bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial effect of a weight-stable, low-fat/low-saturated fat/low-glycaemic index diet to reduce liver fat in older subjects
Authors: Utzschneider Kristina M. , Bayer-Carter Jennifer L. , Arbuckle Matthew D. , Tidwell Jaime M. , Richards Todd L. , Craft Suzanne
Published: July 2012

Non-alcoholic fatty liver disease is associated with insulin resistance and dyslipidaemia and can progress to steatohepatitis and cirrhosis. We sought to determine whether dietary fat and saturated fat content alter liver fat in the absence of weight change in an older population. Liver fat was quantified by magnetic resonance spectroscopy before and after 4 weeks on an isoenergetic low-fat/low-saturated fat/low-glycaemic index (LGI) (LSAT: 23 % fat/7 % saturated fat/GI < 55) or a high-fat/high-saturated fat/high-GI (HSAT: 43 % fat/24 % saturated fat/GI>70) diet in older subjects. In the present study, twenty subjects (seven males/thirteen females; age 69·3 (sem1·6) years, BMI 26·9 (sem0·8) kg/m2) were randomised to the LSAT diet and fifteen subjects (six males/nine females; age 68·6 (sem1·8) years, BMI 28·1 (sem0·9) kg/m2) to the HSAT diet. Weight remained stable. Liver fat decreased significantly on the LSAT diet (median 2·2 (interquartile range (IQR) 3·1) to 1·7 (IQR 1·8) %,P= 0·002) but did not change on the HSAT diet (median 1·2 (IQR 4·1) to 1·6 (IQR 3·9) %). The LSAT diet lowered fasting glucose and total cholesterol, HDL-cholesterol and LDL-cholesterol and raised TAG (P< 0·05), while the HSAT diet had no effect on glucose or HDL-cholesterol but increased total cholesterol and LDL-cholesterol (P< 0·05). Fasting insulin and homeostasis model of insulin resistance did not change significantly on either diet, but the Matsuda index of insulin sensitivity improved on the LSAT diet (P< 0·05). Assignment to the LSATv.HSAT diet was a predictor of changes in lipid parameters but not liver fat. We conclude that diet composition may be an important factor in the accumulation of liver fat, with a low-fat/low-saturated fat/LGI diet being beneficial.
Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45–75 years
Authors: Wang Yu , Li Xiaoying , Qin Xianhui , Cai Yefeng , He Mingli , Sun Liming , Li Jianping , Zhang Yan , Tang Genfu , Wang Binyan , Sun Ningling , Xu Xin , Liu Lisheng , Xu Xiping , Huo Yong
Published: July 2012

We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 μmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51·6 % (42·7 % in women and 65·6 % in men). The OR of hyperhomocysteinaemia were 1·52 (95 % CI 1·39, 1·67) and 2·32 (95 % CI 2·07, 2·61) for participants aged 55–65 and 65–75 v. 45–55 years; 1·27 (95 % CI 1·18, 1·37) for participants with a BMI ≥ 25 v. < 25 kg/m2; 1·14 (95 % CI 1·06, 1·23) for participants with v. without antihypertensive treatment; 1·09 (95 % CI 1·00, 1·18) for residents inland v. coastal; 0·89 (95 % CI 0·82, 0·97) and 0·83 (95 % CI 0·74, 0·92) for participants with moderate and high v. low physical activity levels; 1·54 (95 % CI 1·41, 1·68) and 2·47 (95 % CI 2·17, 2·81) for participants with a glomerular filtration rate 60–90 and < 60 v. ≥ 90 ml/min per 1·73 m2; and 1·20 (95 % CI 1·07, 1·35) and 3·81 (95 % CI 3·33, 4·36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12·1 (interquartile range (IQR) 9·2–14·5) v. 11·9 (IQR 9·3–14·0) μmol/l, P= 0·005; women: geometric mean 10·3 (IQR 8·3–13·0) v. 9·6 (IQR 7·8–11·6) μmol/l, P= 0·010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12·1 (IQR 9·2–14·4) v. 11·7 (IQR 9·2–14·0), P= 0·016) and in male non-drinkers (yes v. no) (geometric mean 12·3 (IQR 9·4–14·8) v. 11·7 (IQR 9·1–13·9), P= 0·014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.
(n + 1)-TENSOR NORMS OF LAPRESTÉ'S TYPE
Authors: LÓPEZ MOLINA J. A.
Published: July 2012

We study an (n + 1)-tensor norm αr extending to (n + 1)-fold tensor products, the classical one of Lapresté in the case n = 1. We characterise the maps of the minimal and the maximal multi-linear operator ideals related to αr in the sense of Defant and Floret (A. Defant and K. Floret, Tensor norms and operator ideals, North Holland Mathematical Studies, no. 176 (North Holland, Amsterdam, Netherlands, 1993). As an application we give a complete description of the reflexivity of the αr-tensor product (⊗j = 1n + 1 ℓuj, αr).
Influence of elevated atmospheric carbon dioxide and supplementary irrigation on greenhouse gas emissions from a spring wheat crop in southern Australia
Authors: LAM S. K. , CHEN D. , NORTON R. , ARMSTRONG R. , MOSIER A. R.
Published: July 2012

