bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Controlled Trial comparing the effectiveness of structured-play (ENGAGE) and behavior management (TRIPLE P) in reducing problem behaviors in preschoolers
Authors: Healey Dione , Healey Matthew 
Published: March 2019

AbstractChildren’s behavior problems are a growing concern in our society; and are associated with a wide array of adverse lifespan outcomes. Current treatments are not without limitations and while effective for many, do not help all children. As such, additional treatment options are required. Sixty families of children aged 3 and 4 years participated. In order to participate, children needed to have a T-score of 60 or above on the parent rated Hyperactivity subscale on the BASC-2. Families were randomly assigned to either a structured play-based intervention (ENGAGE; n = 29), or to the current gold standard treatment for preschool behavior problems, behavior management (Triple P; n = 31). This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR); trial number ACTRN12617001432303; trial web address: http://www.anzctr.org.au/ACTRN12617001432303.aspx; date registered; 10/10/2017. ENGAGE was found to be as effective as Triple P in reducing parent-rated problem behaviors in pre-schoolers (i.e., Hyperactivity, Attention Problems, and Aggression); with gains maintained over a 12-month follow-up period, for both interventions. These findings indicate that structured play is an equally effective alternative way to manage difficult behavior in preschoolers and compliments our current treatment options.
Exploiting heat shock protein expression to develop a non-invasive diagnostic tool for breast cancer
Authors: Crouch Brian T. , Gallagher Jennifer , Wang Roujia , Duer Joy , Hall Allison , Soo Mary Scott , Hughes Philip , Haystead Timothy , Ramanujam Nirmala 
Published: March 2019

AbstractLeveraging the unique surface expression of heat shock protein 90 (Hsp90) in breast cancer provides an exciting opportunity to develop rapid diagnostic tests at the point-of-care setting. Hsp90 has previously been shown to have elevated expression levels across all breast cancer receptor subtypes. We have developed a non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens and validated our approach in clinical samples from breast cancer patients across estrogen receptor positive, Her2-overexpressing, and triple negative receptor subtypes. Utilizing a pre-clinical biopsy model, we optimized three imaging parameters that may affect the specificity of HS-27 based diagnostics – time between tissue excision and staining, agent incubation time, and agent dose, and translated our strategy to clinical breast cancer samples. Findings indicated that HS-27 florescence was highest in tumor tissue, followed by benign tissue, and finally followed by mammoplasty negative control samples. Interestingly, fluorescence in tumor samples was highest in Her2+ and triple negative subtypes, and inversely correlated with the presence of tumor infiltrating lymphocytes indicating that HS-27 fluorescence increases in aggressive breast cancer phenotypes. Development of a Gaussian support vector machine classifier based on HS-27 fluorescence features resulted in a sensitivity and specificity of 82% and 100% respectively when classifying tumor and benign conditions, setting the stage for rapid and automated tissue diagnosis at the point-of-care.
Water-Deprived Parasitic Wasps (Pachycrepoideus vindemmiae) Kill More Pupae of a Pest (Drosophila suzukii) as a Water-Intake Strategy
Authors: Bezerra Da Silva Cherre Sade , Price Briana Elizabeth , Walton Vaughn M. 
Published: March 2019

AbstractMost organisms must ingest water to compensate for dehydration. In parasitic wasps, the importance of water and the behaviors driving its consumption are poorly understood. Here, we describe a water-intake strategy of Pachycrepoideus vindemmiae, a parasitoid of spotted-wing drosophila (SWD, Drosophila suzukii). Longevity measurements indicated that P. vindemmiae benefits from drinking water and from host-feeding on the water-rich hemolymph of SWD pupae. After exposing wasps to different water regimens, we observed increased host-feeding in water-deprived wasps despite honey availability. This resulted in greater SWD mortality because the host-feeding process killed the pupae, and because wasps that engaged in greater host-feeding parasitized more hosts. Behavioral observations showed that the host-feeding time of water-deprived wasps doubled compared to water-fed individuals. Host-feeding did not affect parasitoid offspring mortality. We conclude that P. vindemmiae benefits from ingesting water and that it host-feeds on SWD pupae as a water-intake strategy. These are interesting findings not only because water has rarely been reported as a critical nutrient for adult parasitoids, but especially because preying for the purpose of hydration is not a common strategy in nature. This strategy enhances parasitoid survival and reproduction, with positive consequences for its host-killing capacity and potential as a biocontrol agent.
Differential Sensitivity to Plasmodium yoelii Infection in C57BL/6 Mice Impacts Gut-Liver Axis Homeostasis
Authors: Denny Joshua E. , Powers Joshua B. , Castro Hector F. , Zhang Jingwen , Joshi-Barve Swati , Campagna Shawn R. , Schmidt Nathan W. 
Published: March 2019

