Grooming behaviour of honey bees (Hymenoptera: Apidae) on varroa (Mesostigmata: Varroidae)

Resumen: Entre los factores que pueden ayudar a disminuir y controlar la población de Varroa destructor en colonias de Apis mellifera está el comportamiento de acicalamiento. Este comportamiento consiste en la capacidad de la abeja de detectar, morder y eliminar los parásitos en etapa forética. En esta investigación se analizó la presencia del comportamiento de acicalamiento en colonias de abejas a través de la observación de ácaros dañados. Para ello se utilizaron seis colonias de abejas de la especie A. mellifera en colmenas tipo Langstroth, las cuales se evaluaron diariamente durante 30 días en abril y mayo del año 2008. Las muestras correspondieron a la caída diaria de ácaros a placas de metal con vaselina, ubicada en el piso de cada colmena por un periodo de 24 horas. Los resultados indicaron 95% de varroas caídas muertas y 5% vivas de un total de 2.005 varroas. Se encontró un 49% de ácaros con daños y 51% sin daños. Con base en lo observado existe la posibilidad de elegir colonias con comportamiento de acicalamiento de importancia como daño dorsal y daño completo sobre el acaro, lo cual puede ser muy útil para estudiar selección de abejas y diseñar estrategias de manejo integrado del ácaro V. destructor

Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic

Indexación: Web of ScienceTwo ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization, activating its RNase. IPA also inhibits PERK but, paradoxically, activates it at low concentrations, resulting in a bell-shaped activation profile. We reconstituted IPA-activation of PERK-mediated eIF2α phosphorylation from purified components. We estimate that under conditions of maximal activation less than 15% of PERK molecules in the reaction are occupied by IPA. We propose that IPA binding biases the PERK kinase towards its active conformation, which trans-activates apo-PERK molecules. The mechanism by which partial occupancy with an inhibitor can activate kinases may be wide-spread and carries major implications for design and therapeutic application of kinase inhibitors.https://elifesciences.org/content/4/e0543

One health surveillance for rabies : a case study of integrated bite case management in Albay Province, Philippines

Canine rabies is a significant public health concern and economic burden in the Philippines. Animal Bite Treatment Centers (ABTCs) that provide post-exposure prophylaxis (PEP) to bite patients have been established across the country, but the incidence of bite patient presentations has grown unsustainably, whilst rabies transmission in domestic dogs has not been controlled. Moreover, weak surveillance leads to low case detection and late outbreak responses. Here we investigated the potential for Integrated Bite Case Management (IBCM) to improve rabies detection in Albay province. Using information obtained from animal bite histories combined with phone follow-ups and field investigations, we demonstrated that IBCM resulted in a fourfold increase in case detection over 13 months of study compared to the prior period. Bite patient incidence across Albay was very high (>600/100,000 persons/year) with PEP administered mostly indiscriminately. Clinic attendance reflected availability of PEP and proximity to ABTCs rather than rabies incidence (<3% of patient presentations were from “probable” or confirmed rabies exposures) and is therefore not a suitable indicator of rabies burden. Further analysis of the IBCM data suggests that rabies transmission is mostly localized with focal cases from the previous month and current cases in neighbouring villages being most predictive of future rabies occurrence. We conclude that investigations of suspicious biting incidents identified through IBCM have potential to foster intersectoral relationships, and collaborative investments between public health and veterinary services, enabling the One Health ethos to be applied in a more sustainable and equitable way. Triage of patients and investigations of suspect dogs offer an effective tool for improved PEP provisioning and reduction of unnecessary expenditure, whilst targeted field investigations should lead to increased and earlier detection of rabid dogs. Given the enduring risk of re-introductions from neighbouring populations, enhanced surveillance is critical to achieving and maintaining rabies freedom

BiP Binding to the ER-Stress Sensor Ire1 Tunes the Homeostatic Behavior of the Unfolded Protein Response

Computational modeling and experimentation in the unfolded protein response reveals a role for the ER-resident chaperone protein BiP in fine-tuning the system's response dynamics

Rapid in-country sequencing of whole virus genomes to inform rabies elimination programmes.

Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries

The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

Climate resilience in agriculture: Key concepts for community-based adaptation

These primer was produced for a project under CCAFs, jointly implemented by the International Institute of Rural Reconstruction (IIRR), Philippines and the World Agroforestry Center (ICRAF), Vietnam Country Office. CCAFS Project No.: P55-FPI-SEA-ICRA

An intestinal epithelial defect conferring ER stress results in inflammation involving both innate and adaptive immunity

We recently characterized Winnie mice carrying a missense mutation in Muc2, leading to severe endoplasmic reticulum stress in intestinal goblet cells and spontaneous colitis. In this study, we characterized the immune responses due to this intestinal epithelial dysfunction. In Winnie, there was a fourfold increase in activated dendritic cells (DCs; CD11c+ major histocompatibility complex (MHC) class IIhi) in the colonic lamina propria accompanied by decreased colonic secretion of an inhibitor of DC activation, thymic stromal lymphopoietin (TSLP). Winnie also displayed a significant increase in mRNA expression of the mucosal TH17 signature genes Il17a, IL17f, Tgfb, and Ccr6, particularly in the distal colon. Winnie mesenteric lymph node leukocytes secreted multiple TH1, TH2, and TH17 cytokines on activation, with a large increase in interleukin-17A (IL-17A) progressively with age. A major source of mucosal IL-17A in Winnie was CD4+ T lymphocytes. Loss of T and B lymphocytes in Rag1-/- × Winnie (RaW) crosses did not prevent spontaneous inflammation but did prevent progression with age in the colon but not the cecum. Adoptive transfer of naive T cells into RaW mice caused more rapid and severe colitis than in Rag1-/-, indicating that the epithelial defect results in an intestinal microenvironment conducive to T-cell activation. Thus, the Winnie primary epithelial defect results in complex multicytokine-mediated colitis involving both innate and adaptive immune components with a prominent IL-23/TH17 response, similar to that of human ulcerative colitis

Integrative Analysis of Many Weighted Co-Expression Networks Using Tensor Computation

The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks