bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left ventricular function by echocardiogram in children with sickle cell anaemia in Mumbai, Western India
Authors: Tidake Abhay , Gangurde Pranil , Taksande Anup , Mahajan Ajay , Nathani Pratap 
Published: December 2014

AbstractIntroductionCardiovascular events and complications are the leading cause of mortality and morbidity in patients with sickle cell disease. Cardiac abnormalities occur frequently and at an early stage in sickle cell anaemia patients, despite being more evident in adulthood. Sickle cell anaemia patients are increasingly able to reach adulthood owing to improved healthcare, and may, therefore, suffer the consequences of chronic cardiac injury. Thus, the study of cardiac abnormalities is essential in childrenObjectiveThe aim of this study was to determine the echocardiographic changes in left ventricular function in children suffering from sickle cell disease in Mumbai, Western India.MethodsThe study comprised of 48 cases of sickle cell anaemia and 30 non-anaemic controls with normal haemoglobin and electrophoresis pattern. M-mode, two-dimensional, and Doppler echocardiographic measurements of patients and controls were performed according to the criteria of the American Echocardiography Society.ResultsOn Doppler study, the A wave height was increased and the E/A ratio was decreased, whereas the deceleration and isovolumetric relaxation times were prolonged, which is typically seen in slowed or impaired myocardial relaxation (p<0.001). Although chamber dilatations were present, echocardiographic parameters showed no statistically significant correlation with severity of anaemia and age among the sickle cell patients.ConclusionsWe conclude that the increased left ventricular stiffness, compared with controls, might be due to fibrosis related to ischaemia caused by SS disease in addition to wall hypertrophy.
Time trends in socio-economic inequalities in stunting prevalence: analyses of repeated national surveys
Authors: Restrepo-Méndez María Clara , Barros Aluísio JD , Black Robert E , Victora Cesar G 
Published: December 2014

AbstractObjectiveMuch is known about national trends in child undernutrition, but there is little information on how socio-economic inequalities are evolving over time. We aimed to assess socio-economic inequalities in stunting prevalence over time.DesignWe selected nationally representative surveys carried out since the mid-1990s for which information was available on asset indices and on child anthropometry. We identified twenty-five countries that had at least two surveys over an interval of 10 years or more, totalling eighty-seven surveys. Stunting prevalence was calculated according to wealth quintiles. Absolute and relative inequalities were calculated and time trends were obtained by regression.SettingNationally representative household surveys from twenty-five low- and middle-income countries.SubjectsChildren <5 years of age.ResultsNational prevalence declined significantly in twenty-two of the twenty-five countries. In eighteen out of twenty-five countries, relative reductions were higher among the rich than among the poor. Overall, there was no indication that inequalities improved. Striking examples are Nepal, with a 17·0 percentage points decline in stunting per decade, but where inequalities increased sharply; and Brazil, where stunting fell by 6·7 percentage points and inequalities were all but eliminated.ConclusionsGlobal progress in reducing stunting has not been accompanied by improved equity, but countries varied markedly in how successful they were in reducing prevalence among the poorest children. It is important to document how some countries were able to reduce inequalities, so that these lessons can be used to foster global progress, particularly in light of the increased importance of within-country inequalities in the post-2015 agenda.
DISTRIBUTED PROXIMAL-GRADIENT METHOD
FOR CONVEX OPTIMIZATION WITH INEQUALITY CONSTRAINTS
Authors: LI JUEYOU , WU CHANGZHI , WU ZHIYOU , LONG QIANG , WANG XIANGYU 
Published: December 2014

AbstractWe consider a distributed optimization problem over a multi-agent network, in which
the sum of several local convex objective functions is minimized subject to global
convex inequality constraints. We first transform the constrained optimization
problem to an unconstrained one, using the exact penalty function method. Our
transformed problem has a smaller number of variables and a simpler structure than
the existing distributed primal–dual subgradient methods for constrained
distributed optimization problems. Using the special structure of this problem, we
then propose a distributed proximal-gradient algorithm over a time-changing
connectivity network, and establish a convergence rate depending on the number of
iterations, the network topology and the number of agents. Although the transformed
problem is nonsmooth by nature, our method can still achieve a convergence rate, ${\mathcal{O}}(1/k)$, after $k$ iterations, which is faster than the rate, ${\mathcal{O}}(1/\sqrt{k})$, of existing distributed subgradient-based methods. Simulation
experiments on a distributed state estimation problem illustrate the excellent
performance of our proposed method.
MODAL LOGICS OF METRIC SPACES
Authors: BEZHANISHVILI GURAM , GABELAIA DAVID , LUCERO-BRYAN JOEL 
Published: December 2014

