bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of a palliative care unit on mortality rate and length of stay for medical intensive care unit patients
Authors: Digwood Glen , Lustbader Dana , Pekmezaris Renee , Lesser Martin L. , Walia Rajni , Frankenthaler Michael , Hussain Erfan
Published: November 2011

Objective: This study evaluates the impact of a 10-bed inpatient palliative care unit (PCU) on medical intensive care unit (MICU) mortality and length of stay (LOS) for terminally ill patients following the opening of an inpatient PCU. We hypothesized that MICU mortality and LOS would be reduced through the creation of a more appropriate location of care for critically ill MICU patients who were dying.

Method: We performed a retrospective electronic database review of all MICU discharges from January 1, 2006 through December 31, 2009 (5,035 cases). Data collected included MICU mortality, MICU LOS, and mean age. The PCU opened on January 1, 2008. We compared location of death for MICU patients during the 2-year period before and the 2-year period after the opening of the PCU.

Results: Our data showed that the mean MICU mortality and MICU LOS both significantly decreased following the opening of the PCU, from 21 to 15.8% (p = 0.003), and from 4.6 to 4.0 days (p = 0.014), respectively.

Significance of results: The creation of an inpatient PCU resulted in a statistically significant reduction in both MICU mortality rate and MICU LOS, as terminally ill patients were transitioned out of the MICU to the PCU for end-of-life care. Our data support the hypothesis that a dedicated inpatient PCU, capable of providing care to patients requiring mechanical ventilation or vasoactive agents, can protect terminally ill patients from an ICU death, while providing more appropriate care to dying patients and their loved ones.
Automatic transport model data assimilation in Laplace space
Authors: Barnhart K. S. , Illangasekare T. H.
Published: November 2011

Emerging in situ sensors and distributed network technologies have the potential to monitor dynamic hydrological and environmental processes more effectively than traditional monitoring and data acquisition techniques by sampling at greater spatial and temporal resolutions. Since sensor networks supply data with little or no delay, applications exist where automatic or real‐time assimilation of this data would be useful, for example, during smart remediation procedures where tracking of the plume response will reinforce real‐time decisions. As a foray into this new data context, we consider the estimation of hydraulic conductivity when incorporating subsurface plume concentration data. Current practice optimizes the model in the time domain, which is often slow and very nonlinear. Instead, we perform model inversion in Laplace space and are able to do so because data gathered using new technologies can be sampled densely in time. An intermediate‐scale synthetic aquifer is used to illustrate the developed technique.
Corticofugal projections from the anterior olfactory nucleus target olfactory bulb principal cells
Authors: Illig Kurt
Published: November 2011

The anterior olfactory nucleus (AON) is a cortical structure reciprocally connected with the olfactory bulb (OB) and the piriform cortex. Here, using small extracellular and intracellular injections to trace the terminal projections in the OB from individual cells in the rat AON, and examining the morphology and distribution of these projections, I report that these projections appear to preferentially target and directly synapses with mitral cells. These findings suggests that the AON acts to modulate incoming olfactory information based on ongoing processing, perhaps in a way that tunes the OB to signal the presence of particular odors.
Dipeptidyl Peptidases: Substrates and Therapeutic Targeting in Human Health and Disease
Authors: Wilson Claire H. , Abbott Catherine A.
Published: November 2011

Enzymatic members of the dipeptidyl peptidase (DP) 4-like gene family have been implicated in a wide range of diseases including type II diabetes, rheumatoid arthritis, wound healing and cancer. DP4 is a clinically validated target for the treatment of type II diabetes. Evidence supporting the role of DPs in immune function is increasing such that the development of further targeted therapeutics seems promising. Elucidation of DP substrates will help to reveal additional roles for this unique protease family, opening the door for further therapeutic avenues. Here, we provide an introduction to the biochemical properties of DP4, fibroblast activation protein (FAP), DP8 and DP9, and discuss their biological substrates, physiological roles, and the potential for therapeutic targeting of this family.
The Metalloproteases Meprin α and β: Pathophysiological Roles in Inflammation, Cardiovascular Disease, Cancer, and Fibrosis
Authors: Becker-Pauly Christoph
Published: November 2011

The metalloproteases meprin α and β exhibit unique functions in health and disease. Belonging to the metzincin superfamily, the meprins are two out of seven astacin zinc-endopeptidases in humans, representing the largest secreted protease known (oligomerized meprin α) and the only membrane-bound family member (meprin β).

