bluuebunny/crossref_metadata_2025 huggingface dataset:
CDS: A Fold-Change Based Statistical Test for Concomitant Identification of Distinctness and Similarity in Gene Expression Analysis
Authors: Tchitchek Nicolas , Golib Dzib José Felipe , Targat Brice , Noth Sebastian , Benecke Arndt , Lesne Annick
Published: June 2012

The problem of identifying differential activity such as in gene expression is a major defeat in biostatistics and bioinformatics. Equally important, however much less frequently studied, is the question of similar activity from one biological condition to another. The fold-change, or ratio, is usually considered a relevant criterion for stating difference and similarity between measurements. Importantly, no statistical method for concomitant evaluation of similarity and distinctness currently exists for biological applications. Modern microarray, digital PCR (dPCR), and Next-Generation Sequencing (NGS) technologies frequently provide a means of coefficient of variation estimation for individual measurements. Using fold-change, and by making the assumption that measurements are normally distributed with known variances, we designed a novel statistical test that allows us to detect concomitantly, thus using the same formalism, differentially and similarly expressed genes (http://cds.ihes.fr). Given two sets of gene measurements in different biological conditions, the probabilities of making type I and type II errors in stating that a gene is differentially or similarly expressed from one condition to the other can be calculated. Furthermore, a confidence interval for the fold-change can be delineated. Finally, we demonstrate that the assumption of normality can be relaxed to consider arbitrary distributions numerically. The Concomitant evaluation of Distinctness and Similarity (CDS) statistical test correctly estimates similarities and differences between measurements of gene expression. The implementation, being time and memory efficient, allows the use of the CDS test in high-throughput data analysis such as microarray, dPCR, and NGS experiments. Importantly, the CDS test can be applied to the comparison of single measurements (N = 1) provided the variance (or coefficient of variation) of the signals is known, making CDS a valuable tool also in biomedical analysis where typically a single measurement per subject is available.
A large increase of the CO2 sink in the western tropical North Atlantic from 2002 to 2009
Authors: Park Geun‐Ha , Wanninkhof Rik
Published: June 2012

Determining a robust trend of surface ocean carbon dioxide (CO2) for a period shorter than a decade is challenging due to large seasonal variability and a sparsity of data. Here, we estimate the multiannual trend of surface CO2in the region of 19°N–20°N, 65°W–68°W for the period of 2002–2009. We used an unprecedented number of high‐quality underway data of the fugacity of CO2 in surface seawater (fCO2SW) collected from 137 cruises using an automated system onboard the cruise ship Explorer of the Seas. The growth rate of fCO2SWwas estimated by two de‐seasonalization approaches that showed similar and significantly lower values than the atmospheric increases, leading to a large increase in the CO2 sink. The seasonal difference in the trends was significant, with fCO2SW values in winter showing no increase, while summer fCO2SW values lagged only slightly with the atmosphere. We attribute the lack of an increase in winter fCO2SWvalues to sea surface temperature changes, which are closely correlated with the El Niño‐Southern Oscillation cycle, and to changes in the mixed layer depth. The slower increase of fCO2SWis also related to decreases in salinity. The 8‐year averaged annual net sea‐air CO2 flux was −0.06 ± 0.18 mol m−2 yr−1 compared to a climatology that shows a flux out of the ocean of +0.11 mol m−2 yr−1. The increasing flux differs from previous, mostly longer‐term results for regional studies and time series stations in the North Atlantic, which suggests a decrease or no change in oceanic CO2 uptake.
Interannual variability of H218O in precipitation over the Asian monsoon region
Authors: Ishizaki Yasuhiro , Yoshimura Kei , Kanae Shinjiro , Kimoto Masahide , Kurita Naoyuki , Oki Taikan
Published: June 2012

The stable isotopic composition of water has been used as a paleoproxy to reconstruct past climates over the Asian monsoon region, but the main controls on the variability of isotopes of water in precipitation have not been characterized quantitatively in this region. Therefore, we used an atmospheric general circulation model incorporating stable water isotope physics to quantitatively estimate the relative contributions to isotope variability in precipitation falling in the Asian monsoon region. As in previous research, we identified two primary factors controlling the interannual variability of δ18Oprecip (defined as (Rsample/RVSMOW − 1) × 1000, where RVSMOW is the 18O ratio in Vienna Standard Mean Ocean Water) and its correlation with El Niño–Southern Oscillation (ENSO) events: the amount of precipitation at the observation site, and distillation during transport from source regions. Two sensitivity experiments revealed that distillation during transport from source regions was the dominant controlling factor; at Bangkok, Bombay, and Hong Kong, the amount of local precipitation contributed 27%, 33%, and 25% while distillation processes contributed 70%, 60%, and 70%, respectively. Similarly, distillation processes accounted for 80%, 82%, and 83% of observed differences in δ18Oprecip between El Niño and La Niña years at these three cities, respectively. Therefore, interannual variability of δ18Oprecipat the three stations primarily reflects distillation during transport from source regions, and it is also governed by the large‐scale tropical variability (ENSO).
Sediment entrainment by debris flows: In situ measurements from the headwaters of a steep catchment
Authors: McCoy S. W. , Kean J. W. , Coe J. A. , Tucker G. E. , Staley D. M. , Wasklewicz T. A.
Published: June 2012

Debris flows can dramatically increase their volume, and hence their destructive potential, by entraining sediment. Yet quantitative constraints on rates and mechanics of sediment entrainment by debris flows are limited. Using an in situ sensor network in the headwaters of a natural catchment we measured flow and bed properties during six erosive debris‐flow events. Despite similar flow properties and thicknesses of bed sediment entrained across all events, time‐averaged entrainment rates were significantly faster for bed sediment that was saturated prior to flow arrival compared with rates for sediment that was dry. Bed sediment was entrained from the sediment‐surface downward in a progressive fashion and occurred during passage of dense granular fronts as well as water‐rich, inter‐surge flow.En massefailure of bed sediment along the sediment‐bedrock interface was never observed. Large‐magnitude, high‐frequency fluctuations in total normal basal stress were dissipated within the upper 5 cm of bed sediment. Within this near surface layer, concomitant fluctuations in Coulomb frictional resistance are expected, irrespective of the influence of pore fluid pressure or fluctuations in shear stress. If the near‐surface sediment was wet as it was overridden by a flow, additional large‐magnitude, high‐frequency pore pressure fluctuations were measured in the near‐surface bed sediment. These pore pressure fluctuations propagated to depth at subsonic rates and in a diffusive manner. The depth to which large excess pore pressures propagated was typically less than 10 cm, but scaled as (D/fi)0.5, in which D is the hydraulic diffusivity and fiis the frequency of a particular pore pressure fluctuation. Shallow penetration depths of granular‐normal‐stress fluctuations and excess pore pressures demonstrate that only near‐surface bed sediment experiences the full dynamic range of effective‐stress fluctuations, and as a result, can be more easily entrained than deeper sediment. These data provide robust tests for mechanical models of entrainment and demonstrate that a debris flow over wet bed sediment will be larger than the same flow over dry bed sediment.
Morphometric dating of the fluvial landscape response to a tectonic perturbation
Authors: Demoulin Alain
Published: June 2012

Despite constant progress in numerical and field studies of landscape evolution, time evolution is still poorly constrained in many uplifted areas where low denudation rates prevent the use of low temperature thermochronology, especially outside high relief mountainous areas. Here, I show that regional statistics of the landscape metric R involving hypsometric integrals at three nested levels of a catchment are able to isolate the time effect on landscape geometry during the latter's transient response to a tectonic perturbation. Analysis of 210 catchments from 9 regions of known uplift age worldwide shows that the regionally characteristic, R‐derivedSRindex is in inverse power law relation with the time elapsed since a base level lowering. Suggesting a response time of ∼5 My, this finding has important implications for quantifying the rate of landform evolution and determining whether a landscape has reached steady‐state form.
On the spatial distribution of high winds off southeast Greenland
Authors: Harden B. E. , Renfrew I. A.
Published: June 2012

The spatial distribution of barrier winds along southeast Greenland has been investigated through idealized modeling of unidirectional flow towards an isolated mountain. The regions of enhanced surface wind speed seen in previous studies are reproduced and shown to be primarily the result of promontories in the orography along the southeast coast (the maxima disappear in experiments without the promontories). Two mechanisms are proposed to explain these enhancements. Firstly, a reduction in pressure experienced by the flow as it passes a promontory results in an acceleration akin to that of easterly tip jets at Cape Farewell. Secondly, mountain waves observed along the southeast coast are accompanied by strong, low‐level downslope winds in the lee of the promontories. Both mechanisms contribute to the simulated wind speed maxima.
Equatorially confined warm trapped ions at around 100 eV near the plasmapause
Authors: Yamauchi M. , Dandouras I. , Rème H. , El‐Lemdani Mazouz F.
Published: June 2012

Near the equatorial plasmapause at around 4–5 Earth radius (RE) geocentric distance, pancake distributed tens of eV ions are sometimes found, as previously reported by Olsen et al. (1987). Cluster CIS data during perigee traversals in 2001–2002 (nearly 200 traversals) revealed new features of these equatorially‐trapped warm ions. (1) The characteristic energy of He+ is often higher than that of H+. (2) Some events show non‐thermal ring distribution for He+ rather than superthermal pancake distribution. H+can also have the ring distribution in such events. (3) While majority of the events are dispersion‐free, some events show energy‐time dispersion, indicating drifts from different local times. (4) The time scale of the development is about an hour, which is much shorter than the drifting time of these ions around the Earth. Cluster statistics also confirmed some results from the previous studies: (5) These ions are confined within a few degrees of latitudinal range near the equator, and have nearly 90° pitch angles. (6) At a geocentric distance of about 4–4.5 REwhere Cluster traversed the equator during its perigee, the probability of observing clear events is about 40–45% in the noon and dusk sectors and about 20–25% in the night‐to‐dawn sector. (7) They are dominated by H+ with variable content of He+. The He+/H+ ratio is much less than 5% for the majority of the cases.
The shifting probability distribution of global daytime and night‐time temperatures
Authors: Donat Markus G. , Alexander Lisa V.
Published: June 2012

Using a global observational dataset of daily gridded maximum and minimum temperatures we investigate changes in the respective probability density functions of both variables using two 30‐year periods; 1951–1980 and 1981–2010. The results indicate that the distributions of both daily maximum and minimum temperatures have significantly shifted towards higher values in the latter period compared to the earlier period in almost all regions, whereas changes in variance are spatially heterogeneous and mostly less significant. However asymmetry appears to have decreased but is altered in such a way that it has become skewed towards the hotter part of the distribution. Changes are greater for daily minimum (night‐time) temperatures than for daily maximum (daytime) temperatures. As expected, these changes have had the greatest impact on the extremes of the distribution and we conclude that the distribution of global daily temperatures has indeed become “more extreme” since the middle of the 20th century.
Terrestrial VLF transmitter injection into the magnetosphere
Authors: Cohen M. B. , Inan U. S.
Published: June 2012

Very Low Frequency (VLF, 3–30 kHz) radio waves emitted from ground sources (transmitters and lightning) strongly impact the radiation belts, driving electron precipitation via whistler‐electron gyroresonance, and contributing to the formation of the slot region. However, calculations of the global impacts of VLF waves are based on models of trans‐ionospheric propagation to calculate the VLF energy reaching the magnetosphere. Limited comparisons of these models to individual satellite passes have found that the models may significantly (by >20 dB) overestimate amplitudes of ground based VLF transmitters in the magnetosphere. To form a much more complete empirical picture of VLF transmitter energy reaching the magnetosphere, we present observations of the radiation pattern from a number of ground‐based VLF transmitters by averaging six years of data from the DEMETER satellite. We divide the slice at ∼700 km altitude above a transmitter into pixels and calculate the average field for all satellite passes through each pixel. There are enough data to see 25 km features in the radiation pattern, including the modal interference of the subionospheric signal mapped upwards. Using these data, we deduce the first empirical measure of the radiated power into the magnetosphere from these transmitters, for both daytime and nighttime, and at both the overhead and geomagnetically conjugate region. We find no detectable variation of signal intensity with geomagnetic conditions at low and mid latitudes (L < 2.6). We also present evidence of ionospheric heating by one VLF transmitter which modifies the trans‐ionospheric absorption of signals from other transmitters passing through the heated region.
A simple extension of “An alternative approach to sea surface aerodynamic roughness” by Zhiqiu Gao, Qing Wang, and Shouping Wang
Authors: Gao Zhiqiu , Wang Linlin , Bi Xueyan , Song Qingtao , Gao Yuchao
Published: June 2012

Based on the data previously collected during the Humidity Exchange over the Sea Main Experiment (HEXMAX), the methods used to parameterize aerodynamic roughness (z0), friction velocity (u*), and the neutral drag coefficient (CDN) under moderate wind speed conditions originally proposed by Gao et al. (2006) were extended by using the nondimensional significant wave height (gHs/u*2 or gHs/U10N2) instead of wave age (cp/u* or cp/U10N), where g is the acceleration of gravity, Hs is the significant wave height, U10Nis the horizontal wind speed at 10‐m height under the neutral atmospheric condition, andcp is the phase velocity of the peak wave spectrum. The results show (1) u* = 0.024U10N(gHs/U10N2)−1/4, (2) z0 = 10 × exp[−4.797(gHs/u*2)1/6] or z0 = 10 × exp[−16.613(gHs/U10N2)1/4], and (3) CDN = 0.007(gHs/u*2)−1/3 or CDN = 5.76 × 10−4(gHs/U10N2)−1/2. The present parameterization schemes were experimentally tested.
Expected future changes in the African monsoon between 2030 and 2070 using some CMIP3 and CMIP5 models under a medium‐low RCP scenario
Authors: Monerie Paul‐Arthur , Fontaine Bernard , Roucou Pascal
Published: June 2012

The accuracy of African Monsoon (AM) simulations together with expected future changes are presented using eight available CMIP5/AR5 AOGCMs under the RCP4.5 emission scenario and eight CMIP3/AR4 AOGCMs under the A1b scenario, with a multimodel approach and the “one model one vote” concept. The results refer to the ‘present’ period (1960–1999) and to a ‘future horizon’ (2031–2070), and are discussed in terms of monsoon dynamics and climate change. Overall the new simulations seem more realistic. They exhibit more accurate rainfall patterns, although some biases reported in CMIP3 models remain. The future changes show an inverse tendency regarding rainfall amounts with less (more) rainfall expected over the western (central‐eastern) Sahel. The deficits are associated with increasing air subsidence and the surplus with a more intense monsoon circulation. An African Rainfall Pattern Index (ARPI), based on standardized rainfall differences between these regions, is defined for capturing the rainfall contrast over the period from 1900 to 2100. This index increases suggesting that the contrasted rainfall anomaly pattern at Sahelian latitudes is expected to occur more frequently in the future.
Estimates of North American summertime planetary boundary layer depths derived from space‐borne lidar
Authors: McGrath‐Spangler Erica L. , Denning A. Scott
Published: June 2012

The planetary boundary layer (PBL) mediates exchanges of energy, moisture, momentum, carbon, and pollutants between the surface and the atmosphere. This paper is a first step in producing a space‐based estimate of PBL depth that can be used to compare with and evaluate model‐based PBL depth retrievals, inform boundary layer studies, and improve understanding of the above processes. In clear sky conditions, space‐borne lidar backscatter is frequently affected by atmospheric properties near the PBL top. Spatial patterns of 5‐year mean mid‐day summertime PBL depths over North America were estimated from the CALIPSO lidar backscatter and are generally consistent with model reanalyses and AMDAR (Aircraft Meteorological DAta Reporting) estimates. The rate of retrieval is greatest over the subtropical oceans (near 100%) where overlying subsidence limits optically thick clouds from growing and attenuating the lidar signal. The general retrieval rate over land is around 50% with decreased rates over the Southwestern United States and regions with high rates of convection. The lidar‐based estimates of PBL depth tend to be shallower than aircraft estimates in coastal areas. Compared to reanalysis products, lidar PBL depths are greater over the oceans and areas of the boreal forest and shallower over the arid and semiarid regions of North America.
Evaluations of cirrus contamination and screening in ground aerosol observations using collocated lidar systems
Authors: Huang Jingfeng , Hsu N. Christina , Tsay Si‐Chee , Holben Brent N. , Welton Ellsworth J. , Smirnov Alexander , Jeong Myeong‐Jae , Hansell Richard A. , Berkoff Timothy A. , Liu Zhaoyan , Liu Gin‐Rong , Campbell James R. , Liew Soo Chin , Barnes John E.
Published: June 2012

Cirrus clouds, particularly subvisual high thin cirrus with low optical thickness, are difficult to screen in operational aerosol retrieval algorithms. Collocated aerosol and cirrus observations from ground measurements, such as the Aerosol Robotic Network (AERONET) and the Micro‐Pulse Lidar Network (MPLNET), provide us with an unprecedented opportunity to systematically examine the susceptibility of operational aerosol products to cirrus contamination. Quality assured aerosol optical thickness (AOT) measurements were also tested against the Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) vertical feature mask (VFM) and the Moderate Resolution Imaging Spectroradiometer (MODIS) thin cirrus screening parameters for the purpose of evaluating cirrus contamination. Key results of this study include: (1) quantitative evaluations of data uncertainties in AERONET AOT retrievals are conducted; although AERONET cirrus screening schemes are successful in removing most cirrus contamination, strong residuals displaying strong spatial and seasonal variability still exist, particularly over thin cirrus prevalent regions during cirrus peak seasons; (2) challenges in matching up different data for analysis are highlighted and corresponding solutions proposed; and (3) estimates of the relative contributions from cirrus contamination to aerosol retrievals are discussed. The results are valuable for better understanding and further improving ground aerosol measurements that are critical for aerosol‐related climate research.
On the relationship between Nd isotopic composition and ocean overturning circulation in idealized freshwater discharge events
Authors: Rempfer Johannes , Stocker Thomas F. , Joos Fortunat , Dutay Jean‐Claude
Published: June 2012

Using a cost‐efficient climate model, the effect of changes in overturning circulation on neodymium isotopic composition,ϵNd, is systematically examined for the first time. Idealized sequences of abrupt climate changes are induced by the application of periodic freshwater fluxes to the North Atlantic (NA) and the Southern Ocean (SO), thus mainly affecting either the formation of North Atlantic Deep Water (NADW) or Antarctic Bottom Water (AABW). Variations in ϵNd reflect weakening and strengthening of the formation of NADW and AABW, changes in ϵNdof end‐members are relatively small. Relationships betweenϵNd and the strength of NADW or AABW are more pronounced for AABW than for NADW. Atlantic patterns of variations in ϵNd systematically differ between NA and SO experiments. Additionally, the signature of changes in ϵNd in the Atlantic and the Pacific is alike in NA but opposite in SO experiments. Discrimination between NA and SO experiments is therefore possible based on the Atlantic pattern of variations in ϵNd and the contrariwise behavior of ϵNd in the Atlantic and the Pacific. In further experiments we examined the effect of variations in magnitudes of particle export fluxes. Within the examined range, and although settling particles represent the only sink of Nd, their effects on ϵNd are relatively small. Our results confirm the large potential of ϵNd as a paleocirculation tracer but also indicate its limitations of quantitative reconstructions of changes in the Atlantic Meridional Ocean Circulation.
Functional and ecological consequences of saprotrophic fungus–grazer interactions
Authors: Crowther Thomas W , Boddy Lynne , Hefin Jones T
Published: June 2012

Saprotrophic fungi are key regulators of nutrient cycling in terrestrial ecosystems. They are the primary agents of plant litter decomposition and their hyphal networks, which grow throughout the soil–litter interface, represent highly dynamic channels through which nutrients are readily distributed. By ingesting hyphae and dispersing spores, soil invertebrates, including Arthropoda, Oligochaetae and Nematoda, influence fungal-mediated nutrient distribution within soil. Fungal physiological responses to grazing include changes to hydrolytic enzyme production and respiration rates. These directly affect nutrient mineralisation and the flux of CO2 between terrestrial and atmospheric pools. Preferential grazing may also exert selective pressures on saprotrophic communities, driving shifts in fungal succession and community composition. These functional and ecological consequences of grazing are intrinsically linked, and influenced by invertebrate grazing intensity. High-intensity grazing often reduces fungal growth and activity, whereas low-intensity grazing can have stimulatory effects. Grazing intensity is directly related to invertebrate abundance, and varies dramatically between species and functional groups. Invertebrate diversity and community composition, therefore, represent key factors determining the functioning of saprotrophic fungal communities and the services they provide.
Metagenome, metatranscriptome and single-cell sequencing reveal microbial response to Deepwater Horizon oil spill
Authors: Mason Olivia U , Hazen Terry C , Borglin Sharon , Chain Patrick S G , Dubinsky Eric A , Fortney Julian L , Han James , Holman Hoi-Ying N , Hultman Jenni , Lamendella Regina , Mackelprang Rachel , Malfatti Stephanie , Tom Lauren M , Tringe Susannah G , Woyke Tanja , Zhou Jizhong , Rubin Edward M , Jansson Janet K
Published: June 2012

The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea.
Dimerization is necessary for MIM-mediated membrane deformation and endocytosis
Authors: Cao Meng , Zhan Tailan , Ji Min , Zhan Xi
Published: June 2012

MIM [missing in metastasis; also called MTSS1 (metastasis suppressor 1)] is an intracellular protein that binds to actin and cortactin and has an intrinsic capacity to sense and facilitate the formation of protruded membranous curvatures implicated in cell-ular polarization, mobilization and endocytosis. The N-terminal 250 amino acids of MIM undergo homodimerization and form a structural module with the characteristic of an I-BAR [inverse BAR (Bin/amphiphysin/Rvs)] domain. To discern the role of the dimeric configuration in the function of MIM, we designed several peptides able to interfere with MIM dimerization in a manner dependent upon their lengths. Overexpression of one of the peptides effectively abolished MIM-mediated membrane protrusions and transferrin uptake. However, a peptide with a high potency inhibiting MIM dimerization failed to affect its binding to actin and cortactin. Thus the results of the present study indicate that the dimeric configuration is essential for MIM-mediated membrane remodelling and serves as a proper target to develop antagonists specifically against an I-BAR-domain-containing protein.
Crystal structure of the dopamine N-acetyltransferase–acetyl-CoA complex provides insights into the catalytic mechanism
Authors: Cheng Kuo-Chang , Liao Jhen-Ni , Lyu Ping-Chiang
Published: June 2012

The daily cycle of melatonin biosynthesis in mammals is regulated by AANAT (arylalkylamine N-acetyltransferase; EC 2.3.1.87), making it an attractive target for therapeutic control of abnormal melatonin production in mood and sleep disorders. Drosophila melanogaster Dat (dopamine N-acetyltransferase) is an AANAT. Until the present study, no insect Dat structure had been solved, and, consequently, the structural basis for its acetyl-transfer activity was not well understood. We report in the present paper the high-resolution crystal structure for a D. melanogaster Dat–AcCoA (acetyl-CoA) complex obtained using one-edge (selenium) single-wavelength anomalous diffraction. A binding study using isothermal titration calorimetry suggested that the cofactor bound to Dat first before substrate. Examination of the complex structure and a substrate-docked model indicated that Dat contains a novel AANAT catalytic triad. Site-directed mutagenesis, kinetic studies and pH-rate profiles confirmed that Glu47, Ser182 and Ser186 were critical for catalysis. Collectively, the results of the present study suggest that Dat possesses a specialized active site structure dedicated to a catalytic mechanism.
Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors
Authors: Shi Xiaozhong , Seldin David C. , Garry Daniel J.
Published: June 2012

Previous studies have established that Foxk1 (forkhead box k1) plays an important role in skeletal muscle regeneration. Foxk1 regulates the cell-cycle progression of myogenic progenitors by repressing the cell-cycle inhibitor gene p21. However, the underlying mechanism is not well understood. In the present study, we report the identification of Sds3 (suppressor of defective silencing 3) as an adaptor protein that recruits the Sin3 [SWI (switch)-independent 3]–HDAC (histone deacetylase) repression complex and binds Foxk1. Using GST (glutathione transferase) pull-down assays, we defined the interaction between the Foxk1 FHA (forkhead-associated domain) domain and phospho-Thr49 in Sds3. We demonstrated that the transcriptional repression of Foxk1 is dependent on the Sin3–Sds3 repression complex, and knockdown of Sds3 results in cell-cycle arrest. We further identified the protein kinase CK2 as the protein kinase for Sds3 Thr49 and demonstrated that the protein kinase activity of CK2 is required for proper cell-cycle progression. Analysis of CK2 mutant mice reveals perturbation of skeletal muscle regeneration due to the dysregulation of cell-cycle kinetics. Overall, these studies define a CK2–Sds3–Foxk1 cascade that modulates gene expression and regulates skeletal muscle regeneration.
An aminoquinazoline inhibitor of the essential bacterial cell wall synthetic enzyme GlmU has a unique non-protein-kinase-like binding mode
Authors: Larsen Nicholas A. , Nash Tory J. , Morningstar Marshall , Shapiro Adam B. , Joubran Camil , Blackett Carolyn J. , Patten Arthur D. , Boriack-Sjodin P. Ann , Doig Peter
Published: June 2012

GlmU is a bifunctional enzyme with acetyltransferase and uridyltransferase activities, and is essential for the biosynthesis of the bacterial cell wall. Inhibition results in a loss of cell viability. GlmU is therefore considered a potential target for novel antibacterial agents. A HTS (high-throughput screen) identified a series of aminoquinazolines with submicromolar potency against the uridyltransferase reaction. Biochemical and biophysical characterization showed competition with UTP binding. We determined the crystal structure of a representative aminoquinazoline bound to the Haemophilus influenzae isoenzyme at a resolution of 2.0 Å. The inhibitor occupies part of the UTP site, skirts the outer perimeter of the GlcNAc1-P (N-acetylglucosamine-1-phosphate) pocket and anchors a hydrophobic moiety into a lipophilic pocket. Our SAR (structure–activity relationship) analysis shows that all of these interactions are essential for inhibitory activity in this series. The crystal structure suggests that the compound would block binding of UTP and lock GlmU in an apo-enzyme-like conformation, thus interfering with its enzymatic activity. Our lead generation effort provides ample scope for further optimization of these compounds for antibacterial drug discovery.
Erythrocyte storage increases rates of NO and nitrite scavenging: implications for transfusion-related toxicity
Authors: Stapley Ryan , Owusu Benjamin Y. , Brandon Angela , Cusick Marianne , Rodriguez Cilina , Marques Marisa B. , Kerby Jeffrey D. , Barnum Scott R. , Weinberg Jordan A. , Lancaster Jack R. , Patel Rakesh P.
Published: June 2012

Storage of erythrocytes in blood banks is associated with biochemical and morphological changes to RBCs (red blood cells). It has been suggested that these changes have potential negative clinical effects characterized by inflammation and microcirculatory dysfunction which add to other transfusion-related toxicities. However, the mechanisms linking RBC storage and toxicity remain unclear. In the present study we tested the hypothesis that storage of leucodepleted RBCs results in cells that inhibit NO (nitric oxide) signalling more so than younger cells. Using competition kinetic analyses and protocols that minimized contributions from haemolysis or microparticles, our data indicate that the consumption rates of NO increased ~40-fold and NO-dependent vasodilation was inhibited 2–4-fold comparing 42-day-old with 0-day-old RBCs. These results are probably due to the formation of smaller RBCs with increased surface area: volume as a consequence of membrane loss during storage. The potential for older RBCs to affect NO formation via deoxygenated RBC-mediated nitrite reduction was also tested. RBC storage did not affect deoxygenated RBC-dependent stimulation of nitrite-induced vasodilation. However, stored RBCs did increase the rates of nitrite oxidation to nitrate in vitro. Significant loss of whole-blood nitrite was also observed in stable trauma patients after transfusion with 1 RBC unit, with the decrease in nitrite occurring after transfusion with RBCs stored for >25 days, but not with younger RBCs. Collectively, these data suggest that increased rates of reactions between intact RBCs and NO and nitrite may contribute to mechanisms that lead to storage-lesion-related transfusion risk.
Combination renin–angiotensin system blockade and angiotensin-converting enzyme 2 in experimental myocardial infarction: implications for future therapeutic directions
Authors: Burchill Luke J. , Velkoska Elena , Dean Rachael G. , Griggs Karen , Patel Sheila K. , Burrell Louise M.
Published: June 2012

The RAS (renin–angiotensin system) is activated after MI (myocardial infarction), and RAS blockade with ACEis [ACE (angiotensin-converting enzyme) inhibitors] or ARBs (angiotensin receptor blockers) slows but does not completely prevent progression to heart failure. Cardiac ACE is increased after MI and leads to the formation of the vasoconstrictor AngII (angiotensin II). The enzyme ACE2 is also activated after MI and degrades AngII to generate the vasodilator Ang-(1–7) [angiotensin-(1–7)]. Overexpression of ACE2 offers cardioprotective effects in experimental MI, but there is conflicting evidence as to whether the benefits of ACEis and ARBs are mediated through increasing ACE2 after MI. In the present study, we assessed the effect of an ACEi and ARB, alone and in combination, on cardiac ACE2 in a rat MI model. MI rats received vehicle, ACEi (ramipril; 1 mg/kg of body weight), ARB (valsartan; 10 mg/kg of body weight) or combination (ramipril at 1 mg/kg of body weight and valsartan at 10 mg/kg of body weight) orally for 28 days. Sham-operated rats were also studied and received vehicle alone. MI increased LV (left ventricular) mass (P<0.0001), impaired cardiac contractility (P<0.05) and activated cardiac ACE2 with increased gene (P<0.05) and protein expression (viable myocardium, P<0.05; border zone, P<0.001; infarct, P<0.05). Ramipril and valsartan improved remodelling (P<0.05), with no additional effect of dual therapy. Although ramipril inhibited ACE, and valsartan blocked the angiotensin receptor, neither treatment alone nor in combination augmented cardiac ACE2 expression. These results suggest that the cardioprotective effects of ramipril and valsartan are not mediated through up-regulation of cardiac ACE2. Strategies that do augment ACE2 after MI may be a useful addition to standard RAS blockade after MI.
Knorpelregeneration nach valgisierender Tibiakopfosteotomie. Ergebnisse einer arthroskopischen Studie
Authors: Spahn G. , Klinger H. , Harth P. , Hofmann G.
Published: June 2012

