bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal vascular injuries and intravitreal human embryonic stem cell‐derived haemangioblasts
Authors: Wang Jin‐Da , An Ying , Zhang Jing‐Shang , Wan Xiu‐Hua , Zhang Wei , Lanza Robert , Lu Shi‐Jiang , Jonas Jost B. , Xu Liang 
Published: June 2017

AbstractObjectiveTo investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen‐induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion.MethodsHuman embryonic stem cell‐derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate‐buffered saline (PBS). We examined the vasculature integrity in the mice with OIR, the blood–retina barrier in the rats with induced DR, and retinal thickness and retinal ganglion cell density in retina flat mounts of the rats with the retinal ischaemic–reperfusion retinopathy.ResultsIn the OIR model, the study group versus control groups showed a significantly (p < 0.001) smaller retinal avascular area [5.1 ± 2.7%;n = 18 animals versus 12.2 ± 2.8% (PBS group; n = 10 animals) and versus 11.8 ± 3.7% (EC group; n = 8 animals)] and less retinal neovascularization [6.3 ± 2.5%;n = 18 versus 15.2 ± 6.3% (n = 10; PBS group) and versus 15.8 ± 3.3% (n = 8; EC group)]. On retinal flat mounts, hESC‐HBs were integrated into damaged retinal vessels and stained positive for PECAM (CD31) as EC marker. In the DR model, the study group versus the EC control group showed a significantly (p = 0.001) better blood–retina barrier function as measured at 2 days after the intravitreal injections [study group: 20.2 ± 12.8 μl/(g × hr); n = 6; versus EC control group: 52.9 ± 9.9 μl/(g × hr; n = 6)]. In the retinal ischaemia–reperfusion model, the groups did not differ significantly in retinal thickness and retinal ganglion cell density at 2, 5 and 7 days after baseline.ConclusionBy integrating into damaged retinal vessels and differentiating into ECs, intravitreally administered hESC‐HBs may have partially repaired a retinal vascular injury caused by OIR model and DR.
A novel double nucleotide variant in the ferritin‐L iron‐responsive element in a Finnish patient with hereditary hyperferritinaemia‐cataract syndrome
Authors: Mattila Roosa‐Maria , Sainio Annele , Järveläinen Marketta , Pursiheimo Juha , Järveläinen Hannu 
Published: June 2017

AbstractPurposeTo present a novel Finnish double nucleotide variant in the iron‐responsive element (IRE) of the ferritin L‐chain gene (FTL) leading to hyperferritinaemia‐cataract syndrome (HHCS).MethodsGenomic DNA extracted from peripheral blood leucocytes and synthetized with three different primers flanking the IRE in the FTL 5′‐untranslated region of the FTL was used in polymerase chain reaction (PCR). Thereafter, Sanger sequencing was performed on the 487‐bp and 602‐bp PCR amplification products with specific primers to reveal FTL IRE mutations.ResultsA 58‐year‐old female patient with elevated serum ferritin level (1339 μg/l) was diagnosed with HHCS after extensive workup. Genetic testing identified a novel double point mutation g.48965355G>C (chr19, hg19) and g.48965356G>T (chr19, hg19) in the lower stem region of the IRE canonical structure of the FTL.ConclusionAfter excluding other causes, elevated serum ferritin level in a person with early onset cataract is indicative for HHCS, a genetic disorder caused by mutation in the IRE of the FTL.
Recombinant human serum albumin for corneal preservation
Authors: Parekh Mohit , Elbadawy Hossein , Salvalaio Gianni , Amoureux Marie‐Claude , Di Iorio Enzo , Fortier Denis , Ponzin Diego , Ferrari Stefano , Ruzza Alessandro 
Published: June 2017

