bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute von Willebrand Factor Secretion from the Endothelium In Vivo: Assessment through Plasma Propeptide (vWf:AgII) Levels
Authors: Vischer Ulrich M , Ingerslev Jørgen , Wollheim Claes B , Mestries Jean-Claude , Tsakiris Dimitrios A , Haefeli Walter E , Kruithof Egbert K O 
Published: July 2018

SummaryElevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 µg/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.
C5a Induces Tissue Factor Activity on Endothelial Cells
Authors: Ikeda Kei , Nagasawa Kohei , Horiuchi Takahiko , Tsuru Tomomi , Nishizaka Hiroaki , Niho Yoshiyuki 
Published: July 2018

SummaryTissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for blood coagulation factor VIIa. The induction of TF on the surface of endothelial cells is initiated by various stimuli including lipopolysaccharide, interleukin-1β, and tumor necrosis factor α. We have demonstrated that recombinant human C5a induces TF activity in a dose-dependent fashion in human umbilical vein endothelial cells (HUVEC). Peak activity (4.9-fold increase) was obtained 3-6 h after treatment with 10 μM C5a. TF mRNA as assessed by RT-PCR method was also significantly increased (3.75-fold) after 3 h incubation with C5a, suggesting that C5a induces TF activity on HUVEC, at least in part, by enhancing the level of TF mRNA. The increase in TF activity by C5a was inhibited by methylprednisolone. The induction of TF on endothelial cells by C5a may represent one of many potential interrelationships between the inflammatory and coagulation schemes.
Developing theories of change for social programmes: co-producing evidence-supported quality improvement
Authors: Ghate Deborah 
Published: July 2018

AbstractFor much of the past two decades, expensive and often imported evidence-based programmes (EBPs) developed by clinician-researchers have been much in vogue in the family and parenting support field, as in many other areas of social provision. With their elaborate infrastructures, voluminous research bases and strict licensing criteria, they have seemed to offer certainty of success over less packaged, less well-evidenced locally developed approaches. Yet recently, evaluation research is showing that success is not assured. EBPs can and regularly do fail, at substantial cost to the public purse. In times of severe resource pressure, a pressing question is, therefore, whether lower cost, home-grown, practitioner-developed programmes—the sort often overlooked by policy-makers —can deliver socially significant and scientifically convincing outcomes at lower cost and at least on a par with their better resourced cousins. This paper shows how the application of techniques increasingly used in implementation science (the science of effective delivery) could help level the playing field. Processes for doing this including co-produced theory of change development and validation are illustrated with reference to the Family Links Ten Week Nurturing Programme (FLNP-10), a popular manualised group-based parenting support programme, designed and disseminated since the 1990s by a UK-based purveyor organisation. The paper draws out general principles for formulating and structuring strong theories of change for practice improvement projects. The work shows that novel application of implementation science-informed techniques can help home-grown programmes to compete scientifically by strengthening their design and delivery, and preparing the ground for better and fairer evaluation.
Bugs, ants, wasps, moths and other insect species.
Authors: Roques A. , Preda C. , Augustin S. , Auger-Rozenberg M. A. 
Published: July 2018

Abstract

A total of 43 insect species non-native to Europe are so far considered to affect human welfare through their biting, urticating and allergenic properties, or by causing domestic nuisances. They involve several orders. In Hymenoptera, species in two families, Formicidae (ants) and Vespidae (wasps and hornets), are known to cause disturbance and health problems. Several moth species (Lepidoptera) have urticating larvae which may induce painful urticarial and allergic reactions. Bugs in five Hemipteran families have direct impacts on health, such as bed bugs and kissing bugs, which are vectors of pathogens, but most are considered to be household pests, causing nuisances to people when invading houses or aggregating on walls. Several non-native species of cockroaches that develop in synanthropic habitats have body parts, saliva or faeces containing powerful indoor allergens, and they can also facilitate mechanical transmission of pathogens to humans. Some species of Siphonaptera (fleas) and Phthiraptera (lice), which are obligate ectoparasitic insects of warm-blooded animals, are of high importance for human health because they cause itches and skin infection, and transmit major diseases such as bubonic plague and murine typhus.
Invasive freshwater invertebrates and fishes: impacts on human health.
Authors: Souty-Grosset C. , Anastácio P. , Reynolds J. , Tricarico E. 
Published: July 2018

Abstract

Inland waters are subject to more widespread biotic invasions than terrestrial ecosystems. During the last century, 756 aquatic species were introduced in Europe, frequently carrying new parasites for native fauna and humans. The consequences of such invasions are the loss of the invaders' original parasites, the introduction of new parasites, or new intermediate hosts or vectors for existing parasites. Many parasites are water-borne and need aquatic species to complete their transmission cycles. The list of 100 of the World's Worst Invasive Alien Species (Lowe et al., 2000) does not take into account human health problems, so a risk assessment of the consequences of invasive freshwater alien species requires more attention. Here we review the direct and indirect impacts of invasive freshwater alien species on human health. Direct impacts include the injuries or allergies and new contaminants (bacteria, toxins), and their role as intermediate hosts to human parasites. Indirect impacts include the effects of the chemicals needed to control these aliens, changes to ecosystem services making the invaded area less suitable for recreational human use and damage to cultivation/aquaculture affecting human well-being in developing countries. A clear management response is urgently needed to halt their spread and reduce or minimize the risk of human and wildlife disease.
Risks for human health related to invasive alien reptiles and amphibians.
Authors: Pauwels O. S. G. , Pantchev N. 
Published: July 2018

Abstract

More than 100 amphibian and reptile species have established populations outside their natural geographical range, mostly as a consequence of the international pet trade. About 40 zoonoses are associated with reptiles and amphibians. The main zoonotic risks from alien invasive reptiles and amphibians are salmonellosis and probably also vibriosis from a bacteriological point of view, pentastomids, sparganosis and potentially trichinellosis from a parasitical point of view, and West Nile virus. There are also new and emerging pathogens, e.g. atypical Brucella spp., with zoonotic potential. Transmission of pathogens from introduced reptile and amphibian species to humans is limited by the important physiological differences between them and humans, the secretive or shy habits of most introduced species and the rarity of direct contact (with the notable exception of a few exotic species eaten by humans). Locally, alien reptiles include venomous species and large species able to inflict bites of medical concern. In certain areas some species (mainly anuran amphibians) are generating noise pollution affecting human well-being. Given the continued increase of invasive alien population establishments with time, the spread of alien arthropod vectors and aggravating factors such as climate change, it is expected that alien reptiles and amphibians and their associated pathogens will generate more public health concern in the future.
A hybridde novogenome assembly of the honeybee,Apis mellifera, with chromosome-length scaffolds
Authors: Wallberg Andreas , Bunikis Ignas , Pettersson Olga Vinnere , Mosbech Mai-Britt , Childers Anna K. , Evans Jay D. , Mikheyev Alexander S. , Robertson Hugh M. , Robinson Gene E. , Webster Matthew T. 
Published: July 2018

AbstractBackgroundThe ability to generate long sequencing reads and access long-range linkage information is revolutionizing the quality and completeness of genome assemblies. Here we use a hybrid approach that combines data from four genome sequencing and mapping technologies to generate a new genome assembly of the honeybeeApis mellifera. We first generated contigs based on PacBio sequencing libraries, which were then merged with linked-read 10x Chromium data followed by scaffolding using a BioNano optical genome map and a Hi-C chromatin interaction map, complemented by a genetic linkage map.ResultsEach of the assembly steps reduced the number of gaps and incorporated a substantial amount of additional sequence into scaffolds. The new assembly (Amel_HAv3) is significantly more contiguous and complete than the previous one (Amel_4.5), based mainly on Sanger sequencing reads. N50 of contigs is 120-fold higher (5.381 Mbp compared to 0.053 Mbp) and we anchor >98% of the sequence to chromosomes. All of the 16 chromosomes are represented as single scaffolds with an average of three sequence gaps per chromosome. The improvements are largely due to the inclusion of repetitive sequence that was unplaced in previous assemblies. In particular, our assembly is highly contiguous across centromeres and telomeres and includes hundreds ofAvaIandAluIrepeats associated with these features.ConclusionsThe improved assembly will be of utility for refining gene models, studying genome function, mapping functional genetic variation, identification of structural variants, and comparative genomics.
Identification of pyroptosis inhibitors that target a reactive cysteine in gasdermin D
Authors: Hu Jun Jacob , Liu Xing , Zhao Jingxia , Xia Shiyu , Ruan Jianbin , Luo Xuemei , Kim Justin , Lieberman Judy , Wu Hao 
Published: July 2018

