bluuebunny/crossref_metadata_2025 huggingface dataset:
Mantle Q structure from S‐P differential attenuation measurements
Authors: Oki Satoko , Shearer Peter M.
Published: December 2008

We describe a new one‐dimensional Q model for short‐period body waves derived from a data set of 15,000 differential t* measurements of teleseismic P and S waves recorded in broadband seismograms. Measured t* values are little affected by the source time function or instrument response since the P and S waves are recorded at the same station from the same event. We process the data using a waveform cross‐correlation method applied to the first half cycle of the waveforms to avoid reflection and conversion effects. We invert our t* measurements for a two‐layer QS model. Our new Q model has about the same attenuation in the upper mantle and less attenuation in the lower mantle than models derived from longer period data sets. This implies that the frequency dependence of Q is more apparent in the lower mantle and that the effects of attenuation in the upper mantle are approximately constant at frequencies below about 1 Hz. We also observe lateral variations of attenuation in the uppermost mantle by solving for station and event terms, which exhibit correlations with regional tectonics.
A dynamic model for the global cycling of anthropogenic vanadium
Authors: Hope Bruce K.
Published: December 2008

Vanadium is a major trace metal in fossil fuels. Combustion of residual fuel oils and coal in industrialized economies is recognized as the major source of anthropogenic vanadium. A dynamic mass balance model assessed the influence of anthropogenic inputs on the global distribution and cycling of vanadium between 1700 and 2400 assuming different fossil fuel consumption and V production (mining) scenarios. Anthropogenic V sources were divided into fossil fuel combustion, industrial, and domestic (nonindustrial human activity). By 2050, inputs of anthropogenic V could comprise ≈75–85% of those to the atmosphere, ≈21–33% to ocean dissolved, ≈9–13% to ocean particulate, and ≈28–43% of inputs to land; with between ≈61–64% of all anthropogenic inputs attributable to fossil fuel combustion. Contributions from combustion and industrial sources, although dominant relative to contributions from domestic sources between 1900 and 2100, were estimated to peak between 2000 and 2050. Accumulation of anthropogenic V on land and in the ocean apparently occurs because natural removal processes are unable to cope with increasing amounts and rates of anthropogenic contributions. Impacts or hazards associated with anthropogenic inputs are unlikely to be discernible or significant on a global scale, but may be measurable and meaningful at smaller scales (coastal waters, continental shelves, and bays), in the locality of specific sources, or given an unfavorable exposure scenario.
Use of GPS receivers as a soil moisture network for water cycle studies
Authors: Larson Kristine M. , Small Eric E. , Gutmann Ethan D. , Bilich Andria L. , Braun John J. , Zavorotny Valery U.
Published: December 2008

Measurements of soil moisture, both its global distribution and temporal variations, are required to study the water and carbon cycles. A global network ofin situsoil moisture stations is needed to supplement datasets from satellite sensors. We demonstrate that signals routinely recorded by Global Positioning System (GPS) receivers for precise positioning applications can also be related to surface soil moisture variations. Over a three month interval, GPS‐derived estimates from a 300 m2area closely match soil moisture fluctuations in the top 5 cm of soil measured with conventional sensors, including the rate and amount of drying following six precipitation events. Thousands of GPS receivers that exist worldwide could be used to estimate soil moisture in near real‐time, with L‐band signals that complement future satellite missions.
Equatorial superrotation in shallow atmospheres
Authors: Scott R. K. , Polvani L. M.
Published: December 2008

Simple, shallow‐water models have been successful in reproducing two key observables in the atmospheres of the giant planets: the formation of robust, and fully turbulent, latitudinal jets and the decrease of the zonal wind amplitude with latitude. However, they have to date consistently failed in reproducing the strong prograde (superrotating) equatorial winds that are often observed on such planets. In this paper we show that shallow water models not only can give rise to superrotating winds, but can do so very robustly, provided that the physical process of large‐scale energy dissipation by radiative relaxation is taken into account. When energy is removed by linear friction, equatorial superrotation does not develop; when energy is removed by radiative relaxation, superrotation develops at apparently any deformation radius.
Makassar Strait throughflow, 2004 to 2006
Authors: Gordon A. L. , Susanto R. D. , Ffield A. , Huber B. A. , Pranowo W. , Wirasantosa S.
Published: December 2008

The transfer of Pacific water into the Indian Ocean through the Indonesian seas affects the heat and freshwater budgets of both oceans. The observed transport in the Makassar Strait, the primary Indonesian throughflow pathway, from January 2004 through November 2006 is 11.6 ± 3.3 Sv (Sv = 106 m3/s). This transport is 27% larger than observed during 1997 when a strong El Niño suppressed the flow. The 2004‐06 Makassar transport displays clear seasonal behavior, with associated heat and freshwater variability, in contrast to the El Niño dominated 1997 transport. The 2004‐06 transport reached maximum values towards the end of the northwest and southeast monsoons, with minimum transport are in October‐December. A sustained high transport is observed in early 2006, perhaps in response to an La Niña condition. The maximum throughflow occurs within the thermocline, as in 1997, though the longer 2004‐06 measurements also reveal a shallowing of transport as speeds increase. The transport‐weighted temperature is 15.6°C in 2004‐06, nearly 1°C warmer than that observed in 1997, presumably a consequence of El Niño.
Evidence in magnetic clouds for systematic open flux transport on the Sun
Authors: Crooker N. U. , Kahler S. W. , Gosling J. T. , Lepping R. P.
Published: December 2008

