bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-linked enzyme aggregates (CLEAs) of selected lipases: a procedure for the proper calculation of their recovered activity
Authors: Guauque Torres María del Pilar , Foresti María Laura , Ferreira María Luján 
Published: May 2013

Abstract
In the last few years, synthesis of carrier-free immobilized biocatalysts by cross-linking of enzyme aggregates has appeared as a promising technique. Cross-linked enzyme aggregates (CLEAs) present several interesting advantages over carrier-bound immobilized enzymes, such as highly concentrated enzymatic activity, high stability of the produced superstructure, important production costs savings by the absence of a support, and the fact that no previous purification of the enzyme is needed. However, the published literature evidences that a) much specific non-systematic exploratory work is being done and, b) recovered activity calculations in CLEAs still need to be optimized. In this context, this contribution presents results of an optimized procedure for the calculation of the activity retained by CLEAs, based on the comparison of their specific activity relative to their free enzyme counterparts. The protocol implies determination of precipitable protein content in commercial enzyme preparations through precipitation with ammonium sulphate and a protein co-feeder. The identification of linear ranges of activity versus concentration/amount of protein in the test reaction is also required for proper specific activity determinations. By use of mass balances that involve the protein initially added to the synthesis medium, and the protein remaining in the supernatant and washing solutions (these last derived from activity measurements), the precipitable protein present in CLEAs is obtained, and their specific activity can be calculated. In the current contribution the described protocol was applied to CLEAs of Thermomyces lanuginosa lipase, which showed a recovered specific activity of 11.1% relative to native lipase. The approach described is simple and can easily be extended to other CLEAs and also to carrier-bound immobilized enzymes for accurate determination of their retained activity.
The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitors
Authors: Chang Wen-Wei , Lin Ruey-Jen , Yu John , Chang Wen-Ying , Fu Chiung-Hui , Lai Alan Chuan-Ying , Yu Jyh-Cherng , Yu Alice L 
Published: May 2013

Abstract
Introduction
Dysregulation of the insulin-like growth factor-1 receptor (IGF-1R)/phosphatidylinositol-3-kinase (PI3K)/Akt pathway was shown to correlate with breast cancer disease progression. Cancer stem cells are a subpopulation within cancer cells that participate in tumor initiation, radio/chemoresistance and metastasis. In breast cancer, breast cancer stem cells (BCSCs) were identified as CD24-CD44+ cells or cells with high intracellular aldehyde dehydrogenase activity (ALDH+). Elucidation of the role of IGF-1R in BCSCs is crucial to the design of breast cancer therapies targeting BCSCs.

Methods
IGF-1R expression in BCSCs and noncancer stem cells sorted from xenografts of human primary breast cancers was examined by fluorescence-activated cell sorting (FACS), western blot analysis and immunoprecipitation. The role of IGF-1R in BCSCs was assessed by IGF-1R blockade with chemical inhibitor and gene silencing. Involvement of PI3K/Akt/mammalian target of rapamycin (mTOR) as the downstream pathway was studied by their phosphorylation status upon IGF-1R inhibition and the effects of chemical inhibitors of these signaling molecules on BCSCs. We also studied 16 clinical specimens of breast cancer for the expression of phosphor-Akt in the BCSCs by FACS.

Results
Expression of phosphorylated IGF-1R was greater in BCSCs than in non-BCSCs from xenografts of human breast cancer, which were supported by western blot and immunoprecipitation experiments. The sorted IGF-1R-expressing cells displayed features of cancer stem/progenitors such as mammosphere formation in vitro and tumorigenicity in vivo, both of which were suppressed by knockdown of IGF-1R. A specific inhibitor of the IGF-1R, picropodophyllin suppressed phospho-AktSer473 and preferentially decreased ALDH+ BCSC populations of human breast cancer cells. Furthermore, picropodophyllin inhibited the capacity of CD24-CD44+ BCSCs to undergo the epithelial-mesenchymal transition process with downregulation of mesenchymal markers. Inhibitors of signal molecules downstream of IGF-1R including PI3K/Akt/mTOR also reduced the ALDH+ population of breast cancer cells. Furthermore, the mTOR inhibitor, rapamycin, suppressed BCSCs in vitro and in vivo.