AbstractIt is a classic result (McKinsey & Tarski, 1944; Rasiowa & Sikorski, 1963) that if we interpret modal diamond as topological closure, then the modal logic of any dense-in-itself metric space is the well-known modal system S4. In this paper, as a natural follow-up, we study the modal logic of an arbitrary metric space. Our main result establishes that modal logics arising from metric spaces form the following chain which is order-isomorphic (with respect to the ⊃ relation) to the ordinalω+ 3:$S4.Gr{z_1} \supset S4.Gr{z_2} \supset S4.Gr{z_3} \supset \cdots \,S4.Grz \supset S4.1 \supset S4.$It follows that the modal logic of an arbitrary metric space is finitely axiomatizable, has the finite model property, and hence is decidable.
Die Erfassung von Ängsten im Urteil von Kindern/Jugendlichen und ihren Eltern
Authors: Dose Christina , Görtz-Dorten Anja , Breuer Dieter , Goletz Hildegard , Döpfner Manfred 
Published: December 2014

Zusammenfassung. Ziel dieser Arbeit ist die Analyse der psychometrischen Qualität des Fremd- und des Selbstbeurteilungsbogens zur Erfassung von Angst- und Zwangsstörungen (FBB-ANZ/SBB-ANZ) in zwei klinischen Stichproben (n = 182 bzw. n = 130). Ergänzend wurde die Faktorenstruktur der Bögen in zwei Feldstichproben (n = 724 bzw. n = 281) untersucht. Für die Skalen beider Fragebögen ergaben sich größtenteils zufriedenstellende interne Konsistenzen (.59 ≤ α ≤ .93). Exploratorische Hauptachsenanalysen mit Promax-Rotation ergaben stichprobenübergreifend für beide Fragebögen Faktoren, welche die a priori definierten, ICD-10- und DSM-IV-basierten Subskalen weitgehend abbilden. Zwischen den Subskalen innerhalb der Fragebögen zeigten sich geringe bis moderate Interkorrelationen, die für eine gute Abgrenzbarkeit der Skalen sprechen. Es fanden sich größtenteils moderate Beurteilerübereinstimmungen zwischen den korrespondierenden Skalen des Fremd- und Selbstbeurteilungsbogens. Die Ergebnisse weisen darauf hin, dass die Fragebögen überwiegend reliable und valide Instrumente darstellen. Weiterer Untersuchungsbedarf besteht insbesondere hinsichtlich der konvergenten und divergenten Validität der Subskalen.
Defective sarcoplasmic reticulum–mitochondria calcium exchange in aged mouse myocardium
Authors: Fernandez-Sanz C , Ruiz-Meana M , Miro-Casas E , Nuñez E , Castellano J , Loureiro M , Barba I , Poncelas M , Rodriguez-Sinovas A , Vázquez J , Garcia-Dorado D 
Published: December 2014

AbstractMitochondrial alterations are critically involved in increased vulnerability to disease during aging. We investigated the contribution of mitochondria–sarcoplasmic reticulum (SR) communication in cardiomyocyte functional alterations during aging. Heart function (echocardiography) and ATP/phosphocreatine (NMR spectroscopy) were preserved in hearts from old mice (>20 months) with respect to young mice (5–6 months). Mitochondrial membrane potential and resting O2 consumption were similar in mitochondria from young and old hearts. However, maximal ADP-stimulated O2 consumption was specifically reduced in interfibrillar mitochondria from aged hearts. Second generation proteomics disclosed an increased mitochondrial protein oxidation in advanced age. Because energy production and oxidative status are regulated by mitochondrial Ca2+, we investigated the effect of age on mitochondrial Ca2+ uptake. Although no age-dependent differences were found in Ca2+ uptake kinetics in isolated mitochondria, mitochondrial Ca2+ uptake secondary to SR Ca2+ release was significantly reduced in cardiomyocytes from old hearts, and this effect was associated with decreased NAD(P)H regeneration and increased mitochondrial ROS upon increased contractile activity. Immunofluorescence and proximity ligation assay identified the defective communication between mitochondrial voltage-dependent anion channel and SR ryanodine receptor (RyR) in cardiomyocytes from aged hearts associated with altered Ca2+ handling. Age-dependent alterations in SR Ca2+ transfer to mitochondria and in Ca2+ handling could be reproduced in cardiomyoctes from young hearts after interorganelle disruption with colchicine, at concentrations that had no effect in aged cardiomyocytes or isolated mitochondria. Thus, defective SR–mitochondria communication underlies inefficient interorganelle Ca2+ exchange that contributes to energy demand/supply mistmach and oxidative stress in the aged heart.
Tax contributes apoptosis resistance to HTLV-1-infected T cells via suppression of Bid and Bim expression
Authors: Mühleisen A , Giaisi M , Köhler R , Krammer P H , Li-Weber M 
Published: December 2014

