bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nature and nurture: a case of transcending haematological pre‐malignancies in a pair of monozygotic twins adding possible clues on the pathogenesis of B‐cell proliferations
Authors: Hansen Marcus C. , Nyvold Charlotte G. , Roug Anne S. , Kjeldsen Eigil , Villesen Palle , Nederby Line , Hokland Peter 
Published: March 2015

SummaryWe describe a comprehensive molecular analysis of a pair of monozygotic twins, who came to our attention when one experienced amaurosis fugax and was diagnosed with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic B‐cell chronic lymphocytic leukaemia (B‐CLL). Although JAK2−, Twin B was subsequently shown to have a benign monoclonal B‐cell lymphocytosis (MBL). Flow cytometric and molecular analyses of the B‐cell compartments revealed different immunoglobulin light and heavy chain usage in each twin. We hypothesized that whole exome sequencing could help delineating the pattern of germline B‐cell disorder susceptibility and reveal somatic mutations potentially contributing to the differential patterns of pre‐malignancy. Comparing bone marrow cells and T cells and employing in‐house engineered integrative analysis, we found aberrations in Twin A consistent with a myeloid neoplasm, i.e. in TET2, RUNX1, PLCB1 and ELF4. Employing the method for detecting high‐ranking variants by extensive annotation and relevance scoring, we also identified shared germline variants in genes of proteins interacting with B‐cell receptor signalling mediators and the WNT‐pathway, including IRF8, PTPRO, BCL9L, SIT1 and SIRPB1, all with possible implications in B‐cell proliferation. Similar patterns of IGHV‐gene usage to those demonstrated here have been observed in inherited acute lymphoblastic leukaemia. Collectively, these findings may help in facilitating identification of putative master gene(s) involved in B‐cell proliferations in general and MBL and B‐CLL in particular.
Immune parameter analysis of children with sickle cell disease on hydroxycarbamide or chronic transfusion therapy
Authors: Nickel Robert S. , Osunkwo Ifeyinwa , Garrett Aneesah , Robertson Jennifer , Archer David R. , Promislow Daniel E.L. , Horan John T. , Hendrickson Jeanne E. , Kean Leslie S. 
Published: March 2015

SummarySickle cell disease (SCD) is increasingly appreciated as an inflammatory condition associated with alterations in immune phenotype and function. In this cross‐sectional study we performed a multiparameter analysis of 18 immune markers in 114 paediatric SCD patients divided by treatment group [those receiving hydroxycrabamide (HC, previously termed hydroxyurea), chronic transfusion (CT), or no disease‐modifying therapy] and 29 age‐matched African American healthy controls. We found global elevation of most immune cell counts in SCD patients receiving no disease‐modifying therapy at steady state. Despite the decrease in percentage of haemoglobin S associated with CT therapy, the abnormal cellular immune phenotype persisted in patients on CT. In contrast, in both univariate and multivariate analysis, treatment with HC was associated with normalization of the vast majority of leucocyte populations. This study provides additional support for HC treatment in SCD, as it appears that HC decreases the abnormally elevated immune cell counts in patients with SCD.
Salidroside ameliorates insulin resistance through activation of a mitochondria‐associated AMPK/PI3K/Akt/GSK3β pathway
Authors: Zheng Tao , Yang Xiaoyan , Wu Dan , Xing Shasha , Bian Fang , Li Wenjing , Chi Jiangyang , Bai Xiangli , Wu Guangjie , Chen Xiaoqian , Zhang Yonghui , Jin Si 
Published: March 2015

Background and PurposeRecent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP‐activated protein kinase (AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms.Experimental ApproachThe therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg−1·day−1) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro.Key ResultsSalidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose‐dependently induced an increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen synthase kinase 3β (GSK3β) in hepatocytes. Furthermore, salidroside‐stimulated AMPK activation was found to suppress the expression of PEPCK and glucose‐6‐phosphatase. Salidroside‐induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ATP ratio.Conclusions and ImplicationsSalidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria‐related AMPK/PI3K/Akt/GSK3β pathway
Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators ofP2X7 receptors
Authors: Helliwell R M , ShioukHuey C O , Dhuna K , Molero J C , Ye J‐M , Xue C C , Stokes L 
Published: March 2015

