bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐distance dispersal during the middle–late Pleistocene explains the bipolar disjunction of Carex maritima (Cyperaceae)
Authors: Villaverde Tamara , Escudero Marcial , Luceño Modesto , Martín‐Bravo Santiago 
Published: June 2015

AbstractAimWe set out to explain the bipolar distribution of Carex maritima, clarifying the direction and timing of dispersal. We also tested mountain‐hopping and direct long‐distance dispersal hypotheses, as well as the relationship of C. maritima with biotic and abiotic factors that could explain the bipolar distribution.LocationArctic/boreal latitudes of both hemispheres.MethodsMolecular and bioclimatic data were obtained for C. maritima and related species from section Foetidae. We sequenced two (rps16 and 5′trnK intron) plastid DNA regions (cpDNA) and the external and internal transcribed spacers (ETS and ITS) of the nuclear ribosomal gene region (nrDNA) and inferred phylogenetic relationships, divergence time estimates and biogeographical patterns using maximum likelihood, statistical parsimony, Bayesian inference and ecological niche modelling.ResultsCarex maritima populations from the Southern Hemisphere were genetically and ecologically differentiated from their northern counterparts and formed a monophyletic group nested within a paraphyletic C. maritima. Divergence time analysis estimated a middle–late Pleistocene divergence of the southern lineage (0.23 Ma; 95% highest posterior density: 0.03–0.51 Ma). Southern Hemisphere populations are more stenotopic than the Northern Hemisphere ones, which tolerate harsher conditions.Main conclusionsOur results point to a middle–late Pleistocene migration of C. maritima by long‐distance dispersal, either directly or via mountain‐hopping, from the Northern Hemisphere to the Southern Hemisphere.
Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1‐mediated mitochondrial fission
Authors: Zhang Jinjin , Xu Pan , Wang Youlei , Wang Meirong , Li Hongbo , Lin Shengcui , Mao Cuiping , Wang Bingsi , Song Xiaodong , Lv Changjun 
Published: June 2015

AbstractPromotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin‐related protein‐1 (Drp1)‐mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro‐apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin‐induced mitochondrial fission and apoptosis in myofibroblasts. Drp1‐associated genes, such as Bcl‐2‐associated X protein, cytochrome c, tumour suppressor gene p53 and p53‐up‐regulated modulator of apoptosis, were highly up‐regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1‐dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.
Shp‐2 contributes to anti‐RSV activity in human pulmonary alveolar epithelial cells by interfering with the IFN‐α‐induced Jak/Stat1 pathway
Authors: Wang Saisai , Zheng Gang , Zhao Lifang , Xu Feng , Qian Jing 
Published: June 2015

AbstractSrc homology phosphotyrosyl phosphatase 2 (Shp‐2) is a ubiquitously expressed protein that is involved in a variety of cellular processes, including antiviral interferon signalling pathways. In this study, we investigated the role of Shp‐2 in the host cell interactions of human respiratory syncytial virus (RSV). We report significant changes in the expression of Shp‐2 in human pulmonary alveolar epithelial cells (A549) upon RSV infection. We also report that blocking Shp‐2 does not affect viral replication or virus‐induced interferon‐alpha (IFN‐α) production. Interestingly, whereas A549 cells were activated by IFN‐α, the blocking of Shp‐2 resulted in increased viral replication that was associated with the reduced expression of the IFN‐stimulated genes of 2′,5′‐oligoadenylate synthetases and Mx1, and the concomitant inhibition of Stat1 tyrosine phosphorylation. Our findings suggest that Shp‐2 contributes to the control of RSV replication and progeny production in pulmonary alveolar epithelial cells by interfering with IFN‐α‐induced Jak/Stat1 pathway activation rather than by affecting the production of IFN‐α itself.
Feasibility of immediate placement of single‐tooth implants in the aesthetic zone: a 1‐year randomized controlled trial
Authors: Slagter Kirsten W. , Meijer Henny J.A. , Bakker Nicolaas A. , Vissink Arjan , Raghoebar Gerry M. 
Published: June 2015

