bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prey capturing and feeding apparatus of dragonfly nymph
Authors: Kundanati Lakshminath , Das Prashant , Pugno Nicola M. 
Published: February 2019

AbstractAquatic predatory insects, like the nymphs of a dragonfly, use rapid movements to catch their prey. Dragonfly nymphs are voracious predators that feed on smaller aquatic organisms. In this study, we examine dragonfly nymph (Libellulidae: Insecta: Odonata)mouthparts that are used in prey capturing and feeding. In particular, we characterise the morphology of the labium and mechanical properties of the mandibles of the nymph. Additionally, we record and analyse the preying mechanism using high-speed photography. The morphological details suggest that the prey capturing mechanism is a complex grasping mechanism with additional sensory organs that might aid in sensing the surroundings. The times taken for the extension and retraction of labial organ during prey capture was 187±54 ms. The Young’s modulus and hardness of the mandibles samples were 9.1±1.9 GPa and 0.85±0.13 GPa. Gradation in the mechanical properties was also observed in the mandible tip regions with increased properties at the tip end. The overall mechanism with its sensory capabilities provides a unique design to develop bioinspired underwater deployable mechanisms.
Y-Family DNA Polymerases Have Three Structural Elements That Promote Accurate dCTP Insertion And Minimize dATP/dGTP/dTTP Misinsertion Opposite a N2-dG Adduct of Benzo[a]pyrene
Authors: Sholder Gabriel , Tonzi Peter , Chandani Sushil , Loechler Edward L. 
Published: February 2019

ABSTRACTTo bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N2-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N2-dG. To investigate structural differences between Y-Family-classes, Dpo4 (a canonical η/V-class-member) is modified to make it more κ/IV-like, as evaluated via primer-extension studies with a BP-N2-dG-containing template. Three protein structural elements are identified that promote fidelity. (1) Watson-Crick-like [dCTP:BP-N2-dG] pairing requires the BP-moiety to be in the minor groove. Thus, as expected, dCTP insertion is facilitated by having large openings in the protein surface that can accommodate BP-bulk in the minor groove. The BP-moiety is also in the minor groove during dATP and dTTP misinsertion, though evidence suggests that each of these three minor groove BP-conformations differ. (2) Plugging an opening on the major groove side of the protein suppresses dGTP misinsertion, implying BP-N2-dG bulk is in the major groove during Hoogsteensyn-adduct-dG:dGTP pairing. (3) Y-Family DNAPs have non-covalent bridges (NCBs) holding their little finger-domain in contact with their catalytic core-domain; dATP/dGTP/dTTP misinsertions are suppressed by the quantity and quality of NCBs, including one near and another distal to the active site on the minor groove side. In conclusion, three protein structural elements enhance dCTP and/or suppress dATP/dGTP/dTTP insertion; four different BP-adduct conformations are responsible for the four different dNTP insertional pathways opposite BP-N2-dG; generalizations about Y-Family structure are also considered.
Real-time, functional intra-operative localization of rat cavernous nerve network using near-infrared cyanine voltage-sensitive dye imaging
Authors: Kang Jeeun , Le Hanh N. D. , Karakus Serkan , Malla Adarsha P. , Harraz Maged M. , Kang Jin U. , Burnett Arthur L. , Boctor Emad M. 
Published: February 2019

AbstractDespite current progress achieved in the surgical technique of radical prostatectomy, post-operative complications such as erectile dysfunction and urinary incontinence persist at high incidence rates. In this paper, we present a methodology for functional intra-operative localization of the cavernous nerve (CN) network for nerve-sparing radical prostatectomy using near-infrared cyanine voltage-sensitive dye (VSD) imaging, which visualizes membrane potential variations in the CN and its branches (CNB) in real time. As a proof-of-concept experiment, we demonstrate a functioning complex nerve network in response to electrical stimulation of the CN, which was clearly differentiated from surrounding tissues in anin vivorat prostate model. Stimulation of an erection was confirmed by correlative intracavernosal pressure (ICP) monitoring. Within 10 minutes, we performed trans-fascial staining of the CN by direct VSD administration. Our findings suggest the applicability of VSD imaging for real-time, functional imaging guidance during nerve-sparing radical prostatectomy.
Senescence and Defense Pathways Contribute to Heterosis
Authors: Gonzalez-Bayon Rebeca , Shen Yifei , Groszmann Michael , Zhu Anyu , Wang Aihua , Allu Annapurna D. , Dennis Elizabeth S. , Peacock W. James , Greaves Ian K. 
Published: February 2019