Most magnetic clouds encountered by spacecraft at 1 AU display a mix of unidirectional suprathermal electrons signaling open field lines and counterstreaming electrons signaling loops connected to the Sun at both ends. Assuming the open fields were originally loops that underwent interchange reconnection with open fields at the Sun, we determine the sense of connectedness of the open fields found in 72 of 97 magnetic clouds identified by the Wind spacecraft in order to obtain information on the location and sense of the reconnection and resulting flux transport at the Sun. The true polarity of the open fields in each magnetic cloud was determined from the direction of the suprathermal electron flow relative to the magnetic field direction. Results indicate that the polarity of all open fields within a given magnetic cloud is the same 89% of the time, implying that interchange reconnection at the Sun most often occurs in only one leg of a flux rope loop, thus transporting open flux in a single direction, from a coronal hole near that leg to the foot point of the opposite leg. This pattern is consistent with the view that interchange reconnection in coronal mass ejections systematically transports an amount of open flux sufficient to reverse the polarity of the heliospheric field through the course of the solar cycle. Using the same electron data, we also find that the fields encountered in magnetic clouds are only a third as likely to be locally inverted as not. While one might expect inversions to be equally as common as not in flux rope coils, consideration of the geometry of spacecraft trajectories relative to the modeled magnetic cloud axes leads us to conclude that the result is reasonable.
Intense warming and salinification of intermediate waters of southern origin in the eastern subpolar North Atlantic in the 1990s to mid‐2000s
Authors: Sarafanov Artem , Falina Anastasia , Sokov Alexey , Demidov Alexander
Published: December 2008

Recent thermohaline changes in the layer of intermediate waters (IW) advected into the eastern subpolar North Atlantic from lower latitudes are quantified using the data from the repeated transatlantic sections. Positive trends in temperature and salinity in the IW density class at ∼53°N (0.049°C/a and 0.0088/a, 1992–2002) and ∼60°N (0.044°C/a and 0.0085/a, 1997–2005) are derived. The unexpectedly high rates of the IW warming and salinification cannot be explained solely by the long‐term and recent decadal changes at the intermediate levels in the midlatitude North Atlantic and appear to be a consequence of the northward advance of the source water masses caused by the North Atlantic Oscillation‐induced contraction of the subpolar gyre.
Blockade of Angiotensin II Attenuates VEGF-Mediated Blood—Retinal Barrier Breakdown in Diabetic Retinopathy
Authors: Kim Jeong Hun , Kim Jin Hyoung , Yu Young Suk , Cho Chang Sik , Kim Kyu-Won
Published: December 2008

Diabetic retinopathy (DR) is the leading cause of vision loss as a major complication of diabetes mellitus. The blood—retinal barrier (BRB) breakdown is a critical early event in the pathogenesis of DR. It has been known that the rennin-angiotensin system (RAS) is important in the progression of the DR via angiotensin II (Ang II), the effector of RAS. In this study, we showed that blockade of Ang II attenuates vascular endothelial growth factor (VEGF)-mediated BRB breakdown in DR. In streptozotocin-induced diabetes, retinal vascular permeability increased with upregulation of VEGF, where Ang II and its receptors were upregulated. Ang II induced VEGF expression in retinal endothelial cells accompanied by loss of tight junction proteins. However, the blockade of Ang II by perindopril, an angiotensin converting enzyme (ACE) inhibitor, inhibited upregulation of VEGF, and prevented the loss of tight junction proteins. Moreover, inhibition of Ang II by perindopril attenuated increased vascular permeability of diabetic retina accompanied by recovery of tight junction proteins in retinal vessels. Therefore, we suggest that the RAS involves in increased vascular permeability during early stage of DR, which is mediated by VEGF. Furthermore, the ACE inhibitor may have a therapeutic potential in the treatment of diabetic BRB breakdown.
Effect of 20-HETE Inhibition on Infarct Volume and Cerebral Blood Flow after Transient Middle Cerebral Artery Occlusion
Authors: Renic Marija , Klaus Judith A , Omura Tomohiro , Kawashima Naoya , Onishi Michihito , Miyata Noriyuki , Koehler Raymond C , Harder David R , Roman Richard J
Published: December 2008

This study examined the effects of an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis, N-(3-chloro-4-morpholin-4-yl)phenyl- N'-hydroxyimido formamide (TS-011), on infarct volume, volume at risk, cerebral blood flow (CBF), and levels of cytochrome P450 (CYP450) eicosanoids in the brain after transient occlusion of the middle cerebral artery (t-MCAO) in rats. TS-011 (0.1 mg/kg, iv) reduced cortical infarct volume by approximately 70% and total infarct volume by 55%. TS-011 had no effect on the volume at risk or CBF during or up to 30 mins after the ischemic period. TS-011 reduced the delayed fall in CBF seen 2 h after reperfusion. The levels of CYP450 eicosanoids were similar in the ischemic and contralateral hemispheres after t-MCAO. TS-011 reduced 20-HETE levels in cerebral tissue by 80% but had no effect on the levels of EETs. Administration of another 20-HETE inhibitor, HET0016 (0.01 to 1.0 mg/kg, iv) or a 20-HETE antagonist 20-hydroxyeicosa-6( Z),15( Z)-dienoic acid (10 mg/kg, iv) also reduced infarct size. These results indicate that inhibitors of the synthesis or vasoconstrictor effects of 20-HETE reduce infarct size in rats after cerebral ischemia. The effects of TS-011 are not associated with changes in the area at risk or CBF and may be because of a potential protective effect in neurons subjected to ischemic stress.
Hypercytokinemia: Increased or decreased innate immunity?
Authors: Watve Milind , Mandani Sonam , Belsare Prajakta
Published: December 2008

The adipose tissue is an active endocrine organ which secretes proinflammatory cytokines and chemokines resulting into raised serum levels. Hypercytokinemia has been interpreted as raised level of innate immunity and its evolution is interpreted as a response to increased chances of infection under starvation conditions in which the thrifty phenotype evolved. If starvation and infection challenges co-occurred during hunter gatherer life, thrifty genotype and infection resistant genotype may have co-evolved. An inherent weakness of this explanation is that in obesity or insulin resistance there is no evidence of increased resistance to infections. The raised levels of inflammatory cytokines have not been demonstrated to combat infections or enhance wound healing. We suggest that the raised chemokine levels actually decrease peripheral innate immunity. The normal movement of monocyte-macrophages and neutrophils from blood vessels to injured tissue is under a chemokine gradient. A gradient results from the difference between the basal levels of chemokines and those secreted by the injured tissue. Increase in the basal level is expected to weaken the gradient thereby decreasing extravasation and infiltration. Using diffusion kinetics we show that a small rise in basal levels can cause substantial reduction in cell infiltration. This interpretation is consistent with the behavioural switch hypothesis proposed by Watve and Yajnik which suggests that obesity and insulin resistance mark a transition from “soldier” to “diplomat” lifestyle. Hypercytokinemia may have evolved as a mechanism of disinvestment in peripheral innate immunity since the diplomat lifestyle is less injury prone. We evaluate the two alternative hypotheses by available evidence.
Obesity as a perceived social signal
Authors: Mankar Manasee , Joshi Radhika , Belsare Prajakta , Jog Maithili , Watve Milind
Published: December 2008

Fat accumulation has been classically considered as a means of energy storage. Obese people are theorized as metabolically ‘thrifty’, saving energy during times of food abundance. However, recent research has highlighted many neuro-behavioral and social aspects of obesity, with a suggestion that obesity, abdominal obesity in particular, may have evolved as a social signal. We tested here whether body proportions, and abdominal obesity in particular, are perceived as signals revealing personality traits. Faceless drawings of three male body forms namely lean, muscular and feminine, each with and without abdominal obesity were shown in a randomized order to a group of 222 respondents. A list of 30 different adjectives or short descriptions of personality traits was given to each respondent and they were asked to allocate the most appropriate figure to each of them independently. The traits included those directly related to physique, those related to nature, attitude and moral character and also those related to social status. For 29 out of the 30 adjectives people consistently attributed specific body forms. Based on common choices, the 30 traits could be clustered into distinct ‘personalities’ which were strongly associated with particular body forms. A centrally obese figure was perceived as “lethargic, greedy, political, money-minded, selfish and rich”. The results show that body proportions are perceived to reflect personality traits and this raises the possibility that in addition to energy storage, social selection may have played some role in shaping the biology of obesity.
Membrane-targeted synergistic activity of docosahexaenoic acid and lysozyme against Pseudomonas aeruginosa
Authors: Martinez Jose G. , Waldon Michael , Huang Qiyu , Alvarez Sandra , Oren Ami , Sandoval Natalie , Du Ming , Zhou Feimeng , Zenz Alexandra , Lohner Karl , Desharnais Robert , Porter Edith
Published: December 2008

Antimicrobial polypeptides, including lysozymes, have membrane perturbing activity and are well-documented effector molecules of innate immunity. In cystic fibrosis, a hereditary disease with frequent lung infection with Pseudomonas aeruginosa, the non-esterified fatty acid DA (docosahexaenoic acid), but not OA (oleic acid), is decreased, and DA supplementation has been shown to improve the clinical condition in these patients. We hypothesized that DA may, either alone or in conjunction with lysozyme, exert antibacterial action against Ps. aeruginosa. We found that DA and lysozyme synergistically inhibit the metabolic activity of Ps. aeruginosa, in contrast with OA. Electron microscopy and equilibrium dialysis suggest that DA accumulates in the bacterial membrane in the presence of lysozyme. Surface plasmon resonance with live bacteria and differential scanning calorimetry studies with bacterial model membranes reveal that, initially, DA facilitates lysozyme incorporation into the membrane, which in turn allows influx of more DA, leading to bacterial cell death. The present study elucidates a molecular basis for the synergistic action of non-esterified fatty acids and antimicrobial polypeptides, which may be dysfunctional in cystic fibrosis.
Peroxiredoxin 4knockout results in elevated spermatogenic cell death via oxidative stress
Authors: Iuchi Yoshihito , Okada Futoshi , Tsunoda Satoshi , Kibe Noriko , Shirasawa Nobuyuki , Ikawa Masahito , Okabe Masaru , Ikeda Yoshitaka , Fujii Junichi
Published: December 2008