AbstractAimTo assess whether outcome of immediate implant placement and immediate provisionalization after 1 year was non‐inferior to immediate implant placement and delayed provisionalization regarding Marginal Bone Level (MBL).Materials and MethodsForty patients with a failing tooth in the aesthetic zone were randomly assigned for immediate implant placement with immediate (n = 20) or delayed (n = 20) provisionalization. Follow‐up was at 1 month and after 1 year. The study was powered to detect a difference in MBL of <0.9 mm. Apart from MBL, soft tissue peri‐implant parameters, aesthetic indexes and patient satisfaction were assessed.ResultsAfter 1 year, MBL changes were −0.75 ± 0.69 mesially and −0.68 ± 0.65 distally mm for the immediate group and −0.70 ± 0.64 and −0.68 ± 0.64 mm for the delayed group respectively (NS). Regarding differences in means, non‐inferiority was observed after 1 year (mesially: Group A versus B: difference in mean 0.08 mm (95% CI −0.38 to 0.53, p = 0.71 distally: Group A versus B: difference in mean 0.09 mm (95% CI −0.37 to 0.56 mm, p = 0.66).No significant differences in the other outcome variables were observed.ConclusionsThis study showed that immediate placement and immediate provisionalization was non‐inferior to immediate placement with delayed provisionalization. In addition, although not powered for these outcome variables, no clinically relevant differences in other outcomes were observed (www.isrtcn.com: ISRCTN57251089).
Heterogeneity of Notch signaling in astrocytes and the effects of GFAP and vimentin deficiency
Authors: Lebkuechner Isabell , Wilhelmsson Ulrika , Möllerström Elin , Pekna Marcela , Pekny Milos 
Published: June 2015

AbstractAstrocytes have multiple roles in the CNS including control of adult neurogenesis. We recently showed that astrocyte inhibition of neurogenesis through Notch signaling depends on the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Here, we used real‐time quantitative PCR to analyze gene expression in individual mouse astrocytes in primary cultures and in GFAPPOS or Aldh1L1POS astrocytes freshly isolated from uninjured, contralesional and lesioned hippocampus 4 days after entorhinal cortex lesion. To determine the Notch signaling competence of individual astrocytes, we measured the mRNA levels of Notch ligands and Notch1 receptor. We found that whereas most cultured and freshly isolated astrocytes were competent to receive Notch signals, only a minority of astrocytes were competent to send Notch signals. Injury increased the fraction of astrocyte subpopulation unable to send and receive Notch signals, thus resembling primary astrocytes in vitro. Astrocytes deficient of GFAP and vimentin showed decreased Notch signal sending competence and altered expression of Notch signaling pathway‐related genes Dlk2, Notch1, and Sox2. Furthermore, we identified astrocyte subpopulations based on their mRNA and protein expression of nestin and HB‐EGF. This study improves our understanding of astrocyte heterogeneity, and points to astrocyte cytoplasmic intermediate filaments as targets for neural cell replacement strategies.
imageWe previously demonstrated that Notch signaling from astrocytes to neural stem cells, that inhibits neurogenesis, depends on the intermediate filament (nanofilament) system of astrocytes. Here we report the existence of four subpopulations of astrocytes with respect to their Notch signaling competence. We show that the fraction of astrocytes that are Notch signaling incompetent increases after brain injury and corresponds to the fraction of Notch signaling incompetent astrocytes in primary astrocyte cultures. We also demonstrate that the subpopulation of Notch signal sending competent astrocytes decreases when their intermediate filament system is genetically ablated.
Glucose is a positive modulator for the activation of human recombinant glycine receptors
Authors: Breitinger Ulrike , Raafat Karim M. , Breitinger Hans‐Georg 
Published: June 2015