Zielstellung: Die hohe Tibiakopfosteotomie (HTO) stellt ein etabliertes Verfahren bei der Behandlung unikompartimenteller medialer Gonarthrosen dar. Diese Studie wurde mit dem Ziel durchgeführt, eine mögliche Knorpelregeneration nach HTO in Beziehung zu den bei der Indexoperation angewandten arthroskopischen Knorpeltherapieverfahren zu untersuchen. Dazu wurden 1,5 Jahre nach medial öffnender HTO im Rahmen der Metallentfernung Kontrollarthroskopien durchgeführt. Material und Methode: Bei 135 Patienten (72 Männer und 63 Frauen; Altersmittelwert 48,8 Jahre) erfolgte nach knöcherner Konsolidierung einer Opening-Wedge-HTO (1,5 Jahre) die Metallentfernung mit gleichzeitiger Kontrollarthroskopie. Die Schwere der Knorpelschäden wurde durch das ICRS-Schema (International Cartilage Repair Society) bestimmt. Ergebnisse: Bei ursprünglich Grad III konnte im Bereich des medialen Femurkondyls in 40,4 % und im Bereich des medialen Tibiaplateaus in sogar 62,3 % eine verbesserte Knorpelqualität festgestellt werden. Dagegen kam es in 13,1 % im Bereich des MFC und 8,5 % im Bereich des TM zu einer Verschlechterung der ursprünglichen Grad-III-Läsionen in einen kompletten Defekt (Grad-IV-Schaden). Am besten schnitten dabei diejenigen Patienten ab, bei denen im Verlauf der Indexoperation eine Thermoablation durchgeführt wurde. Alle kompletten Defekte wurden anlässlich der Indexoperation durch Mikrofrakturierung nach Steadman behandelt. In knapp ⅔ der ehemaligen Defekte am MFC und in etwa ⅓ der ehemaligen TM-Defekte wurde dabei im Verlauf der Kontrollarthroskopie eine Auffüllung der ehemaligen Defektzone mit in der Hakenprobe stabilen Regeneraten nachgewiesen. Schlussfolgerungen: Die medial öffnende HTO in Kombination mit einer arthroskopischen Knorpeltherapie erbringt einerseits ein gutes klinisches Outcome und andererseits kommt es bei einem Teil der Patienten zu einer partiellen Regeneration der geschädigten Knorpelflächen. Ein Zusammenhang zwischen klinischem Outcome und der Knorpelregeneration konnte jedoch nicht sicher nachgewiesen werden. Nach unseren Untersuchungen ist die klinische Verbesserung in erster Linie auf die Wiederherstellung physiologischer Achsverhältnisse zurückzuführen. Inwieweit die Knorpelregeneration möglicherweise aber das Langzeitresultat beeinflusst, bleibt ungewiss.
Determining the growth responses of Phyla canescens to shoot and root damage as a platform to better-informed weed-management decisions
Authors: Julien M. H. , Xu C.-Y. , Bourne A. , Gellender M. , De Clerck-Floate R.
Published: June 2012

Understanding the responses of invasive plants to control methods is important in developing effective management strategies. Lippia (Phyla canescens (Kunth) Greene : Verbenaceae) is an invasive, perennial, clonal forb for which few control options exist for use in the Australian natural and agro-ecosystems it threatens. To help inform management decisions, lippia’s growth responses to damage it may experience during proposed control measures, i.e. cutting, crushing, twisting, were assessed in three glasshouse experiments using either whole plants or plant pieces. Plants quickly recovered from severe damage through growth from shoot and root buds at stem nodes. After shoot and root removal, the relative growth rate of the remaining plant was twice that of controls, suggesting tolerance to damage. Lacking buds, root pieces and isolated stem internodes were incapable of responding. Crushing and cutting individual ramets and plant pieces induced the largest responses, including release of axillary buds on damage or removal of apical buds, but full recovery was not achieved. Lippia will be difficult to control because of its ability to rapidly propagate from stem fragments possessing undamaged or damaged nodes; thus, the full impact of control methods that increase fragmentation (e.g. grazing) should be assessed before implementation. Our results also suggest that the most effective biological agents will be those that limit lippia’s vegetative growth and spread, such as shoot- or crown-feeding insects.
Similarities in recruitment but differences in persistence in two related native and invasive trees: relevance of regenerative and vegetative attributes
Authors: Tecco Paula A. , Ferreras Ana E. , Gurvich Diego E. , Funes Guillermo
Published: June 2012

Ecological theory predicts that the success of exotic plants in new environments depends on a combination of both regenerative and vegetative attributes. Identifying those attributes may benefit from approaches that specifically compare related exotic and native species, thereby overcoming strong habitat dependence and phylogenetic bias. Gleditsia triacanthos L. (Fabaceae) is described as an aggressive woody invader in a broad range of ecosystems of Argentina, where it coexists with other leguminous trees. In the present study, we assessed whether the success of G. triacanthos in the lower areas of Chaco woodlands of central Argentina is determined (1) by differences from the dominant native, Prosopis alba, in its combination of several attributes that enhance the invader’s competitive ability, (2) by differences from P. alba in few key attributes that facilitate its spread, or (3) by strong functional similarities in response to environmental filtering by the invaded system. Our comparison of 19 functional traits of both species showed that regenerative and vegetative trends may vary independently, and that two contrasting strategies seem to underlie the success of G. triacanthos in this region. On the one hand, the invader might benefit by sharing regenerative attributes with the native relative that dominates the community, which is evidently a successful way of recruiting in the system. On the other hand, as recruitment is ensured, the species differs in several vegetative attributes, which may enhance its competitive ability in terms of growth rates and nutrient uptake.
Burning creates contrasting demographic patterns in Polygala lewtonii (Polygalaceae): a cradle-to-grave analysis of multiple cohorts in a perennial herb
Authors: Weekley Carl W. , Menges Eric S.
Published: June 2012