Background and PurposeTheP2X7 receptor is anATP‐gated ion channel predominantly expressed in immune cells and plays a key role in inflammatory processes. Ginseng is a well‐knownChinese herb with both pro‐ and anti‐inflammatory properties and many of its actions have been ascribed to constituent ginsenosides. We screened a number of ginsenoside compounds for pharmacological activity atP2X7 receptors, that might contribute to the reported immunomodulatory actions of ginseng.Experimental ApproachWe used several assays to measure responses ofP2X7 receptors,ATP‐mediated dye uptake, intracellular calcium measurement and whole‐cell patch‐clamp recordings.HEK‐293 cells stably expressing humanP2X7 receptors were used in addition to mouse macrophages endogenously expressingP2X7 receptors.Key ResultsFour ginsenosides of the protopanaxdiol series,Rb1,Rh2, Rd and the metabolite compoundK(CK) potentiated the dye uptake responses ofP2X7 receptors, whereas other ginsenosides tested were ineffective (1–10 μM). The potentiation was rapid in onset, required a threshold concentration ofATP(>50 μM) and had anEC50of 1.08 μM.CKmarkedly enhancedATP‐activatedP2X7 currents, probably via an extracellular site of action. One of the consequences of this potentiation effect is a sustained rise in intracellularCa2+that could account for the decrease in cell viability in mouse macrophages after a combination of 500 μMATPand 10 μMCKthat are non‐toxic when applied alone.Conclusions and ImplicationsThis study identifies selected ginsenosides as novel potent allosteric modulators ofP2X7 channels that may account for some of the reported immune modulatory actions of protopanaxdiol ginsenosidesin vivo.
Involvement of fibrocytes in asthma and clinical implications
Authors: Mattoli S. 
Published: March 2015

SummaryBloodborne fibrocytes are bone marrow‐derived cells that participate in immune responses and exhibit pro‐inflammatory and matrix remodelling properties. In patients with asthma receiving an adequate treatment, the blood fibrocyte count is very low and comparable to that obtained in healthy individuals. In these patients, a transient increase in fibrocyte numbers in the peripheral blood and in the airways occurs in concomitance with increased bronchial inflammation and reflects disease worsening and the need for more intensive treatment. Persistently elevated numbers of fibrocytes in the peripheral blood and in the bronchial mucosa are observed in chronically undertreated or corticosteroid‐resistant asthma and are associated with persistent airway inflammation and ongoing remodelling of the bronchial wall. The asthmatic bronchial epithelium is the main source of fibrocyte chemoattractants in asthma and contributes with T helper type 2 lymphocytes and eosinophils to promote the proliferation and pro‐remodelling function of recruited fibrocytes. The presence of elevated numbers of fibrocytes in the bronchial mucosa of allergic patients with undertreated or treatment‐resistant asthma may also increase the risk of acute exacerbations because these cells can amplify T helper type 2 lymphocyte‐driven inflammation on every exposure to the clinically relevant allergen and can promote further inflammation on rhinovirus infections by allowing viral replication and releasing additional pro‐inflammatory factors. Improved methods for the isolation and functional analysis of pure populations of viable circulating fibrocytes have allowed a better understanding of the effector role of these cells. A reliable and clinically applicable assay has been developed to measure blood fibrocyte counts as outcome measure in future clinical trials. New therapeutic agents are needed to block both persistent inflammation and fibrocytosis in corticosteroid‐resistant asthma.
Mating frequency positively associates with fitness in Ophraella communa
Authors: ZHOU ZHONG‐SHI , RASMANN SERGIO , ZHENG HAI‐YAN , WATSON ALAN , GUO JIAN‐YING , WANG JIAN‐GUO , WAN FANG‐HAO 
Published: March 2015

