bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term erosional hot spots in the southern Brazilian coast
Authors: Alves Albano Ribeiro
Published: February 2009

The southern Brazilian coast is a sandy barrier adorned by subtle shoreline perturbations widespread in a rhythmical pattern. Previous works indicated that short‐ and long‐term shoreline changes are not alongshore uniform. They are based on coastline position monitoring, geomorphological evidences, historical cartographic documents, and aerial photography. Moreover, these studies associated the main observed erosional sites with high rates of sediment drift and energy focusing due to wave refraction. Nevertheless, the role of the highly oblique incident waves in driving shoreline changes was not considered. A recently derived sediment diffusion equation showed the possibility of coastal instability induced by incident waves with high obliqueness, as opposed to the traditional approach. Therefore, this paper applied these concepts to wave climate and performed coastal instability analysis to explain shoreline changes at an undulating littoral. Calculations showed wave climate yielding a negative instability index (−0.13) when using a 42‐month‐long time series of wave parameters obtained from a forecasting numerical model. Also, the calculated direction asymmetry on wave climate revealed a net littoral drift. Consequently, the sites between troughs and updrift flanks of shoreline undulations are expected to exhibit erosive processes. This is the case in the most conspicuous long‐term erosional hot spots at the southern Brazilian coast, which was pointed out in earlier studies. Therefore, coastal instability and littoral sediment drift analysis explained the main morphodynamic processes governing shoreline changes at the study area.
Land surface temperature from Ka band (37 GHz) passive microwave observations
Authors: Holmes T. R. H. , De Jeu R. A. M. , Owe M. , Dolman A. J.
Published: February 2009

An alternative to thermal infrared satellite sensors for measuring land surface temperature (Ts) is presented. The 37 GHz vertical polarized brightness temperature is used to derive Ts because it is considered the most appropriate microwave frequency for temperature retrieval. This channel balances a reduced sensitivity to soil surface characteristics with a relatively high atmospheric transmissivity. It is shown that with a simple linear relationship, accurate values for Ts can be obtained from this frequency, with a theoretical bias of within 1 K for 70% of vegetated land areas of the globe. Barren, sparsely vegetated, and open shrublands cannot be accurately described with this single channel approach because variable surface conditions become important. The precision of the retrieved land surface temperature is expected to be better than 2.5 K for forests and 3.5 K for low vegetation. This method can be used to complement existing infrared derived temperature products, especially during clouded conditions. With several microwave radiometers currently in orbit, this method can be used to observe the diurnal temperature cycles with surprising accuracy.
Overview of observations from the RADAGAST experiment in Niamey, Niger: 2. Radiative fluxes and divergences
Authors: Slingo A. , White H. E. , Bharmal N. A. , Robinson G. J.
Published: February 2009

Broadband shortwave and longwave radiative fluxes observed both at the surface and from space during the Radiative Atmospheric Divergence using ARM Mobile Facility, GERB data and AMMA Stations (RADAGAST) experiment in Niamey, Niger, in 2006 are presented. The surface fluxes were measured by the Atmospheric Radiation Measurement (ARM) Program Mobile Facility (AMF) at Niamey airport, while the fluxes at the top of the atmosphere (TOA) are from the Geostationary Earth Radiation Budget (GERB) instrument on the Meteosat‐8 satellite. The data are analyzed as daily averages, in order to minimize sampling differences between the surface and top of atmosphere instruments, while retaining the synoptic and seasonal changes that are the main focus of this study. A cloud mask is used to identify days with cloud versus those with predominantly clear skies. The influence of temperature, water vapor, aerosols, and clouds is investigated. Aerosols are ubiquitous throughout the year and have a significant impact on both the shortwave and longwave fluxes. The large and systematic seasonal changes in temperature and column integrated water vapor (CWV) through the dry and wet seasons are found to exert strong influences on the longwave fluxes. These influences are often in opposition to each other, because the highest temperatures occur at the end of the dry season when the CWV is lowest, while in the wet season the lowest temperatures are associated with the highest values of CWV. Apart from aerosols, the shortwave fluxes are also affected by clouds and by the seasonal changes in CWV. The fluxes are combined to provide estimates of the divergence of radiation across the atmosphere throughout 2006. The longwave divergence shows a relatively small variation through the year, because of a partial compensation between the seasonal variations in the outgoing longwave radiation (OLR) and surface net longwave radiation. A simple model of the greenhouse effect is used to interpret this result in terms of the dependence of the normalized greenhouse effect at the TOA and of the effective emissivity of the atmosphere at the surface on the CWV. It is shown that, as the CWV increases, the atmosphere loses longwave energy to the surface with about the same increasing efficiency with which it traps the OLR. When combined with the changes in temperature, this maintains the atmospheric longwave divergence within the narrow range that is observed. The shortwave divergence is mainly determined by the CWV and aerosol loadings and the effect of clouds is much smaller than on the component fluxes.
Particulate emissions from commercial shipping: Chemical, physical, and optical properties
Authors: Lack Daniel A. , Corbett James J. , Onasch Timothy , Lerner Brian , Massoli Paola , Quinn Patricia K. , Bates Timothy S. , Covert David S. , Coffman Derek , Sierau Berko , Herndon Scott , Allan James , Baynard Tahllee , Lovejoy Edward , Ravishankara A. R. , Williams Eric
Published: February 2009