AbstractHybrids are used extensively in agriculture due to their superior performance in seed yield and plant growth, yet the molecular mechanisms underpinning hybrid performance are not well understood. Recent evidence has suggested that a decrease in basal defense response gene expression regulated by reduced levels of salicylic acid (SA) may be important for vigor in certain hybrid combinations. Decreasing levels of SA in the Arabidopsis (Arabidopsis thaliana) accession C24 through the introduction of the SA catabolic enzyme salicylate1 hydroxylase (NahG) increases plant size, phenocopying the large-sized C24/Landsberg erecta (Ler) F1 hybrids. C24♀ × Ler♂ F1 hybrids and C24 NahG lines shared differentially expressed genes and pathways associated with plant defense and leaf senescence including decreased expression of SA biosynthetic genes and SA response genes. The expression of TL1 BINDING TRANSCRIPTION FACTOR1, a key regulator in resource allocation between growth and defense, was decreased in both the F1 hybrid and the C24 NahG lines, which may promote growth. Both C24 NahG lines and the F1 hybrids showed decreased expression of the key senescence-associated transcription factors WRKY53, NAC-CONTAINING PROTEIN29, and ORESARA1 with a delayed onset of senescence compared to C24 plants. The delay in senescence resulted in an extension of the photosynthetic period in the leaves of F1 hybrids compared to the parental lines, potentially allowing each leaf to contribute more resources toward growth.
US and Chinese yield curve responses to RMB exchange rate policy shocks
Authors: Hong Zhiwu , Niu Linlin , Zeng Gengming 
Published: February 2019

Purpose
Using a discrete-time version of the arbitrage-free Nelson–Siegel (AFNS) term structure model, the authors examine how yield curves in the US and China react to exchange rate policy shocks as China introduces gradual reforms to make its exchange rate regime more flexible. The paper aims to discuss this issue.

Design/methodology/approach
The authors characterize the specification of the discrete-time AFNS model, prove the uniqueness of the solution for model identification, perform specification analysis on its canonical form and detail the MCMC estimation method with a fast and reliable prior extraction step.

Findings
Model decomposition reveals that in the US yield responses, changes in risk premia for medium- to long-term yields dominate changes in yield expectation for short- to medium-term yields, indicating that the portfolio rebalancing effect due to varying risk perception is stronger than the signaling effect due to policy rate expectation.

Practical implications
The results are helpful in diagnosing market sentiment and exchange rate risk pricing as China further internationalizes its currency.

Originality/value
The methodology can be easily extended to study yield curve responses to other scenarios of policy shocks or regime changes.
Late flowering time enhances insect pollination of turnip rape
Authors: Toivonen Marjaana , Herzon Irina , Rajanen Hanne , Toikkanen Jenni , Kuussaari Mikko 
Published: February 2019

Abstract

Ecological intensification has been proposed as a strategy to mitigate the impacts of conventional intensive land use on pollinators and insect pollination. However, research has concentrated on the effects of land management on pollinator abundance and diversity, while studies directly measuring pollination services are still lacking for many crops and regions.

This study examines the effects of landscape heterogeneity, pesticide use intensity and flowering time on insect pollination of turnip rape Brassica rapa ssp. oleifera, a major oil crop at high latitudes. The field experiment included monitoring pollinator visits on turnip rape flowers and measuring yield in 34 spring‐sown turnip rape fields in Southern Finland. The fields were situated in two landscape types that differed in the cover of arable land and represented independent gradients of pesticide use intensity and flowering time.

Based on flower visits and number of seeds per silique, turnip rape was best pollinated in fields with late flowering time. The result suggests a temporal mismatch between crop flowering and the availability of pollination service in early sown fields. The increase in flower visits during summer was steeper among fields with low than high pesticide use, possibly due to a faster colony growth of important bee pollinators.

