Laser glass is a highly engineered optical material that enables the amplification of light in laser systems. It is known for being the heart of the largest laser facilities ever built, where ...thousands of neodymium-doped meter-sized slabs of laser glass create intense beams of near-infrared laser radiation used to study fusion reactions. Or if doped with ytterbium and erbium, laser glass can be made into millimeter-sized components empowering range-finders and dermatological lasers. Decades of development have poised laser glass for the next challenge on the horizon: amplifying light for sustainable inertial fusion energy power plants.
Intrinsically disordered proteins are frequent targets for functional regulation through post-translational modification due to their high accessibility to modifying enzymes and the strong influence ...of changes in primary structure on their chemical properties. While lysine N
-acetylation was first observed as a common modification of histone tails, proteomic data suggest that lysine acetylation is ubiquitous among both nuclear and cytosolic proteins. However, compared with our biophysical understanding of the other common post-translational modifications, mechanistic studies to document how lysine N
-acetyl marks are placed, utilized to transduce signals, and eliminated when signals need to be turned off, have not kept pace with proteomic discoveries. Herein we report a nuclear magnetic resonance method to monitor N
-lysine acetylation through enzymatic installation of a
C-acetyl probe on a protein substrate, followed by detection through
C direct-detect spectroscopy. We demonstrate the ease and utility of this method using histone H3 tail acetylation as a model. The clearest advantage to this method is that it requires no exogenous tags that would otherwise add steric bulk, change the chemical properties of the modified lysine, or generally interfere with downstream biochemical processes. The non-perturbing nature of this tagging method is beneficial for application in any system where changes to local structure and chemical properties beyond those imparted by lysine modification are unacceptable, including intrinsically disordered proteins, bromodomain containing protein complexes, and lysine deacetylase enzyme assays.
This study was concerned with indentifying reasons behind patterns of social media (Web 2.0) usage associated with eight of Australia's major health professions. Attention was given to uncovering ...some of the more significant motivations for the resistance or adoption of Web 2.0 technologies for health care delivery and practice promotion by Australian health professionals. Surveys were developed from a common set of questions with specific variations between professions negotiated with professional health societies. Survey questions were constructed in an attempt to identify Web 2.0 adoption trends. An online survey was used to collect data. Initial data preparation involved the development of one integrated SPSS file to incorporate all responses from the eight surveys undertaken. Initial data analysis applied Frequencies and Crosstabs to the identified groups and provided a profile of respondents by key business and demographic characteristics. Of the 935 respondents, 9.5% of participants indicated that they used Web 2.0 for their professional work, 19.1% of them did not use it for work but used it for their personal needs and 71.3% of them did not use Web 2.0 at all. Participants have indicated that the main reason for 'choosing not to adopt' Web 2.0 applications as a way of delivering health care to their patients is due to the health professionals’ lack of understanding of Web 2.0 (83.3%), while the main reason for 'choosing to adopt' Web 2.0 applications is the perception of Web 2.0 as a quick and effective method of communication (73.0%). This study has indicated that Australian health professionals 'choose not to adopt’ Web 2.0 usage as a way of delivering health care primarily due to 'a lack of understanding as to how social media would be used in health care’ (83.3%). This study identifies that Australian health professionals are interacting with Web 2.0 technologies in their private lives but are failing to see how such technologies might be used throughout their professions. Australian health professionals are willing to undertake online educational courses (n = 553, 58%) designed to upskill them about how Web 2.0 may be used for practice promotion and health care delivery.
The pancreatic and duodenal homeobox 1 (PDX1) is a central regulator of glucose-dependent transcription of insulin in pancreatic β cells. PDX1 transcription factor activity is integral to the ...development and sustained health of the pancreas; accordingly, deciphering the complex network of cellular cues that lead to PDX1 activation or inactivation is an important step toward understanding the etiopathologies of pancreatic diseases and the development of novel therapeutics. Despite nearly 3 decades of research into PDX1 control of Insulin expression, the molecular mechanisms that dictate the function of PDX1 in response to glucose are still elusive. The transcriptional activation functions of PDX1 are regulated, in part, by its two intrinsically disordered regions, which pose a barrier to its structural and biophysical characterization. Indeed, many studies of PDX1 interactions, clinical mutations, and posttranslational modifications lack molecular level detail. Emerging methods for the quantitative study of intrinsically disordered regions and refined models for transactivation now enable us to validate and interrogate the biochemical and biophysical features of PDX1 that dictate its function. The goal of this review is to summarize existing PDX1 studies and, further, to generate a comprehensive resource for future studies of transcriptional control via PDX1.
Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange ...monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies. In the future, this new and exciting development should see broad application to a range of tight macromolecular interactions.
We measure a large set of observables in inclusive charged current muon neutrino scattering on argon with the MicroBooNE liquid argon time projection chamber operating at Fermilab. We evaluate three ...neutrino interaction models based on the widely used GENIE event generator using these observables. The measurement uses a data set consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2016 with the Fermilab Booster Neutrino Beam, which has an average neutrino energy of 800MeV, using an exposure corresponding to 5.0×1019 protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to separate neutrino interactions from cosmic ray background events. We find that GENIE models consistently describe the shapes of a large number of kinematic distributions for fixed observed multiplicity.