Conclusion
Our data support the notion that IGF-1R is a marker of stemness, and IGF-1R and its downstream PI3K/Akt/mTOR pathway are attractive targets for therapy directed against breast cancer stem/progenitors.
Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage
Authors: Schiefecker Alois J , Pfausler Bettina , Beer Ronny , Sohm Florian , Sabo Jan , Knauseder Viktoria , Fischer Marlene , Dietmann Anelia , Hackl Werner O , Thomé Claudius , Schmutzhard Erich , Helbok Raimund 
Published: May 2013

Abstract
Introduction
Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH).

Methods
We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs).

Results
One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion.

Conclusions
Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH.
Dietary Vitamin D Restriction in Pregnant Female Mice Is Associated With Maternal Hypertension and Altered Placental and Fetal Development
Authors: Liu Nancy Q. , Ouyang Yi , Bulut Yasemin , Lagishetty Venu , Chan Shiao Y. , Hollis Bruce W. , Wagner Carol , Equils Ozlem , Hewison Martin 
Published: May 2013

Abstract
Epidemiology has linked vitamin D deficiency with preeclampsia in humans. We hypothesized that low vitamin D status in pregnant mice may lead to symptoms of preeclampsia. Female BL6 mice were raised on vitamin D-sufficient or -deficient diets from weeks 4 of age and then mated with vitamin D-sufficient BL6 males at week 8. The resulting pregnant mice were either allowed to deliver pups and monitored for blood pressure (BP) and weight of offspring or euthanized at day 14 or 18 of gestation (E14 or E18) for analysis of serum, placental/kidney tissues, and fetuses. At E14 serum concentrations of 25-hydroxyvitamin D (30.1 ± 5.0 vs 1.8 ± 0.6 ng/mL, P &lt; .001) and 1,25-dihydroxyvitamin D (119.5 ± 18.7 vs 37.4 ± 5.1 pg/mL, P &lt; .01) were higher in sufficient vs deficient pregnant mice. At E14 BP was significantly elevated in vitamin D-deficient pregnant mice relative to vitamin D-sufficient mice for both systolic BP (124.89 ± 2.28 vs 105.34 ± 3.61 mm Hg, P &lt; .001) and mean arterial pressure (115.33 ± 1.93 vs 89.33 ± 5.02 mm Hg, P &lt; .001). This elevation continued through pregnancy until 7 days postpartum (PP7) but returned to baseline by PP14. Analysis of maternal kidneys showed increased expression of mRNA for renin and the angiotensin II receptor (3- and 4-fold, respectively) in vitamin D-deficient vs -sufficient mice at E14. Histological analysis of E14 placentas from vitamin D-deficient mice showed decreased vascular diameter within the labyrinth region. E14 and E18 fetuses from vitamin D-deficient mice were larger than those from vitamin D-sufficient mothers. However, by PP14 pups from vitamin D-deficient mothers weighed significantly less than those from vitamin D-sufficient mothers. Resupplementation of vitamin D periconceptually partially reversed the effects of vitamin D deficiency. These data provide further evidence that low vitamin D status may predispose pregnant women to dysregulated placental development and elevated blood pressure.
Interface Shear Strength Testing of Geogrid-Reinforced Construction and Demolition Materials
Authors: Arulrajah A. , Rahman M. A. , Piratheepan J. , Bo M. W. , Imteaz M. A. 
Published: May 2013

Abstract
The interface shear strength properties of geogrid-reinforced recycled construction and demolition (C&D) materials were determined in this research to assess the viability of using geogrid-reinforced C&D materials as alternative construction materials. The C&D materials investigated were recycled concrete aggregate (RCA), crushed brick (CB), and reclaimed asphalt pavement (RAP). Biaxial and triaxial geogrids were tested as the geogrid-reinforcement materials. The interface shear strength properties of the C&D materials were ascertained by using a large direct shear test (DST) equipment. Large-scale DST was conducted for unreinforced and geogrid-reinforced C&D materials. The interface peak and residual shear strength property of unreinforced and geogrid-reinforced RCA was found to be higher than that of CB and RAP. RAP was found to have the lowest interface shear strength properties of the C&D materials. The higher strength triaxial geogrids were found to attain higher interface shear strength properties than that of the lower strength biaxial geogrids. The DST results, however, indicated that the interface shear strength properties of the geogrid-reinforced C&D materials were less than that of the respective material without reinforcement. This can be attributed to the lack of interlock between the geogrids and the recycled C&D aggregates, as well as the current conventional testing method for DST that induces a shear plane at the boundary between the lower and upper boxes where the geogrid is placed. The unreinforced and geogrid-reinforced RCA, CB, and RAP were found to meet the peak and residual shear strength requirements for typical construction materials in civil engineering applications.
Computational Inference Methods for Selective Sweeps Arising in Acute HIV Infection
Authors: Leviyang Sivan 
Published: May 2013

