bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating ischaemia‐reperfusion injury with prostaglandin E1 reduces the risk of early hepatocellular carcinoma recurrence following liver transplantation
Authors: Kornberg A. , Witt U. , Kornberg J. , Friess H. , Thrum K. 
Published: August 2015

SummaryBackgroundSurgical stress by hepatic ischaemia‐reperfusion (I/R) is supposed to promote intra‐ and extrahepatic tumour recurrence. Treatment with prostaglandin E1 (PGE1) has been shown to attenuate hepatic I/R injury in liver transplant patients, but the potential anti‐cancer effects have not been analysed.AimTo evaluate the impact of PGE1 therapy on risk of hepatocellular carcinoma (HCC) recurrence in liver transplant patients.MethodsA retrospective review of 106 liver transplant patients with HCC was conducted. Fifty‐nine patients underwent early post‐liver transplantation (LT) treatment with the stable PGE1 analogue alprostadil. Administration of alprostadil was correlated with outcome in uni‐ and multivariate analysis. Subgroup analysis focused on patients with HCC beyond the Milan criteria (Milan Out) on radiographic imaging.ResultsThree‐ and 5‐year recurrence‐free survival rates were 87.9% and 85.7% in the PGE1‐group, but only 65.3% and 63.1% in the non‐PGE1‐population (P = 0.003). Multivariate Cox regression analysis identified absence of PGE1‐treatment (HR = 11.42), along with presence of poor tumour grading (HR = 2.69) and microvascular tumour invasion (HR = 35.8) to be independently associated with early (within 12 months) HCC recurrence. In Milan Out‐patients, only therapy with PGE1 (HR = 5.09) and well/moderate tumour differentiation (HR = 6.51) were independent promoters of recurrence‐free survival.ConclusionsTreating hepatic ischaemia‐reperfusion injury with alprostadil reduces the risk of early HCC recurrence following LT. In particular patients with HCC exceeding the Milan criteria seem to benefit from PGE1‐treatment. The molecular mechanisms of the anti‐tumour effects need to be further assessed.
The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood
Authors: Reiss C. , Mindukshev I. , Bischoff V. , Subramanian H. , Kehrer L. , Friebe A. , Stasch J.‐P. , Gambaryan S. , Walter U. 
Published: August 2015

Background and PurposeStimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function.Experimental ApproachThe effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC‐specific effects of riociguat were determined by comparing wild‐type and platelet‐specific sGC‐knockout mice.Key ResultsRiociguat induced cGMP synthesis and subsequent PKG activation in human platelets, suggesting that the inhibitory effects are mediated by cGMP signalling. This finding was confirmed when sGC‐knockout platelets were not inhibited by riociguat. In washed human platelets, 100 nM riociguat reduced ADP‐induced GPIIb/IIIa activation, while a 10‐fold higher concentration was required to reduce convulxin‐stimulated GPIIb/IIIa activation. Riociguat inhibited ADP‐induced platelet shape change and aggregation, while ATP‐induced shape change remained unaffected. However, in PRP and whole blood, 50–100 μM riociguat was required to inhibit platelet activation and aggregation. Riociguat in combination with iloprost significantly inhibited platelet aggregation, even in whole blood.Conclusions and ImplicationsRiociguat inhibits platelet activation in whole blood only at concentrations above 50 μM, while the plasma concentrations in riociguat‐treated patients are 150 to 500 nM. This finding indicates that riociguat treatment does not affect platelet function in patients. Nevertheless, the possibility that riociguat acts synergistically with iloprost to inhibit platelet activation should be considered.
Crucial role of the orexin‐B C‐terminus in the induction of OX1 receptor‐mediated apoptosis: analysis by alanine scanning, molecular modelling and site‐directed mutagenesis
Authors: Nicole Pascal , Couvineau Pierre , Jamin Nadege , Voisin Thierry , Couvineau Alain 
Published: August 2015

