Exploring the transcriptomic data of the Australian paralysis tick, Ixodes holocyclus

Ixodes holocyclus is the paralysis tick commonly found in Australia. I. holocyclus does not cause paralysis in the primary host – bandicoots, but markedly affects secondary hosts such as companion animals, livestock and humans. Holocyclotoxins are the neurotoxin molecules in I. holocyclus responsible for paralysis symptoms. There is a limited understanding of holocyclotoxins due to the difficulties in purifying and expressing these toxins in vitro. Next-generation sequencing technologies were utilised for the first time to generate transcriptome data from two cDNA samples –salivary glands samples collected from female adult ticks engorged on paralysed companion animals and on bandicoots. Contigencoded proteins in each library were annotated according to their best BLAST match against several databases and functionally assigned into six protein categories: housekeeping, transposable elements, pathogen-related, hypothetical, secreted and novel. The “secreted protein” category is comprised of ten protein families: enzymes, protease inhibitors, antigens, mucins, immunity-related, lipocalins, glycinerich, putative secreted, salivary and toxin-like. Comparisons of contig representation between the two libraries reveal the differential expression of tick proteins collected from different hosts. This study provides a preliminary description of the I. holocyclus tick salivary gland transcriptome

Exploring the Transcriptomic Data of the Australian Paralysis Tick, Ixodes Holocyclus

Ixodes holocyclus is the paralysis tickcommonly found in Australia. I. holocyclus does notcause paralysis in the primary host – bandicoots, butmarkedly affects secondary hosts such as companionanimals, livestock and humans. Holocyclotoxins are theneurotoxin molecules in I. holocyclus responsible forparalysis symptoms. There is a limited understanding ofholocyclotoxins due to the difficulties in purifying andexpressing these toxins in vitro. Next-generationsequencing technologies were utilised for the first time togenerate transcriptome data from two cDNA samples –salivary glands samples collected from female adult ticksengorged on paralysed companion animals and onbandicoots. Contig-encoded proteins in each librarywere annotated according to their best BLAST matchagainst several databases and functionally assigned intosix protein categories: housekeeping, transposableelements, pathogen-related, hypothetical, secreted andnovel. The “secreted protein” category is comprised often protein families: enzymes, protease inhibitors,antigens, mucins, immunity-related, lipocalins, glycinerich,putative secreted, salivary and toxin-like.Comparisons of contig representation between the twolibraries reveal the differential expression of tickproteins collected from different hosts. This studyprovides a preliminary description of the I. holocyclustick salivary gland transcriptome

Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer

INTRODUCTION: There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer. METHOD: The study population (n = 300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR. RESULTS: The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P = 0.0012) and with progesterone negative tumors (P = 0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P = 0.0053 and P = 0.0199, respectively). CONCLUSION: Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols

The health impacts of waste-to-energy emissions: A systematic review of the literature

Waste-to-energy (WtE) processes, or the combustion of refuse-derived fuel (RDF) for energygeneration, has the potential to reduce landfill volume while providing a renewable energy source.We aimed to systematically review and summarise current evidence on the potential health effects(benefits and risks) of exposure to WtE/RDF-related combustion emissions.We searched PubMed and Google Scholar using terms related to health and WtE/RDFcombustion emissions, following PRISMA guidelines. Two authors independently screened titles,abstracts and then full-texts of original, peer-reviewed research articles published until 20th March2020, plus their relevant references. Overall quality of included epidemiological studies were ratedusing an amended Navigation framework.We found 19 articles from 269 search results that met our inclusion criteria, including twoepidemiological studies, five environmental monitoring studies, seven health impact or riskassessments (HIA/HRA), and five life-cycle assessments. We found a dearth of health studiesrelated to the impacts of exposure to WtE emissions. The limited evidence suggests thatwell-designed and operated WtE facilities using sorted feedstock (RDF) are critical to reducepotential adverse health (cancer and non-cancer) impacts, due to lower hazardouscombustion-related emissions, compared to landfill or unsorted incineration. Poorly fed WtEfacilities may emit concentrated toxins with serious potential health risks, such as dioxins/furansand heavy metals; these toxins may remain problematic in bottom ash as a combustion by-product.Most modelling studies estimate that electricity (per unit) generated from WtE generally emits lesshealth-relevant air pollutants (also less greenhouse gases) than from combustion of fossil fuels (e.g.coal). Some modelled estimates vary due to model sensitivity for type of waste processed, modelinputs used, and facility operational conditions.We conclude that rigorous assessment (e.g. HRA including sensitivity analyses) of WtEfacility/technological characteristics and refuse type used is necessary when planning/proposing facilities to protect human health as the technology is adopted worldwide

