An immature B cell population from peripheral blood serves as surrogate marker for monitoring tumor angiogenesis and anti-angiogenic therapy in mouse models

Tumor growth depends on the formation of new blood vessels (tumor angiogenesis) either from preexisting vessels or by the recruitment of bone marrow-derived cells. Despite encouraging results obtained with preclinical cancer models, the therapeutic targeting of tumor angiogenesis has thus far failed to deliver an enduring clinical response in cancer patients. One major obstacle for improving anti-angiogenic therapy is the lack of validated biomarkers, which allow patient stratification for suitable treatment and a rapid assessment of therapy response. Toward these goals, we have employed several mouse models of tumor angiogenesis to identify cell populations circulating in their blood that correlated with the extent of tumor angiogenesis and therapy response. Flow cytometry analyses of different combinations of cell surface markers that define subsets of bone marrow-derived cells were performed on peripheral blood mononuclear cells from tumor-bearing and healthy mice. We identified one cell population, CD45dimVEGFR1⁻CD31low, that was increased in levels during active tumor angiogenesis in a variety of transgenic and syngeneic transplantation mouse models of cancer. Treatment with various anti-angiogenic drugs did not affect CD45dimVEGFR1⁻CD31low cells in healthy mice, whereas in tumor-bearing mice, a consistent reduction in their levels was observed. Gene expression profiling of CD45dimVEGFR1⁻CD31low cells characterized these cells as an immature B cell population. These immature B cells were then directly validated as surrogate marker for tumor angiogenesis and of pharmacologic responses to anti-angiogenic therapies in various mouse models of cancer

Challenges and approaches in data management of LTE trials in tropical field sites: Experiences from two trials in India and Bolivia

Quality data is the key commodity of research projects. But with the size of a research project, number of parties involved and range of data collected, the complexity of data management increases significantly. In long-term experiments (LTE), continuity and comparability of collected data throughout the study duration is important but being challenged by personnel changes and development in infrastructure and technology, as well as changes to the trial itself. Managing a longterm trial remotely at field sites in the tropics adds another layer of challenges, including timely transfer of new data, time consuming pre-processing and validation of data between field and scientific staff, data literacy of local field staff and language barriers due to varying levels of English and local languages within the project team. We share our challenges in data management and the strategies and tools used in the context of two LTE trials with field sites in India and Bolivia, managed by local partner organizations and coordinated by the Research Institute of Organic Agriculture in Switzerland, highlighting the technical infrastructure in use, definition of responsibilities and workflows. Our main considerations are a) finding a balance between data security, easy and timely sharing of data in both directions and minimising number of different data repositories and file versions, b) the use of simple, well-known tools that are flexible enough to consider (evolving) needs of different involved parties including field staff, and c) the importance of quick data availability for analysis to serve as a basis for decision making in trial management

Productivity and income in 5 different cocoa production systems

Cocoa agroforestry systems, combining cocoa with timber and fruit trees, are mainly promoted for their environmental benefits. Knowledge gaps exist about the economic performance of such systems. Here we present the productivity and income of 5 cocoa production systems from planting to entering the mature stage 11 years)

El Panel de Desigualtats Socials a Catalunya (PaD): una aportació singular a la història de l'anàlisi longitudinal a Catalunya

L'article descriu les principals fites metodològiques del Panel de Desigualtats Socials a Catalunya (PaD). El PaD és una enquesta pionera en les ciències socials al nostre país en l'ús de la perspectiva longitudinal sobre la base d'una mostra panel pura. El text mostra les especificitats d'aquesta eina en els àmbits del qüestionari, la mostra, el treball de camp i les matrius de dades, i repassa algunes de les aportacions inèdites en l'àmbit de la pobresa, el treball o la mobilitat social, així com l'estat de la recerca amb dades PaD actuals. La possibilitat de seguir els mateixos individus durant anys permet formular preguntes de tipus dinàmic, sobre les trajectòries dels individus i sobre els efectes dels canvis que es produeixen en les seves vides, i aconseguir noves respostes que permeten ampliar el coneixement existent. Actualment, el PaD compleix deu anys de la seva existència.This article describes the main methodological milestones of the Panel on Social Inequalities in Catalonia (PaD). The PaD is a pioneer survey in Catalonia on social sciences concerning the use of a longitudinal perspective based on a pure panel sample. The text shows the specificity of this tool when it comes to the questionnaire, the sample, fieldwork and data matrices, and it reviews some of the latest findings in the field of poverty, employment or social mobility along with the situation in terms of the research conducted using PaD data at present. Being able to follow the same individuals for a number of years makes it possible to ask dynamic questions on the backgrounds of individuals and the effects of changes occurring in their lives, whilst obtaining new answers allowing us to expand on existing knowledge. As of the present time, the PaD has been in existence for 10 years

The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells

The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells

Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy

Mammalian target of rapamycin (mTOR), a central regulator of growth and metabolism, has tissue-specific functions depending on whether it is part of mTOR complex 1 (mTORC1) or mTORC2. We have previously shown that mTORC1 is required for adaptive cardiac hypertrophy and maintenance of function under basal and pressure-overload conditions. In the present study, we aimed to identify functions of mTORC2 in the heart.; Using tamoxifen-inducible cardiomyocyte-specific gene deletion, we generated mice deficient for cardiac rapamycin-insensitive companion of mTOR (rictor), an essential and specific component of mTORC2. Under basal conditions, rictor deficiency did not affect cardiac growth and function in young mice and also had no effects in adult mice. However, transverse aortic constriction caused dysfunction in the rictor-deficient hearts, whereas function was maintained in controls after 1 week of pressure overload. Adaptive increases in cardiac weight and cardiomyocyte cross-sectional area, fibrosis, and hypertrophic and metabolic gene expression were not different between the rictor-deficient and control mice. In control mice, maintained function was associated with increased protein levels of rictor, protein kinase C (PKC)βII, and PKCδ, whereas rictor ablation abolished these increases. Rictor deletion also significantly decreased PKCε at baseline and after pressure overload. Our data suggest that reduced PKCε and the inability to increase PKCβII and PKCδ abundance are, in accordance with their known function, responsible for decreased contractile performance of the rictor-deficient hearts.; Our study demonstrates that mTORC2 is implicated in maintaining contractile function of the pressure-overloaded male mouse heart

A bio-inspired amplification cascade for the detection of rare cancer cells

The main cause of cancer-related death is due to cancer cell spreading and formation of secondary tumors in distant organs, the so-called metastases. Metastatic cancer cells are detectable in the blood of cancer patients as circulating tumor cells (CTC) and may be exploited for prognostic and monitoring purposes, including in breast cancer. Due to their very low frequency, however, their quantitative detection remains a challenge in clinical practice. Nature has developed mechanisms to amplify rare biological events or weak signals, such as intracellular signaling pathways, cytokine networks or the coagulation cascades. At the National Center for Competence in Research (NCCR) in Bio-Inspired Materials we are coupling gold nanoparticle-based strategies with fibrinogen and DNA bio-inspired amplification cascades to develop an in vitro test to specifically and sensitively detect CTCs in patients' blood. In this article, we describe the biological context, the concept of bio-inspired amplification, and the approaches chosen. We also discuss limitations, open questions and further potential biomedical applications of such an approach

What is the contribution of organic agriculture to sustainable development? A synthesis of twelve years (2007-2019) of the “long-term farming systems comparisons in the tropics (SysCom)”

The SysCom Program compares different agricultural production systems (primarily organic and conventional) in three tropical countries (Kenya, India, and Bolivia). This report aims to provide a synthesis of the findings of 12 years of research in the three countries in a way that is easily comprehensible by specialists and non-specialist alike. It focuses on productivity, profitability, soil fertility, and other aspects of system performance such as product quality, biodiversity, resource use efficiency, and agroecosystem resilience. The report is divided into eight main sections: The first section, conclusions, addresses the findings with regards to the question, “What is the contribution of organic agriculture to sustainable development?”. This section is dedicated to the readers who are only interested in a short comprehensive overview of the results. The second section, the introduction, explains the program’s background and objectives. The following sections present the main findings on productivity, profitability, soil fertility, and other aspects of system performance. These sections start with a summary of the key findings, which are then explained in more detail on the concrete research results. They are designed for readers interested in an in-depth understanding of the facts behind inferences as well as the methodology. At the end of each subsection, references to the relevant scientific publications are provided for further reading. Technical jargon has been kept to a minimum and wherever possible explanations are provided in footnotes. The seventh section includes policy recommendations and offers sound advice for policy development. Finally, the annexes provide more information about the SysCom program, including the programs’ phases, a detailed description of the different sites and the local contexts, as well as SysCom’s capacity building and dissemination efforts

A rational and iterative process for targeted nanoparticle design and validation

The lack of understanding of fundamental nano-bio interactions, and difficulties in designing particles stable in complex biological environments are major limitations to their translation into biomedical clinical applications. Here we present a multi- parametric approach to fully characterize targeted nanoparticles, and emphasizes the significant effect that each detail in the synthetic process can have on downstream in vitro results. Through an iterative process, particles were designed, synthesized and tested for physico-chemical and bio-interactive properties which allowed the optimization of nanoparticle functionality. Taken together all interative steps demonstrate that we have synthesized a multifunctional gold nanoparticles that can detect ERBB2-positive breast cancer cells while showing stealth-like behavior toward ERBB2-negative cells and excellent physicochemical stability

System Thinking and Citizen Participation Is Still Missing in One Health Initiatives - Lessons From Fifteen Evaluations.

Tackling complex public health challenges requires integrated approaches to health, such as One Health (OH). A key element of these approaches is the integration of knowledge across sectors, disciplines and stakeholders. It is not yet clear which elements of knowledge integration need endorsement to achieve best outcomes. This paper assesses 15 OH initiatives in 16 African, Asian and European countries to identify opportunities to improve knowledge integration and to investigate geographic influences on knowledge integration capacities. Two related evaluation tools, both relying on semi-quantitative questionnaires, were applied to two sets of case studies. In one tool, the questions relate to operations and infrastructure, while the other assigns questions to the three phases of "design," "implementation," and "evaluation" of the project life cycle. In both, the question scores are aggregated using medians. For analysis, extreme values were identified to highlight strengths and weaknesses. Seven initiatives were assessed by a single evaluator external to the initiative, and the other eight initiatives were jointly assessed by several internal and external evaluators. The knowledge integration capacity was greatest during the project implementation stage, and lowest during the evaluation stage. The main weaknesses pointing towards concrete potential for improvement were identified to be a lack of consideration of systemic characteristics, missing engagement of external stakeholders and poor bridging of knowledge, amplified by the absence of opportunities to learn and evolve in a collective process. Most users were unfamiliar with the systems approach to evaluation and found the use of the tools challenging, but they appreciated the new perspective and saw benefits in the ensuing reflections. We conclude that systems thinking and associated practises for OH require not only specific education in OH core competencies, but also methodological and institutional measures to endorse broad participation. To facilitate meta-analyses and generic improvement of integrated approaches to health we suggest including knowledge integration processes as elements to report according to the COHERE guidelines