Comparative genome analysis of Fusobacterium nucleatum

Fusobacterium nucleatum is considered to be a key oral bacterium in recruiting periodontal pathogens into subgingival dental plaque. Currently F. Nucleatum can be subdivided into five subspecies. Our previous genome analysis of F. Nucleatum W1481 (referred to hereafter asW1481), isolated from an 8-mmperiodontal pocket in a patient with chronic periodontitis, suggested the possibility of a new subspecies. To further investigate the biology and relationships of this possible subspecies with other known subspecies, we performed comparative analysis between W1481 and 35 genome sequences represented by the five known Fusobacterium subspecies.Our analyses suggest thatW1481ismost likely anew F. Nucleatum subspecies, supported by evidence fromphylogenetic analysesandmaximaluniquematchindices(MUMi). Interestingly,wefoundahorizontally transferredW1481-specificgenomicisland harboring the tripartite ATP-independent (TRAP)-like transporter genes, suggesting this bacterium might have a high-Affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate.Moreover, we found virulence genes in theW1481 genome that may provide a strong defense mechanism which might enable it to colonize and survive within the host by evading immune surveillance. This comparative study provides better understanding of F. Nucleatum and the basis for future functional work on this important pathogen

LiPISC: A Lightweight and Flexible Method for Privacy-Aware Intersection Set Computation

Privacy-aware intersection set computation (PISC) can be modeled as secure multi-party computation. The basic idea is to compute the intersection of input sets without leaking privacy. Furthermore, PISC should be sufficiently flexible to recommend approximate intersection items. In this paper, we reveal two previously unpublished attacks against PISC, which can be used to reveal and link one input set to another input set, resulting in privacy leakage. We coin these as Set Linkage Attack and Set Reveal Attack. We then present a lightweight and flexible PISC scheme (LiPISC) and prove its security (including against Set Linkage Attack and Set Reveal Attack)

A performance comparison of the contiguous allocation strategies in 3D mesh connected multicomputers

The performance of contiguous allocation strategies can be significantly affected by the distribution of job execution times. In this paper, the performance of the existing contiguous allocation strategies for 3D mesh multicomputers is re-visited in the context of heavy-tailed distributions (e.g., a Bounded Pareto distribution). The strategies are evaluated and compared using simulation experiments for both First-Come-First-Served (FCFS) and Shortest-Service-Demand (SSD) scheduling strategies under a variety of system loads and system sizes. The results show that the performance of the allocation strategies degrades considerably when job execution times follow a heavy-tailed distribution. Moreover, SSD copes much better than FCFS scheduling strategy in the presence of heavy-tailed job execution times. The results also show that the strategies that depend on a list of allocated sub-meshes for both allocation and deallocation have lower allocation overhead and deliver good system performance in terms of average turnaround time and mean system utilization

Weak signals in healthcare: The case study of the Mid-Staffordshire NHS Foundation Trust

Most organisational disasters have warning signals prior to the event occurring, which are increasingly appearing in accident reports. In the case of the Mid-Staffordshire Disaster, the disaster was not as a result of component failure or human error but rather an organisation that drifted into failure with precursory warning signals being ignored. It has been estimated that between 400 and 1200 patients died as a result of poor care between 2004 and 2009. The aim of this study was to identify the precursory signals and their rationalizations that occurred during this event. Qualitative document analysis was used to analyse the independent and public inquiry reports. Signals were present on numerous system levels. At a person level, there were cases of staff trying to make management aware of the problems, as well as the campaign “Cure the NHS” started by bereaved relatives. At an organisational level, examples of missed signals included the decrease in the trust’s star rating due to failure to meet targets, the NHS care regulator voicing concern regarding the unusually high death rates and auditors’ reports highlighting concerns regarding risk management. At an external level, examples included negative peer reviews from various external organizations

Numerical study on load-bearing capabilities of beam-like lattice structures with three different unit cells