Prx (peroxiredoxin) is a multifunctional redox protein with thioredoxin-dependent peroxidase activity. Prx4 is present as a secretory protein in most tissues, whereas in sexually mature testes it is anchored in the ER (endoplasmic reticulum) membrane of spermatogenic cells via an uncleaved N-terminal hydrophobic peptide. We generated a Prx4 knockout mouse to investigate the function of Prx4 in vivo. Prx4−/y mice lacking Prx4 expression in all cells were obtained by mating Prx4flox/+ female mice with Cre-transgenic male mice that ubiquitously expressed Cre recombinase. The resulting Prx4−/y male mice were fertile, and most organs were nearly normal in size, except for testicular atrophy. The number of deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive spermatogenic cells was higher in Prx4−/y mice than in Prx4+/y mice and increased remarkably in response to warming the lower abdomen at 43 °C for 15 min. Cells reactive to antibodies against 4-hydroxynonenal and 8-hydroxyguanine were high in the Prx4−/y mice and concomitant with elevated oxidation of lipid and protein thiols. The cauda epididymis of Prx4−/y mice contained round spermatocytes, which were not found in Prx4+/y mice, and displayed oligozoospermia. However, mature spermatozoa from the epididymis of Prx4−/y mice exhibited normal fertilization In vitro. Taken together, these results indicate that spermatogenic cells lacking Prx4 are more susceptible to cell death via oxidative damage than their wild-type counterparts. Our results suggest that the presence of Prx4, most likely the membrane-bound form, is important for spermatogenesis, but not an absolute requisite.
The TGF-β, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer
Authors: Assinder Stephen J. , Dong Qihan , Kovacevic Zaklina , Richardson Des R.
Published: December 2008

A key to the development of improved pharmacological treatment strategies for cancer is an understanding of the integration of biochemical pathways involved in both tumorigenesis and cancer suppression. Furthermore, genetic markers that may predict the outcome of targeted pharmacological intervention in an individual are central to patient-focused treatment regimens rather than the traditional ‘one size fits all’ approach. Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is a holy grail. This review will describe the evidence that demonstrates the integration of three established pathways: the tumour-suppressive TGF-β (transforming growth factor-β) pathway, the tumorigenic PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathway and the tumour-suppressive PTEN (phosphatase and tensin homologue deleted on chromosome 10) pathway. It will discuss gene polymorphisms and somatic mutations in relevant genes and highlight novel pharmaceutical agents that target key points in these integrated pathways.
Bicarbonate transport in cell physiology and disease
Authors: Cordat Emmanuelle , Casey Joseph R.
Published: December 2008

The family of mammalian bicarbonate transport proteins are involved in a wide-range of physiological processes. The importance of bicarbonate transport follows from the biochemistry of HCO3− itself. Bicarbonate is the waste product of mitochondrial respiration. HCO3− undergoes pH-dependent conversion into CO2 and in doing so converts from a membrane impermeant anion into a gas that can diffuse across membranes. The CO2–HCO3− equilibrium forms the most important pH buffering system of our bodies. Bicarbonate transport proteins facilitate the movement of membrane-impermeant HCO3− across membranes to accelerate disposal of waste CO2, control cellular and whole-body pH, and to regulate fluid movement and acid/base secretion. Defects of bicarbonate transport proteins manifest in diseases of most organ systems. Fourteen gene products facilitate mammalian bicarbonate transport, whose physiology and pathophysiology is discussed in the present review.
Optical properties for armchair-edge graphene nanoribbons
Authors: Liao Wenhu , Zhou Guanghui , Xi Fu
Published: December 2008

We theoretically investigate the optical properties of semiconductor- and metal-type armchair-edge graphene nanoribbon irradiated under an external longitudinal polarized electromagnetic field at low temperatures, respectively. Within the framework of linear response theory in the perturbation regime, we examine the real conductance, dielectric function, and electron energy loss spectra of the systems. It is demonstrated that by numerical examples, some photon-assisted intersubband transitions from visible to ultraviolet light exist with different selection rules from those of both zigzag-edge graphene nanoribbon and single-walled carbon nanotube. Our results are of particular significance for exploring new effects of dimensional reduction in graphene and its optoelectronic applications.
Maximizing performance for higher K gate dielectrics
Authors: Robertson John
Published: December 2008

Further scaling of complementary metal oxide semiconductor gate stacks will require gate dielectrics with a higher dielectric constant (K) than HfO2. We point out that this will require strategies to minimize the overall effective oxide thickness of the gate stack, and not just maximizing the dielectric constant, so that the channel mobility is not impaired and there is still control of the flatband voltages. This may require retention of a SiO2-based interfacial layer, and attention should be paid to the flatband voltages of lanthanide oxides. Phase control of HfO2 and ZrO2 by addition of group IV elements offers simpler advances.
Photonic crystal superlattice employed as left-handed planoconcave lens
Authors: Saado Y. , Neve-Oz Y. , Golosovsky M. , Davidov D. , Frenkel A.
Published: December 2008

We demonstrate focusing of the microwave radiation by a planoconcave lens based on photonic crystal superlattice. The superlattice consists of dielectric rods of two different diameters. The structural modulation results in a narrow transmission subband inside the band gap. The subband is characterized by a negative refractive index and high transmission efficiency. This negative refractive index arises from the Brillouin zone folding in the lattice with the composite unit cell. The full width at half maximum of the focal spot of our lens is 0.36λ×0.42λ, which is close to the Abbe limit, and the power enhancement is 2.2.
Effect of transverse mode structure on the far field pattern of metal-metal terahertz quantum cascade lasers
Authors: Gellie P. , Maineult W. , Andronico A. , Leo G. , Sirtori C. , Barbieri S. , Chassagneux Y. , Coudevylle J. R. , Colombelli R. , Khanna S. P. , Linfield E. H. , Davies A. G.
Published: December 2008

