bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowerment assessment and influential factors among patients with type 2 diabetes
Authors: Tol Azar , Baghbanian Abdolvahab , Mohebbi Bahram , Shojaeizadeh Davoud , Azam Kamal , Shahmirzadi Sima Esmaeeli , Asfia Abolghasem
Published: January 2013

Background

Diabetic patients need high awareness of disease prevention to adopt self-management behaviors in their daily life. Central to this activity is patients’ empowerment. Current study was conducted to assess empowerment score and its related factors among type 2 diabetic patients.

Method

A cross-sectional study carried out over a period of nine months during 2010–2011. All patients with a diagnosis of type 2 diabetes including those referring to four hospitals affiliated with Tehran University of Medical Sciences were recruited. A total of 688 diabetic patients were identified who met the inclusion criteria and were all included in the study. Patients’ empowerment was measured by Diabetes Empowerment Scale reflecting three dimensions including managing psychosocial aspect of diabetes, assessing dissatisfaction and readiness to change and Setting and achieving diabetes goal. Collected data was analysed using SPSS software version 11.5.

Results

As total, 688 were available for analysis, ranging from 37–81 years old with mean of 54.41 years (SD = 8.22). The Mean duration of the disease was approximately 6.67 years (SD = 4.58). Dimensions of ‘managing the psychosocial aspect of diabetes’, ‘assessing dissatisfaction and readiness to change’ and ‘setting and achieving diabetes goal’ were all measured and scored for each patient. The mean score for each domain was 25.75 ± 5.55, 24.78 ± 7.54, 27.63 ± 7.90, respectively. Data analysis revealed a statistically significant reverse relationship between age and ‘assessing dissatisfaction and readiness to change’ and ‘setting and achieving diabetes goal’. In addition, disease duration had a statistically significant reverse relationship with ‘assessing dissatisfaction and readiness to change’.

Conclusion

Patients with type 2 diabetes have the potential to be empowered to manage their chronic disease if they are actively informed and educated.
Limk2 mediates semaphorin signalling in cortical interneurons migrating through the subpallium
Authors: Andrews William D. , Zito Arianna , Memi Fani , Jones Gareth , Tamamaki Nobuaki , Parnavelas John G.
Published: January 2013

En route to the neocortex, interneurons migrate around and avoid the developing striatum. This is due to the chemorepulsive cues of class 3 semaphorins (Sema3A and Sema3F) acting through neuropilin and plexin co-receptors expressed in interneurons. In a recent genetic screen aimed at identifying novel components that may play a role in interneuron migration, we identified LIM-kinase 2 (Limk2), a kinase previously shown to be involved in cell movement and in Sema7A-PlexinC1 signalling. Here we show that Limk2 is differentially expressed in interneurons, with a higher expression in the subpallium compared to cortex, suggesting it may play a role in their migration through the subpallium. Chemotactic assays, carried out with small interfering RNAs (siRNAs), revealed that Limk2-siRNA transfected interneurons are less responsive to Sema3A, but respond to Sema3F. Lack of responsiveness to Sema3A resulted in their aberrant invasion of the developing striatum, as demonstrated in brain slice preparations and in in utero electroporated mouse embryos with the same siRNAs. Our results reveal a previously unknown role for Limk2 in interneuron migration and Sema3A signalling.
Mitochondrial NDUFS3 regulates the ROS-mediated onset of metabolic switch in transformed cells
Authors: Suhane Sonal , Kanzaki Hirotaka , Arumugaswami Vaithilingaraja , Murali Ramachandran , Ramanujan V. Krishnan
Published: January 2013

Aerobic glycolysis in transformed cells is an unique metabolic phenotype characterized by a hyperactivated glycolytic pathway even in the presence of oxygen. It is not clear if the onset of aerobic glycolysis is regulated by mitochondrial dysfunction and, if so, what the metabolic windows of opportunity available to control this metabolic switch (mitochondrial to glycolytic) landscape are in transformed cells. Here we report a genetically-defined model system based on the gene-silencing of a mitochondrial complex I subunit, NDUFS3, where we demonstrate the onset of metabolic switch in isogenic human embryonic kidney cells by differential expression of NDUFS3. By means of extensive metabolic characterization, we demonstrate that NDUFS3 gene silencing systematically introduces mitochondrial dysfunction thereby leading to the onset of aerobic glycolysis in a manner dependent on NDUFS3 protein levels. Furthermore, we show that the sustained imbalance in free radical dynamics is a necessary condition to sustain the observed metabolic switch in cell lines with the most severe NDUFS3 suppression. Together, our data reveal a novel role for mitochondrial complex I subunit NDUFS3 in regulating the degree of mitochondrial dysfunction in living cells, thereby setting a “metabolic threshold” for the observation of aerobic glycolysis phenotype within the confines of mitochondrial dysfunction.
Establishment and mitotic characterization of newDrosophilaacentriolar cell lines fromDSas-4mutant
Authors: Lecland Nicolas , Debec Alain , Delmas Audrey , Moutinho-Pereira Sara , Malmanche Nicolas , Bouissou Anais , Dupré Clémence , Jourdan Aimie , Raynaud-Messina Brigitte , Maiato Helder , Guichet Antoine
Published: January 2013

