bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelets fuel the inflammasome activation of innate immune cells
Authors: Rolfes Verena , Ribeiro Lucas S. , Hawwari Ibrahim , Böttcher Lisa , Rosero Nathalia , Maasewerd Salie , Santos Marina Lima S. , Schmidt Susanne V. , Rothe Maximilian , Stunden H. James , Carvalho Luzia H. , Fontes Cor J. , Arditi Moshe , Latz Eicke , Franklin Bernardo S. 
Published: October 2019

ABSTRACTThe inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogenous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets, the second most abundant cells in the blood, boost the inflammasome capacity of human macrophages and neutrophils, and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC nucleation, caspase-1 activity, and IL-1β maturation. Platelet depletion attenuated LPS-induced IL-1β in vivo, and platelet counts correlate with plasma concentrations of IL-1β in malaria patients. Furthermore, a platelet gene signature was enriched among the highest expressed transcripts in IL-1β-driven autoinflammatory diseases. The platelet-mediated enhancement of inflammasome activation was independent of cell-to-cell contacts, platelet-derived lipid mediators, purines, nucleic acids and a host of platelet cytokines, and involved the triggering of calcium sensing receptors on macrophages by a calcium-dependent protein commonly released by platelets and megakaryocytes. Finally, we report that platelets provide an additional layer of regulation of inflammasomes in vivo.
AMP-activated protein kinase is a key regulator of acute neurovascular permeability
Authors: Dragoni Silvia , Caridi Bruna , Karatsai Eleni , Burgoyne Thomas , Sarker Mosharraf H. , Turowski Patric 
Published: October 2019

ABSTRACTMany neuronal and retinal disorders are associated with pathological hyperpermeability of the microvasculature. We have used explants of rodent retinae to measure and manipulate acute neurovascular permeability and signal transduction to study the role of AMP-activated protein kinase (AMPK). Following stimulation with either vascular endothelial growth factor (VEGF-A) or bradykinin (BK), AMPK was rapidly and strongly phosphorylated and acted as a key mediator of permeability downstream of Ca2+ and Ca2+/calmodulin-dependent protein kinase kinase (CAMKK). Accordingly, AMPK agonists potently induced acute retinal vascular leakage. AMPK activation led to phosphorylation of endothelial nitric oxide synthase (eNOS), which in turn increased VE-cadherin phosphorylation on Y685. In parallel, AMPK also mediated phosphorylation of p38 MAP kinase and HSP27, indicating that it regulated paracellular junctions and cellular contractility, both previously associated with endothelial permeability. Endothelial AMPK provided a missing link in neurovascular permeability, connecting Ca2+ transients to the activation of eNOS and p38, irrespective of the permeability-inducing factor used. Collectively, the ex-vivo retina model was easily accessible and, due to its compatibility with small molecule antagonists/agonists and siRNA, constitutes a reliable tool to study regulators and mechanism of neurovascular permeability.
SOFIevaluator: a strategy for the quantitative quality assessment of SOFI data
Authors: Moeyaert Benjamien , Vandenberg Wim , Dedecker Peter 
Published: October 2019

AbstractSuper-resolution fluorescence imaging techniques allow optical imaging of specimens beyond the diffraction limit of light. Super-resolution optical fluctuation imaging (SOFI) relies on computational analysis of stochastic blinking events to obtain a super-resolved image. As with some other super-resolution methods, this strong dependency on computational analysis can make it difficult to gauge how well the resulting images reflect the underlying sample structure. We herein report SOFIevaluator, an unbiased and parameter-free algorithm for calculating a set of metrics that describes the quality of super-resolution fluorescence imaging data for SOFI. We additionally demonstrate how SOFIevaluator can be used to identify fluorescent proteins that perform well for SOFI imaging under different imaging conditions.
Computational and experimental evidence to the permeability of withanolides across the normal cell membrane
Authors: Wadhwa R. , Yadav N. S. , Katiyar S. P , Yaguchi T. , Lee C. , Ahn H. , Yun C-O. , Kaul S. C , Sundar D. 
Published: October 2019