The effect of elevated carbon dioxide (CO2) concentration on greenhouse gas (GHG) emission from semi-arid cropping systems is poorly understood. Closed static chambers were used to measure the fluxes of nitrous oxide (N2O), CO2and methane (CH4) from a spring wheat (Triticum aestivumL. cv. Yitpi) crop-soil system at the Australian grains free-air carbon dioxide enrichment (AGFACE) facility at Horsham in southern Australia in 2009. The targeted atmospheric CO2concentrations (hereafter CO2concentration is abbreviated as [CO2]) were 390 (ambient) and 550 (elevated) μmol/mol for both rainfed and supplementary irrigated treatments. Gas measurements were conducted at five key growth stages of wheat. Elevated [CO2] increased the emission of N2O and CO2by 108 and 29%, respectively, with changes being greater during the wheat vegetative stage. Supplementary irrigation reduced N2O emission by 36%, suggesting that N2O was reduced to N2in the denitrification process. Irrigation increased CO2flux by 26% at ambient [CO2] but not at elevated [CO2], and had no impact on CH4flux. The present results suggest that under future atmospheric [CO2], agricultural GHG emissions at the vegetative stage may be higher and irrigation is likely to reduce the emissions from semi-arid cropping systems.
A review of factors influencing milk urea concentration and its relationship with urinary urea excretion in lactating dairy cattle
Authors: SPEK J. W. , DIJKSTRA J. , VAN DUINKERKEN G. , BANNINK A.
Published: July 2012

Milk urea nitrogen (MUN) concentration in dairy cows may serve as an on-farm indicator to guide nutritional strategies and to help reduce emissions of nitrogen (N) to the environment. Excretion of urinary urea nitrogen (UUN) is positively related to MUN, but the relationship is highly variable. The accuracy of MUN as a predictor of UUN may improve when various factors that affect this relationship can be taken into account. The current review discusses the impact of a number of UUN : MUN ratio influencing factors related to: physiological mechanisms in the dairy cow, farm management, differences between individual cows, nutrition and analysis methods for MUN. Factors related to variation in water intake, urine production, dietary protein level, body weight (BW) and time and frequency of feeding and milking are shown to affect MUN and its relationship with UUN. In addition, a number of factors are discussed that are likely to affect this relationship such as biological rhythm, renal reabsorption of urea during periods of protein deficiency and breeding value for MUN. Accounting for these above-mentioned factors in the relationship between MUN and UUN might substantially improve the applicability and accuracy of MUN as a predictor of protein utilization efficiency and UUN.
MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse
Authors: Onwuameze O. E. , Nam K. W. , Epping E. A. , Wassink T. H. , Ziebell S. , Andreasen N. C. , Ho B.-C.
Published: July 2012

Background

Adolescent marijuana use is associated with increased risk for schizophrenia. We previously reported that marijuana misuse in conjunction with specific cannabinoid receptor 1 (CNR1) genetic variants (rs12720071-G-allele carriers) contributed to white-matter (WM) brain volume deficits in schizophrenia patients. In this study, we assessed the influence of another cannabinoid-related gene, mitogen-activated protein kinase 14 (MAPK14), and potential MAPK14–CNR1 gene–gene interactions in conferring brain volume abnormalities among schizophrenia patients with marijuana abuse/dependence. MAPK14 encodes a member of the MAPK family involved in diverse cellular processes, including CNR1-induced apoptosis.

Method

We genotyped 235 schizophrenia patients on nine MAPK14 tag single nucleotide polymorphisms (tSNPs). Approximately one quarter of the sample had marijuana abuse or dependence. Differential effects of MAPK14 tSNPs on brain volumes across patients with versus without marijuana abuse/dependence were examined using ANCOVA.

Results

Of the MAPK14 tSNPs, only rs12199654 had significant genotype effects and genotype × marijuana misuse interaction effects on WM volumes. rs12199654-A homozygotes with marijuana abuse/dependence had significantly smaller total cerebral and lobar WM volumes. The effects of MAPK14 rs12199654 on WM volume deficits remained significant even after controlling for the CNR1 rs12720071 genotype. There were significant main effects of the MAPK14 CNR1 diplotype and diplotype × marijuana interaction on WM brain volumes, with both genetic variants having additive contributions to WM volume deficits only in patients with marijuana misuse.

Conclusions

Given that CNR1-induced apoptosis is preceded by increased MAPK phosphorylation, our study suggests that potential MAPK14–CNR1 gene–gene interactions may mediate brain morphometric features in schizophrenia patients with heavy marijuana use.
An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders
Authors: Linscott R. J. , van Os J.
Published: July 2012

Background

The psychosis-proneness–persistence–impairment model of psychotic disorder incorporates notions of both phenomenological and temporal continuity (persistence) of psychotic experiences (PE), but not structural continuity. Specific testable propositions of phenomenological continuity and persistence are identified.

Method

Propositions are tested by systematic reviews of the epidemiology of PE, persistence of PE and disorder outcomes, and meta-analyses (including Monte Carlo permutation sampling, MCPS) of reported rates and odds ratios (ORs).

