bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients’ knowledge about pharmacists, technicians, and physicians
Authors: Perrault Evan K , Newlon Jenny L 
Published: September 2019

Abstract

Purpose
Including pharmacists within care teams can lead to positive health benefits, yet pharmacists remain underused. Misperceptions about pharmacists’ duties and expertise compared to physicians’ may contribute. This study sought to determine how well patients know the differences between pharmacists, technicians, and physicians regarding their duties and levels of education about medications. It also investigated how patients’ perceptions affect their likelihood to initiate interactions with pharmacists, as well as reasons why they choose not to speak with pharmacists.

Methods
An online survey of 477 U.S. adults was administered via Amazon’s Mechanical Turk. Participants’ knowledge of pharmacists’, pharmacy technicians’, and medical doctors’ education and expertise were measured. Logistic regression determined whether patients’ attitudes toward pharmacists predicted patient–pharmacist interactions. Participants’ reasons for choosing to not talk to pharmacists about their medications were assessed via an open-ended response.

Results
Patients generally know the duties pharmacists can perform compared to duties of technicians, but they incorrectly believe that physicians have more years of drug education than do pharmacists. Patients who have more positive attitudes toward pharmacists versus doctors are more likely to initiate interactions with pharmacists. Not seeing a need to interact, believing their doctors told them everything, or their ability to find information elsewhere (e.g., the Internet) were the 3 most cited reasons for not interacting with a pharmacist.

Conclusion
Reaching across disciplinary lines to colleagues in health communication may assist the pharmacy profession in finding ways to increase patients’ knowledge and perceptions about the important role pharmacists can play, thereby increasing the likelihood of patients wanting to interact with pharmacists.
Distinct cellular mediators drive the Janus Faces of Toll-like Receptor 4 regulation of network excitability which impacts working memory performance after brain Injury
Authors: Korgaonkar Akshata A. , Li Ying , Nguyen Susan , Guevarra Jenieve , Pang Kevin C H , Santhakumar Vijayalakshmi 
Published: September 2019

AbstractThe mechanisms by which the neurophysiological and inflammatory responses to brain injury contribute to memory impairments are not fully understood. Recently, we reported that the innate immune receptor, toll-like receptor 4 (TLR4) enhances AMPA receptor (AMPAR) currents and excitability in the dentate gyrus after fluid percussion brain injury (FPI) while limiting excitability in controls. Here we examine the cellular mediators underlying TLR4 regulation of dentate excitability and its impact on memory performance. In ex vivo slices, astrocytic and microglial metabolic inhibitors selectively abolished TLR4 antagonist modulation of excitability in controls, without impacting FPI rats, demonstrating that glial signaling contributes to TLR4 regulation of excitability in controls. In glia-depleted neuronal cultures from naïve mice, TLR4 ligands bidirectionally modulated AMPAR charge transfer demonstrating the ability of neuronal TLR4 to regulate excitability, as observed after brain injury. In vivo TLR4 antagonism reduced early post-injury increases in mediators of MyD88-dependent and independent TLR4 signaling without altering expression in controls. Blocking TNFα, a downstream effector of TLT4, mimicked effects of TLR4 antagonist and occluded TLR4 agonist modulation of excitability in slices from both control and FPI rats. Functionally, transiently blocking TLR4 in vivo improved impairments in working memory observed one week and one month after FPI, while the same treatment impaired memory function in uninjured controls. Together these data identify that distinct cellular signaling mechanisms converge on TNFα to mediate TLR4 modulation of network excitability in the uninjured and injured brain and demonstrate a role for TLR4 in regulation of working memory function.HighlightsTLR4 suppresses dentate excitability in controls through signaling involving gliaNeuronal TLR4 signaling underlies enhanced dentate excitability after brain injuryTNFα contributes to TLR4 regulation of excitability in the injured brainAltering TLR4 signaling impacts working memory performanceTLR4 signaling is a potential target to improve working memory after brain trauma
GDNF/RET signaling pathway activation eliminates Lewy Body pathology in midbrain dopamine neurons
Authors: Chmielarz Piotr , Er Şafak , Konovalova Julia , Bandrés Laura , Hlushchuk Irena , Albert Katrina , Panhelainen Anne , Luk Kelvin , Airavaara Mikko , Domanskyi Andrii 
Published: September 2019