Fire drives the population dynamics of many plants. By following successive cohorts of Polygala lewtonii Small (Polygalaceae), a short-lived herb endemic to fire-maintained Florida sandhills, in both burned and unburned microsites, we investigated how fire affected vital rates throughout cohort lifetimes. We followed cohorts from before to 6 years after a prescribed fire in 220 25-cm-radius quadrats, recording survival and seedling recruitment quarterly, and growth and fecundity annually. Fire effects were most pronounced in the first 2 post-burn quarterly censuses, when cohorts in burned (v. unburned) quadrats had seven-fold higher seedling recruitment, significantly higher seedling survival, and a 16.7% gain (v. 1.2% loss) in quadrat occupancy. Plants in burned (v. unburned) quadrats also flowered earlier, were more likely to survive to reproduce and had longer lifespans. The negative effects of density on survival were relaxed in burned quadrats for the first 2 censuses. Burning creates contrasting demographic trajectories for burned v. unburned cohorts. In burned microsites, higher seedling recruitment and survival, earlier flowering and longer lifespans combine to produce a greater contribution to the seedbank and, thus, to population viability. The present study documents the pyro-demographic mechanisms linking the life history of a perennial herb with a frequent fire regime.
Structure, function and secretory products of the peltate glands of Centrolobium tomentosum (Fabaceae, Faboideae)
Authors: Matos Esmeire Cruz , Paiva Élder Antônio Sousa
Published: June 2012

The glandular structures of Centrolobium tomentosum Guill. ex Benth. have been little studied despite the economic importance of this species. We describe here the distribution, development, structure and ultrastructure of the secretory cells of the peltate glands found on the vegetative organs of this species. Stem apices and leaves in various stages of development were collected and prepared for examination by light, scanning and transmission electron microscopy. Chemical analyses and conventional histochemical tests to determine the chemical nature of the secretory products were also carried out. Peltate glands occur on aerial vegetative organs during their primary growth stage. These trichomes are structurally stable, persisting throughout the development of the organ. During the initial stages of the gland development, cell separation creates a central space that expands as secretions accumulate. Maximum secretion rates occur during this phase and the secreting cells characteristically have well developed smooth and rough endoplasmic reticulum, and high numbers of plastids and mitochondria. During the later stages of the secretory phase, the central cells show symptoms of cell death and are incorporated in to the secretions. At trichome maturity, the central space is delimited by a uniseriate epithelium. In addition to the resin, which is the main secretory product, an extensive three-dimensional carbohydrate matrix was observed that extended throughout the central space, apparently giving support to the resin droplets. The terpenic nature of the secretion was confirmed by thin-layer chromatography. Given the terpenic nature of the secretion and the permanence of trichomes throughout all phases of leaf development, it is postulated that the resin-secreting trichomes act to protect the plant against herbivores.
A putative hybrid of Eucalyptus largiflorens growing on salt- and drought-affected floodplains has reduced specific leaf area and leaf nitrogen
Authors: Koerber Georgia R. , Seekamp Jack V. , Anderson Peter A. , Whalen Molly A. , Tyerman Stephen D.
Published: June 2012

A putative hybrid between Eucalyptus largiflorens F.Muell. and Eucalyptus gracilis F.Muell., called green box, has attracted attention for its ability to grow on the salt- and drought-affected Chowilla floodplain of the Murray River in South Australia. Relationships between carbon isotope discrimination (Δ13C) and the ratio of substomatal to ambient CO2 (ci/ca) indicated that green box was not as water use efficient as E. largiflorens. Specific leaf area of green box and E. gracilis was significantly lower compared with E. largiflorens (38.38 and 36.96 versus 43.71 cm2 g–1). Leaf nitrogen for green box and E. gracilis was significantly lower compared with E. largiflorens (12.66 and 11.35 versus 15.07 mg g–1 dry weight, P = 0.004 and 0.001, respectively) and leaf carbon of E. gracilis was significantly higher compared with green box and E. largiflorens (541.75 versus 514.90 and 519.82 mg g–1 dry weight, P = 0.002 and 0.011 respectively). There were significantly (P = 0.016) more occurrences of elevated ci/ca below a minimum gs in E. gracilis compared with E. largiflorens, with green box being intermediate (means = 21.6, 6.8 and 9.4). After 10 years, E. largiflorens trunk circumference had significantly increased (P = 0.017) and height had significantly decreased (P = 0.026) due to visible dieback. Green box and E. gracilis grew slower, conserving resources, illustrating a useful strategy to consider when choosing plants for revegetation efforts.