In animal cells the centrosome is commonly viewed as the main cellular structure driving microtubule (MT) assembly into the mitotic spindle apparatus. However, additional pathways, such as those mediated by chromatin and augmin, are involved in the establishment of functional spindles. The molecular mechanisms involved in these pathways remain poorly understood, mostly due to limitations inherent to current experimental systems available. To overcome these limitations we have developed six new Drosophila cell lines derived from Drosophila homozygous mutants for DSas-4, a protein essential for centriole biogenesis. These cells lack detectable centrosomal structures, astral MT, with dispersed pericentriolar proteins D-PLP, Centrosomin and γ-tubulin. They show poorly focused spindle poles that reach the plasma membrane. Despite being compromised for functional centrosome, these cells could successfully undergo mitosis.

Live-cell imaging analysis of acentriolar spindle assembly revealed that nascent MTs are nucleated from multiple points in the vicinity of chromosomes. These nascent MTs then grow away from kinetochores allowing the expansion of fibers that will be part of the future acentriolar spindle. MT repolymerization assays illustrate that acentriolar spindle assembly occurs “inside-out” from the chromosomes. Colchicine-mediated depolymerization of MTs further revealed the presence of a functional Spindle Assembly Checkpoint (SAC) in the acentriolar cells. Finally, pilot RNAi experiments open the potential use of these cell lines for the molecular dissection of anastral pathways in spindle and centrosome assembly.
Essential role of grim-led programmed cell death for the establishment of corazonin-producing peptidergic nervous system during embryogenesis and metamorphosis in Drosophila melanogaster
Authors: Lee Gyunghee , Sehgal Ritika , Wang Zixing , Nair Sudershana , Kikuno Keiko , Chen Chun-Hong , Hay Bruce , Park Jae H.
Published: January 2013

In Drosophila melanogaster, combinatorial activities of four death genes, head involution defective (hid), reaper (rpr), grim, and sickle (skl), have been known to play crucial roles in the developmentally regulated programmed cell death (PCD) of various tissues. However, different expression patterns of the death genes also suggest distinct functions played by each. During early metamorphosis, a great number of larval neurons unfit for adult life style are removed by PCD. Among them are eight pairs of corazonin-expressing larval peptidergic neurons in the ventral nerve cord (vCrz). To reveal death genes responsible for the PCD of vCrz neurons, we examined extant and recently available mutations as well as RNA interference that disrupt functions of single or multiple death genes. We found grim as a chief proapoptotic gene and skl and rpr as minor ones. The function of grim is also required for PCD of the mitotic sibling cells of the vCrz neuronal precursors (EW3-sib) during embryonic neurogenesis. An intergenic region between grim and rpr, which, it has been suggested, may enhance expression of three death genes in embryonic neuroblasts, appears to play a role for the vCrz PCD, but not for the EW3-sib cell death. The death of vCrz neurons and EW3-sib is triggered by ecdysone and the Notch signaling pathway, respectively, suggesting distinct regulatory mechanisms of grim expression in a cell- and developmental stage-specific manner.
Light-activation of the Archaerhodopsin H+-pump reverses age-dependent loss of vertebrate regeneration: sparking system-level controls in vivo
Authors: Adams Dany Spencer , Tseng Ai-Sun , Levin Michael
Published: January 2013

Optogenetics, the regulation of proteins by light, has revolutionized the study of excitable cells, and generated strong interest in the therapeutic potential of this technology for regulating action potentials in neural and muscle cells. However, it is currently unknown whether light-activated channels and pumps will allow control of resting potential in embryonic or regenerating cells in vivo. Abnormalities in ion currents of non-excitable cells are known to play key roles in the etiology of birth defects and cancer. Moreover, changes in transmembrane resting potential initiate Xenopus tadpole tail regeneration, including regrowth of a functioning spinal cord, in tails that have been inhibited by natural inactivity of the endogenous H+-V-ATPase pump. However, existing pharmacological and genetic methods allow neither non-invasive control of bioelectric parameters in vivo nor the ability to abrogate signaling at defined time points. Here, we show that light activation of a H+-pump can prevent developmental defects and induce regeneration by hyperpolarizing transmembrane potentials. Specifically, light-dependent, Archaerhodopsin-based, H+-flux hyperpolarized cells in vivo and thus rescued Xenopus embryos from the craniofacial and patterning abnormalities caused by molecular blockade of endogenous H+-flux. Furthermore, light stimulation of Arch for only 2 days after amputation restored regenerative capacity to inhibited tails, inducing cell proliferation, tissue innervation, and upregulation of notch1 and msx1, essential genes in two well-known endogenous regenerative pathways. Electroneutral pH change, induced by expression of the sodium proton exchanger, NHE3, did not rescue regeneration, implicating the hyperpolarizing activity of Archaerhodopsin as the causal factor. The data reveal that hyperpolarization is required only during the first 48 hours post-injury, and that expression in the spinal cord is not necessary for the effect to occur. Our study shows that complex, coordinated sets of stable bioelectric events that alter body patterning—prevention of birth defects and induction of regeneration—can be elicited by the temporal modulation of a single ion current. Furthermore, as optogenetic reagents can be used to achieve that manipulation, the potential for this technology to impact clinical approaches for preventive, therapeutic, and regenerative medicine is extraordinary. We expect this first critical step will lead to an unprecedented expansion of optogenetics in biomedical research and in the probing of novel and fundamental biophysical determinants of growth and form.
Elevated expression of the V-ATPase C subunit triggers JNK-dependent cell invasion and overgrowth in a Drosophila epithelium
Authors: Petzoldt Astrid G. , Gleixner Eva Maria , Fumagalli Arianna , Vaccari Thomas , Simons Matias
Published: January 2013