AbstractThe inhibitory glycine receptor (GlyR), a cys–loop ion channel receptor, mediates rapid synaptic inhibition in spinal cord, brainstem and higher centres of the mammalian central nervous system. Here, modulation of GlyR function by glucose and fructose was examined in recombinant alpha1 and alpha1/beta GlyRs using patch‐clamp methods. Glucose was a positive modulator of the receptor, reducing the average EC50 for glycine up to 4.5‐fold. Glucose reduced cell‐to‐cell variability of glycine‐mediated currents by stabilizing receptors with low EC50. Pre‐incubation with sugars for several hours also produced augmentation of current responses that persisted after sugar removal. Potentiation by sugars was most significant in the range between 5 and 20 mM, with EC50 values ~ 10 mM, i.e. at physiological levels. Addition of glucose had no significant influence on responses mediated by the other GlyR agonists like taurine, β‐alanine or ivermectin, indicating that glucose specifically augmented glycine receptor‐mediated responses, and did not act through indirect metabolic effects. Receptor modulation by glucose may account for differences in constants reported in the literature and may be clinically relevant for disorders with elevated blood glucose levels.image
Glucose and related sugars are essential metabolites. We identified glucose and fructose as positive modulators of the human inhibitory glycine receptor, a neuronal ligand‐gated ion channel. Receptor‐mediated currents were enhanced at physiological concentrations (~ 10 mM of sugar). Direct modulation of a synaptic receptor by glucose is relevant in clinical cases of elevated blood glucose, and may be considered in experimental protocols.
Dickkopf‐related protein 3 is a potential Aβ‐associated protein in Alzheimer's Disease
Authors: Bruggink Kim A. , Kuiperij H. Bea , Gloerich Jolein , Otte‐Höller Irene , Rozemuller Annemieke J.M. , Claassen Jurgen A.H.R. , Küsters Benno , Verbeek Marcel M. 
Published: June 2015

AbstractAmyloid‐β (Aβ) is the most prominent protein in Alzheimer's disease (AD) senile plaques. In addition, Aβ interacts with a variety of Aβ‐associated proteins (AAPs), some of which can form complexes with Aβ and influence its clearance, aggregation or toxicity. Identification of novel AAPs may shed new light on the pathophysiology of AD and the metabolic fate of Aβ. In this study, we aimed to identify new AAPs by searching for proteins that may form soluble complexes with Aβ in CSF, using a proteomics approach. We identified the secreted Wnt pathway protein Dickkopf‐related protein 3 (Dkk‐3) as a potential Aβ‐associated protein. Using immunohistochemistry on human AD brain tissue, we observed that (i) Dkk‐3 co‐localizes with Aβ in the brain, both in diffuse and classic plaques. (ii) Dkk‐3 is expressed in neurons and in blood vessel walls in the brain and (iii) is secreted by leptomeningeal smooth muscle cells in vitro. Finally, measurements using ELISA revealed that (iv) Dkk‐3 protein is abundantly present in both cerebrospinal fluid and serum, but its levels are similar in non‐demented controls and patients with AD, Lewy body dementia, and frontotemporal dementia. Our study demonstrates that Dkk‐3 is a hitherto unidentified Aβ‐associated protein which, given its relatively high cerebral concentrations and co‐localization with Aβ, is potentially involved in AD pathology.
imageIn this study, we propose that Dickkopf‐related protein‐3 (Dkk‐3) might be a novel Amyloid‐β (Aβ) associated protein. We demonstrate that Dkk‐3 is expressed in the brain, especially in vessel walls, and co‐localizes with Aβ in senile plaques. Furthermore, Dkk‐3 levels in cerebrospinal fluid strongly correlate with Aβ40 levels, but were not suitable to discriminate non‐demented controls and patients with dementia.
The pathogenic role of the inflammasome in neurodegenerative diseases
Authors: Freeman Leslie C. , Ting Jenny P.‐Y. 
Published: June 2015

AbstractThe inflammasome is a large macromolecular complex that contains multiple copies of a receptor or sensor of pathogen‐derived or damage‐derived molecular patterns, pro‐caspase‐1, and an adaptor called ASC (apoptotic speck containing protein with a CARD), which results in caspase‐1 maturation. Caspase‐1 then mediates the release of pro‐inflammatory cytokines such as IL‐1β and IL‐18. These cytokines play critical roles in mediating immune responses during inflammation and innate immunity. Broader studies of the inflammasome over the years have implicated their roles in the pathogenesis of a variety of inflammatory diseases. Recently, studies have shown that the inflammasome modulates neuroinflammatory cells and the initial stages of neuroinflammation. A secondary cascade of events associated with neuroinflammation (such as oxidative stress) has been shown to activate the inflammasome, making the inflammasome a promising therapeutic target in the modulation of neurodegenerative diseases. This review will focus on the pathogenic role that inflammasomes play in neurologic diseases such as Alzheimer's disease, traumatic brain injury, and multiple sclerosis.
imageWe here review the role of the inflammasome in the pathogenesis of traumatic brain injury (TBI). TBI is initiated by physical force exerted to head, resulting in neuronal injury and death. Primary insult is followed by a secondary cascade of events following neuroinflammation such as mitochondrial dysfunction, production of reactive oxygen species, potassium effluxes, and release of circulating DNA. These events can potentially trigger the activation of NLRP3, NLRP1, and AIM2 during TBI but have yet to be confirmed (dashed lines). NLRP3, NLRP1, and AIM2 associate with the adaptor protein ASC, which initiates the cleavage of pro‐caspase‐1 to the mature form of caspase‐1 which cleaves pro‐IL‐1β and pro‐IL‐18 into their mature forms of IL‐1β and IL‐18.
Mutual induction of transcription factorPPARγ and microRNAs miR‐145 and miR‐329
Authors: Dharap Ashutosh , Pokrzywa Courtney , Murali Shruthi , Kaimal Balarama , Vemuganti Raghu 
Published: June 2015

