bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of putative insulin‐like peptides and components of insulin signaling pathways in parasitic platyhelminths by the use of genome‐wide screening
Authors: Wang Shuai , Luo Xuenong , Zhang Shaohua , Yin Cai , Dou Yongxi , Cai Xuepeng 
Published: November 2013

No endogenous insulin‐like peptides in parasitic flatworms have been reported. Insulin receptors from flukes and tapeworms have been shown to interact directly with the host‐derived insulin molecule, which suggests the exploitation of host‐derived insulin. In this study, a strategy of genome‐wide searches followed by comprehensive analyses of strictly conserved features of the insulin family was used to demonstrate the presence of putative insulin‐like peptides in the genomes of six tapeworms and two flukes. In addition, whole insulin signaling pathways were annotated on a genome‐wide scale. Two putative insulin‐like peptide genes in each genome of tapeworms and one insulin‐like peptide gene in each genome of flukes were identified. The comprehensive analyses revealed that all of these peptides showed the common features shared by other members of the insulin family, and the phylogenetic analysis implied a putative gene duplication event in the Cestoda during the evolution of insulin‐like peptide genes. The quantitative expression analysis and immunolocalization results suggested a putative role of these peptides in reproduction. Entire sets of major components of the classic insulin signaling pathway were successfully identified, suggesting that this pathway in parasitic flatworms might also regulate many other important biological activities. We believe that the identification of the insulin‐like peptides gives us a better understanding of the insulin signaling pathway in these parasites, as well as host–parasite interactions.DatabaseNucleotide sequence data are available in the GenBank database under the accession numbers KF551231 and KF551230.
Structural and biochemical characterization of fructose‐1,6/sedoheptulose‐1,7–bisphosphatase from the cyanobacterium Synechocystis strain 6803
Authors: Feng Lingling , Sun Yao , Deng Hui , Li Ding , Wan Jian , Wang Xiaofeng , Wang Weiwei , Liao Xun , Ren Yanliang , Hu Xiaopeng 
Published: November 2013

Cyanobacterial fructose–1,6/sedoheptulose‐1,7–bisphosphatase (cy–FBP/SBPase) plays a vital role in gluconeogenesis and in the photosynthetic carbon reduction pathway, and is thus a potential enzymatic target for inhibition of harmful cyanobacterial blooms. Here, we describe the crystal structure of cy–FBP/SBPase in complex with AMP and fructose‐1,6–bisphosphate (FBP). The allosteric inhibitor AMP and the substrate FBP exhibit an unusual binding mode when in complex with cy–FBP/SBPase. Binding mode analysis suggested that AMP bound to the allosteric sites near the interface across the up/down subunit pairs C1C4 and C2C3 in the center of the tetramer, while FBP binds opposite to the interface between the horizontal subunit pairs C1C2 or C3C4. We identified a series of residues important for FBP and AMP binding, and suggest formation of a disulfide linkage between Cys75 and Cys99. Further analysis indicates that cy–FBP/SBPase may be regulated through ligand binding and alteration of the structure of the enzyme complex. The interactions between ligands and cy–FBP/SBPase are different from those of ligand‐bound structures of other FBPase family members, and thus provide new insight into the molecular mechanisms of structure and catalysis of cy–FBP/SBPase. Our studies provide insight into the evolution of this enzyme family, and may help in the design of inhibitors aimed at preventing toxic cyanobacterial blooms.DatabaseStructural data have ben submitted to the Protein Data Bank under accession numbers 3ROJ and 3RPL.Structured digital abstractcy-FBP/SBPase and cy-FBP/SBPase bind by x-ray crystallography (View interaction).
Crystal structures of highly specific phosphinic tripeptide enantiomers in complex with the angiotensin‐I converting enzyme
Authors: Masuyer Geoffrey , Akif Mohd , Czarny Bertrand , Beau Fabrice , Schwager Sylva L. U. , Sturrock Edward D. , Isaac R. Elwyn , Dive Vincent , Acharya K. Ravi 
Published: November 2013