The C subunit of the vacuolar H+-ATPase or V-ATPase regulates the activity and assembly of the proton pump at cellular membranes. It has been shown to be strongly upregulated in oral squamous cell carcinoma, a highly metastatic epithelial cancer. In addition, increased V-ATPase activity appears to correlate with invasiveness of cancer cells, but the underlying mechanism is largely unknown. Using the Drosophila wing imaginal epithelium as an in vivo model system, we demonstrate that overexpression of Vha44, the Drosophila orthologue of the C subunit, causes a tumor-like tissue transformation in cells of the wing epithelium. Overexpressing cells are excluded from the epithelium and acquire invasive properties while displaying high apoptotic rates. Blocking apoptosis in these cells unmasks a strong proliferation stimulus, leading to overgrowth. Furthermore, we show that excess Vha44 greatly increases acidification of endocytic compartments and interferes with endosomal trafficking. As a result, cargoes such as GFP-Lamp1 and Notch accumulate in highly acidified enlarged endolysosomal compartments. Consistent with previous reports on the endocytic activation of Eiger/JNK signaling, we find that V-ATPase stimulation by Vha44 causes JNK signaling activation whereas downmodulation of JNK signaling rescues the invasive phenotypes. In summary, our in vivo-findings demonstrate that increased levels of V-ATPase C subunit induce a Eiger/JNK-dependent cell transformation within an epithelial organ that recapitulates early carcinoma stages.
The fraction of strongly bound cross-bridges is increased in mice that carry the myopathy-linked myosin heavy chain mutation MYH4L342Q
Authors: Lindqvist Johan , Iwamoto Hiroyuki , Blanco Gonzalo , Ochala Julien
Published: January 2013

Myosinopathies have emerged as a new group of diseases and are caused by mutations in genes encoding myosin heavy chain (MyHC) isoforms. One major hallmark of these diseases is skeletal muscle weakness or paralysis, but the underlying molecular mechanisms remain unclear. Here, we have undertaken a detailed functional study of muscle fibers from Myh4arl mice, which carry a mutation that provokes an L342Q change within the catalytic domain of the type IIb skeletal muscle myosin protein MYH4. Because homozygous animals develop rapid muscle-structure disruption and lower-limb paralysis, they must be killed by postnatal day 13, so all experiments were performed using skeletal muscles from adult heterozygous animals (Myh4arl/+). Myh4arl/+ mice contain MYH4L342Q expressed at 7% of the levels of the wild-type (WT) protein and are overtly and histologically normal. However, mechanical and X-ray diffraction pattern analyses of single membrane-permeabilized fibers revealed, upon maximal Ca2+ activation, higher stiffness as well as altered meridional and equatorial reflections in Myh4arl/+ mice when compared with age-matched WT animals. Under rigor conditions, by contrast, no difference was observed between Myh4arl/+ and WT mice. Altogether, these findings prove that, in adult MYH4L342Q heterozygous mice, the transition from weak to strong myosin cross-bridge binding is facilitated, increasing the number of strongly attached myosin heads, thus enhancing force production. These changes are predictably exacerbated in the type IIb fibers of homozygous mice, in which the embryonic myosin isoform is fully replaced by MYH4L342Q, leading to a hypercontraction, muscle-structure disruption and lower-limb paralysis. Overall, these findings provide important insights into the molecular pathogenesis of skeletal myosinopathies.
piRNA dynamics in divergent zebrafish strains reveal long-lasting maternal influence on zygotic piRNA profiles
Authors: Kaaij Lucas J.T. , Hoogstrate Suzanne W. , Berezikov Eugene , Ketting René F.
Published: January 2013

