bluuebunny/crossref_metadata_2025 huggingface dataset:
Gulf of Trieste: A changing ecosystem
Authors: Conversi A. , Peluso T. , Fonda‐Umani S.
Published: March 2009

Understanding the impact of climate change on zooplankton populations is of major importance, as they represent the basis for higher trophic levels in the marine food web. In this study we analyze the 36‐year copepod abundance time series in the Gulf of Trieste, northern Adriatic, to investigate its interannual variability, with particular attention to species trends and phenology. Following the analysis of the local winter sea surface temperature, two periods are identified: 1970–1987 and 1988–2005. These periods are characterized by ecosystem‐wide changes: an approximate doubling in total copepod abundance, the arrival of a new species (Diaixis pygmoea), the rise (Paracalanus parvus, Oncaea spp., Oithona spp., and Euterpina acutifrons) or decline (Pseudocalanus elongatus, Clausocalanus spp.) of several taxa, and changes in the phenology in several species, with predominantly forward shifts in the timing of the maximum peak. While Acartia clausi remains the dominant species, there is a general trend toward smaller species in the second period. Our results also indicate the large, possibly critical, reduction in the abundance of the species Pseudocalanus elongatus. We hypothesize that the changes in copepod abundances and community composition in the Gulf of Trieste are related to the general warming in the sea surface temperature and associated northerly displacement of the ecosystem and to the changes in the Mediterranean circulation that began at the end of the 1980s and affected the whole basin in the following years as part of the phenomenon called the Eastern Mediterranean Transient.
Numerical simulations of the atmospheric and land conditions over the Jinta oasis in northwestern China with satellite‐derived land surface parameters
Authors: Meng Xianhong , Lü Shihua , Zhang Tangtang , Guo Jüxin , Gao Yanhong , Bao Yan , Wen Lijuan , Luo Siqiong , Liu Yuanpu
Published: March 2009

Mesoscale meteorological modeling is an important tool to help understand the energy budget of the oasis, while some of its initial field data are rough limited to describe the atmosphere and land conditions over a small oasis. Local factors including land surface parameters and their interaction with the atmosphere play a dominant role in the local circulation. Therefore, in this study, land surface parameters such as land‐use types, vegetation cover fraction, and surface layer soil moisture are derived by satellite remote sensing data from EOS Moderate Resolution Imaging Spectroradiometer (EOS/MODIS), and soil moisture at 10 cm and 200 cm depth are obtained by combining surface layer soil moisture with experiential statistics. Then the parameters are used to specify the respective options in the MM5 model. Comparison with the observations shows that the modeling including satellite values leads to improved meteorological simulations in the Jinta oasis, both for the oasis effect and the local wind circulation, especially for description of the inhomogeneous characteristics over the oasis. Replacing values in the initial field with data obtained from remote sensing removes the number of unknowns in the model and increases the accuracy of the energy budget. This work is a very valuable addition to current numerical research on local circumfluence over the oasis areas.
Case studies of aerosol remote sensing in the vicinity of clouds
Authors: Redemann Jens , Zhang Qin , Russell Philip B. , Livingston John M. , Remer Lorraine A.
Published: March 2009

Studying the spatial variability of aerosol properties in the vicinity of clouds is essential to our ability to determine aerosol direct and indirect effects on climate. In this paper, we describe aerosol observations collected near cloud edges by an airborne Sun photometer over dark ocean waters. Focusing on case studies of aerosol measurements near eight cloud edges within a dissipating stratiform cloud deck, we compare the airborne Sun photometer observations to retrievals of aerosol properties using the standard Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol algorithm applied to 500‐m‐resolution MODIS spectral reflectances. We find a persistent, spectrally neutral increase in the Sun photometer–derived aerosol optical depth (AOD) of up to 10% (0.015) in the 2‐km distances closest to the edges of several distinct clouds. At midvisible wavelengths, the MODIS AOD retrievals show similar increases toward cloud edges, although a larger increase in AOD is found in the MODIS along‐scan direction. At short‐wave infrared (SWIR) wavelengths (1240–2130 nm), the MODIS‐derived AOD increases near cloud edges are of the order of 0.03 and as such three times as large as the Sun photometer–derived values. Hence, in contrast to recently discussed “bluing” of aerosols near cloud edges, i.e., a preferential apparent increase in the visible reflectances of clear‐sky pixels due to 3‐D radiative transfer effects in the vicinity of clouds, we find a “reddening” of aerosols in the MODIS 500‐m‐resolution aerosol retrievals near clouds. This “reddening” in our study can be traced to larger absolute increases in SWIR reflectances when compared to visible reflectances near clouds, which in turn seem to stem from larger electronic cross talk in the MODIS SWIR bands (5–7). We note that the lack of “bluing” in our MODIS observations is likely due to the small geometric and optical thicknesses of the clouds considered.
Channelization on plateaus with arbitrary shapes
Authors: Pornprommin A. , Izumi N. , Tsujimoto T.
Published: March 2009