Human somatic angiotensin‐I converting enzyme (ACE) is a zinc‐dependent dipeptidyl carboxypeptidase and a central component of the renin angiotensin aldosterone system (RAAS). Its involvement in the modulation of physiological actions of peptide hormones has positioned ACE as an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the crystal structures of the two catalytic domains of human ACE (N‐ and C‐) in complex with FI, the S enantiomer of the phosphinic ACE/ECE‐1 (endothelin converting enzyme) dual inhibitor FII, to a resolution of 1.91 and 1.85 Å, respectively. In addition, we have determined the structure of AnCE (an ACE homologue from Drosophila melanogaster) in complex with both isomers. The inhibitor FI (S configuration) can adapt to the active site of ACE catalytic domains and shows key differences in its binding mechanism mostly through the reorientation of the isoxazole phenyl side group at the P1′ position compared with FII (R configuration). Differences in binding are also observed between FI and FII in complex with AnCE. Thus, the new structures of the ACE–inhibitor complexes presented here provide useful information for further exploration of ACE inhibitor pharmacophores involving phosphinic peptides and illustrate the role of chirality in enhancing drug specificity.DatabaseStructural data are available in the Protein Data Bank databases under accession numbers 4ca5, 4ca6, 4ca7, 4ca8.
Nocturnal polyuria and decreased serum testosterone: Is there an association in men with lower urinary tract symptoms?
Authors: Kim Jin Wook , Oh Mi Mi , Yoon Cheol Yong , Bae Jae Hyun , Kim Je Jong , Moon Du Geon 
Published: November 2013

ObjectivesTo investigate the putative association between nocturia and decreased serum testosterone in men with lower urinary tract symptoms.MethodsFrequency volume charts and serum testosterone levels of patients visiting the outpatient clinic for lower urinary tract symptoms were collected and analyzed. Age, prostate volume, body mass index and the presence of comorbidities were accounted for. Frequency volume charts were analyzed for pathophysiological components of nocturnal polyuria, global polyuria, decreased nocturnal bladder capacity and increased frequency to identify associated risks. Frequency volume charts were also used to chart 8‐h changes of volume, frequency and capacity to identify time diurnal interactions with risk factors based on serum testosterone levels.ResultsA total of 2180 patients were enrolled in the study. Multivariate analysis showed testosterone decreased 0.142 ng/mL for every increase in nocturia, independent of other factors. Logistic regression analysis showed a significant difference between pathophysiological components. Decreased testosterone was shown to carry a significant independent risk for overall nocturia (odds ratio 1.60, 95% confidence interval 1.013–2.527, P = 0.044), and particularly nocturnal polyuria (odds ratio 1.934, 95% confidence interval 1.001–3.737, P = 0.027). Repeated measurement models showed patients with serum testosterone below 2.50 ng/mL to have a paradoxical increase in nocturnal urine volume at night.ConclusionsNocturia, especially nocturnal polyuria, is associated with decreased serum testosterone. Patients with low serum testosterone show increased nocturnal urine output.
Measurement of the Isotopic Composition of Molybdenum in Geological Samples by MC‐ICP‐MS using a Novel Chromatographic Extraction Technique
Authors: Li Jie , Liang Xi‐Rong , Zhong Li‐Feng , Wang Xuan‐Ce , Ren Zhong‐Yuan , Sun Sheng‐Ling , Zhang Zhao‐Feng , Xu Ji‐Feng 
Published: November 2013

A novel preconcentration method is presented for the determination of Mo isotope ratios by multi‐collector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) in geological samples. The method is based on the separation of Mo by extraction chromatography using N‐benzoyl‐N‐phenylhydroxylamine (BPHA) supported on a microporous acrylic ester polymeric resin (Amberlite CG‐71). By optimising the procedure, Mo could be simply and effectively separated from virtually all matrix elements with a single pass through a small volume of BPHA resin (0.5 ml). This technique for separation and enrichment of Mo is characterised by high selectivity, column efficiency and recovery (~ 100%), and low total procedural blank (~ 0.18 ng). A 100Mo‐97Mo double spike was mixed with samples before digestion and column separation, which enabled natural mass‐dependent isotopic fractionation to be determined with a measurement reproducibility of < 0.09‰ (δ98/95Mo, 2s) by MC‐ICP‐MS. The mean δ98/95MoSRM 3134 (NIST SRM 3134 Mo reference material; Lot No. 891307) composition of the IAPSO seawater reference material measured in this study was 2.00 ± 0.03‰ (2s, n = 3), which is consistent with previously published values. The described procedure facilitated efficient and rapid Mo isotopic determination in various types of geological samples.
Global biogeography of scaly tree ferns (Cyatheaceae): evidence for Gondwanan vicariance and limited transoceanic dispersal
Authors: Korall Petra , Pryer Kathleen M. 
Published: November 2013

