bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased oxidative stress and CaMKII activity contribute to electro‐mechanical defects in cardiomyocytes from a murine model of Huntington's disease
Authors: Joviano‐Santos Julliane Vasconcelos , Santos‐Miranda Artur , Botelho Ana Flávia Machado , de Jesus Itamar Couto Guedes , Andrade Jéssica Neves , de Oliveira Barreto Tatiane , Magalhães‐Gomes Matheus Proença S. , Valadão Priscila Aparecida Costa , Cruz Jader dos Santos , Melo Marília Martins , Guatimosim Silvia , Guatimosim Cristina 
Published: November 2018

Huntington's disease (HD) is a neurodegenerative genetic disorder. Although described as a brain pathology, there is evidence suggesting that defects in other systems can contribute to disease progression. In line with this, cardiovascular defects are a major cause of death in HD. To date, relatively little is known about the peripheral abnormalities associated with the disease. Here, we applied a range of assays to evaluate cardiac electro‐mechanical properties in vivo, using a previously characterized mouse model of HD (BACHD), and in vitro, using cardiomyocytes isolated from the same mice. We observed conduction disturbances including QT interval prolongation in BACHD mice, indicative of cardiac dysfunction. Cardiomyocytes from these mice demonstrated cellular electro‐mechanical abnormalities, including a prolonged action potential, arrhythmic contractions, and relaxation disturbances. Cellular arrhythmia was accompanied by an increase in calcium waves and increased Ca2+/calmodulin‐dependent protein kinase II activity, suggesting that disruption of calcium homeostasis plays a key part. We also described structural abnormalities in the mitochondria of BACHD‐derived cardiomyocytes, indicative of oxidative stress. Consistent with this, imbalances in superoxide dismutase and glutathione peroxidase activities were detected. Our data provide an in vivo demonstration of cardiac abnormalities in HD together with new insights into the cellular mechanistic basis, providing a possible explanation for the higher cardiovascular risk in HD.
Modelled net carbon gain responses to climate change in boreal trees: Impacts of photosynthetic parameter selection and acclimation
Authors: Stinziano Joseph R. , Bauerle William L. , Way Danielle A. 
Published: November 2018

AbstractBoreal forests are crucial in regulating global vegetation‐atmosphere feedbacks, but the impact of climate change on boreal tree carbon fluxes is still unclear. Given the sensitivity of global vegetation models to photosynthetic and respiration parameters, we determined how predictions of net carbon gain (C‐gain) respond to variation in these parameters using a stand‐level model (MAESTRA). We also modelled how thermal acclimation of photosynthetic and respiratory temperature sensitivity alters predicted net C‐gain responses to climate change. We modelled net C‐gain of seven common boreal tree species under eight climate scenarios across a latitudinal gradient to capture a range of seasonal temperature conditions. Physiological parameter values were taken from the literature together with different approaches for thermally acclimating photosynthesis and respiration. At high latitudes, net C‐gain was stimulated up to 400% by elevated temperatures and CO2 in the autumn but suppressed at the lowest latitudes during midsummer under climate scenarios that included warming. Modelled net C‐gain was more sensitive to photosynthetic capacity parameters (Vcmax, Jmax, Arrhenius temperature response parameters, and the ratio of Jmax to Vcmax) than stomatal conductance or respiration parameters. The effect of photosynthetic thermal acclimation depended on the temperatures where it was applied: acclimation reduced net C‐gain by 10%–15% within the temperature range where the equations were derived but decreased net C‐gain by 175% at temperatures outside this range. Thermal acclimation of respiration had small, but positive, impacts on net C‐gain. We show that model simulations are highly sensitive to variation in photosynthetic parameters and highlight the need to better understand the mechanisms and drivers underlying this variability (e.g., whether variability is environmentally and/or biologically driven) for further model improvement.
Transgenerational lipid‐reducing activity of benzylisoquinoline alkaloids in Caenorhabditis elegans
Authors: Chow Yit‐Lai , Sato Fumihiko 
Published: November 2018