AbstractInflammasomes are multi-protein signalling scaffolds that assemble in response to invasive pathogens and sterile danger signals to activate inflammatory caspases (1/4/5/11), which trigger inflammatory death (pyroptosis) and processing and release of pro-inflammatory cytokines1,2. Inflammasome activation contributes to many human diseases, including inflammatory bowel disease, gout, type II diabetes, cardiovascular disease, Alzheimer’s disease, and sepsis, the often fatal response to systemic infection3–6. The recent identification of the pore-forming protein gasdermin D (GSDMD) as the final pyroptosis executioner downstream of inflammasome activation presents an attractive drug target for these diseases7–11. Here we show that disulfiram, a drug used to treat alcohol addiction12, and Bay 11-7082, a previously identified NF-κB inhibitor13, potently inhibit GSDMD pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells. Moreover, disulfiram, administered at a clinically well-tolerated dose, inhibits LPS-induced septic death and IL-1β secretion in mice. Both compounds covalently modify a conserved Cys (Cys191 in human and Cys192 in mouse GSDMD) that is critical for pore formation8,14. Inflammatory caspases employ Cys active sites, and many previously identified inhibitors of inflammatory mediators, including those against NLRP3 and NF-κB, covalently modify reactive cysteine residues15. Since NLRP3 and noncanonical inflammasome activation are amplified by cellular oxidative stress16–22, these redox-sensitive reactive cysteine residues may regulate inflammation endogenously, and compounds that covalently modify reactive cysteines may inhibit inflammation by acting at multiple steps. Indeed, both disulfiram and Bay 11-7082 also directly inhibit inflammatory caspases and pleiotropically suppress multiple processes in inflammation triggered by both canonical and noncanonical inflammasomes, including priming, puncta formation and caspase activation. Hence, cysteine-reactive compounds, despite their lack of specificity, may be attractive agents for reducing inflammation.
Osmia bicornis is rarely an adequate regulatory surrogate species. Comparing its acute sensitivity towards multiple insecticides with regulatory Apis mellifera endpoints
Authors: Uhl Philipp , Awanbor Osarobo , Schulz Robert S. , Brühl Carsten A. 
Published: July 2018

AbstractBee species provide essential ecosystem services and maintain floral biodiversity. However, there is an ongoing decline of wild and domesticated bee species. Since agricultural pesticide use is a key driver of this process, there is a need for a protective risk assessment. To achieve a more protective registration process, two wild bee species, Osmia bicornis and Bombus terrestris, were proposed by the European Food Safety Authority as additional test surrogates. We investigated the acute toxicity (median lethal dose, LD50) of multiple commercial insecticide formulations towards the red mason bee (O. bicornis) and compared these values to honey bee (Apis mellifera) regulatory endpoints. In two thirds of all cases O. bicornis was less sensitive than the honey bee. By applying an assessment factor of 10 on the honey bee endpoint a protective level was achieved for 87% (13 out 15) of all evaluated products. Our results show that O. bicornis as a non-sensitive species is rarely an adequate additional surrogate species for lower tier risk assessment. Given the currently limited database, the honey bee seems sufficiently protective in acute scenarios as long as a reasonable assessment factor is applied. However, additional surrogate species such as O. bicornis and B. terrestris are still relevant for ecologically meaningful higher tier studies.
MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity
Authors: Gao Yanxia , Li Jiaheng , Zhang Zhen , Zhang Ruihan , Pollock Andrew , Sun Tao 
Published: July 2018

AbstractProopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) in mammalian hypothalamus play important roles in regulating appetite, energy expenditure, and glucose and fat metabolisms. Diet-induced obesity often show sex-specific difference. But the underlying mechanisms remain unclear. Here we show that microRNA (miRNA) miR-7 and miR-17-92 are expressed in the mouse ARC, and mostly in POMC neurons. Knockdown of miR-7 and knockout of miR-17-92 specifically in POMC neurons aggravate diet-induced obesity only in females and males, respectively. Moreover, gene expression profile analysis identifies sex-differential genes in male and female ARCs in wildtype adult mice. Interestingly, these genes that normally show low-expression in the female and male ARCs display upregulated expression in female miR-7 knockdown and male miR-17-92 knockout mice, respectively. Our results demonstrate an important role of miRNAs in regulating sex-specific diet-induced obesity, likely through modulating expression of target genes that show sex-differential expression in the ARC of hypothalamus.
Structured environments fundamentally alter dynamics and stability of ecological communities
Authors: Vallespir Nick , Ursell Lowery & Tristan 
Published: July 2018