The initiation of channels and the factors that control their spacing is one of the most fundamental problems in geomorphology. Here we present an analysis of channelization that is downstream driven, so called because channelization is initiated at some point away from the divide where the Froude critical flow is achieved. By using two novel techniques, the “frozen time approach” and the “momentary stability concept,” we are able, for the first time, to investigate downstream‐driven channelization that occurs on a plateau with an evolving base profile. The “frozen time approach” assumes that the time evolution of the base state can be ignored in the linearized equations, whereas the “momentary stability concept” assumes that an unsteady base state becomes momentarily unstable to a disturbance when the growth of the disturbance is faster than the evolution of the base state. The analysis shows that an arbitrary slope profile is momentarily unstable and incised by channels before it evolves into a steady base state if the topographic curvature at the location where the Froude critical flow is achieved is sufficiently small. As the curvature decreases further, dominant channel spacing increases slightly in a purely erosional case, while clear dominant channel spacing tends not to appear in an erosional‐depositional case. It is also found from the analysis that in both cases, the channel spacing is on the order of 1000 times the Froude critical depth. The results are compared with field observations and experiments, and they show satisfactory agreement.
Differences in the Indonesian seaway in a coupled climate model and their relevance to Pliocene climate and El Niño
Authors: Jochum M. , Fox‐Kemper B. , Molnar P. H. , Shields C.
Published: March 2009

A fully coupled general circulation model is used to investigate the hypothesis that during Pliocene times tectonic changes in the Indonesian seas modified the Indo‐Pacific heat transport and thus increased the zonal sea surface temperature gradient in the equatorial Pacific to its large, current magnitude. We find that widening the Indonesian seaway by moving the northern tip of New Guinea south of the equator leads to an increased inflow of South Pacific waters into the Indian Ocean, but because of potential vorticity constraints on cross‐equatorial flow it also leads to reductions in both the inflow of North Pacific waters and the total Indonesian throughflow transport. The reduced throughflow is matched by increased eastward transport of warm and fresh North Pacific surface waters along the equator to the central equatorial Pacific. As a result, the Intertropical Convergence Zone lies closer to the equator and the western Pacific Warm Pool expands farther east than for present‐day conditions. This reduces the delayed oscillator component of El Niño–Southern Oscillation (ENSO) and enhances the role of stochastic perturbations. Thus, with a more open Indonesian seaway, ENSO becomes weaker and more irregular.
Transforming Growth Factor-β Signaling Alters Substrate Permeability and Tight Junction Protein Expression at the Blood-Brain Barrier during Inflammatory Pain
Authors: Ronaldson Patrick T , DeMarco Kristin M , Sanchez-Covarrubias Lucy , Solinsky Christine M , Davis Thomas P
Published: March 2009

Our laboratory has shown that peripheral inflammatory pain induced by λ-carrageenan (CIP) can increase blood-brain barrier (BBB) permeability and alter tight junction (TJ) protein expression leading to changes in BBB functional integrity. However, the intracellular signaling mechanisms involved in this pathophysiologic response have not been elucidated. Transforming growth factor (TGF)-β signaling pathways are known to regulate vascular integrity and permeability. Therefore, we examined the function of TGF-β signaling at the BBB in rats subjected to CIP. During CIP, serum TGF-β1 and protein expression of the TGF-β receptor activin receptor-like kinase-5 (ALK5) were reduced. Brain permeability to 14C-sucrose was increased and expression of TJ proteins (i.e., claudin-5, occludin, zonula occluden (ZO-1)) were also altered after 3 h CIP. Pharmacological inhibition of ALK5 with the selective inhibitor SB431542 further enhanced brain uptake of 14C-sucrose, increased TJ protein expression (i.e., claudin-3, claudin-5, occludin, ZO-1), and decreased nuclear expression of TGF-β/ALK5 signaling molecules (i.e., Smad2, Smad3), which suggests a role for TGF-β/ALK5 signaling in the regulation of BBB integrity. Interestingly, administration of exogenous TGF-β before CIP activated the TGF-β/ALK5 pathway and reduced BBB permeability to 14C-sucrose. Taken together, our data show that TGF-β/ALK5 signaling is, in part, involved in the regulation of BBB functional integrity.
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, THE OBESITY SOCIETY, AND AMERICAN SOCIETY FOR METABOLIC & BARIATRIC SURGERY MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE PERIOPERATIVE NUTRITIONAL, METABOLIC, AND NONSURGICAL SUPPORT OF THE BARIATRIC SURGERY PATIENT
Authors: Mechanick Jeffrey I. , Kushner Robert F. , Sugerman Harvey J. , Gonzalez‐Campoy J. Michael , Collazo‐Clavell Maria L. , Spitz Adam F. , Apovian Caroline M. , Livingston Edward H. , Brolin Robert , Sarwer David B. , Anderson Wendy A. , Dixon John
Published: March 2009

American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery Medical Guidelines for Clinical Practice are systematically developed statements to assist health‐care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied.