We characterize particulate emissions on the basis of chemical, physical, and optical properties from commercial vessels. Observations during the Texas Air Quality Study/Gulf of Mexico Atmospheric Composition and Climate Study 2006 field campaign provide chemical and physical characteristics including sulfate (SO42−) mass, organic matter (OM) mass, black carbon (BC) mass, particulate matter (PM) mass, number concentrations (condensation nuclei (CN) > 5 nm), and cloud condensation nuclei (CCN). Optical characterization included multiple wavelength visible light absorption and extinction, extinction relative humidity dependence, and single scatter albedo (SSA). The global contribution of shipping PM was calculated to be 0.90 Tg a−1, in good agreement with previous inventories (0.91 and 1.13 Tg a−1 from Eyring et al. (2005a) and Wang et al. [2008]). Observed PM composition was 46% SO42−, 39% OM, and 15% BC and differs from inventories that used 81%, 14%, and 5% and 31%, 63%, and 6% SO42−, OM, and BC, respectively. SO42− and OM mass were found to be dependent on fuel sulfur content as were SSA, hygroscopicity, and CCN concentrations. BC mass was dependent on engine type and combustion efficiency. A plume evolution study conducted on one vessel showed conservation of particle light absorption, decrease in CN > 5 nm, increase in particle hygroscopicity, and an increase in average particle size with distance from emission. These results suggest emission of small nucleation mode particles that subsequently coagulate/condense onto larger BC and OM. This work contributes to an improved understanding of the impacts of ship emissions on climate and air quality and will also assist in determining potential effects of altering fuel standards.
A new model to simulate the Martian mesoscale and microscale atmospheric circulation: Validation and first results
Authors: Spiga Aymeric , Forget François
Published: February 2009

The Laboratoire de Météorologie Dynamique (LMD) Mesoscale Model is a new versatile simulator of the Martian atmosphere and environment at horizontal scales ranging from hundreds of kilometers to tens of meters. The model combines the National Centers for Environmental Prediction(NCEP)‐National Center for Atmospheric Research (NCAR) fully compressible nonhydrostatic Advanced Research Weather Research and Forecasting (ARW‐WRF) dynamical core, adapted to Mars, with the LMD‐general circulation model (GCM) comprehensive set of physical parameterizations for the Martian dust, CO2, water, and photochemistry cycles. Since LMD‐GCM large‐scale simulations are also used to drive the mesoscale model at the boundaries of the chosen domain of interest, a high level of downscaling consistency is reached. To define the initial state and the atmosphere at the domain boundaries, a specific “hybrid” vertical interpolation from the coarse‐resolution GCM fields to the high‐resolution mesoscale domain is used to ensure the stability and the physical relevancy of the simulations. Used in synoptic‐scale mode with a cyclic domain wrapped around the planet, the mesoscale model correctly replicates the main large‐scale thermal structure and the zonally propagating waves. The model diagnostics of the near‐surface pressure, wind, and temperature daily cycles in Chryse Planitia are in accordance with the Viking and Pathfinder measurements. Afternoon gustiness at the respective landing sites is adequately accounted for on the condition that convective adjustment is turned off in the mesoscale simulations. On the rims of Valles Marineris, intense daytime anabatic (∼30 m s−1) and nighttime katabatic (∼40 m s−1) winds are predicted. Within the canyon corridors, topographical channeling can amplify the wind a few kilometers above the ground, especially during the night. Through large‐eddy simulations in Gusev Crater, the model describes the mixing layer growth during the afternoon, and the associated dynamics: convective motions, overlying gravity waves, and dust devil–like vortices. Modeled temperature profiles are in satisfactory agreement with the Miniature Thermal Emission Spectrometer (Mini‐TES) measurements. The ability of the model to transport tracers at regional scales is exemplified by the model's prediction for the altitude of the Tharsis topographical water ice clouds in the afternoon. Finally, a nighttime “warm ring” at the base of Olympus Mons is identified in the simulations, resulting from adiabatic warming by the intense downslope winds along the flanks of the volcano. The surface temperature enhancement reaches +20 K throughout the night. Such a phenomenon may have adversely affected the thermal inertia derivations in the region.
Visualization of Interfirm Relations in a Converging Mobile Ecosystem
Authors: Basole Rahul C
Published: February 2009

The mobile ecosystem is characterized by a large and complex network of companies interacting with each other, directly and indirectly, to provide a broad array of mobile products and services to end-customers. With the convergence of enabling technologies, the complexity of the mobile ecosystem is increasing multifold as new actors are emerging, new relations are formed, and the traditional distribution of power is shifted. Drawing on theories of network science, complex systems, interfirm relationships, and the creative art and science of visualization, this paper identifies key players and maps the complex structure and dynamics of nearly 7000 global companies and over 18,000 relationships in the converging mobile ecosystem. Our approach enables decision makers to (i) visually explore the complexity of interfirm relations in the mobile ecosystem, (ii) discover the relation between current and emerging segments, (iii) determine the impact of convergence on ecosystem structure, (iv) understand a firm's competitive position, and (v) identify interfirm relation patterns that may influence their choice of innovation strategy or business models.
The Role of (Personal) Network Effects and Switching Costs in Determining Mobile Users’ Choice
Authors: Maicas Juan Pablo , Polo Yolanda , Sese Francisco Javier
Published: February 2009

