Expanding the Anti-Phl p 7 Antibody Toolkit: An Anti-Idiotype Nanobody Inhibitor.

We have previously produced a toolkit of antibodies, comprising recombinant human antibodies of all but one of the human isotypes, directed against the polcalcin family antigen Phl p 7. In this work, we complete the toolkit of human antibody isotypes with the IgD version of the anti-Phl p 7 monoclonal antibody. We also raised a set of nanobodies against the IgD anti-Phl p 7 antibody and identify and characterize one paratope-specific nanobody. This nanobody also binds to the IgE isotype of this antibody, which shares the same idiotype, and orthosterically inhibits the interaction with Phl p 7. The 2.1 Å resolution X-ray crystal structure of the nanobody in complex with the IgD Fab is described

Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity

Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45–2.75 Å. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cμ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes

Examining the Experience of Teen-to-Teen Crisis Line Work for Adolescent Volunteers: A Pilot Study

Suicidal thoughts and behaviors are high and increasing among youth. Crisis lines are one of the oldest downstream approaches for suicide prevention, which have demonstrated effectiveness for adults and preliminary effectiveness for youth. Teen-to-teen (t2t) crisis lines are a unique resource where adolescent volunteers help their similarly aged peers (through texts, chats, calls, and emails). However, no research to date has examined the impacts of t2t crisis line volunteering on the youth. The goal of this pilot study is to begin to evaluate the experience of t2t crisis lines for the youth volunteers. Adolescent (n=20, ages 15-20) volunteers were recruited from two of the largest crisis lines in the U.S. – Teen Line and YouthLine. Enrolled volunteers were administered surveys assessing positive/helpful experiences, negative/unhelpful experiences, and motivations for joining the t2t crisis line. Volunteers were assessed up to five times over the course of one year; once at baseline and then every three months for up to one year (baseline, 3-month follow-up, 6-month follow-up, 9-month follow-up, 12-month/1-year follow-up). Direct content analysis was used to examine the experiences and motivations of volunteering on the crisis line. Preliminary results indicate that all volunteers reported some positive aspects of the t2t line experience, and many reported some negative aspects as well.https://digitalcommons.odu.edu/gradposters2023_sciences/1011/thumbnail.jp

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children

Background Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years. Methods There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012–December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE). Results Comparing 2014 with 2016–2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6–21.8) for all pneumococci and 39.2% (95% CI 26.7–46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7–33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4–35.8) by 2018, with a decrease of 36.3% (95% CI 23.8–46.9) for VT IPD and an increase of 101.4% (95% CI 62.0–145.4) for non-VT IPD. Conclusions Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology

Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Initiation of sub-surface micro-cracks and white etching areas from debonding at non-metallic inclusions in wind turbine gearbox bearing

In this study, a failed planetary bearing from a wind turbine gearbox was destructively examined to investigate the initiation of micro-cracks and butterflies at non-metallic inclusions, and the effect of debonding between these inclusions and the steel matrix. The butterflies were scanned using Atomic Force Microscopy (AFM) to show the topography that could not be assessed by using other microscopy techniques. Nano-indentation was conducted across a butterfly wing and a non-metallic inclusion to measure the hardness at the interface with the steel matrix. It was found that the White Etching Areas (WEA) in the region of the butterfly wing was a damaged material that showed tearing at the debonding gap between the inclusion and steel matrix. This study highlighted the effect of debonding on the initiation of micro-cracks, WEA and inclusion cracking. A direct relationship was found between the size of inclusions and the total length of inclusions and micro-cracks or butterfly wings. The depth of the observed sub-surface damage was correlated with the sub-surface stress distribution and these results suggested that surface traction could be an important contributing factor to the subsurface damage initiation