AbstractPoor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in the clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs - withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that withaferin-A, but not withanone, could proficiently transverse through the model membrane. The free energy profiles obtained were in accordance with the physico-chemical properties of the investigated drug molecules. It was observed that the polar head group of the bilayer exhibits high resistance for the passage of withanone as compared to withaferin-A, while the interior of the membrane behaves similarly for both withanolides. The solvation analysis revealed that the high solvation of terminal O5 oxygen of withaferin-A was the major driving force. The impact of the favorable interaction of terminal oxygen (O5) of withaferin-A with the phosphate of the membrane led to its smooth passage across the bilayer. The computational predictions were validated by raising and recruiting unique antibodies that react to withaferin-A and withanone. Further, the time-lapsed analyses of control and treated human normal and cancer cells, demonstrated proficient permeation of withaferin-A, but not withanone, through normal cells. These data strongly validated our computational method for predicting permeability and hence bioavailability of candidate compounds in the drug development process.Statement of significanceWhat determines the bioavailability of a drug? Does the ability to cross cell membrane determine this? A combined simulation/experimental study of the permeability of two natural drugs - withanolides (Wi-A and Wi-N) across the cell membrane was conducted. In the computational portion of the study, steered MD simulations were performed to investigate the propensity of the two molecules to permeate across the cell. It is found that Wi-A proceeds relatively simply across the cell compared to Wi-N. This trend was found to be consistent with experiment. This work is an important step towards understanding the molecular basis of permeability of natural drug molecules.
Imidazole-imidazole hydrogen bonding in the pH sensing Histidine sidechains of Influenza A M2
Authors: Movellan Kumar Tekwani , Wegstroth Melanie , Overkamp Kerstin , Leonov Andrei , Becker Stefan , Andreas Loren B. 
Published: October 2019

ABSTRACTThe arrangement of histidine sidechains in influenza A M2 tetramer determines their pKa values, which define pH controlled proton conduction critical to the virus lifecycle. Both water associated and hydrogen bonded Imidazole–Imidazolium histidine quaternary structures have been proposed, based on crystal structures, and NMR chemical shifts, respectively. Here we show, using the conduction domain construct of M2 in lipid bilayers, that the imidazole rings are hydrogen bonded even at a pH of 7.8 in the neutral charge state.An intermolecular 8.9 ± 0.3 Hz 2hJNN hydrogen bond is observed between H37 Nε and Nδ recorded in a fully protonated sample with 100 kHz magic-angle spinning. This interaction could not be detected in the drug-bound sample.
Interacting effects of landscape and management on plant–solitary bee networks in olive orchards
Authors: Martínez‐Núñez Carlos , Manzaneda Antonio J. , Lendínez Sandra , Pérez Antonio J. , Ruiz‐Valenzuela Luis , Rey Pedro J. 
Published: October 2019

AbstractUnderstanding how multi‐scale environmental heterogeneity shapes the structure and functions of animal and plant communities is pivotal in agroecology. Our capacity to ensure the provision of ecosystem services (ES), the sustainability of agroecosystems and the efficiency of agri‐environmental schemes (AES) relies on this knowledge.There is growing interest in how biodiversity and ES are affected by the interplay between landscape characteristics and agricultural management (e.g., intermediate landscape complexity hypothesis; ILCH). However, studies have typically focused on classical measures of community structure (e.g., species abundance, richness and biodiversity), tending to neglect the effects on the structure and stability of ecological networks and the increased risk of biotic homogenization (i.e., loss of β‐diversity).In this work, we use bee trap nests to sample pollen–solitary bee mutualistic networks in 9 pairs of olive groves under different management regimes (conventional vs. organic) in a landscape complexity gradient in southern Spain. We analyse the mutualistic networks at farm level to test the ILCH and study how agricultural practices and landscape complexity interact to affect the properties of these networks. We also explore the effects on spatial biotic homogenization by performing multivariate analyses of the composition and abundance of bee–plant communities and their pairwise interactions.The results show that solitary bee–plant networks have greater complexity and stability on organic olive farms embedded in relatively heterogeneous landscapes. Differences from conventional management were higher in landscapes of intermediate complexity but were non‐significant on olive farms located in simpler landscapes. β‐diversity of bees, plants and their pairwise interactions was also greater on organic olive farms.In conclusion, human‐induced environmental heterogeneity interacts at different scales to shape plant–solitary bee networks in olive groves, which may have important implications for ES provision and the effectiveness of agri‐environmental measures.A freePlain Language Summarycan be found within the Supporting Information of this article.
Seagrass ecosystem metabolic carbon capture in response to green turtle grazing across Caribbean meadows
Authors: Johnson Robert A. , Gulick Alexandra G. , Constant Nerine , Bolten Alan B. , Smulders Fee O. H. , Christianen Marjolijn J. A. , Nava Mabel I. , Kolasa Keith , Bjorndal Karen A. 
Published: October 2019

Abstract

Increasing green turtle abundance will lead to increased grazing within seagrass habitats—ecosystems that are important for carbon sequestration and storage. However, it is not well understood how carbon dynamics in these ecosystems respond to grazing and whether a response differs among meadows or locations.

We measured seagrass ecosystem metabolism in grazed and ungrazed areas of Thalassia testudinum meadows with established green turtle foraging areas across the Greater Caribbean and Gulf of Mexico. We sampled meadows from five locations that differed in seagrass and environmental characteristics. Established meadows of the invasive seagrass Halophila stipulacea were also present at two of these locations, and we measured ecosystem metabolism in these meadows for comparison to grazed and ungrazed areas of the native T. testudinum.

Across all individual sites, rates of net ecosystem production (NEP) ranged from 56% to 96% lower in grazed areas than ungrazed areas of T. testudinum meadows. Rates of NEP were also strongly, positively correlated with above‐ground seagrass biomass across sites. While metabolic carbon capture rates were lower in grazed areas, heterotrophic respiration was not stimulated, and grazing therefore did not result in significant metabolic remineralization of carbon in these meadows. NEP in H. stipulacea meadows was similar to rates in T. testudinum meadows at all three sites, suggesting that metabolic carbon capture may remain similar in Caribbean meadows where this invasive seagrass is replacing native species.

Synthesis. Our results show that there is a consistent response in metabolic carbon dynamics to green turtle grazing in T. testudinum meadows across the Greater Caribbean region. An increase in grazing will not likely stimulate remineralization of carbon as these important habitats are returned to a natural grazed state.
Annual and cropping season environmental production conditions effects on smallholder technical efficiency in sub‐Saharan Africa: Evidence from Ethiopia
Authors: Baffoe‐Bonnie Anthony , Kostandini Genti 
Published: October 2019

AbstractThis article investigates the impact of environmental production conditions on smallholder farmers’ technical efficiency in Ethiopia for wheat, maize, and sorghum farming. We use a household panel data set with annual and cropping season environmental production conditions to estimate the technical efficiency scores. The results show that including environmental production conditions in the stochastic frontier has a significant impact on farmers’ technical efficiency scores. Technical efficiency scores improve when environmental production conditions are incorporated in the stochastic frontier. Thus, accounting for environmental production conditions reduces the inefficiencies that otherwise may be attributed to the characteristics of smallholder farmers.
The whole and its parts: why and how to disentangle plant communities and synusiae in vegetation classification
Authors: Berg Christian , Ewald Jörg , Hobohm Carsten , Dengler Jürgen 
Published: October 2019

AbstractMost plant communities consist of different structural and ecological subsets, ranging from cryptogams to different tree layers. The completeness and approach with which these subsets are sampled have implications for vegetation classification. Non‐vascular plants are often omitted or sometimes treated separately, referring to their assemblages as “synusiae” (e.g. epiphytes on bark, saxicolous species on rocks). The distinction of complete plant communities (phytocoenoses or holocoenoses) from their parts (synusiae or merocoenoses) is crucial to avoid logical problems and inconsistencies in the resulting classification systems. We here describe theoretical differences between the phytocoenosis as a whole and its parts, and outline consequences of this distinction for practice and terminology in vegetation classification. To implement a clearer separation, we call for modifications of the International Code of Phytosociological Nomenclature and the EuroVegChecklist. We believe that these steps will make vegetation classification systems better applicable and raise recognition of the importance of non‐vascular plants in the vegetation as well as their interplay with vascular plants.
Do lianas shape ant communities in an early successional tropical forest?
Authors: Adams Benjamin J. , Gora Evan M. , van Breugel Michiel , Estrada‐Villegas Sergio , Schnitzer Stefan A. , Hall Jefferson S. , Yanoviak Stephen P. 
Published: October 2019

