bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐inflammatory drugs decrease infection of brain endothelial cells withEHV‐1 in vitro
Authors: Goehring L. S. , Brandes K. , Ashton L. V. , Wittenburg L. A. , Olea‐Popelka F. J. , Lunn D. P. , Soboll Hussey G. 
Published: November 2016

SummaryBackgroundEquine herpesvirus‐associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus‐1 (EHV‐1) during cell‐associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection.ObjectivesEvaluating the role of anti‐inflammatory drugs in decreasing endothelial cell infection withEHV‐1.Study designIn vitro assay, crossover design, multiple drug testing.MethodsIn vitro modified infectious centre assay using immortalised carotid artery endothelial cells or primary brain endothelial cells with plaque counts per well as outcome. Cells were either anti‐inflammatory drug treated or left untreated.ResultsSignificant reduction of plaque count when cells were treated compared with untreated cells. No dose‐dependent effect when drug concentrations were increased to 10× dose. Treatment of both peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) is required for significant plaque count reduction.Main limitationsIn vitro study.ConclusionsAnti‐inflammatory drugs decrease infection of endothelial cells likely by reducing contact betweenEHV‐1 infectedPBMCand endothelial cells in vitro. The role of adhesion molecules in this process needs further investigation. In vitro results suggest anti‐inflammatory drug therapy duringEHV‐1 infection and viraemia in horses could be clinically relevant.
Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss
Authors: Misumi Kento , Hayashi Akimasa , Shibahara Junji , Arita Junichi , Sakamoto Yoshihiro , Hasegawa Kiyoshi , Kokudo Norihiro , Fukayama Masashi 
Published: November 2016

AimsBAP1 and PBRM1 expression loss has been observed in multiple cancers, including intrahepatic cholangiocarcinoma (ICC). We investigated BAP1 and PBRM1 expression in ICC using immunohistochemistry, and analysed its association with clinicopathological and genetic features, including two histological subtypes.Methods and resultsWhole‐section slides of 108 consecutive primary ICC cases were immunostained against BAP1 and PBRM1. Complete loss of BAP1 and PBRM1 was observed in 21 (19.4%) and 25 (23.1%) cases, respectively, and partial loss was identified in four (3.7%) and nine (8.4%) cases. In all cases, normal bile ducts were strongly and diffusely positive for both BAP1 and PBRM1. ICC with BAP1 loss showed lower serum CA19‐9 levels, less perineural invasion, rare mucin production, weaker immunoreactivity against S‐100P and stronger immunoreactivity against N‐cadherin and NCAM. IDH mutations were identified more frequently in ICCs with BAP1 loss. All ICC with BAP1 loss corresponded to small‐duct type ICC. Multivariate Cox regression analysis showed that BAP1 loss was an independent prognostic factor for both overall and recurrence‐free survival (P < 0.05). Conversely, PBRM1 loss was found in both small‐duct type and large‐duct type ICC, and was not associated significantly with any specific characteristics, including prognosis.ConclusionBAP1 and PBRM1 loss is seen frequently in ICC. ICC with BAP1 loss shares features of small‐duct type ICC.
NLRP3 inflammasome may regulate inflammatory response of human periodontal ligament fibroblasts in an apoptosis‐associated speck‐like protein containing a CARD (ASC)‐dependent manner
Authors: Lu W. L. , Song D. Z. , Yue J. L. , Wang T. T. , Zhou X. D. , Zhang P. , Zhang L. , Huang D. M. 
Published: November 2016

AbstractAimTo explore the role of NLRP3 (NACHT [nucleotide‐binding oligomerization], LRR [leucine‐rich repeat] and PYD [pyrin domain] domains‐containing protein 3) inflammasome in the inflammatory response of human periodontal ligament fibroblasts (HPDLFs).MethodologyThe expression of NLRP3 and apoptosis‐associated speck‐like protein containing a CARD (ASC) in inflammatory periapical tissues and HPDLFs was examined by immunohistochemical and immunofluorescent staining. HPDLFs were stimulated with muramyl dipeptide (MDP) and lipopolysaccharide (LPS) from E. coli with or without the silencing of ASC. The expression of NLRP3, ASC and caspase‐1 was examined using quantitative real‐time polymerase chain reaction. The secretion of proinflammatory cytokines, including interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) was measured in the cell supernatant with an enzyme‐linked immunosorbent assay. Data were statistically analysed using independent sample t‐tests.ResultsImmunohistochemistry and immunocytochemistry staining revealed that NLRP3 and ASC were expressed in HPDLFs and inflammatory periapical tissues. MDP and LPS promoted the expression of NLRP3, ASC and caspase‐1 in HPDLFs (P < 0.05). The secretion of proinflammatory cytokines was also increased with MDP and LPS stimulation (P < 0.05). After silencing ASC, the secretion of IL‐1β induced by MDP and LPS was significantly attenuated (P < 0.05).ConclusionIn HPDLFs, MDP and LPS activated NLRP3 inflammasome and induced IL‐1β secretion. ASC plays an important role in this inflammatory response.
The Problem of Predation in Zoopolis
Authors: Cormier Andrée‐Anne , Rossi Mauro 
Published: November 2016

AbstractIn this article, we argue that the phenomenon of predation is the source of several problems for Donaldson and Kymlicka's account of our duties towards wild and liminal animals. According to them, humans should adopt a general policy of non‐intervention with respect to predatory behaviour involving wild and liminal animals. They justify this recommendation by appealing to the status of those animals as, respectively, members of sovereign communities and denizens of human‐animal societies. Our goal is not to question their recommendation, but to challenge the reasons given in its support. On the one hand, we argue that, insofar as wild animal communities are incapable of dealing with massive predation, they do not possess the competence required for sovereignty. Moreover, we argue that, even if we leave the issue of competence aside, attributing sovereignty rights to communities including both predators and preys may not be the best way to protect wild animals’ fundamental interests. On the other hand, we argue that there exist two important disanalogies between human denizens and liminal animals, which render Donaldson and Kymlicka's denizenship framework problematic. We suggest that the ultimate justification for a general policy of non‐intervention lies in the significant risk of causing greater harm by acting otherwise, due to our limited knowledge and resources.
The general dynamic model of island biogeography revisited at the level of major flowering plant families
Authors: Lenzner Bernd , Weigelt Patrick , Kreft Holger , Beierkuhnlein Carl , Steinbauer Manuel J. 
Published: November 2016

AbstractAimThe general dynamic model (GDM) proposed by Whittaker et al. () has become a widely accepted theoretical framework in island biogeography. In this study, we explore whether GDM predictions hold when overall plant diversity is deconstructed into major plant families.Location101 islands from 14 oceanic archipelagos world‐wide.MethodsOccurrence data for all species of nine large, cosmopolitan flowering plant families were used to test predictions derived from the GDM. We analysed the effects of island area and age on species richness as well as number and percentage of single‐island endemic species per family using mixed‐effect models.ResultsTotal species and endemic richness as well as the percentage of endemic species showed the predicted hump‐shaped relationship with island age. The overall pattern was mainly driven by few species‐rich plant families. Varying patterns were found for individual families, some of them opposing the general trend. In most cases, native and endemic species richness peaked much earlier in the island life cycle than suggested by the GDM. The contribution of area to the explained variation of all dependent variables was much higher than that of island age.Main conclusionsThe results suggest that biodiversity‐age relationships reported for large taxonomic groups like plants are driven by only a few species‐rich clades. The way these families influence the overall patterns of species richness and endemism is related to family‐specific properties, such as evolutionary history or dispersal strategies. Deviances from the GDM predictions can hence largely be explained by family characteristics and considering taxon‐specific traits may help to further improve the explanatory power of the GDM. Families not following the expectations, like Orchidaceae, may be particularly valuable candidates to unveil so far neglected drivers of island biogeographical patterns.
Protein SUMOylation is Involved in Cell‐cycle Progression and Cell Morphology in Giardia lamblia
Authors: Di Genova Bruno M. , da Silva Richard C. , da Cunha Júlia P.C. , Gargantini Pablo R. , Mortara Renato A. , Tonelli Renata R. 
Published: November 2016

AbstractThe unicellular protozoa Giardia lamblia is a food‐ and waterborne parasite that causes giardiasis. This illness is manifested as acute and self‐limited diarrhea and can evolve to long‐term complications. Successful establishment of infection by Giardia trophozoites requires adhesion to host cells and colonization of the small intestine, where parasites multiply by mitotic division. The tight binding of trophozoites to host cells occurs by means of the ventral adhesive disc, a spiral array of microtubules and associated proteins such as giardins. In this work we show that knock down of the Small Ubiquitin‐like MOdifier (SUMO) results in less adhesive trophzoites, decreased cell proliferation and deep morphological alterations, including at the ventral disc. Consistent with the reduced proliferation, SUMO knocked‐down trophozoites were arrested in G1 and in S phases of the cell cycle. Mass spectrometry analysis of anti‐SUMO immunoprecipitates was performed to identify SUMO substrates possibly involved in these events. Among the identified SUMOylation targets, α‐tubulin was further validated by Western blot and confirmed to be a SUMO target in Giardia trophozoites.
Genetics of adrenocortical tumours
Authors: Åkerström T. , Carling T. , Beuschlein F. , Hellman P. 
Published: November 2016

AbstractThe recently available genomic sequencing techniques have led to breakthroughs in understanding of the underlying genetic mechanisms in adrenocortical tumours. Disease‐causing mutations have been described for aldosterone‐producing adenomas, cortisol‐producing adenomas and adrenocortical carcinomas. Further, knowledge gained from transcriptome analyses and methylation arrays has provided new insights into the development of these tumours. Elucidation of the genomic landscape of adrenocortical tumours and improved techniques may in the future be useful for early diagnosis through the detection of mutated DNA in the circulation. Moreover, compounds that bind specifically to altered proteins may be used as screening targets or therapeutic agents. Regulation of cortisol release by interaction with an altered subunit in adenylate cyclase may be more complex, but may provide a new option for regulating steroid release. Information about derangements in adrenocortical carcinoma is already helpful for determining patient prognosis. With further knowledge, we may be able to identify novel biomarkers that effectively and noninvasively help in differentiating between benign and malignant disease. It is clear that the next few years will provide much novel information that hopefully will aid in the treatment of patients with adrenocortical tumours.
Incidence of new‐onset autoimmune disease in girls and women with pre‐existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study
Authors: Grönlund O. , Herweijer E. , Sundström K. , Arnheim‐Dahlström L. 
Published: November 2016

AbstractObjectiveTo assess whether quadrivalent human papillomavirus (qHPV) vaccination is associated with increased incidence of new‐onset autoimmune disease in girls and women with pre‐existing autoimmune disease.MethodsThis register‐based open cohort study included all girls and women between 10 and 30 years of age in Sweden in 2006–2012 diagnosed with at least one of 49 prespecified autoimmune diseases (n = 70 265). Incidence rate ratios were estimated for new‐onset autoimmune disease within 180 days of qHPV vaccination using Poisson regression adjusting for, country of birth, parental country of birth, parental income and parental education.ResultsA total of 70 265 girls and women had at least one of the 49 predefined autoimmune diseases; 16% of these individuals received at least one dose of qHPV vaccine. In unvaccinated girls and women, 5428 new‐onset autoimmune diseases were observed during 245 807 person‐years at a rate of 22.1 (95% CI 21.5–22.7) new events per 1000 person‐years. In vaccinated girls and women, there were 124 new events during 7848 person‐years at a rate of 15.8 (95% CI 13.2–18.8) per 1000 person‐years. There was no increase in the incidence of new‐onset autoimmune disease associated with qHPV vaccination during the risk period; on the contrary, we found a slightly reduced risk (incidence rate ratio 0.77, 95% CI 0.65–0.93).ConclusionIn this nationwide study, qHPV vaccination was not associated with increased incidence of new‐onset autoimmune disease in girls and women with pre‐existing autoimmune disease.
Melatonin synergizes the chemotherapeutic effect of 5‐fluorouracil in colon cancer by suppressing PI3K/AKT and NF‐κB/iNOS signaling pathways
Authors: Gao Yue , Xiao Xiangsheng , Zhang Changlin , Yu Wendan , Guo Wei , Zhang Zhifeng , Li Zhenglin , Feng Xu , Hao Jiaojiao , Zhang Kefang , Xiao Bingyi , Chen Miao , Huang Wenlin , Xiong Shunbin , Wu Xiaojun , Deng Wuguo 
Published: November 2016

Abstract5‐Fluorouracil (5‐FU) is one of the most commonly used chemotherapeutic agents in colon cancer treatment, but has a narrow therapeutic index limited by its toxicity. Melatonin exerts antitumor activity in various cancers, but it has never been combined with 5‐FU as an anticolon cancer treatment to improve the chemotherapeutic effect of 5‐FU. In this study, we assessed such combinational use in colon cancer and investigated whether melatonin could synergize the antitumor effect of 5‐FU. We found that melatonin significantly enhanced the 5‐FU‐mediated inhibition of cell proliferation, colony formation, cell migration and invasion in colon cancer cells. We also found that melatonin synergized with 5‐FU to promote the activation of the caspase/PARP‐dependent apoptosis pathway and induce cell cycle arrest. Further mechanism study demonstrated that melatonin synergized the antitumor effect of 5‐FU by targeting the PI3K/AKT and NF‐κB/inducible nitric oxide synthase (iNOS) signaling. Melatonin in combination with 5‐FU markedly suppressed the phosphorylation of PI3K, AKT, IKKα, IκBα, and p65 proteins, promoted the translocation of NF‐κB p50/p65 from the nuclei to cytoplasm, abrogated their binding to the iNOS promoter, and thereby enhanced the inhibition of iNOS signaling. In addition, pretreatment with a PI3K‐ or iNOS‐specific inhibitor synergized the antitumor effects of 5‐FU and melatonin. Finally, we verified in a xenograft mouse model that melatonin and 5‐FU exerted synergistic antitumor effect by inhibiting the AKT and iNOS signaling pathways. Collectively, our study demonstrated that melatonin synergized the chemotherapeutic effect of 5‐FU in colon cancer through simultaneous suppression of multiple signaling pathways.
High fodder value and feeding likelihood favour endozoochorous plant dispersal
Authors: Gilhaus Kristin , Freitag Martin , Kunze Svenja , Hölzel Norbert 
Published: November 2016

AbstractQuestionsIn pasture‐dominated landscapes, endozoochory by large herbivores is an important vector of plant dispersal. Conditions influencing the potential for endozoochorous dispersal of plant species by grazers are, however, still poorly known. Here, we assess the impact of feeding habits and functional traits on the likelihood of endozoochorous dispersal by cattle (ruminants) and horses (non‐ruminants).LocationPasture of 27 ha in NW Germany, year‐round grazed by free‐ranging cattle and horses.MethodsVegetation relevés were established in 45 plots, from which dung samples of cattle and horses were collected. The number and composition of seedlings emerging from dung samples were compared with the vegetation of the study site in terms of plant functional trait composition. For the first time, feeding habits were included in the analysis. GLMs were used to identify traits that increased the potential for endozoochorous dispersal.ResultsA total of 65 species germinated from the dung samples. These species had higher average fodder and nutrient indicator values than the species composition of the vegetation. In particular, species found in horse dung were more tolerant of grazing and had more elongated seeds. The likelihood of endozoochorous dispersal was higher for common than for rare species and was influenced by feeding habits.ConclusionsThe likelihood of plant species being dispersed endozoochorously can be linked to different functional traits and is dependent on the type of grazer and the population size of target species in the vegetation. Differences between cattle and horses in seed dispersal may result from species‐specific grazing habits and different digestion modes.
Hereditary haemorrhagic telangiectasia: to transplant or not to transplant – is there a right time for liver transplantation?
Authors: Muller Yannick D. , Oppliger Roland , Breguet Romain , Meyer Philippe , Rubbia‐Brandt Laura , Petignat Pierre‐Auguste , Harr Thomas , Dayer Eric , Seebach Jörg D. 
Published: November 2016