ABSTRACTAimScaly tree ferns, Cyatheaceae, are a well‐supported group of mostly tree‐forming ferns found throughout the tropics, the subtropics and the south‐temperate zone. Fossil evidence shows that the lineage originated in the Late Jurassic period. We reconstructed large‐scale historical biogeographical patterns of Cyatheaceae and tested the hypothesis that some of the observed distribution patterns are in fact compatible, in time and space, with a vicariance scenario related to the break‐up of Gondwana.LocationTropics, subtropics and south‐temperate areas of the world.MethodsThe historical biogeography of Cyatheaceae was analysed in a maximum likelihood framework using Lagrange. The 78 ingroup taxa are representative of the geographical distribution of the entire family. The phylogenies that served as a basis for the analyses were obtained by Bayesian inference analyses of mainly previously published DNA sequence data using MrBayes. Lineage divergence dates were estimated in a Bayesian Markov chain Monte Carlo framework using beast.ResultsCyatheaceae originated in the Late Jurassic in either South America or Australasia. Following a range expansion, the ancestral distribution of the marginate‐scaled clade included both these areas, whereas Sphaeropteris is reconstructed as having its origin only in Australasia. Within the marginate‐scaled clade, reconstructions of early divergences are hampered by the unresolved relationships among the Alsophila, Cyathea and Gymnosphaera lineages. Nevertheless, it is clear that the occurrence of the Cyathea and Sphaeropteris lineages in South America may be related to vicariance, whereas transoceanic dispersal needs to be inferred for the range shifts seen in Alsophila and Gymnosphaera.Main conclusionsThe evolutionary history of Cyatheaceae involves both Gondwanan vicariance scenarios as well as long‐distance dispersal events. The number of transoceanic dispersals reconstructed for the family is rather few when compared with other fern lineages. We suggest that a causal relationship between reproductive mode (outcrossing) and dispersal limitations is the most plausible explanation for the pattern observed.
Causes of warm‐edge range limits: systematic review, proximate factors and implications for climate change
Authors: Cahill Abigail E. , Aiello‐Lammens Matthew E. , Caitlin Fisher‐Reid M. , Hua Xia , Karanewsky Caitlin J. , Ryu Hae Yeong , Sbeglia Gena C. , Spagnolo Fabrizio , Waldron John B. , Wiens John J. 
Published: November 2013

AbstractAimThe factors that set species range limits underlie many patterns in ecology, evolution, biogeography and conservation. These factors have been the subject of several reviews, but there has been no systematic review of the causes of warm‐edge limits (low elevations and latitudes). Understanding these causes is urgent, given that the factors that set these limits might also drive extinction at warm edges as global climate changes. Many authors have suggested that warm‐edge limits are set by biotic factors (particularly competition) whereas others have stressed abiotic factors (particularly temperature). We synthesize the known causes of species' warm‐edge range limits, with emphasis on the underlying mechanisms (proximate causes).LocationGlobal.MethodsWe systematically searched the literature for studies testing the causes of warm‐edge range limits.ResultsWe found 125 studies that address the causes of warm‐edge limits, from a search including > 4000 studies. Among the species in these studies, abiotic factors are supported more often than biotic factors in setting species range limits at warm edges, in contrast to the widely held view that biotic factors are more important. Studies that test both types of factors support abiotic factors significantly more frequently. In addition, only 23 studies (61 species) identified proximate causes of these limits, and these overwhelmingly support physiological tolerances to abiotic factors (primarily temperature). Only eight species with identified proximate causes were tested for both biotic and abiotic factors, but the majority support abiotic factors.Main conclusionsAlthough it is often assumed that warm‐edge limits are set by biotic factors, our review shows that abiotic factors are supported more often among the species in these 125 studies. However, few studies both identify proximate causes and test alternative mechanisms, or examine the interaction between biotic and abiotic factors. Filling these gaps should be a high priority as warm‐edge populations are increasingly driven to extinction by climate change.
Spring frost and growing season length co‐control the cold range limits of broad‐leaved trees
Authors: Kollas Chris , Körner Christian , Randin Christophe F. 
Published: November 2013

AbstractAimThe aim of this study was to test, based on biological theory, which facet of temperature is most closely associated with the elevational and latitudinal low‐temperature limits of seven European broad‐leaved tree species. We compared three temperature‐related potential constraints across three study regions: (1) absolute minimum temperature within 100 years; (2) lowest temperatures during the period of bud‐break; and (3) length and temperature of the growing season.LocationWestern and Eastern Swiss Alps (1165–2160 m a.s.l.) and southern Sweden (57° N–59° N).MethodsIn situ temperature was recorded at the high‐elevation and high‐latitude limits of seven broad‐leaved tree species and correlated with temperatures at the nearest weather stations, in order to reconstruct the temperature regime for the past 50 years. By applying generalized extreme value distribution theory, we estimated the lowest temperatures recurring during the life span of a tree.ResultsAt their high‐elevation limits, five out of the seven tree species experienced winter minimum temperatures considerably warmer than their known maximum freezing resistance in winter. For the bud‐break period, potentially damaging temperatures occurred at both the elevational and the latitudinal limits and for all four species for which phenological data were available. Three out of five species for which a latitudinal replicate was available showed a similar length of growing season at their respective elevational and latitudinal limits. The mean temperature during the growing season was always warmer at a species’ latitudinal limit than at its elevational limit, and hence this variable does not bear general explanatory power for the range limit.Main conclusionsLow‐temperature extremes during bud‐break are the most likely candidates for controlling the elevational and latitudinal limits of broad‐leaved tree species. The absolute minimum temperature in winter and the mean temperature during the growing season are unlikely to constrain the cold limits of these species. Thus, the results call for the use of temperature data (extremes) during key stages of spring phenology when attempting to explain the low‐temperature range limits and to predict the potential range shifts of deciduous tree species.
Instrumental and Constitutional Differentiation in the European Union
Authors: Schimmelfennig Frank , Winzen Thomas 
Published: November 2013