1. Why animals mate multiple times, owing to the lack of immediate fitness benefits, presents an intriguing problem for evolutionary biologists. Yet, the profusion of this behaviour suggests it must be maintained by natural selection via increased performance.2. The possible benefits of multiple mating using the leaf beetles Ophraella communa LeSage, the biological control agent of the invasive common ragweed Ambrosia artemisiifolia L., were studied and the fitness consequences of single, twice, three, four, and unrestricted mating events were assessed.3. Overall, it was observed that the number of copulation events was positively associated with fitness parameters of the insects. Insects performed the best under unrestricted mating regimes, with average increases of 48% in longevity, 75% in fecundity, and 55% in egg hatch rate. In addition, females that experienced unrestricted access to mates maintained very high viability over their entire reproductive lives. Nevertheless, insects also performed better when allowed to mate four times compared with once or twice.4. The present findings thus support the hypothesis that multiple‐mating behaviour is maintained owing to increased fitness benefits in the current and the next generation. Selection for re‐mating is, therefore, expected in field populations, which is likely to happen naturally owing to the aggregate lifestyle of O. communa.
Increased bilirubin levels in de novo Parkinson's disease
Authors: Moccia M. , Picillo M. , Erro R. , Longo K. , Amboni M. , Santangelo G. , Palladino R. , Allocca R. , Caporale O. , Triassi M. , Pellecchia M. T. , Barone P. , Vitale C. 
Published: March 2015

Background and purposeOxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO−bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression.MethodsA cross‐sectional case−control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug‐naïve PD subjects and controls. Afterwards, PD subjects were included in a 2‐year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels.ResultsSeventy‐five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2‐year follow‐up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa‐equivalent daily dosage (P = 0.012) were found.ConclusionsParkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.
Comparative genomics reveals conservation of filaggrin and loss of caspase‐14 in dolphins
Authors: Strasser Bettina , Mlitz Veronika , Fischer Heinz , Tschachler Erwin , Eckhart Leopold 
Published: March 2015

AbstractThe expression of filaggrin and its stepwise proteolytic degradation are critical events in the terminal differentiation of epidermal keratinocytes and in the formation of the skin barrier to the environment. Here, we investigated whether the evolutionary transition from a terrestrial to a fully aquatic lifestyle of cetaceans, that is dolphins and whales, has been associated with changes in genes encoding filaggrin and proteins involved in the processing of filaggrin. We used comparative genomics, PCRs and re‐sequencing of gene segments to screen for the presence and integrity of genes coding for filaggrin and proteases implicated in the maturation of (pro)filaggrin. Filaggrin has been conserved in dolphins (bottlenose dolphin, orca and baiji) but has been lost in whales (sperm whale and minke whale). All other S100 fused‐type genes have been lost in cetaceans. Among filaggrin‐processing proteases, aspartic peptidase retroviral‐like 1 (ASPRV1), also known as saspase, has been conserved, whereas caspase‐14 has been lost in all cetaceans investigated. In conclusion, our results suggest that filaggrin is dispensable for the acquisition of fully aquatic lifestyles of whales, whereas it appears to confer an evolutionary advantage to dolphins. The discordant evolution of filaggrin, saspase and caspase‐14 in cetaceans indicates that the biological roles of these proteins are not strictly interdependent.
UVB induces epidermal 11β‐hydroxysteroid dehydrogenase type 1 activity in vivo
Authors: Tiganescu Ana , Hupe Melanie , Jiang Yan J. , Celli Anna , Uchida Yoshikazu , Mauro Theodora M. , Bikle Daniel D. , Elias Peter M. , Holleran Walter M. 
Published: March 2015