Transposable elements (TEs) are mobile genetic elements that can have many deleterious effects on the fitness of their host. The germline-specific PIWI pathway guards the genome against TEs, deriving its specificity from sequence complementarity between PIWI-bound small RNAs (piRNAs) and the TEs. The piRNAs are derived from so-called piRNA clusters. Recent studies have demonstrated that the piRNA repertoire can be adjusted to accommodate recent TE invasions by capturing invading TEs in piRNA loci. Thus far, no information concerning piRNA divergence is available from vertebrates. We present piRNA analyses of two relatively divergent zebrafish strains. We find that significant differences in the piRNA populations have accumulated, most notably among active class I TEs. This divergence can be split into differences in piRNA abundance per element and differences in sense/antisense polarity ratios. In crosses between animals of the different strains, many of these differences are resolved in the progeny. However, some differences remain, often leaning to the maternally contributed piRNA population. These differences can be detected at least two generations later. Our data illustrate, for the first time, the fluidity of piRNA populations in vertebrates and how the established diversity is transmitted to future generations.
HnRNPH1/H2, U1 snRNP, and U11 snRNP cooperate to regulate the stability of the U11-48K pre-mRNA
Authors: Turunen Janne J. , Verma Bhupendra , Nyman Tuula A. , Frilander Mikko J.
Published: January 2013

Alternative splicing (AS) is a major contributor to proteome diversity, but it also regulates gene expression by introducing premature termination codons (PTCs) that destabilize transcripts, typically via the nonsense-mediated decay (NMD) pathway. Such AS events often take place within long, conserved sequence elements, particularly in genes encoding various RNA binding proteins. AS-NMD is often activated by the protein encoded by the same gene, leading to a self-regulating feedback loop that maintains constant protein levels. However, cross-regulation between different RNA binding proteins is also common, giving rise to finely tuned regulatory networks. Recently, we described a feedback mechanism regulating two protein components of the U12-dependent spliceosome (U11-48K and U11/U12-65K) through a highly conserved sequence element. These elements contain a U11 snRNP-binding splicing enhancer (USSE), which, through the U11 snRNP, activates an upstream U2-type 3′ss, resulting in the degradation of the U11-48K mRNA by AS-NMD. Through phylogenetic analysis, we now identify a G-rich sequence element that is conserved in fishes as well as mammals. We show that this element binds hnRNPF/H proteins in vitro. Knockdown of hnRNPH1/H2 or mutations in the G-run both lead to enhanced activation of the 3′ss in vivo, suggesting that hnRNPH1/H2 proteins counteract the 3′ss activation. Furthermore, we provide evidence that U1 binding immediately downstream from the G-run similarly counteracts the U11-mediated activation of the alternative 3′ss. Thus, our results elucidate the mechanism in which snRNPs from both spliceosomes together with hnRNPH1/H2 proteins regulate the recognition and activation of the highly conserved alternative splice sites within the U11-48K pre-mRNA.
Reexamining Discrete Approximations to Continuous Distributions
Authors: Hammond Robert K. , Bickel J. Eric
Published: January 2013

Discretization is a common decision analysis technique for which many methods are described in the literature and employed in practice. The accuracy of these methods is typically judged by how well they match the mean, variance, and possibly higher moments of the underlying continuous probability distribution. Previous authors have analyzed the accuracy of differing discretization methods across a limited set of distributions drawn from particular families (e.g., the bell-shaped beta distributions). In this paper, we extend this area of research by (i) using the Pearson distribution system to consider a wide range of distribution shapes and (ii) including common, but previously unexplored, discretization methods. In addition, we propose new three-point discretizations tailored to specific distribution types that improve upon existing methods.
Approximating Joint Probability Distributions Given Partial Information
Authors: Montiel Luis V. , Bickel J. Eric
Published: January 2013

In this paper, we propose new methods to approximate probability distributions that are incompletely specified. We compare these methods to the use of maximum entropy and quantify the accuracy of all methods within the context of an illustrative example. We show that within the context of our example, the methods we propose are more accurate than existing methods.
Lifts of Convex Sets and Cone Factorizations
Authors: Gouveia João , Parrilo Pablo A. , Thomas Rekha R.
Published: January 2013

In this paper, we address the basic geometric question of when a given convex set is the image under a linear map of an affine slice of a given closed convex cone. Such a representation or lift of the convex set is especially useful if the cone admits an efficient algorithm for linear optimization over its affine slices. We show that the existence of a lift of a convex set to a cone is equivalent to the existence of a factorization of an operator associated to the set and its polar via elements in the cone and its dual. This generalizes a theorem of Yannakakis that established a connection between polyhedral lifts of a polytope and nonnegative factorizations of its slack matrix. Symmetric lifts of convex sets can also be characterized similarly. When the cones live in a family, our results lead to the definition of the rank of a convex set with respect to this family. We present results about this rank in the context of cones of positive semidefinite matrices. Our methods provide new tools for understanding cone lifts of convex sets.
A Note on Roth's Consensus Property of Many-to-One Matching
Authors: Li Jianrong
Published: January 2013

Roth (Roth AE (1985) Conflict and coincidence of interest in job matching: Some new results and open questions. Math. Oper. Res. 10(3):379–389) claimed that (i) if each firm is allowed to select its most preferred subset of employees from those that assigned to it at two different stable matchings, then the choices result in a stable matching; and (ii) the set of stable matchings is a lattice under the partial order of the firms' common interests. Here, we provide counterexamples that show that these claims are incorrect, and we explain the flaws in Roth's reasoning.
Inverse Polynomial Optimization
Authors: Lasserre Jean B.
Published: January 2013

We consider the inverse optimization problem associated with the polynomial program [Formula: see text] and a given current feasible solution [Formula: see text]. We provide a systematic numerical scheme to compute an inverse optimal solution. That is, we compute a polynomial [Formula: see text] (which may be of the same degree as f, if desired) with the following properties: (a) y is a global minimizer of [Formula: see text] on K with a Putinar's certificate with an a priori degree bound d fixed, and (b) [Formula: see text] minimizes [Formula: see text] (which can be the l1, l2 or l∞-norm of the coefficients) over all polynomials with such properties. Computing [Formula: see text] reduces to solving a semidefinite program whose optimal value also provides a bound on how far f(y) is from the unknown optimal value f*. The size of the semidefinite program can be adapted to the available computational capabilities. Moreover, if one uses the l1-norm, then [Formula: see text] takes a simple and explicit canonical form. Some variations are also discussed.
Confidence Regions for Stochastic Variational Inequalities
Authors: Lu Shu , Budhiraja Amarjit
Published: January 2013

The sample average approximation (SAA) method is a basic approach for solving stochastic variational inequalities (SVI). It is well known that under appropriate conditions the SAA solutions provide asymptotically consistent point estimators for the true solution to an SVI. It is of fundamental interest to use such point estimators along with suitable central limit results to develop confidence regions of prescribed level of significance for the true solution. However, standard procedures are not applicable because the central limit theorem that governs the asymptotic behavior of SAA solutions involves a discontinuous function evaluated at the true solution of the SVI. This paper overcomes such a difficulty by exploiting the precise geometric structure of the variational inequalities and by appealing to certain large deviations probability estimates, and proposes a method to build asymptotically exact confidence regions for the true solution that are computable from the SAA solutions. We justify this method theoretically by establishing a precise limit theorem, apply it to complementarity problems, and test it with a linear complementarity problem.
The Clarke Generalized Gradient for Functions Whose Epigraph Has Positive Reach
Authors: Colombo Giovanni , Marigonda Antonio , Wolenski Peter R.
Published: January 2013

We consider the class of continuous functions that map an open set Ω ⫅ ℝn to ℝ with an epigraph having (locally) positive reach with an additional property. This class contains all finite convex and C1, 1 functions, but also ones that are not necessarily Lipschitz continuous. We provide a representation formula for the Clarke generalized gradient of such functions using convex combinations and limits of gradients at differentiability points, thus offering an alternative to the well-known proximal normal formula by replacing a pointedness assumption by one of positive reach. Our proof consists of a detailed analysis of singularities using methods taken from both nonsmooth analysis and geometric measure theory, and is based on an induction argument. As an application, we prove for a particular class of Hamilton-Jacobi equations that an a.e. solution whose hypograph has positive reach and satisfies an additional property is indeed the unique viscosity solution.
Weak Recovery Conditions from Graph Partitioning Bounds and Order Statistics
Authors: d'Aspremont Alexandre , El Karoui Noureddine
Published: January 2013

We study a weaker formulation of the nullspace property which guarantees recovery of sparse signals from linear measurements by 𝓁1 minimization. We require this condition to hold only with high probability, given a distribution on the nullspace of the coding matrix A. Under some assumptions on the distribution of the reconstruction error, we show that testing these weak conditions means bounding the optimal value of two classical graph partitioning problems: the k-Dense-Subgraph and MaxCut problems. Both problems admit efficient, relatively tight relaxations, and we use a randomization argument to produce new approximation bounds for k-Dense-Subgraph. We test the performance of our results on several families of coding matrices.
Light-driven hydrogen evolution system with glutamic-acid-modified
zinc porphyrin as photosensitizer and [FeFe]-hydrogenase model as
catalyst
Authors: Yu Shan , Wang Feng , Wang Jing-Jing , Wang Hong-Yan , Chen Bin , Feng Ke , Tung Chen-Ho , Wu Li-Zhu
Published: January 2013

An intermolecular light-driven hydrogen evolution system with free
glutamic-acid-modified zinc tetra(p-phenyl) porphyrin
(Glu-ZnP) as a photosensitizer and
[Fe2(CO)6(μ-adt)C6H5] [μ-adt =
N(CH2S)2] (Badt) as a catalyst has
been constructed. Using phenylmercaptan (BSH) as electron donor
and acetic acid (HOAc) as proton source, hydrogen was obtained after irradiation
with visible light for 2 h; the efficiency is comparable to that of the similar
intramolecular dyad. Steady-state and time-resolved spectroscopy and cyclic
voltammetry show that both the first and the second electron transfer from
singlet
1*

Glu-ZnP to
Badt and reduced Badt are
thermodynamically feasible. However, the competition of electron transfer from
singlet
1*

