The challenge of social networking in the field of environment and health

<p>Abstract</p> <p>Background</p> <p>The fields of environment and health are both interdisciplinary and trans-disciplinary, and until recently had little engagement in social networking designed to cross disciplinary boundaries. The EU FP6 project HENVINET aimed to establish integrated social network and networking facilities for multiple stakeholders in environment and health. The underlying assumption is that increased social networking across disciplines and sectors will enhance the quality of both problem knowledge and problem solving, by facilitating interactions. Inter- and trans-disciplinary networks are considered useful for this purpose. This does not mean that such networks are easily organized, as openness to such cooperation and exchange is often difficult to ascertain.</p> <p>Methods</p> <p>Different methods may enhance network building. Using a mixed method approach, a diversity of actions were used in order to investigate the main research question: which kind of social networking activities and structures can best support the objective of enhanced inter- and trans-disciplinary cooperation and exchange in the fields of environment and health. HENVINET applied interviews, a role playing session, a personal response system, a stakeholder workshop and a social networking portal as part of the process of building an interdisciplinary and trans-disciplinary network.</p> <p>Results</p> <p>The interviews provided support for the specification of requirements for an interdisciplinary and trans-disciplinary network. The role playing session, the personal response system and the stakeholder workshop were assessed as useful tools in forming such network, by increasing the awareness by different disciplines of other’s positions. The social networking portal was particularly useful in delivering knowledge, but the role of the scientist in social networking is not yet clear.</p> <p>Conclusions</p> <p>The main challenge in the field of environment and health is not so much a lack of scientific problem knowledge, but rather the ability to effectively communicate, share and use available knowledge for policy making. Structured social network facilities can be useful by policy makers to engage with the research community. It is beneficial for scientists to be able to integrate the perspective of policy makers in the research agenda, and to assist in co-production of policy-relevant information. A diversity of methods need to be applied for network building: according to the fit-for-purpose-principle. It is useful to know which combination of methods and in which time frame produces the best results.</p> <p>Networking projects such as HENVINET are created not only for the benefit of the network itself, but also because the applying of the different methods is a learning tool for future network building. Finally, it is clear that the importance of specialized professionals in enabling effective communication between different groups should not be underestimated.</p

Potato NPH3/RPT2-like protein StNRL1, targeted by a Phytophthora infestans RXLR effector, is a susceptibility factor

Plant pathogens deliver effectors to manipulate host processes. We know little about how fungal and oomycete effectors target host proteins to promote susceptibility, yet such knowledge is vital to understand crop disease. We show that either transient expression in Nicotiana benthamiana, or stable transgenic expression in potato (Solanum tuberosum), of the Phytophthora infestans RXLR effector Pi02860 enhances leaf colonization by the pathogen. Expression of Pi02860 also attenuates cell death triggered by the P. infestans microbe-associated molecular pattern INF1, indicating that the effector suppresses pattern-triggered immunity. However, the effector does not attenuate cell death triggered by Cf4/Avr4 coexpression, showing that it does not suppress all cell death activated by cell surface receptors. Pi02860 interacts in yeast two-hybrid assays with potato NPH3/RPT2-LIKE1 (NRL1), a predicted CULLIN3-associated ubiquitin E3 ligase. Interaction of Pi02860 in planta was confirmed by coimmunoprecipitation and bimolecular fluorescence complementation assays. Virus-induced gene silencing of NRL1 in N. benthamiana resulted in reduced P. infestans colonization and accelerated INF1-mediated cell death, indicating that this host protein acts as a negative regulator of immunity. Moreover, whereas NRL1 virus-induced gene silencing had no effect on the ability of the P. infestans effector Avr3a to suppress INF1-mediated cell death, such suppression by Pi02860 was significantly attenuated, indicating that this activity of Pi02860 is mediated by NRL1. Transient overexpression of NRL1 resulted in the suppression of INF1-mediated cell death and enhanced P. infestans leaf colonization, demonstrating that NRL1 acts as a susceptibility factor to promote late blight disease

Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania

SummaryThis study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged ≥18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned (‘Serengeti’) strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania

Auto-Pharm: Automatic Medicine Supplier

The average elderly patient takes more than five prescription medications per day.&nbsp;Auto-Pharm prevents senior citizens from making errors in their medications. The Auto-Pharm system contains two parts: the first one is a User Online Website, which sets the dosage and the schedule of each medication. The second part is the physical machine which provides the pill on schedule. The Auto-Pharm device has fewer buttons than its competitors.&nbsp

ADMarker: A Multi-Modal Federated Learning System for Monitoring Digital Biomarkers of Alzheimer's Disease

Alzheimer's Disease (AD) and related dementia are a growing global health challenge due to the aging population. In this paper, we present ADMarker, the first end-to-end system that integrates multi-modal sensors and new federated learning algorithms for detecting multidimensional AD digital biomarkers in natural living environments. ADMarker features a novel three-stage multi-modal federated learning architecture that can accurately detect digital biomarkers in a privacy-preserving manner. Our approach collectively addresses several major real-world challenges, such as limited data labels, data heterogeneity, and limited computing resources. We built a compact multi-modality hardware system and deployed it in a four-week clinical trial involving 91 elderly participants. The results indicate that ADMarker can accurately detect a comprehensive set of digital biomarkers with up to 93.8% accuracy and identify early AD with an average of 88.9% accuracy. ADMarker offers a new platform that can allow AD clinicians to characterize and track the complex correlation between multidimensional interpretable digital biomarkers, demographic factors of patients, and AD diagnosis in a longitudinal manner

Novel epigenetic network biomarkers for early detection of esophageal cancer

BACKGROUND: Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity. RESULTS: Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett's Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status. CONCLUSIONS: Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation

DNMT3B PWWP mutations cause hypermethylation of heterochromatin

The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1 and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3 marked heterochromatin in a PWWP-independent mannerthat is facilitated by the protein’s N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome

Infectivity of Plasmodium falciparum in malaria-naive individuals is related to knob expression and cytoadherence of the parasite

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo. However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence

Genetic prediction of complex traits: integrating infinitesimal and marked genetic effects

Genetic prediction for complex traits is usually based on models including individual (infinitesimal) or marker effects. Here, we concentrate on models including both the individual and the marker effects. In particular, we develop a ''Mendelian segregation'' model combining infinitesimal effects for base individuals and realized Mendelian sampling in descendants described by the available DNA data. The model is illustrated with an example and the analyses of a public simulated data file. Further, the potential contribution of such models is assessed by simulation. Accuracy, measured as the correlation between true (simulated) and predicted genetic values, was similar for all models compared under different genetic backgrounds. As expected, the segregation model is worthwhile when markers capture a low fraction of total genetic variance. (Résumé d'auteur