Results

Estimates of the incidence and prevalence of PE obtained from 61 cohorts revealed a median annual incidence of 2.5% and a prevalence of 7.2%. Meta-analysis of risk factors identified age, minority or migrant status, income, education, employment, marital status, alcohol use, cannabis use, stress, urbanicity and family history of mental illness as important predictors of PE. The mode of assessment accounted for significant variance in the observed rates. Across cohorts, the probability of persistence was very strongly related to the rate of PE at baseline. Of those who report PE, ∼20% go on to experience persistent PE whereas for ∼80%, PE remit over time. Of those with baseline PE, 7.4% develop a psychotic disorder outcome.

Conclusions

Compelling support is found for the phenomenological and temporal continuity between PE and psychotic disorder and for the fundamental proposition that this relationship is probabilistic. However, imprecision in epidemiological research design, measurement limitations and the epiphenomenological nature of PE invite further robust scrutiny of the continuity theory.
A FUNCTIONAL VERSION OF THE ARCH MODEL
Authors: Hörmann Siegfried , Horváth Lajos , Reeder Ron
Published: July 2012

Improvements in data acquisition and processing techniques have led to an almost continuous flow of information for financial data. High-resolution tick data are available and can be quite conveniently described by a continuous-time process. It is therefore natural to ask for possible extensions of financial time series models to a functional setup. In this paper we propose a functional version of the popular autoregressive conditional heteroskedasticity model. We will establish conditions for the existence of a strictly stationary solution, derive weak dependence and moment conditions, show consistency of the estimators, and perform a small empirical study demonstrating how our model matches with real data.
A long-term predictive validity study: Can the CDI Short Form be used to predict language and early literacy skills four years later?
Authors: CAN DILARA DENIZ , GINSBURG-BLOCK MARIKA , GOLINKOFF ROBERTA MICHNICK , HIRSH-PASEK KATHRYN
Published: July 2012

This longitudinal study examined the predictive validity of the MacArthur Communicative Developmental Inventories-Short Form (CDI-SF), a parent report questionnaire about children's language development (Fenson, Pethick, Renda, Cox, Dale & Reznick, 2000). Data were first gathered from parents on the CDI-SF vocabulary scores for seventy-six children (mean age=1 ; 10). Four years later (mean age=6 ; 1), children were assessed on language outcomes (expressive vocabulary, syntax, semantics and pragmatics) and code-related skills, including phonemic awareness, word recognition and decoding skills. Hierarchical regression analyses revealed that early expressive vocabulary accounted for 17% of the variance in picture vocabulary, 11% of the variance in syntax, and 7% of the variance in semantics, while not accounting for any variance in pragmatics in kindergarten. CDI-SF scores did not predict code-related skills in kindergarten. The importance of early vocabulary skills for later language development and CDI-SF as a valuable research tool are discussed.
U.S. Policy, Cultural Heritage, and U.S. Borders
Authors: Luke Christina
Published: July 2012

This article situates the discussion of illicit trafficking in antiquities in the context of the relationship between the U.S. Departments of State and Homeland Security. The main argument is that U.S. cultural heritage policy is part of a broader agenda of political discourse that links matters of heritage to wider concerns of security. If the underlying goal of the U.S. State Department is mutual understanding through open dialogue, how can initiatives that focus on the criminal networks and security, efforts tackled by the Department of Homeland Security, contribute to building a positive image for the United States abroad? Here I explore strategic aspects of U.S. cultural policies and federally supported programs aimed at mitigating against the illicit trade in antiquities as part of building and maintaining cultural relations.
Operation of TEAM I in a User Environment at NCEM
Authors: Ercius Peter , Boese Markus , Duden Thomas , Dahmen Ulrich
Published: July 2012

TEAM I is the final product of the Transmission Electron Aberration-corrected Microscope (TEAM) Project, a collaborative project funded by the Department of Energy with the goal of designing and building a platform for a next generation aberration-corrected electron microscope capable of image resolution of up to 50 pm. The TEAM instrument incorporates a number of new technologies, including spherical- and chromatic-aberration correction, an all-piezo-electric sample stage and an active-pixel direct electron detector. This article describes the functionality of this advanced instrumentation, its response to changes in environment or operating conditions, and its stability during daily operation within the National Center for Electron Microscopy user facility.
Phosphodiesterase-2 inhibitor reverses corticosterone-induced neurotoxicity and related behavioural changes via cGMP/PKG dependent pathway
Authors: Xu Ying , Pan Jianchun , Chen Ling , Zhang Chong , Sun Jiao , Li Jianxin , Nguyen Linda , Nair Neetu , Zhang Hanting , O'Donnell James M.
Published: July 2012

