\u3cem\u3eDrosophila\u3c/em\u3e Vitelline Membrane Assembly: A Critical Role for an Evolutionarily Conserved Cysteine in the “VM domain” of sV23

The vitelline membrane (VM), the oocyte proximal layer of the Drosophila eggshell, contains four major proteins (VMPs) that possess a highly conserved “VM domain” which includes three precisely spaced, evolutionarily conserved, cysteines (CX7CX8C). Focusing on sV23, this study showed that the three cysteines are not functionally equivalent. While substitution mutations at the first (C123S) or third (C140S) cysteines were tolerated, females with a substitution at the second position (C131S) were sterile. Fractionation studies showed that sV23 incorporates into a large disulfide linked network well after its secretion ceases, suggesting that post-depositional mechanisms are in place to restrict disulfide bond formation until late oogenesis, when the oocyte no longer experiences large volume increases. Affinity chromatography utilizing histidine tagged sV23 alleles revealed small sV23 disulfide linked complexes during the early stages of eggshell formation that included other VMPs, namely sV17 and Vml. The early presence but late loss of these associations in an sV23 double cysteine mutant suggests that reorganization of disulfide bonds may underlie the regulated growth of disulfide linked networks in the vitelline membrane. Found within the context of a putative thioredoxin active site (CXXS) C131, the critical cysteine in sV23, may play an important enzymatic role in isomerizing intermolecular disulfide bonds during eggshell assembly

Most, but not All, Yeast Strains in the Deletion Library Contain the [PIN+] Prion

The yeast deletion library is a collection of over 5100 single gene deletions that has been widely used by the yeast community. The presence of a non-Mendelian element, such as a prion, within this library could affect the outcome of many large-scale genomic studies. We previously showed that the deletion library parent strain contained the [PIN+] prion. [PIN+] is the misfolded infectious prion form of the Rnq1 protein that displays distinct fluorescent foci in the presence of RNQ1–GFP and exists in different physical conformations, called variants. Here, we show that over 97% of the library deletion strains are [PIN+]. Of the 141 remaining strains that have completely (58) or partially (83) lost [PIN+], 139 deletions were able to efficiently maintain three different [PIN+] variants despite extensive growth and storage at 4 °C. One strain, cue2Δ, displayed an alteration in the RNQ1–GFP fluorescent shape, but the Rnq1p prion aggregate shows no biochemical differences from the wild-type. Only strains containing a deletion of either HSP104 or RNQ1 are unable to maintain [PIN+], indicating that 5153 non-essential genes are not required for [PIN+] propagation. Copyright © 2009 John Wiley & Sons, Ltd

An intelligent decision support system to prevent and control of dengue

Prevention and control of dengue fever are considered as a complex problem in day-to-day life. Noticeable changes in the human population growth, life style, and climate would cause more dengue outbreak in all over the world. The Government of India has developed a number of prevention and control strategies to protect individuals from dengue fever. Though, the strategies provided by the government are not identified based on people, space and time. In order to overcome this issue, the proposed approach presents various alternatives such as vaccination, disease surveillance, vector control, proper sanitation and increased accessed to safe drinking water, strengthening public health activities, awareness creation, and improving nutrition foods for women and child. The proposed alternatives are selected based on people, space and time criteria’s such as low temperature and heavy rain, high mean temperature and high humidity, water accumulation and rainfall resources and facilities, social culture variable and social demographic variable. The selection of alternatives based on multiple criteria’s is considered as a complex problem in decision-making framework. In general, decision makers and administrators are often used linguistic terms to give their opinions. This paper uses fuzzy logic based VIKOR (VIsekriterijumska optimizacija i KOmpromisno Resenje) method to analyze the linguistic terms collected from the decision makers and rank the best alternatives based on multiple criteria’s

Implications of the Actin Cytoskeleton on the Multi-Step Process of [ PSI+] Prion Formation

Yeast prions are self-perpetuating misfolded proteins that are infectious. In yeast, [PSI+] is the prion form of the Sup35 protein. While the study of [PSI+] has revealed important cellular mechanisms that contribute to prion propagation, the underlying cellular factors that influence prion formation are not well understood. Prion formation has been described as a multi-step process involving both the initial nucleation and growth of aggregates, followed by the subsequent transmission of prion particles to daughter cells. Prior evidence suggests that actin plays a role in this multi-step process, but actin’s precise role is unclear. Here, we investigate how actin influences the cell’s ability to manage newly formed visible aggregates and how actin influences the transmission of newly formed aggregates to future generations. At early steps, using 3D time-lapse microscopy, several actin mutants, and Markov modeling, we find that the movement of newly formed aggregates is random and actin independent. At later steps, our prion induction studies provide evidence that the transmission of newly formed prion particles to daughter cells is limited by the actin cytoskeletal network. We suspect that this limitation is because actin is used to possibly retain prion particles in the mother cell

