bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergence of pathway analysis and pattern recognition predicts sensitization to latest generation TRAIL therapeutics by IAP antagonism
Authors: Vetma Vesna , Guttà Cristiano , Peters Nathalie , Praetorius Christian , Hutt Meike , Seifert Oliver , Meier Friedegund , Kontermann Roland , Kulms Dagmar , Rehm Markus 
Published: February 2020

AbstractSecond generation TRAIL-based therapeutics, combined with sensitising co-treatments, have recently entered clinical trials. However, reliable response predictors for optimal patient selection are not yet available. Here, we demonstrate that a novel and translationally relevant hexavalent TRAIL receptor agonist, IZI1551, in combination with Birinapant, a clinically tested IAP antagonist, efficiently induces cell death in various melanoma models, and that responsiveness can be predicted by combining pathway analysis, data-driven modelling and pattern recognition. Across a panel of 16 melanoma cell lines, responsiveness to IZI1551/Birinapant was heterogeneous, with complete resistance and pronounced synergies observed. Expression patterns of TRAIL pathway regulators allowed us to develop a combinatorial marker that predicts potent cell killing with high accuracy. IZI1551/Birinapant responsiveness could be predicted not only for cell lines, but also for 3D tumour cell spheroids and for cells directly isolated from patient melanoma metastases (80–100% prediction accuracies). Mathematical parameter reduction identified 11 proteins crucial to ensure prediction accuracy, with x-linked inhibitor of apoptosis protein (XIAP) and procaspase-3 scoring highest, and Bcl-2 family members strongly represented. Applied to expression data of a cohort ofn = 365 metastatic melanoma patients in a proof of concept in silico trial, the predictor suggested that IZI1551/Birinapant responsiveness could be expected for up to 30% of patient tumours. Overall, response frequencies in melanoma models were very encouraging, and the capability to predict melanoma sensitivity to combinations of latest generation TRAIL-based therapeutics and IAP antagonists can address the need for patient selection strategies in clinical trials based on these novel drugs.
Preferential gene retention increases the robustness of cold regulation in Brassicaceae and other plants after polyploidization
Authors: Song Xiao-Ming , Wang Jin-Peng , Sun Peng-Chuan , Ma Xiao , Yang Qi-Hang , Hu Jing-Jing , Sun Sang-Rong , Li Yu-Xian , Yu Ji-Gao , Feng Shu-Yan , Pei Qiao-Ying , Yu Tong , Yang Nan-Shan , Liu Yin-Zhe , Li Xiu-Qing , Paterson Andrew H. , Wang Xi-Yin 
Published: February 2020

AbstractCold stress profoundly affects plant growth and development and is a key factor affecting the geographic distribution and evolution of plants. Plants have evolved adaptive mechanisms to cope with cold stress. Here, through the genomic analysis of Arabidopsis, threeBrassicaspecies and 17 other representative species, we found that both cold-related genes (CRGs) and their collinearity were preferentially retained after polyploidization followed by genome instability, while genome-wide gene sets exhibited a variety of other expansion mechanisms. The cold-related regulatory network was increased inBrassicaceaegenomes, which were recursively affected by polyploidization. By combining our findings regarding the selective retention ofCRGsfrom this ecological genomics study with the available knowledge of cold-induced chromosome doubling, we hypothesize that cold stress may have contributed to the success of polyploid plants through both increasing polyploidization and selectively maintainingCRGsduring evolution. This hypothesis requires further biological and ecological exploration to obtain solid supporting evidence, which will potentially contribute to understanding the generation of polyploids and to the field of ecological genomics.
MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response
Authors: Qiu Huan , Jin Bang-Ming , Wang Zhan-Feng , Xu Bin , Zheng Qi-Fan , Zhang Li , Zhu Ling-Yu , Shi Shuang , Yuan Jun-Bo , Lin Xiao , Gao Shu-Bin , Jin Guang-Hui 
Published: February 2020

AbstractThe MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1−/− driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.
Comparative structural investigations of nuclear waste glass alteration layers and sol-gel synthesized aerogels
Authors: Reiser Joelle T. , Ryan Joseph V. , Weber Marc H. , Ilavsky Jan , Olszta Matthew J. , Schreiber Daniel K. , Wall Nathalie A. 
Published: February 2020

AbstractWhile various glass alteration layer formation mechanisms have been debated in recent years, the glass alteration community generally agrees that more information on physical properties of the alteration layers is needed to further the understanding of their impacts on overall glass alteration. In this work, pore volumes and solid structures of glass (International Simple Glass, ISG) alteration layers formed in solutions of various pH conditions in initially dilute conditions at 90 °C are evaluated with positron annihilation spectroscopy, small-angle X-ray scattering, and scanning transmission electron microscopy. Pore volumes of alteration layers formed at pH 9 were found to be at their lowest near the surfaces of the alteration layers. Solid structures of alteration layers are compared with those of synthetic aerogels of comparable compositions produced under various pH conditions. Alteration layers formed at pH 11 on ISG were shown to contain large structures (>10 nm) similar to synthetic aerogels created under neutral and basic conditions whereas alteration layers formed at pH 9 did not. Available dissolved silica species defined by silica solubility were proposed to have the greatest impact on alteration layer structure.
Matching STR and SNP genotyping to discriminate between wild boar, domestic pigs and their recent hybrids for forensic purposes
Authors: Lorenzini Rita , Fanelli Rita , Tancredi Francesco , Siclari Antonino , Garofalo Luisa 
Published: February 2020

AbstractThe genetic discrimination between phylogenetically close taxa can be challenging if their gene pools are not differentiated and there are many shared polymorphisms. The gene flow between wild boar (Sus scrofa) and domestic pig (S. s. domesticus) has never been interrupted from domestication onwards, due to non-stop natural and human-mediated crossbreeding. To date there are no individual genetic markers that are able to distinguish between the two forms, nor even to identify effectively their hybrids. We developed a combined molecular protocol based on multiplex porcine-specific STR-profiling system and new real time PCR-based assays of single polymorphisms in the NR6A1 and MC1R genes to gain high diagnostic power in the differentiation of wild boar, pig and hybrids for forensic purposes. The combined approach correctly assigned individuals to one or the other parental gene pool and identified admixed genotypes. Evidence was found for substantial reduction of false negative results by using multiple marker systems jointly, compared to their use individually. Our protocol is a powerful and cost-effective diagnostic tool that can easily be adopted by most forensic laboratories to assist authorities contrast food adulteration, assure veterinary public health and fight against wildlife crimes, like poaching and illegal detention of wild animals.
Factors associated with platelet reactivity during dual antiplatelet therapy in patients with diabetes after acute coronary syndrome
Authors: Tatarunas Vacis , Kupstyte-Kristapone Nora , Zvikas Vaidotas , Jakstas Valdas , Zaliunas Remigijus , Lesauskaite Vaiva 
Published: February 2020

AbstractAntiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478–10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073–1.210, respectively, p < 0.001). Ticagrelor use decreased the odds of developing high on-treatment platelet reactivity (OR: 0.238, 95% CI: 0.097–0.585, p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.
The outcomes of bariatric surgery on rheumatoid arthritis disease activity: a prospective cohort study
Authors: Xu Fang , Yu Chao , Li De-Guan , Yan Qiang , Zhang Shang-Xin , Yang Xiao-Dong , Zhang Zhen 
Published: February 2020

AbstractRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Overweight and obesity can aggravate disease activity and clinical outcome in patients with RA. However, the role of bariatric surgery in inducing weight loss in the treatment of RA has not been confirmed. In this 12-month prospective cohort study, RA patients with obesity who were referred to our hospital were included. Thirty-two patients were classified into the bariatric surgery group according to the patient’s decision after a comprehensive assessment of surgery indications, and 33 patients received only pharmacotherapy for RA. At the 12-month follow-up, the response rates of ACR20, ACR50 and ACR70 were 75.0% vs. 51.5%, 53.1% vs. 39.4% and 31.3% vs. 21.2% in the bariatric surgery and non-surgery groups, respectively (all p < 0.05); the mean DAS28-ESR, DAS28-CRP and cDAI scores were 1.5 ± 0.9 vs. 2.4 ± 1.4, 1.2 ± 0.9 vs. 2.2 ± 1.7 and 9.5 ± 6.8 vs. 15.8 ± 12.5, respectively, in surgical patients compared to non-surgical patients (all p < 0.05). Compared to baseline, after 12 months, a significant reduction was observed in the use of leflunomide, biological agents, combination treatments, and NSAIDs in both groups (p < 0.05 or p < 0.01). However, there was no difference in medication use between the 2 groups either at baseline or at the 12-month follow-up (all p > 0.05). Compared to non-surgical patients, in RA patients with obesity, weight loss after bariatric surgery was associated with lower disease activity. Medication tapering for RA in patients who underwent bariatric surgery was not superior to that in non-surgical patients.
Bees increase crop yield in an alleged pollinator-independent almond variety
Authors: Sáez Agustin , Aizen Marcelo A. , Medici Sandra , Viel Matias , Villalobos Ethel , Negri Pedro 
Published: February 2020

AbstractWild pollinators are declining and the number of managed honey bee colonies is growing slower than agricultural demands for pollination. Because of these contrasting trends in pollinator demand and availability, breeding programs for many pollinator-dependent crops have focused on reducing the need for pollinators. Although numerous crop varieties are now available in the market with the label of pollinator-independent, the real dependence of these varieties on pollinators is mostly unknown. We evaluated the hypothesis of pollinator independence in the Independence almond variety, the fastest growing variety in California that is the main almond production region in the world. In this presumed pollinator-independent variety, we measured the effect of honey bees on fruit set, yield, and kernel nutritional quality at tree level. Fruit set was 60% higher in bee-pollinated than bee-isolated trees, which translated into a 20% increase in kernel yield. Despite its effect on almond production, there was no evidence that bee visitation affected almond nutritional quality. Based on these results, we recommend the use of bees, whether they are wild or managed, to maximize yield even in self-fertile almond varieties.
Memorization of daily routines by children with Down syndrome assisted by a playful virtual environment
Authors: da Cruz Netto Ovidio Lopes , Rodrigues Silvia Cristina Martini , de Castro Marcus Vasconcelos , da Silva Diego Pereira , da Silva Robson Rodrigues , de Souza Richard Ribeiro Brancato , de Souza Adriana A. Ferreira , Bissaco Marcia Aparecida Silva 
Published: February 2020

AbstractA child with Down syndrome, like any other child, may benefit from interacting with memory stimuli, but needs additional support and help. The use of special teaching methods, which add playfulness and use of the computer, can enhance the memory processes of these children. In this work, we present the virtual environment “Nossa Vida (Our Life)”, which was developed to assist children with Down syndrome to memorize action sequences of their daily routine. A daily routine memorization test (DRMT), consisting of a weekly reminder of typical daily routines completed by the children and parents, was performed before (pre-test) and after (post-test) the intervention. The work involved a multidisciplinary team and assessed the effectiveness of the test performed by 30 children with Down syndrome from APAE, a special education school for children with intellectual disabilities in São Paulo, Brazil. The children were separated into two groups (Experimental - GE and Control - GC) with homogeneity and normality of the data. Two hypotheses were tested in this study: H0 and H1, where: H0 = There is no statistical difference between memorizing daily tasks between individuals with Down syndrome who used our ludic virtual environment and those who used the conventional memory method.H1 = There is a difference between the group of subjects with Down Syndrome who used our virtual game environment and the group that did not use it in relation to memorizing the daily task. This produces t = -14.98 and p <0.0001, with H1 being accepted. The results showed that the EG presented significance in relation to the CG and the evolution mean of the children in the EG was 81.82% higher. According to experts (psychologist and pedagogue) from APAE and parents, the playful activities implemented in this virtual environment have been of great interest to children, who had fun, tested hypotheses and questioned them about the sequences of actions performed in their routine daily.
Elites, communities and the limited benefits of mentorship in electronic music
Authors: Janosov Milán , Musciotto Federico , Battiston Federico , Iñiguez Gerardo 
Published: February 2020

AbstractWhile the emergence of success in creative professions, such as music, has been studied extensively, the link between individual success and collaboration is not yet fully uncovered. Here we aim to fill this gap by analyzing longitudinal data on the co-releasing and mentoring patterns of popular electronic music artists appearing in the annual Top 100 ranking of DJ Magazine. We find that while this ranking list of popularity publishes 100 names, only the top 20 is stable over time, showcasing a lock-in effect on the electronic music elite. Based on the temporal co-release network of top musicians, we extract a diverse community structure characterizing the electronic music industry. These groups of artists are temporally segregated, sequentially formed around leading musicians, and represent changes in musical genres. We show that a major driving force behind the formation of music communities is mentorship: around half of musicians entering the top 100 have been mentored by current leading figures before they entered the list. We also find that mentees are unlikely to break into the top 20, yet have much higher expected best ranks than those who were not mentored. This implies that mentorship helps rising talents, but becoming an all-time star requires more. Our results provide insights into the intertwined roles of success and collaboration in electronic music, highlighting the mechanisms shaping the formation and landscape of artistic elites in electronic music.
Nitrogen sufficiency enhances thermal tolerance in habitat-forming kelp: implications for acclimation under thermal stress
Authors: Fernández Pamela A. , Gaitán-Espitia Juan Diego , Leal Pablo P. , Schmid Matthias , Revill Andrew T. , Hurd Catriona L. 
Published: February 2020

AbstractLocal and global changes associated with anthropogenic activities are impacting marine and terrestrial ecosystems. Macroalgae, especially habitat-forming species like kelp, play critical roles in temperate coastal ecosystems. However, their abundance and distribution patterns have been negatively affected by warming in many regions around the globe. Along with global change, coastal ecosystems are also impacted by local drivers such as eutrophication. The interaction between global and local drivers might modulate kelp responses to environmental change. This study examines the regulatory effect of NO3− on the thermal plasticity of the giant kelp Macrocystis pyrifera. To do this, thermal performance curves (TPCs) of key temperature-dependant traits–growth, photosynthesis, NO3− assimilation and chlorophyll a fluorescence–were examined under nitrate replete and deplete conditions in a short-term incubation. We found that thermal plasticity was modulated by NO3− but different thermal responses were observed among traits. Our study reveals that nitrogen, a local driver, modulates kelp responses to high seawater temperatures, ameliorating the negative impacts on physiological performance (i.e. growth and photosynthesis). However, this effect might be species-specific and vary among biogeographic regions – thus, further work is needed to determine the generality of our findings to other key temperate macroalgae that are experiencing temperatures close to their thermal tolerance due to climate change.
CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis
Authors: Ju Linling , Sun Yan , Xue Hong , Chen Lin , Gu Chunyan , Shao Jianguo , Lu Rujian , Luo Xi , Wei Jue , Ma Xiong , Bian Zhaolian 
Published: February 2020

AbstractNon-alcoholic fatty liver disease (NAFLD) is characterized by increased uptake and accumulation of lipids in hepatocytes. Simple steatosis may progress to non-alcoholic steatohepatitis (NASH) with inflammation, hepatocellular injury and fibrosis. CCN1 is an important matrix protein that regulates cell death and promotes immune cell adhesion and may potentially control this process. The role of CCN1 in NASH remains unclear. We investigated the role of CCN1 in the pathogenesis of steatohepatitis. CCN1 upregulation was found to be closely related with steatosis in patients with NASH, obese mice and a FFA-treated hepatocyte model. Controlling the expression of CCN1 in murine NASH models demonstrated that CCN1 increased the severity of steatosis and inflammation. From the sequence results, we found that fatty acid metabolism genes were primarily involved in the MCD mice overexpressing CCN1 compared to the control. Then, the expression of fatty acid metabolism genes was determined using a custom-designed pathway-focused qPCR-based gene expression array. Expression analysis showed that CCN1 overexpression significantly upregulated the expression of fatty acid metabolism-associated genes. In vitro analysis revealed that CCN1 increased the intracellular TG content, the pro-inflammatory cytokines and the expression level of apoptosis-associated proteins in a steatosis model using murine primary hepatocytes. We identified CCN1 as an important positive regulator in NASH.
Diabetes and all-cause mortality, a 18-year follow-up study
Authors: Salehidoost Rezvan , Mansouri Asieh , Amini Massoud , Aminorroaya Yamini Sima , Aminorroaya Ashraf 
Published: February 2020