AbstractDetrimental consequences of ultraviolet radiation (UVR) in skin include photoageing, immunosuppression and photocarcinogenesis, processes also significantly regulated by local glucocorticoid (GC) availability. In man, the enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) generates the active GC cortisol from cortisone (or corticosterone from 11‐dehydrocorticosterone in rodents). 11β‐HSD1 oxo‐reductase activity requires the cofactor NADPH, generated by hexose‐6‐phosphate dehydrogenase. We previously demonstrated increased 11β‐HSD1 levels in skin obtained from photoexposed versus photoprotected anatomical regions. However, the direct effect of UVR on 11β‐HSD1 expression remains to be elucidated. To investigate the cutaneous regulation of 11β‐HSD1 following UVR in vivo, the dorsal skin of female SKH1 mice was irradiated with 50, 100, 200 and 400 mJ/cm2 UVB. Measurement of transepidermal water loss, 11β‐HSD1 activity, mRNA/protein expression and histological studies was taken at 1, 3 and 7 days postexposure. 11β‐HSD1 and hexose‐6‐phosphate dehydrogenase mRNA expression peaked 1 day postexposure to 400 mJ/cm2 UVB before subsequently declining (days 3 and 7). Corresponding increases in 11β‐HSD1 protein and enzyme activity were observed 3 days postexposure coinciding with reduced GC receptor mRNA expression. Immunofluorescence studies revealed 11β‐HSD1 localization to hyperproliferative epidermal keratinocytes in UVB‐exposed skin. 11β‐HSD1 expression and activity were also induced by 200 and 100 (but not 50) mJ/cm2 UVB and correlated with increased transepidermal water loss (indicative of barrier disruption). UVB‐induced 11β‐HSD1 activation represents a novel mechanism that may contribute to the regulation of cutaneous responses to UVR exposure.
Efficient transposition of the youngest miniature inverted repeat transposable element family of yellow fever mosquito in yeast
Authors: Fattash Isam , Lee Chia‐Ni , Mo Kaiguo , Yang Guojun 
Published: March 2015

Miniature inverted repeat transposable elements (MITEs) are often the most numerous DNA transposons in plant and animal genomes. The dramatic amplification of MITE families during evolution is puzzling, because the transposase sources for the vast majority of MITE families are unknown. The yellow fever mosquito genome contains > 220‐Mb MITE sequences; however, transposition activity has not been demonstrated for any of the MITE families. The Gnome elements are the youngest MITE family in this genome, with at least 116 identical copies. To test whether the putative autonomous element Ozma is capable of mobilizing Gnome and its two sibling MITEs, analyses were performed in a yeast transposition assay system. Whereas the wild‐type transposase resulted in very low transposition activity, mutations in the region containing a putative nuclear export signal motif resulted in a dramatic (at least 4160‐fold) increase in transposition frequency. We have also demonstrated that each residue of the novel DD37E motif is required for the activity of the Ozma transposase. Footprint sequences left at the donor sites suggest that the transposase may cleave between the second and the third nucleotides from the 5' ends of the elements. The excised elements reinsert specifically at dinucleotide ‘TA’, ~ 55% of them in yeast genes. The elements described in this article could potentially be useful as genetic tools for genetic manipulation of mosquitoes.
Local and transnational care relations: relatedness and family practice among au pairs in Denmark
Authors: DALGAS KARINA MÄRCHER , OLWIG KAREN FOG 
Published: March 2015

AbstractAn increasing number of young women from the Global South have become au pairs in the Global North since the turn of the millennium. Through ethnographic analysis of three cases of au pairing in Denmark, involving Filipina and Caribbean women, this article discusses the nature of the local as well as transnational family relations in which these women are embedded as au pairs, and the opportunities and restraints that they present. We use anthropological theory to conceptualize family and kinship in terms of notions and practices of relatedness. This offers a useful framework for elucidating the different moral and contractual obligations and expectations associated with these varying family relations, the power asymmetries with which they are linked, and the agency that the au pairs display as they seek to position themselves in the most favourable way in relation to the multi‐directional ties in which they are involved.
Green Synthesis of ZnO Nanoparticles and Its Application in the Degradation of Some Dyes
Authors: Davar Fatemeh , Majedi Ali , Mirzaei Alireza 
Published: March 2015

A novel ZnO photocatalyst was synthesized by a green method using lemon juice and zinc acetate as precursors, and then the effect of sucrose addition on the initial precursors was investigated. The samples were characterized by field‐emission scanning electron microscopy, X‐ray diffraction, Fourier transform infrared, UV‐visible, and photoluminescence analysis. The result showed that the as‐obtained products with the mix of lemon juice (30 mL) and sucrose had a spherical morphology with the mean particle size of about 21.5 nm. The photocatalytic activity of this sample was tested for the degradation of methyl orange, methyl red and methylene blue solutions. The results also revealed the good photocatalytic activity for the degradation of these three organic dyes. Furthermore, as‐synthesized sample was used in decolorization processes and the treatment of textile dyes (reactive blue 21).
The impact of three nursing staffing models on nursing outcomes
Authors: Yang Pei‐Hsuan , Hung Chich‐Hsiu , Chen Yu‐Chin 
Published: March 2015

AbstractAimTo examine the impact of application of different nursing staffing models on patient safety, quality of care and nursing costs.BackgroundOne proposed means of addressing the staff shortage while decreasing nursing costs is the application of nursing staffing models. However, the optimal proportion of registered nurses to nurse aides remains unclear.DesignA retrospective cohort study.MethodsTo examine a total of 667 inpatients of a 20‐bed respiratory care centre at a medical centre located in southern Taiwan. Three mixed models of nursing staffing, where the portion of nurses compared with nurse aides was 76% (n = 213), 100% (n = 209) and 92% (n = 245), were applied during three different periods between 2006 – 2010.ResultsThe 76% RNs group made fewer medication errors than the 100% RNs group; the 76% and 92% RNs groups had a higher rate of urinary tract infections; the 92% RNs group had a lower rate of bloodstream infections; the 76% RNs group had a lower rate of ventilator weaning; and the 76% and 92% RNs groups incurred higher nursing costs.ConclusionsUse of different nursing staffing models that substitute nurse aides for RNs may negatively affect patient safety and quality of care and increase nursing costs. To avoid this risk, hospitals should employ and train their own nurse aides and develop a training system and education materials for RN and nurse aides.
The vascularized periosteum flap as novel tissue engineering model for repair of cartilage defects
Authors: Harhaus Leila , Huang Jung‐Ju , Kao Shu‐Wei , Wu Yen‐Lin , Mackert Gina Alicia , Höner Bernd , Cheng Ming‐Huei , Kneser Ulrich , Cheng Chao‐Min 
Published: March 2015

AbstractPeriosteum is a promising tissue engineering scaffold in research of cartilage repair; so far however, periosteum transfers have not been realized successfully because of insufficient nourishment of the graft. In a translational approach we, for the first time, designed a vascularized periosteum flap as ‘independent’ biomaterial with its own blood supply to address this problem and to reconstruct circumscript cartilage defects. In six 3‐month‐old New Zealand rabbits, a critical size cartilage defect of the medial femur condyle was created and covered by a vascularized periosteum flap pedicled on the saphenous vessels. After 28 days, formation of newly built cartilage was assessed macroscopically, histologically and qualitatively via biomechanical compression testing, as well as on molecular biological level via immunohistochemistry. All wounds healed completely, all joints were stable and had full range of motion. All flaps survived and were perfused through their pulsating pedicles. They showed a stable attachment to the bone, although partially incomplete adherence. Hyaline cartilage with typical columnar cell distribution and positive Collagen II staining was formed in the transferred flaps. Biomechanical testing revealed a significantly higher maximum load than the positive control, but a low elasticity. This study proved that vascularization of the periosteum flap is the essential step for flap survival and enables the flap to transform into cartilage. Reconstruction of circumscript cartilage defects seems to be possible. Although these are the first results out of a pilot project, this technique, we believe, can have a wide range of potential applications and high relevance in the clinical field.