AbstractExperimental models of malaria have shown that infection with specific Plasmodium species in certain mouse strains can transiently modulate gut microbiota and cause intestinal shortening, indicating a disruption of gut homeostasis. Importantly, changes in gut homeostasis have not been characterized in the context of mild versus severe malaria. We show that severe Plasmodium infection in mice disrupts homeostasis along the gut-liver axis in multiple ways compared to mild infection. High parasite burden results in a larger influx of immune cells in the lamina propria and mice with high parasitemia display specific metabolomic profiles in the ceca and plasma during infection compared to mice with mild parasitemia. Liver damage was also more pronounced and longer lasting during severe infection, with concomitant changes in bile acids in the gut. Finally, severe Plasmodium infection changes the functional capacity of the microbiota, enhancing bacterial motility and amino acid metabolism in mice with high parasite burden compared to a mild infection. Taken together, Plasmodium infections have diverse effects on host gut homeostasis relative to the severity of infection that may contribute to enteric bacteremia that is associated with malaria.
A dynamically interacting flexible loop assists oligomerisation of the Caenorhabditis elegans centriolar protein SAS-6
Authors: Busch Julia M. C. , Erat Michèle C. , Blank Iris D. , Musgaard Maria , Biggin Philip C. , Vakonakis Ioannis 
Published: March 2019

AbstractCentrioles are conserved organelles fundamental for the organisation of microtubules in animal cells. Oligomerisation of the spindle assembly abnormal protein 6 (SAS-6) is an essential step in the centriole assembly process and may act as trigger for the formation of these organelles. SAS-6 oligomerisation is driven by two independent interfaces, comprising an extended coiled coil and a dimeric N-terminal globular domain. However, how SAS-6 oligomerisation is controlled remains unclear. Here, we show that in the Caenorhabditis elegans SAS-6, a segment of the N-terminal globular domain, unresolved in crystallographic structures, comprises a flexible loop that assists SAS-6 oligomerisation. Atomistic molecular dynamics simulations and nuclear magnetic resonance experiments suggest that transient interactions of this loop across the N-terminal dimerisation interface stabilise the SAS-6 oligomer. We discuss the possibilities presented by such flexible SAS-6 segments for the control of centriole formation.
Metal-enhanced fluorescence and excited state dynamics of carotenoids in thin polymer films
Authors: Lee Jaebeom , Song Junghyun , Lee Daedu , Pang Yoonsoo 
Published: March 2019

AbstractMetal-enhanced fluorescence of carotenoids, all-trans-β-carotene and 8′-apo-β-carotene-8′-al dispersed in thin layers of polystyrene and polyethylene glycol were investigated by time-resolved fluorescence spectroscopy. The weak emission signals of carotenoids in polymer films were increased by 4–40 times in the presence of a silver island film and the emission lifetimes of both carotenoids were measured as significantly shortened. The energy transfer from the intermediate states of carotenoids to the silver islands and the subsequent surface plasmon coupled emission were proposed for the mechanisms of metal-enhanced fluorescence. The fluorescence enhancements of carotenoids in the polymer films were also investigated statistically over a wide area of the silver island films.
Common skin bacteria protect their host from oxidative stress through secreted antioxidant RoxP
Authors: Andersson Tilde , Ertürk Bergdahl Gizem , Saleh Karim , Magnúsdóttir Helga , Stødkilde Kristian , Andersen Christian Brix Folsted , Lundqvist Katarina , Jensen Anders , Brüggemann Holger , Lood Rolf 
Published: March 2019