Phosphodiesterase 2 (PDE2) is an enzyme responsible for hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to restrict intracellular signalling of these second messenger molecules. This study investigated how PDE2 inhibitor Bay 60-7550 affects the dysregulated glucocorticoid signalling in neuronal cells and regulates depressive behaviours after chronic stress in mice. We found that exposure of hippocampal neurons to corticosterone resulted in time- and concentration-dependent increases in PDE2 expression. These intriguing findings were confirmed in the hippocampal cell line HT-22. After corticosterone exposure for 24 h, HT-22 cells showed a concentration-dependent increase in mRNA levels for PDE2 subtypes, PDE2A1 and 2A3, as well as for the total PDE2A protein expression. Bay 60-7550 was found to reverse the cell lesion induced by corticosterone (50 µm). This neuroprotective effect was blocked by pretreatment with protein kinase G inhibitor KT5823, but not protein kinase A inhibitor H89, suggesting the involvement of cGMP-dependent signalling. Although Bay 60-7550 treatment for 24 h did not change the levels of phosphorylated mitogen-activated protein kinases ERK1/2 (pERK) and phosphorylated cAMP response element-binding protein (pCREB), it down-regulated pERK at 2 h and up-regulated a CREB co-activator, CREB-binding protein, at 24 h. Both of these effects were blocked by KT 5823. Furthermore, Bay 60-7550 reversed corticosterone-induced down-regulation of brain-derived neurotrophic factor protein levels 24 h after corticosterone exposure. In behavioural testing, Bay 60-7550 produced antidepressant-like effects and reduced corticosterone levels in stressed mice, further supporting the involvement of a PDE2-dependent pathway in mediating Bay 60-7550's effect during stress hormone insults.
Analysing Aporia
Authors: BOHLMAN PHILIP V.
Published: July 2012

This essay draws upon approaches from music analysis, the cultural study of music, and the philosophy of language to examine the meaning and function of borders in music. Drawing upon Jacques Derrida's concept of multiple aporias as metaphors for understanding the relationship of life to death, the essay begins by exploring three functions of aporia at the borders in music: 1) a line to be crossed; 2) a zone of difference; 3) an area of impossibility and unknowability. Three case studies provide a comparative framework that seeks to extend my analytical approaches beyond specific cultural, geographic, and historical repertories. In the first case study I examine the function of caesura at the borders between oral and written tradition in epic; in the second, I examine the coterminous moment of emptiness and fullness known askhāliin South Asian music; in the third, I analyse the compositional language employed by Viktor Ullmann (1898–1944) in his concentration-camp melodrama,Die Weise von Liebe und Tod des Cornets Christoph Rilke, to represent the musical transcendence of death in the Holocaust. By analysing aporia in such different traditions I demonstrate the ways in which they open possibilities for understanding the sameness that connects music from radically different musical traditions.
The Impact of Specifying Suicide as the Cause of Death in an Obituary
Authors: Sand Elizabeth , Gordon Kathryn H. , Bresin Konrad
Published: July 2012

Background: Historically, people who die by suicide and those who survive them have been perceived more negatively than those affected by other types of death (e.g., Reynolds & Cimbolic, 1988 ). Yet, it is unclear whether these negative perceptions actually lead to decreased social and emotional support for people bereaved by suicide. Aims: To examine whether specifying suicide as the cause of death in an obituary impacts perceptions of a decedent and willingness to provide support to the decedent’s family. Method: A group of 253 participants were randomly assigned to read one of three fictional obituaries that were identical except for the stated cause of death (suicide, cancer, or drug overdose). Participants responded to questions about the decedent and behaviors toward the family. Results: Consistent with our prediction, people depicted as dying by suicide were viewed more negatively than decedents depicted as dying due to cancer. Contrary to our prediction, participants endorsed similar levels of willingness to provide support to the bereaved family regardless of the type of death specified in the obituary. Conclusions: The findings suggest that, even though those who die by suicide are viewed more negatively, their survivors may receive support that is similar to people bereaved by other types of death.
Final slate for AGU elections this fall
Authors: Anonymous
Published: July 2012

Your vote is important! This fall, AGU members will elect leaders for the next term (1 January 2013 to 31 December 2014). This issue of Eos provides details about the upcoming election and information on candidates for open AGU Board and Council positions as well as section and focus group secretary positions. All regular and student members who joined or renewed their membership by 1 July 2012 are eligible to vote in this year's election of AGU leaders. The election will be held electronically, and all members must have a valid e‐mail address on file at AGU to receive login credentials from the company conducting the election.
Multi‐pass whistler gain in a magnetospheric cavity due to induced nonlinear scattering
Authors: Ganguli Gurudas , Rudakov Leonid , Crabtree Christopher , Mithaiwala Manish
Published: July 2012

Multi‐pass gain in whistler energy is possible in the radiation belts if the wave amplitude is sufficiently large. Large amplitude magnetospherically reflected whistlers can induce nonlinear scattering and form a magnetospheric cavity filled with nearly isotropic spectrum of wave vectors perpendicular to the magnetic field with low obliqueness. This increases the wave‐particle resonance time and maintains a large pitch angle scattering rate. Enhanced pitch angle scattering and precipitation of trapped electrons into the radiation belt loss cone provides a proportionate gain in the whistler energy.
Using daily satellite observations to estimate emissions of short‐lived air pollutants on a mesoscopic scale
Authors: Mijling B. , van der A R. J.
Published: July 2012

