bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal Metrics of Multisensory Processing Change in the Elderly
Authors: Basharat Aysha , Mahoney Jeannette R. , Michael-Barnett-Cowan  
Published: March 2019

AbstractOlder adults exhibit greater multisensory response time (RT) facilitation by violating the race model more than younger adults; this is commonly interpreted as an enhancement in perception. Older adults typically exhibit wider temporal binding windows (TBWs) and points of subjective simultaneity (PSS) that are farther from true simultaneity as compared to younger adults when simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks are utilized; this is commonly interpreted as an impairment in perception. Here we explore the relation between the three tasks in younger and older adults in order to better understand the underlying mechanisms that subserve audiovisual multisensory temporal processing. Our results confirm previous reports showing that audiovisual RT, TBWs and PSSs change with age, and we show for the first time a significant positive relation between the magnitude of race model violation in younger adults as a function of the PSS obtained from the audiovisual TOJ task with (r: 0.49,p: 0.007), that is absent among the elderly (r: 0.13,p: 0.58). Furthermore, we find no evidence for the relation between race model violation as a function of the PSS obtained from the audiovisual SJ task in both younger (r: −0.01,p: 0.94) and older adults (r: 0.1,p: 0.66). Our results confirm previous reports that i) audiovisual temporal processing changes with age; ii) there is evidence for distinct neural networks involved in simultaneity and temporal order perception; and iii) common processing between race model violation and temporal order judgment is impaired in the elderly.
A lineage-resolved molecular atlas of C. elegans embryogenesis at single cell resolution
Authors: Packer Jonathan S. , Zhu Qin , Huynh Chau , Sivaramakrishnan Priya , Preston Elicia , Dueck Hannah , Stefanik Derek , Tan Kai , Trapnell Cole , Kim Junhyong , Waterston Robert H. , Murray John I. 
Published: March 2019

AbstractC. elegans is an animal with few cells, but a striking diversity of cell types. Here, we characterize the molecular basis for their specification by profiling the transcriptomes of 84,625 single embryonic cells. We identify 284 terminal and pre-terminal cell types, mapping most single cell transcriptomes to their exact position in C. elegans’ invariant lineage. We use these annotations to perform the first quantitative analysis of the relationship between lineage and the transcriptome for a whole organism. We find that a strong lineage-transcriptome correlation in the early embryo breaks down in the final two cell divisions as cells adopt their terminal fates and that most distinct lineages that produce the same anatomical cell type converge to a homogenous transcriptomic state. Users can explore our data with a graphical application “VisCello”.
Machine learning-guided channelrhodopsin engineering enables minimally-invasive optogenetics
Authors: Bedbrook Claire N. , Yang Kevin K. , Robinson J. Elliott , Gradinaru Viviana , Arnold Frances H. 
Published: March 2019

AbstractWe have engineered light-gated channelrhodopsins (ChRs) whose current strength and light sensitivity enable minimally-invasive neuronal circuit interrogation. Current ChR tools applied to the mammalian brain require intracranial surgery for transgene delivery and implantation of invasive fiber-optic cables to produce light-dependent activation of a small volume of brain tissue [~1 mm3]. To enable optogenetics for large brain volumes and without the need for invasive implants, our ChR engineering approach leverages the significant literature of ChR variants to train statistical models for the design of new, high-performance ChRs. With Gaussian Process models trained on a limited experimental set of 102 functionally characterized ChR variants, we designed high-photocurrent ChRs with unprecedented light sensitivity; three of these, ChRger1, ChRger2, and ChRger3, enable optogenetic activation of the nervous system via minimally-invasive systemic transgene delivery with rAAV-PHP.eB, which was not possible previously due to low per-cell transgene copy produced by systemic delivery. These engineered ChRs enable light-induced neuronal excitation without invasive intracranial surgery for virus delivery or fiber optic implantation, i.e. they enable minimally-invasive optogenetics.
C-type lectins CTL4 and CTLMA2: conserved heterodimeric structure and glycan specificity in Anopheles mosquitoes
Authors: Bishnoi Ritika , Contet Alicia , Day Christopher J , Hou David Chun-Feng , Profitt Lauren A. , Singla Deepak , Sousa Gregory L. , Jennings Michael P , Povelones Michael , Valentine Ann M. , Baxter Richard H. G. 
Published: March 2019

AbstractThe C-type lectins CTL4 and CTLMA2 cooperatively influence Plasmodium infection in the malaria vector Anopheles. Here we report the purification and biochemical characterization of CTL4 and CTLMA2 from An. gambiae and An. albimanus. CTL4 and CTLMA2 are known to form a disulfide-bridged heterodimer via an N-terminal tri-cysteine CXCPC motif. We demonstrate in vitro that CTL4 and CTLMA2 intermolecular disulfide formation is promiscuous within this motif. Furthermore, CTL4 and CTLMA2 exhibit charge complementarity that promotes the formation of higher oligomeric states at physiological pH. Both lectins bind specific sugars, with an apparent preference for glycosaminoglycan motifs comprising β1-3/β1-4 linkages between glucose (Glc), galactose (Gal) and their respective hexosamines. Small-angle x-ray scattering data supports a compact heterodimer between the CTL domains. Recombinant CTL4/CTLMA2 is functional in vivo, reversing the enhancement of phenoloxidase activity in dsCTL4-treated mosquitoes. We propose these molecular features underline a common function for CTL4/CTLMA2 in mosquitoes, with species and strain-specific variation in degrees of activity in response to Plasmodium infection.Author SummaryMosquitoes of the genus Anopheles are vectors for the single-celled parasite Plasmodium, the causative agent of malaria. Mosquitoes, like all insects, utilize the process of melanization for both wound healing and defense against pathogens. CTL4 and CTLMA2 are two proteins found in Anopheles mosquitoes that act as inhibitors of melanization, so understanding their molecular function is important to understanding the immune response of Anopheles mosquitoes to Plasmodium infection. We have purified CTL4 and CTLMA2 from two species of Anopheles and studied their molecular properties with a variety of biochemical and biophysical techniques. We also verified that our purified protein is functional by injecting it into mosquitoes. We learned that CTL4 and CTLMA2 are joined together by a disulfide bond between any one of three cysteine residues near the N-terminus of each protein. The CTL4/CTLMA2 complex is compact, but can associate into larger structures in solution, probably because of a loop in each protein that carries an opposite charge. The proteins cooperatively bind calcium and sugars, specifically glycosaminoglycan sugars, which are typically present in the connective tissues of insects. This information will aid in further investigations of the function of CTL4 and CTLMA2.
Influenza A matrix protein M1 is sufficient to induce lipid membrane deformation
Authors: Dahmani Ismail , Ludwig Kai , Chiantia Salvatore 
Published: March 2019

AbstractThe matrix protein M1 of the Influenza A virus is considered to mediate viral assembly and budding at the plasma membrane (PM) of infected cells. In order for a new viral particle to form, the PM lipid bilayer has to bend into a vesicle towards the extracellular side. Studies in cellular models have proposed that different viral proteins might be responsible for inducing membrane curvature in this context (including M1), but a clear consensus has not been reached. In this study, we use a combination of fluorescence microscopy, cryogenic transmission electron microscopy (cryo-TEM), cryo-electron tomography (cryo-ET) and scanning fluorescence correlation spectroscopy (sFCS) to investigate M1-induced membrane deformation in biophysical models of the PM. Our results indicate that M1 is indeed capable to cause membrane curvature in lipid bilayers containing negatively-charged lipids, in the absence of other viral components. Furthermore, we prove that simple protein binding is not sufficient to induce membrane restructuring. Rather, it appears that stable M1-M1 interactions and multimer formation are required in order to alter the bilayer three-dimensional structure, through the formation of a protein scaffold. Finally, our results suggest that, in a physiological context, M1-induced membrane deformation might be modulated by the initial bilayer curvature and the lateral organization of membrane components (i.e. the presence of lipid domains).
Social status in mouse social hierarchies is associated with variation in oxytocin and vasopressin 1a receptor densities
Authors: Lee Won , Hiura Lisa C , Yang Eilene , Broekman Katherine A , Ophir Alexander G , Curley James P 
Published: March 2019

AbstractThe neuropeptides oxytocin and vasopressin and their receptors have established roles in the regulation of mammalian social behavior including parental care, sex, affiliation and pair-bonding, but less is known regarding their relationship to social dominance and subordination within social hierarchies. We have previously demonstrated that male mice can form stable linear dominance hierarchies with individuals occupying one of three classes of social status: alpha, subdominant, subordinate. Alpha males exhibit high levels of aggression and rarely receive aggression. Subdominant males exhibit aggression towards subordinate males but also receive aggression from more dominant individuals. Subordinate males rarely exhibit aggression and receive aggression from more dominant males. Here, we examined whether variation in social status was associated with levels of oxytocin (OTR) and vasopressin 1a (V1aR) receptor binding in socially relevant brain regions. We found that socially dominant males had significantly higher OTR binding in the nucleus accumbens core than subordinate animals. Alpha males also had higher OTR binding in the anterior olfactory nucleus, posterior part of the cortical amygdala and rostral lateral septum compared to more subordinate individuals. Conversely, alpha males had lower V1aR binding in the rostral lateral septum and lateral preoptic area compared to subordinates. These observed relationships have two potential explanations. Preexisting individual differences in the patterns of OTR and V1aR binding may underlie behavioral differences that promote or inhibit the acquisition of social status. More likely, the differential social environments experienced by dominant and subordinate animals may shift receptor expression, potentially facilitating the expression of adaptive social behaviors.HighlightsMice living in social hierarchies express different levels of oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) binding in various brain regions according to their social status.Alphas and subdominants have higher OTR binding in the nucleus accumbens compared to subordinates.Alphas have higher OTR binding in the anterior olfactory nucleus compared to subdominants and subordinates.Alphas have higher OTR and lower V1aR binding in the rostral lateral septum compared to subordinates.Alphas have lower V1aR binding in the lateral preoptic area compared to subordinates.
Sensitive determination of proteolytic proteoforms in limited microscale proteome samples
Authors: Weng Samuel S.H. , Demir Fatih , Ergin Enes K. , Dirnberger Sabrina , Uzozie Anuli , Tuscher Domenic , Nierves Lorenz , Tsui Janice , Huesgen Pitter F. , Lange Philipp F. 
Published: March 2019

AbstractProtein N-termini reveal fundamental regulatory mechanisms and their perturbation in disease. Current terminome identification approaches are limited to whole organs or expandable cultured cells. We present a robust, sensitive, scalable and automatable method for system-wide identification of thousands of N-termini from minute samples. Identification of distinct N- terminal profiles in sorted immune cells, subcellular compartments, clinical biopsies, plasma from pediatric cancer patients, and protease substrates in Arabidopsis seedlings demonstrate broad applicability.
Older age is associated with a reduced likelihood of ambulance transport to a trauma centre after major trauma in Perth
Authors: Brown Elizabeth , Tohira Hideo , Bailey Paul , Fatovich Daniel , Pereira Gavin , Finn Judith 
Published: March 2019

AbstractObjectiveTo describe the characteristics and outcomes of older adult (≥65 years) major trauma patients in comparison with younger adults (16–64 years). To determine whether older age is associated with a reduced likelihood of transport (directly or indirectly) to a major trauma centre and whether this is associated with in‐hospital mortality.MethodsA retrospective cohort study of major trauma patients transported to hospital by St John Ambulance paramedics in Perth, Western Australia, between 1 January 2013 and 31 December 2016. Multivariate logistic regression was used to test the relationship between age and major trauma centre transport. Multivariate logistic regression analysis using inverse probability of treatment weighting was used to determine if major trauma centre transport was associated with in‐hospital mortality in older adults.ResultsOne thousand six hundred and twenty‐five patients were included; of these 576 (35%) were ≥65 years. In comparison with younger adults, older adults had more falls as their mechanism of injury (n = 358 [62%] versus n = 102 [10%], P ≤ 0.001) and more major head injuries (n = 472 [82%] versus n = 609 [58%], P ≤ 0.001). Older adults had lower odds (adjusted odds ratio 0.52, 95% confidence interval [CI] 0.35–0.78) of major trauma centre transport and this was associated with 1.7 times the likelihood of in‐hospital mortality (95% CI 1.04–2.7).ConclusionsOlder adults who were not transported to the trauma centre had an increased odds of in‐hospital mortality. However, older age was associated with a significantly reduced likelihood of trauma centre transport. With the aging population, the development of specific prehospital triage criteria to enable the complexities of this higher‐risk population to be identified is important.
Adherence to medication in adults with Cystic Fibrosis: An investigation using objective adherence data and the Theoretical Domains Framework
Authors: Arden Madelynne A. , Drabble Sarah , O'Cathain Alicia , Hutchings Marlene , Wildman Martin 
Published: March 2019