AbstractCutibacterium acnes is an abundant skin commensal with several proposed mutualistic functions. A protein with strong antioxidant activity was recently identified from the C. acnes secretome. This protein, termed RoxP, facilitated aerobic bacterial growth in vitro and ex vivo. As reducing events naturally occurred outside of the bacterial cell, it was further hypothesized that RoxP could also serve to modulate redox status of human skin. The biological function of RoxP was here assessed in vitro and in vivo, through oxidatively stressed cell cultures and through protein quantification from skin affected by oxidative disease (actinic keratosis and basal cell carcinoma), respectively. 16S rDNA amplicon deep sequencing and single locus sequence typing was used to correlate bacterial prevalence to cutaneous RoxP abundances. We show that RoxP positively influence the viability of monocytes and keratinocytes exposed to oxidative stress, and that a congruent concentration decline of RoxP can be observed in skin affected by oxidative disease. Basal cell carcinoma was moreover associated with microbial dysbiosis, characterized by reduced C. acnes prevalence. C. acnes’s secretion of RoxP, an exogenous but naturally occurring antioxidant on human skin, is likely to positively influence the human host. Results furthermore attest to its prospective usability as a biopharmaceutical.
Epigenetic and transcriptional profiling of triple negative breast cancer
Authors: Perreault Andrea A. , Sprunger Danielle M. , Venters Bryan J. 
Published: March 2019

AbstractThe human HCC1806 cell line is frequently used as a preclinical model for triple negative breast cancer (TNBC). Given that dysregulated epigenetic mechanisms are involved in cancer pathogenesis, emerging therapeutic strategies target chromatin regulators, such as histone deacetylases. A comprehensive understanding of the epigenome and transcription profiling in HCC1806 provides the framework for evaluating efficacy and molecular mechanisms of epigenetic therapies. Thus, to study the interplay of transcription and chromatin in the HCC1806 preclinical model, we performed nascent transcription profiling using Precision Run-On coupled to sequencing (PRO-seq). Additionally, we mapped the genome-wide locations for RNA polymerase II (Pol II), the histone variant H2A.Z, seven histone modifications, and CTCF using ChIP-exo. ChIP-exonuclease (ChIP-exo) is a refined version of ChIP-seq with near base pair precision mapping of protein-DNA interactions. In this Data Descriptor, we present detailed information on experimental design, data generation, quality control analysis, and data validation. We discuss how these data lay the foundation for future analysis to understand the relationship between the nascent transcription and chromatin.
A dataset of neonatal EEG recordings with seizure annotations
Authors: Stevenson N. J. , Tapani K. , Lauronen L. , Vanhatalo S. 
Published: March 2019

AbstractNeonatal seizures are a common emergency in the neonatal intensive care unit (NICU). There are many questions yet to be answered regarding the temporal/spatial characteristics of seizures from different pathologies, response to medication, effects on neurodevelopment and optimal detection. The dataset presented in this descriptor contains EEG recordings from human neonates, the visual interpretation of the EEG by the human experts, supporting clinical data and codes to assist access. Multi-channel EEG was recorded from 79 term neonates admitted to the NICU at the Helsinki University Hospital. The median recording duration was 74 min (IQR: 64 to 96 min). The presence of seizures in the EEGs was annotated independently by three experts. An average of 460 seizures were annotated per expert in the dataset; 39 neonates had seizures and 22 were seizure free, by consensus. The dataset can be used as a reference set of neonatal seizures, in studies of inter-observer agreement and for the development of automated methods of seizure detection and other EEG analyses.
Dynamic homeostasis modeling of Zn isotope ratios in the human body
Authors: Jaouen Klervia , Pouilloux Laurent , Balter Vincent , Pons Marie-Laure , Hublin Jean-Jacques , Albarède Francis 
Published: March 2019