Pollinator community in turnip rape fields was more diverse in heterogeneous landscapes with less arable land than in homogeneous field‐dominated landscapes, suggesting higher stability of pollination services in diverse landscapes.

Total yield per plant was positively related to pesticide use intensity. The relationship between insect pollination and total yield was weakened by high compensation capacity of turnip rape, the plants producing more flowers under poor pollination.

Synthesis and applications. Crop pollination can be enhanced by shifting sowing time to better match crop flowering to the peak availability of the most important pollinators. Reduced pesticide use may also enhance pollination services but can lead to the total yield reduction due to pests. This highlights the need for pollinator‐friendly pest control methods to maintain turnip rape yields while conserving pollination services.
In Vitro Bioaccessibility of Tart Cherry Anthocyanins in a Health Supplement Mix Containing Mineral Clay
Authors: Singh Anika , Kitts David D. 
Published: February 2019

AbstractThe study reports on the in vitro bioaccessibility of anthocyanins present in tart cherry extracts formulated with a mineral clay to produce a novel natural health product. Results show that tart cherry anthocyanins are stable and bioaccessible after gastric digestion but were largely transformed or degraded (>70%) after duodenal digestion. This contrasted the fact that total antioxidant capacity of tart cherry extract using oxygen radical absorbance capacity assay increased almost two‐fold after GI digestion. There was no significant difference between anthocyanin recovery when present the mineral clay formulation, compared to control, thus the presence of the cationic‐based mineral clay was not a factor in reducing anthocyanin bioaccessibility, or increasing antioxidant capacity. In vitro digestion of foods or natural health products should be included in protocols that aim to assess overall bioaccessibility and bioactivity of those anthocyanins present in tart cherry.Practical ApplicationThis research investigates the impact of having a mineral clay–based matrix on bioaccessiblity of tart cherry anthocyanins. This study describes the anthocyanin composition of tart cherry and the effect of cations present in mineral clay on final total bioavailability following in vitro simulation of human gastrointestinal digestion.
The Informativeness of Relative Performance Information and Its Effect on Effort Allocation in a Multitask Environment
Authors: Hannan R. Lynn , McPhee Gregory P. , Newman Andrew H. , Tafkov Ivo D. , Kachelmeier Steven J. 
Published: February 2019

ABSTRACTPrior research documents that providing relative performance information (RPI) motivates employees to increase effort; however, a potential downside of RPI is that it also motivates employees to distort their effort allocations between tasks such that it can be detrimental to overall firm performance. This study investigates via an experiment how the informativeness of RPI affects employees' effort allocations and performance in a multitask environment. We investigate the informativeness of two RPI design choices that are observed in practice: detail level and temporal aggregation. Regarding detail level, firms may provide each employee's performance ranking on tasks, which is less informative than providing the actual performance score of each employee. Regarding temporal aggregation, firms may provide RPI that is reset each period, which is less informative than RPI that is based on cumulative performance. We find RPI detail level and temporal aggregation interact to influence effort distortion. Specifically, we find that, compared to reset RPI, cumulative RPI leads to greater distortion of effort away from firm‐preferred allocations and that this effect is magnified when RPI provides actual performance scores rather than performance rankings. Finally, high levels of effort distortion hurt overall performance, thereby demonstrating the potentially detrimental effect of effort distortion on performance. Results of our study enhance our understanding of how firms can use their control over the design of RPI to enhance its usefulness in directing employees' effort in multitask environments by highlighting the role that informativeness of information can have on employee behavior.
Extranuclear DNA accumulates in aged cells and contributes to senescence and inflammation
Authors: Lan Yuk Yuen , Heather James M. , Eisenhaure Thomas , Garris Christopher Stuart , Lieb David , Raychowdhury Raktima , Hacohen Nir 
Published: February 2019

