX approach not only increases the well-posedness of the updating problem, it also allows to detect potential inaccuracies in the FE model.