Abstract
Recent research performed on volunteers and patients suggested that diet, health, and basal metabolic rates (BMR) are factors controlling the bodily Zn isotope compositions (isotopic homeostasis). However, our poor understanding of the variability of Zn distribution among the different organs and fluids of the human body, and the ensuing isotope fractionation, limits the use of this isotopic system as a typical diagnostic tool for cancers and for past hominin diet reconstructions. Using box model calculations, we investigated the dynamics of Zn isotope variability in blood and other body tissues as well as the consistency of the hypothesis of heavy Zn isotope accumulation through time in the human body. We compare the results of the model with data obtained from control feeding experiments and from archeological samples. Model simulations indicate that the absence of an aging drift in non-circumpolar populations cannot be explained by their lower BMR. We argue that the drift observed in the blood of a circumpolar population results from a differential diet between young and older individuals in this population. When applied to the δ66Zn measured in blood, bones, or teeth, the present box model also offers insight into the isotope composition of the human diet, and therefore into its nature. Applying the model to isotopic observations on the remains of past hominins is a promising tool for diet reconstruction.
Proline residues in scavenger receptor-BI's C-terminal region support efficient cholesterol transport
Authors: Proudfoot Sarah C. , Sahoo Daisy 
Published: March 2019

Abstract
High-density lipoproteins (HDLs) facilitate reverse cholesterol transport, a process in which HDL removes cholesterol from circulation and carries it to the liver for biliary excretion. Reverse cholesterol transport is also facilitated by HDL's high-affinity receptor, scavenger receptor-BI (SR-BI), by mechanisms that are not fully understood. To improve our understanding of SR-BI function, we previously solved the NMR (nuclear magnetic resonance) structure of a peptide encompassing amino acids 405–475 of SR-BI. This segment of SR-BI, that includes the functionally critical C-terminal transmembrane domain and part of the extracellular domain, also contains four conserved proline (Pro) residues. We hypothesized that these proline residues support SR-BI in a conformation that allows for efficient cholesterol transport. To test this, we generated individual Pro-to-alanine mutations in full-length SR-BI and transiently expressed the mutant receptors in COS-7 cells to measure the effects on SR-BI-mediated cholesterol transport functions. Our findings reveal that HDL cell association and uptake of HDL-cholesteryl esters are impaired by mutation of Pro-412, Pro-438, or the transmembrane proline kink residue (Pro-459). In addition, SR-BI-mediated cholesterol efflux and membrane cholesterol distribution are impaired by mutation of Pro-412 or Pro-438, indicating that these residues are essential for a fully functional SR-BI receptor. Furthermore, we demonstrate that Pro-408 is necessary for proper SR-BI expression, but mutation of Pro-408 does not cause SR-BI to become misfolded or rapidly degraded by the proteasome or the lysosome. We conclude that key proline residues play an important role in SR-BI function by allowing for the efficient transport of cholesterol between cells and HDL.
NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer
Authors: Velloso Fernando J. , Trombetta-Lima Marina , Anschau Valesca , Sogayar Mari C. , Correa Ricardo G. 
Published: March 2019

Abstract
Innate immunity comprises several inflammation-related modulatory pathways which receive signals from an array of membrane-bound and cytoplasmic pattern recognition receptors (PRRs). The NLRs (NACHT (NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein) and Leucine-Rich Repeat (LRR) domain containing proteins) relate to a large family of cytosolic innate receptors, involved in detection of intracellular pathogens and endogenous byproducts of tissue injury. These receptors may recognize pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs), activating host responses against pathogen infection and cellular stress. NLR-driven downstream signals trigger a number of signaling circuitries, which may either initiate the formation of inflammasomes and/or activate nuclear factor κB (NF-κB), stress kinases, interferon response factors (IRFs), inflammatory caspases and autophagy. Disruption of those signals may lead to a number of pro-inflammatory conditions, eventually promoting the onset of human malignancies. In this review, we describe the structures and functions of the most well-defined NLR proteins and highlight their association and biological impact on a diverse number of cancers.
Membrane trafficking in osteoclasts and implications for osteoporosis
Authors: Ng Pei Ying , Brigitte Patricia Ribet Amy , Pavlos Nathan John 
Published: March 2019