These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

The American Society for Parenteral & Enteral Nutrition fully endorses sections of these guidelines that address the metabolic and nutritional management of the bariatric surgical patient.
The Caricature Effect in Drawing: Evidence for the Use of Categorical Relations When Drawing Abstract Pictures
Authors: Rosielle Luke J , Hite Lesley A
Published: March 2009

Five experiments were conducted to determine how novice and expert drawers represent relative size for the purposes of drawing. Participants were shown images of two-part or three-part geometric figures composed of two spatially separated shapes. In each picture there was a small but noticeable relative-size difference between the constituent shapes (one part of the picture was always 25% larger than another part). Participants later drew the pictures from memory. The results showed that novice and expert drawers consistently exaggerated the relative size relationship between the shapes in the picture when attempting to draw it from memory and when copying (the ‘caricature effect’), although the effect was reduced for the experts. The results are consistent with the idea that people represent size in memory using categorical descriptors (eg ‘smaller than’, ‘larger than’) rather than as precise metrics. Further, the results suggest that the process of becoming a skilled drawer may involve overcoming this categorical bias.
Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver
Authors: Klieverik Lars P. , Janssen Sarah F. , Riel Annelieke van , Foppen Ewout , Bisschop Peter H. , Serlie Mireille J. , Boelen Anita , Ackermans Mariëtte T. , Sauerwein Hans P. , Fliers Eric , Kalsbeek Andries
Published: March 2009

Thyrotoxicosis increases endogenous glucose production (EGP) and induces hepatic insulin resistance. We have recently shown that these alterations can be modulated by selective hepatic sympathetic and parasympathetic denervation, pointing to neurally mediated effects of thyroid hormone on glucose metabolism. Here, we investigated the effects of central triiodothyronine (T
3
) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T
3
or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T
3
microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T
3
microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T
3
microdialysis in the PVN increased EGP by 11 ± 4% (
P
= 0.020), while EGP decreased by 5 ± 8% (ns) in vehicle-treated rats (T
3
vs. Veh,
P
= 0.030). Plasma glucose increased by 29 ± 5% (
P
= 0.0001) after T
3
microdialysis versus 8 ± 3% in vehicle-treated rats (T
3
vs. Veh,
P
= 0.003). Similar effects were observed after i.c.v. T
3
administration. Effects of PVN T
3
microdialysis were independent of plasma T
3
, insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T
3
microdialysis on EGP. We conclude that stimulation of T
3
-sensitive neurons in the PVN of euthyroid rats increases EGP via sympathetic projections to the liver, independently of circulating glucoregulatory hormones. This represents a unique central pathway for modulation of hepatic glucose metabolism by thyroid hormone.
Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites
Authors: Belouzard Sandrine , Chu Victor C. , Whittaker Gary R.
Published: March 2009

The coronavirus spike protein (S) plays a key role in the early steps of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion. In some cases, the S protein is proteolytically cleaved at the S1–S2 boundary. In the case of the severe acute respiratory syndrome coronavirus (SARS-CoV), it has been shown that virus entry requires the endosomal protease cathepsin L; however, it was also found that infection of SARS-CoV could be strongly induced by trypsin treatment. Overall, in terms of how cleavage might activate membrane fusion, proteolytic processing of the SARS-CoV S protein remains unclear. Here, we identify a proteolytic cleavage site within the SARS-CoV S2 domain (S2′, R797). Mutation of R797 specifically inhibited trypsin-dependent fusion in both cell–cell fusion and pseudovirion entry assays. We also introduced a furin cleavage site at both the S2′ cleavage site within S2 793-KPTKR-797 (S2′), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2′ position allowed trypsin-independent cell–cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1–S2 position. Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2′), acting in concert with the S1–S2 cleavage site to mediate membrane fusion and virus infectivity.
Folding kinetics of the human prion protein probed by temperature jump
Authors: Hart Tanya , Hosszu Laszlo L. P. , Trevitt Clare R. , Jackson Graham S. , Waltho Jonathan P. , Collinge John , Clarke Anthony R.
Published: March 2009

Temperature-jump perturbation was used to examine the relaxation kinetics of folding of the human prion protein. Measured rates were very fast (≈3,000 s
−1
), with the extrapolated folding rate constant at ≈20 °C in physiological conditions reaching 20,000 s
−1
. By a mutational analysis of core residues, we found that only 2, on the interface of helices 2 and 3, have significant ϕ-values in the transition state. Interestingly, a mutation sandwiched between the above 2 residues on the helix–helix contact interface had very little effect on the overall free energy of folding but led to the formation of a monomeric misfolded state, which had to unfold to acquire the native PrP
C
conformation. Another mutation that led to a marked destabilization of the native fold also formed a misfolded intermediate, but this was aggregation-prone despite the native state of this mutant being soluble. Taken together, the data imply that this fast-folding protein has a transition state that is not compact (
m
value analysis gives a β
t
value of only 0.3) but contains a developing nucleus between helices 2 and 3. The fact that a mutation in this nucleus had a negligible effect on stability but still led to formation of aberrant conformations during folding implies an easily perturbed folding mechanism. It is notable that in inherited forms of human prion disease, where point mutations produce a lethal dominant condition, 20 of the 33 amino acid replacements occur in the helix-2/3 sequence.
Structural plasticity of an acid-activated chaperone allows promiscuous substrate binding
Authors: Tapley Timothy L. , Körner Jan L. , Barge Madhuri T. , Hupfeld Julia , Schauerte Joseph A. , Gafni Ari , Jakob Ursula , Bardwell James C. A.
Published: March 2009

HdeA has been shown to prevent acid-induced aggregation of proteins. With a mass of only 9.7 kDa, HdeA is one of the smallest chaperones known. Unlike other molecular chaperones, which are typically complex, multimeric ATP-dependent machines, HdeA is known to undergo an acid-induced dimer to monomer transition and functions at low pH as a disordered monomer without the need for energy factors. Thus, HdeA must possess features that allow it to bind substrates and regulate substrate affinity in a small and energy-independent package. To understand better how HdeA accomplishes this, we studied the conformational changes that accompany a shift to low pH and substrate binding. We find that the acid-induced partial unfolding and monomerization that lead to HdeA activation occur very rapidly (
k
>3.5 s
−1
). Activation exposes the hydrophobic dimer interface, which we found to be critical for substrate binding. We show by intramolecular FRET that the partially unfolded character of active HdeA allows the chaperone to adopt different conformations as required for the recognition and high-affinity binding of different substrate proteins. These efficient adaptations help to explain how a very small protein is rapidly activated and can bind a broad range of substrate proteins in a purely pH-regulated manner.
Knockdown of limiting-CO
2
–induced gene
HLA3
decreases HCO
3
−
transport and photosynthetic Ci affinity in
Chlamydomonas reinhardtii
Authors: Duanmu Deqiang , Miller Amy R. , Horken Kempton M. , Weeks Donald P. , Spalding Martin H.
Published: March 2009

The CO
2
-concentrating mechanism (CCM) of
Chlamydomonas reinhardtii
and other microalgal species is essential for photosynthetic growth in most natural settings. A great deal has been learned regarding the CCM in cyanobacteria, including identification of inorganic carbon (Ci; CO
2
and HCO
3
−
) transporters; however, specific knowledge of analogous transporters has remained elusive in eukaryotic microalgae such as
C. reinhardtii
. Here we investigated whether the limiting-CO
2
–inducible, putative ABC-type transporter HLA3 might function as a HCO
3
−
transporter by evaluating the effect of pH on growth, photosynthetic Ci affinity, and [
14
C]-Ci uptake in very low CO
2
conditions following RNA interference (RNAi) knockdown of
HLA3
mRNA levels in wild-type and mutant cells. Although knockdown of
HLA3
mRNA alone resulted in only modest but high-pH–dependent decreases in photosynthetic Ci affinity and Ci uptake, the combination of nearly complete knockdown of
HLA3
mRNA with mutations in
LCIB
(which encodes limiting-Ci–inducible plastid-localized protein required for normal Ci uptake or accumulation in low-CO
2
conditions) and/or simultaneous, apparently off-target knockdown of
LCIA
mRNA (which encodes limiting-Ci–inducible plastid envelope protein reported to transport HCO
3
−
) resulted in dramatic decreases in growth, Ci uptake, and photosynthetic Ci affinity, especially at pH 9, at which HCO
3
−
is the predominant form of available Ci. Collectively, the data presented here provide compelling evidence that HLA3 is directly or indirectly involved in HCO
3
−
transport, along with additional evidence supporting a role for LCIA in chloroplast envelope HCO
3
−
transport and a role for LCIB in chloroplast Ci accumulation.
A
Mycobacterium tuberculosis
ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold
Authors: Andersson Charlotta S. , Högbom Martin
Published: March 2009

Chlamydia trachomatis
R2c is the prototype for a recently discovered group of ribonucleotide reductase R2 proteins that use a heterodinuclear Mn/Fe redox cofactor for radical generation and storage. Here, we show that the
Mycobacterium tuberculosis
protein Rv0233, an R2 homologue and a potential virulence factor, contains the heterodinuclear manganese/iron-carboxylate cofactor but displays a drastic remodeling of the R2 protein scaffold into a ligand-binding oxidase. The first structural characterization of the heterodinuclear cofactor shows that the site is highly specific for manganese and iron in their respective positions despite a symmetric arrangement of coordinating residues. In this protein scaffold, the Mn/Fe cofactor supports potent 2-electron oxidations as revealed by an unprecedented tyrosine-valine crosslink in the active site. This wolf in sheep's clothing defines a distinct functional group among R2 homologues and may represent a structural and functional counterpart of the evolutionary ancestor of R2s and bacterial multicomponent monooxygenases.
Probing the intrinsically oil-wet surfaces of pores in North Sea chalk at subpore resolution
Authors: Hassenkam T. , Skovbjerg L. L. , Stipp S. L. S.
Published: March 2009

Pore surface properties control oil recovery. This is especially true for chalk reservoirs, where pores are particularly small. Wettability, the tendency for a surface to cover itself with fluid, is traditionally defined by the angle a droplet makes with a surface, but this macroscopic definition is meaningless when the particles are smaller than even the smallest droplet. Understanding surface wetting, at the pore scale, will provide clues for more effective oil recovery. We used a special mode of atomic force microscopy and a hydrophobic tip to collect matrices of 10,000 force curves over 5- × 5-μm
2
areas on internal pore surfaces and constructed maps of topography, adhesion, and elasticity. We investigated chalk samples from a water-bearing formation in the Danish North Sea oil fields that had never seen oil. Wettability and elasticity were inhomogeneous over scales of 10s of nanometers, smaller than individual chalk particles. Some areas were soft and hydrophobic, whereas others showed no correlation between hardness and adhesion. We conclude that the macroscopic parameter, “wetting,” averages the nanoscopic behavior along fluid pathways, and “mixed-wet” samples have patches with vastly different properties. Development of reservoir hydrophobicity has been attributed to infiltrating oil, but these new results prove that wettability and elasticity are inherent properties of chalk. Their variability, even on single particles, must result from material originally present during sedimentation or material sorbed from the pore fluid some time later.
Pseudo-Outbreak ofLegionella pneumophilaSerogroup 8 Infection Associated With a Contaminated Ice Machine in a Bronchoscopy Suite
Authors: Schuetz A. N. , Hughes R. L. , Howard R. M. , Williams T. C. , Nolte F. S. , Jackson D. , Ribner B. S.
Published: March 2009

Objective.

To investigate the marked increase noted over an 8-month period in the number ofLegionella pneumophilaisolates recovered from bronchoalveolar lavage fluid specimens obtained during bronchoscopy in our healthcare system.

Setting.

Bronchoscopy suite that serves a 580-bed tertiary care center and a large, multisite, faculty practice plan with approximately 2 million outpatient visits per year.

Methods.

Cultures of environmental specimens from the bronchoscopy suite were performed, including samples from the air and water filters, bronchoscopes, and the ice machine, with the aim of identifyingLegionellaspecies. Specimens were filtered and acid-treated and then inoculated on buffered charcoal yeast extract agar. Serogrouping was performed on all isolates recovered from patient and environmental samples.

Results.

AUL. pneumophilaisolates recovered from patients were serogroup 8, a serogroup that is not usually recovered in our facility. An epidemiologic investigation of the bronchoscopy suite revealed the ice machine to be contaminated withL. pneumophilaserogroup 8. Patients were exposed to the organism as a result of a recently adopted practice in the bronchoscopy suite that involved directly immersing uncapped syringes of sterile saline in contaminated ice baths during the procedures. At least 1 patient was ill as a result of the pseudo-outbreak. Molecular typing of isolates recovered from patient and environmental samples revealed that the isolates were indistinguishable.

Conclusions.

Extensive cleaning of the ice machine and replacement of the machine's water filter ended the pseudo-outbreak. This episode emphasizes the importance of using aseptic technique when performing invasive procedures, such as bronchoscopies. It also demonstrates the importance of reviewing procedures in all patient areas to ensure compliance with facility policies for providing a safe patient environment.
A web application to perform linkage disequilibrium and linkage analyses on a computational grid
Authors: Hernández-Sánchez Jules , Grunchec Jean-Alain , Knott Sara
Published: March 2009

Motivation: Unravelling the genetic architecture of complex traits requires large amounts of data, sophisticated models and large computational resources. The lack of user-friendly software incorporating all these requisites is delaying progress in the analysis of complex traits.

Methods: Linkage disequilibrium and linkage analysis (LDLA) is a high-resolution gene mapping approach based on sophisticated mixed linear models, applicable to any population structure. LDLA can use population history information in addition to pedigree and molecular markers to decompose traits into genetic components. Analyses are distributed in parallel over a large public grid of computers in the UK.

Results: We have proven the performance of LDLA with analyses of simulated data. There are real gains in statistical power to detect quantitative trait loci when using historical information compared with traditional linkage analysis. Moreover, the use of a grid of computers significantly increases computational speed, hence allowing analyses that would have been prohibitive on a single computer.

Availability: The authors have implemented LDLA within the freely available GridQTL software (www.gridqtl.org.uk).

Contact:  jules.hernandez@ed.ac.uk
Ex situ target-strength measurements of Japanese anchovy (Engraulis japonicus) in the coastal Northwest Pacific
Authors: Kang Donhyug , Cho Sungho , Lee Changwon , Myoung Jung-Goo , Na Jungyul
Published: March 2009

Kang, D., Cho, S., Lee, C., Myoung, J-G. and Na, J. 2009. Ex situ target-strength measurements of Japanese anchovy (Engraulis japonicus) in the coastal Northwest Pacific. – ICES Journal of Marine Science, 66: 1219–1224. The Japanese anchovy (Engraulis japonicus) is an important species in regard to the fisheries and ecology of the coastal Northwest Pacific. Measurements of ex situ target strength (TS; dB re 1 m2) were made on live anchovy using 38, 120, and 200 kHz split-beam echosounders. The fish were tethered using small hooks attached to their mouths. During the acoustic measurements, an underwater video camera was used to continuously monitor fish behaviour and tilt-angle (θ). Data for 35 individual anchovy ranging from immature to adult sizes (total lengths LT = 4.8–12.2 cm) were analysed. Least-squares regression fits of TS vs. log(LT) were: TS38 kHz = 20 log(LT) − 65.8 (r2 = 0.82), TS120 kHz = 20 log(LT) − 68.4 (r2 = 0.84), and TS200 kHz = 20 log(LT) − 69.1 (r2 = 0.71). The LT vs. wet weight (W; g) relationship for these fish was W = 0.0036 LT3.204. The mean θ for anchovy swimming freely in a large seawater tank was 9.1° (s.d. = 13.1°). These ex situ measurements of TS, LT, W, and θ can be applied to improve acoustic estimates of Japanese anchovy biomass.
Depth as a potential driver of genetic structure of Sebastes mentella across the North Atlantic Ocean
Authors: Stefánsson Magnús Örn , Reinert Jákup , Sigurðsson Þorsteinn , Kristinsson Kristján , Nedreaas Kjell , Pampoulie Christophe
Published: March 2009

Stefánsson, M. Ö., Reinert, J., Sigurðsson, Þ., Kristinsson, K., Nedreaas, K., and Pampoulie, C. 2009. Depth as a potential driver of genetic structure of Sebastes mentella across the North Atlantic Ocean. – ICES Journal of Marine Science, 66: 680–690. A primary question that remains to be answered about the fishery for Sebastes mentella is whether it exploits several stocks within the North Atlantic Ocean. To address this issue, 1240 redfish were collected from several fishing grounds in late 2006 and early 2007 and genotyped at 12 microsatellite loci. Contemporary allele frequencies were compared with archived data to examine the temporal stability of the genetic structure. The analyses all revealed the presence of three genetically distinguishable clusters, which persisted throughout the study period, suggesting that the genetic structure detected is genuine. Cluster D included fish from the deep Irminger Sea and west Faroe Islands, and Cluster I included fish only from the Icelandic shelf. All other fish grouped in a third cluster (S). Further analyses revealed that the genetic pattern observed was not primarily attributable to isolation by distance, but rather to depth distribution.
Differential involvement of dopamine D1 receptor and MEK signaling pathway in the ventromedial prefrontal cortex in consolidation and reconsolidation of recognition memory
Authors: Maroun Mouna , Akirav Irit
Published: March 2009

We investigated MEK and D1 receptors in the ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of recognition memory in rats nonhabituated to the experimental context (NH) or with reduced arousal due to extensive prior habituation (H). The D1 receptor antagonist enhanced consolidation and impaired reconsolidation in NH but impaired consolidation with no effect on reconsolidation in H. The D1 receptor agonist had no effect on consolidation in either H or NH but impaired reconsolidation in both groups. The MEK inhibitor impaired consolidation and reconsolidation, regardless of arousal. Thus, vmPFC D1 receptors and MEK show differential involvement in memory and arousal.
Amyloid beta mediates memory formation
Authors: Garcia-Osta Ana , Alberini Cristina M.
Published: March 2009

The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid β (1–42) peptide (Aβ[1–42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated, endogenous Aβ in normal hippocampi mediates learning and memory formation. Furthermore, hippocampal injection of picomolar concentrations of exogenous Aβ(1–42) enhances memory consolidation. Correlative data suggest that Aβ peptides may exert their function via nicotinic acethylcoline receptors. Hence, Aβ peptides, including Aβ(1–42), play an important physiological role in hippocampal memory formation.
Sex influences on the neurobiology of learning and memory
Authors: Andreano Joseph M. , Cahill Larry
Published: March 2009

In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an advantage on spatial tasks, and females on verbal tasks, there is increasing evidence that sex differences are more widespread than previously supposed. Differing performance between the sexes have been observed on a number of common learning tasks in both the human and animal literature, many neither purely spatial nor verbal. We review sex differences reported in various areas to date, while attempting to identify common features of sexually dimorphic tasks, and to place these differences in a neurobiological context. This discussion focuses on studies of four classes of memory tasks for which sex differences have been frequently reported: spatial, verbal, autobiographical, and emotional memory. We conclude that the female verbal advantage extends into numerous tasks, including tests of spatial and autobiographical abilities, but that a small but significant advantage may exist for general episodic memory. We further suggest that for some tasks, stress evokes sex differences, which are not normally observed, and that these differences are mediated largely by interactions between stress and sex hormones.
Mitogen-Activated Protein Kinases 3 and 6 Are Required for Full Priming of Stress Responses inArabidopsis thaliana
Authors: Beckers Gerold J.M. , Jaskiewicz Michal , Liu Yidong , Underwood William R. , He Sheng Yang , Zhang Shuqun , Conrath Uwe
Published: March 2009

In plants and animals, induced resistance (IR) to biotic and abiotic stress is associated with priming of cells for faster and stronger activation of defense responses. It has been hypothesized that cell priming involves accumulation of latent signaling components that are not used until challenge exposure to stress. However, the identity of such signaling components has remained elusive. Here, we show that during development of chemically induced resistance in Arabidopsis thaliana, priming is associated with accumulation of mRNA and inactive proteins of mitogen-activated protein kinases (MPKs), MPK3 and MPK6. Upon challenge exposure to biotic or abiotic stress, these two enzymes were more strongly activated in primed plants than in nonprimed plants. This elevated activation was linked to enhanced defense gene expression and development of IR. Strong elicitation of stress-induced MPK3 and MPK6 activity is also seen in the constitutive priming mutant edr1, while activity was attenuated in the priming-deficient npr1 mutant. Moreover, priming of defense gene expression and IR were lost or reduced in mpk3 or mpk6 mutants. Our findings argue that prestress deposition of the signaling components MPK3 and MPK6 is a critical step in priming plants for full induction of defense responses during IR.
Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo
Authors: Shibata Hiroyuki , Yamakoshi Hiroyuki , Sato Atsuko , Ohori Hisatsugu , Kakudo Yuichi , Kudo Chieko , Takahashi Yayoi , Watanabe Mika , Takano Hiroshi , Ishioka Chikashi , Noda Tetsuo , Iwabuchi Yoshiharu
Published: March 2009

Curcumin (diferuloylmethane) has chemopreventive and chemotherapeutic potentials against various types of cancers. We have developed a series of curcumin analogs to improve its low bioavailability by enhancing its potentials. The newly synthesized analog GO‐Y030 [(1E, 4E)‐1,5‐bis‐(3,5(‐bismethoxymethoxyphenyl) penta‐1,4‐dien‐3‐one] showed a 30‐fold greater growth suppression in vitro via similar molecular mechanisms to curcumin. The availability of this analog was examined by using a mouse model harboring the germ‐line mutation of Apc, Apc580D/+, in vivo. Apc580D/+ mice had a very limited survival time with an intestinal obstruction due to polyposis. The average tumor number in mice fed GO‐Y030 was reduced to 61.2% of those that were fed the basal diet (P < 0.05). Compared with Apc580D/+ mice fed the basal diet (median survival time = 166.5 days), a significantly prolonged lifespan (213 days) was observed in Apc580D/+ mice fed GO‐Y030. The chemopreventive effect with GO‐Y030 was improved, compared with curcumin (191 days). The survival benefit corresponded to the diminished intestinal tumor incidence in Apc580D/+ mice fed GO‐Y030. No adverse reactions were observed, judging from body weight or biochemical data concerning liver and renal damage. Degradation of accumulated β‐catenin with curcumin is one of the major mechanisms of chemoprevention in colorectal carcinogenesis. It was demonstrated that the number of β‐catenin‐positive adenoma cells in Apc580D/+ mice fed GO‐Y030 was reduced. (Cancer Sci 2009; 100: 956–960)
EBAG9 inducing hyporesponsiveness of T cells promotes tumor growth and metastasis in 4T1 murine mammary carcinoma
Authors: Hong Xuejun , Liu Yang , Hu Guili , Zhao Dekuang , Shen Jiangen , Shen Fenping , Cao Xuetao , Wang Qingqing
Published: March 2009

The estrogen receptor‐binding fragment‐associated gene 9 (EBAG9) has been identified as an estrogen‐responsive gene and was recently identified as a tumor‐promoting and prognostic factor for renal cell carcinoma. We investigated whether EBAG9 expression was correlated with primary tumor growth and distant tumor metastasis in a murine breast carcinoma model. Knockdown expression of EBAG9 by small interfering RNA significantly suppressed tumor growth and metastasis in vivo in a highly malignant, spontaneously metastasizing 4T1 mouse mammary carcinoma model. 4T1 cells stably overexpressing EBAG9 developed larger and faster tumor growth and lung metastasis compared with parental 4T1 or 4T1 expressing vector alone. Strong specific cytotoxic T lymphocyte activity and enhanced γ‐interferon and interleukin‐2 productions were induced in mice that received EBAG9 small interfering RNA therapy. Gene silencing of EBAG9 prolonged the survival of tumor‐bearing mice and induced more intensive infiltration of CD8+ T cells in tumor mass. EBAG9 induced apoptosis of T cells, enhanced glycogen synthase kinase 3β phosphorylation and inhibited γ‐interferon production of T cells when T lymphocytes were cocultured with 4T1 cells overexpressing EBAG9. Furthermore, overexpression of EBAG9 in 4T1 cells was accompanied with enhanced expression of chemokine (C‐X‐C motif) receptor 4, which might be involved in tumor metastasis. Taken together, our results suggested that EBAG9 promoted primary 4T1 mammary carcinoma growth and distant metastasis, and EBAG9 small interfering RNA exerted overt regression of tumor growth and metastasis. These findings might provide insights into the mechanism through which tumors evade immunosurveillance and provide a strategy for therapeutic intervention of cancer metastases. (Cancer Sci 2009; 100: 961–969)
Hereditary diffuse gastric cancer: A manifestation of lost cell polarity
Authors: Humar Bostjan , Guilford Parry
Published: March 2009

Hereditary diffuse gastric cancer is a cancer syndrome caused by germline mutations in the gene for the cell adhesion protein E‐cadherin (CDH1). E‐cadherin plays a central role in the maintenance of cell polarity and its loss during tumorigenesis is associated with poorly differentiated cancers and a poor prognosis. Hereditary diffuse gastric cancer is dominated by diffuse‐type gastric adenocarcinoma, often with signet ring cell morphology. Large numbers of stage T1a signet ring cell carcinomas exist in the stomachs of CDH1 mutation carriers from a young age, and these foci sometimes show enrichment to the transition zone between the body and antrum. Generally these signet ring cell carcinomas are hypoproliferative, lack Wnt pathway activation, and are relatively indolent. However, a small proportion of the T1a foci contain cells that are poorly differentiated, display mesenchymal features, and express activated c‐Src and its downstream targets. These same features are observed in more advanced stages of hereditary diffuse gastric cancer progression, suggesting that an epithelial–mesenchymal transition is required for tumor invasion beyond the muscularis mucosae. Hereditary diffuse gastric cancer initiation requires somatic down‐regulation of the second CDH1 allele, which in most cases is caused by DNA promoter hypermethylation. Subsequent to CDH1 down‐regulation, lost polarity in gastric stem or progenitor cells would be predicted to interfere with mitotic spindle orientation and the segregation of cell fate determinants. We predict that this disruption of cell division results in daughter cells being deposited in the lamina propria where their population expands and partially differentiates, resulting in the formation of foci of signet ring cells. (Cancer Sci 2009; 100: 1151–1157)
Role of the miR‐106b‐25 microRNA cluster in hepatocellular carcinoma
Authors: Li Yang , Tan Weiqi , Neo Thomas W.L. , Aung Myat O. , Wasser Shanthi , Lim Seng G. , Tan Theresa M.C.
Published: March 2009

MicroRNAs are tiny RNA molecules which serve as important post‐transcriptional regulators of gene expression. Dysregulated expression of microRNAs has been observed in human cancers, indicating that microRNAs may function as oncogenes or as tumor suppressors. To date, the microRNAs encoded by the oncogenic miR‐17‐92 cluster, and its paralog the miR‐106b‐25 cluster, are among those which are differentially expressed in human cancers. In this study, we examined and confirmed the over‐expression of these clusters in hepatocellular carcinoma and in hepatoma‐derived cells. At least 50% of the tumor samples showed a greater than two‐fold increase in the expression for miR‐18 and for the miR‐106b‐25 cluster when compared with the corresponding paired non‐tumor samples. Knock‐down studies for the miR‐106b‐25 cluster, which includes miR‐106b, miR‐93 and miR‐25, showed that the expression of the cluster is necessary for cell proliferation and for anchorage‐independent growth. In tumors with high expression of this cluster, reduced expression of the BH3‐only protein Bim, a miR‐25 target, was observed. We further identified the transcription factor E2F1 as a target gene for miR‐106b and miR‐93 and it is likely that one of the roles of the miR‐106b‐25 cluster is to prevent excessively high E2F1 expression, which may then cause apoptosis. We conclude that there is aberrant expression of microRNAs encoded by the oncogenic miR‐17‐92 cluster and the miR‐106b‐25 cluster in hepatocellular carcinoma. The consistent overexpression of the miR‐106b‐25 cluster and its role in cell proliferation and anchorage‐independent growth points to the oncogenic potential of this cluster. (Cancer Sci 2009; 100: 1234–1242)
Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma
Authors: Morioka Kazuhito , Tanikawa Chizu , Ochi Kensuke , Daigo Yataro , Katagiri Toyomasa , Kawano Hirotaka , Kawaguchi Hiroshi , Myoui Akira , Yoshikawa Hideki , Naka Norifumi , Araki Nobuto , Kudawara Ikuo , Ieguchi Makoto , Nakamura Kozo , Nakamura Yusuke , Matsuda Koichi
Published: March 2009

Osteosarcoma is the most prevalent bone malignant tumor in children and adolescents, and displays heterogeneous histology and high propensity for distant metastasis. Although adjuvant chemotherapy remarkably improved treatment outcome over the past few decades, prognosis for osteosarcoma patients with pulmonary metastasis is still unsatisfactory. To identify novel therapeutic targets for osteosarcoma, we investigated the gene expression profile of osteosarcomas by cDNA microarray analysis and found transactivation of receptor tyrosine kinase‐like orphan receptor 2 (ROR2) expression in the majority of osteosarcoma samples. Treatment of osteosarcoma cell lines with siRNA against ROR2 significantly inhibited cell proliferation and migration. We also identified wingless‐type MMTV integration site family, member 5B (WNT5B) as a putative ROR2 ligand and that the physiological interaction of WNT5B and ROR2 could enhance cell migration, indicating the possible roles of ROR2 and WNT5B in the metastatic property of osteosarcoma cells. Taken together, our findings revealed that the WNT5B/ROR2 signaling pathway is a promising therapeutic target for osteosarcoma. (Cancer Sci 2009; 100: 1227–1233)
Level of reactive oxygen species induced by p21WAF(1)/CIP(1) is critical for the determination of cell fate
Authors: Inoue Takafumi , Kato Kiyoko , Kato Hidenori , Asanoma Kazuo , Kuboyama Ayumi , Ueoka Yousuke , Yamaguchi Shin‐ichiro , Ohgami Tatsuhiro , Wake Norio
Published: March 2009

p21WAF(1)/CIP(1) is a well‐known cell cycle regulatory protein which is overexpressed in several cancer cell lines, and known to determine cell fate. We generated three recombinant adenovirus vectors that expressed either the full‐length p21 (Ad‐p21F), a p21 mutant with a deletion of the C‐terminal proliferative cell nuclear antigen (PCNA) binding domain (Ad‐p21N), or a p21 mutant with a deletion of the N‐terminal cyclin‐dependent kinase binding domain (Ad‐p21C). We transfected these vectors into five cancer cell lines. Premature senescence was induced in all of the lines only following transfection with Ad‐p21N and Ad‐p21F. In addition, apoptosis was also induced in LoVo and HCT116 cells that harbored wild‐type p53 and the reactive oxygen species (ROS) level was higher than in senescent cells. Finally, the induction of apoptosis was inhibited by using siRNA to downregulate p53. This observation implies that there is a feedback signaling loop involving p21/ROS/p53 in apoptotic responses. It appears to be, at least in part, driven by high levels of p21 protein. Next, we investigated the cell death effect of endogenous p21 protein on cell fate using sodium butyrate (NaB). Treatment with 1 mM NaB or 2 to 5 mM NaB induced senescence or apoptosis, respectively. The level of intracellular ROS in 5 mM NaB treated cells was 2‐fold higher, compared with that in 1 mM NaB treated cells. We also demonstrated that DNA damage response signals including ataxia telangiectasia mutated, γH2AX, and p38 MAPK were involved in NaB‐induced cell death. The magnitude of intracellular ROS levels in response to p21 elicited either senescence or apoptosis in the cancer cell lines. (Cancer Sci 2009; 100: 1275–1283)