AbstractThe human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). HTLV-1 Tax has been shown to have a prosurvival role in infected T cells by enhancing expression of the Bcl-2 family of antiapoptotic proteins. In this study, we show that the expression of proapoptotic BH3-only proteins Bim (Bcl-2-interacting mediator of cell death) and Bid (BH3-interacting domain death agonist) is diminished in HTLV-1-infected leukemic cells. Using a Tax-inducible system and a transient overexpression approach, we demonstrate that Tax downregulates Bid and Bim expression at the transcriptional level. We show that reinforced expression of Bim and Bid in HTLV-1-infected T-cell lines sensitizes CD95/TRAIL- and anticancer drug-induced apoptosis. Furthermore, we show that Tax suppresses Bid and Bim expression by enhancing hypoxia-inducible factor-1α (HIF-1α) protein expression. siRNA knockdown of HIF-1α or chemical inhibition of the transactivation activity of HIF-1α resulted in an increase in Bid and Bim expression and, consequently, in an increase in CD95/TRAIL- and anticancer drug-induced apoptosis in HTLV-1-infected leukemic T-cell lines. Our study provides evidence that besides upregulation of prosurvival Bcl-2 proteins, Tax may also confer apoptosis resistance to HTLV-1-infected T cells by suppressing the expression of the proapoptotic BH3-only proteins Bim and Bid.
SBF-1 exerts strong anticervical cancer effect through inducing endoplasmic reticulum stress-associated cell death via targeting sarco/endoplasmic reticulum Ca2+-ATPase 2
Authors: Li W , Ouyang Z , Zhang Q , Wang L , Shen Y , Wu X , Gu Y , Shu Y , Yu B , Wu X , Sun Y , Xu Q 
Published: December 2014

AbstractCervical cancer is one of the most common carcinomas in the genital system. In the present study, we report that SBF-1, a synthetic steroidal glycoside, has a strong antigrowth activity against human cervical cancer cells in vitro and in vivo. SBF-1 suppressed the growth, migration and colony formation of HeLa cells. In addition, severe endoplasmic reticulum (ER) stress was triggered by SBF-1, and 4-phenyl-butyric acid, a chemical chaperone, partially reversed SBF-1-induced cell death. To uncover the target protein of SBF-1, the compound was labeled with biotin. The biotin-labeled SBF-1 bound to sarco/ER Ca2+-ATPase 2 (SERCA2) and colocalized with SERCA2 in HeLa cells. Moreover, SBF-1 inhibited SERCA activity, depleted ER Ca2+ and increased cytosolic Ca2+ levels. 1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, a chelator of Ca2+, partially blocked SBF-1-induced ER stress and growth inhibition. Importantly, knockdown of SERCA2 increased the sensitivity of HeLa cells to SBF-1-induced ER stress and cell death, whereas overexpression of SERCA2 decreased this sensitivity. Furthermore, SBF-1 induced growth suppression and apoptosis in HeLa xenografts, which is closely related to the induction of ER stress and inhibition of SERCA activity. Finally, SERCA2 expression was elevated in human cervical cancer tissues (n=299) and lymph node metastasis (n=8), as compared with normal cervix tissues (n=23), with a positive correlation with clinical stages. In all, these results suggest that SBF-1 disrupts Ca2+ homeostasis and causes ER stress-associated cell death through directly binding to SERCA2 and inhibiting SERCA activity. Our findings also indicate that SERCA2 is a potential therapeutic target for human cervical cancer.
An activated unfolded protein response promotes retinal degeneration and triggers an inflammatory response in the mouse retina
Authors: Rana T , Shinde V M , Starr C R , Kruglov A A , Boitet E R , Kotla P , Zolotukhin S , Gross A K , Gorbatyuk M S 
Published: December 2014

