A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 A resolution.

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like ('Johnson') for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001

Targeted treatment for chronic lymphocytic leukemia

The treatment of chronic lymphocytic leukemia (CLL) has evolved over the last few decades. Recognition has increased of several key components of CLL biology currently manipulated for therapeutics. A milestone in the treatment of CLL was reached with the incorporation of immunotherapy with conventional chemotherapy. The fludarabine/cyclophosphamide/rituximab combination has demonstrated survival advantage for the first time in the treatment of CLL. Several other biological compounds are being explored with the hope of improving responses, impacting survival, and ultimately curing CLL. Important agents being tested are targeted on CLL surface molecules and their ligands, signal transduction protein and oncogenes. This review provides a brief summary of the recent advances made in preclinical and clinical investigation of selected promising therapeutic agents, which lead the target-directed therapeutic approach

Rhinitis as a risk factor for depressive mood in pre-adolescents: a new approach to this relationship

BACKGROUND: Respiratory allergic symptoms impact on social life and school activities, influencing the patient's mood states. We evaluated the relationships between allergic respiratory diseases and depressive/anxious mood in a large sample of Italian middle school students, using the partial directed acyclic graph (P-DAG). METHODS: We studied 1283 subjects aged 10-13. A health respiratory questionnaire including questions relevant to socioeconomic status (HCI) and a test for depression and anxiety were administered. All subjects performed spirometry and skin prick tests. RESULTS: A causal role of rhinitis on depression was found: the likelihood of being depressed increased from 11.2 to 17.7%, when rhinitis was present. Moreover, a direct effect of low HCI on depressive mood was shown (p < 0.0001) as well as the correlation between anxiety and depression (p < 0.0001). Gender was not a direct causal factor for depressive mood, but their relation was mediated through anxious mood. Anxiety appeared to have a stronger association with depression than gender. Allergic sensitization was significantly related to both asthma and rhinitis (p < 0.0001, respectively). Asthma and rhinitis were also directly associated (p < 0.0001). Conversely, asthma was not directly associated with depressive mood, but their relation was mediated through rhinitis. Body mass index (BMI) and impaired lung function (IPF) were not associated with the other variables. CONCLUSIONS: The use of this novel approach to analyzing the dynamic relationships allowed us to find a causal role of rhinitis on depressive state. Moreover, anxious condition and low socioeconomic status contributed to induce depressive mood

ARGONNE RADIUM STUDIES. Evaluation of Clinical Effect Versus Dose in Radium Dial Painters. Final Report.

The ultimate goal of the study of the long- term effects of radium in humans is to delineate the dose- response curve. The shape of this curve is of great importance in setting the maximum permissible amount of any radioactive material to which humans may be exposed. Various theories of clinical effects versus dose have been postulated

Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze

The authors would like to thank the study participants and their parents. The recruitment and sampling of this cohort was funded by the Chief Scientist Office, Edinburgh, UK (CAF/10/06). The follow up received no funding.Peer reviewedPostprin

An examination of writing pauses in the handwriting of children with Developmental Coordination Disorder.

This article has been made available through the Brunel Open Access Publishing Fund.Difficulties with handwriting are reported as one of the main reasons for the referral of children with Developmental Coordination Disorder (DCD) to healthcare professionals. In a recent study we found that children with DCD produced less text than their typically developing (TD) peers and paused for 60% of a free-writing task. However, little is known about the nature of the pausing; whether they are long pauses possibly due to higher level processes of text generation or fatigue, or shorter pauses related to the movements between letters. This gap in the knowledge-base creates barriers to understanding the handwriting difficulties in children with DCD. The aim of this study was to characterise the pauses observed in the handwriting of English children with and without DCD. Twenty-eight 8-14 year-old children with a diagnosis of DCD participated in the study, with 28 TD age and gender matched controls. Participants completed the 10 min free-writing task from the Detailed Assessment of Speed of Handwriting (DASH) on a digitising writing tablet. The total overall percentage of pausing during the task was categorised into four pause time-frames, each derived from the literature on writing (250 ms to 2 s; 2-4 s; 4-10 s and >10 s). In addition, the location of the pauses was coded (within word/between word) to examine where the breakdown in the writing process occurred. The results indicated that the main group difference was driven by more pauses above 10 s in the DCD group. In addition, the DCD group paused more within words compared to TD peers, indicating a lack of automaticity in their handwriting. These findings may support the provision of additional time for children with DCD in written examinations. More importantly, they emphasise the need for intervention in children with DCD to promote the acquisition of efficient handwriting skill

Using a synthesis of the research literature related to the aetiology of adolescent idiopathic scoliosis to provide ideas on future directions for success

This review is atypical by design. It has used a synthesis of the available literature relating to the aetiology of AIS to draw attention to the lack of progress in this area despite intensive research for more than 100 years. The review has argued that if progress is to be made in this area then significant changes in approach to the problem must be made. Such changes have been outlined and major areas of potential focus identified with the intention of creating debate and discussion. There is no doubt that people are working hard in this area of research but this review has deliberately attempted to question its achievements and future directions

Handwriting speed in children with Developmental Coordination Disorder: Are they really slower?

This is the post-print version of the final paper published in Research in Developmental Disabilities. The published article is available at the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.Handwriting difficulties are often included in descriptions of Developmental Coordination Disorder (DCD). They are cited as the most common reason for referral to health professionals following parent and teacher concerns about slow and untidy writing. The aim of this study was to compare handwriting performance in English children with and without DCD across a range of writing tasks, to gain a better understanding of the nature of ‘slowness’ so commonly reported. Twenty-eight 8–14 year-old children with a diagnosis of DCD participated in the study, with 28 typically developing age and gender matched controls. Participants completed the four handwriting tasks from the Detailed Assessment of Speed of Handwriting (DASH) and wrote their own name; all on a digitising writing tablet. The number of words written, speed of pen movements and the time spent pausing during the tasks were calculated. The findings confirmed what many professionals report, that children with DCD produce less text than their peers. However, this was not due to slow movement execution, but rather a higher percentage of time spent pausing. Discussion centres on the understanding of the pausing phenomenon in children with DCD and areas for further research.Oxford Brookes Universit

Real-time simulated storm surge predictions during Hurricane Michael (2018)

Storm surge caused by tropical cyclones can cause overland flooding and lead to loss of life while damaging homes, businesses, and critical infrastructure. In 2018, Hurricane Michael made landfall near Mexico Beach, FL, on 10 October with peak wind speeds near 71.9 m s-1 (161 mph) and storm surge over 4.5 m NAVD88. During Hurricane Michael, water levels and waves were predicted near real-time using a deterministic, depth-averaged, high-resolution ADCIRC+SWAN model of the northern Gulf of Mexico. The model was forced with an asymmetrical parametric vortex model (GAHM) based on Michael's National Hurricane Center (NHC) forecast track and strength. The authors report errors between simulated and observed water level time-series, peak water level, and timing of peak for NHC Advisories. Forecasts of water levels were within 0.5 m of observations, and the timing of peak water levels was within 1 hr as early as 48 hr before Michael’s eventual landfall. We also examined the effect of adding far-field meteorology in our TC vortex model for use in real-time forecasts. In general, we found that including far-field meteorology by blending the TC vortex with a basin-scale NWP product improved water level forecasts. However, we note that divergence between the NHC forecast track and the forecast track of the meteorological model supplying the far-field winds represents a potential limitation to operationalizing a blended wind field surge product. The approaches and data reported herein provide a transparent assessment of water level forecasts during Hurricane Michael and highlight potential future improvements for more accurate predictions