We elucidate the effects of the lateral mode structure on the far field pattern of metal-metal ridge-waveguide terahertz quantum cascade lasers. By introducing a 6-μm-wide metal gap on the top metal contact, we suppress odd-parity lateral modes and drastically modify the far field pattern. Measurements are in good qualitative agreement with full three-dimensional finite-difference-time-domain modeling. Experimental evidence of nonuniform current pumping on the intensity distribution of the guided mode (and hence the far field pattern) is also presented and explained in terms of gain guiding.
Dielectric and structural properties of thin SrHfO3 layers on TiN
Authors: Lupina G. , Kozłowski G. , Dabrowski J. , Dudek P. , Lippert G. , Müssig H.-J.
Published: December 2008

We studied several properties of thin amorphous and polycrystalline SrHfO3 layers on TiN in the context of memory capacitor applications. Amorphous SrHfO3 has the dielectric constant κ=21 and is transformed upon rapid thermal annealing into polycrystalline SrHfO3 with κ=35. We discuss the influence of the annealing treatment on leakage currents, and briefly discuss, on the basis of ab initio calculations, the possible role of vacancylike defects and Ti contamination.
Atomic force microscopy cantilever dynamics in liquid in the presence of tip sample interaction
Authors: de Beer Sissi , van den Ende Dirk , Mugele Frieder
Published: December 2008

We analyze the dynamics of an atomic force microscopy (AFM) cantilever oscillating in liquid at subnanometer amplitude in the presence of tip-sample interaction. We present AFM measurements of oscillatory solvation forces for octamethylcyclotetrasiloxane on highly oriented pyrolitic graphite and compare them to a harmonic oscillator model that incorporates the effect of the finite driving force for a typical AFM configuration with acoustic driving. In contrast to the general belief, we find—in both experiments and modeling—that the tip-sample interaction gives rise to a pronounced signature in the phase at driving frequencies well below resonance.
Electrokinetics of colloidal particles in nonpolar media containing charged inverse micelles
Authors: Strubbe Filip , Beunis Filip , Marescaux Matthias , Verboven Bart , Neyts Kristiaan
Published: December 2008

We have compared optical tracking and electric current measurements to study the electrokinetics of colloidal particles in nonpolar media containing charged inverse micelles. Particle trajectories are measured in response to a voltage step, revealing spatial and temporal variations of the electric field when space-charge layers are created by charged inverse micelles. The particle trajectories and current measurements are in good agreement with simulations and analytical approximations based on drift and diffusion of charges. Electrohydrodynamic effects observed at high concentrations of charged inverse micelles are explained by injection of charged inverse micelles from the bulk into the space-charge layers.
Science and Uncertainty in South Africa's Elephant Culling Debate
Authors: Dickson Paul , Adams William M
Published: December 2008

We analyse the debate about the culling of elephants in South Africa's national parks. This pits the need to reduce elephant density and grazing pressure to prevent environmental damage against animal-welfare concerns about the killing of elephants. This complex debate is characterised by factual uncertainty and moral complexity. The procull storyline suggests that high elephant densities pose a risk to biodiversity. The anticull standpoint critiques this position as politically and economically motivated and lacking in adequate scientific support. Both procull and anticull positions draw on science as a source of authority, and on the precautionary principle as a framework for making decisions. They differ in their interpretation of the scientific evidence for serious impacts of high elephant densities, the relations between scientific, ethical, and economic arguments, and the way uncertainty and the idea of a precautionary approach are used. A decision to resume culling of elephants in South Africa was made in February 2008, but debate continues.
Synteny and candidate gene prediction using an anchored linkage map of
Astyanax mexicanus
Authors: Gross Joshua B. , Protas Meredith , Conrad Melissa , Scheid Paul E. , Vidal Oriol , Jeffery William R. , Borowsky Richard , Tabin Clifford J.
Published: December 2008

The blind Mexican cave tetra,
Astyanax mexicanus
, is a unique model system for the study of parallelism and the evolution of cave-adapted traits. Understanding the genetic basis for these traits has recently become feasible thanks to production of a genome-wide linkage map and quantitative trait association analyses. The selection of suitable candidate genes controlling quantitative traits remains challenging, however, in the absence of a physical genome. Here, we describe the integration of multiple linkage maps generated in four separate crosses between surface, cave, and hybrid forms of
A. mexicanus
. We performed exhaustive BLAST analyses of genomic markers populating this integrated map against sequenced genomes of numerous taxa, ranging from yeast to amniotes. We found the largest number of identified sequences (228), with the most expect (E) values <10
−5
(95), in the zebrafish
Danio rerio
. The most significant hits were assembled into an “anchored” linkage map with
Danio
, revealing numerous regions of conserved synteny, many of which are shared across critical regions of identified quantitative trait loci (QTL). Using this anchored map, we predicted the positions of 21 test genes on the integrated linkage map and verified that 18 of these are found in locations homologous to their chromosomal positions in
D. rerio
. The anchored map allowed the identification of four candidate genes for QTL relating to rib number and eye size. The map we have generated will greatly accelerate the production of viable lists of additional candidate genes involved in the development and evolution of cave-specific traits in
A. mexicanus
.
The
Caenorhabditis elegans
vulva: A post-embryonic gene regulatory network controlling organogenesis
Authors: Ririe Ted O. , Fernandes Jolene S. , Sternberg Paul W.
Published: December 2008