AbstractNeurodegenerative diseases are associated with proteostasis disturbances and accumulation of fibrillar proteins into insoluble aggregates. Progressive age-related degeneration of dopamine neurons is a primary cause of motor dysfunctions in Parkinson’s disease (PD) and substantial evidence supports critical involvement of α-synuclein (α-syn) in the etiology of PD. α-syn is a cytosolic protein present in high concentrations in pre-synaptic neuronal terminals and a primary constituent of intracellular protein aggregates known as Lewy Neurites or Lewy Bodies. Progression of Lewy pathology is a characteristic feature in the PD brains caused by the prion-like self-templating properties of misfolded α-syn. Modelling Lewy pathology progression with application of exogenously prepared α-syn preformed fibrils, we discovered that glial cell line-derived neurotrophic factor (GDNF) prevented formation of α-syn aggregates in dopamine neurons in culture andin vivoafter viral vector expression of GDNF. These effects were abolished by CRISPR/Cas9-mediated deletion of receptor tyrosine kinaseRet, the major GDNF signaling pathway. Similar to GDNF, expression of mutated constitutively active RET (RET_MEN2B) was able to protect dopamine neurons. GDNF protection against α-syn pathology progression was abolished by Src and attenuated by Akt pathway inhibitors. For the first time, we have shown the neurotrophic factor-mediated protection against the misfolded α-syn propagation in dopamine neurons, uncovered underlying receptor and intracellular signaling pathways. These results for the first time demonstrate that activation of GDNF/RET signaling can be an effective therapeutic approach to prevent Lewy pathology spread at early stages of PD.
Why is the explicit component of motor adaptation limited in elderly adults?
Authors: Vandevoorde Koenraad , Orban de Xivry Jean-Jacques 
Published: September 2019

AbstractThe cognitive component of motor adaptation declines with aging. Yet, in other motor tasks, older adults appear to rely on cognition to improve their motor performance. It is unknown why older adults are not able to do so in motor adaptation. In order to solve this apparent contradiction, we tested the possibility that older adults require more cognitive resources in unperturbed reaching compared to younger adults, which leaves fewer resources available for the cognitive aspect of motor adaptation. Two cognitive-motor dual-task experiments were designed to test this. The cognitive load of unperturbed reaching was assessed via dual-task costs during the baseline period of visuomotor rotation experiments, which provided us with an estimation of the amount of cognitive resources used during unperturbed reaching. However, since we did not observe a link between dual-task costs and explicit adaptation in both experiments, we failed to confirm this hypothesis. Instead, we observed that explicit adaptation was mainly associated with visuospatial working memory capacity. This suggests that visuospatial working memory of an individual might be linked to the extent of explicit adaptation for young and older adults.
Transcriptomic Profiling of Developing Melanocortin Neurons Reveals a Role for Prdm12 in Energy Balance
Authors: Chen Xiameng , Wyler Steven C. , Li Li , Arnold Amanda G. , Wan Rong , Xu Pin , Liu Chen 
Published: September 2019