Fatigue-induced changes of impedance and performance in target tracking

Kinematic variability is caused, in part, by force fluctuations. It has been shown empirically and numerically that the effects of force fluctuations on kinematics can be suppressed by increasing joint impedance. Given that force variability increases with muscular fatigue, we hypothesized that joint impedance would increase with fatigue to retain a prescribed accuracy level. To test this hypothesis, subjects tracked a target by elbow flexion and extension both with fatigued and unfatigued elbow flexor and extensor muscles. Joint impedance was estimated from controlled perturbations to the elbow. Contrary to the hypothesis, elbow impedance decreased, whereas performance, expressed as the time-on-target, was unaffected by fatigue. Further analysis of the data revealed that subjects changed their control strategy with increasing fatigue. Although their overall kinematic variability increased, task performance was retained by staying closer to the center of the target when fatigued. In conclusion, the present study reveals a limitation of impedance modulation in the control of movement variability

Analysis of meniscal degeneration and meniscal gene expression

<p>Abstract</p> <p>Background</p> <p>Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells.</p> <p>Methods</p> <p>Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR.</p> <p>Results</p> <p>The grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many of the genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (<it>HLA-DPA1</it>), integrin, beta 2 (<it>ITGB2</it>), ectonucleotide pyrophosphatase/phosphodiesterase 1 (<it>ENPP1</it>), ankylosis, progressive homolog (<it>ANKH</it>) and fibroblast growth factor 7 (<it>FGF7</it>), were expressed at significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (<it>ADAMTS5</it>) and prostaglandin E synthase (<it>PTGES</it>), were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific.</p> <p>Conclusion</p> <p>Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA.</p

Membership nominations in international scientific assessments

International scientific assessments are transnational knowledge-based expert networks with a mandate to advise policymakers. A well-known example is the Millennium Ecosystem Assessment (MA), which synthesized research on ecosystem services between 2001 and 2005, utilizing the knowledge of 1,360 expert members. Little, however, is known about the membership composition and the driving forces behind membership nominations in the MA and similar organizations. Here we introduce a survey data set on recruitment in the MA and analyse nomination patterns among experts as a complex network. The results indicate that membership recruitment was governed by prior contacts in other transnational elite organizations and a range of other factors related to personal affinity. Network analysis demonstrates how some core individuals were particularly influential in shaping the overall membership composition of the group. These findings add to recently noted concerns about the lack of diversity of views represented in international scientific assessments