AbstractAlmost half of lowland tropical forests are at various stages of regeneration following deforestation or fragmentation. Changes in tree communities along successional gradients have predictable bottom‐up effects on consumers. Liana (woody vine) assemblages also change with succession, but their effects on animal succession remain unexplored. Here we used a large‐scale liana removal experiment across a forest successional chronosequence (7–31 years) to determine the importance of lianas to ant community structure. We conducted 1,088 surveys of ants foraging on and living in trees using tree trunk baiting and hand‐collecting techniques at 34 paired forest plots, half of which had all lianas removed. Ant species composition, β‐diversity, and species richness were not affected by liana removal; however, ant species co‐occurrence (the coexistence of two or more species in a single tree) was more frequent in control plots, where lianas were present, versus removal plots. Forest stand age had a larger effect on ant community structure than the presence of lianas. Mean ant species richness in a forest plot increased by ca. 10% with increasing forest age across the 31‐year chronosequence. Ant surveys from forest >20 years old included more canopy specialists and fewer ground‐nesting ant species versus those from forests <20 years old. Consequently, lianas had a minimal effect on arboreal ant communities in this early successional forest, where rapidly changing tree community structure was more important to ant species richness and composition.
6‐mm‐short and 11‐mm‐long implants compared in the full‐arch rehabilitation of the edentulous mandible: A 3‐year multicenter randomized controlled trial
Authors: Guida Luigi , Annunziata Marco , Esposito Umberto , Sirignano Massimiliano , Torrisi Paolo , Cecchinato Denis 
Published: October 2019

AbstractObjectiveThe aim of this multicenter parallel‐group randomized controlled trial is to compare 6‐mm‐short with 11‐mm‐long implants in the rehabilitation of totally edentulous mandible in a completely comparable clinical situation, from anatomical, surgical, and prosthetic point of view.Material and methodsThirty patients were selected in three study centers to receive a fixed full‐arch mandibular rehabilitation supported by five inter‐foraminal implants. Patients were randomly allocated, at the time of surgery, half to the test group (6‐mm‐long implants) and half to the control group (11‐mm‐long implants). No bone augmentation procedure was performed. After 3 months, a screw‐retained full‐arch prosthesis with distal cantilevers was positioned (baseline). Peri‐implant marginal bone level change (MBLc), implant and prosthesis survival rate, and biological/technical complications were evaluated after 1 and 3 years.ResultsThirty subjects (150 implants) were evaluated after 1 year and 28 (140 implants) after 3 years. No implant or prosthesis loss occurred. No significant inter‐group difference for biological/technical complications was registered. No statistically significant (p > .025) intra‐group or inter‐group difference in the mean MBLc values was registered. The mean MBLc was 0.01 ± 0.19 mm and −0.04 ± 0.21 mm at 1 year, and −0.10 ± 0.24 mm and 0.02 ± 0.25 mm at 3 years (test and control groups, respectively).Conclusions6‐mm‐short implants may be a reliable option when used in the rehabilitation of total edentulous mandibles. These results need to be confirmed by longer follow‐up data from well‐designed randomized controlled clinical trials.
Vascular ultrasound for monitoring of inflammatory activity in Takayasu arteritis
Authors: Svensson Christina , Eriksson Per , Zachrisson Helene 
Published: October 2019