Emission inventories of air pollutants are crucial information for policy makers and form important input data for air quality models. Using satellite observations for emission estimates has important advantages over bottom‐up emission inventories: they are spatially consistent, have high temporal resolution, and enable updates shortly after the satellite data become available. We present a new algorithm specifically designed to use daily satellite observations of column concentrations for fast updates of emission estimates of short‐lived atmospheric constituents on a mesoscopic scale (∼25 × 25 km2). The algorithm needs only one forward model run from a chemical transport model to calculate the sensitivity of concentration to emission, using trajectory analysis to account for transport away from the source. By using a Kalman filter in the inverse step, optimal use of the a priori knowledge and the newly observed data is made. We apply the algorithm for NOx emission estimates of East China, using the CHIMERE model on a 0.25 degree resolution together with tropospheric NO2column retrievals of the OMI and GOME‐2 satellite instruments. Closed loop tests show that the algorithm is capable of reproducing new emission scenarios. Applied with real satellite data, the algorithm is able to detect emerging sources (e.g., new power plants), and improves emission information for areas where proxy data are not or badly known (e.g., shipping emissions). Chemical transport model runs with the daily updated emission estimates provide better spatial and temporal agreement between observed and simulated concentrations, facilitating improved air quality forecasts.
Variations in the abundances of potassium and thorium on the surface of Mercury: Results from the MESSENGER Gamma‐Ray Spectrometer
Authors: Peplowski Patrick N. , Lawrence David J. , Rhodes Edgar A. , Sprague Ann L. , McCoy Timothy J. , Denevi Brett W. , Evans Larry G. , Head James W. , Nittler Larry R. , Solomon Sean C. , Stockstill‐Cahill Karen R. , Weider Shoshana Z.
Published: July 2012

A technique for converting gamma‐ray count rates measured by the Gamma‐Ray Spectrometer on the MESSENGER spacecraft to spatially resolved maps of the gamma‐ray emission from the surface of Mercury is utilized to map the surface distributions of the elements Si, O, and K over the planet's northern hemisphere. Conversion of the K gamma‐ray count rates to elemental abundances on the surface reveals variations from 300 to 2400 ppm. A comparison of these abundances with models for the maximum surface temperature suggests the possibility that a temperature‐related process is controlling the K abundances on the surface as well as providing K to the exosphere. The abundances of K and Th have been determined for several geologically distinct regions, including Mercury's northern smooth plains and the plains interior to the Caloris basin. The lack of a significant variation in the measured Th abundances suggests that there may be considerable variability in the K/Th abundance ratio over the mapped regions.
Admixture and recombination among
Toxoplasma gondii
lineages explain global genome diversity
Authors: Minot Samuel , Melo Mariane B. , Li Fugen , Lu Diana , Niedelman Wendy , Levine Stuart S. , Saeij Jeroen P. J.
Published: July 2012

Toxoplasma gondii
is a highly successful protozoan parasite that infects all warm-blooded animals and causes severe disease in immunocompromised and immune-naïve humans. It has an unusual global population structure: In North America and Europe, isolated strains fall predominantly into four largely clonal lineages, but in South America there is great genetic diversity and the North American clonal lineages are rarely found. Genetic variation between
Toxoplasma
strains determines differences in virulence, modulation of host-signaling pathways, growth, dissemination, and disease severity in mice and likely in humans. Most studies on
Toxoplasma
genetic variation have focused on either a few loci in many strains or low-resolution genome analysis of three clonal lineages. We use whole-genome sequencing to identify a large number of SNPs between 10
Toxoplasma
strains from Europe and North and South America. These were used to identify haplotype blocks (genomic regions) shared between strains and construct a
Toxoplasma
haplotype map. Additional SNP analysis of RNA-sequencing data of 26
Toxoplasma
strains, representing global diversity, allowed us to construct a comprehensive genealogy for
Toxoplasma gondii
that incorporates sexual recombination. These data show that most current isolates are recent recombinants and cannot be easily grouped into a limited number of haplogroups. A complex picture emerges in which some genomic regions have not been recently exchanged between any strains, and others recently spread from one strain to many others.
Cryo-transmission electron microscopy structure of a gigadalton peptide fiber of de novo design
Authors: Sharp Thomas H. , Bruning Marc , Mantell Judith , Sessions Richard B. , Thomson Andrew R. , Zaccai Nathan R. , Brady R. Leo , Verkade Paul , Woolfson Derek N.
Published: July 2012

Nature presents various protein fibers that bridge the nanometer to micrometer regimes. These structures provide inspiration for the de novo design of biomimetic assemblies, both to address difficulties in studying and understanding natural systems, and to provide routes to new biomaterials with potential applications in nanotechnology and medicine. We have designed a self-assembling fiber system, the SAFs, in which two small α-helical peptides are programmed to form a dimeric coiled coil and assemble in a controlled manner. The resulting fibers are tens of nm wide and tens of μm long, and, therefore, comprise millions of peptides to give gigadalton supramolecular structures. Here, we describe the structure of the SAFs determined to approximately 8 Å resolution using cryotransmission electron microscopy. Individual micrographs show clear ultrastructure that allowed direct interpretation of the packing of individual α-helices within the fibers, and the construction of a 3D electron density map. Furthermore, a model was derived using the cryotransmission electron microscopy data and side chains taken from a 2.3 Å X-ray crystal structure of a peptide building block incapable of forming fibers. This was validated using single-particle analysis techniques, and was stable in prolonged molecular-dynamics simulation, confirming its structural viability. The level of self-assembly and self-organization in the SAFs is unprecedented for a designed peptide-based material, particularly for a system of considerably reduced complexity compared with natural proteins. This structural insight is a unique high-resolution description of how α-helical fibrils pack into larger protein fibers, and provides a basis for the design and engineering of future biomaterials.
Global economic potential for reducing carbon dioxide emissions from mangrove loss
Authors: Siikamäki Juha , Sanchirico James N. , Jardine Sunny L.
Published: July 2012