AbstractThis study compared mortality rates and decline in life expectancy of Iranian patients with type 2 diabetes (T2DM) with the general population. A retrospective study of 2451 patients with T2DM was conducted in the Isfahan Endocrine and Metabolism Research Center, Iran, between 1992 and 2010. The mean (SD) of diabetes duration and median (Q1,Q3) of follow-up period were 15.5(8.0) and 8(5, 10) years. The main outcome was all-cause mortality. 732(29.87%) of patients died during the follow-up. Overall mortality rates (95%CI) per 1000 person-years in men and women were 56.3(52.0–62.1) and 27.3(24.5–30.4), respectively. The relative risks (95%CI) of all-cause mortality in males vs. females with T2DM aged 45–49, 50–54, 55–59, 60–64, 65–69, 70–74 were [3.02(1.49–6.11) vs. 2.09(0.96–4.57)], [4.05(2.73–6.01) vs. 2.29(1.52–3.45)], [4.13(3.26–5.24) vs. 1.70(1.23–2.35)], [2.42(1.90–3.07) vs. 1.82(1.46–2.27)], [2.36(2.02–2.76) vs. 1.49(1.25–1.78)] and [1.71(1.50–1.95) vs. 1.04(0.88–1.23)] times more than the general population, respectively. Men and women living with diabetes lost an average of 13.2(6.3) and 13.9(6.0) life-years from the year of diagnosis, respectively (p = 0.101). The estimated life-years lost were greater in younger patients and a gradual decline was observed with increasing the age at diagnosis. In conclusion, Iranians with diabetes had higher risk of death and lower life expectancy compared to the general population.
Effect of T. spiralis Serine protease inhibitors on TNBS-induced experimental colitis mediated by Macrophages
Authors: Xu Jingyun , Wu Lijia , Yu Pengcheng , Sun Yichun , Lu Yixin 
Published: February 2020

AbstractInflammatory bowel disease (IBD) is an autoimmune disease with increasing incidence rate, and divided into ulcerative colitis (UC) and Crohn’s disease (CD). And more and more experimental evidence supports that immune disorder is important in the pathogenesis of IBD. Our previous experiments have confirmed that TsKaSPI and TsAdSPI recombinant proteins could relieve TNBS (2,4,6-Trinitrobenzenesulfonic acid solution)-induced colitis. Therefore, we speculate that macrophages play a certain role in the process of recombinant protein relieving colitis. In this experiment, 96 male BALB/c mice aged 6–8 weeks were randomly divided into two groups: the prevention group and the therapy group. Changes of the ratio of M1/M2 phenotypic macrophages in spleens and MLNs, key factors in the IL-33/ST2 and IL-6/JAK2/STAT3 signaling pathway were detected. The purpose is to analyze the specific role played by macrophages and their secreted cytokines in the immunomodulation of colitis by Trichinella spiralis (T. spiralis) Serine protease inhibitors. The results showed that the percentage of M1 phenotypic macrophages was decreased and M2 phenotypic macrophages was increased in the TsKaSPI + TNBS, TsAdSPI + TNBS group compared with the PBS + TNBS group in the prevention group. Meanwhile, the expression of IL-33 and ST2 were significantly decreased. The key factors of IL-6/JAK2/STAT3 signaling pathway were all significantly increased. In addition, in the therapy group, we found similar results. This experiment demonstrated that macrophages have a certain impact during this process of recombinant protein relieving mouse CD model.