Background and PurposeOrexins (A and B) are hypothalamic peptides that interact with OX1 and OX2 receptors and are involved in the sleep/wake cycle. We previously demonstrated that OX1 receptors are highly expressed in colon cancer tumours and colonic cancer cell lines where orexins induce apoptosis and inhibit tumour growth in preclinical animal models. The present study explored the structure–function relationships of orexin‐B and OX1 receptors.Experimental ApproachThe contribution of all orexin‐B residues in orexin‐B‐induced apoptosis was investigated by alanine scanning. To determine which OX1 receptor domains are involved in orexin‐B binding and apoptosis, a 3D model of OX1 receptor docked to the orexin‐B C‐terminus (AA‐20–28) was developed. Substitution of residues present in OX1 receptor transmembrane (TM) domains by site‐directed mutagenesis was performed.Key ResultsAlanine substitution of orexin‐B residues, L11, L15, A22, G24, I25, L26 and M28, altered orexin‐B's binding affinity. Substitution of these residues and of the Q16, A17, S18, N20 and T27 residues inhibited apoptosis in CHO‐S–OX1 receptor cells. The K120, P123, Y124, N318, K321, F340, T341, H344 and W345 residues localized in TM2, TM3, TM6 and TM7 of OX1 receptors were shown to play a role in orexin‐B recognition and orexin‐B/OX1 receptor‐induced apoptosis.Conclusions and ImplicationsThe C‐terminus of orexin‐B (i) plays an important role in its pro‐apoptotic effect; and (ii) interacts with some residues localized in the OX1 receptor TM. This study defines the structure–function relationship for orexin‐B recognition by human OX1 receptors and orexin‐B/OX1 receptor‐induced apoptosis, an important step for the future development of new agonist molecules.
Which Beta Is Best? On the Information Content of Option‐implied Betas
Authors: Baule Rainer , Korn Olaf , Saßning Sven 
Published: August 2015

AbstractOption‐implied betas are a promising alternative to historical beta estimators, because they are inherently forward‐looking and can incorporate new information immediately and fully. Recently, different implied beta estimators have been developed, but very little is known about their properties and information content. This paper presents a first systematic comparison between six different implied beta estimators, providing guidance for applications and identifying directions for further improvement. The analysis identifies explanatory factors for the predictive performance of implied estimators both in the cross section of stocks and over time. Furthermore, the analysis reveals patterns in the term structure of implied betas.
The impact of oral health on daily performances and its association with clinical variables in a population in Zambia
Authors: Andersson P , Kavakure J , Lingström P 
Published: August 2015

AbstractObjectiveThe aim of this study was to investigate oral impacts on daily performance and to relate these data to oral clinical variables.Material and methodsThe study was performed at a dental clinic in Livingstone, Zambia, and included 78 subjects (mean age 28, range 15–48 years) consecutively recruited in connection with a dental care visit. Data were collected through a structured interview using the Oral Impacts on Daily Performances (OIDP) index measuring oral health‐related quality of life followed by a clinical examination.ResultsOral health affected one or more daily performances during the last 6 months for 61.5% of the subjects. ‘Difficulty of eating and enjoying food’ was the performance reported most frequently (42.3%), and ‘speaking and pronouncing clearly’ was least often reported (10.3%). DMFT was 3.8, ±3.6 (mean ± SD; range 0–15). A majority of the individuals had periodontal pockets ≥4 mm (mean 4.3, ±2.6) (94.9%) and gingival bleeding on probing >20% (88.5%). Two or more decayed teeth were shown to be significantly associated (OR 4.6, CI 1.2–17.1) with one or more oral impacts on daily performances in a multivariate logistic regression analysis.ConclusionsThis study shown that there is a significant association between decayed teeth and oral impacts on daily performances. More research is needed, however, for deeper understanding of oral health problems and their impacts on daily life in Zambia.
Concentration of Omega‐3 polyunsaturated fatty acids by polymeric membrane
Authors: Ghasemian Samaneh , Sahari Mohammad Ali , Barzegar Mohsen , Gavlighi Hassan Ahmadi 
Published: August 2015

SummaryOmega‐3 is a polyunsaturated fatty acid (PUFA), which is an essential nutrient for health. Through this, the ω3‐PUFA concentration has increasingly gained interest. In this study, the concentration of ω3‐PUFA of Lantern fish oil was investigated through utilisation of membrane separation. Between tested membranes, it was observed that ETNA01PP separates ω3‐PUFA more selectively. Additionally, effects of main parameters affecting the ω3‐PUFA concentration, including temperature (20–40 °C), pressure (3–5 bar) and stirring rate (0–200 rpm), were evaluated through Box–Behnken design of experiment. According to anova, all these parameters showed significant impact on ω3‐PUFA concentration. To determine the optimal process parameters, the Derringer's desirability prediction tool was employed in which the highest ω3‐PUFA concentration of 35.1058 wt. % was estimated. The obtained optimal condition was found to be the temperature of 36.19 °C, pressure of 4.82 bar and stirring rate of 43.01 rpm with a desirability value of 0.99.
Combination of SYBR Green II and TaqMan Probe in the adulteration detection of Dendrobium devonianum by fluorescent quantitative PCR
Authors: Yan Wenjin , Zhang Jingzi , Zheng Rui , Sun Yulong , Ren Jie , Ding Xiaoyu 
Published: August 2015