Meprins activate or release growth factors (e.g. IL-1β, IL-18, TGFα, and VEGF-A) and other biologically active peptides, and are involved in inflammatory diseases, such as Crohn's disease or ulcerative colitis.

In vitro, both proteases exhibit gelatinolytic activity, revealing a possible link to tumor progression and metastasis. This is supported by cellular evidence from meprin β knockout mice, in which macrophage migration through the extracellular matrix was diminished. However, in fibrotic skin it has been demonstrated that meprin α and β enhance matrix assembly, by cleaving off the propeptides of fibrillar collagen. Hence, fundamental knowledge of their biological activity is necessary to assess meprin metalloproteases as therapeutic targets.

For example, the meprin inhibitor actinonin, a naturally occurring hydroxamate derivate, has been shown to be protective against acute renal failure, a pathology strongly related to meprin activity.
Glutamate Carboxypeptidase II as a Therapeutic Target
Authors: Hlouchová Klára , BaŘinka Cyril , Konvalinka Jan
Published: November 2011

Glutamate carboxypeptidase II (GCPII; EC 3.4.17.21) is a Zn2+-dependent metalloprotease of the M28 peptidase family. It is also known as prostate-specific membrane antigen, N-acetylated-α-linked acidic dipeptidase, or folate hydrolase I. In the brain, the enzyme cleaves the peptide neurotransmitter N-acetyl-l-aspartyl-l-glutamate (NAAG) into N-acetyl-l-aspartate and free glutamate, a potent and potentially neurotoxic neurotransmitter. The folate hydrolase activity of GCPII facilitates the absorption of dietary folates in the small intestine by cleaving γ-linked glutamates from folyl-poly-γ-glutamates. While the physiological function of GCPII in the prostate is not known, its expression levels are elevated in metastatic prostate carcinoma. Furthermore, the enzyme is also expressed in the cancer-associated neovasculature of most solid tumors. In the nervous system, GCPII inhibition leads to an increase in NAAG concentration and has been shown to be neuroprotective in animal models of ischemic or traumatic brain injury, neuropathic pain, or amyotrophic lateral sclerosis. In tumors, GCPII represents a very promising target for specific diagnostics, imaging, and targeted delivery of anticancer drugs. The present chapter reviews the expression of GCPII in various tissues, its splice variants, orthologs, and paralogs, and summarizes available information on the physiological function and proteolytic activity of the enzyme. Furtermore, its 3-D structure, substrate specificity and binding mode of available specific inhibitors are described in more detail. Finally, current and potential applications of inhibitors and ligands of GCPII for the diagnostics, imaging, and experimental therapy of neurodegenerative diseases and prostate cancer are discussed.
Targeting Dipeptidyl Peptidase-4 (DPP-4) and Fibroblast Activation Protein (FAP) for Diabetes and Cancer Therapy
Authors: Keane F. M. , Chowdhury S. , Yao T.-W. , Nadvi N. A. , Gall M. G. , Chen Y. , Osborne B. , Ribeiro A. J. V. , Church W. B. , McCaughan G. W. , Gorrell M. D. , Yu D. M. T.
Published: November 2011