SummaryBackgroundTakayasu arteritis (TA) is a rare large‐vessel arteritis that primarily affects the aorta and its major branches. The aim of this study was to describe the value of high frequency ultrasound for monitoring of inflammatory activity.MethodsTwenty‐five patients, range 11–71 years, diagnosed with TA were investigated with duplex ultrasound (DUS) including follow‐up studies. Twenty‐five healthy controls were also investigated. Nine patients had newly diagnosed active TA. Sixteen patients had stable/inactive disease at baseline DUS, and TA was diagnosed median 4·5 years previously. Intima–media thickness (IMT), vessel and lumen diameter were measured in the carotid arteries, central neck arteries and the aortic arch. The vessel walls were studied qualitatively. The Takayasu ultrasound index was created for inflammatory activity scoring.ResultsIntima–media thickness in common carotid artery (CCA) was (median and 25–75 percentile parenthetic) 2·3 mm (1·7–2·9) in clinically active TA, 1·2 mm (1·1–1·6) in clinically stable TA (P<0·001) and 0·5 mm (0·5–0·6) in healthy controls (P<0·001). Clinically active TA had prominent increase in IMT and/or increased vessel diameter, and/or intramural arteries, and/or hypoechogenic areas interpreted as oedema in the vessel wall. TA in clinical remission was characterized by increased IMT with medium to high echogenicity with or without fibrotic stripes. The Takayasu ultrasound index was higher in patients with active disease versus treated disease, 2·55 (1·60–3·05) versus 1·30 (1·00–1·58), (P = 0·003).ConclusionDUS is an excellent tool to monitor inflammatory changes in the vessel wall in TA. Further DUS studies in larger patient populations are warranted.
Neck as mediastinal extension: Diagnosis of sarcoidosis by core biopsy of cervical lymph nodes
Authors: Fahim Ahmed , Qasim Muhammad Mahzooz , Rosewarne David 
Published: October 2019

AbstractBackgroundSarcoidosis is a multi‐system granulomatous disease. The diagnostic procedures for histological confirmation are invasive and a less invasive approach to diagnostic pathway is warranted. The utility of diagnostic value of neck ultrasound was retrospectively evaluated. A histological diagnosis was made by ultrasound‐guided head and neck core biopsy to confirm clinically and radiologically suspected sarcoidosis.MethodsTwenty‐five patients were referred for sonographic evaluation of the head and neck after CT scan in an attempt to avoid the use of more invasive tests. These patients had mediastinal adenopathy, but not clinically apparent neck nodes. Where no cervical lymph node suitable for biopsy was seen, parotid glands were biopsied if deemed abnormal.ResultsA diagnosis of sarcoidosis was made in all cases where a core biopsy of cervical lymph nodes was attempted. The cervical lymph nodes in this cohort were not particularly enlarged, short‐axis dimensions being less than 10mm in majority, and they did not have any sonographic appearances to mark them as pathological. Nevertheless histological examination revealed non‐caseating granulomas in all cases. In further two cases, where no neck nodes were seen, a histological diagnosis of sarcoidosis was made from biopsy of diffusely abnormal parotid glands.ConclusionsGiven the clear advantages of cervical diagnosis in terms of invasiveness and economy compared to mediastinal alternatives, it is suggested that where the expertise for core biopsy of normal‐sized cervical lymph nodes is readily available, the technique may be considered as a first‐line investigation for the diagnosis of sarcoidosis.
Light aerobic exercise modulates executive function and cortical excitability
Authors: Morris Timothy P. , Fried Peter J. , Macone Joanna , Stillman Alexandra , Gomes‐Osman Joyce , Costa‐Miserachs David , Tormos Muñoz Jose Maria , Santarnecchi Emiliano , Pascual‐Leone Alvaro 
Published: October 2019

AbstractSingle bouts of aerobic exercise can modulate cortical excitability and executive cognitive function, but less is known about the effect of light‐intensity exercise, an intensity of exercise more achievable for certain clinical populations. Fourteen healthy adults (aged 22 to 30) completed the following study procedures twice (≥7 days apart) before and after 30 min of either light aerobic exercise (cycling) or seated rest: neurocognitive battery (multitasking performance, inhibitory control and spatial working memory), paired‐pulse TMS measures of cortical excitability. Significant improvements in response times during multitasking performance and increases in intracortical facilitation (ICF) were seen following light aerobic exercise. Light aerobic exercise can modulate cortical excitability and some executive function tasks. Populations with deficits in multitasking ability may benefit from this intervention.