Network effects and switching costs are two major economic forces in information technology industries. Although the consequences of these mechanisms on competition and firm strategy have been well documented in the literature, research on their impact on customer behavior has received less attention. In this study, the authors investigate the role of personal network effects and switching costs in explaining customer choice in the Spanish mobile telecommunications industry. Personal network effects are present when an individual user's utility increases more when some individuals adopt (social network) than when others do. Switching costs refer to costs associated with the process of switching from one provider to another. In addition, this paper studies the drivers of personal network effects and switching behavior. The results reveal that personal network effects and switching costs play a key role in determining mobile users’ choice: the probability that a customer selects a mobile phone company increases with the number of members of her social network already subscribed to that firm, and switching costs are significantly present in the mobile phone market making switching providers costly. Concerning the drivers of both mechanisms, the authors find that relationship characteristics (length, depth and breadth) and demographics differently affect personal network effects perceptions and consumer switching behavior. Implications for decision makers are discussed.
Distinguishing medium-range order in metallic glasses using fluctuation electron microscopy: A theoretical study using atomic models
Authors: Wen J. , Cheng Y. Q. , Wang J. Q. , Ma E.
Published: February 2009

We have simulated the variance in the diffracted electron intensity as a function of scattering vector in fluctuation electron microscopy for a range of fully amorphous and nanocrystal-containing metallic glass models. Variance peaks are obvious for glasses that contain well-developed short-to-medium range order but absent for their parent liquids. The variance peaks are very sensitive to the presence and especially the size of the nanocrystal embryos or nuclei embedded in the glass matrix but much less so to the variations in the type or degree of the cluster ordering developed in fully amorphous materials.
Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts
Authors: Hussain Ashiq , Saraiva Luis R. , Korsching Sigrun I.
Published: February 2009

Trace amine-associated receptors (TAARs) in mammals recently have been shown to function as olfactory receptors. We have delineated the
taar
gene family in jawless, cartilaginous, and bony fish (zero, 2, and >100 genes, respectively). We conclude that
taar
genes are evolutionary much younger than the related OR and ORA/V1R olfactory receptor families, which are present already in lamprey, a jawless vertebrate. The 2 cartilaginous fish genes appear to be ancestral for 2
taar
classes, each with mammalian and bony fish (teleost) representatives. Unexpectedly, a whole new clade, class III, of
taar
genes originated even later, within the teleost lineage.
Taar
genes from all 3 classes are expressed in subsets of zebrafish olfactory receptor neurons, supporting their function as olfactory receptors. The highly conserved TAAR1 (shark, mammalian, and teleost orthologs) is not expressed in the olfactory epithelium and may constitute the sole remnant of a primordial, nonolfactory function of this family. Class III comprises three-fourths of all teleost
taar
genes and is characterized by the complete loss of the aminergic ligand-binding motif, stringently conserved in the other 2 classes. Two independent intron gains in class III
taar
genes represent extraordinary evolutionary dynamics, considering the virtual absence of intron gains during vertebrate evolution. The d
N
/d
S
analysis suggests both minimal global negative selection and an unparalleled degree of local positive selection as another hallmark of class III genes. The accelerated evolution of class III teleost
taar
genes conceivably might mark the birth of another olfactory receptor gene family.
Uncovering the rules for protein–protein interactions from yeast genomic data
Authors: Wang Jin , Li Chunhe , Wang Erkang , Wang Xidi
Published: February 2009

Identifying protein–protein interactions is crucial for understanding cellular functions. Genomic data provides opportunities and challenges in identifying these interactions. We uncover the rules for predicting protein–protein interactions using a frequent pattern tree (FPT) approach modified to generate a minimum set of rules (mFPT), with rule attributes constructed from the interaction features of the yeast genomic data. The mFPT prediction accuracy is benchmarked against other commonly used methods such as Bayesian networks and logistic regressions under various statistical measures. Our study indicates that mFPT outranks other methods in predicting the protein–protein interactions for the database used. We predict a new protein–protein interaction complex whose biological function is related to premRNA splicing and new protein–protein interactions within existing complexes based on the rules generated. Our method is general and can be used to discover the underlying rules for protein–protein interactions, genomic interactions, structure-function relationships, and other fields of research.
Phylogenomic analyses support the monophyly of Excavata and resolve relationships among eukaryotic “supergroups”
Authors: Hampl Vladimir , Hug Laura , Leigh Jessica W. , Dacks Joel B. , Lang B. Franz , Simpson Alastair G. B. , Roger Andrew J.
Published: February 2009

Nearly all of eukaryotic diversity has been classified into 6 suprakingdom-level groups (supergroups) based on molecular and morphological/cell-biological evidence; these are Opisthokonta, Amoebozoa, Archaeplastida, Rhizaria, Chromalveolata, and Excavata. However, molecular phylogeny has not provided clear evidence that either Chromalveolata or Excavata is monophyletic, nor has it resolved the relationships among the supergroups. To establish the affinities of Excavata, which contains parasites of global importance and organisms regarded previously as primitive eukaryotes, we conducted a phylogenomic analysis of a dataset of 143 proteins and 48 taxa, including 19 excavates. Previous phylogenomic studies have not included all major subgroups of Excavata, and thus have not definitively addressed their interrelationships. The enigmatic flagellate
Andalucia
is sister to typical jakobids. Jakobids (including
Andalucia
), Euglenozoa and Heterolobosea form a major clade that we name Discoba. Analyses of the complete dataset group Discoba with the mitochondrion-lacking excavates or “metamonads” (diplomonads, parabasalids, and Preaxostyla), but not with the final excavate group,
Malawimonas
. This separation likely results from a long-branch attraction artifact. Gradual removal of rapidly-evolving taxa from the dataset leads to moderate bootstrap support (69%) for the monophyly of all Excavata, and 90% support once all metamonads are removed. Most importantly, Excavata robustly emerges between unikonts (Amoebozoa + Opisthokonta) and “megagrouping” of Archaeplastida, Rhizaria, and chromalveolates. Our analyses indicate that Excavata forms a monophyletic suprakingdom-level group that is one of the 3 primary divisions within eukaryotes, along with unikonts and a megagroup of Archaeplastida, Rhizaria, and the chromalveolate lineages.
Antidiabetic drug metformin (Glucophage
R
) increases biogenesis of Alzheimer's amyloid peptides via up-regulating
BACE1
transcription
Authors: Chen Yaomin , Zhou Kun , Wang Ruishan , Liu Yun , Kwak Young-Don , Ma Tao , Thompson Robert C. , Zhao Yongbo , Smith Layton , Gasparini Laura , Luo Zhijun , Xu Huaxi , Liao Francesca-Fang
Published: February 2009

Epidemiological, clinical and experimental evidence suggests a link between type 2 diabetes and Alzheimer's disease (AD). Insulin modulates metabolism of β-amyloid precursor protein (APP) in neurons, decreasing the intracellular accumulation of β-amyloid (Aβ) peptides, which are pivotal in AD pathogenesis. The present study investigates whether the widely prescribed insulin-sensitizing drug, metformin (Glucophage
R
), affects APP metabolism and Aβ generation in various cell models. We demonstrate that metformin, at doses that lead to activation of the AMP-activated protein kinase (AMPK), significantly increases the generation of both intracellular and extracellular Aβ species. Furthermore, the effect of metformin on Aβ generation is mediated by transcriptional up-regulation of β-secretase (BACE1), which results in an elevated protein level and increased enzymatic activity. Unlike insulin, metformin exerts no effect on Aβ degradation. In addition, we found that glucose deprivation and various tyrphostins, known inhibitors of insulin-like growth factors/insulin receptor tyrosine kinases, do not modulate the effect of metformin on Aβ. Finally, inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin's effect on Aβ generation and
BACE1
transcription, suggesting an AMPK-dependent mechanism. Although insulin and metformin display opposing effects on Aβ generation, in combined use, metformin enhances insulin's effect in reducing Aβ levels. Our findings suggest a potentially harmful consequence of this widely prescribed antidiabetic drug when used as a monotherapy in elderly diabetic patients.
Crystal structure of the Borna disease virus matrix protein (BDV-M) reveals ssRNA binding properties
Authors: Neumann Piotr , Lieber Diana , Meyer Sylke , Dautel Philipp , Kerth Andreas , Kraus Ina , Garten Wolfgang , Stubbs Milton T.
Published: February 2009

Borna disease virus (BDV) is a neurotropic enveloped RNA virus that causes a noncytolytic, persistent infection of the central nervous system in mammals. BDV belongs to the order
Mononegavirales
, which also includes the negative-strand RNA viruses (NSVs) Ebola, Marburg, vesicular stomatitis, rabies, mumps, and measles. BDV-M, the matrix protein (M-protein) of BDV, is the smallest M-protein (16.2 kDa) among the NSVs. M-proteins play a critical role in virus assembly and budding, mediating the interaction between the viral capsid, envelope, and glycoprotein spikes, and are as such responsible for the structural stability and individual form of virus particles. Here, we report the 3D structure of BDV-M, a full-length M-protein structure from a nonsegmented RNA NSV. The BDV-M monomer exhibits structural similarity to the N-terminal domain of the Ebola M-protein (VP40), while the surface charge of the tetramer provides clues to the membrane association of BDV-M. Additional electron density in the crystal reveals the presence of bound nucleic acid, interpreted as cytidine-5′-monophosphate. The heterologously expressed BDV-M copurifies with and protects ssRNA oligonucleotides of a median length of 16 nt taken up from the expression host. The results presented here show that BDV-M would be able to bind RNA and lipid membranes simultaneously, expanding the repertoire of M-protein functionalities.
Sequence context effect for hMSH2-hMSH6 mismatch-dependent activation
Authors: Mazurek Anthony , Johnson Christopher N. , Germann Markus W. , Fishel Richard
Published: February 2009

Numerous DNA mismatches and lesions activate MutS homologue (MSH) ATPase activity that is essential for mismatch repair (MMR). We have found that a mismatch embedded in a nearest-neighbor sequence context containing symmetric 3′-purines (2 × 3′-purines) enhanced, whereas symmetric 3′-pyrimidines (2 × 3′-pyrimidines) reduced, hMSH2-hMSH6 ATPase activation. The 3′-purine/pyrimidine effect was most evident for G-containing mispairs. A similar trend pervaded mismatch binding (
K
D
) and the melting of unbound oligonucleotides (
T
m
; Δ
G
). However, these latter measures did not accurately predict the hierarchy of MSH ATPase activation. NMR studies of imino proton lifetime, solvent accessibility, and NOE connectivity suggest that sequence contexts that provoke improved MSH-activation displayed enhanced localized DNA flexibility: a dynamic DNA signature that may account for the wide range of lesions that activate MSH functions.
Crystal structure of human CDK4 in complex with a D-type cyclin
Authors: Day Philip J. , Cleasby Anne , Tickle Ian J. , O'Reilly Marc , Coyle Joe E. , Holding Finn P. , McMenamin Rachel L. , Yon Jeff , Chopra Rajiv , Lengauer Christoph , Jhoti Harren
Published: February 2009

The cyclin D1–cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G
1
phase of the cell cycle. Among the cyclin/CDKs, CDK4 and cyclin D1 are the most frequently activated by somatic genetic alterations in multiple tumor types. Thus, aberrant regulation of the CDK4/cyclin D1 pathway plays an essential role in oncogenesis; hence, CDK4 is a genetically validated therapeutic target. Although X-ray crystallographic structures have been determined for various CDK/cyclin complexes, CDK4/cyclin D1 has remained highly refractory to structure determination. Here, we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 Å. Although CDK4 is bound to cyclin D1 and has a phosphorylated T-loop, CDK4 is in an inactive conformation and the conformation of the heterodimer diverges from the previously known CDK/cyclin binary complexes, which suggests a unique mechanism for the process of CDK4 regulation and activation.
The structure of CDK4/cyclin D3 has implications for models of CDK activation
Authors: Takaki T. , Echalier A. , Brown N. R. , Hunt T. , Endicott J. A. , Noble M. E. M.
Published: February 2009

Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G
1
phase of the cell cycle and stimulate the expression of genes required for G
1
progression by phosphorylation of the product of the retinoblastoma gene, pRb. To elaborate the molecular pathway of CDK4 activation and substrate selection we have determined the structure of nonphosphorylated CDK4/cyclin D3. This structure of an authentic CDK/cyclin complex shows that cyclin binding may not be sufficient to drive the CDK active site toward an active conformation. Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27
Kip1
. Unlike CDK2/cyclin A, CDK4/cyclin D3 can be inactivated by treatment with λ-phosphatase, implying that phosphorylated T172 is accessible to a generic phosphatase while bound to a cyclin. Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes.
Impaired attentional selection following lesions to human pulvinar: Evidence for homology between human and monkey
Authors: Snow Jacqueline C. , Allen Harriet A. , Rafal Robert D. , Humphreys Glyn W.
Published: February 2009

We examined the contributions of the human pulvinar to goal directed selection of visual targets in 3 patients with chronic, unilateral lesions involving topographic maps in the ventral pulvinar. Observers completed 2 psychophysical tasks in which they discriminated the orientation of a lateralized target grating in the presence of vertically-aligned distracters. In experiment 1, where distracter contrast was varied while target contrast remained constant, the patients' contralesional contrast thresholds for discriminating the orientation of grating stimuli were elevated only when the task required selection of a visual target in the face of competition from a salient distracter. Attentional selectivity was restored in the patients in experiment 2 where target contrast was varied while distracter contrast remained constant. These observations provide the first evidence that the human pulvinar plays a necessary role in modulating physical saliency in attentional selection, and supports a homology in global pulvinar structure between humans and monkey.
The multifunctional histone-like protein Lsr2 protects mycobacteria against reactive oxygen intermediates
Authors: Colangeli R. , Haq A. , Arcus V. L. , Summers E. , Magliozzo R. S. , McBride A. , Mitra A. K. , Radjainia M. , Khajo A. , Jacobs W. R. , Salgame P. , Alland D.
Published: February 2009

Mycobacterium tuberculosis
has evolved a number of strategies to survive within the hostile environment of host phagocytes. Reactive nitrogen and oxygen intermediates (RNI and ROI) are among the most effective antimycobacterial molecules generated by the host during infection. Lsr2 is a
M. tuberculosis
protein with histone-like features, including the ability to regulate a variety of transcriptional responses in mycobacteria. Here we demonstrate that Lsr2 protects mycobacteria against ROI in vitro and during macrophage infection. Furthermore, using macrophages derived from NOS
−/−
and Phox
−/−
mice, we demonstrate that Lsr2 is important in protecting against ROI but not RNI. The protection provided by Lsr2 protein is not the result of its ability to either bind iron or scavenge hydroxyl radicals. Instead, electron microscopy and DNA-binding studies suggest that Lsr2 shields DNA from reactive intermediates by binding bacterial DNA and physically protecting it. Thus, Lsr2 appears to be a unique protein with both histone-like properties and protective features that may be central to
M. tuberculosis
pathogenesis. In addition, evidence indicates that
lsr2
is an essential gene in
M. tuberculosis
. Because of its essentiality, Lsr2 may represent an excellent candidate as a drug target.
Impact of deforestation in the Amazon basin on cloud climatology
Authors: Wang Jingfeng , Chagnon Frédéric J. F. , Williams Earle R. , Betts Alan K. , Renno Nilton O. , Machado Luiz A. T. , Bisht Gautam , Knox Ryan , Bras Rafael L.
Published: February 2009

Shallow clouds are prone to appear over deforested surfaces whereas deep clouds, much less frequent than shallow clouds, favor forested surfaces. Simultaneous atmospheric soundings at forest and pasture sites during the Rondonian Boundary Layer Experiment (RBLE-3) elucidate the physical mechanisms responsible for the observed correlation between clouds and land cover. We demonstrate that the atmospheric boundary layer over the forested areas is more unstable and characterized by larger values of the convective available potential energy (CAPE) due to greater humidity than that which is found over the deforested area. The shallow convection over the deforested areas is relatively more active than the deep convection over the forested areas. This greater activity results from a stronger lifting mechanism caused by mesoscale circulations driven by deforestation-induced heterogeneities in land cover.
Mimicking the folding pathway to improve homology-free protein structure prediction
Authors: DeBartolo Joe , Colubri Andrés , Jha Abhishek K. , Fitzgerald James E. , Freed Karl F. , Sosnick Tobin R.
Published: February 2009

Since the demonstration that the sequence of a protein encodes its structure, the prediction of structure from sequence remains an outstanding problem that impacts numerous scientific disciplines, including many genome projects. By iteratively fixing secondary structure assignments of residues during Monte Carlo simulations of folding, our coarse-grained model without information concerning homology or explicit side chains can outperform current homology-based secondary structure prediction methods for many proteins. The computationally rapid algorithm using only single (φ,ψ) dihedral angle moves also generates tertiary structures of accuracy comparable with existing all-atom methods for many small proteins, particularly those with low homology. Hence, given appropriate search strategies and scoring functions, reduced representations can be used for accurately predicting secondary structure and providing 3D structures, thereby increasing the size of proteins approachable by homology-free methods and the accuracy of template methods that depend on a high-quality input secondary structure.
Multipoint molecular recognition within a calix[6]arene funnel complex
Authors: Coquière David , de la Lande Aurélien , Martí Sergio , Parisel Olivier , Prangé Thierry , Reinaud Olivia
Published: February 2009

A multipoint recognition system based on a calix[6]arene is described. The calixarene core is decorated on alternating aromatic subunits by 3 imidazole arms at the small rim and 3 aniline groups at the large rim. This substitution pattern projects the aniline nitrogens toward each other when Zn(II) binds at the Tris-imidazole site or when a proton binds at an aniline. The XRD structure of the monoprotonated complex having an acetonitrile molecule bound to Zn(II) in the cavity revealed a constrained geometry at the metal center reminiscent of an entatic state. Computer modeling suggests that the aniline groups behave as a tritopic monobasic site in which only 1 aniline unit is protonated and interacts with the other 2 through strong hydrogen bonding. The metal complex selectively binds a monoprotonated diamine vs. a monoamine through multipoint recognition: coordination to the metal ion at the small rim, hydrogen bonding to the calix-oxygen core, CH/π interaction within the cavity's aromatic walls, and H-bonding to the anilines at the large rim.
Directed evolution of adeno-associated virus to an infectious respiratory virus
Authors: Excoffon Katherine J. D. A. , Koerber James T. , Dickey David D. , Murtha Matthew , Keshavjee Shaf , Kaspar Brian K. , Zabner Joseph , Schaffer David V.
Published: February 2009

Respiratory viruses evolve to maintain infectivity levels that permit spread yet prevent host and virus extinction, resulting in surprisingly low infection rates. Respiratory viruses harnessed as gene therapy vectors have illustrated this limitation. We used directed evolution in an organotypic human airway model to generate a highly infectious adeno-associated virus. This virus mediated gene transfer more than 100-fold better than parental strains and corrected the cystic fibrosis epithelial Cl
−
transport defect. Thus, under appropriate selective pressures, viruses can evolve to be more infectious than observed in nature, a finding that holds significant implications for designing vectors for gene therapy and for understanding emerging pathogens.
Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms
Authors: El-Chemaly Souheil , Malide Daniela , Zudaire Enrique , Ikeda Yoshihiko , Weinberg Benjamin A. , Pacheco-Rodriguez Gustavo , Rosas Ivan O. , Aparicio Marta , Ren Ping , MacDonald Sandra D. , Wu Hai-Ping , Nathan Steven D. , Cuttitta Frank , McCoy J. Philip , Gochuico Bernadette R. , Moss Joel
Published: February 2009