AbstractDifferentiation has become a salient feature of European integration. Yet systematic empirical evidence is lacking about its origins, duration and variation across countries and policies. This article provides such evidence from a new data set on differentiation in European Union treaty law. In addition, it is argued that two logics of treaty‐based differentiation are at work. ‘Instrumental differentiation’ originates in enlargement and is motivated by efficiency and distributional concerns. ‘Constitutional differentiation’ has its origins in treaty revisions and is motivated by concerns about national sovereignty and identity. It is driven by Eurosceptic Member States that are opposed ideologically, or fear popular resistance, to the supranational centralization of core state powers.
Manufacturing Esprit de Corps: The Case of the European External Action Service
Authors: Juncos Ana E. , Pomorska Karolina 
Published: November 2013

AbstractThe creation of the European External Action Service (EEAS) begs the question of whether its officials might develop an esprit de corps − understood as the emergence of shared beliefs and values among the individuals within a group and their desire to achieve a common goal − and how this might be achieved. Since the EEAS is composed of officials originating from different institutions, this contribution discusses the challenges associated with aggregating different beliefs and values within the Service. The article examines five factors that have the potential to promote organizational esprit de corps, including communication, leadership, public image, trust and training. It concludes that the first two years of operation of the Service do not bode well for the emergence of an esprit de corps and that, consequently, this might undermine the coherence and effectiveness of the EEAS itself.
Caregiver—child mental health: a prospective study in conflict and refugee settings
Authors: Panter‐Brick Catherine , Grimon Marie‐Pascale , Eggerman Mark 
Published: November 2013

BackgroundIn humanitarian settings, family‐level drivers of mental health are insufficiently documented; we examined the strength of caregiver—child associations with two‐wave, family‐level Afghan data.MethodsWe recruited a gender‐balanced sample of 681 caregiver—child dyads (n = 1,362 respondents) using stratified random‐sampling in government schools in Kabul (364 dyads) and refugee schools in Peshawar (317 dyads). One year after baseline, we re‐interviewed 64% of Kabul and 31% of Peshawar cohorts (n = 331 dyads, 662 respondents), retaining fewer Peshawar families due to refugee repatriation. In multivariable analyses adjusted for baseline, we assessed the extent to which caregiver mental health (Self‐Report Questionnaire, SRQ‐20) was associated with child symptom scores of post‐traumatic stress (Child Revised Impact of Events Scale, CRIES), depression (Depression Self‐Rating Scale, DSRS), psychiatric difficulties, impact, and prosocial strength (Strength and Difficulties Questionnaire, SDQ).ResultsCaregiver mental health was prospectively associated with all eight measures of child mental health at follow‐up, adjusted for baseline. For post‐traumatic stress, caregiver mental health had a predictive impact comparable to the child experiencing one or two lifetime trauma events. For depression, caregiver mental health approached the predictive impact of female gender. Thus a one SD change in caregiver SRQ‐20 was associated with a 1.04 point change on CRIES and a 0.65 point change in DSRS. For multi‐informant SDQ data, caregiver—child associations were strongest for caregiver ratings. For child‐rated outcomes, associations were moderated by maternal literacy, a marker of family‐level dynamics. Both adults and children identified domestic violence and quality of home life as independent risk and protective factors.ConclusionsIn the context of violence and displacement, efforts to improve child mental health require a thoughtful consideration of the mental health cascade across generations and the cluster of adversities that impact family wellbeing. We identify culturally meaningful leverage points for building family‐level resilience, relevant to the prevention and intervention agenda in global mental health.
Modeling human neurological disorders with induced pluripotent stem cells
Authors: Imaizumi Yoichi , Okano Hideyuki 
Published: November 2013

AbstractHuman induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient‐specific genetic information. For example, disease‐specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi‐omics analysis of neural cells originating from patient‐derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large‐scale screening of chemical libraries with disease‐specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient‐derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs.
imageThe production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient‐specific genetic information. Furthermore, innovations of gene‐editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases‐specific iPS cell research and described recently obtained knowledge in the form of actual examples.