AbstractDuring the first weeks of human immunodeficiency virus-1 (HIV-1) infection, cytotoxic T-lymphocytes (CTLs) select for multiple escape mutations in the infecting HIV population. In recent years, methods that use escape mutation data to estimate rates of HIV escape have been developed, thereby providing a quantitative framework for exploring HIV escape from CTL response. Current methods for escape-rate inference focus on a specific HIV mutant selected by a single CTL response. However, recent studies have shown that during the first weeks of infection, CTL responses occur at one to three epitopes and HIV escape occurs through complex mutation pathways. Consequently, HIV escape from CTL response forms a complex, selective sweep that is difficult to analyze. In this work, we develop a model of initial infection, based on the well-known standard model, that allows for a description of multi-epitope response and the complex mutation pathways of HIV escape. Under this model, we develop Bayesian and hypothesis-test inference methods that allow us to analyze and estimate HIV escape rates. The methods are applied to two HIV patient data sets, concretely demonstrating the utility of our approach.
Assessing Genome-Wide Statistical Significance for Large p Small n Problems
Authors: Diao Guoqing , Vidyashankar Anand N 
Published: May 2013

Abstract
Assessing genome-wide statistical significance is an important issue in genetic studies. We describe a new resampling approach for determining the appropriate thresholds for statistical significance. Our simulation results demonstrate that the proposed approach accurately controls the genome-wide type I error rate even under the large p small n situations.
A Continuous Method for Gene Flow
Authors: Palczewski Michal , Beerli Peter 
Published: May 2013

Abstract
Most modern population genetics inference methods are based on the coalescence framework. Methods that allow estimating parameters of structured populations commonly insert migration events into the genealogies. For these methods the calculation of the coalescence probability density of a genealogy requires a product over all time periods between events. Data sets that contain populations with high rates of gene flow among them require an enormous number of calculations. A new method, transition probability-structured coalescence (TPSC), replaces the discrete migration events with probability statements. Because the speed of calculation is independent of the amount of gene flow, this method allows calculating the coalescence densities efficiently. The current implementation of TPSC uses an approximation simplifying the interaction among lineages. Simulations and coverage comparisons of TPSC vs. MIGRATE show that TPSC allows estimation of high migration rates more precisely, but because of the approximation the estimation of low migration rates is biased. The implementation of TPSC into programs that calculate quantities on phylogenetic tree structures is straightforward, so the TPSC approach will facilitate more general inferences in many computer programs.
Asymptotic Distributions of Coalescence Times and Ancestral Lineage Numbers for Populations with Temporally Varying Size
Authors: Chen Hua , Chen Kun 
Published: May 2013

Abstract
The distributions of coalescence times and ancestral lineage numbers play an essential role in coalescent modeling and ancestral inference. Both exact distributions of coalescence times and ancestral lineage numbers are expressed as the sum of alternating series, and the terms in the series become numerically intractable for large samples. More computationally attractive are their asymptotic distributions, which were derived in Griffiths (1984) for populations with constant size. In this article, we derive the asymptotic distributions of coalescence times and ancestral lineage numbers for populations with temporally varying size. For a sample of size n, denote by Tm the mth coalescent time, when m + 1 lineages coalesce into m lineages, and An(t) the number of ancestral lineages at time t back from the current generation. Similar to the results in Griffiths (1984), the number of ancestral lineages, An(t), and the coalescence times, Tm, are asymptotically normal, with the mean and variance of these distributions depending on the population size function, N(t). At the very early stage of the coalescent, when t → 0, the number of coalesced lineages n − An(t) follows a Poisson distribution, and as m → n, n(n−1)Tm/2N(0) follows a gamma distribution. We demonstrate the accuracy of the asymptotic approximations by comparing to both exact distributions and coalescent simulations. Several applications of the theoretical results are also shown: deriving statistics related to the properties of gene genealogies, such as the time to the most recent common ancestor (TMRCA) and the total branch length (TBL) of the genealogy, and deriving the allele frequency spectrum for large genealogies. With the advent of genomic-level sequencing data for large samples, the asymptotic distributions are expected to have wide applications in theoretical and methodological development for population genetic inference.
Pigment Pattern Formation in the Guppy,Poecilia reticulata, Involves the Kita and Csf1ra Receptor Tyrosine Kinases
Authors: Kottler Verena A , Fadeev Andrey , Weigel Detlef , Dreyer Christine 
Published: May 2013