Big Data Analytics in Healthcare Internet of Things

Nowadays, wearable medical devices play a vital role in many environments such as continuous health monitoring of individuals, road traffic management, weather forecasting, and smart home. These sensor devices continually generate a huge amount of data and stored in cloud computing. This chapter proposes Internet of Things (IoT) architecture to store and process scalable sensor data (big data) for healthcare applications. Proposed architecture consists of two main sub-architecture, namely, MetaFog-Redirection (MF-R) and Grouping & Choosing (GC) architecture. Though cloud computing provides scalable data storage, it needs to be processed by an efficient computing platforms. There is a need for scalable algorithms to process the huge sensor data and identify the useful patterns. In order to overcome this issue, this chapter proposes a scalable MapReduce-based logistic regression to process such huge amount of sensor data. Apache Mahout consists of scalable logistic regression to process large data in distributed manner. This chapter uses Apache Mahout with Hadoop Distributed File System to process the sensor data generated by the wearable medical devices

Big Data Knowledge System in Healthcare

The health care systems are rapidly adopting large amounts of data, driven by record keeping, compliance and regulatory requirements, and patient care. The advances in healthcare system will rapidly enlarge the size of the health records that are accessible electronically. Concurrently, fast progress has been made in clinical analytics. For example, new techniques for analyzing large size of data and gleaning new business insights from that analysis is part of what is known as big data. Big data also hold the promise of supporting a wide range of medical and healthcare functions, including among others disease surveillance, clinical decision support and population health management. Hence, effective big data based knowledge management system is needed for monitoring of patients and identify the clinical decisions to the doctor. The chapter proposes a big data based knowledge management system to develop the clinical decisions. The proposed knowledge system is developed based on variety of databases such as Electronic Health Record (EHR), Medical Imaging Data, Unstructured Clinical Notes and Genetic Data. The proposed methodology asynchronously communicates with different data sources and produces many alternative decisions to the doctor

A Response-aware Traffic Offloading Scheme using Regression Machine Learning for User-Centric Large-Scale Internet of Things

Resource allocation and management in an Internet of Things (IoT) paradigm requires precise request and response processing irrespective of its scalability support. Unpredictable traffic patterns and user density demands reliable offloading for handling user request traffic and service response. Considering the need for large-scale IoT in an account of its interoperability and heterogeneous support, this manuscript introduces a response-aware traffic offloading scheme (RTOS) for delay-sensitive user requests. This offloading scheme is supported by a multivariate spline regression machine learning model for classifying traffic for reducing the failure rate. The splines are adaptive based on the classified traffic for performing independent and shared offloading. The computation process for determining the offloading model is inherited from the cyber-physical system (CPS) coupled with the IoT-Cloud architecture. The information from the knowledge base and event logs are exploited for decision-making in employing the offloading method for the classified traffic. The simulation analysis of this scheme shows that it is effective in improving the request processing ratio and reducing processing, response time, and delay. The simulation is performed for the varying user density and traffic flows

A long view of liberal peace and its crisis

The ‘crisis’ of liberal peace has generated considerable debate in International Relations. However, analysis is inhibited by a shared set of spatial, cultural and temporal assumptions that rest on and reproduce a problematic separation between self-evident ‘liberal’ and ‘non-liberal’ worlds, and locates the crisis in presentist terms of the latter’s resistance to the former’s expansion. By contrast, this article argues that efforts to advance liberal rule have always been interwoven with processes of alternative order-making, and in this way are actively integral, not external, to the generation of the subjectivities, contestations, violence and rival social orders that are then apprehended as self-evident obstacles and threats to liberal peace and as characteristic of its periphery. Making visible these intimate relations of co-constitution elided by representations of liberal peace and its crisis requires a long view and an analytical frame that encompasses both liberalism and its others in the world. The argument is developed using a Foucauldian governmentality framework and illustrated with reference to Sri Lanka

Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes

Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of prions. De novo appearance of the [PSI+] prion, which is the aggregated form of the Sup35 protein, is dramatically enhanced by transient overexpression of SUP35 in the presence of the prion form of the Rnq1 protein, [PIN+]. When fused to GFP and overexpressed in [ps−] [PIN+] cells, Sup35 forms fluorescent rings, and cells with these rings bud off [PSI+] daughters. We investigated the effects of over 400 gene deletions on this de novo induction of [PSI+]. Two classes of gene deletions were identified. Class I deletions (bug1Δ, bem1Δ, arf1Δ, and hog1Δ) reduced the efficiency of [PSI+] induction, but formed rings normally. Class II deletions (las17Δ, vps5Δ, and sac6Δ) inhibited both [PSI+] induction and ring formation. Furthermore, class II deletions reduced, while class I deletions enhanced, toxicity associated with the expanded glutamine repeats of the huntingtin protein exon 1 that causes Huntington's disease. This suggests that prion formation and polyglutamine aggregation involve a multi-phase process that can be inhibited at different steps.National Institutes of Health (U.S.) (grant GM56350)National Institutes of Health (U.S.) (NSRA F32 postdoctoral fellowship GM072340)National Institutes of Health (U.S.) (grant GM25874)Howard Hughes Medical Institut

M6 Membrane Protein Plays an Essential Role in Drosophila Oogenesis

We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. In this work we focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, we found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, we propose that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila