bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Parkinson's disease‐associated gene PINK1 protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Drp1
Authors: Zhao Yanxin , Chen Fangzhe , Chen Shufen , Liu Xueyuan , Cui Mei , Dong Qiang 
Published: June 2013

AbstractOur previous study has shown that PTEN‐induced novel kinase 1 (PINK1) knocking down significantly induced mitochondrial fragmentation. Although PINK1 is proved to be associated with autosomal recessive parkinsonism and its function in this chronic pathological process is widely studied, its role in acute energy crisis such as ischemic stroke is poorly known. In this study by employing an oxygen–glucose deprivation (OGD) neuronal model, we explored the function of PINK1 in cerebral ischemia. Human PINK1, two PINK1 mutants W437X and K219M, or Pink1 shRNA were transduced before OGD using lentiviral delivery. Our results showed that over‐expression of wild‐type PINK1 significantly ameliorated OGD induced cell death and energy disturbance including reduced ATP generation and collapse of mitochondrial membrane potential. PINK1 over‐expression also reversed OGD increased mitochondrial fragmentation, and suppressed the translocation of the mitochondrial fission protein dynamin‐related protein 1 (Drp1) from the cytosol to the mitochondria. Transduction of the mutant PINK1 failed to provide any protective effect, while knockdown of Pink1 significantly increased the severity of OGD‐induced neuronal damage. Importantly, inhibition of Drp1 reversed the effects of knocking down Pink1 on neuronal death and ATP production in response to OGD. This study demonstrates that PINK1 prevents ischemic damage in neurons by attenuating mitochondrial translocation of Drp1, which maintains mitochondrial function and inhibits ischemia‐induced mitochondrial fission. These novel findings implicate a pivotal role of PINK1 regulated mitochondrial dynamics in the pathology of ischemic stroke.
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In this study by employing an oxygen–glucose deprivation (OGD) neuronal model, we explored the function of PINK1 in cerebral ischemia. We indicated that PINK1 significantly ameliorated OGD induced cell death and energy disturbance including reduced ATP generation and collapse of mitochondrial membrane potential by attenuating mitochondrial translocation of Drp1, which maintains mitochondrial function and inhibits ischemia‐induced mitochondrial fission.
E‐cadherin downregulation and Twist overexpression since early stages of oral carcinogenesis
Authors: de Freitas Silva Brunno Santos , Yamamoto‐Silva Fernanda Paula , Pontes Hélder Antônio Rebelo , Pinto Júnior Décio dos Santos 
Published: June 2013

There is some evidence of Twist participation in oral carcinogenesis; however, little is known about its interaction with E‐cadherin in oral squamous cell carcinoma (OSCC) development. This experimental study included an immunohistochemical analysis of Twist and E‐cadherin proteins in paraffin‐embedded specimens of oral leukoplakia (OL), OSCC, and normal oral mucosa. In addition, it was also performed a Western blot and double‐immunofluorescence analysis of Twist and E‐cadherin expression in OSCC cell lines. Significant differences in Twist and E‐cadherin immunoexpression were observed between normal oral mucosa and OL, with an inverse relation since the earliest stages of oral dysplasia (r = −0,512; P < 0.001). Western blot and double‐immunofluorescence analysis showed differences in Twist and E‐cadherin expression among human oral keratinocytes and OSCC cell lines suggesting that downregulation of E‐cadherin occurs in a dependent manner of Twist in OSCC. Our results showed a possible value of Twist and E‐cadherin in the prediction of risk of oral epithelium malignant transformation.
Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM‐induced autophagy or BAX
Authors: Liu Kai , Lou Jinli , Wen Tao , Yin Jiming , Xu Bin , Ding Wei , Wang Anna , Liu Daojie , Zhang Chao , Chen Dexi , Li Ning 
Published: June 2013

AbstractBackground & AimsApoptosis mediated by p53 plays a pathological role in the progression of hepatosteatosis. It is noteworthy that p53 can promote the expression of damage‐regulated autophagy modulator (DRAM), an inducer of autophagy‐mediated apoptosis. However, the relationship between p53‐mediated apoptosis and autophagy in hepatosteatosis remains elusive. This study aimed to examine how p53 orchestrates autophagy and apoptosis to affect hepatosteatosis.MethodsHepG2 cells were treated with oleic acid (OA) for 24 h to induce hepatosteatosis. Mice were fed a high‐fat diet for 20 or 40 weeks to induce hepatosteatosis.ResultsOA induced a dose‐dependent increase in steatosis severity and apoptosis. OA also induced autophagy, which was a critical inducer of apoptosis in mild steatosis induced by 400 μM OA, but not in the more severe steatosis induced by 800 and 1200 μM OA. p53 inhibition by siRNA mostly blocked OA‐induced apoptosis and autophagy. Moreover, OA‐induced autophagy was DRAM‐dependent and primarily occurred in the mitochondria (mitophagy), where DRAM was localized. In severe steatosis induced by 1200 μM OA, apoptosis was mainly dependent on p53‐induced expression of BAX, which was also localized to the mitochondria. Our in vivo study showed that p53 expression increased in both mild and severe hepatosteatosis. Increased DRAM expression and autophagy were identified in mild hepatosteatosis, whereas greater BAX expression was observed in severe hepatosteatosis.Conclusionsp53 may induce apoptosis via different mechanisms. DRAM‐mediated mitophagy is a primary apoptotic inducer in mild hepatosteatosis, whereas p53‐induced BAX expression mainly induces apoptosis in severe hepatosteatosis.
Determination of ethyl glucuronide in hair improves evaluation of long‐term alcohol abstention in liver transplant candidates
Authors: Sterneck Martina , Yegles Michel , Rothkirch von Gregor , Staufer Katharina , Vettorazzi Eik , Schulz Karl‐Heinz , Tobias Niels , Graeser Christian , Fischer Lutz , Nashan Bjoern , Andresen‐Streichert Hilke 
Published: June 2013

AbstractBackground & AimsPrior to listing patients for Orthotopic liver transplantation (OLT) an abstention period of 6 months is required. Ethyl glucuronide in the hair is a new reliable marker for the assessment of alcohol consumption. Here, the diagnostic value of determining the ethyl glucuronide concentration in the hair of liver transplant candidates was evaluated.MethodsIn 63 transplant candidates with alcoholic liver cirrhosis and 25 control patients with cirrhosis of other aetiologies alcohol markers, i.e. hEtG, urine EtG, blood ethanol, methanol and carbohydrate deficient transferrin were determined in parallel to an interview with a psychologist.ResultsA total of 19 (30%) transplant candidates admitted alcohol consumption within the last 6 months, while 39/63 (62%) were positive for at least one alcohol marker. In 52% of the 44 candidates denying alcohol consumption, abstention was disproved by detecting at least one positive alcohol marker, in 83% of cases by a positive hEtG result. In the control patients stating abstention from alcohol all hEtG tests were negative. No impact of renal or liver function on hEtG results was detected. A specificity of 98% and a positive predictive value of 92% were calculated for testing hEtG in proximal hair segment and applying a cut‐off of 30 pg/mg.ConclusionsIn 52% of patients denying alcohol consumption within the last 6 months, alcohol abstention was disproved, in 83% of cases by hEtG testing. Therefore, hEtG is a promising new marker for the evaluation of long‐term alcohol abstention in liver transplant candidates.
miR146a impairs the IFN‐induced anti‐HBV immune response by downregulating STAT1 in hepatocytes
Authors: Hou Zhao H. , Han Qiu J. , Zhang Cai , Tian Zhi G. , Zhang Jian 
Published: June 2013

AbstractBackground & AimsPrevious studies have shown that hepatitis B virus (HBV) interferes with host antiviral immunity via multiple pathways. In clinical practice, interferon resistance is a serious issue for treatment of HBV infection. Now, miRNAs have been reported to be widely involved in antiviral immunity and have become a novel tool to study virus–host interaction. We question whether miRNAs play a role in HBV‐induced interferon resistance in hepatocytes.MethodsMiRNAs levels in HepG2 and HepG2.2.15 cells were compared by qRT‐PCR. The effects of miR146a on HBV infection were characterized by interference miR146a level, followed by the quantification of HBV mRNA, DNA and antigens. We employed qRT‐PCR and western blot to study the effects of miR146a on the IFN‐α signalling pathway. The miR146a promoter activity was validated by a luciferase reporter assay.ResultsHBV infection impaired IFN‐α signalling pathway in hepatocytes. MiR146a was upregulated in HBV+ HepG2.2.15 cells, and the transcriptional activity of miR146a in HepG2.2.15 cells was increased compared with HepG2 cells. HBV infection, especially the introduction of HBx, induced miR146a expression in vitro. Moreover, miR146a attenuated the production of type I interferon‐induced antiviral factors. Low STAT1 levels were noticed in HBV+ HCC cells, and the luciferase reporter assay showed that STAT1 was post‐transcriptionally downregulated by miR146a. Furthermore, the silencing of miR146a by antisense inhibitors enhanced IFN‐α‐mediated anti‐HBV efficiency.ConclusionsOur findings demonstrate that HBV infection promotes miR146a transcription, which represses STAT1 and results in interferon resistance. These observations reveal a novel role for miR146a in HBV immunopathogenesis, and provide a potential target for the therapeutic recovery of IFN‐α‐induced anti‐HBV effects.
Tfh and plasma cells are correlated with hypergammaglobulinaemia in patients with autoimmune hepatitis
Authors: Ma Liang , Qin Junjie , Ji Huifan , Zhao Pingwei , Jiang Yanfang 
Published: June 2013

AbstractBackgroundThis study aimed at examining the numbers of different subsets of circulating Tfh and B cells in patients with new onset autoimmune hepatitis (AIH).MethodsA total of 17 patients with new onset AIH and 17 age‐/gender‐matched healthy controls (HC) were examined for the numbers of ICOS+, PD‐1+ and IL‐21+ Tfh cells, CD27+, CD38+, CD95+, CD86+ and IL‐10+ B cells were quantified by flow cytometry. The concentrations of serum IL‐21 and IL‐10 were examined.ResultsIn comparison with that in the HC, significantly increased numbers of circulating CD38+, CD86+ or CD95+ B cells, ICOS+ and PD‐1+ Tfh cells and increased levels of serum IL‐21, but reduced numbers of CD27+, IL‐10+ B cells were detected in the patients. The concentrations of serum IL‐21 and IL‐10 were positively correlated with the numbers of CD4+CXCR5+ TFH and CD19+CD5+CD1d+ B cells respectively. The numbers of ICOS+ or PD‐1+ Tfh cells were correlated positively with CD86+ or CD95+ B cells in those patients respectively. The numbers of CD38+ B cells, ICOS+ or PD‐1+ Tfh cells were correlated positively with the concentrations of serum IgG or IgM in the patients respectively; the concentrations of serum IL‐21 were correlated positively with serum IgG, IgA and IgM and the concentrations of serum IL‐10 were correlated negatively with serum IgG and IgM in the patients.ConclusionCirculating activated Tfh and plasma cells may be associated with hypergammaglobulinaemia during the pathogenic process of AIH in humans.
Relaxin decreases the severity of established hepatic fibrosis in mice
Authors: Bennett Robert G. , Heimann Dean G. , Singh Sudhir , Simpson Ronda L. , Tuma Dean J. 
Published: June 2013

AbstractBackground & AimsHepatic fibrosis is characterized by excess collagen deposition, decreased extracellular matrix degradation and activation of the hepatic stellate cells. The hormone relaxin has shown promise in the treatment of fibrosis in a number of tissues, but the effect of relaxin on established hepatic fibrosis is unknown. The aim of this study was to determine the effect of relaxin on an in vivo model after establishing hepatic fibrosisMethodsMale mice were made fibrotic by carbon tetrachloride treatment for 4 weeks, followed by treatment with two doses of relaxin (25 or 75 μg/kg/day) or vehicle for 4 weeks, with continued administration of carbon tetrachloride.ResultsRelaxin significantly decreased total hepatic collagen and smooth muscle actin content at both doses, and suppressed collagen I expression at the higher dose. Relaxin increased the expression of the matrix metalloproteinases MMP13 and MMP3, decreased the expression of MMP2 and tissue inhibitor of metalloproteinase 2 (TIMP2) and increased the overall level of collagen‐degrading activity. Relaxin decreased TGFβ‐induced Smad2 nuclear localization in mouse hepatic stellate cells.ConclusionsThe results suggest that relaxin reduced collagen deposition and HSC activation in established hepatic fibrosis despite the presence of continued hepatic insult. This reduced fibrosis was associated with increased expression of the fibrillar collagen‐degrading enzyme MMP13, decreased expression of TIMP2, and enhanced collagen‐degrading activity, and impaired TGFβ signalling, consistent with relaxin's effects on activated fibroblastic cells. The results suggest that relaxin may be an effective treatment for the treatment of established hepatic fibrosis.
Notch signaling mediates melanoma–endothelial cell communication and melanoma cell migration
Authors: Howard Jason D. , Moriarty Whei F. , Park JinSeok , Riedy Katherine , Panova Izabela P. , Chung Christine H. , Suh Kahp‐Yang , Levchenko Andre , Alani Rhoda M. 
Published: June 2013