Mangroves are among the most threatened and rapidly disappearing natural environments worldwide. In addition to supporting a wide range of other ecological and economic functions, mangroves store considerable carbon. Here, we consider the global economic potential for protecting mangroves based exclusively on their carbon. We develop unique high-resolution global estimates (5′ grid, about 9 × 9 km) of the projected carbon emissions from mangrove loss and the cost of avoiding the emissions. Using these spatial estimates, we derive global and regional supply curves (marginal cost curves) for avoided emissions. Under a broad range of assumptions, we find that the majority of potential emissions from mangroves could be avoided at less than $10 per ton of CO
2
. Given the recent range of market price for carbon offsets and the cost of reducing emissions from other sources, this finding suggests that protecting mangroves for their carbon is an economically viable proposition. Political-economy considerations related to the ability of doing business in developing countries, however, can severely limit the supply of offsets and increases their price per ton. We also find that although a carbon-focused conservation strategy does not automatically target areas most valuable for biodiversity, implementing a biodiversity-focused strategy would only slightly increase the costs.
Functional epialleles at an endogenous human centromere
Authors: Maloney Kristin A. , Sullivan Lori L. , Matheny Justyne E. , Strome Erin D. , Merrett Stephanie L. , Ferris Alyssa , Sullivan Beth A.
Published: July 2012

Human centromeres are defined by megabases of homogenous alpha-satellite DNA arrays that are packaged into specialized chromatin marked by the centromeric histone variant, centromeric protein A (CENP-A). Although most human chromosomes have a single higher-order repeat (HOR) array of alpha satellites, several chromosomes have more than one HOR array.
Homo sapiens
chromosome 17 (HSA17) has two juxtaposed HOR arrays, D17Z1 and D17Z1-B. Only D17Z1 has been linked to CENP-A chromatin assembly. Here, we use human artificial chromosome assembly assays to show that both D17Z1 and D17Z1-B can support de novo centromere assembly independently. We extend these in vitro studies and demonstrate, using immunostaining and chromatin analyses, that in human cells the centromere can be assembled at D17Z1 or D17Z1-B. Intriguingly, some humans are functional heterozygotes, meaning that CENP-A is located at a different HOR array on the two HSA17 homologs. The site of CENP-A assembly on HSA17 is stable and is transmitted through meiosis, as evidenced by inheritance of CENP-A location through multigenerational families. Differences in histone modifications are not linked clearly with active and inactive D17Z1 and D17Z1-B arrays; however, we detect a correlation between the presence of variant repeat units of D17Z1 and CENP-A assembly at the opposite array, D17Z1-B. Our studies reveal the presence of centromeric epialleles on an endogenous human chromosome and suggest genomic complexities underlying the mechanisms that determine centromere identity in humans.
Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents
Authors: Tóth Balázs , Csanády László
Published: July 2012

The Ca
2+
-permeable cation channel transient receptor potential melastatin 2 (TRPM2) plays a key role in pathogen-evoked phagocyte activation, postischemic neuronal apoptosis, and glucose-evoked insulin secretion, by linking these cellular responses to oxidative stress. TRPM2 channels are coactivated by binding of intracellular ADP ribose and Ca
2+
to distinct cytosolically accessible sites on the channels. These ligands likely regulate the activation gate, conserved in the voltage-gated cation channel superfamily, that comprises a helix bundle formed by the intracellular ends of transmembrane helix six of each subunit. For several K
+
and TRPM family channels, activation gate opening requires the presence of phosphatidylinositol-bisphosphate (PIP
2
) in the inner membrane leaflet. Most TRPM family channels inactivate upon prolonged stimulation in inside-out patches; this “rundown” is due to PIP
2
depletion. TRPM2 currents also run down within minutes, but the molecular mechanism of this process is unknown. Here we report that high-affinity PIP
2
binding regulates Ca
2+
sensitivity of TRPM2 activation. Nevertheless, TRPM2 inactivation is not due to PIP
2
depletion; rather, it is state dependent, sensitive to permeating ions, and can be completely prevented by mutations in the extracellular selectivity filter. Introduction of two negative charges plus a single-residue insertion, to mimic the filter sequence of TRPM5, results in TRPM2 channels that maintain unabated maximal activity for over 1 h, and display altered permeation properties but intact ADP ribose/Ca
2+
-dependent gating. Thus, upon prolonged stimulation, the TRPM2 selectivity filter undergoes a conformational change reminiscent of that accompanying C-type inactivation of voltage-gated K
+
channels. The noninactivating TRPM2 variant will be invaluable for gating studies.
Simulated versus observed patterns of warming over the extratropical Northern Hemisphere continents during the cold season
Authors: Wallace John M. , Fu Qiang , Smoliak Brian V. , Lin Pu , Johanson Celeste M.
Published: July 2012