AbstractPurposeTo study the performance of a completely synthetic organ culture (OC) preservation system containing recombinant human serum albumin (rHSA) for preservation of human donor corneas.MethodsTwenty‐four paired donor corneas were randomly collected, and one cornea from each donor was preserved in synthetic (experimental) and serum‐based media (control). The tissues were assessed at day 0; after 6 days of preservation at room temperature (RT) in Cornea Trans® and Cornea Prep II®; after 28 days at 31°C in Cornea Syn® [with rHSA] and Cornea Max® [with foetal calf serum (FCS)] and; 4‐day post deswelling in Cornea Trans® and Cornea Jet®. Thickness was determined with optical coherence tomography (OCT) and transparency with a validated, custom device. Morphology, endothelial cell density (ECD) and mortality were observed after treating the tissues with Trypan blue and sucrose. Glucose uptake by the cells was analysed. Data were compared using non‐parametric paired Wilcoxon tests with p < 0.05 deemed significant. Histology using periodic acid‐schiff (PAS), expressions of p63, CK12, αSMA and ZO‐1 were analysed, and cell apoptosis postpreservation was studied.ResultsCorneas stored in synthetic media showed a higher and statistically significant value as compared to serum‐based media in terms of viable endothelial cell density (VECD), mortality, morphology and glucose uptake postpreservation. Histology showed presence of all the layers, all the markers were expressed, and no apoptosis was observed in either media.ConclusionThe new synthetic preservation system containing rHSA (and other confidential constituents) showed better preservation effects than traditional media containing serum.
Assessing the conservation value of secondary savanna for large mammals in the Brazilian Cerrado
Authors: Ferreira Guilherme B. , Ahumada Jorge A. , Oliveira Marcelo J. R. , de Pinho Fernando F. , Barata Izabela M. , Carbone Chris , Collen Ben 
Published: June 2017

AbstractDebate about the conservation value of secondary habitats has tended to focus on tropical forests, increasingly recognizing the role of secondary forests for biodiversity conservation. However, there remains a lack of information about the conservation value of secondary savannas. Here, we conducted a camera trap survey to assess the effect of secondary vegetation on large mammals in a Brazilian Cerrado protected area, using a single‐season occupancy framework to investigate the response of individual species (species‐level models) and of all species combined (community‐level models). In addition, we investigated the cost effectiveness of different sampling designs to monitor globally threatened species in the study area. At the community level, savanna that regenerated from eucalyptus plantation had similar occupancy estimate as old growth areas. At the species level, none of the ten species individually assessed seemed to respond to succession stage, with greater support for the effect of other covariates on occupancy, such as distance from water and vegetation physiognomy. These results demonstrate that secondary vegetation does not appear to negatively impact large mammals in the study area and suggest that, given a favorable context, Cerrado mammals can recolonize and use secondary savannas that regenerated from clearcut. However, our study area should be considered a best‐case scenario, as it retained key ecological attributes of high‐value secondary habitats. Our simulations showed that a sampling design with 60 camera trap sites surveyed during nine occasions is appropriate to monitor most globally threatened species in the study area, and could be a useful starting point for new monitoring initiatives in other Cerrado areas.
Protected areas buffer the Brazilian semi‐arid biome from climate change
Authors: Acosta Salvatierra Luis H. , Ladle Richard J. , Barbosa Humberto , Correia Ricardo A. , Malhado Ana C. M. 
Published: June 2017

AbstractThe Caatinga is a botanically unique semi‐arid ecosystem in northeast Brazil whose vegetation is adapted to the periodic droughts that characterize this region. However, recent extreme droughts events caused by anthropogenic climate change have challenged its ecological resilience. Here, we evaluate how deforestation and protection status affect the response of the Caatinga vegetation to drought. Specifically, we compared vegetation responses to drought in natural and deforested areas as well as inside and outside protected areas, using a time‐series of satellite‐derived Normalized Difference Vegetation Index (NDVI) and climatic data for 2008–2013. We observed a strong effect of deforestation and land protection on overall vegetation productivity and in productivity dynamics in response to precipitation. Overall, deforested areas had significantly lower NDVI and delayed greening in response to precipitation. By contrast, strictly protected areas had higher productivity and considerable resilience to low levels of precipitation, when compared to sustainable use or unprotected areas. These results highlight the importance of protected areas in protecting ecosystem processes and native vegetation in the Caatinga against the negative effects of climate change and deforestation. Given the extremely small area of the Caatinga currently under strict protection, the creation of new conservation areas must be a priority to ensure the sustainability of ecological processes and to avoid further desertification.
Discovery of alkyl bis(oxy)dibenzimidamide derivatives as novel protein arginine methyltransferase 1 (PRMT1) inhibitors
Authors: Zhang Wei‐yao , Lu Wen‐chao , Jiang Hao , Lv Zheng‐bing , Xie Yi‐qian , Lian Fu‐lin , Liang Zhong‐jie , Jiang Yu‐xi , Wang Da‐jin , Luo Cheng , Jin Jia , Ye Fei 
Published: June 2017

Protein arginine methylation, a post‐translational modification critical for a variety of biological processes, is catalyzed by protein arginine N‐methyltransferases (PRMTs). In particular, PRMT1 is responsible for over 85% of the arginine methylation in mammalian cells. Dysregulation of PRMT1 is involved in diverse pathological diseases including cancers. However, most current PRMT1 inhibitors are lack of specificity, efficacy, and bioavailability. Herein, a series of alkyl bis(oxy)dibenzimidamide derivatives were identified as selective PRMT1 inhibitors. Among them, the most potent compound corresponds to hexamidine (IC50 = 5.9 ± 1.7 μm), which is an antimicrobial agent. The binding between hexamidine and PRMT1 was further validated by thermal shift assays and nuclear magnetic resonance (NMR) experiments. Molecular docking and NMR assays indicated that hexamidine occupied the substrate binding pocket. Furthermore, hexamidine effectively blocked cell proliferation in cancer cell lines related to PRMT1 overexpression. Taken together, this study has provided a druggable scaffold targeting PRMT1 as well as a new way to repurpose old drugs which is a complementary tool for the discovery of new lead compounds.
Aryl‐ and heteroaryl‐substituted phenylalanines as AMPA receptor ligands
Authors: Szymańska Ewa , Chałupnik Paulina , Johansen Tommy N. , Nielsen Birgitte , Cuñado Moral Ana Maria , Pickering Darryl S. , Więckowska Anna , Kieć‐Kononowicz Katarzyna 
Published: June 2017

A series of racemic unnatural amino acids was rationally designed on the basis of recently published X‐ray structures of the GluA2 LBD with bound phenylalanine‐based antagonists. Twelve new diaryl‐ or aryl/heteroaryl‐substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)‐2‐amino‐3‐(3′‐hydroxy‐5‐(1H‐pyrazol‐4‐yl)‐[1,1′‐biphenyl]‐3‐yl)propanoic acid 7e, showed the binding affinity of 4.6 μm for native AMPA receptors and over fourfold lower affinity for kainic acid receptors. Furthermore, 7e was evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. Recently reported X‐ray structures 5CBR and 5CBS, representing two distinct antagonist binding modes, were used as templates for molecular docking of the synthesized series. Binding data supported with molecular modeling confirmed that aryl/heteroaryl‐substituted phenylalanine analogues effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor ligands.
Long noncoding RNA and its contribution to autism spectrum disorders
Authors: Tang Jie , Yu Yizhen , Yang Wei 
Published: June 2017

SummaryRecent studies have indicated that long noncoding RNAs (lncRNAs) play important roles in multiple processes, such as epigenetic regulation, gene expression regulation, development, nutrition‐related and other diseases, toxic response, and response to drugs. Although the functional roles and mechanisms of several lncRNAs have been discovered, a better understanding of the vast majority of lncRNAs remains elusive. To understand the functional roles and mechanisms of lncRNAs is critical because these transcripts represent the majority of the transcriptional output of the mammalian genome. Recent studies have also suggested that lncRNAs are more abundant in the human brain and are involved in neurodevelopment and neurodevelopmental disorders, including autism spectrum disorders (ASDs). In this study, we review several known functions of lncRNAs and the potential contribution of lncRNAs to ASDs and to other genetic syndromes that have a similar clinical presentation to ASDs, such as fragile X syndrome and Rett syndrome.
Comparison of different insulin pump makes under routine care conditions in adults with Type 1 diabetes
Authors: Leelarathna L. , Roberts S. A. , Hindle A. , Markakis K. , Alam T. , Chapman A. , Morris J. , Urwin A. , Jinadev P. , Rutter M. K. 
Published: June 2017

AbstractAimsTo compare long‐term HbA1c changes associated with different insulin pumps during routine care in a large cohort of adults with Type 1 diabetes representative of other clinic populations.MethodsObservational, retrospective study of 508 individuals starting pump therapy between 1999 and 2014 (mean age, 40 years; 55% women; diabetes duration, 20 years; 94% Type 1 diabetes; median follow‐up, 3.7 years). Mixed linear models compared covariate‐adjusted HbA1c changes associated with different pump makes.ResultsThe pumps compared were: 50% Medtronic, 24% Omnipod, 14% Roche and 12% Animas. Overall HbA1c levels improved and improvements were maintained during a follow‐up extending to 10 years (HbA1c: pre‐continuous subcutaneous insulin infusion (pre‐CSII) vs. 12 months post CSII, 71 (61, 82) vs. 66 (56, 74) mmol/mol; 8.7 (7.7, 9.6) vs. 8.2 (7.3, 8.9)%; P < 0.0001). The percentage of individuals with HbA1c ≥ 64 mmol/mol (8.0%) reduced from a pre‐CSII level of 68% to 55%. After adjusting for baseline confounders, there were no between‐pump differences in HbA1c lowering (P = 0.44), including a comparison of patch pumps with traditional catheter pumps (P = 0.63). There were no significant (P < 0.05) between‐pump differences in HbA1c lowering in pre‐specified subgroups stratified by pre‐pump HbA1c, age or diabetes duration. HbA1c lowering was positively related to baseline HbA1c (P < 0.001) and diabetes duration (P = 0.017), and negatively related to the number of years of CSII use (P = 0.024).ConclusionsUnder routine care conditions, there were no covariate‐adjusted differences in HbA1c lowering when comparing different pump makes, including a comparison of patch pumps vs. traditional catheter pumps. Therefore, the choice of CSII make should not be influenced by the desired degree of HbA1c lowering.
Do different characteristics of two emasculators make a difference in equine castration?
Authors: Comino F. , Giusto G. , Caramello V. , Gandini M. 
Published: June 2017

SummaryBackgroundThe Serra and Reimer emasculators are frequently used in equine orchiectomy. They differ in jaw profile and the mechanism by which they achieve haemostasis.ObjectivesTo investigate whether the haemostatic capacities of the Reimer and Serra emasculators in open and closed castration differ, to compare the haemostatic capacities of each emasculator in both open and closed castration, and to assess whether the tensile strength of the parietal tunic in closed castration differs according to whether a Reimer or Serra emasculator is used.Study designEx vivo randomised study.MethodsEighty equine cadaver testes were randomly assigned to two groups for, respectively, open and closed castration. Each group was divided into two subgroups for castration with a Serra or Reimer castrator, respectively. Testicular artery leaking pressure was measured by dye injection. In closed castration, the tensile strength of the parietal tunic was measured with a tensiometer.ResultsIn open castration, the Reimer emasculator resisted significantly higher pressure (median: 706.1 mmHg; interquartile range [IQR]: 597.6–735.5 mmHg) than the Serra emasculator (median: 349.4 mmHg; IQR: 261.1–468.9 mmHg) (P<0.001), whereas no difference was found in closed castration (Serra emasculator, median: 382.5 mmHg [IQR: 294.2–568.2 mmHg]; Reimer emasculator, median: 419.2 mmHg [IQR: 294.2–616.0 mmHg]). The Reimer emasculator resisted significantly higher pressure in the open (median: 706.1 mmHg; IQR: 597.6–735.5 mmHg) compared with the closed (median: 419.2 mmHg; IQR: 294.2–616.0 mmHg) technique (P = 0.03). Parietal tunic tensile strength did not differ significantly by emasculator (mean ± s.d.: Serra, 12.65 ± 7.35; Reimer, 17.55 ± 11.76).Main limitationsLimitations are inherent to the ex vivo study design. Post‐surgery implications were investigated only in the short term and no account was taken of tissue inflammation and oedema, which may influence the integrity of the tissue.ConclusionsThese results suggest it may be preferable to use a Reimer emasculator in open castration. In this ex vivo model of closed castration, no differences between the emasculators were observed.
Dynamic response and microstructure evolution of the finite steel target subjected to high velocity impact by copper explosively formed projectile
Authors: Liu J.F. , Long Y. , Ji C. , Zhong M.S. 
Published: June 2017