Bias in the physical examination of patients with lumbar radiculopathy

<p>Abstract</p> <p>Background</p> <p>No prior studies have examined systematic bias in the musculoskeletal physical examination. The objective of this study was to assess the effects of bias due to prior knowledge of lumbar spine magnetic resonance imaging findings (MRI) on perceived diagnostic accuracy of the physical examination for lumbar radiculopathy.</p> <p>Methods</p> <p>This was a cross-sectional comparison of the performance characteristics of the physical examination with blinding to MRI results (the 'independent group') with performance in the situation where the physical examination was not blinded to MRI results (the 'non-independent group'). The reference standard was the final diagnostic impression of nerve root impingement by the examining physician. Subjects were recruited from a hospital-based outpatient specialty spine clinic. All adults age 18 and older presenting with lower extremity radiating pain of duration ≤ 12 weeks were evaluated for participation. 154 consecutively recruited subjects with lumbar disk herniation confirmed by lumbar spine MRI were included in this study. Sensitivities and specificities with 95% confidence intervals were calculated in the independent and non-independent groups for the four components of the radiculopathy examination: 1) provocative testing, 2) motor strength testing, 3) pinprick sensory testing, and 4) deep tendon reflex testing.</p> <p>Results</p> <p>The perceived sensitivity of sensory testing was higher with prior knowledge of MRI results (20% vs. 36%; p = 0.05). Sensitivities and specificities for exam components otherwise showed no statistically significant differences between groups.</p> <p>Conclusions</p> <p>Prior knowledge of lumbar MRI results may introduce bias into the pinprick sensory testing component of the physical examination for lumbar radiculopathy. No statistically significant effect of bias was seen for other components of the physical examination. The effect of bias due to prior knowledge of lumbar MRI results should be considered when an isolated sensory deficit on examination is used in medical decision-making. Further studies of bias should include surgical clinic populations and other common diagnoses including shoulder, knee and hip pathology.</p

Unlimited multistability in multisite phosphorylation systems

Reversible phosphorylation on serine, threonine and tyrosine is the most widely studied posttranslational modification of proteins (1, 2). The number of phosphorylated sites on a protein (n) shows a significant increase from prokaryotes, with n less than or equal to 7 sites, to eukaryotes, with examples having n greater than or equal to 150 sites (3). Multisite phosphorylation has many roles (4, 5) and site conservation indicates that increasing numbers of sites cannot be due merely to promiscuous phosphorylation. A substrate with n sites has an exponential number (2^n) of phospho-forms and individual phospho-forms may have distinct biological effects (6, 7). The distribution of these phospho-forms and how this distribution is regulated have remained unknown. Here we show that, when kinase and phosphatase act in opposition on a multisite substrate, the system can exhibit distinct stable phospho-form distributions at steady state and that the maximum number of such distributions increases with n. Whereas some stable distributions are focused on a single phospho-form, others are more diffuse, giving the phospho-proteome the potential to behave as a fluid regulatory network able to encode information and flexibly respond to varying demands. Such plasticity may underlie complex information processing in eukaryotic cells (8) and suggests a functional advantage in having many sites. Our results follow from the unusual geometry of the steady-state phospho-form concentrations, which we show to constitute a rational algebraic curve, irrespective of n. We thereby reduce the complexity of calculating steady states from simulating 3 times 2^n differential equations to solving two algebraic equations, while treating parameters symbolically. We anticipate that these methods can be extended to systems with multiple substrates and multiple enzymes catalysing different modifications, as found in posttranslational modification 'codes' (9) such as the histone code (10, 11). Whereas simulations struggle with exponentially increasing molecular complexity, mathematical methods of the kind developed here can provide a new language in which to articulate the principles of cellular information processing (12)

Identifying patterns of alumni commitment in key strategic relationship programmes

Higher education institutions (HEIs) need to understand their alumni when drawing strategic relationship programmes. This paper aims to identify clusters of alumni based on their commitment relationship and to analyse factors influencing their intention to collaborate with the HEI. The study took place at a Portuguese university, considering a dataset of 1075 of alumni asserting intention to collaborate. First, a cluster analysis was conducted to identify patterns of commitment relationship. Secondly, a logistic regression was run to identify determinants of intention to collaborate. Both techniques revealed the decisive role of HEI commitment in the process. Relationship advantages and positive feelings towards the HEI were also pointed out as important. Alumni asserted recommendations, further training, sharing experiences and giving help as ways to collaborate with HEI. Regression results suggest that sociodemographic variables such as gender, marital status and volunteering are significantly associated with a probability to collaborate. Results also show that affiliation in sororities/fraternities and participation in extracurricular activities are significantly associated with that collaborative intention. The findings provide clues to support strategic relationship programmes based on consistent marketing campaigns, while bringing value to the literature in the European context, where alumni culture requires real insights to evolve.info:eu-repo/semantics/publishedVersio