A suite of the historical simulations run with the Intergovernmental Panel on Climate Change Fourth Assessment Report (IPCC AR4) models forced by greenhouse gases, aerosols, stratospheric ozone depletion, and volcanic eruptions and a second suite of simulations forced by increasing CO
2
concentrations alone are compared with observations for the reference interval 1965–2000. Surface air temperature trends are disaggregated by boreal cold (November-April) versus warm (May-October) seasons and by high latitude northern (
N
: 40°–90 °N) versus southern (
S
: 60 °S–40 °N) domains. A dynamical adjustment is applied to remove the component of the cold-season surface air temperature trends (over land areas poleward of 40 °N) that are attributable to changing atmospheric circulation patterns. The model simulations do not simulate the full extent of the wintertime warming over the high-latitude Northern Hemisphere continents during the later 20th century, much of which was dynamically induced. Expressed as fractions of the concurrent trend in global-mean sea surface temperature, the relative magnitude of the dynamically induced wintertime warming over domain
N
in the observations, the simulations with multiple forcings, and the runs forced by the buildup of greenhouse gases only is 7∶2∶1, and roughly comparable to the relative magnitude of the concurrent sea-level pressure trends. These results support the notion that the enhanced wintertime warming over high northern latitudes from 1965 to 2000 was mainly a reflection of unforced variability of the coupled climate system. Some of the simulations exhibit an enhancement of the warming along the Arctic coast, suggestive of exaggerated feedbacks.
Molecular basis for the action of the collagen-specific chaperone Hsp47/SERPINH1 and its structure-specific client recognition
Authors: Widmer Christine , Gebauer Jan M. , Brunstein Elena , Rosenbaum Sabrina , Zaucke Frank , Drögemüller Cord , Leeb Tosso , Baumann Ulrich
Published: July 2012

Collagen is the most abundant protein in animals and is a major component of the extracellular matrix in tissues such as skin and bone. A distinctive structural feature of all collagen types is a unique triple-helical structure formed by tandem repeats of the consensus sequence Xaa-Yaa-Gly, in which Xaa and Yaa frequently are proline and hydroxyproline, respectively. Hsp47/SERPINH1 is a procollagen-specific molecular chaperone that, unlike other chaperones, specifically recognizes the folded conformation of its client. Reduced functional levels of Hsp47 were reported in severe recessive forms of osteogenesis imperfecta, and homozygous knockout is lethal in mice. Here we present crystal structures of Hsp47 in its free form and in complex with homotrimeric synthetic collagen model peptides, each comprising one Hsp47-binding site represented by an arginine at the Yaa-position of a Xaa-Yaa-Gly triplet. Two of these three binding sites in the triple helix are occupied by Hsp47 molecules, which bind in a head-to-head fashion, thus making extensive contacts with the leading and trailing strands of the collagen triple helix. The important arginine residue within the Xaa-Arg-Gly triplet is recognized by a conserved aspartic acid. The structures explain the stabilization of the triple helix as well as the inhibition of collagen-bundle formation by Hsp47. In addition, we propose a pH-dependent substrate release mechanism based on a cluster of histidine residues.
HIV-1 Gag co-opts a cellular complex containing DDX6, a helicase that facilitates capsid assembly
Authors: Reed Jonathan C. , Molter Britta , Geary Clair D. , McNevin John , McElrath Julie , Giri Samina , Klein Kevin C. , Lingappa Jaisri R.
Published: July 2012

To produce progeny virus, human immunodeficiency virus type I (HIV-1) Gag assembles into capsids that package the viral genome and bud from the infected cell. During assembly of immature capsids, Gag traffics through a pathway of assembly intermediates (AIs) that contain the cellular adenosine triphosphatase ABCE1 (ATP-binding cassette protein E1). In this paper, we showed by coimmunoprecipitation and immunoelectron microscopy (IEM) that these Gag-containing AIs also contain endogenous processing body (PB)–related proteins, including AGO2 and the ribonucleic acid (RNA) helicase DDX6. Moreover, we found a similar complex containing ABCE1 and PB proteins in uninfected cells. Additionally, knockdown and rescue studies demonstrated that the RNA helicase DDX6 acts enzymatically to facilitate capsid assembly independent of RNA packaging. Using IEM, we localized the defect in DDX6-depleted cells to Gag multimerization at the plasma membrane. We also confirmed that DDX6 depletion reduces production of infectious HIV-1 from primary human T cells. Thus, we propose that assembling HIV-1 co-opts a preexisting host complex containing cellular facilitators such as DDX6, which the virus uses to catalyze capsid assembly.
Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane
Authors: Schmidt Nadine , Basu Sreya , Sladecek Stefan , Gatti Sabrina , van Haren Jeffrey , Treves Susan , Pielage Jan , Galjart Niels , Brenner Hans Rudolf
Published: July 2012

Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane. Agrin acted in part by locally activating phosphatidylinositol 3-kinase and inactivating GSK3β, which led to the local capturing of dynamic microtubules at agrin-induced acetylcholine receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2, microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei with their selective gene expression programs were all reduced. Thus, the cascade linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype.
The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development
Authors: Courtois Aurélien , Schuh Melina , Ellenberg Jan , Hiiragi Takashi
Published: July 2012

The transition from meiosis to mitosis, classically defined by fertilization, is a fundamental process in development. However, its mechanism remains largely unexplored. In this paper, we report a surprising gradual transition from meiosis to mitosis over the first eight divisions of the mouse embryo. The first cleavages still largely share the mechanism of spindle formation with meiosis, during which the spindle is self-assembled from randomly distributed microtubule-organizing centers (MTOCs) without centrioles, because of the concerted activity of dynein and kinesin-5. During preimplantation development, the number of cellular MTOCs progressively decreased, the spindle pole gradually became more focused, and spindle length progressively scaled down with cell size. The typical mitotic spindle with centrin-, odf2-, kinesin-12–, and CP110-positive centrosomes was established only in the blastocyst. Overall, the transition from meiosis to mitosis progresses gradually throughout the preimplantation stage in the mouse embryo, thus providing a unique system to study the mechanism of centrosome biogenesis in vivo.
A MATLAB toolbox for structural kinetic modeling
Authors: Girbig Dorothee , Selbig Joachim , Grimbs Sergio
Published: July 2012

Summary: Structural kinetic modeling (SKM) enables the analysis of dynamical properties of metabolic networks solely based on topological information and experimental data. Current SKM-based experiments are hampered by the time-intensive process of assigning model parameters and choosing appropriate sampling intervals for Monte-Carlo experiments. We introduce a toolbox for the automatic and efficient construction and evaluation of structural kinetic models (SK models). Quantitative and qualitative analyses of network stability properties are performed in an automated manner. We illustrate the model building and analysis process in detailed example scripts that provide toolbox implementations of previously published literature models.

Availability: The source code is freely available for download at http://bioinformatics.uni-potsdam.de/projects/skm.

Contact:  girbig@mpimp-golm.mpg.de
miR-203 Regulates Nociceptive Sensitization after Incision by Controlling Phospholipase A2 Activating Protein Expression
Authors: Sun Yuan , Li Xiang-Qi , Sahbaie Peyman , Shi Xiao-You , Li Wen-Wu , Liang De-Yong , Clark J. David
Published: July 2012

Background

After incision keratinocytes in the epidermis become activated to produce a range of pain-related mediators. microRNA 203 (miR-203) is known to be involved in keratinocyte growth, differentiation, and skin inflammation. We hypothesized that one or more of these mediators might be under the control of miR-203.

Methods

The expression of miR-203 and its target gene, phospholipase A2 activating protein (PLAA), were examined after hind paw incision in mice. We investigated the local effect of intraplantar PLAA peptide injection in normal mice and the effects of a selective secretory phospholipase A2 inhibitor (HK064) on PLAA or incision-induced mechanical allodynia. Last, we investigated the role of substance P signaling in regulating miR-203 and PLAA expression in vitro and in vivo.

Results

Levels of miR-203 were strongly down-regulated in keratinocytes after incision. Informatics-based approaches identified PLAA as a likely candidate for regulation by miR-203. PLAA caused mechanical allodynia and conditioned place aversion but not thermal sensitization. HK064 reduced mechanical allodynia after incision and after intraplantar injection of PLAA. Using preprotachykinin gene knockout mice or with neurokinin-1 selective antagonist LY303870 treatment, we observed that substance P-mediated signaling was also required for miR-203 and PLAA regulation after incision. Finally, using the rat epidermal keratinocyte cell line, we observed that a miR-203 mimic molecule could block the substance P-induced increase in PLAA expression observed under control conditions.

Conclusions

miR-203 may regulate expression of the novel nociceptive mediator PLAA after incision. Furthermore, the regulation of miR-203 and PLAA levels is reliant upon intact substance P signaling.
Smoothed Particle Hydrodynamics Simulation of Wave Overtopping Characteristics for Different Coastal Structures
Authors: Pu Jaan Hui , Shao Songdong
Published: July 2012

This research paper presents an incompressible smoothed particle hydrodynamics (ISPH) technique to investigate a regular wave overtopping on the coastal structure of different types. The SPH method is a mesh-free particle modeling approach that can efficiently treat the large deformation of free surface. The incompressible SPH approach employs a true hydrodynamic formulation to solve the fluid pressure that has less pressure fluctuations. The generation of flow turbulence during the wave breaking and overtopping is modeled by a subparticle scale (SPS) turbulence model. Here the ISPH model is used to investigate the wave overtopping over a coastal structure with and without the porous material. The computations disclosed the features of flow velocity, turbulence, and pressure distributions for different structure types and indicated that the existence of a layer of porous material can effectively reduce the wave impact pressure and overtopping rate. The proposed numerical model is expected to provide a promising practical tool to investigate the complicated wave-structure interactions.