Summary‘Zipi Fengdou’ is a restorative food made of the stem of Dendrobium devonianum, Paxt., whose high commercial value presents the constant risk of adulteration with cheaper ‘Foudou’ products made from other Dendrobium species. Therefore, this study developed two assays capable of detecting D. devonianum based on SYBR Green II and TaqMan probe real‐time PCR. By performing the diagnostic real‐time PCR based on SYBR Green II, two DNA fragments (163 and 159 bp) were specifically amplified from the internal transcribed spacer (ITS) region of D. devonianum. The average cycle threshold (Ct) values of two D. devonianum samples collected from different Chinese provinces were shown to be 16.65 for ITS1‐4 and 16.38 for ITS2‐1, which were significantly (P < 0.001, SPSS) different from those of the reference Dendrobium species used as adulterants of ‘Zipi Fengdou’ (34.94 for ITS1‐4, 34.67 for ITS2‐1). Moreover, in the assay based on TaqMan probe real‐time PCR, two TaqMan probes were designed and tested for the quantitative detection of D. devonianum in commercial samples labelled as ‘Zipi Fengdou’. As a result, this assay specifically and sensitively distinguished the processed Fengdou’ sample of D. devonianum from those of adulterant Dendrobium species.
Prognostic Value of 24-H ABPM in Acute Ischemic Stroke for Short-, Medium-, and Long-Term Outcome: A Systematic Review and Meta-Analysis
Authors: Kakaletsis Nikolaos , Ntaios George , Milionis Haralampos , Haidich Anna-Bettina , Makaritsis Konstantinos , Savopoulos Christos , Berge Eivind , Hatzitolios Apostolos I. 
Published: August 2015

Background The association of blood pressure levels during the acute phase of ischemic stroke with outcome remains controversial. Aims The objective of this systematic review is to assess the predictive value for stroke outcome assessed by the modified Rankin scale score of systolic and diastolic blood pressure, measured by ambulatory blood pressure monitoring methods during the acute phase of ischemic stroke, compared with the values of casually derived blood pressure measurement on admission. Methods We searched for studies with patients admitted within 24 h of stroke onset, and who had ambulatory blood pressure monitoring during the first 24 h of admission. We identified studies that reported blood pressure in those with good outcome and in those with poor outcome at end of follow-up, and performed a meta-analysis of the effect of mean blood pressure on outcome. Results High systolic and diastolic blood pressure levels derived with ambulatory blood pressure monitoring were associated with poor short-, medium-, and long-term outcome, but the same was not found for casual blood pressure measurements. An increase in systolic blood pressure of 9·1 mmHg (95% confidence interval: 6·6–11·6, P < 0·001; I2 = 9%) and an increase in diastolic blood pressure of 2·3 mmHg (95% confidence interval: 0·8–3·7, P = 0·002; I2 = 0%) were associated with poor outcome. Conclusions Higher systolic and diastolic blood pressure levels derived with ambulatory blood pressure monitoring were associated with poor outcome. The same was not found for higher casual blood pressure measurements on admission, and it is possible that ambulatory blood pressure monitoring conveys better prognostic information.
Co‐evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity
Authors: de Groot Natasja G. , Blokhuis Jeroen H. , Otting Nel , Doxiadis Gaby G. M. , Bontrop Ronald E. 
Published: August 2015

SummaryResearchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi‐gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well‐defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi‐gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species’ immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families.
NK cells: tuned by peptide?
Authors: Das Jayajit , Khakoo Salim I. 
Published: August 2015

SummaryNatural killer cells express multiple receptors for major histocompatibility complex (MHC) class I, including the killer cell immunoglobulin‐like receptors (KIRs) and the C‐type lectin‐like CD94:NKG2 receptors. The KIR locus is extremely polymorphic, paralleling the diversity of its classical MHC class I ligands. Similarly, the conservation of the NKG2 family of receptors parallels the conservation of MHC‐E, the ligand for CD94:NKG2A/C/E. Binding of both CD94:NKG2 heterodimers and KIR to their respective MHC class I ligand is peptide dependent, and despite the evolution of these receptors, they have retained the property of peptide selectivity. Such peptide selectivity affects these two systems in different ways. HLA‐E binding non‐inhibitory peptides augment inhibition at CD94:NKG2A, while HLA‐C binding non‐inhibitory peptides antagonize inhibition at KIR2DL2/3, implying that KIRs are specialized to respond positively to changes in peptide repertoire. Thus, while specific KIRs, such as KIR2DL3, are associated with beneficial outcomes from viral infections, viral peptides augment inhibition at CD94:NKGA. Conversely, NKG2A‐positive NK cells sense MHC class I downregulation more efficiently than KIRs. Thus, these two receptor:ligand systems appear to have complementary functions in recognizing changes in MHC class I.
Human KIR repertoires: shaped by genetic diversity and evolution
Authors: Manser Angela R. , Weinhold Sandra , Uhrberg Markus 
Published: August 2015

SummaryKiller cell immunoglobulin‐like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals’ immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I‐encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types.
Ly49 receptors: evolution, genetic diversity, and impact on immunity
Authors: Rahim Mir Munir A. , Makrigiannis Andrew P. 
Published: August 2015