AbstractEpigenetic mechanisms allow for transgenerational memory of an ancestor's environment and can affect the gene expression, physiology and phenotype of that ancestor's descendants, independent of DNA sequence alteration. Among many model organisms, Caenorhabditis elegans has been instrumental in studies of transgenerational inheritance, most of which have focused on the effects of external stressors of the parent worm on the life span and stress resistance of future generations. In this work, we used Nile red staining of accumulated lipids in C. elegans to investigate the transgenerational effect of two benzylisoquinoline alkaloids, namely, berberine and sanguinarine. Our results showed that a reduction in Nile red fluorescence can be propagated to subsequent worm generations. Using mutant worms, we found that the transgenerational effect requires the ASH‐2 component of the histone H3K4me3 complex and the HRDE‐1 worm Argonaute protein. Ash‐2 is also required for transgenerational inheritance of the xenobiotic response in the worm. Our study offers new insights into transmissible drug effects across multiple generations and suggests the importance of such analyses in the drug development process.
Caries severity declined besides persistent untreated primary teeth over a 22‐year period: Trends among children in Goiânia, Brazil
Authors: Freire Maria do Carmo Matias , Daher Anelise , Costa Luciane Rezende , Corrêa‐Faria Patrícia , de Brito Letícia Candine , Bönecker Marcelo José Strazzeri , de Abreu Mauro Henrique Nogueira Guimarães 
Published: November 2018

BackgroundEvidence of time trends in early childhood caries in low‐ and middle‐income countries in the second decade of the year 2000 is scarce.AimTo assess the trends in early childhood caries prevalence and severity in 2‐ to 5‐year‐old children over a 22‐year period (1993‐2015) in Goiânia, Midwest Brazil. Additionally, we aimed to investigate the changes regarding affected dental arches and teeth.DesignA time‐lag analysis of trends in caries was carried out using data from three cross‐sectional studies based on the World Health Organization diagnostic criteria, in 1993 (N = 1362), 2001 (N = 1620), and 2015 (N = 548).ResultsCaries prevalence declined from 45.1% in 1993 to 29.0% in 2015. Prevalence of severe caries (dmft ≥ 6) in 2015 was nearly one‐third of that found in 1993, and the SiC index (mean dmft of the highest tertile) decreased from 4.55 to 3.32. Decline was higher in the 1993‐2001 than in the 2001‐2015 time‐lag. Posterior teeth and second molars had the greatest reductions. High proportions of untreated caries were found in all ages and survey years.ConclusionThere were significant changes in caries prevalence and severity, marked by a striking decline from 1993 to 2001, followed by a less prominent decrease up to 2015, and high levels of untreated caries.
Efficacy of a socioemotional learning programme in a sample of children with intellectual disability
Authors: Faria Sónia M. M. , Esgalhado Graça , Pereira Cristina M. G. 
Published: November 2018

AbstractSocioemotional learning (SEL) is the process of developing social and emotional competences through which the child learns to recognize and manage emotions, care for others, make good decisions, behave responsibly and ethically, develop positive relationships and avoid negative behaviours (Promoting social and emotional learning: Guidelines for educators, 1997). To promote the development of these competences, specific programmes are developed. This study aims to analyse the impact of a SEL programme among children with intellectual disability. Two groups were established, control and experimental, and the Test of Emotion Comprehension (TEC) (Test of emotion comprehension – TEC, 2000; Les émotions à l'école, émotions et apprentissage, 2004) was applied to both as pre‐ and post‐test. The programme was implemented in the experimental group, based on simply illustrated stories alluding the basic emotions. The findings suggest that the programme is effective in the development of socioemotional competences (SEC) in subjects with intellectual disabilities, evidencing the positive effects that the intervention programme had with the experimental group.
TSG101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG10
Authors: Liu Zhiyi , Tian Zilu , Cao Kuan , Zhang Bin , Wen Quan , Zhou Xinyu , Yang Weibin , Wang Tao , Shi Hengliang , Wang Renhao 
Published: November 2018

AbstractThe tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up‐regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up‐regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10.
Pharmacological effects of berberine on mood disorders
Authors: Fan Jie , Zhang Kun , Jin Yang , Li Bingjini , Gao Shuohui , Zhu Jiaming , Cui Ranji 
Published: November 2018

AbstractBerberine, a natural isoquinoline alkaloid, is used in herbal medicine and has recently been shown to have efficacy in the treatment of mood disorders. Furthermore, berberine modulates neurotransmitters and their receptor systems within the central nervous system. However, the detailed mechanisms of its action remain unclear. This review summarizes the pharmacological effects of berberine on mood disorders. Therefore, it may be helpful for potential application in the treatment of mood disorders.
Efficient method for isolation of reticulocyte RNA from healthy individuals and hemolytic anaemia patients
Authors: Skulski Michał , Bartoszewski Rafał , Majkowski Michał , Machnicka Beata , Kuliczkowski Kazimierz , Sikorski Aleksander F. , Bogusławska Dżamila M. 
Published: November 2018

AbstractDespite enormous progress and development of high‐throughput methods in genome‐wide mRNA analyses, data on the erythroid transcriptome are still limited, even though they could be useful in medical diagnostics and personalized therapy as well as in research on normal and pathological erythroid maturation. Although obtaining normal and pathological reticulocyte transcriptome profiles should contribute greatly to our understanding of the molecular bases of terminal erythroid differentiation as well as the mechanisms of the hematological diseases, a basic limitation of these studies is the difficulty of efficient reticulocyte RNA isolation from human peripheral blood. The restricted number of possible parallel experiments primarily concern healthy individuals with the lowest number of reticulocytes in the peripheral blood and a low RNA content. In the present study, an efficient method for reticulocyte RNA isolation from healthy individuals and hemolytic anaemia patients is presented. The procedure includes leukofiltration, Ficoll‐Paque gradient centrifugation, Percoll gradient centrifugation, and negative (CD45 and CD61) immunomagnetic separation. This relatively fast and simple four‐stage method was successfully applied to obtain a reticulocyte‐rich population from healthy subjects, which was used to efficiently isolate the high‐quality RNA essential for successful NGS‐based transcriptome analysis.
DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
Authors: Liu Jie , Li Juan , Li Pingping , Jiang Yina , Chen He , Wang Ruiqi , Cao Fang , Liu Peijun 
Published: November 2018

AbstractTamoxifen (TAM) is a primary drug for treatment of estrogen receptor positive breast cancer. However, TAM resistance remains a serious threat to breast cancer patients and may be attributed to increased stemness of breast cancer. Here, we show that discs large homolog 5 (DLG5) expression is down‐regulated in TAM‐resistant breast cancer and cells. DLG5 silencing decreased the sensitivity to TAM and increased the frequency and stemness of CD44+/CD24− breast cancer stem cells (BCSCs) and TAZ, a transducer of the Hippo pathway, expression in MCF7 cells while DLG5 overexpression had opposite effects. TAZ silencing restored the sensitivity to TAM and reduced the frequency and stemness in TAM‐resistant breast cancer cells. Taken together, our data indicate that down‐regulated DLG5 expression increases the stemness of breast cancer cells by enhancing TAZ expression, contributing to TAM resistance in breast cancer.
Evodiamine inhibits RANKL‐induced osteoclastogenesis and prevents ovariectomy‐induced bone loss in mice
Authors: Jin Haiming , Yao Lingya , Chen Kai , Liu Yuhao , Wang Qingqing , Wang Ziyi , Liu Qian , Cao Zhen , Kenny Jacob , Tickner Jennifer , Wang Xiangyang , Xu Jiake 
Published: November 2018

AbstractPostmenopausal osteoporosis (PMO) is a progressive bone disease characterized by the over‐production and activation of osteoclasts in elderly women. In our study, we investigated the anti‐osteoclastogenic effect of evodiamine (EVO) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage (BMM)‐derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL‐induced transcriptional activity of IκBα. RANKL‐induced Ca2+ oscillations were also abrogated by EVO. In vivo, an ovariectomized (OVX) mouse model was established to mimic PMO, and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL‐induced osteoclastogenesis through NF‐κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO.
Immunometabolism features of metabolic deregulation and cancer
Authors: Wang Xue , Ping Feng‐Feng , Bakht Sahar , Ling Jingjing , Hassan Waseem 
Published: November 2018

AbstractImmunometabolism is a branch dealing at the interface of immune functionalities and metabolic regulations. Considered as a bidirectional trafficking, metabolic contents and their precursors bring a considerable change in immune cells signal transductions which as a result affect the metabolic organs and states as an implication. Lipid metabolic ingredients form a major chunk of daily diet and have a proven contribution in immune cells induction, which then undergo metabolic pathway shuffling inside their ownself. Lipid metabolic states activate relevant metabolic pathways inside immune cells that in turn prime appropriate responses to outside environment in various states including lipid metabolic disorders itself and cancers as an extension. Although data on Immunometabolism are still growing, but scientific community need to adjust and readjust according to recent data on given subject. This review attempts to provide current important data on Immunometabolism and consequently its metabolic ramifications. Incumbent data on various lipid metabolic deregulations like obesity, metabolic syndrome, obese asthma and atherosclerosis are analysed. Further, metabolic repercussions on cancers and its immune modalities are also analysed.
Age‐related ultrastructural changes of the basement membrane in the mouse blood‐brain barrier
Authors: Ceafalan Laura Cristina , Fertig Tudor Emanuel , Gheorghe Teodora Cristina , Hinescu Mihail Eugen , Popescu Bogdan Ovidiu , Pahnke Jens , Gherghiceanu Mihaela 
Published: November 2018

AbstractThe blood‐brain barrier (BBB) is essential for a functional neurovascular unit. Most studies focused on the cells forming the BBB, but very few studied the basement membrane (BM) of brain capillaries in ageing. We used transmission electron microscopy and electron tomography to investigate the BM of the BBB in ageing C57BL/6J mice. The thickness of the BM of the BBB from 24‐month‐old mice was double as compared with that of 6‐month‐old mice (107 nm vs 56 nm). The aged BBB showed lipid droplets gathering within the BM which further increased its thickness (up to 572 nm) and altered its structure. The lipids appeared to accumulate toward the glial side of the BM. Electron tomography showed that the lipid‐rich BM regions are located in small pockets formed by the end‐feet of astrocytes. These findings suggest an imbalance of the lipid metabolism and that may precede the structural alteration of the BM. These alterations may favour the accretion of abnormal proteins that lead to neurodegeneration in ageing. These findings warrant further investigation of the BM of brain capillaries and of adjoining cells as potential targets for future therapies.
High proportion of transient neonatal zinc deficiency causing alleles in the general population
Authors: Golan Yarden , Lehvy Adrian , Horev Guy , Assaraf Yehuda G. 
Published: November 2018

AbstractLoss of function (LoF) mutations in the zinc transporter SLC30A2/ZnT2 result in impaired zinc secretion into breast milk consequently causing transient neonatal zinc deficiency (TNZD) in exclusively breastfed infants. However, the frequency of TNZD causing alleles in the general population is yet unknown. Herein, we investigated 115 missense SLC30A2/ZnT2 mutations from the ExAC database, equally distributed in the entire coding region, harboured in 668 alleles in 60 706 healthy individuals of diverse ethnicity. To estimate the frequency of LoF SLC30A2/ZnT2 mutations in the general population, we used bioinformatics tools to predict the potential impact of these mutations on ZnT2 functionality, and corroborated these predictions by a zinc transport assay in human MCF‐7 cells. We found 14 missense mutations that were markedly deleterious to zinc transport. Together with two conspicuous LoF mutations in the ExAC database, 26 SLC30A2/ZnT2 alleles harboured deleterious mutations, suggesting that at least 1 in 2334 newborn infants are at risk to develop TNZD. This high frequency of TNZD mutations combined with the World Health Organization‐promoted increase in the rate of exclusive breastfeeding highlights the importance of genetic screening for inactivating SLC30A2/ZnT2 mutations in the general population for the early diagnosis and prevention of TNZD.
Otx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells
Authors: Xiong Yu , Ji Hongpei , You Zhipeng , Yao Fei , Zhou Rongrong , Song Weitao , Xia Xiaobo 
Published: November 2018

AbstractRetinal Müller glial cells have the potential of neurogenic retinal progenitor cells, and could reprogram into retinal‐specific cell types such as photoreceptor cells. How to promote the differentiation of Müller cells into photoreceptor cells represents a promising therapy strategy for retinal degeneration diseases. This study aimed to enhance the transdifferentiation of rat Müller cells‐derived retinal stem cells (MC‐RSCs) into photoreceptor‐like cells and explore the signalling mechanism. We dedifferentiated rat Müller cells into MC‐RSCs which were infected with Otx2 overexpression lentivirus or control. The positive rate of photoreceptor‐like cells among MC‐RSCs treated with Otx2 overexpression lentivirus was significantly higher compared to control. Furthermore, pre‐treatment with Crx siRNA, Nrl siRNA, or GSK‐3 inhibitor SB‐216763 reduced the positive rate of photoreceptor‐like cells among MC‐RSCs treated with Otx2 overexpression lentivirus. Finally, Otx2 induced photoreceptor precursor cells were injected into subretinal space of N‐methyl‐N‐nitrosourea induced rat model of retinal degeneration and partially recovered retinal degeneration in the rats. In conclusion, Otx2 enhances transdifferentiation of MC‐RSCs into photoreceptor‐like cells and this is associated with the inhibition of Wnt signalling. Otx2 is a potential target for gene therapy of retinal degenerative diseases.
Mast cell tetrahydrobiopterin contributes to itch in mice
Authors: Zschiebsch Katja , Fischer Caroline , Wilken‐Schmitz Annett , Geisslinger Gerd , Channon Keith , Watschinger Katrin , Tegeder Irmgard 
Published: November 2018

AbstractGTP cyclohydrolase (GCH1) governs de novo synthesis of the enzyme cofactor, tetrahydrobiopterin (BH4), which is essential for biogenic amine production, bioactive lipid metabolism and redox coupling of nitric oxide synthases. Overproduction of BH4 via upregulation of GCH1 in sensory neurons is associated with nociceptive hypersensitivity in rodents, and neuron‐specific GCH1 deletion normalizes nociception. The translational relevance is revealed by protective polymorphisms of GCH1 in humans, which are associated with a reduced chronic pain. Because myeloid cells constitute a major non‐neuronal source of BH4 that may contribute to BH4‐dependent phenotypes, we studied here the contribution of myeloid‐derived BH4 to pain and itch in lysozyme M Cre‐mediated GCH1 knockout (LysM‐GCH1−/−) and overexpressing mice (LysM‐GCH1‐HA). Unexpectedly, knockout or overexpression in myeloid cells had no effect on nociceptive behaviour, but LysM‐driven GCH1 knockout reduced, and its overexpression increased the scratching response in Compound 48/80 and hydroxychloroquine‐evoked itch models, which involve histamine and non‐histamine dependent signalling pathways. Mechanistically, GCH1 overexpression increased BH4, nitric oxide and hydrogen peroxide, and these changes were associated with increased release of histamine and serotonin and degranulation of mast cells. LysM‐driven GCH1 knockout had opposite effects, and pharmacologic inhibition of GCH1 provided even stronger itch suppression. Inversely, intradermal BH4 provoked scratching behaviour in vivo and BH4 evoked an influx of calcium in sensory neurons. Together, these loss‐ and gain‐of‐function experiments suggest that itch in mice is contributed by BH4 release plus BH4‐driven mediator release from myeloid immune cells, which leads to activation of itch‐responsive sensory neurons.