AbstractRecent studies on the endoplasmic reticulum stress have shown that the unfolded protein response (UPR) is involved in the pathogenesis of inherited retinal degeneration caused by mutant rhodopsin. However, the main question of whether UPR activation actually triggers retinal degeneration remains to be addressed. Thus, in this study, we created a mouse model for retinal degeneration caused by a persistently activated UPR to assess the physiological and morphological parameters associated with this disease state and to highlight a potential mechanism by which the UPR can promote retinal degeneration. We performed an intraocular injection in C57BL6 mice with a known unfolded protein response (UPR) inducer, tunicamycin (Tn) and examined animals by electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT) and histological analyses. We detected a significant loss of photoreceptor function (over 60%) and retinal structure (35%) 30 days post treatment. Analysis of retinal protein extracts demonstrated a significant upregulation of inflammatory markers including interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and IBA1. Similarly, we detected a strong inflammatory response in mice expressing either Ter349Glu or T17M rhodopsin (RHO). These mutant rhodopsin species induce severe retinal degeneration and T17M rhodopsin elicits UPR activation when expressed in mice. RNA and protein analysis revealed a significant upregulation of pro- and anti-inflammatory markers such as IL-1β, IL-6, p65 nuclear factor kappa B (NF-kB) and MCP-1, as well as activation of F4/80 and IBA1 microglial markers in both the retinas expressing mutant rhodopsins. We then assessed if the Tn-induced inflammatory marker IL-1β was capable of inducing retinal degeneration by injecting C57BL6 mice with a recombinant IL-1β. We observed ~19% reduction in ERG a-wave amplitudes and a 29% loss of photoreceptor cells compared with control retinas, suggesting a potential link between pro-inflammatory cytokines and retinal pathophysiological effects. Our work demonstrates that in the context of an established animal model for ocular disease, the persistent activation of the UPR could be responsible for promoting retinal degeneration via the UPR-induced pro-inflammatory cytokine IL-1β.
Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking
Authors: Kievit Rogier A. , Davis Simon W. , Mitchell Daniel J. , Taylor Jason R. , Duncan John ,   Cam-CAN Research team, Tyler Lorraine K. , Brayne Carol , Bullmore Ed , Calder Andrew , Cusack Rhodri , Dalgleish Tim , Matthews Fiona , Marslen-Wilson William , Rowe James , Shafto Meredith , Campbell Karen , Cheung Teresa , Geerligs Linda , McCarrey Anna , Tsvetanov Kamen , Williams Nitin , Bates Lauren , Emery Tina , Erzinçlioglu Sharon , Gadie Andrew , Gerbase Sofia , Georgieva Stanimira , Hanley Claire , Parkin Beth , Troy David , Allen Jodie , Amery Gillian , Amunts Liana , Barcroft Anne , Castle Amanda , Dias Cheryl , Dowrick Jonathan , Fair Melissa , Fisher Hayley , Goulding Anna , Grewal Adarsh , Hale Geoff , Hilton Andrew , Johnson Frances , Johnston Patricia , Kavanagh-Williamson Thea , Kwasniewska Magdalena , McMinn Alison , Norman Kim , Penrose Jessica , Roby Fiona , Rowland Diane , Sargeant John , Squire Maggie , Stevens Beth , Stoddart Aldabra , Stone Cheryl , Thompson Tracy , Yazlik Ozlem , Barnes Dan , Dixon Marie , Hillman Jaya , Mitchell Joanne , Villis Laura , Henson Richard N.A. 
Published: December 2014

AbstractAgeing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing.
Slow unloading leads to DNA-bound β2-sliding clamp accumulation in live Escherichia coli cells
Authors: Moolman M. Charl , Krishnan Sriram Tiruvadi , Kerssemakers Jacob W. J. , van den Berg Aafke , Tulinski Pawel , Depken Martin , Reyes-Lamothe Rodrigo , Sherratt David J. , Dekker Nynke H. 
Published: December 2014