ObjectivesAdherence to nebulizer treatment in adults with Cystic Fibrosis (CF) is poor, and interventions are needed. This research aimed to identify the factors affecting nebulizer adherence using the Theoretical Domains Framework (TDF) and to compare these for participants with different levels of adherence.DesignData‐prompted interviews using the TDF.MethodsEighteen semi‐structured interviews were conducted with adults with CF during which objectively measured adherence data were discussed. Framework analysis was used to code the data into TDF domains, and inductive qualitative content analysis was used to code different beliefs and experiences. Aspects of the TDF that differed between participants with different adherence levels were explored.ResultsFactors influencing adherence to treatment included all 14 domains of the TDF, 10 of which appeared to vary by adherence level: Skills; Memory and decision‐making; and Behavioural regulation; Environmental context and resources; Social influences; Beliefs about consequences; Beliefs about capability; Reinforcement; Social role and identify; Intentions; Optimism; and Emotions.ConclusionsThis study is the first to use objectively measured adherence data in a data‐prompted interview using the TDF framework to systematically assess the full range of factors potentially influencing adherence. The results highlighted that interventions need to consider issues of capability, opportunity, and motivation. Interventions that challenge dysfunctional beliefs about adherence and which support the development of routines or habits and problem‐solving may be particularly useful for adults with CF.
Statement of contributionWhat is already known?

Adherence to medication in adults with cystic fibrosis is poor.

Previous research has identified a range of contributing factors in relation to subjective reports of adherence.

There is a wide discrepancy between self‐reported adherence and objectively measured adherence.

What this study adds

A data‐prompted interview using objectively measured adherence data enabled the systematic assessment of potential factors that could be targeted in an intervention to increase adherence.

There were some differences in the factors that were identified by high and low adherers.

There is not one‐size fits all intervention for adherence to medication in cystic fibrosis.
Design, synthesis, and evaluation of novel heteroaryldihydropyrimidine derivatives as non‐nucleoside hepatitis B virus inhibitors by exploring the solvent‐exposed region
Authors: Yu Ji , Jia Haiyong , Guo Xiaowei , Desta Samuel , Zhang Shuo , Zhang Jian , Ding Xiao , Liang Xiaohong , Liu Xinyong , Zhan Peng 
Published: March 2019

AbstractIn continuation of our efforts toward the discovery of potent non‐nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent‐exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non‐nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti‐HBV DNA replication activity compared to lamivudine. In particular, compound II‐1 displayed the most potent activity against HBV DNA replication (IC50 = 0.35 ± 0.04 μM). The preliminary structure–activity relationships of the new compounds were summarized, which may help in discovering more potent anti‐HBV agents via rational drug design.
Baicalein inhibits matrix metalloproteinase 1 expression via activation ofTRPV1‐Ca‐ERKpathway in ultraviolet B–irradiated human dermal fibroblasts
Authors: Huang Kuo‐Feng , Ma Kuo‐Hsing , Chang Yen‐Jung , Lo Liang‐Chuan , Jhap Tian‐You , Su Yu‐Hua , Liu Pei‐Shan , Chueh Sheau‐Huei 
Published: March 2019