AbstractThe dynamic deformation of the finite steel target subjected to high velocity impact of copper explosively formed projectile is investigated by optical, scanning, and transmission electron microscopy. Morphology analysis of fracture surfaces indicates that the copper remainder plated to the crater wall shows extremely plastic deformation, which consists of elongated parabolic dimples, and the mild carbon steel target exhibits excellent brittle features that material fails mainly along the cleavage facets on the rear surface of target under strong impact of explosively formed projectile. In the surface of crater, the whole part of copper remainder and partial material of steel target undergoes completely dynamic recrystallization. The layer thickness of dynamic recrystallization zone, which displays an extreme plastic flow in solid state, is about 21.3 μm in steel target, and the average size of the refined grains significantly decreases to approximately 200 nm. Theoretically calculated results indicate that the temperature increase is associated with shock wave and plastic deformation of steel target and can reach 1352 K, which is 0.75Tm (where Tm is the melting temperature of steel target). The change in microhardness from the crater wall to the matrix of target is consistent with micro‐deformation of grains, and maximum microhardness is observed on the interface between dynamic recrystallization and severe plastic deformation zones of steel target.
Transient trade‐off between climate benefit and biodiversity loss of harvesting stumps for bioenergy
Authors: Snäll Tord , Johansson Victor , Jönsson Mari , Ortiz Carina , Hammar Torun , Caruso Alexandro , Svensson Måns , Stendahl Johan 
Published: June 2017

AbstractTo replace fossil fuel and thereby mitigate climate change, harvesting of wood such as stumps for bioenergy will likely increase. Coarse deadwood is an important resource for biodiversity and stumps comprise the main part of the coarse deadwood in managed forests. We provide the first integrated analysis of the long‐term climate and biodiversity impacts of a whole landscape. We simultaneously project climate and biodiversity impacts of harvesting stumps to substitute for fossil coal, assuming scenarios with different proportions of the landscape with stump harvest (10, 50, 80%) the coming 50 years. A life cycle approach was used to calculate future global temperature changes and future metapopulation changes in six epixylic lichens. Metapopulation dynamics were projected using colonization and extinction models based on times series data. Harvesting stumps from ≥50% of the clear‐cut forest land benefits climate with a net global temperature reduction >0.5·10−9 K ha−1 after 50 years if assuming substitution of fossil coal. For all scenarios, using stump bioenergy leads to immediate (within 1 year) reductions in temperature of 50% compared to using fossil coal, increasing to 70% reduction after 50 years. However, large‐scale stump harvest inflicted substantial metapopulation declines for five of six lichens. High stump harvest levels (≥50%) put common lichens at risk of becoming red‐listed following the IUCN criteria. The net temperature reduction (cooling effect) from substituting fossil coal with stumps harvested for bioenergy increased over time, while lichen metapopulations stabilized at lower equilibria after two to three decades. This indicates that trade‐offs between climate and metapopulations of commons species are transient, where climate benefits become more prevalent in the long term. As both objectives are important for meeting (inter‐)national climate and biodiversity targets, integrated analyses such as this should be encouraged and urged to guide policymaking about large‐scale implementation of stump harvest.