Glu-ZnP to Badt
with intersystem crossing from singlet

1*

Glu-ZnP to triplet

3*

Glu-ZnP, inefficient
electron transfer from triplet

3*

Glu-ZnP to
Badt, and the lower energy of triplet

3*

Glu-ZnP and possible

3*

Badt to that of yielded
charge-separated state of
Glu-ZnP

+·
-Badt
−· were
believed to be the obstacles for efficient hydrogen evolution.
Dimerization and Viscosity of Acetic Acid Vapor
Authors: Vogel Eckhard , Bich Eckard
Published: January 2013

Results of new relative measurements on the vapor of acetic acid are reported. The measurements were based on a single calibration at room temperature with a theoretically calculated viscosity value of argon. Nineteen isochoric series, differing in density, were performed in an all-quartz oscillating-disk viscometer from 298 to 598 K and for densities between 0.5 and 61 mol m-3. The uncertainty of the experimental data is ±0.5% at low densities and ±(0.3−0.4)% at high densities increasing with temperature. This is inferior compared with measurements on simple gases due to adsorption effects on quartz at low temperatures and to thermal decomposition at high temperatures. Isotherms recalculated from the original isochoric data show with decreasing density a strong curvature with negative slope, particularly at low temperatures. The further evaluation accounts for the fact that a strong dimerization depending on temperature occurs in acetic acid vapor. The isotherms, resulting from an association model which considers additional interactions between monomers and dimers, show a smaller curvature in terms of the mole fraction of monomers. Viscosity values for monomers and dimers were deduced using a simplified equation for the viscosity of a gas mixture. These values are restricted to 570 K due to thermal decomposition and low mole fractions of the dimers at high temperature. Furthermore, viscosity values for the saturated vapor could be determined at low temperatures.
Melville’s Motley Crew: History and Constituent Power in Billy Budd
Authors: Drysdale David J.
Published: January 2013

This essay reads Herman Melville’s final novel Billy Budd (written 1886–1891) in light of recent scholarly interventions into "oceanic studies." Melville’s parable of authority and resistance reveals how oceanic forms of power are contained and appropriated by national discourse. Focusing especially on the vexed relationship between the eponymous "Handsome Sailor" and Captain Vere, the essay claims that Billy Budd depicts the conflict between the transformative potential of what Peter Linebaugh and Marcus Rediker term "hydrarchy" and the "formed, measured forms" favored by Vere and the nation-state he represents. In narrating Billy Budd’s incorporation into the machinery of state power on board the Bellipotent, Melville’s novella reveals the complicity between official accounts of history and the counterinsurgent project of colonial power. Even as Melville depicts this process of historical fashioning, however, he also points to ways in which such a logic might be resisted by a canny reader who looks to the "ragged edges" of narrative.
Atorvastatin administration is associated with dose-related changes in IGF bioavailability
Authors: Narayanan Ram P , Gittins Matthew , Siddals Kirk W , Oliver Robert L , Hudson Julie E , White Anne , Durrington Paul , Davies Robert R , Rutter Martin K , Gibson J Martin
Published: January 2013

Objective

IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.

Design and methods

We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (s.d.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg).

Results

Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: −3 (−21 to 14) ng/ml; IGF2: −23 (−65 to 18) ng/ml and IGFBP3: −0.34 (−0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant −0.41 (−0.69 to 0.13, P=0.004).

Conclusion

IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.
Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome
Authors: Chen Xinwang , Jia Xiao , Qiao Jie , Guan Youfei , Kang Jihong
Published: January 2013

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Dysfunction of adipose tissue has been implicated in the pathophysiology of PCOS. Increasing evidence shows that the dysregulated expression of adipokines, the secreted products of adipose tissue, plays an important role in the pathology of PCOS. Here, we review the role of several identified adipokines that may act as a link between obesity and PCOS. PCOS also reciprocally influences the profile of adipokines. Insight into the underlying mechanisms will help better understand the pathology of PCOS and identify new therapeutic targets of this syndrome.
A Computational Approach to Developing Mathematical Models of Polyploid Meiosis
Authors: Rehmsmeier Marc
Published: January 2013

Mathematical models of meiosis that relate offspring to parental genotypes through parameters such as meiotic recombination frequency have been difficult to develop for polyploids. Existing models have limitations with respect to their analytic potential, their compatibility with insights into mechanistic aspects of meiosis, and their treatment of model parameters in terms of parameter dependencies. In this article I put forward a computational approach to the probabilistic modeling of meiosis. A computer program enumerates all possible paths through the phases of replication, pairing, recombination, and segregation, while keeping track of the probabilities of the paths according to the various parameters involved. Probabilities for classes of genotypes or phenotypes are added, and the resulting formulas are simplified by the symbolic-computation system Mathematica. An example application to autotetraploids results in a model that remedies the limitations of previous models mentioned above. In addition to the immediate implications, the computational approach presented here can be expected to be useful through opening avenues for modeling a host of processes, including meiosis in higher-order ploidies.
Vps Factors Are Required for Efficient Transcription Elongation in Budding Yeast
Authors: Gaur Naseem A , Hasek Jiri , Brickner Donna Garvey , Qiu Hongfang , Zhang Fan , Wong Chi-Ming , Malcova Ivana , Vasicova Pavla , Brickner Jason H , Hinnebusch Alan G
Published: January 2013

There is increasing evidence that certain Vacuolar protein sorting (Vps) proteins, factors that mediate vesicular protein trafficking, have additional roles in regulating transcription factors at the endosome. We found that yeast mutants lacking the phosphatidylinositol 3-phosphate [PI(3)P] kinase Vps34 or its associated protein kinase Vps15 display multiple phenotypes indicating impaired transcription elongation. These phenotypes include reduced mRNA production from long or G+C-rich coding sequences (CDS) without affecting the associated GAL1 promoter activity, and a reduced rate of RNA polymerase II (Pol II) progression through lacZ CDS in vivo. Consistent with reported genetic interactions with mutations affecting the histone acetyltransferase complex NuA4, vps15Δ and vps34Δ mutations reduce NuA4 occupancy in certain transcribed CDS. vps15Δ and vps34Δ mutants also exhibit impaired localization of the induced GAL1 gene to the nuclear periphery. We found unexpectedly that, similar to known transcription elongation factors, these and several other Vps factors can be cross-linked to the CDS of genes induced by Gcn4 or Gal4 in a manner dependent on transcriptional induction and stimulated by Cdk7/Kin28-dependent phosphorylation of the Pol II C-terminal domain (CTD). We also observed colocalization of a fraction of Vps15-GFP and Vps34-GFP with nuclear pores at nucleus–vacuole (NV) junctions in live cells. These findings suggest that Vps factors enhance the efficiency of transcription elongation in a manner involving their physical proximity to nuclear pores and transcribed chromatin.
A Novel Generalized Ridge Regression Method for Quantitative Genetics
Authors: Shen Xia , Alam Moudud , Fikse Freddy , Rönnegård Lars
Published: January 2013

As the molecular marker density grows, there is a strong need in both genome-wide association studies and genomic selection to fit models with a large number of parameters. Here we present a computationally efficient generalized ridge regression (RR) algorithm for situations in which the number of parameters largely exceeds the number of observations. The computationally demanding parts of the method depend mainly on the number of observations and not the number of parameters. The algorithm was implemented in the R package bigRR based on the previously developed package hglm. Using such an approach, a heteroscedastic effects model (HEM) was also developed, implemented, and tested. The efficiency for different data sizes were evaluated via simulation. The method was tested for a bacteria-hypersensitive trait in a publicly available Arabidopsis data set including 84 inbred lines and 216,130 SNPs. The computation of all the SNP effects required <10 sec using a single 2.7-GHz core. The advantage in run time makes permutation test feasible for such a whole-genome model, so that a genome-wide significance threshold can be obtained. HEM was found to be more robust than ordinary RR (a.k.a. SNP-best linear unbiased prediction) in terms of QTL mapping, because SNP-specific shrinkage was applied instead of a common shrinkage. The proposed algorithm was also assessed for genomic evaluation and was shown to give better predictions than ordinary RR.
Correcting Coalescent Analyses for Panel-Based SNP Ascertainment
Authors: McGill James R , Walkup Elizabeth A , Kuhner Mary K
Published: January 2013

Single-nucleotide polymorphism (SNP) data are routinely obtained by sequencing a region of interest in a small panel, constructing a chip with probes specific to sites found to vary in the panel, and using the chip to assay subsequent samples. The size of the chip is often reduced by removing low-frequency alleles from the set of SNPs. Using coalescent estimation of the scaled population size parameter, Θ, as a test case, we demonstrate the loss of information inherent in this procedure and develop corrections for coalescent analysis of SNPs obtained via a panel. We show that more accurate Θ-estimates can be recovered if the panel size is known, but at considerable computational cost as the panel individuals must be explicitly modeled in the analysis. We extend this technique to apply to the case where rare alleles have been omitted from the SNP panel. We find that when appropriate corrections for panel ascertainment and rare-allele omission are used, the biases introduced by ascertainment are largely correctable, but recovered estimates are less accurate than would be obtained with fully sequenced data. This method is then applied to recombinant multiple population data to investigate the effects of recombination and migration on the estimate of Θ.
Genetic Dissection of a Major Anthocyanin QTL Contributing to Pollinator-Mediated Reproductive Isolation Between Sister Species ofMimulus
Authors: Yuan Yao-Wu , Sagawa Janelle M , Young Riane C , Christensen Brian J , Bradshaw Harvey D
Published: January 2013