We measure a large set of observables in inclusive charged current muon neutrino scattering on argon with the MicroBooNE liquid argon time projection chamber operating at Fermilab. We evaluate three ...neutrino interaction models based on the widely used GENIE event generator using these observables. The measurement uses a data set consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2016 with the Fermilab Booster Neutrino Beam, which has an average neutrino energy of Formula omitted, using an exposure corresponding to Formula omitted protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to separate neutrino interactions from cosmic ray background events. We find that GENIE models consistently describe the shapes of a large number of kinematic distributions for fixed observed multiplicity.
Classified as a biosafety level 4 (BSL4) select agent, Nipah virus (NiV) is a deadly henipavirus in the
family, with a nearly 75% mortality rate in humans, underscoring its global and animal health ...importance. Elucidating the process of viral particle production in host cells is imperative both for targeted drug design and viral particle-based vaccine development. However, little is understood concerning the functions of cellular machinery in paramyxoviral and henipaviral assembly and budding. Recent studies showed evidence for the involvement of multiple NiV proteins in viral particle formation, in contrast to the mechanisms understood for several paramyxoviruses as being reliant on the matrix (M) protein alone. Further, the levels and purposes of cellular factor incorporation into viral particles are largely unexplored for the paramyxoviruses. To better understand the involvement of cellular machinery and the major structural viral fusion (F), attachment (G), and matrix (M) proteins, we performed proteomics analyses on virus-like particles (VLPs) produced from several combinations of these NiV proteins. Our findings indicate that NiV VLPs incorporate vesicular trafficking and actin cytoskeletal factors. The involvement of these biological processes was validated by experiments indicating that the perturbation of key factors in these cellular processes substantially modulated viral particle formation. These effects were most impacted for NiV-F-modulated viral particle formation either autonomously or in combination with other NiV proteins, indicating that NiV-F budding relies heavily on these cellular processes. These findings indicate a significant involvement of the NiV fusion protein, vesicular trafficking, and actin cytoskeletal processes in efficient viral particle formation.
Nipah virus is a zoonotic biosafety level 4 agent with high mortality rates in humans. The genus to which Nipah virus belongs,
, includes five officially recognized pathogens; however, over 20 species have been identified in multiple continents within the last several years. As there are still no vaccines or treatments for NiV infection, elucidating its process of viral particle production is imperative both for targeted drug design as well as for particle-based vaccine development. Developments in high-throughput technologies make proteomic analysis of isolated viral particles a highly insightful approach to understanding the life cycle of pathogens such as Nipah virus.
Introduction: This study was concerned with identifying motivations and trends associated with a health website recommendation from eight of Australia's major health professions to the health ...consumer. Health professions included in this study are: psychiatrists, general practitioners, social workers, dietitians, chiropractors, physiotherapists, optometrists and pharmacists. Methods: An online survey (www.limesurvey.org) was developed from a common set of questions negotiated between all eight health professions. Survey questions were constructed in an attempt to identify participants' reasons for or against recommending a health website to a patient. A 5-point scale (not, slightly, neutral, moderately, strongly) to measure influence was used throughout the question set. Results: This study indicates that Australian general practitioners (GPs) were the highest Australian health professionals to undertake a health website recommendation (86%), followed by psychiatrists (80%), with the lowest being physiotherapists (42%) and optometrists (33%). A profile of the Australian health professional who recommends a health website is identified as male, aged above 50 years, has had more than 10 years experience, works in a major city, is in private practice and has patient numbers exceeding 500 in a 12-month period (2009). Conclusion: Recommendations from this study include the need to develop mechanisms that identify high-quality online medical information and the development and implementation of Continuing Professional Development (CPD) courses which up-skill health professionals concerning the recommendation of health websites for health care delivery.
Speckle-type POZ protein (SPOP) is a ubiquitin ligase adaptor that binds substrate proteins and facilitates their proteasomal degradation. Most SPOP substrates present multiple SPOP-binding (SB) ...motifs and undergo liquid–liquid phase separation with SPOP. Pancreatic and duodenal homeobox 1 (Pdx1), an insulin transcription factor, is downregulated by interaction with SPOP. Unlike other substrates, only one SB motif has previously been reported within the Pdx1 C-terminal intrinsically disordered region (Pdx1-C). Given this difference, we aimed to determine the specific mode of interaction of Pdx1 with SPOP and how it is similar or different to that of other SPOP substrates. Here, we identify a second SB motif in Pdx1-C, but still find that the resulting moderate valency is insufficient to support phase separation with SPOP in cells. Although Pdx1 does not phase separate with SPOP, Pdx1 and SPOP interaction prompts SPOP relocalization from nuclear speckles to the diffuse nucleoplasm. Accordingly, we find that SPOP-mediated ubiquitination activity of Pdx1 occurs in the nucleoplasm and that highly efficient Pdx1 turnover requires both SB motifs. Our results suggest that the subnuclear localization of SPOP–substrate interactions and substrate ubiquitination may be directed by the properties of the substrate itself.
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