ABSTRACTThe dynamics and stability of ecological communities are intimately linked with the specific interactions – like cooperation or predation – between constituent species. In microbial communities, like those found in soils or the mammalian gut, physical anisotropies produced by fluid flow and chemical gradients impact community structure and ecological dynamics, even in structurally isotropic environments. Though natural communities existing in physically unstructured environments is rare, the role of environmental structure in determining community dynamics and stability remains poorly studied. To address this gap, we used modified Lotka-Volterra simulations of competitive microbial communities to characterize the effects of surface structure on community dynamics. We find that environmental structure has profound effects on communities, in a manner dependent on the specific pattern of interactions between community members. For two mutually competing species, eventual extinction of one competitor is effectively guaranteed in isotropic environments. However, addition of environmental structure enables long-term coexistence of both species via local ‘pinning’ of competition interfaces, even when one species has a significant competitive advantage. In contrast, while three species competing in an intransitive loop (as in a game of rock-paper-scissors) coexist stably in isotropic environments, structural anisotropy disrupts the spatial patterns on which coexistence depends, causing chaotic population fluctuations and subsequent extinction cascades. These results indicate that the stability of microbial communities strongly depends on the structural environment in which they reside. Therefore, a more complete ecological understanding, including effective manipulation and interventions in natural communities of interest, must account for the physical structure of the environment.SIGNIFICANCEMany microbial communities of ecological and medical importance reside in complex and heterogeneous environments, such as soils or intestinal tracts. While many studies consider the effects of flow or chemical gradients in structuring these communities, how the physical structure of the environment shapes community dynamics and outcomes remains poorly understood. Using simulations of competitive microbial communities, we show that stability and dynamics qualitatively shift in environments with complex surface structures compared to open isotropic environments. Therefore, in addition to biochemical interactions between species, our work suggests that the physical structure of the environment is an equally important determinant of dynamics and stability in microbial communities, in a manner dependent on the specific patterns of interactions within that community.
Inversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems
Authors: Tveito Aslak , Jæger Karoline Horgmo , Huebsch Nathaniel , Charrez Berenice , Edwards Andrew G. , Wall Samuel , Healy Kevin E. 
Published: July 2018

AbstractWhile cardiomyocytes differentiated from human induced pluripotent stems cells (hiPSCs) hold great promise for drug screening, the electrophys-iological properties of these cells can be variable and immature, producing results that are significantly different from their human adult counterparts. Here, we describe a computational framework to address this limitation, and show how in silico methods, applied to measurements on immature cardiomyocytes, can be used to both identify drug action and to predict its effect in mature cells. Our synthetic and experimental results indicate that optically obtained waveforms of voltage and calcium from microphysiological systems can be inverted into information on drug ion channel blockage, and then, through assuming functional invariance of proteins during maturation, this data can be used to predict drug induced changes in mature ventricular cells. Together, this pipeline of measurements and computational analysis could significantly improve the ability of hiPSC derived cardiomycocytes to predict dangerous drug side effects.
Can we obtain in vivo transmural mean hoop stress of the aortic wall without knowing patient-specific material properties and residual deformations?
Authors: Liu Minliang , Liang Liang , Liu Haofei , Zhang Ming , Martin Caitlin , Sun Wei 
Published: July 2018

AbstractIt is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g. the pressure-diameter curves. In an effort to enable personalized analysis of the aortic wall stress, approaches have been developed to incorporate experimentally-derived residual deformations into in vivo loaded geometries in finite element simulations using thick-walled models. Solid elements are typically used to account for “bending-like” residual deformations. Yet, the difficulty in obtaining patient-specific residual deformations and material properties has become one of the biggest challenges of these thick-walled models. In thin-walled models, fortunately, static determinacy offers an appealing prospect that allows for the calculation of the thin-walled membrane stress without patient-specific material properties. The membrane stress can be computed using forward analysis by enforcing an extremely stiff material property as penalty treatment, which is referred to as the forward penalty approach. However, thin-walled membrane elements, which have zero bending stiffness, are incompatible with the residual deformations, and therefore, it is often stated as a limitation of thin-walled models. In this paper, by comparing the predicted stresses from thin-walled models and thick-walled models, we demonstrate that the transmural mean hoop stress is the same for the two models and can be readily obtained from in vivo clinical images without knowing the patient-specific material properties and residual deformations. Computation of patient-specific mean hoop stress can be greatly simplified by using membrane model and the forward penalty approach, which may be clinically valuable.