Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts

Scattering of hydrogen molecules from a reactive surface: Strong off-specular and rotationally inelastic diffraction

Six-dimensional quantum dynamical calculations of the scattering of H_2 from a Pd(100) surface using a potential energy surface derived from density-functional theory calculations are presented. Due to the corrugation and anisotropy of the PES strong off-specular and rotationally inelastic diffraction is found. The dependence of the diffraction intensitities on the incident kinetic energy is closely examined. In particular we focus on the quantum oscillations for normal and off-normal incidence.Comment: RevTeX, 5 pages, 5 figures, to appear in Chem. Phys. Let

Virulence of Malaria Is Associated with Differential Expression of Plasmodium falciparum var Gene Subgroups in a Case-Control Study

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by ∼60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcript

Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression

Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements

Telephone Advice and Triage within Paediatric Oncology.

The topic of telephone triage is of particular interest to the author who works in a paediatric Oncology Unit which is the principal treatment centre for children’s cancers within the Merseyside and Cheshire Cancer Network. This Unit provides 24 hour telephone advice for patients, families and carers. In addition, professionals within the network access the line for specialist information to support patients who are receiving on-going treatment for cancer, in particular, designated shared care centres and community teams who provide care nearer to home. To help develop good practice, the Oncology Unit developed a protocol supported by nine separate algorithms and a proforma upon which to document the ‘Telephone Consultation Notes’ made by the nurse (or other health professional). Having completed the handwritten documentation the policy requires the member of staff to further document these details on Meditech. The nine algorithms relate to nine separate health triggers which reflect the core of telephone triage calls and these algorithms aim to guide safe and appropriate practice and indicate what action the nurse should take. This study was developed in response to this initiative. The aim of this study was to explore triage trained nurses’ experiences of providing telephone triage in one NHS children’s oncology setting. This study was underpinned by a two phase, exploratory mixed methods design although the main focus was on the qualitative data generated in the second phase. Phase 1 involved analysis of logged telephone consultation notes. In Phase 2 selected nurses working within the setting who had received training in the triage protocol and who had logged calls within the study period were interviewed. In Phase 1, a total of 221 telephone triage calls (from parents or District General Hospitals) were logged as being received over the four months of data collection and were analysed and eight nurses (6 female and 2 male) participated in the second interview phase of the study. Following analysis of the data four main themes were identified in relation to telephone triage protocols as a means of (1) managing remote communication; (2) promoting safe and legal nursing actions; (3) ensuring best evidence-based practice; and (4) documenting comprehensive assessment Telephone triage is a relatively new development, particularly within children’s oncology care and whilst it provides parents with 24 hour access to advice and support it also creates challenges. Remote, hands-off assessment is not easy and whilst protocols can guide practice and support the practitioner to make clinical decisions it is clear that nurses in this study did not always adhere to the protocol. The study highlighted that nurses rely on their ward-based, face-to-face knowledge and skills and that this is not always readily transferable to telephone triage. Nurses expressed both levels of confidence and levels of uncertainty about their role in telephone triage. Recommendations for practice are proposed based on the findings of this study

Relationships between hydrogen bonds and halogen bonds in biomolecular engineering

2019 Fall.Includes bibliographical references.In this dissertation, we will explore the interconnectedness between halogen bonds (X-bonds) and hydrogen bonds in rational biomolecular engineering efforts. As X-bonds are not readily designed into biomolecules, we aim to show how they can be advantageous for molecular design. We will begin by considering how X-bonds compare to H-bonds and show how the two can work in harmony to provide enhanced stabilizing potential. In two unique protein engineering efforts we will show 1) how the X-bond can be just as specifying in terms of molecular assembly as compared to the H-bond, and 2) how it can coordinate with the H-bond to increase protein stability. One study shows the specifying potential the X-bond possesses in terms of coiled-coil assembly. While the study points to a direct application of a sensing probe, the scope of the work will aid others using coiled-coils for materials purpose, designing protein interfaces or potential ligand binding sites. In the other protein engineering study, we will survey how a protein with an intrinsically disordered region responds to hydrogen enhanced halogen bond engineering. We show how we can drastically increase the thermal stability of the protein through minimal change to its primary sequence. This study lends itself to exploring bigger structure-function questions and how the stabilizing capacity of halogen bonds fits into this. Through this work we aspire to show how useful X-bonds can be for biological engineering efforts by exhibiting their specifying and stabilizing characteristics in these settings

Modeling the uptake of plug-in vehicles in a heterogeneous car market using a consumer segmentation approach

There is broad agreement on the need for substantial use of low carbon vectors in the long term in the transport sector. Electrification, via mass market adoption of plug-in vehicles (i.e. battery electric and plug-in hybrid electric vehicles), has emerged as a front runner for road transport across the globe, but there are concerns that the pace and extent implied by many modelling studies is problematic and that assessment of (a) the heterogeneity in the market, (b) other low carbon vectors (e.g. conventional hybrids, hydrogen fuel cell) and (c) life cycle energy and environmental impacts have been relatively neglected. This paper aims to fill these gaps by examining the timing, scale and impacts of the uptake of plug-in vehicles in the heterogeneous UK car market from a consumer perspective. To achieve this aim it (a) brings together a bespoke disaggregated model of the transport-energy-environment system (the UK Transport Carbon Model) with previous work by the authors on heterogeneity in the demand for and supply of plug-in vehicles and (b) applies the improved model to develop future low carbon scenarios that assess the potential impact of different investment pathways and policy approaches to the electrification of cars with the view to meeting the UK’s legally binding carbon budgets to 2050. The results show the importance of accounting for the heterogeneity in and dynamic nature of the car market in terms of new technology adoption by private consumers, so called ‘user choosers’ and fleet managers, as well as accounting for potential effects on wider life cycle emissions resulting from different uptake pathways. It allows an assessment of the effectiveness of different policy instruments, market conditions (vehicle supply, private vs fleet market, vehicle segments) and social factors (consumer awareness, range “anxiety”, perceived charging requirements) on different consumer segments, thus providing more policy-focused conclusions on the likely pathways to high penetration of plug-in vehicles that may be required to meet future carbon and air quality targets

A 50-hour intensified IPR training program for counselors

Thesis (Ph. D.)--Michigan State University. Department of Counseling, Personnel Services, and Educational Psychology, 1973Includes bibliographical references (pages 119-123

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

From 'trading zones' to 'buffer zones': Art and metaphor in the communication of psychiatric genetics to publics

Psychiatric genetics has a difficult relationship with the public given its unshakeable connection to eugenics. Drawing from a five-year public engagement programme that emerged from an internationally renowned psychiatric genetics centre, we propose the concept of the Buffer Zone to consider how an exchange of viewpoints between groups of people – including psychiatric geneticists and lay publics - who are often uneasy in one another’s company can be facilitated through the use of art and metaphor. The artwork at the exhibitions provided the necessary socio-cultural context for scientific endeavours, whilst also enabled public groups to be part of, and remain in, the conversation. Crucial to stress is that this mitigation was not to protect the science; it was to protect the discussion