AbstractBackground & AimsHereditary haemorrhagic telangiectasia is characterized by arterio‐venous malformations (AVM). It frequently involves the liver without clinical symptoms, but may lead to biliary ischaemia, portal hypertension, or fatal high‐output heart failure. The indication of liver transplantation is controversial.MethodsHerein, we report the case of a 65‐year‐old female patient with a ‘double Osler syndrome’ consisting of hereditary haemorrhagic telangiectasia (HHT) and type I hereditary angioedema diagnosed at the age of 25 and 22 years respectively.ResultsHereditary angioedema was treated with danazol for several decades until multiple hypoechogenic liver masses were detected. Albeit danazol treatment was replaced by C1 esterase inhibitor infusions, hepatocellular carcinoma was diagnosed at the age of 64 and the patient was listed for liver transplantation. HHT was marked by recurrent epistaxis until the age of 63 when severe intestinal bleeding occurred. At the age of 65, severe dyspnoea (NYHA class IV) developed and rapidly progressive high‐output cardiac failure was diagnosed. Despite argon plasma coagulation to control bleeding from intestinal angiodysplasia, and treatment with bevacizumab to inhibit angiogenesis, the patient died from severe gastrointestinal bleeding associated with cardiogenic shock at the age of 66 before being transplanted.ConclusionThe indication to list this patient for liver transplantation was debated several times before the diagnosis of hepatocellular carcinoma because of good general condition and low MELD score. Precise guidelines for screening and management of patients with hepatic HHT need to be better defined.
Hereditary hemorrhagic telangiectasia: to transplant or not to transplant?
Authors: Dupuis‐Girod Sophie , Buscarini Elisabetta 
Published: November 2016

AbstractThis report comments the case reported by Muller et al. which describes a combination of at least two different indications for orthotopic liver transplant (OLT) in a same patient: hepatocarcinoma and HHT complicated with severe liver involvement and high output cardiac failure. This case report highlighted that the clear time for OLT in HHT can be difficult to determine. In HHT, if intensive medical approach is not efficient, OLT, has to be considered. In the case of Muller et al., the patient was correctly listed for OLT for a single hepatocellular carcinoma, however, he did not receive a sufficient priority so as to avoid worsening of liver vascular malformations complications. Bevacizumab may be a therapeutic option in the treatment of complicated liver VMs in HHT, However, the recurrence of symptoms after withdrawal of the drug make it unsuitable as a replacement for OLT in the cure of complicated liver VMs in HHT. In the case reported by Muller et al. the right “OLT window” after bevacizumab was lost.The right time for OLT in severe complicated liver VMs in HHT does exist but, as this case illustrates, it can be very difficult to determine. As OLT is a radical cure for liver VMs, with excellent outcomes, it should be the therapeutic choice in patients under the age of 65 years. Bevacizumab may be an interesting option, either for patients over the age of 65 years, or those who are poor candidates for surgery; if these latter respond to bevacizumab they should be re‐ evaluated for OLT (with a “fast‐ track”) as the prognosis of severe complicated liver VMs is very poor.
Hereditary haemorrhagic telangiectasia: to transplant or not to transplant?
Authors: Sabbà Carlo 
Published: November 2016

AbstractThe Association of hereditary hemorrhagic telangiectasia (HHT) and type I hereditary angioedema is a very rare condition in medicine. The case reported by Muller et al., describes the coexistence of the two diseases and emphasizes the need for listing HHT patients for liver transplantation in case indications occurs, such as the presence of HCC, abnormally increased cardiac output, and gastrointestinal bleeding as reported for this case. The case described by Mueller et al. is anecdotal for the usefulness of liver transplantation in HHT patients and shows that liver transplantation may be the best supportive care and, sometimes, the unique and final therapeutic option for these patients.