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In the current paper, we develop an approach to early science pedagogy that is based on insights about how complex adaptive systems function. Complexity approaches have an important advantage over traditional information-processing approaches: They anticipate the proverbial 'mind with a mind of its own' without having to postulate exclusively mental constructs. They also offer insights about key determinants of learning and effective pedagogy, again without postulating exclusively mental constructs. For complex adaptive systems, learning depends on the presence of sufficiently salient novelty (i.e., variability), and it depends on the presence of sufficiently salient repetitions or ordered patterns (i.e., stability). Science learning, therefore, requires science-relevant novelty and science-relevant patterns of order. Equipped with these insights, we address two challenges of early science pedagogy: (1) how to combine children's self-guided explorations with teachers' strategic interventions, and (2) how to minimize the chances of generating misconceptions about science. The answer lies in creating a learning context that maximizes science-relevant variability and science-relevant stability. If both aspects are abundantly available, a child's self-guided explorations are effective. Conversely, if either aspect is missing, efforts must be made to add them strategically to a child's experience. Adding science-relevant stability is particularly challenging, yet crucial to avoid science misconceptions.

Introduction: Problem‐solving skills (PSS) help to provide a systematic approach to dealing with and managing complex problems. The overall aim of this study was to assess the acceptability and feasibility of developing and adapting a prison‐based PSS workbook for adults within a medium‐ and low‐secure hospital. Method: We used the Medical Research Council framework in our participatory mixed methods study incorporating an adapted survey (to identify what types of problems people experience in secure hospitals), a series of three interactive workshops (to co‐produce two case study examples for a workbook) and we gathered feedback from patients and hospital staff on the acceptability and feasibility of the workbook. Data from the survey were used to inform the case study examples, and the feedback from patients and hospital staff was descriptively summarised and the results consolidated. Results: In total, 82 (51%) patients took part in the survey; 22 patients and 49 hospital staff provided feedback on the workbook. The survey results indicated that patients regularly experience problems while in the hospital. Patients reported problems relating to restrictions of freedom and boredom. The workshops produced two case studies for the workbooks, with mainly positive patient and staff feedback. More work is required to improve the visual representation of the characters in the case studies, the amount and content of the language and the mechanism of the intervention delivery. Conclusion: The adaptation process proved acceptable and feasible to both patients and staff. The co‐production methodology for the workbook and feedback from patients and staff was an effective way of iteratively refining the materials to ensure that they were both meaningful and acceptable to staff and patients. Subsequent work is required to develop the workbook and evaluate the feasibility of the intervention delivery, recruitment rates, uptake and adherence to the PSS using a randomised controlled trial. Patient or Public Contribution: At each stage of the project consultation with patients and/or hospital staff was involved. [ABSTRACT FROM AUTHOR]

Decisions about progress through an academic programme are made by Boards of Examiners, on the basis of students' course assessments. For most students such pass/fail grading decisions are straightforward. However, for those students whose results are borderline (either at a pass/fail boundary or boundaries between grades) the exercise of some discretion by university staff is required. In the interests of the transparency of the exercise of this discretion and to increase the chances that the "right" decision is made, we tested the validity of the second version of the Objective Borderline Method (OBM2) decision-making tool in a medical programme. Our results suggest that application of OBM2 provides valid data to help university staff make robust decisions about a student's progression through a programme, and with which to defend these decisions if that should be required.