Abstract
Osteoclasts are large multinucleated cells exquisitely adapted to resorb bone matrix. Like other eukaryotes, osteoclasts possess an elaborate ensemble of intracellular organelles through which solutes, proteins and other macromolecules are trafficked to their target destinations via membrane-bound intermediaries. During bone resorption, membrane trafficking must be tightly regulated to sustain the structural and functional polarity of the osteoclasts’ membrane domains. Of these, the ruffled border (RB) is most characteristic, functioning as the osteoclasts' secretory apparatus. This highly convoluted organelle is classically considered to be formed by the targeted fusion of acidic vesicles with the bone-facing plasma membrane. Emerging findings disclose new evidence that the RB is far more complex than previously envisaged, possessing discrete subdomains that are serviced by several intersecting endocytic, secretory, transcytotic and autophagic pathways. Bone-resorbing osteoclasts therefore serve as a unique model system for studying polarized membrane trafficking. Recent advances in high-resolution microscopy together with the convergence of genetic and cell biological studies in humans and in mice have helped illuminate the major membrane trafficking pathways in osteoclasts and unmask the core molecular machinery that governs these distinct vesicle transport routes. Among these, small Rab GTPases, their binding partners and members of the endocytic sorting nexin family have emerged as critical regulators. This mini review summarizes our current understanding of membrane trafficking in osteoclasts, the key molecular participants, and discusses how these transport machinery may be exploited for the development of new therapies for metabolic disorders of bone-like osteoporosis.
LRRK2 links genetic and sporadic Parkinson's disease
Authors: Kluss Jillian H. , Mamais Adamantios , Cookson Mark R. 
Published: March 2019

Abstract
The past two decades in research has revealed the importance of leucine-rich repeat kinase 2 (LRRK2) in both monogenic and sporadic forms of Parkinson's disease (PD). In families, mutations in LRRK2 can cause PD with age-dependent but variable penetrance and genome-wide association studies have found variants of the gene that are risk factors for sporadic PD. Functional studies have suggested that the common mechanism that links all disease-associated variants is that they increase LRRK2 kinase activity, albeit in different ways. Here, we will discuss the roles of LRRK2 in areas of inflammation and vesicular trafficking in the context of monogenic and sporadic PD. We will also provide a hypothetical model that links inflammation and vesicular trafficking together in an effort to outline how these pathways might interact and eventually lead to neuronal cell death. We will also highlight the translational potential of LRRK2-specific kinase inhibitors for the treatment of PD.
Transcription in cyanobacteria: a distinctive machinery and putative mechanisms
Authors: Riaz-Bradley Amber 
Published: March 2019

Abstract
Transcription in cyanobacteria involves several fascinating features. Cyanobacteria comprise one of the very few groups in which no proofreading factors (Gre homologues) have been identified. Gre factors increase the efficiency of RNA cleavage, therefore helping to maintain the fidelity of the RNA transcript and assist in the resolution of stalled RNAPs to prevent genome damage. The vast majority of bacterial species encode at least one of these highly conserved factors and so their absence in cyanobacteria is intriguing. Additionally, the largest subunit of bacterial RNAP has undergone a split in cyanobacteria to form two subunits and the SI3 insertion within the integral trigger loop element is roughly 3.5 times larger than in Escherichia coli. The Rho termination factor also appears to be absent, leaving cyanobacteria to rely solely on an intrinsic termination mechanism. Furthermore, cyanobacteria must be able to respond to environment signals such as light intensity and tightly synchronise gene expression and other cell activities to a circadian rhythm.
Recent developments in genetic/genomic medicine
Authors: Horton Rachel H. , Lucassen Anneke M. 
Published: March 2019

Abstract
Advances in genetic technology are having a major impact in the clinic, and mean that many perceptions of the role and scope of genetic testing are having to change. Genomic testing brings with it a greater opportunity for diagnosis, or predictions of future diagnoses, but also an increased chance of uncertain or unexpected findings, many of which may have impacts for multiple members of a person’s family. In the past, genetic testing was rarely able to provide rapid results, but the increasing speed and availability of genomic testing is changing this, meaning that genomic information is increasingly influencing decisions around patient care in the acute inpatient setting. The landscape of treatment options for genetic conditions is shifting, which has evolving implications for clinical discussions around previously untreatable disorders. Furthermore, the point of access to testing is changing with increasing provision direct to the consumer outside the formal healthcare setting. This review outlines the ways in which genetic medicine is developing in light of technological advances.