Syndromic Surveillance and Bioterrorism-related Epidemics

To facilitate rapid detection of a future bioterrorist attack, an increasing number of public health departments are investing in new surveillance systems that target the early manifestations of bioterrorism-related disease. Whether this approach is likely to detect an epidemic sooner than reporting by alert clinicians remains unknown. The detection of a bioterrorism-related epidemic will depend on population characteristics, availability and use of health services, the nature of an attack, epidemiologic features of individual diseases, surveillance methods, and the capacity of health departments to respond to alerts. Predicting how these factors will combine in a bioterrorism attack may be impossible. Nevertheless, understanding their likely effect on epidemic detection should help define the usefulness of syndromic surveillance and identify approaches to increasing the likelihood that clinicians recognize and report an epidemic

Αβ Hinders Nuclear Targeting of AICD and Fe65 in Primary Neuronal Cultures

The intracellular domain of the Alzheimer’s amyloid precursor protein (AICD) has been described as an important player in the transactivation of specific genes. It results from proteolytic processing of the Alzheimer’s amyloid precursor protein (APP), as does the neurotoxic Aβ peptide. Although normally produced in cells, Aβ is typically considered to be a neurotoxic peptide, causing devastating effects. By exposing primary neuronal cultures to relatively low Aβ concentrations, this peptide was shown to affect APP processing. Our findings indicate that APP C-terminal fragments are increased with concomitant reduction in the expression levels of APP itself. AICD nuclear immunoreactivity detected under control conditions was dramatically reduced in response to Aβ exposure. Additionally, intracellular protein levels of Fe65 and GSK3 were also decreased in response to Aβ. APP nuclear signaling is altered by Aβ, affecting not only AICD production but also its nuclear translocation and complex formation with Fe65. In effect, Aβ can trigger a physiological negative feedback mechanism that modulates its own production

Phylogeography and Molecular Epidemiology of Yersinia pestis in Madagascar

Plague, caused by the bacterium Yersinia pestis, has been a problem in Madagascar since it was introduced in 1898. It mainly affects the central highlands, but also has caused several large outbreaks in the port city of Mahajanga, after it was reintroduced there in the 1990s. Despite its prevalence, the genetic diversity and related geographic distribution of different genetic groups of Y. pestis in Madagascar has been difficult to study due to the great genetic similarity among isolates. We subtyped a set of Malagasy isolates and identified two major genetic groups that were subsequently divided into 11 and 4 subgroups, respectively. Y. pestis appears to be maintained in several geographically separate subpopulations. There is also evidence for multiple long distance transfers of Y. pestis, likely human mediated. Such transfers have resulted in the reintroduction and establishment of plague in the port city of Mahajanga where there is evidence for multiple transfers both from and to the central highlands. The maintenance and spread of Y. pestis in Madagascar is a dynamic and highly active process that relies on the natural cycle between the primary host, the black rat, and its flea vectors as well as human activity

Identifying challenges and opportunities for improved nutrient management through U.S.D.A's Dairy Agroecosystem Working Group

Nutrient management is a priority of U.S. dairy farms, although specific concerns vary across regions and management systems. To elucidate challenges and opportunities to improving nutrient use efficiencies, the USDA’s Dairy Agroecosystems Working Group investigated 10 case studies of confinement (including open lots and free stall housing) and grazing operations in the seven major U.S. dairy producing states. Simulation modeling was carried out using the Integrated Farm Systems Model over 25 years of historic weather data. Dairies with a preference for importing feed and exporting manure, common for simulated dry lot dairies of the arid west, had lower nutrient use efficiencies at the farm gate than freestall and tie-stall dairies in humid climates. Phosphorus (P) use efficiencies ranged from 33 to 82% of imported P, while N use efficiencies were 25 to 50% of imported N. When viewed from a P budgeting perspective, environmental losses of P were generally negligible, especially from dry lot dairies. Opportunities for greater P use efficiency reside primarily in increasing on-farm feed production and reducing excess P in diets. In contrast with P, environmental losses of nitrogen (N) were 50 to 75% of annual farm N inputs. For dry lot dairies, the greatest potential for N conservation is associated with ammonia (NH3) control from housing, whereas for freestall and tie-stall operations, N conservation opportunities vary with soil and manure management system. Given that fertilizer expenses are equivalent to 2 to 6% of annual farm profits, cost incentives do exist to improve nutrient use efficiencies. However, augmenting on-farm feed production represents an even greater opportunity, especially on large operations with high animal unit densities