AbstractThe ubiquitous sliding clamp facilitates processivity of the replicative polymerase and acts as a platform to recruit proteins involved in replication, recombination and repair. While the dynamics of the E. coli β2-sliding clamp have been characterized in vitro, its in vivo stoichiometry and dynamics remain unclear. To probe both β2-clamp dynamics and stoichiometry in live E. coli cells, we use custom-built microfluidics in combination with single-molecule fluorescence microscopy and photoactivated fluorescence microscopy. We quantify the recruitment, binding and turnover of β2-sliding clamps on DNA during replication. These quantitative in vivo results demonstrate that numerous β2-clamps in E. coli remain on the DNA behind the replication fork for a protracted period of time, allowing them to form a docking platform for other enzymes involved in DNA metabolism.
Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle
Authors: Littlejohn Mathew D. , Henty Kristen M. , Tiplady Kathryn , Johnson Thomas , Harland Chad , Lopdell Thomas , Sherlock Richard G. , Li Wanbo , Lukefahr Steven D. , Shanks Bruce C. , Garrick Dorian J. , Snell Russell G. , Spelman Richard J. , Davis Stephen R. 
Published: December 2014

AbstractLactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation.
Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications
Authors: van de Werken Christine , van der Heijden Godfried W. , Eleveld Cindy , Teeuwssen Miriam , Albert Mareike , Baarends Willy M. , Laven Joop S. E. , Peters Antoine H. F. M. , Baart Esther B. 
Published: December 2014

AbstractThe different configurations of maternal and paternal chromatin, acquired during oogenesis and spermatogenesis, have to be rearranged after fertilization to form a functional embryonic genome. In the paternal genome, nucleosomal chromatin domains are re-established after the protamine-to-histone exchange. We investigated the formation of constitutive heterochromatin (cHC) in human preimplantation embryos. Our results show that histones carrying canonical cHC modifications are retained in cHC regions of sperm chromatin. These modified histones are transmitted to the oocyte and contribute to the formation of paternal embryonic cHC. Subsequently, the modifications are recognized by the H3K9/HP1 pathway maternal chromatin modifiers and propagated over the embryonic cleavage divisions. These results are in contrast to what has been described for mouse embryos, in which paternal cHC lacks canonical modifications and is initially established by Polycomb group proteins. Our results show intergenerational epigenetic inheritance of the cHC structure in human embryos.
A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1
Authors: Rettenmaier T. Justin , Sadowsky Jack D. , Thomsen Nathan D. , Chen Steven C. , Doak Allison K. , Arkin Michelle R. , Wells James A. 
Published: December 2014

Significance
Allosteric sites in protein kinases offer opportunities for developing more selective inhibitors, but these sites are challenging to target because they involve protein–protein interfaces. We designed a site-directed approach to screen for molecules that bind to an allosteric peptide docking site on the protein kinase PDK1. We discovered molecules that structurally mimic the natural peptide ligand and inhibit PDK1 in cells. We also found that combining allosteric and ATP-competitive inhibitors completely blocked the activation of oncogenic kinases downstream of PDK1. This approach could be adapted to target an analogous allosteric site found on many other kinases.
Structural basis of HIV-1 capsid recognition by PF74 and CPSF6
Authors: Bhattacharya Akash , Alam Steven L. , Fricke Thomas , Zadrozny Kaneil , Sedzicki Jaroslaw , Taylor Alexander B. , Demeler Borries , Pornillos Owen , Ganser-Pornillos Barbie K. , Diaz-Griffero Felipe , Ivanov Dmitri N. , Yeager Mark 
Published: December 2014

Significance
Events that occur between entry of the HIV-1 capsid into the cytoplasm of the target cell and the delivery of the viral genetic material into the nucleus constitute some of the less well understood processes in the viral life cycle. We demonstrated that PF74, a small-molecule inhibitor of HIV-1, and the host proteins CPSF6 and NUP153 bind to a preformed pocket within the CA protein hexamers that exist within the assembled capsid. Our results suggest that key features of the CA hexameric lattice remain intact upon docking at the nuclear pore. In addition, low molecular weight ligands that better mimic virus–host, protein–protein interactions at the intersubunit interfaces within the assembled viral capsid may offer novel avenues for therapeutic intervention.