The
Caenorhabditis elegans
vulva is an elegant model for dissecting a gene regulatory network (GRN) that directs postembryonic organogenesis. The mature vulva comprises seven cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique pattern of spatial and temporal gene expression. The mechanisms that specify these cell types in a precise spatial pattern are not well understood. Using reverse genetic screens, we identified novel components of the vulval GRN, including
nhr-113
in vulA. Several transcription factors (
lin-11
,
lin-29
,
cog-1
,
egl-38
, and
nhr-67
) interact with each other and act in concert to regulate target gene expression in the diverse vulval cell types. For example,
egl-38
(Pax2/5/8) stabilizes the vulF fate by positively regulating vulF characteristics and by inhibiting characteristics associated with the neighboring vulE cells.
nhr-67
and
egl-38
regulate
cog-1,
helping restrict its expression to vulE. Computational approaches have been successfully used to identify functional
cis
-regulatory motifs in the
zmp-1
(zinc metalloproteinase) promoter. These results provide an overview of the regulatory network architecture for each vulval cell type.
Mechanism of a prototypical synthetic membrane-active antimicrobial: Efficient hole-punching via interaction with negative intrinsic curvature lipids
Authors: Yang Lihua , Gordon Vernita D. , Trinkle Dallas R. , Schmidt Nathan W. , Davis Matthew A. , DeVries Clarabelle , Som Abhigyan , Cronan John E. , Tew Gregory N. , Wong Gerard C. L.
Published: December 2008

Phenylene ethynylenes comprise a prototypical class of synthetic antimicrobial compounds that mimic antimicrobial peptides produced by eukaryotes and have broad-spectrum antimicrobial activity. We show unambiguously that bacterial membrane permeation by these antimicrobials depends on the presence of negative intrinsic curvature lipids, such as phosphatidylethanolamine (PE) lipids, found in high concentrations within bacterial membranes. Plate-killing assays indicate that a PE-knockout mutant strain of
Escherichia coli
drastically out-survives the wild type against the membrane-active phenylene ethynylene antimicrobials, whereas the opposite is true when challenged with traditional metabolic antibiotics. That the PE deletion is a lethal mutation in normative environments suggests that resistant bacterial strains do not evolve because a lethal mutation is required to gain immunity. PE lipids allow efficient generation of negative curvature required for the circumferential barrel of an induced membrane pore; an inverted hexagonal H
II
phase, which consists of arrays of water channels, is induced by a small number of antimicrobial molecules. The estimated antimicrobial occupation in these water channels is nonlinear and jumps from ≈1 to 3 per 4 nm of induced water channel length as the global antimicrobial concentration is increased. By comparing to exactly solvable 1D spin models for magnetic systems, we quantify the cooperativity of these antimicrobials.
How the Dorsal gradient works: Insights from postgenome technologies
Authors: Hong Joung-Woo , Hendrix David A. , Papatsenko Dmitri , Levine Michael S.
Published: December 2008

Gradients of extracellular signaling molecules and transcription factors are used in a variety of developmental processes, including the patterning of the
Drosophila
embryo, the establishment of diverse neuronal cell types in the vertebrate neural tube, and the anterior–posterior patterning of vertebrate limbs. Here, we discuss how a gradient of the maternal transcription factor Dorsal produces complex patterns of gene expression across the dorsal–ventral (DV) axis of the early
Drosophila
embryo. The identification of 60–70 Dorsal target genes, along with the characterization of ≈35 associated regulatory DNAs, suggests that there are at least six different regulatory codes driving diverse DV expression profiles.
Compensatory IKKα activation of classical NF-κB signaling during IKKβ inhibition identified by an RNA interference sensitization screen
Authors: Lam Lloyd T. , Davis R. Eric , Ngo Vu N. , Lenz Georg , Wright George , Xu Weihong , Zhao Hong , Yu Xin , Dang Lenny , Staudt Louis M.
Published: December 2008

A subtype of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like (ABC) DLBCL, depends on constitutive nuclear factor-κB (NF-κB) signaling for survival. Small molecule inhibitors of IκB kinase β (IKKβ), a key regulator of the NF-κB pathway, kill ABC DLBCL cells and hold promise for the treatment of this lymphoma type. We conducted an RNA interference genetic screen to investigate potential mechanisms of resistance of ABC DLBCL cells to IKKβ inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500 protein kinases for shRNAs that would increase the killing of an ABC DLBCL cell line in the presence of a small molecule IKKβ inhibitor. Two independent shRNAs targeting IKKα synergized with the IKKβ inhibitor to kill three different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly, IKKα shRNAs blocked the classical rather than the alternative NF-κB pathway in ABC DLBCL cells, as judged by inhibition of IκBα phosphorylation. IKKα shRNA toxicity was reversed by coexpression of wild-type but not kinase inactive forms of IKKα, suggesting that IKKα may directly phosphorylate IκBα under conditions of IKKβ inhibition. In models of physiologic NF-κB pathway activation by CARD11 or tumor necrosis factor-α, compensatory IKKα activity was also observed with IKKβ inhibition. These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKα and IKKβ, possibly through CARD11 inhibition.
Insights into the P-to-Q conversion in the catalytic cycle of methane monooxygenase from a synthetic model system
Authors: Xue Genqiang , Fiedler Adam T. , Martinho Marlène , Münck Eckard , Que Lawrence
Published: December 2008

For the catalytic cycle of soluble methane monooxygenase (sMMO), it has been proposed that cleavage of the O–O bond in the (μ-peroxo)diiron(III) intermediate P gives rise to the diiron(IV) intermediate Q with an Fe
2
(μ–O)
2
diamond core, which oxidizes methane to methanol. As a model for this conversion, (μ–oxo) diiron(III) complex 1 ([Fe
III
2
(μ–O)(μ–O
2
H
3
)(L)
2
]
3+
, L = tris(3,5-dimethyl-4-methoxypyridyl-2-methyl)amine) has been treated consecutively with one eq of H
2
O
2
and one eq of HClO
4
to form 3 ([Fe
IV
2
(μ–O)
2
(L)
2
]
4+
). In the course of this reaction a new species, 2, can be observed before the protonation step; 2 gives rise to a cationic peak cluster by ESI-MS at
m
/
z
1,399, corresponding to the {[Fe
2
O
3
L
2
H](OTf)
2
}
+
ion in which 1 oxygen atom derives from 1 and the other two originate from H
2
O
2
. Mössbauer studies of 2 reveal the presence of two distinct, exchange coupled iron(IV) centers, and EXAFS fits indicate a short Fe–O bond at 1.66 Å and an Fe–Fe distance of 3.32 Å. Taken together, the spectroscopic data point to an HO-Fe
IV
-O-Fe
IV
= O core for 2. Protonation of 2 results in the loss of H
2
O and the formation of 3. Isotope labeling experiments show that the [Fe
IV
2
(μ–O)
2
] core of 3 can incorporate both oxygen atoms from H
2
O
2
. The reactions described here serve as the only biomimetic precedent for the conversion of intermediates P to Q in the sMMO reaction cycle and shed light on how a peroxodiiron(III) unit can transform into an [Fe
IV
2
(μ–O)
2
] core.
Replacement of normal with mutant alleles in the genome of normal human cells unveils mutation-specific drug responses
Authors: Di Nicolantonio Federica , Arena Sabrina , Gallicchio Margherita , Zecchin Davide , Martini Miriam , Flonta Simona Emilia , Stella Giulia Maria , Lamba Simona , Cancelliere Carlotta , Russo Mariangela , Geuna Massimo , Appendino Giovanni , Fantozzi Roberto , Medico Enzo , Bardelli Alberto
Published: December 2008

Mutations in oncogenes and tumor suppressor genes are responsible for tumorigenesis and represent favored therapeutic targets in oncology. We exploited homologous recombination to knock-in individual cancer mutations in the genome of nontransformed human cells. Sequential introduction of multiple mutations was also achieved, demonstrating the potential of this strategy to construct tumor progression models. Knock-in cells displayed allele-specific activation of signaling pathways and mutation-specific phenotypes different from those obtainable by ectopic oncogene expression. Profiling of a library of pharmacological agents on the mutated cells showed striking sensitivity or resistance phenotypes to pathway-targeted drugs, often matching those of tumor cells carrying equivalent cancer mutations. Thus, knock-in of single or multiple cancer alleles provides a pharmacogenomic platform for the rational design of targeted therapies.
A robust automated system elucidates mouse home cage behavioral structure
Authors: Goulding Evan H. , Schenk A. Katrin , Juneja Punita , MacKay Adrienne W. , Wade Jennifer M. , Tecott Laurence H.
Published: December 2008

Patterns of behavior exhibited by mice in their home cages reflect the function and interaction of numerous behavioral and physiological systems. Detailed assessment of these patterns thus has the potential to provide a powerful tool for understanding basic aspects of behavioral regulation and their perturbation by disease processes. However, the capacity to identify and examine these patterns in terms of their discrete levels of organization across diverse behaviors has been difficult to achieve and automate. Here, we describe an automated approach for the quantitative characterization of fundamental behavioral elements and their patterns in the freely behaving mouse. We demonstrate the utility of this approach by identifying unique features of home cage behavioral structure and changes in distinct levels of behavioral organization in mice with single gene mutations altering energy balance. The robust, automated, reproducible quantification of mouse home cage behavioral structure detailed here should have wide applicability for the study of mammalian physiology, behavior, and disease.
Ion–water hydrogen-bond switching observed with 2D IR vibrational echo chemical exchange spectroscopy
Authors: Moilanen David E. , Wong Daryl , Rosenfeld Daniel E. , Fenn Emily E. , Fayer M. D.
Published: December 2008

The exchange of water hydroxyl hydrogen bonds between anions and water oxygens is observed directly with ultrafast 2D IR vibrational echo chemical exchange spectroscopy (CES). The OD hydroxyl stretch of dilute HOD in H2O in concentrated (5.5 M) aqueous solutions of sodium tetrafluoroborate (NaBF4) displays a spectrum with a broad water-like band (hydroxyl bound to water oxygen) and a resolved, blue shifted band (hydroxyl bound to BF4−). At short time (200 fs), the 2D IR vibrational echo spectrum has 4 peaks, 2 on the diagonal and 2 off-diagonal. The 2 diagonal peaks are the 0–1 transitions of the water-like band and the hydroxyl-anion band. Vibrational echo emissions at the 1–2 transition frequencies give rise to 2 off-diagonal peaks. On a picosecond time scale, additional off-diagonal peaks grow in. These new peaks arise from chemical exchange between water hydroxyls bound to anions and hydroxyls bound to water oxygens. The growth of the chemical exchange peaks yields the time dependence of anion–water hydroxyl hydrogen bond switching under thermal equilibrium conditions as Taw= 7 ± 1 ps. Pump-probe measurements of the orientational relaxation rates and vibrational lifetimes are used in the CES data analysis. The pump-probe measurements are shown to have the correct functional form for a system undergoing exchange.
Incremental steps toward incompatibility revealed by Arabidopsis epistatic interactions modulating salicylic acid pathway activation
Authors: Alcázar Rubén , García Ana V. , Parker Jane E. , Reymond Matthieu
Published: December 2008

Plant growth is influenced by genetic factors and environmental cues. Genotype-by-environment interactions are governed by complex genetic epistatic networks that are subject to natural selection. Here we describe a novel epistatic interaction modulating growth in response to temperature common to 2 Arabidopsis recombinant inbred line (RIL) populations (L
er
× Kas-2 and L
er
× Kond). At 14 °C, lines with specific allele combinations at interacting loci (incompatible interactions) have severe growth defects. These lines exhibit deregulated cell death programs and enhanced disease resistance. At 20 °C, growth defects are suppressed, but a positive trait of enhanced resistance is retained. Mapping of 1 interacting QTL to a cluster of
RPP1
-like
TIR-NB-LRR
genes on chromosome 3 is consistent with our finding that environmentally conditioned epistasis depends on activation of the salicylic acid (SA) stress signaling pathway. The nature of the epistatic interaction conforms to the Dobzhansky-Muller model of genetic incompatibility with incomplete penetrance for reproductive isolation. Variation in fitness of different incompatible lines reveals the presence of additional modifiers in the genetic background. We propose that certain interacting loci lead to an optimal balance between growth and resistance to pathogens by modulating SA signaling under specific environments. This could allow the accumulation of additional incompatibilities before reaching complete reproductive isolation.
Text for context, trial for trialogue
Authors: Pascual Esther
Published: December 2008

This paper deals with a prosecutor’s closing argument in a murder trial I did fieldwork on in California in 2000. This discourse is analyzed through the conceptual blend of the deceased victim ‘testifying’ through legal evidence. The emergence and argumentative power of this blend is examined vis à vis the participants’ knowledge of the embedding discourse and trial as well as their conceptualizations of what a trial is. I suggest a definition of a trial as a ‘semantic network’ (Langacker, 1987), which combines lawyers’ common definitions with the nature of factive and fictive interaction in Western courts (Pascual, 2002, 2006). The claim is that language users (meta)operate with intertwined layers of context conceptualization, constraining conceptual blending operations. The paper integrates cognitive linguistics with cognitive sociology (Cicourel, 1973) and cognitive and linguistic anthropology (Hutchins, 1990; Duranti, 1997). It also calls for the qualitative study of language through in-depth enthnography that ensures data validity.
Language planning for Italian regional languages (“dialects”)
Authors: Coluzzi Paolo
Published: December 2008

In addition to twelve recognized minority languages (Law no. 482/1999), Italy features a number of non-recognized so-called “dialects” that is difficult to state, but which renowned linguists like Tullio De Mauro and Giulio Lepschy calculate as ranging between 12 and 15. These languages are still spoken (and sometimes written) by slightly less than half of the Italian population and are the first languages of a significant part of it. Some of them even have a history of (semi)official usage and feature large and interesting literary traditions. An introduction on the linguistic situation in Italy, the classification of its “dialects” and their state of endangerment, is followed by discussion of the present (scant) legislation and action being taken to protect the seven language varieties chosen as case studies: Piedmontese, Western Lombard/Milanese, Venetan, Ligurian/Genoese, Roman, Neapolitan and Sicilian. These language planning strategies are discussed particularly in terms of graphization (corpus planning), status and acquisition planning, even when, as in most cases, this “planning” may be uncoordinated and even unconscious. The article closes with a few general considerations and with some suggestions on how these initiatives could be improved.
La tradition manuscrite des Fables de Marie de France: Le manuscrit 474 de la Bibliothèque du Château de Chantilly (X), un témoin négligé
Authors: Halgrain Mohan
Published: December 2008

Les "Fables" de Marie de France font partie des textes français du Moyen Âge les plus appréciés de leurs contemporains, si l’on en croit le grand nombre de copies qui nous en est parvenu. Karl Warnke, pour son édition de 1898, en avait, en effet, recensé vingt-trois. Or ce chiffre est venu s’accroître depuis, avec la découverte d’un très petit fragment du texte à Nottingham, mais surtout grâce à un nouveau recensement des témoins effectué par Françoise Vielliard en 1989 et qui a permis la "découverte" de deux nouveaux manuscrits. C’est l’un d’entre eux qui est ici évoqué, d’un point de vue codicologique d’abord, mais surtout à travers sa très forte tendance à modifier le texte original, qui fait de lui le manuscrit de loin le plus remanieur de la tradition. Nous nous sommes ainsi attaché à cerner la nature et les raisons de ces nombreux remaniements, avant d’aborder finalement les quelques cruciales questions d’ordre éditorial que pose un tel document.
'Hares on the Hearthstones' in medieval England
Authors: Hardwick Paul
Published: December 2008

This paper explores the curious image of ‘the hare on the hearthstone’ – a sign of the impending Day of Doom in late medieval literature – investigating reasons why such an apparently harmless creature should be considered a harbinger of misfortune. By addressing a broad range of written sources, it builds up a picture of the hare as a symbol of otherness and instability whose intrusion into the very centre of domestic security would indeed provide a cause for profound unease.