The design and analysis of lattice structures manufactured using Additive Manufacturing (AM) technique is a new approach to create lightweight high-strength components. However, it is difficult for engineers to choose the proper unit cell for a certain function structure and loading case. In this paper, three beam-like lattice structures with triangular prism, square prism and hexagonal prism were designed, manufactured by SLM process using AlSi10Mg and tested. The mechanical performances of lattice structures with equal relative density, equal base area and height, and equal length for all unit cells were conducted by Finite Element Analysis (FEA). It was found that effective Young’s modulus is proportional to relative density, but with different affecting levels. When the lattice structures are designed with the same relative density or the same side lengths, the effective Young’s modulus of lattice structure with triangular prism exhibits the maximum value for both cases. When the lattice structures are designed with the same base areas for all unit cells, the effective Young’s modulus of lattice structures with square prism presents the maximum. FEA results also show that the maximum stress of lattice structures with triangular prisms in each comparison is at the lowest level and the stiffness-to-mass ratio remains at the maximum value, showing the overwhelming advantages in terms of mechanical strength. The excellent agreements between numerical results and experimental tests reveal the validity of FEA methods applied. The results in this work provide an explicit guideline to fabricate beam-like lattice structures with the best tensile and bending capabilities

Pangolin genomes and the evolution of mammalian scales and immunity

Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity.University of Malaya and Ministry of Education, Malaysia [UM.C/HIR/MOHE/08]; UMRG grant from the University of Malaya and Ministry of Education, Malaysia [RG541-13HTM]; Russian Ministry of Science [11.G34.31.0068]; NIH-NHGRI grant [5U54HG00307907]SCI(E)[email protected]

A Genome-Wide Screen for Genetic Variants That Modify the Recruitment of REST to Its Target Genes

Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies—various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation—these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP–seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism

De novo sequencing, assembly and analysis of eight different transcriptomes from the Malayan pangolin

Pangolins are scale-covered mammals, containing eight endangered species. Maintaining pangolins in captivity is a significant challenge, in part because little is known about their genetics. Here we provide the first large-scale sequencing of the critically endangered Manis javanica transcriptomes from eight different organs using Illumina HiSeq technology, yielding ~75 Giga bases and 89,754 unigenes. We found some unigenes involved in the insect hormone biosynthesis pathway and also 747 lipids metabolism-related unigenes that may be insightful to understand the lipid metabolism system in pangolins. Comparative analysis between M. javanica and other mammals revealed many pangolin-specific genes significantly over-represented in stress-related processes, cell proliferation and external stimulus, probably reflecting the traits and adaptations of the analyzed pregnant female M. javanica. Our study provides an invaluable resource for future functional works that may be highly relevant for the conservation of pangolins

Identification of Human Fibroblast Cell Lines as a Feeder Layer for Human Corneal Epithelial Regeneration

There is a great interest in using epithelium generated in vitro for tissue bioengineering. Mouse 3T3 fibroblasts have been used as a feeder layer to cultivate human epithelia including corneal epithelial cells for more than 3 decades. To avoid the use of xeno-components, we evaluated human fibroblasts as an alternative feeder supporting human corneal epithelial regeneration. Five human fibroblast cell lines were used for evaluation with mouse 3T3 fibroblasts as a control. Human epithelial cells isolated from fresh corneal limbal tissue were seeded on these feeders. Colony forming efficiency (CFE) and cell growth capacity were evaluated on days 5–14. The phenotype of the regenerated epithelia was evaluated by morphology and immunostaining with epithelial markers. cDNA microarray was used to analyze the gene expression profile of the supportive human fibroblasts. Among 5 strains of human fibroblasts evaluated, two newborn foreskin fibroblast cell lines, Hs68 and CCD1112Sk, were identified to strongly support human corneal epithelial growth. Tested for 10 passages, these fibroblasts continually showed a comparative efficiency to the 3T3 feeder layer for CFE and growth capacity of human corneal epithelial cells. Limbal epithelial cells seeded at 1×104 in a 35-mm dish (9.6 cm2) grew to confluence (about 1.87–2.41×106 cells) in 12–14 days, representing 187–241 fold expansion with over 7–8 doublings on these human feeders. The regenerated epithelia expressed K3, K12, connexin 43, p63, EGFR and integrin β1, resembling the phenotype of human corneal epithelium. DNA microarray revealed 3 up-regulated and 10 down-regulated genes, which may be involved in the functions of human fibroblast feeders. These findings demonstrate that commercial human fibroblast cell lines support human corneal epithelial regeneration, and have potential use in tissue bioengineering for corneal reconstruction