AbstractIncreased matrix metalloproteinase 1 (MMP‐1) expression is a feature of photo‐aged skin. We investigated the effects of baicalein and sulphoraphane on ultraviolet B (UVB) irradiation–inducedMMP‐1 expression and apoptosis using human dermal fibroblasts.UVBirradiation not only increasedMMP‐1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells fromUVBirradiation–induced apoptosis, but only baicalein inhibitedMMP‐1 expression.UVBirradiation activated 12‐lipoxygenase, and its product, 12‐hydroxyeicosatetraenoic acid, activatedTRPV1 channels. The resultingUVBirradiation–induced Ca2+increase was blocked by the 12‐lipoxygenase inhibitor baicalein and theTRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane.UVBirradiation also increasedROSgeneration and decreased Nrf2 protein levels.UVBirradiation–inducedMMP‐1 expression was blocked by the Ca2+chelatorBAPTA, by capsazepine and byTRPV1 silencing. However, induction was unaffected by the antioxidant N‐acetylcysteine.ERKphosphorylation andJNKphosphorylation were induced byUVBirradiation, but onlyERKphosphorylation was Ca2+sensitive. IncreasedMMP‐1 expression was blocked byPD98059, but not bySP600125. Thus, increasedMMP‐1 expression is mediated by increased cytosolic Ca2+andERKphosphorylation.UVBirradiation–inducedROSgeneration is also Ca2+sensitive, andUVBirradiation–induced apoptosis is caused by increasedROS. Thus, baicalein, by blocking theUVBirradiation–induced cytosolic Ca2+increase, protects cells fromUVBirradiation–inducedMMP‐1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellularROS, protects cells from onlyUVB‐induced apoptosis. Thus, targeting 12‐lipoxygenase may provide a therapeutic approach to improving the health of photo‐aged human skin.
Critically examining the knowledge base required to mechanistically project climate impacts: A case study of Europe's fish and shellfish
Authors: Catalán Ignacio A. , Auch Dominik , Kamermans Pauline , Morales‐Nin Beatriz , Angelopoulos Natalie V. , Reglero Patricia , Sandersfeld Tina , Peck Myron A. 
Published: March 2019

AbstractAn amalgam of empirical data from laboratory and field studies is needed to build robust, theoretical models of climate impacts that can provide science‐based advice for sustainable management of fish and shellfish resources. Using a semi‐systematic literature review, Gap Analysis and multilevel meta‐analysis, we assessed the status of empirical knowledge on the direct effects of climate change on 37 high‐value species targeted by European fisheries and aquaculture sectors operating in marine and freshwater regions. Knowledge on potential climate change‐related drivers (single or combined) on several responses (vital rates) across four categories (exploitation sector, region, life stage, species), was considerably unbalanced as well as biased, including a low number of studies (a) examining the interaction of abiotic factors, (b) offering opportunities to assess local adaptation, (c) targeting lower‐value species. The meta‐analysis revealed that projected warming would increase mean growth rates in fish and mollusks and significantly elevate metabolic rates in fish. Decreased levels of dissolved oxygen depressed rates of growth and metabolism across coherent species groups (e.g., small pelagics, etc.) while expected declines in pH reduced growth in most species groups and increased mortality in bivalves. The meta‐analytical results were influenced by the study design and moderators (e.g., life stage, season). Although meta‐analytic tools have become increasingly popular, when performed on the limited available data, these analyses cannot grasp relevant population effects, even in species with a long history of study. We recommend actions to overcome these shortcomings and improve mechanistic (cause‐and‐effect) projections of climate impacts on fish and shellfish.
Fully sintered alumina with a higher Vickers hardness prepared using a gel‐casting process
Authors: Lee Kuo‐Yang , Chen Chih‐Cheng , Hsiang Hsing‐I , Yen Fu‐Su , Huang Chi‐Yuen 
Published: March 2019

AbstractThe dispersant (commercial ammonium polyacrylate), sintering additive (Mg2+), and chelating agent (EDTA) effects on the Zeta potential and rheological behavior of alumina slurry with high solid content were investigated. The alumina ceramic green microstructures and sintered microstructures prepared using slurries with different additives using the gel‐casting process were also studied. It was observed that the dispersion deteriorated after adding Mg2+. Slurry simultaneously added with dispersant and EDTA‐chelated Mg2+ produced higher absolute Zeta potential value and low viscosity due to EDTA chelating with Mg2+. The sample added with dispersant and EDTA‐chelated Mg2+ exhibited a uniform green microstructure, high relative sintered density (99.5% theoretical density), and a nearly pore‐free microstructure with an average grain size of about 1.5 μm. For the first time to our knowledge, the maximum Vickers hardness (22 GPa) was obtained for alumina simultaneously added with Mg2+ and EDTA, pressureless sintered at 1500°C in air.