AbstractMales of the guppy (Poecilia reticulata) vary tremendously in their ornamental patterns, which are thought to have evolved in response to a complex interplay between natural and sexual selection. Although the selection pressures acting on the color patterns of the guppy have been extensively studied, little is known about the genes that control their ontogeny. Over 50 years ago, two autosomal color loci, blue and golden, were described, both of which play a decisive role in the formation of the guppy color pattern. Orange pigmentation is absent in the skin of guppies with a lesion in blue, suggesting a defect in xanthophore development. In golden mutants, the development of the melanophore pattern during embryogenesis and after birth is affected. Here, we show that blue and golden correspond to guppy orthologs of colony-stimulating factor 1 receptor a (csf1ra; previously called fms) and kita. Most excitingly, we found that both genes are required for the development of the black ornaments of guppy males, which in the case of csf1ra might be mediated by xanthophore–melanophore interactions. Furthermore, we provide evidence that two temporally and genetically distinct melanophore populations contribute to the adult camouflage pattern expressed in both sexes: one early appearing and kita-dependent and the other late-developing and kita-independent. The identification of csf1ra and kita mutants provides the first molecular insights into pigment pattern formation in this important model species for ecological and evolutionary genetics.
Competition Between the Sperm of a Single Male Can Increase the Evolutionary Rate of Haploid Expressed Genes
Authors: Ezawa Kiyoshi , Innan Hideki 
Published: May 2013

AbstractThe population genetic behavior of mutations in sperm genes is theoretically investigated. We modeled the processes at two levels. One is the standard population genetic process, in which the population allele frequencies change generation by generation, depending on the difference in selective advantages. The other is the sperm competition during each genetic transmission from one generation to the next generation. For the sperm competition process, we formulate the situation where a huge number of sperm with alleles A and B, produced by a single heterozygous male, compete to fertilize a single egg. This “minimal model” demonstrates that a very slight difference in sperm performance amounts to quite a large difference between the alleles’ winning probabilities. By incorporating this effect of paternity-sharing sperm competition into the standard population genetic process, we show that fierce sperm competition can enhance the fixation probability of a mutation with a very small phenotypic effect at the single-sperm level, suggesting a contribution of sperm competition to rapid amino acid substitutions in haploid-expressed sperm genes. Considering recent genome-wide demonstrations that a substantial fraction of the mammalian sperm genes are haploid expressed, our model could provide a potential explanation of rapid evolution of sperm genes with a wide variety of functions (as long as they are expressed in the haploid phase). Another advantage of our model is that it is applicable to a wide range of species, irrespective of whether the species is externally fertilizing, polygamous, or monogamous. The theoretical result was applied to mammalian data to estimate the selection intensity on nonsynonymous mutations in sperm genes.
Investigating Incipient Speciation in Arabidopsis lyrata from Patterns of Transmission Ratio Distortion
Authors: Leppälä Johanna , Bokma Folmer , Savolainen Outi 
Published: May 2013

Abstract
Our understanding of the development of intrinsic reproductive isolation is still largely based on theoretical models and thorough empirical studies on a small number of species. Theory suggests that reproductive isolation develops through accumulation of epistatic genic incompatibilities, also known as Bateson–Dobzhansky–Muller (BDM) incompatibilities. We can detect these from marker transmission ratio distortion (TRD) in hybrid progenies of crosses between species or populations, where TRD is expected to result from selection against heterospecific allele combinations in hybrids. TRD may also manifest itself because of intragenomic conflicts or competition between gametes or zygotes. We studied early stage speciation in Arabidopsis lyrata by investigating patterns of TRD across the genome in F2 progenies of three reciprocal crosses between four natural populations. We found that the degree of TRD increases with genetic distance between crossed populations, but also that reciprocal progenies may differ substantially in their degree of TRD. Chromosomes AL6 and especially AL1 appear to be involved in many single- and two-locus distortions, but the location and source of TRD vary between crosses and between reciprocal progenies. We also found that the majority of single- and two-locus TRD appears to have a gametic, as opposed to zygotic, origin. Thus, while theory on BDM incompatibilities is typically illustrated with derived nuclear alleles proving incompatible in hybrid zygotes, our results suggest a prominent role for distortions emerging before zygote formation.