AbstractSystemic inflammation is central to aging‐related conditions. However, the intrinsic factors that induce inflammation are not well understood. We previously identified a cell‐autonomous pathway through which damaged nuclear DNA is trafficked to the cytosol where it activates innate cytosolic DNA sensors that trigger inflammation. These results led us to hypothesize that DNA released after cumulative damage contributes to persistent inflammation in aging cells through a similar mechanism. Consistent with this notion, we found that older cells harbored higher levels of extranuclear DNA compared to younger cells. Extranuclear DNA was exported by a leptomycin B‐sensitive process, degraded through the autophagosome–lysosomal pathway and triggered innate immune responses through the DNA‐sensing cGAS‐STING pathway. Patient cells from the aging diseases ataxia and progeria also displayed extranuclear DNA accumulation, increased pIRF3 and pTBK1, and STING‐dependent p16 expression. Removing extranuclear DNA in old cells using DNASE2A reduced innate immune responses and senescence‐associated (SA) β‐gal enzyme activity. Cells and tissues of Dnase2a−/− mice with defective DNA degradation exhibited slower growth, higher activity of β‐gal, or increased expression of HP‐1β and p16 proteins, while Dnase2a−/−;Sting−/− cells and tissues were rescued from these phenotypes, supporting a role for extranuclear DNA in senescence. We hypothesize a direct role for excess DNA in aging‐related inflammation and in replicative senescence, and propose DNA degradation as a therapeutic approach to remove intrinsic DNA and revert inflammation associated with aging.
Evaluating metronidazole as a novel, safe CYP2A6 phenotyping probe in healthy adults
Authors: Stancil Stephani L. , Pearce Robin E. , Tyndale Rachel F. , Kearns Gregory L. , Vyhlidal Carrie A. , Leeder J. Steven , Abdel‐Rahman Susan 
Published: February 2019

AimsCYP2A6 is a genetically polymorphic enzyme resulting in differential substrate metabolism and health behaviours. Current phenotyping probes for CYP2A6 exhibit limitations related to procurement (deuterated cotinine), toxicity (coumarin), specificity (caffeine) and age‐appropriate administration (nicotine, NIC). In vitro, CYP2A6 selectively forms 2‐hydroxymetronidazole (2HM) from metronidazole (MTZ). The purpose of this study was to evaluate MTZ as a CYP2A6 phenotyping probe drug in healthy adults against the well‐established method of measuring trans‐3‐hydroxycotinine (3HC)/cotinine (COT).MethodsA randomized, cross‐over, pharmacokinetic study was completed in 16 healthy, nonsmoking adults. Separated by a washout period of at least 2 weeks, MTZ 500 mg and NIC gum 2 mg were administered and plasma was sampled over 48 hours and 8 hours, respectively. Correlations of plasma metabolite/parent ratios (2HM/MTZ; 3HC/COT) were assessed by Pearson coefficient. CYP2A6 genotyping was conducted and incorporated as a variable of plasma ratio response.ResultsCorrelations between the plasma ratio 2HM/MTZ and 3HC/COT were ≥ 0.9 at multiple time points (P < 0.001), demonstrating a wide window during which 2HM/MTZ can be queried post‐MTZ dose. CYP2A6 genotype had significant impacts on both MTZ and NIC phenotyping ratios with decreased activity predicted phenotypes demonstrating 2HM/MTZ ratios ≤58% and 3HC/COT ratios ≤56% compared with extensive activity predicted phenotypes at all time points examined in the study (P < 0.05). No adverse events were reported in the MTZ arm while 38% (n = 6) of participants reported mild adverse events in the NIC arm.ConclusionsMetronidazole via 2HM/MTZ performed well as a novel, safe phenotyping probe for CYP2A6 in healthy adults.
Blockage of sphingosine‐1‐phosphate receptor 2 attenuates allergic asthma in mice
Authors: Park Soo‐Jin , Im Dong‐Soon 
Published: February 2019