AbstractThe hypothalamus is a critical regulator of many physiological processes essential for life. In the adult brain, each anatomically-defined hypothalamic nucleus consists of functionally heterogeneous neuronal subpopulations that dictate distinct survival behaviors. Nevertheless, how rich neuronal identities are established in the developing hypothalamus remains poorly understood.Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive.We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons with whole-genome RNA sequencing (RNA-seq). Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons.Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but was absent in NPY/AgRP neurons. Selective ablation of Prdm12 in postmitotic POMC neurons led to early-onset obesity, accelerated linear growth, as well as impaired glucose tolerance, which recapitulates symptoms of POMC/MC4R deficiency in humans. These findings, therefore, establish a previously-unrecognized role for Prdm12 in energy balance. Furthermore, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the developing hypothalamus as well as the developmental origins of diverse survival behaviors.
Quantifying topography-guided actin dynamics across scales using optical flow
Authors: Lee Rachel M. , Campanello Leonard , Hourwitz Matt J. , Omidvar Ava , Alvarez Phillip , Fourkas John T. , Losert Wolfgang 
Published: September 2019

ABSTRACTPeriodic surface topographies with feature sizes comparable to those ofin vivocollagen fibers are used to measure and compare actin dynamics for two representative cell types that have markedly different migratory modes and physiological purposes: slowly migrating epithelial MCF10A cells and polarizing, fast migrating, neutrophil-like HL60 cells. Both cell types exhibit reproducible guidance of actin waves (esotaxis) on these topographies, enabling quantitative comparisons of actin dynamics. We adapt a computer-vision algorithm, optical flow, to measure the directions of actin waves at the submicron scale. Clustering the optical flow into regions that move in similar directions enables micron-scale measurements of actin-wave speed and direction. Although the speed and morphology of actin waves differ between MCF10A and HL60 cells, the underlying actin guidance by nanotopography is similar in both cell types at the micron and sub-micron scales.
Lotus japonicus karrikin receptors display divergent ligand-binding specificities and organ-dependent redundancy
Authors: Carbonnel Samy , Torabi Salar , Griesmann Maximilian , Bleek Elias , Tang Yuhong , Buchka Stefan , Basso Veronica , Shindo Mitsuru , Boyer François-Didier , Wang Trevor L. , Udvardi Michael , Waters Mark , Gutjahr Caroline 
Published: September 2019

AbstractKarrikins (KARs), smoke-derived butenolides, are perceived by the α/β-fold hydrolase KARRIKIN INSENSITIVE2 (KAI2) and are thought to mimic endogenous, yet elusive plant hormones tentatively called KAI2-ligands (KLs). The sensitivity to different karrikin types as well as the number of KAI2 paralogs varies among plant species, suggesting diversification and co-evolution of ligand-receptor relationships. In legumes, which comprise a number of important crops with protein-rich, nutritious seed, KAI2 has duplicated. We report sub-functionalization of KAI2a and KAI2b in the model legume Lotus japonicus and demonstrate that their ability to bind the synthetic ligand GR24ent-5DS differs in vitro as well as in genetic assays in Lotus japonicus and in the heterologous Arabidopsis thaliana background. These differences can be explained by the exchange of a widely conserved phenylalanine in the binding pocket of KAI2a with a tryptophan in KAI2b, which occured independently in KAI2 proteins of several unrelated angiosperms. Furthermore, two polymorphic residues in the binding pocket are conserved across a number of legumes and may contribute to ligand binding preferences. Unexpectedly, L. japonicus responds to diverse synthetic KAI2-ligands in an organ-specific manner. Hypocotyl development responds to KAR1, KAR2 and rac-GR24, while root system development responds only to KAR1. This organ-specificity cannot be explained by receptor-ligand preferences alone, because LjKAI2a is sufficient for karrikin responses in the hypocotyl, while LjKAI2a and LjKAI2b operate redundantly in roots. Our findings open novel research avenues into the evolution and diversity of butenolide ligand-receptor relationships, their ecological significance and the mechanisms controlling diverse developmental responses to different KAI2 ligands.
Protein network structure enables switching between liquid and gel states
Authors: Schmit Jeremy D. , Bouchard Jill J. , Martin Erik W. , Mittag Tanja 
Published: September 2019