Prezygotic barriers play a major role in the evolution of reproductive isolation, which is a prerequisite for speciation. However, despite considerable progress in identifying genes and mutations responsible for postzygotic isolation, little is known about the genetic and molecular basis underlying prezygotic barriers. The bumblebee-pollinated Mimulus lewisii and the hummingbird-pollinated M. cardinalis represent a classic example of pollinator-mediated prezygotic isolation between two sister species in sympatry. Flower color differences resulting from both carotenoid and anthocyanin pigments contribute to pollinator discrimination between the two species in nature. Through fine-scale genetic mapping, site-directed mutagenesis, and transgenic experiments, we demonstrate that a single-repeat R3 MYB repressor, ROSE INTENSITY1 (ROI1), is the causal gene underlying a major quantitative trait locus (QTL) with the largest effect on anthocyanin concentration and that cis-regulatory change rather than coding DNA mutations cause the allelic difference between M. lewisii and M. cardinalis. Together with the genomic resources and stable transgenic tools developed here, these results suggest that Mimulus is an excellent platform for studying the genetics of pollinator-mediated reproductive isolation and the molecular basis of morphological evolution at the most fundamental level—gene by gene, mutation by mutation.
Nonself Recognition Through Intermolecular Disulfide Bond Formation of Ribonucleotide Reductase in Neurospora
Authors: Smith Robert P , Wellman Kenji , Haidari Leila , Masuda Hirohisa , Smith Myron L
Published: January 2013

Type I ribonucleotide reductases (RNRs) are conserved across diverse taxa and are essential for the conversion of RNA into DNA precursors. In Neurospora crassa, the large subunit of RNR (UN-24) is unusual in that it also has a nonself recognition function, whereby coexpression of Oak Ridge (OR) and Panama (PA) alleles of un-24 in the same cell leads to growth inhibition and cell death. We show that coexpressing these incompatible alleles of un-24 in N. crassa results in a high molecular weight UN-24 protein complex. A 63-amino-acid portion of the C terminus was sufficient for un-24PA incompatibility activity. Redox active cysteines that are conserved in type I RNRs and essential for their catalytic function were found to be required for incompatibility activity of both UN-24OR and UN-24PA. Our results suggest a plausible model of un-24 incompatibility activity in which the formation of a complex between the incompatible RNR proteins is potentiated by intermolecular disulfide bond formation.
Compensatory Evolution and the Origins of Innovations
Authors: Rajon Etienne , Masel Joanna
Published: January 2013

Cryptic genetic sequences have attenuated effects on phenotypes. In the classic view, relaxed selection allows cryptic genetic diversity to build up across individuals in a population, providing alleles that may later contribute to adaptation when co-opted—e.g., following a mutation increasing expression from a low, attenuated baseline. This view is described, for example, by the metaphor of the spread of a population across a neutral network in genotype space. As an alternative view, consider the fact that most phenotypic traits are affected by multiple sequences, including cryptic ones. Even in a strictly clonal population, the co-option of cryptic sequences at different loci may have different phenotypic effects and offer the population multiple adaptive possibilities. Here, we model the evolution of quantitative phenotypic characters encoded by cryptic sequences and compare the relative contributions of genetic diversity and of variation across sites to the phenotypic potential of a population. We show that most of the phenotypic variation accessible through co-option would exist even in populations with no polymorphism. This is made possible by a history of compensatory evolution, whereby the phenotypic effect of a cryptic mutation at one site was balanced by mutations elsewhere in the genome, leading to a diversity of cryptic effect sizes across sites rather than across individuals. Cryptic sequences might accelerate adaptation and facilitate large phenotypic changes even in the absence of genetic diversity, as traditionally defined in terms of alternative alleles.
Breakdown in the Process of Incipient Speciation inAnopheles gambiae
Authors: Nwakanma Davis C , Neafsey Daniel E , Jawara Musa , Adiamoh Majidah , Lund Emily , Rodrigues Amabelia , Loua Kovana M , Konate Lassana , Sy Ngayo , Dia Ibrahima , Awolola T Samson , Muskavitch Marc A T , Conway David J
Published: January 2013

Understanding genetic causes and effects of speciation in sympatric populations of sexually reproducing eukaryotes is challenging, controversial, and of practical importance for controlling rapidly evolving pests and pathogens. The major African malaria vector mosquito Anopheles gambiae sensu stricto (s.s.) is considered to contain two incipient species with strong reproductive isolation, hybrids between the M and S molecular forms being very rare. Following recent observations of higher proportions of hybrid forms at a few sites in West Africa, we conducted new surveys of 12 sites in four contiguous countries (The Gambia, Senegal, Guinea-Bissau, and Republic of Guinea). Identification and genotyping of 3499 A. gambiae s.s. revealed high frequencies of M/S hybrid forms at each site, ranging from 5 to 42%, and a large spectrum of inbreeding coefficient values from 0.11 to 0.76, spanning most of the range expected between the alternative extremes of panmixia and assortative mating. Year-round sampling over 2 years at one of the sites in The Gambia showed that M/S hybrid forms had similar relative frequencies throughout periods of marked seasonal variation in mosquito breeding and abundance. Genome-wide scans with an Affymetrix high-density single-nucleotide polymorphism (SNP) microarray enabled replicate comparisons of pools of different molecular forms, in three separate populations. These showed strong differentiation between M and S forms only in the pericentromeric region of the X chromosome that contains the molecular form-specific marker locus, with only a few other loci showing minor differences. In the X chromosome, the M/S hybrid forms were more differentiated from M than from S forms, supporting a hypothesis of asymmetric introgression and backcrossing.