Background and PurposeSphingosine‐1‐phosphate 2 (S1P2) receptors have been implicated in degranulation of mast cells. However, functions of S1P2 receptors have not been investigated in an in vivo model of allergic asthma.Experimental ApproachUsing an ovalbumin (OVA)‐induced asthma model, the function of S1P2 receptors was evaluated in S1P2‐deficient mice or in mice treated with JTE‐013, a selective S1P2 antagonist. Bone marrow‐derived dendritic cells (BMDCs) were used to investigate the roles of S1P2 receptors in dendritic cell maturation and migration.Key ResultsEosinophil accumulation and elevated Th2 cytokine levels in bronchoalveolar lavage fluid and inflamed lung tissues were strongly inhibited by administration of JTE‐013 before OVA sensitization, before OVA challenge, and before both events. In S1P2‐deficient mice, allergic responses were significantly lower than in wild‐type mice. LPS‐ and OVA‐induced maturation of BMDCs was significantly blunted in dendritic cells from S1P2‐deficient mice and by treatment with JTE‐013. Migrations of immature and mature BMDCs were also dependent on S1P2 receptors. It was found that OVA‐challenged mice into which in vitro OVA primed BMDCs from S1P2‐deficient mice were adoptively transferred, had less severe asthma responses than OVA‐challenged mice into which OVA‐primed BMDCs from wild‐type mice were adoptively transferred.Conclusions and ImplicationsPro‐allergic functions of S1P2 receptors were elucidated in a murine asthma model. S1P2 receptors were involved not only in maturation and migration of dendritic cells in the sensitization phase but also in mast cell degranulation in the challenge phase. These results suggest S1P2 receptor as a therapeutic target for allergic asthma.
Prolongation of tumour volume doubling time (midDT) is associated with improvement in disease‐specific survival in patients with rapidly progressive radioactive iodine refractory differentiated thyroid cancer selected for molecular targeted therapy
Authors: Sabra Mona M. , Sherman Eric , Tuttle Robert Michael 
Published: February 2019

SummaryPurposeTo assess molecular targeted therapy (MTT)’s ability to affect tumour volume doubling time (TVDT) and disease‐specific survival (DSS) in patients presenting with lung metastasis from radioactive iodine refractory progressive thyroid cancer.MethodsIn this retrospective study, we examined the clinical characteristics, average tumour volume doubling times of lung metastasis and disease‐specific survival of patients with lung metastasis from differentiated thyroid cancer who were treated with MTT.ResultsThe 5‐year DSS from the distant metastasis (DM) diagnosis was 72% with median survival of 8 years (95% CI: 6.6‐9.5). The median survival was 2.9 years after MTT start (95% CI: 2.1‐3.6). On MTT, lung average tumour volume doubling time (midDT) was prolonged to midDT ≥3 years in 75% of patients with baseline midDT ≤1 year and 100% of patients with midDT 1‐3 years. In patients with rapidly progressive thyroid cancer (midDT ≤1 year at baseline), the median survival was 4.5 years in those with MTT‐achieved midDT ≥3 years (95% CI: 2.9‐6.2), as opposed to 2.3 years (95% CI: 0.3‐4.3) and 0.7 years (95% CI: 0.2‐1.3) in those with MTT‐achieved midDT of 1‐3 years and MTT‐achieved midDT ≤1 year, respectively (log rank P < 0.001).ConclusionLung midDT is a useful and important clinical marker of disease‐specific survival for patients with progressive radioactive iodine refractory (RAIR) metastatic thyroid cancer. In patients with rapidly progressive metastatic RAIR thyroid cancer, molecular targeted therapy prolongs lung tumour volume doubling time and is associated with improved disease‐specific survival.
Targeting RNA: A Transformative Therapeutic Strategy
Authors: Yin Wei , Rogge Mark 
Published: February 2019

The therapeutic pathways that modulate transcription mechanisms currently include gene knockdown and splicing modulation. However, additional mechanisms may come into play as more understanding of molecular biology and disease etiology emerge. Building on advances in chemistry and delivery technology, oligonucleotide therapeutics is emerging as an established, validated class of drugs that can modulate a multitude of genetic targets. These targets include over 10,000 proteins in the human genome that have hitherto been considered undruggable by small molecules and protein therapeutics. The approval of five oligonucleotides within the last 2 years elicited unprecedented excitement in the field. However, there are remaining challenges to overcome and significant room for future innovation to fully realize the potential of oligonucleotide therapeutics. In this review, we focus on the translational strategies encompassing preclinical evaluation and clinical development in the context of approved oligonucleotide therapeutics. Translational approaches with respect to pharmacology, pharmacokinetics, cardiac safety evaluation, and dose selection that are specific to this class of drugs are reviewed with examples. The mechanism of action, chemical evolution, and intracellular delivery of oligonucleotide therapies are only briefly reviewed to provide a general background for this class of drugs.