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b
+
macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b
+
macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.
Inhibition of HIV-1 replication by eIF3f
Authors: Valente Susana T. , Gilmartin Greg M. , Mott Christina , Falkard Brie , Goff Stephen P.
Published: February 2009

Viruses often use host machinery in unusual ways to execute different steps during their replication. To identify host factors critical for virus replication, we screened cDNA expression libraries for genes or gene fragments that could interfere with HIV-1 vector transduction. The DNA clone that most potently inhibited HIV-1 expression encoded the N-terminal 91 aa of the eukaryotic initiation factor 3 subunit f (N91-eIF3f). Overexpression of N91-eIF3f or full-length eIF3f drastically restricted HIV-1 replication by reducing nuclear and cytoplasmic viral mRNA levels. N91-eIF3f and eIF3f specifically targeted the 3′ long terminal repeat (3′LTR) region in the viral mRNA. We show that the 3′ end cleavage of HIV-1 mRNA precursors is specifically reduced in N91-eIF3f expressing cells. Our results suggest a role of eIF3f in mRNA maturation and that it can specifically interfere with the 3′ end processing of HIV-1 mRNAs.
Management of red cell alloimmunized pregnancies using conventional methods compared with that of middle cerebral artery peak systolic velocity
Authors: SAU ASHIS , EL‐MATARY ATEF , NEWTON LYN , WICKRAMARACHCHI D.C. JAGAT
Published: February 2009

The aim of this retrospective study was to find out the effect of change in the management of red cell alloimmunized pregnancies from conventional method of amniocentesis to the Doppler assessment of middle cerebral artery peak systolic velocity (MCA‐PSV). There were 29 alloimmunized pregnancies affected by red cell antibodies. Ten cases were managed by amniocentesis and another 19 were managed by MCA‐PSV measurements. The antenatal management and perinatal outcome of both groups are presented. This study suggests that the non‐invasive monitoring should be the method of choice to monitor alloimmunized pregnancies.
The novel ischemia marker ‘ischemia‐modified albumin’ is increased in normal pregnancies
Authors: GUVEN SULEYMAN , ALVER AHMET , MENTESE AHMET , ILHAN F. CEYLAN , CALAPOGLU MUSTAFA , UNSAL MESUT A.
Published: February 2009

The aim of this prospective case‐control study was to determine the change in serum maternal ischemia‐modified albumin (IMA) during normal pregnancies. A total of 117 pregnant (first trimester (n = 24), second trimester (n = 34), and third trimester (n = 35)) and non‐pregnant healthy women (n = 23) were included. Maternal serum IMA, Malondialdehyde (MDA), and albumin levels were measured. Compared with non‐pregnant women, the cross‐sectional mean IMA levels in pregnant women were significantly increased, while the mean serum MDA and albumin levels were significantly decreased throughout pregnancy. Furthermore, a significant negative correlation between serum IMA and albumin levels (r = −0.354, p<0.001) was found, and there was a weak positive correlation between serum albumin and MDA levels (r = 0.334, p<0.001). Serum IMA, which has recently been developed as a clinical marker of ongoing myocardial ischemia, appears to be elevated in normal pregnancy. This may be due to the physiologic oxidative stress state of pregnancy.
Second line platinum‐based intraperitoneal chemotherapy for advanced ovarian cancer
Authors: MILCZEK TOMASZ , KLASA‐MAZURKIEWICZ DAGMARA , EMERICH JANUSZ , KOBIERSKI JULIUSZ
Published: February 2009

Objective. To report the results of ovarian cancer treatment, where a regimen of intravenous cyclophosphamide followed by intraperitoneal cisplatin or carboplatin was administered as second line treatment. Design. Retrospective observational study on 198 women with stage I–IV histologically documented epithelial ovarian cancer after one or more prior regimens of chemotherapy. Setting. University tertiary referral clinic, Gdansk, Poland. Methods. The study group was recruited from among 593 ovarian cancer patients treated between January 1996 and December 2006. Conditions of inclusion for intraperitoneal treatment were: relapse or recurrence of disease after surgery followed by first line treatment. Recurrences were confirmed through re‐staging laparotomy or second‐look laparotomy. Patients received 90 mg/m2 cisplatin, or carboplatin AUC 6 intraperitoneally and cyclophosphamide 750 mg/m2 intravenously. Four or six courses were planned for each patient. Main outcome measures. Response to treatment defined as complete or partial response, or progressive disease, and survival rates. Results. There were 67 (34%) with complete and 61 (31%) with partial response, while 69 (35%) developed progressive disease. Median survival from the initiation of intraperitoneal chemotherapy (IP) was 51 months and significantly longer for patients who received four cycles of IP: 78 months vs. 20 months for patients who received six intraperitoneal cycles. Conclusions. IP can be used in second line treatment of ovarian cancer, but six treatment cycles appear associated with worse results compared to four.
Regional metabolic changes in the hippocampus and posterior cingulate area detected with 3-Tesla magnetic resonance spectroscopy in patients with mild cognitive impairment and alzheimer disease
Authors: Wang Zhiqun , Zhao Cheng , Yu Lei , Zhou Weidong , Li Kuncheng
Published: February 2009

Background: Magnetic resonance spectroscopy (MRS) plays an important role in early diagnosis of Alzheimer disease (AD). There are many reports on MRS studies among individuals with AD and mild cognitive impairment (MCI). However, very few studies have compared spectroscopic data of different limbic regions among AD and MCI subjects.