SummaryStromal and cellular components within the tumor microenvironment significantly influence molecular signals mediating tumor growth and progression. We recently performed a screen to evaluate critical mediators of melanoma–endothelial communication and identified several molecular pathways associated with these cellular networks, including Notch3. Here, we evaluate the nature of melanoma–endothelial communication mediated by Notch3 and its functional significance. We find that Notch3 is specifically upregulated in melanoma–endothelial cell cocultures and is functionally associated with increased Notch signaling in melanoma cells. Furthermore, induced Notch3 signaling in melanoma cell lines leads to enhanced tumor cell migration without associated increases in tumor cell growth. Additionally, Notch3 expression is specifically associated with malignant patient samples and is not evident in benign nevi. We conclude that Notch3 mediates melanoma–endothelial cell communication and tumor cell migration and may serve as a meaningful therapeutic target for this aggressive malignancy.
Carlactone‐independent seedling morphogenesis in Arabidopsis
Authors: Scaffidi Adrian , Waters Mark T. , Ghisalberti Emilio L. , Dixon Kingsley W. , Flematti Gavin R. , Smith Steven M. 
Published: June 2013

SummaryStrigolactone hormones are derived from carotenoids via carlactone, and act through the α/β–hydrolase D14 and the F–box protein D3/MAX2 to repress plant shoot branching. While MAX2 is also necessary for normal seedling development, D14 and the known strigolactone biosynthesis genes are not, raising the question of whether endogenous, canonical strigolactones derived from carlactone have a role in seedling morphogenesis. Here, we report the chemical synthesis of the strigolactone precursor carlactone, and show that it represses Arabidopsis shoot branching and influences leaf morphogenesis via a mechanism that is dependent on the cytochrome P450 MAX1. In contrast, both physiologically active Z–carlactone and the non‐physiological E isomer exhibit similar weak activity in seedlings, and predominantly signal through D14 rather than its paralogue KAI2, in a MAX2‐dependent but MAX1‐independent manner. KAI2 is essential for seedling morphogenesis, and hence this early‐stage development employs carlactone‐independent morphogens for which karrikins from wildfire smoke are specific surrogates. While the commonly employed synthetic strigolactone GR24 acts non‐specifically through both D14 and KAI2, carlactone is a specific effector of strigolactone signalling that acts through MAX1 and D14.
Adaptation to acidic soil is achieved by increased numbers of cis‐acting elements regulating ALMT1 expression in Holcus lanatus
Authors: Chen Zhi Chang , Yokosho Kengo , Kashino Miho , Zhao Fang‐Jie , Yamaji Naoki , Ma Jian Feng 
Published: June 2013

SummaryYorkshire fog (Holcus lanatus), which belongs to the Poaceae family and is a close relative of the agronomic crop oat (Avena sativa), is a widely adaptable grass species that is able to grow on highly acidic soils with high levels of Al, but the mechanism underlying the high Al tolerance is unknown. Here, we characterized two accessions of H. lanatus collected from an acid plot (soil pH 3.6, HL–A) and a neutral plot (pH 7.1, HL–N) in terms of Al tolerance, organic acid anion secretion and related gene expression. In response to Al (pH 4.5), the HL–A roots secreted approximately twice as much malate as the HL–N roots, but there was no difference in citrate secretion. Cloning of the gene HlALMT1 responsible for malate secretion showed that the encoded amino acid sequence did not differ between two accessions, but the expression level in the outer cell layers of the HL–A roots was twice as high as in the HL–N roots. This difference was not due to the genomic copy number, but was due to the number of cis‐acting elements for an Al‐responsive transcription factor (HlART1) in the promoter region of HlALMT1, as demonstrated by both a yeast one‐hybrid assay and a transient assay in tobacco protoplasts. Furthermore, introduction of HlALMT1 driven by the HL–A promoter into rice resulted in significantly more Al‐induced malate secretion than introduction of HlALMT1 driven by the HL–N promoter. These findings indicate that the adaptation of H. lanatus to acidic soils may be achieved by increasing number of cis‐acting elements for ART1 in the promoter region of the HlALMT1 gene, enhancing the expression of HlALMT1 and the secretion of malate.
Discovery of Plant Phenolic Compounds That Act as Type III Secretion System Inhibitors or Inducers of the Fire Blight Pathogen, Erwinia amylovora
Authors: Khokhani Devanshi , Zhang Chengfang , Li Yan , Wang Qi , Zeng Quan , Yamazaki Akihiro , Hutchins William , Zhou Shan-Shan , Chen Xin , Yang Ching-Hong 
Published: June 2013

ABSTRACT

Erwinia amylovora
causes a devastating disease called fire blight in rosaceous plants. The type III secretion system (T3SS) is one of the important virulence factors utilized by
E. amylovora
in order to successfully infect its hosts. By using a green fluorescent protein (GFP) reporter construct combined with a high-throughput flow cytometry assay, a library of phenolic compounds and their derivatives was studied for their ability to alter the expression of the T3SS. Based on the effectiveness of the compounds on the expression of the T3SS pilus, the T3SS inhibitors 4-methoxy-cinnamic acid (TMCA) and benzoic acid (BA) and one T3SS inducer,
trans
-2-(4-hydroxyphenyl)-ethenylsulfonate (EHPES), were chosen for further study. Both the T3SS inhibitors (TMCA and BA) and the T3SS inducer (EHPES) were found to alter the expression of T3SS through the HrpS-HrpL pathway. Additionally, TMCA altered T3SS expression through the

rsmB
Ea

-RsmA
Ea
system. Finally, we found that TMCA and BA weakened the hypersensitive response (HR) in tobacco by suppressing the T3SS of
E. amylovora
. In our study, we identified phenolic compounds that specifically targeted the T3SS. The T3SS inhibitor may offer an alternative approach to antimicrobial therapy by targeting virulence factors of bacterial pathogens.
Dry/Wet Cycles Change the Activity and Population Dynamics of Methanotrophs in Rice Field Soil
Authors: Ma Ke , Conrad Ralf , Lu Yahai 
Published: June 2013

ABSTRACTThe methanotrophs in rice field soil are crucial in regulating the emission of methane. Drainage substantially reduces methane emission from rice fields. However, it is poorly understood how drainage affects microbial methane oxidation. Therefore, we analyzed the dynamics of methane oxidation rates, composition (using terminal restriction fragment length polymorphism [T-RFLP]), and abundance (using quantitative PCR [qPCR]) of methanotrophpmoAgenes (encoding a subunit of particulate methane monooxygenase) and their transcripts over the season and in response to alternate dry/wet cycles in planted paddy field microcosms.In situmethane oxidation accounted for less than 15% of total methane production but was enhanced by intermittent drainage. The dry/wet alternations resulted in distinct effects on the methanotrophic communities in different soil compartments (bulk soil, rhizosphere soil, surface soil). The methanotrophic communities of the different soil compartments also showed distinct seasonal dynamics. In bulk soil, potential methanotrophic activity and transcription ofpmoAwere relatively low but were significantly stimulated by drainage. In contrast, however, in the rhizosphere and surface soils, potential methanotrophic activity andpmoAtranscription were relatively high but decreased after drainage events and resumed after reflooding. While type II methanotrophs dominated the communities in the bulk soil and rhizosphere soil compartments (and to a lesser extent also in the surface soil), it was thepmoAof type I methanotrophs that was mainly transcribed under flooded conditions. Drainage affected the composition of the methanotrophic community only minimally but strongly affected metabolically active methanotrophs. Our study revealed dramatic dynamics in the abundance, composition, and activity of the various type I and type II methanotrophs on both a seasonal and a spatial scale and showed strong effects of dry/wet alternation cycles, which enhanced the attenuation of methane flux into the atmosphere.
Strain-Dependent Augmentation of Tight-Junction Barrier Function in Human Primary Epidermal Keratinocytes by Lactobacillus and Bifidobacterium Lysates
Authors: Sultana Reshma , McBain Andrew J. , O'Neill Catherine A. 
Published: June 2013

ABSTRACT

In this study, we investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from
Bifidobacterium longum
,
Lactobacillus plantarum
,
Lactobacillus reuteri
,
Lactobacillus fermentum
, or
Lactobacillus rhamnosus
GG. With the exception of
L. fermentum
(which decreased cell viability), all strains markedly enhanced tight-junction barrier function within 24 h, as assessed by measurements of transepithelial electrical resistance (TEER). However,
B. longum
and
L. rhamnosus
GG were the most efficacious, producing dose-dependent increases in resistance that were maintained for 4 days. These increases in TEER correlated with elevated expression of tight-junction protein components. Neutralization of Toll-like receptor 2 abolished both the increase in TEER and expression of tight-junction proteins induced by
B. longum
, but not
L. rhamnosus
GG. These data suggest that some bacterial strains increase tight-junction function via modulation of protein components but the different pathways involved may vary depending on the bacterial strain.