AbstractMicroRNAs (miRNAs) are small non‐codingRNAs that are known to controlmRNAtranslation. Most miRNAs are transcribed from specific genes with well‐defined promoters located throughout the genome. The mechanisms that control miRNAexpression under normal and pathological conditions are not yet understood clearly. Peroxisome proliferator‐activated receptor (PPAR) γ is a ligand‐activated transcription factor that is extensively distributed in theCNS.PPARγ activation induces neuroprotection by modulating genes that contain peroxisome proliferator response elements (PPREs) in their promoters. We presently evaluated ifPPARγ modulates miRNAexpression. When adult rats were treated withPPARγ agonist rosiglitazone, expression of 28 miRNAs altered significantly (12 up‐ and 16 down‐regulated; 3–119 fold) in the cerebral cortex compared to vehicle‐treated controls.In silicoanalysis showed 1–5PPREs in the putative promoter regions (within 1 Kb upstream of the transcription start site) of these miRNAgenes. Cotransfection with aPPARγ constitutively expressing vector significantly induced the miR‐145 and miR‐329 promoter vectors (each have fourPPREs), which was curtailed by point mutations ofPPREs in their promoters. Interestingly, thePPARγ promoter has binding sites for both these miRNAs and transfection with miR‐329 mimic and miR‐145 mimic induced thePPARγ expression. Thus, these studies show a cyclical induction of miRNAs andPPARγ, indicating that the pleiotropic beneficial effects ofPPARγ agonists might be modulated in part by miRNAs and their down‐streammRNAs.imageWe proposed that promoters of many microRNAs contain the binding sites for the transcription factor PPARγ. Activation of PPARγ modulates the expression of these microRNAs. Two such PPARγ‐responsive microRNAs (miR‐145 and miR‐329) bind to PPARγ promoter to induce its expression. This indicates the presence of a feedback loop by which transcription factors and microRNAs can modulate each other.
Management of intestinal bleeding with single‐dose cyclophosphamide in Henoch–Schönlein purpura
Authors: Uluca Ünal , Ece Aydın , Şen Velat , Yel Servet , Tan İlhan , Karabel Duran 
Published: June 2015

AbstractIn these case series, we report on six children (3 girls, 3 boys) aged 5–13 years with Henoch–Schönlein purpura (HSP) who developed severe gastrointestinal (GI) bleeding resistant to both 2 mg/kg or pulse (10–30 mg/kg) i.v. methylprednisolone. All patients responded to single‐dose (500 mg/m2) i.v. cyclophosphamide (CPA) and none of them developed new GI bleeding after CPA treatment. No patients required surgical intervention. Single high‐dose CPA may be beneficial in HSP with severe GI involvement, in which bleeding is non‐responsive to high‐dose steroids.
Responses of Bacterial Communities to Simulated Climate Changes in Alpine Meadow Soil of the Qinghai-Tibet Plateau
Authors: Rui Junpeng , Li Jiabao , Wang Shiping , An Jiaxing , Liu Wen-tso , Lin Qiaoyan , Yang Yunfeng , He Zhili , Li Xiangzhen 
Published: June 2015

ABSTRACT

The soil microbial community plays an important role in terrestrial carbon and nitrogen cycling. However, microbial responses to climate warming or cooling remain poorly understood, limiting our ability to predict the consequences of future climate changes. To address this issue, it is critical to identify microbes sensitive to climate change and key driving factors shifting microbial communities. In this study, alpine soil transplant experiments were conducted downward or upward along an elevation gradient between 3,200 and 3,800 m in the Qinghai-Tibet plateau to simulate climate warming or cooling. After a 2-year soil transplant experiment, soil bacterial communities were analyzed by pyrosequencing of 16S rRNA gene amplicons. The results showed that the transplanted soil bacterial communities became more similar to those in their destination sites and more different from those in their “home” sites. Warming led to increases in the relative abundances in
Alphaproteobacteria
,
Gammaproteobacteria
, and
Actinobacteria
and decreases in
Acidobacteria
,
Betaproteobacteria
, and
Deltaproteobacteria
, while cooling had opposite effects on bacterial communities (symmetric response). Soil temperature and plant biomass contributed significantly to shaping the bacterial community structure. Overall, climate warming or cooling shifted the soil bacterial community structure mainly through species sorting, and such a shift might correlate to important biogeochemical processes such as greenhouse gas emissions. This study provides new insights into our understanding of soil bacterial community responses to climate warming and cooling.
Molecular and Physical Factors That Influence Attachment of Vibrio vulnificus to Chitin
Authors: Williams Tiffany C. , Ayrapetyan Mesrop , Oliver James D. 
Published: June 2015

ABSTRACT

The human pathogen
Vibrio vulnificus
is the leading cause of seafood-related deaths in the United States. Strains are genotyped on the basis of alleles that correlate with isolation source, with clinical (C)-genotype strains being more often implicated in disease and environmental (E)-genotype strains being more frequently isolated from oysters and estuarine waters. Previously, we have shown that the ecologically distinct C- and E-genotype strains of
V. vulnificus
display different degrees of chitin attachment, with C-genotype strains exhibiting reduced attachment relative to their E-genotype strain counterparts. We identified type IV pili to be part of the molecular basis for this observed genotypic variance, as E-genotype strains exhibit higher levels of expression of these genes than C-genotype strains. Here, we used a C-genotype quorum-sensing (QS) mutant to demonstrate that quorum sensing is a negative regulator of type IV pilus expression, which results in decreased chitin attachment. Furthermore, calcium depletion reduced E-genotype strain attachment to chitin, which suggests that calcium is necessary for proper functioning of the type IV pili in E-genotype strains. We also found that starvation or dormancy can alter the efficiency of chitin attachment, which has significant implications for the environmental persistence of
V. vulnificus
. With the increasing incidence of wound infections caused by
V. vulnificus
, we investigated a subset of E-genotype strains isolated from human wound infections and discovered that they attached to chitin in a manner more similar to that of C-genotype strains. This study enhances our understanding of the molecular and physical factors that mediate chitin attachment in
V. vulnificus
, providing insight into the mechanisms that facilitate the persistence of this pathogen in its native environment.
Polar Fixation of Plasmids during Recombinant Protein Production in Bacillus megaterium Results in Population Heterogeneity
Authors: Münch Karin M. , Müller Johannes , Wienecke Sarah , Bergmann Simone , Heyber Steffi , Biedendieck Rebekka , Münch Richard , Jahn Dieter 
Published: June 2015

ABSTRACT

During the past 2 decades,
Bacillus megaterium
has been systematically developed for the gram-per-liter scale production of recombinant proteins. The plasmid-based expression systems employed use a xylose-controlled promoter. Protein production analyses at the single-cell level using green fluorescent protein as a model product revealed cell culture heterogeneity characterized by a significant proportion of less productive bacteria. Due to the enormous size of
B. megaterium
, such bistable behavior seen in subpopulations was readily analyzed by time lapse microscopy and flow cytometry. Cell culture heterogeneity was not caused simply by plasmid loss: instead, an asymmetric distribution of plasmids during cell division was detected during the exponential-growth phase. Multicopy plasmids are generally randomly distributed between daughter cells. However,
in viv
o and
in vitro
experiments demonstrated that under conditions of strong protein production, plasmids are retained at one of the cell poles. Furthermore, it was found that cells with accumulated plasmids and high protein production ceased cell division. As a consequence, the overall protein production of the culture was achieved mainly by the subpopulation with a sufficient plasmid copy number. Based on our experimental data, we propose a model whereby the distribution of multicopy plasmids is controlled by polar fixation under protein production conditions. Thereby, cell lines with fluctuating plasmid abundance arise, which results in population heterogeneity. Our results provide initial insights into the mechanism of cellular heterogeneity during plasmid-based recombinant protein production in a
Bacillus
species.