AbstractBiomolecular condensates are emerging as an important organizational principle within living cells. These condensed states are formed by phase separation, yet little is known about how material properties are encoded within the constituent molecules and how the specificity for being in different phases is established. Here we use analytic theory to explain the phase behavior of the cancer-related protein SPOP and its substrate DAXX. Binary mixtures of these molecules have a phase diagram that contains dilute liquid, dense liquid, and gel states. We show that these discrete phases appear due to a competition between SPOP-DAXX and DAXX-DAXX interactions. The stronger SPOP-DAXX interactions dominate at sub-stoichiometric DAXX concentrations leading to the formation of crosslinked gels. The theory shows that the driving force for gel formation is not the binding energy, but rather the entropy of distributing DAXX molecules on the binding sites. At high DAXX concentrations the SPOP-DAXX interactions saturate, which leads to the dissolution of the gel and the appearance of a liquid phase driven by weaker DAXX-DAXX interactions. This competition between interactions allows multiple dense phases to form in a narrow region of parameter space. We propose that the molecular architecture of phase-separating proteins governs the internal structure of dense phases, their material properties and their functions. Analytical theory can reveal these properties on the long length and time scales relevant to biomolecular condensates.
Engineering a functional NifDK polyprotein resistant to mitochondrial degradation
Authors: Allen Rob , Gregg Christina , Okada Shoko , Menon Amratha , Hussain Dawar , Gillespie Vanessa , Johnston Ema , Warden Andrew , Taylor Matthew , Colgrave Michelle , Byrne Keren , Wood Craig 
Published: September 2019

AbstractTo engineer Mo dependent nitrogenase function in plants expression of proteins NifD and NifK will be an absolute requirement. Although mitochondria have been established as a suitable eukaryotic environment for biosynthesis of oxygen-sensitive enzymes such as NifH, expression of NifD in this organelle has proven difficult due to cryptic NifD degradation. Here we describe a solution to this problem. Using molecular and proteomic methods, we found NifD degradation to be a consequence of mitochondrial endoprotease activity at a specific motif within NifD. Focusing on this functionally sensitive region, we designed NifD variants comprising between one and three amino acid substitutions and distinguished several that were resistant to degradation when expressed in both plant and yeast mitochondria. Nitrogenase activity assays of these resistant variants in E. coli identified a subset that retained function, including a single amino acid (Y100Q) variant. The Y100Q variant also enabled expression of a NifD(Y100Q)-linker-NifK translational polyprotein in plant mitochondria, confirmed by identification of the polyprotein in the soluble fraction of plant extracts. The NifD(Y100Q)-linker-NifK retained function in E. coli based nitrogenase assays, demonstrating this polyprotein permits expression of NifD and NifK in a defined stoichiometry supportive of activity. Our results exemplify how protein design can overcome impediments encountered when expressing synthetic proteins in novel environments. Specifically, these findings outline our progress toward the assembly of the catalytic unit of nitrogenase within mitochondria.
Variation in Soil Properties under Long-Term Irrigated and Non-Irrigated Cropping and Other Land-Use Systems in Dura Catchment, Northern Ethiopia
Authors: Tesfahunegn Gebreyesus Brhane , Gebru Teklebirhan Arefaine 
Published: September 2019