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP’s and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3622-9) contains supplementary material, which is available to authorized users

Internet of Things for Sustainability: Perspectives in Privacy, Cybersecurity, and Future Trends

In the sustainability IoT, the cybersecurity risks to things, sensors, and monitoring systems are distinct from the conventional networking systems in many aspects. The interaction of sustainability IoT with the physical world phenomena (e.g., weather, climate, water, and oceans) is mostly not found in the modern information technology systems. Accordingly, actuation, the ability of these devices to make changes in real world based on sensing and monitoring, requires special consideration in terms of privacy and security. Moreover, the energy efficiency, safety, power, performance requirements of these device distinguish them from conventional computers systems. In this chapter, the cybersecurity approaches towards sustainability IoT are discussed in detail. The sustainability IoT risk categorization, risk mitigation goals, and implementation aspects are analyzed. The openness paradox and data dichotomy between privacy and sharing is analyzed. Accordingly, the IoT technology and security standard developments activities are highlighted. The perspectives on opportunities and challenges in IoT for sustainability are given. Finally, the chapter concludes with a discussion of sustainability IoT cybersecurity case studies

Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling

Canonical Wnt signaling is controlled intracellularly by the level of β-catenin protein, which is dependent on Axin scaffolding of a complex that phosphorylates β-catenin to target it for ubiquitylation and proteasomal degradation. This function of Axin is counteracted through relocalization of Axin protein to the Wnt receptor complex to allow for ligand-activated Wnt signaling. AXIN1 and AXIN2 protein levels are regulated by tankyrase-mediated poly(ADP-ribosyl)ation (PARsylation), which destabilizes Axin and promotes signaling. Mechanistically, how tankyrase limits Axin protein accumulation, and how tankyrase levels and activity are regulated for this function, are currently under investigation. By RNAi screening, we identified the RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins. RNF146 also destabilizes tankyrases TNKS1 and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels. We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. RNF146 is a cytoplasmic protein that also prevents tankyrase protein aggregation at a centrosomal location. Tankyrase auto-PARsylation and PARsylation of Axin is known to lead to proteasome-mediated degradation of these proteins, and we demonstrate that, through ubiquitylation, RNF146 mediates this process to regulate Wnt signaling

Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei

The Gram-negative bacterium, Burkholderia pseudomallei, is a public health problem in southeast Asia and northern Australia and a Centers for Disease Control and Prevention listed Category B potential bioterrorism agent. It is the causative agent of melioidosis, and clinical manifestations vary from acute sepsis to chronic localized and latent infection, which can reactivate decades later. B. pseudomallei is the major cause of community-acquired pneumonia and septicemia in northeast Thailand. In spite of the medical importance of B. pseudomallei, little is known about the mechanisms of pathogenicity and the immunological pathways of host defense. There is no available vaccine, and the mortality rate in acute cases can exceed 40% with 10–15% of survivors relapsing or being reinfected despite prolonged and complete treatments. In this article, we describe cell-mediated immune responses to B. pseudomallei in humans living in northeast Thailand and demonstrate clear evidence of T cell priming in healthy seropositive individuals and patients who recovered from melioidosis. This is the most detailed study yet performed on the cell types that produce interferon-gamma to B. pseudomallei in humans and the antigens that they recognize and the first to study large sample numbers in the primary endemic focus of melioidosis in the world

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone