The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

Pulse combustion: The importance of characteristic times

The response of a valved pulse combustor to changes in the relative timing between the resonant pressure wave and the instantaneous energy release rate has been examined. Experiments were designed to examine the pulse combustor's response to independent changes in the experimental conditions that resulted in nearly independent changes in the fluid dynamic species mixing time, the fluid dynamic mixing time of cold reactants with hot products, the characteristic chemical kinetics time, and the characteristic resonance time. The time scales considered in this study were adjusted independently to modify the coupling between the instantaneous energy release rate and the resonant pressure wave, thereby modifying the magnitude of the pressure oscillations and altering the frequency of operation. All of these experimental observations of the pulse combustor response to variations in characteristic time scales are interpreted in terms of Rayleigh's criterion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28111/1/0000560.pd

BioMagResBank (BMRB) as a partner in the Worldwide Protein Data Bank (wwPDB): new policies affecting biomolecular NMR depositions

We describe the role of the BioMagResBank (BMRB) within the Worldwide Protein Data Bank (wwPDB) and recent policies affecting the deposition of biomolecular NMR data. All PDB depositions of structures based on NMR data must now be accompanied by experimental restraints. A scheme has been devised that allows depositors to specify a representative structure and to define residues within that structure found experimentally to be largely unstructured. The BMRB now accepts coordinate sets representing three-dimensional structural models based on experimental NMR data of molecules of biological interest that fall outside the guidelines of the Protein Data Bank (i.e., the molecule is a peptide with 23 or fewer residues, a polynucleotide with 3 or fewer residues, a polysaccharide with 3 or fewer sugar residues, or a natural product), provided that the coordinates are accompanied by representation of the covalent structure of the molecule (atom connectivity), assigned NMR chemical shifts, and the structural restraints used in generating model. The BMRB now contains an archive of NMR data for metabolites and other small molecules found in biological systems

Haplotype profile comparisons cetween Spodoptera frugiperda (Lepidoptera: Noctuidae) populations from Mexico with those from Puerto Rico, South America, and the United States and their implications to migratory behavior

Fall armyworm [Spodoptera frugiperda (J. E. Smith)] is a major economic pest throughout the Western Hemisphere of maize, cotton, sorghum, and a variety of agricultural grasses and vegetable crops. Previous studies demonstrated extensive annual migrations occurring as far north as Canada from overwintering locations in southern Florida and Texas. In contrast, migratory behavior in the rest of the hemisphere is largely uncharacterized. Understanding the migration patterns of fall armyworm will facilitate efforts to predict the spread of pesticide resistance traits that repeatedly arise in this species and assess the consequences of changing climatic trends on the infestation range. Four independent fall armyworm colonies derived from widely separated populations in Mexico and two field collections were examined for their mitochondrial cytochrome oxidase I (COI) gene haplotypes and compared with other locations. The Mexico populations were most similar in their haplotype profile to those from Texas and South America, but also displayed some distinctive features. The data extend the haplotype distribution map in the Western Hemisphere and confirm that the previously observed regional differences in haplotype frequencies are stable over time. The Mexico collections were associated with haplotypes rarely found elsewhere, suggesting limited migratory interactions with foreign populations, including those in neighboring Texas.Fil: Nagoshi, Rodney N.. United States Department Of Agriculture. Agricultural Research Service; ArgentinaFil: Rosas Garcia, Ninfa M.. Instituto Politécnico Nacional; MéxicoFil: Meagher, Robert L.. United States Department Of Agriculture. Agricultural Research Service; ArgentinaFil: Fleischer, Shelby J.. State University Of Pennsylvania; Estados UnidosFil: Westbrook, John K.. United States Department Of Agriculture. Agricultural Research Service; ArgentinaFil: Sappington, Thomas W.. United States Department Of Agriculture. Agricultural Research Service; ArgentinaFil: Hay Roe, Mirian. United States Department Of Agriculture. Agricultural Research Service; ArgentinaFil: Thomas, Jean M. G.. United States Department Of Agriculture. Agricultural Research Service; ArgentinaFil: Murúa, María Gabriela. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Diesel Combustion: An Integrated View Combining Laser Diagnostics, Chemical Kinetics, And Empirical Validation

This paper proposes a structure for the diesel combustion process based on a combination of previously published and new results. Processes are analyzed with proven chemical kinetic models and validated with data from production-like direct injection diesel engines. The analysis provides new insight into the ignition and particulate formation processes, which combined with laser diagnostics, delineates the two-stage nature of combustion in diesel engines. Data are presented to quantify events occurring during the ignition and initial combustion processes that form soot precursors. A framework is also proposed for understanding the heat release and emission formation processes

Evolutionary Diversification of SPANX-N Sperm Protein Gene Structure and Expression

The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage ∼7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well

In-home evaluation of efficacy and titration of a mandibular advancement device for obstructive sleep apnea

There is increasing evidence that mandibular advancement devices (MADs) can be an effective treatment for some patients with obstructive sleep apnea, a highly prevalent chronic disease. In this study, the objectives were to objectively assess the effectiveness of MAD therapy using a limited channel recorder, and to develop a model for identifying patients who may be appropriate for MAD therapy as the initial treatment option. Thirty patients were prospectively recruited and studied at two independent dentist offices and the participants’ homes. Subjects wore the ARES Unicorder for two nights before insertion of the MAD, and again when the dentist determined that the patient had reached the titration endpoint. Self-reported measures of depression, sleepiness, and quality of life were obtained pre- and posttreatment. The reviewer was blinded to the study status while the physiological signals were being visually inspected. Significant reductions in the apnea/hypopnea index (AHI), hypoxemia measures, and snoring level were observed posttreatment. Twenty-seven of the 30 (90%) patients had a posttreatment AHI (using a 4% desaturation for hypopneas) below a clinical cut-off of 10. All but one patient (97%) exhibited at least a 50% decrease in AHI or had a posttreatment AHI ≤ 10. Significant differences in body mass index, weight, and neck circumference in patients with posttreatment AHIs above and below a clinical cut-off of five were identified. The linear regression used to predict the posttreatment AHI using pretreatment data resulted in an R2 of 0.68. The model correctly predicted two patients who were unable to obtain a posttreatment AHI of 10 or less. This study was designed to demonstrate two models of collaboration between a dental sleep medicine specialist and a sleep medicine physician in the monitoring of a patient treated with a MAD. The outcome data suggest that the limited channel recording system can be used as an alternative to laboratory polysomnography to reduce the cost of MAD treatment, and to improve the quality and consistency of posttreatment patient care

The role of the smartphone in the transition from medical student to foundation trainee: a qualitative interview and focus group study

Background The transition from medical student to junior doctor is one of the most challenging in medicine, affecting both doctor and patient health. Opportunities to support this transition have arisen from advances in mobile technology and increased smartphone ownership. Methods This qualitative study consisted of six in-depth interviews and two focus groups with Foundation Year 1 Trainees (intern doctors) and final year medical students within the same NHS Trust. A convenience sample of 14 participants was recruited using chain sampling. Interviews and focus groups were recorded, transcribed verbatim, analysed in accordance with thematic analysis and presented below in keeping with the standards for reporting qualitative research. Results Participants represented both high and low intensity users. They used their smartphones to support their prescribing practices, especially antimicrobials through the MicroGuide™ app. Instant messaging, via WhatsApp, contributed to the existing bleep system, allowing coordination of both work and learning opportunities across place and time. Clinical photographs were recognised as being against regulations but there had still been occasions of use despite this. Concerns about public and colleague perceptions were important to both students and doctors, with participants describing various tactics employed to successfully integrate phone use into their practices. Conclusion This study suggests that both final year medical students and foundation trainees use smartphones in everyday practice. Medical schools and healthcare institutions should seek to integrate such use into core curricula/training to enable safe and effective use and further ease the transition to foundation training. We recommend juniors are reminded of the potential risks to patient confidentiality associated with smartphone use

Federating structural models and data:Outcomes from a workshop on archiving integrative structures

Structures of biomolecular systems are increasingly computed by integrative modeling. In this approach, a structural model is constructed by combining information from multiple sources, including varied experimental methods and prior models. In 2019, a Workshop was held as a Biophysical Society Satellite Meeting to assess progress and discuss further requirements for archiving integrative structures. The primary goal of the Workshop was to build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are presented here