AbstractThere are limited reports about the impacts of long-term irrigated and non-irrigated cropping and land-use systems (CLUS) on soil properties and nutrient stocks under smallholder farmers’ conditions in developing countries. The objective of this research was to examine variation in soil properties and OC and TN stocks across the different CLUS in Dura sub-catchment, northern Ethiopia. Surveys and discussions on field history were used to identify nine CLUS, namely, tef(Eragrostis tef(Zucc) Trot)) mono-cropping (TM), maize(Zea mays L.)mono-cropping (MM), cauliflower (Brassica oleracea var. botrytis)-maize intercropping (IC1), red beet (Beta Vulgaris)-maize intercropping (IC2), cauliflower-tef-maize rotation (R1), onion (Allium cepaL.)-maize-onion rotation (R2), treated gully (TG), untreated gully (UTG), and natural forest system (NF). A total of 27 composite soil samples were collected randomly from the CLUS for laboratory analysis. Data were subjected to one-way analysis of variance and PCA. The lowest and highest bulk density was determined from NF (1.19 Mg m-3) and UTG (1.77 Mg m-3), respectively. Soil pH, EC and CEC varied significantly among the CLUS. The highest CEC (50.3 cmolckg-1) was under TG followed by NF. The highest soil OC stock (113.6 Mg C ha-1) and TN stock (12.2 Mg C ha-1) were found from NF. The PCA chosen soil properties explained 87% of the soil quality variability among the CLUS. Such soil properties and nutrient stocks variability among the CLUS suggested that introduction of suitable management practices are crucial for sustaining the soil system of the other CLUS.
Task sharing clubfoot treatment in Latin America: a cross-sectional survey of expert opinions
Authors: Martinez Roxana , Smythe Tracey , Pettitt-Schieber Christie , Everhart Jennifer , Hyman Joshua 
Published: September 2019

AbstractWhile the Ponseti method has quickly become the mainstay of clubfoot treatment in most parts of the world, its dissemination and successful implementation in Latin America has been more limited. The additional shortage of orthopedic surgeons in this region makes task sharing a practical approach to address gaps in service provision. We designed an online survey to assess needs, perceptions, and willingness to task share the delivery of the Ponseti method by Ponseti-method-trained physicians across Latin America. Multiple-response questions were summarized and an applied thematic analysis approach was used to analyze free-response questions. We achieved a 66% response rate (31 of 47 experts responded). Our findings illustrate that most physicians feel the need for disseminating and improving Ponseti training, as well as having additional support for clubfoot treatment. While physicians who treat clubfoot have mixed opinions on the role of nonphysicians treating clubfoot, most report logistical concerns and insufficient training as barriers to their inclusion. Given this and the need for improved, more accessible clubfoot care across Latin America, future clubfoot treatment efforts may benefit from incorporating task sharing between orthopedic surgeons and non-physician personnel.
Loss of a novel striated muscle-enriched mitochondrial protein Coq10a enhances postnatal cardiac hypertrophic growth
Authors: Hirose Kentaro , Chang Steven , Yu Hongyao , Wang Jiajia , Barca Emanuele , Chen Xiaoxin , Khyeam Sheamin , Tajima Kazuki , Yoneshiro Takeshi , Kajimura Shingo , Quinzii Catarina M. , Hu Guang , Huang Guo N. 
Published: September 2019

AbstractPostnatal mammalian cardiomyocytes undergo a major transition from hyperplasia (increases in cell numbers) to hypertrophy (expansion in cell size). This process is accompanied by rapid mitochondrial biogenesis and metabolic switches to meet the demand of increased cardiac output. Although most mitochondrial components express ubiquitously, recent transcriptomic and proteomic analyses have discovered numerous tissue-specific mitochondrial proteins whose physiological functions are largely unknown. Here we report that a highly evolutionarily conserved mitochondrial protein Coq10a is predominantly expressed in mammalian cardiac and skeletal muscles, and is highly up-regulated around birth in a thyroid hormone-dependent manner. Deletion ofCoq10aby CRISPR/Cas9 leads to enhanced cardiac growth after birth. Surprisingly, adultCoq10amutant mice maintain the hypertrophic heart phenotype with increased levels of coenzyme Q (CoQ) per cardiomyocyte, preserved cardiac contractile function and mitochondrial respiration, which contrasts with reported mice and humans with mutations in other Coq family genes. Further RNA-seq analysis and mitochondrial characterization suggest an increase of mitochondrial biogenesis in theCoq10amutant heart as a possible consequence of Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1α) activation, consistent with a recent intriguing report that CoQ may function as a natural ligand and partial agonist of Peroxisome Proliferator-Activated Receptor (PPAR) α/γ. Taken together, our study reveals a previously unknown function of a novel striated muscle-enriched mitochondrial protein Coq10a in regulating postnatal heart growth.