Purpose: To compare metabolite changes of different regions in the brain of AD and MCI patients by using 3.0T short-echo-time MRS.

Material and Methods: Metabolite ratios in the hippocampus and posterior cingulate area were compared in a group of patients with AD ( n=16), MCI ( n=16), and normal subjects as a control group ( n=16). Clinical neuropsychological tests were measured in all subjects.

Results: In the hippocampus, there were significant differences in N-acetylaspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr, and mI/NAA ratios among the three groups. However, there were no significant differences in choline (Cho)/Cr ratio among the three groups. In the posterior cingulate area, there were no significant differences in the NAA/Cr, Cho/Cr, and mI/Cr ratios among the three groups. However, there were significant differences in mI/NAA ratio between patients with AD and the control group, and between the AD and MCI groups. In addition, there was significant correlation between mI/NAA ratio and Mini Mental Status Exam (MMSE) score in subjects with AD and MCI.

Conclusion: The study reveals that the elevation of mI/NAA ratio in the hippocampus is more significant than that in the posterior cingulate area, which corresponds to the pathologic procession of AD. The ratios of mI/NAA in the hippocampus and in the posterior cingulate area together provide valuable discrimination among the three groups (AD, MCI, and controls). There is a significant correlation between mI/NAA ratio and cognitive decline.
Primary three-dimensional analysis with perspective-filet view versus primary two-dimensional analysis: Evaluation of lesion detection by inexperienced readers at computed tomographic colonography in symptomatic patients
Authors: Fisichella V. A. , Jäderling F. , Horvath S. , Stotzer P.-O. , Kilander A. , Hellström M.
Published: February 2009

Background: “Perspective-filet view” is a novel three-dimensional (3D) viewing technique for computed tomography colonography (CTC). Studies with experienced readers have shown a sensitivity for perspective-filet view similar to that of 2D or 3D endoluminal fly-through in detection of colorectal lesions. It is not known whether perspective-filet view, compared to axial images, improves lesion detection by inexperienced readers.

Purpose: To compare primary 3D analysis using perspective-filet view (3D Filet) with primary 2D analysis, as used by inexperienced CTC readers. Secondary aims were to compare lesion detection by 3D Filet when used by experienced and inexperienced readers, and to evaluate the effect of combined 3D Filet + 2D analysis.

Material and Methods: Fifty symptomatic patients were prospectively enrolled. An experienced reader performed 3D Filet analysis followed by complete 2D analysis (3D Filet + 2D), before colonoscopy with segmental unblinding. Two inexperienced readers (readers 2 and 3), blinded to CTC and colonoscopy findings, retrospectively performed 3D Filet analysis and, after 5 weeks, 2D analysis. True positives ≥6 mm detected by the inexperienced readers with 3D Filet and/or 2D were combined to obtain 3D Filet + 2D.

Results: Colonoscopy revealed 116 lesions: 16 lesions ≥10 mm, 19 lesions 6–9 mm, and 81 lesions ≤5 mm. For the experienced reader, sensitivities for lesions ≥6 mm with 3D Filet and 3D Filet + 2D were 77% and 83%, respectively. For the inexperienced readers, sensitivities for lesions ≥6 mm with 3D Filet and 2D were 51% and 57% (reader 2) and 40% and 43% (reader 3), respectively. There was no significant difference between 3D Filet and 2D regarding sensitivity and reading time. For lesions ≥6 mm, 3D Filet + 2D improved the sensitivity of reader 2 to 63% and of reader 3 to 51%.

Conclusion: Lesion detection by inexperienced readers using perspective-filet view is comparable to that obtained by 2D. Lesion detection improves by combining 3D Filet + 2D, but not to the level of an experienced reader.
Outcome after percutaneous transluminal angioplasty of arterial stenosis in renal transplant patients
Authors: Hagen G. , Wadström J. , Magnusson M. , Magnusson A.
Published: February 2009

Background: Ensuring graft survival in renal transplant patients is of paramount importance. Early detection and treatment of complications such as transplant renal artery stenosis (TRAS) are essential.

Purpose: To evaluate the technical and clinical success rate of renal transplant patients with stenosis in the transplant renal artery or in the iliac artery after percutaneous transluminal angioplasty (PTA).

Material and Methods: PTA was carried out on 24 patients with TRAS or iliac artery stenosis. Altogether, 28 stenoses were treated with PTA. The immediate technical result and the clinical outcomes after 1 and 3 months were assessed as well as clinical adverse events. A reduction in serum creatinine and/or a reduction in the number of antihypertensive drugs were criteria for clinical success.

Results: The immediate technical success rate after PTA was 93%. The clinical success rate after 1 month was 58%, increasing to 75% after 3 months.

Conclusion: The technical success rate is not equivalent to the clinical success rate when treating TRAS with PTA. Furthermore, there is a delay in clinical response, sometimes of 3 months, after a technically successful PTA.