Bidirectional transcription is an inherent feature of Giardia lamblia promoters and contributes to an abundance of sterile antisense transcripts throughout the genome

A prominent feature of transcription in Giardia lamblia is the abundant production of sterile antisense transcripts (Elmendorf et al. The abundance of sterile transcripts in Giardia lamblia. Nucleic Acids., 29, 4674–4683). Here, we use a computational biology analysis of SAGE data to assess the abundance and distribution of sense and antisense messages in the parasite genome. Sterile antisense transcripts are produced at ∼50% of loci with detectable transcription, yet their abundance at a given locus does not correlate to the abundance of the complementary sense transcripts at that locus or to transcription levels at neighboring loci. These data suggest that sterile antisense transcripts are not simply a local effect of open chromatin structure. Using 5′RACE, we demonstrate that Giardia promoters are a source of antisense transcripts through bidirectional transcription, producing both downstream coding sense and upstream sterile antisense transcripts. We use a dual reporter system to explore roles of specific promoter elements in this bidirectional initiation of transcription and suggest that the degenerate AT-rich nature of TATA and Inr elements in Giardia permits them to function interchangeably. The phenomenon of bidirectional transcription in G. lamblia gives us insight into the interaction between transcriptional machinery and promoter elements, and may be the prominent source of the abundant antisense transcription in this parasite

A novel TOPSIS–CBR goal programming approach to sustainable healthcare treatment

Cancer is one of the most common diseases worldwide and its treatment is a complex and time-consuming process. Specifically, prostate cancer as the most common cancer among male population has received the attentions of many researchers. Oncologists and medical physicists usually rely on their past experience and expertise to prescribe the dose plan for cancer treatment. The main objective of dose planning process is to deliver high dose to the cancerous cells and simultaneously minimize the side effects of the treatment. In this article, a novel TOPSIS case based reasoning goal-programming approach has been proposed to optimize the dose plan for prostate cancer treatment. Firstly, a hybrid retrieval process TOPSIS–CBR [technique for order preference by similarity to ideal solution (TOPSIS) and case based reasoning (CBR)] is used to capture the expertise and experience of oncologists. Thereafter, the dose plans of retrieved cases are adjusted using goal-programming mathematical model. This approach will not only help oncologists to make a better trade-off between different conflicting decision making criteria but will also deliver a high dose to the cancerous cells with minimal and necessary effect on surrounding organs at risk. The efficacy of proposed method is tested on a real data set collected from Nottingham City Hospital using leave-one-out strategy. In most of the cases treatment plans generated by the proposed method is coherent with the dose plan prescribed by an experienced oncologist or even better. Developed decision support system can assist both new and experienced oncologists in the treatment planning process

Network Centrality of Metro Systems

Whilst being hailed as the remedy to the world’s ills, cities will need to adapt in the 21st century. In particular, the role of public transport is likely to increase significantly, and new methods and technics to better plan transit systems are in dire need. This paper examines one fundamental aspect of transit: network centrality. By applying the notion of betweenness centrality to 28 worldwide metro systems, the main goal of this paper is to study the emergence of global trends in the evolution of centrality with network size and examine several individual systems in more detail. Betweenness was notably found to consistently become more evenly distributed with size (i.e. no “winner takes all”) unlike other complex network properties. Two distinct regimes were also observed that are representative of their structure. Moreover, the share of betweenness was found to decrease in a power law with size (with exponent 1 for the average node), but the share of most central nodes decreases much slower than least central nodes (0.87 vs. 2.48). Finally the betweenness of individual stations in several systems were examined, which can be useful to locate stations where passengers can be redistributed to relieve pressure from overcrowded stations. Overall, this study offers significant insights that can help planners in their task to design the systems of tomorrow, and similar undertakings can easily be imagined to other urban infrastructure systems (e.g., electricity grid, water/wastewater system, etc.) to develop more sustainable cities

The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion

Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts. Memory is typically generated via an immune response to a foreign antigen, but functional memory T cells can also be produced from naive cells by homeostatic mechanisms. Using a recently developed method, we studied CD8 T cells, which are specific for model (ovalbumin) and viral (HSV, vaccinia) antigens, in unimmunized mice and found a subpopulation bearing markers of memory cells. Based on their phenotypic markers and by their presence in germ-free mice, these preexisting memory-like CD44hi CD8 T cells are likely to arise via physiological homeostatic proliferation rather than a response to environmental microbes. These antigen-inexperienced memory phenotype CD8 T cells display several functions that distinguish them from their CD44lo counterparts, including a rapid initiation of proliferation after T cell stimulation and rapid IFN-γ production after exposure to proinflammatory cytokines. Collectively, these data indicate that the unprimed antigen-specific CD8 T cell repertoire contains antigen-inexperienced cells that display phenotypic and functional traits of memory cells

Draft Genome Sequencing of Giardia intestinalis Assemblage B Isolate GS: Is Human Giardiasis Caused by Two Different Species?

Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16× coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species