Little has been published on the demographic composition of the clinical and translational science research workforce within the Clinical and Translational Science Awards (CTSA) Program despite the well-documented need for greater diversity in the biomedical research workforce. Analyses of workforce demographic reveal that women and members of underrepresented groups remain persistently underrepresented in the CTSA hub and training components principal investigators. In contrast, in the CTSA Program career development and training programs, females have greater representation as participants, and non-Whites were better represented in training programs. [ABSTRACT FROM AUTHOR]

This study explored the impact of COVID-19 on the mental health and wellbeing and trust support of Tees Esk and Wear Valleys (TEWV) NHS forensic staff using an online google survey during the second wave of the pandemic. Survey respondents were a voluntary cross-sectional sample of 246 TEWV staff working in the forensic directorate staff; this included males (n = 60, 24.5%); with the majority of staff aged between 36–50 years (n = 99, 40.2%) and 50 years or older (n = 80, 32.5%). The results showed that staff working at home and on the front line were both affected by depression, stress and anxiety. Those most at risk were younger staff members. We concluded that the mental health and well-being of staff working should be a priority. It is important to consider targeted support that should be aimed at younger staff members to provide an open culture enabling for those who want support to have readily available signposted resources. Staff working in different settings may have experienced a different impact of COVID-19 on their mental health and wellbeing, and whilst some interventions might be successfully applied across the service, it would be beneficial to understand the unique needs of staff working in specific settings. [ABSTRACT FROM AUTHOR]

The 3-D structure of human lactoferrin was first solved in atomic detail in 1987. Since that time, a variety of proven and postulated activities have been added to the original annotation of lactoferrin as an iron-binding protein. Structural studies have also expanded to include iron-bound and iron-free (apo) forms, mutants, and the lactoferrins of different species. In this review, we take the current information on both structure and function and show that the 3-D structure provides a useful framework for understanding some activities and also points to productive research directions that could help elucidate other reported functions. Some functions relate to iron binding where the role of lactoferrin is to scavenge and retain iron across a wide pH range. We specifically focus on functions that depend on the surface structure of the molecule, identifying features that may determine the many other protective properties of this multifunctional protein. Key words: lactoferrin, protein structure, iron binding, protective functions, glycosylation. La structure tridimensionnelle de la lactoferri-ne humaine a ete d'abord resolue a l'echelle atomique en 1987. Depuis lors, une variete d'activites demontrees ou presumees ont ete ajoutees a la premiere indication que la lactoferrine etait une proteine de liaison du fer. Des etudes structurales se sont aussi developpees pour inclure les formes liee et non liee (apo) au fer, les mutants et les lactoferrines de differentes especes. Dans cet article de revue, nous compilons l'information actuelle portant tant sur la structure que la fonction de la lactoferrine, et nous montrons que la structure tridimensionnelle fournit un canevas utile pour comprendre certaines de ses activites et indique certaines directions productives de recherche qui pourraient nous aider a elucider d'autres fonctions connues. Certaines fonctions sont reliees a la liaison du fer ou le role de la lactoferrine est de desactiver et de retenir le fer a travers un large spectre de pH. Nous nous concentrons specialement sur les fonctions qui dependent de la structure de surface de la molecule, identifiant les caracteristiques qui peuvent determiner les nombreuses autres proprietes protectrices de cette proteine multifonctionnelle. Mots-cles : lactoferrine, structure proteique, liaison du fer, fonctions protectrices, glycosylation., Introduction It is just over 50 years since lactoferrin (Lf) was first isolated and characterized from both human and bovine milks (Johanson et al. 1960; Groves 1960; Montreuil et al. [...]

A study employs the X-ray crystallography technique to analyze the high-resolution crystal structure of a plant carboxylesterase, named Actinidia eriantha (AeCXEI), which is found to be closely related to the hormone-sensitive lipase subgroup structurally. The analysis reveals that the compound binds with paraoxon very easily forming a complex without inducing any change in the structure of the enzyme and hence helps in studying the role of carboxylesterases in plants.

mNeonGreen, an engineered green fluorescent protein (GFP) derived from lancelet, is one of the most brightly fluorescent homologs of Aequorea victoria jellyfish GFP (avGFP) yet reported. In this work, we investigated whether this bright fluorescence might be retained in homologs of mNeonGreen with modified chromophore structures and altered fluorescent hues. We found mNeonGreen to be generally less tolerant than avGFP to chromophore modification by substitution of the key chromophore-forming tyrosine residue with other aromatic amino acids. However, we were ultimately successful in creating a variant, designated as NeonCyan1, with a tryptophan-derived cyan fluorescent protein (CFP)-type chromophore, and two additional mutants with distinct spectral hues. Structural, computational, and photophysical characterization of NeonCyan1 and its variants provided insight into the factors that control the fluorescence emission color. Though not recommended as replacements for contemporary CFP variants, we demonstrate that NeonCyan1 variants are potentially suitable for live cell imaging applications. [ABSTRACT FROM AUTHOR]

Introduction: Pilot projects ("pilots") are important for testing hypotheses in advance of investing more funds for full research studies. For some programs, such as Clinical and Translational Science Awards (CTSAs) supported by the National Center for Translational Sciences, pilots also make up a significant proportion of the research projects conducted with direct CTSA support. Unfortunately, administrative data on pilots are not typically captured in accessible databases. Though data on pilots are included in Research Performance Progress Reports, it is often difficult to extract, especially for large programs like the CTSAs where more than 600 pilots may be reported across all awardees annually. Data extraction challenges preclude analyses that could provide valuable information about pilots to researchers and administrators. Methods: To address those challenges, we describe a script that partially automates extraction of pilot data from CTSA research progress reports. After extraction of the pilot data, we use an established machine learning (ML) model to determine the scientific content of pilots for subsequent analysis. Analysis of ML-assigned scientific categories reveals the scientific diversity of the CTSA pilot portfolio and relationships among individual pilots and institutions. Results: The CTSA pilots are widely distributed across a number of scientific areas. Content analysis identifies similar projects and the degree of overlap for scientific interests among hubs. Conclusion: Our results demonstrate that pilot data remain challenging to extract but can provide useful information for communicating with stakeholders, administering pilot portfolios, and facilitating collaboration among researchers and hubs. [ABSTRACT FROM AUTHOR]

Introduction: Identifying the most effective ways to support career development of early stage investigators in clinical and translational science should yield benefits for the biomedical research community. Institutions with Clinical and Translational Science Awards (CTSA) offer KL2 programs to facilitate career development; however, the sustained impact has not been widely assessed. Methods: A survey comprised of quantitative and qualitative questions was sent to 2144 individuals that had previously received support through CTSA KL2 mechanisms. The 547 responses were analyzed with identifying information redacted. Results: Respondents held MD (47%), PhD (36%), and MD/PhD (13%) degrees. After KL2 support was completed, physicians' time was divided 50% to research and 30% to patient care, whereas PhD respondents devoted 70% time to research. Funded research effort averaged 60% for the cohort. Respondents were satisfied with their career progression. More than 95% thought their current job was meaningful. Two-thirds felt confident or very confident in their ability to sustain a career in clinical and translational research. Factors cited as contributing to career success included protected time, mentoring, and collaborations. Conclusion: This first large systematic survey of KL2 alumni provides valuable insight into the group's perceptions of the program and outcome information. Former scholars are largely satisfied with their career choice and direction, national recognition of their expertise, and impact of their work. Importantly, they identified training activities that contributed to success. Our results and future analysis of the survey data should inform the framework for developing platforms to launch sustaining careers of translational scientists. [ABSTRACT FROM AUTHOR]

Research has been conducted on the proteins of the transferrin family. The role of these proteins in the iron homeostasis in vertebrates has been investigated and discussed.

Crystal structure analysis of the N-lobe half-molecule of human transferrin, which mediates iron transport, reveals a highly conserved iron binding site and hydrogen bonding interaction. Data point out that the binding and release of iron is influenced by the dilysine interaction.

Background and Introduction During the past 10 years, statistical analysis of ground water quality monitoring data from solid and hazardous waste disposal facilities has become routine. The goal of such [...]

Safety behaviors display some similarities to coping behaviors, raising questions about whether the two sets of behaviors display distinct associations with anxiety symptoms. To examine this issue, we conducted two cross-sectional studies in which participants (n = 243 and 157) completed measures of the safety behaviors associated with social anxiety disorder (SAD) and generalized anxiety disorder (GAD), the Brief Ways of Coping Scale (BWOC), and SAD and GAD symptom measures. In Study 1, extant safety-behavior and coping measures were used. In Study 2, the measures were modified so that they followed the same format and instructions. Both studies indicated that the safety behavior measures displayed strong positive associations with their respective symptoms, as did several dysfunctional coping strategies, most notably wishful thinking. These findings provide preliminary empirical support for the conceptual distinction between safety behaviors and coping, and suggest that assessing both concepts provide a nuanced understanding of responding to anxiety-evoking situations. Highlights• Safety-seeking strategies and coping behaviors have striking similarities• We conducted two studies to compare extant measures of the two constructs• Participants were able to distinguish the two set of behaviors• Both safety behaviors and dysfunctional coping were associated with anxiety symptoms [ABSTRACT FROM AUTHOR]

X-ray diffraction studies were conducted to determine the structure of the trigonal crystal form of the beta-lactoglobulin of cows to determine the structural basis of the Tanford transition of this protein. Results of the studies done at different pH levels reveal that conformational changes in the segment spanning amino acid residues 85 to 90 is responsible for the physical and spectroscopic phenomena comprising the Tanford transition of beta-lactoglobulin.

The crystalline structures of the iron-bound, recombinant N-lobe of human serum transferrin has been studied at resolutions 1.6 and 1.8 angstroms. Transferrins are bilobal proteins that bind strongly with ferric iron at two similar binding sites. Both structures have folding patterns that resemble those of previously discovered transferrin and lactoferrin N-lobe structures. Its amino acid sequence has a polypeptide chain that has similar amino- and carboxyl-terminal halves.

Structural and spectral perturbations are seen when oxalate ion is substituted at the binding site for carbonate ion, in lactoferrin protein that belongs to the family of transferrin proteins. However, polypeptide folding and domain closure remain unaffected by the substitution. Oxalate is bound to iron at the C-lobe site of the bilobal transferrin in a symmetric 1,2-bidentate manner, whereas at the N-lobe site, the binding is asymmetric. This happens because oxalate, being a larger anion, displaces the wall forming arginine at the anion binding site.

JOAN ARUZ, KIM BENZEL & JEAN M. EVANS (ed.). Beyond Babylon: art, trade, and diplomacy in the second millennium BC. xxiv+524 pages, 460 b&w & colour illustrations. 2008. New Haven [...]

The binding of copper(II) instead of iron(III) to lactoferrin takes on a different coordination geometry but results in the same protein structure. The substitution, with subsequent crystal structure study, is undertaken to determine the effects of non-Fe metal binding to transferrins. Whereas the two binding sites for iron are the same, copper binds at the N-terminal site via a square pyramidal form and at the C-terminal site with a distorted octahedral. The difference results from the movement of metal ion andanion at each binding site but does not affect the protein structure.

Physicochemical and crystallographic studiesreveal the binding behavior of lactoferrin (Lf) to iron(III) and copper(II). Lfis a glycoprotein that easily binds with iron in biological fluids and thus controls its presence therein. The studies show that binding is done through the carbonate (CO3) anion which locks in bidentate fashion to the metal. Oxalate (C2O4) ions can displace one or both CO3 in a Lf-Cu(II) complex but notin a Lf-Fe(III) complex. In the hybrid (CO3-C2O4) complex, which results when alittle EDTA is present, the CO3 binds specifically at the C-lobe, displacing nearby side chains. A generalized model for anion binding is developed from these results.