SummaryNatural killer (NK) cells express cell surface receptors that recognize class I major histocompatibility complex (MHC‐I) molecules to distinguish between healthy and unhealthy cells. The multigenic and polymorphic nature of the MHC‐I genes has influenced the convergent evolution of similarly polymorphic and diversified NK cell receptor families: the C‐type lectin‐like Ly49 receptors in mice, and the killer cell immunoglobulin‐like receptors (KIRs) in humans. Although structurally distinct, both receptor families have similar functions in terms of MHC‐I recognition and downstream signal transduction, and they regulate multiple aspects of NK cell biology during development and after maturation as fully differentiated and functionally competent cells. The Ly49 gene locus has undergone rapid, lineage‐specific expansions and contractions resulting in multiple distinct haplotypes of variable gene number, allelic diversity, and MHC‐I ligand specificity. This in turn has influenced the type and degree of Ly49 receptor expression on NK cells, and their contribution to immunity in different mouse strains. In this review, we have attempted to describe the evolutionary processes that have shaped strain‐specific Ly49 receptor repertoires, and their impact on NK cell functions during health and disease.
A bird's eye view of NK cell receptor interactions with their MHC class I ligands
Authors: Saunders Philippa M. , Vivian Julian P. , O'Connor Geraldine M. , Sullivan Lucy C. , Pymm Phillip , Rossjohn Jamie , Brooks Andrew G. 
Published: August 2015

SummaryThe surveillance of target cells by natural killer (NK) cells utilizes an ensemble of inhibitory and activating receptors, many of which interact with major histocompatibility complex (MHC) class I molecules. NK cell recognition of MHC class I proteins is important developmentally for the acquisition of full NK cell effector capacity and during target cell recognition, where the engagement of inhibitory receptors and MHC class I molecules attenuates NK cell activation. Human NK cells have evolved two broad strategies for recognition of human leukocyte antigen (HLA) class I molecules: (i) direct recognition of polymorphic classical HLA class I proteins by diverse receptor families such as the killer cell immunoglobulin‐like receptors (KIRs), and (ii) indirect recognition of conserved sets of HLA class I‐derived peptides displayed on the non‐classical HLA‐E for recognition by CD94‐NKG2 receptors. In this review, we assess the structural basis for the interaction between these NK receptors and their HLA class I ligands and, using the suite of published KIR and CD94‐NKG2 ternary complexes, highlight the features that allow NK cells to orchestrate the recognition of a range of different HLA class I proteins.
Activation of human T cells by CD1 and self‐lipids
Authors: de Jong Annemieke 
Published: August 2015

SummaryOver two decades ago, it was discovered that the human T‐cell repertoire contains T cells that do not recognize peptide antigens in the context of MHC molecules but instead respond to lipid antigens presented by CD1 antigen‐presenting molecules. The ability of T cells to ‘see’ lipid antigens bound to CD1 enables these lymphocytes to sense changes in the lipid composition of cells and tissues as a result of infections, inflammation, or malignancies. Although foreign lipid antigens have been shown to function as antigens for CD1‐restricted T cells, many CD1‐restricted T cells do not require foreign antigens for activation but instead can be activated by self‐lipids presented by CD1. This review highlights recent developments in the field, including the identification of common mammalian lipids that function as autoantigens for αβ and γδ T cells, a novel mode of T‐cell activation whereby CD1a itself rather than lipids serves as the autoantigen, and various mechanisms by which the activation of CD1‐autoreactive T cells is regulated. As CD1 can induce T‐cell effector functions in the absence of foreign antigens, multiple mechanisms are in place to regulate this self‐reactivity, and stimulatory CD1‐lipid complexes appear to be tightly controlled in space and time.
Co‐evolution of NK receptors and HLA ligands in humans is driven by reproduction
Authors: Moffett Ashley , Colucci Francesco 
Published: August 2015

SummaryAllogeneic individuals co‐exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply line determines the growth and birth weight of the baby and is subject to stabilizing selection. Invading placental trophoblast cells express human leukocyte antigen class I ligands (HLA‐E, HLA‐G, and HLA‐C) for receptors on maternal uterine natural killer (NK) and myelomonocytic cells, CD94/NKG2, leukocyte immunoglobulin‐like receptor (LILR), and killer immunoglobulin receptor (KIR). Of these, only the KIR/HLA‐C system is highly polymorphic. Different combinations of maternal KIR and fetal HLA‐C variants are correlated with low birth weight and pre‐eclampsia or high birth weight and obstructed labor, the two extremes of the obstetric dilemma. This situation has arisen because of the evolution of bipedalism and subsequently, in the last million years, larger brains. At this point, the human system began to reach a balance between KIR A and KIR B haplotypes and C1 and C2 epitopes of HLA‐C alleles that reflects a functional compromise between the competing demands of immunity and reproduction.