Abstract Background The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically relevant RT mutants. Many structural analogues of rilpivirine are described in the patent literature, but detailed analyses of their antiviral activities have not been published. This work addresses the ability of several of these analogues to inhibit the replication of wild-type (WT) and drug-resistant HIV-1. Results We used a combination of structure activity relationships and X-ray crystallography to examine NNRTIs that are structurally related to rilpivirine to determine their ability to inhibit WT RT and several clinically relevant RT mutants. Several analogues showed broad activity with only modest losses of potency when challenged with drug-resistant viruses. Structural analyses (crystallography or modeling) of several analogues whose potencies were reduced by RT mutations provide insight into why these compounds were less effective. Conclusions Subtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors.

Library staff at California State University, Fullerton carried out a project to determine where budget cuts could be made in their electronic journal subscriptions. The team analyzed usage statistics by journal title, determined pricing for each journal, and created a formula to clearly define the cost effectiveness of continuing or deactivating a subscription. In this presentation, Keri Prelitz and Greg Yorba, with contributions from Ilda Cardenas, explain the special considerations, challenges, and outcomes of the project. Using this information, they will repeat the analysis annually, especially in the wake of additional budget cuts due to the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The accumulation of misfolded proteins is associated with numerous degenerative conditions, cancers and genetic diseases. These pathological imbalances in protein homeostasis (termed proteostasis), result from the improper triage and disposal of damaged and defective proteins from the cell. The ubiquitin-proteasome system is a key pathway for the molecular control of misfolded cytosolic proteins, co-opting a cascade of ubiquitin ligases to direct terminally damaged proteins to the proteasome via modification with chains of the small protein, ubiquitin. Despite the evidence for ubiquitination in this critical pathway, the precise complement of ubiquitin ligases and deubiquitinases that modulate this process remains under investigation. Whilst chaperones act as the first line of defence against protein misfolding, the ubiquitination machinery has a pivotal role in targeting terminally defunct cytosolic proteins for destruction. Recent work points to a complex assemblage of chaperones, ubiquitination machinery and subcellular quarantine as components of the cellular arsenal against proteinopathies. In this review, we examine the contribution of these pathways and cellular compartments to the maintenance of the cytosolic proteome. Here we will particularly focus on the ubiquitin code and the critical enzymes which regulate misfolded proteins in the cytosol, the molecular point of origin for many neurodegenerative and genetic diseases. [ABSTRACT FROM AUTHOR]

Heather Baker reviews Emergency Preparedness for Libraries, Second Edition; Elizabeth Parang reviews Leading Change in Academic Libraries; Robert T. Wilson reviews Makerspace and Collaborative Technologies, a LITA Guide. [ABSTRACT FROM AUTHOR]

Abstract Background Primary human tissues are an invaluable widely used tool for discovery of gene expression patterns which characterize disease states. Tissue processing methods remain unstandardized, leading to unanswered concerns of how to best store collected tissues and maintain reproducibility between laboratories. We subdivided uterine myometrial tissue specimens and stored split aliquots using the most common tissue processing methods (fresh, frozen, RNALater) before comparing quantitative RNA expression profiles on the Affymetrix U133 human expression array. Split samples and inclusion of duplicates within each processing group allowed us to undertake a formal genome-wide analysis comparing the magnitude of result variation contributed by sample source (different patients), processing protocol (fresh vs. frozen vs. 24 or 72 hours RNALater), and random background (duplicates). The dataset was randomly permuted to define a baseline pattern of ANOVA test statistic values against which the observed results could be interpreted. Results 14,639 of 22,283 genes were expressed in at least one sample. Patient subjects provided the greatest sources of variation in the mixed model ANOVA, with replicates and processing method the least. The magnitude of variation conferred by processing method (24 hours RNALater vs 72 hours RNALater vs. fresh vs frozen) was similar to the variability seen within replicates. Subset analysis of the test statistic according to gene functional class showed that the frequency of "outlier" ANOVA results within each functional class is overall no greater than expected by chance. Conclusions Ambient storage of tissues for 24 or 72 hours in RNALater did not contribute any systematic shift in quantitative RNA expression results relative to the alternatives of fresh or frozen tissue. This nontoxic preservative enables decentralized tissue collection for expression array analysis without a requirement for specialized equipment.