In recent years, the dipeptidyl peptidase-4 (DPP-4) enzyme family has created intense pharmaceutical interest. DPP-4 inhibitors have proven successful as a therapy for the growing type 2 diabetes epidemic and have potential to treat other diseases. A large number of recently developed DPP-4 inhibitors are in various phases of clinical development, with four gliptin class inhibitors already in clinical use. The unique distribution of Fibroblast Activation Protein (FAP), the closest relative of DPP-4, has led to numerous investigations of it as a target and marker for epithelial cancers. The roles of the newer members, DPP-8 and DPP-9, are yet to be fully characterized, but early evidence suggests possible roles in various aspects of cell biology and disease. There are a number of favorable circumstances that have contributed to the therapeutic approaches of targeting DPP-4 and FAP. Specific targeting of DPP-4 and FAP is made easier by the small size of this enzyme family and several structural differences at their active sites. Additionally, observations over the past decade that the DPP-4 and FAP gene knockout mice are healthy suggests that selective inhibition of each of these proteases would be safe, and this is reflected in the excellent safety profiles of the DPP-4-selective gliptins. These proteins also have interesting extra-enzymatic activities that are expected to be retained in the presence of protease inhibition. This feature also points to a low likelihood of off-target effects. Thus, an overall understanding of DPP-4 and FAP structure–function relationships, distribution, and enzymatic and extra-enzymatic biological roles provides an insight into their therapeutic usefulness as disease targets.
Impact of Polar Ozone Loss on the Troposphere
Authors: Gillett N. P. , Son S.-W.
Published: November 2011

The chapter reviews the evidence for the influence of Antarctic and Arctic ozone changes on the troposphere and ocean, and the mechanisms underlying this coupling. Antarctic ozone depletion has driven a cooling and strengthening of the polar vortex in austral spring. Models and observations show that this change has also been associated with a strengthening and poleward shift of the midlatitude westerly winds in the Southern Hemisphere troposphere in austral summer, as well as a cooling of the Antarctic troposphere. Antarctic ozone depletion has been associated with summer trends in surface temperature over Antarctica, precipitation over the southern hemisphere, Southern Ocean circulation, and ocean-atmosphere fluxes of carbon dioxide over the Southern Ocean. Both radiative and dynamical mechanisms are thought to be involved in communicating the response to stratospheric ozone depletion to the troposphere. In the Arctic there is some modeling evidence suggestive of a link between ozone depletion and tropospheric circulation changes, but due to the weaker ozone trends and larger internal variability, no such relationship has been identified in the observations.
La résorption radiculaire liée au traitement orthodontique : à
propos d’un cas
Authors: Houb-Dine Afaf , Rerhrhaye Mariam , Ismaili Zouheir , Rerhrhaye Wiam
Published: November 2011

La résorption radiculaire associée au traitement orthodontique est un effet parasite
iatrogène non intentionnel, d’étiologie multifactorielle, qui existe dans presque tous les
traitements orthodontiques. Le cas clinique présenté dans cet article illustre la
résorption radiculaire associée au traitement orthodontique intéressant la 21 qui présente
un antécédent de traumatisme et une perte d’attache modérée chez une patiente apparemment
en bon état de santé générale. Le traitement orthodontique a été mené dans le respect des
impératifs parodontaux avec des forces légères et continues et une maintenance parodontale
per-orthodontique. Dès l’apparition de la résorption radiculaire sur la 21, le traitement
orthodontique actif a été interrompu en vue d’une stabilisation de la lésion tout en
instaurant une surveillance clinique et radiologique régulière.
Le facteur ethnique est-il un indicateur thérapeutique?
Authors: Solmaz Ilknur , Raberin Monique
Published: November 2011

Face au diktat de la beauté imposée par la société à travers des stéréotypes, il est devenu légitime de s’interroger sur le concept universel du “ beau ”. Est-ce que les normes esthétiques en orthodontie, établies à partir d’échantillons de Nord-Américains, peuvent être applicables à d’autres populations? Les différentes analyses céphalométriques menées chez des sujets afro-américains, africains et asiatiques en occlusion normale non traitée mettent en évidence des critères esthétiques éloignés des critères nord-américains. Leurs conclusions relatent comme principal caractère ethnique la biprotrusion alvéolo-dentaire en relation avec un angle naso-labial réduit. Pour le sujet africain, on note très fréquemment une antéro-position du maxillaire avec une position mandibulaire inchangée ou rétruse. Pour le sujet asiatique, une similitude des profils cutanés est rapportée avec une divergence quant aux profils squelettiques : les Japonais présentent une rétrognathie maxillaire plus prononcée; les Chinois montrent souvent une promaxilie et une rétromandibulie. Les Coréens se rapprocheraient des Japonais. Il semble donc nécessaire de constituer des données spécifiques à l’origine ethnique afin d’optimiser le diagnostic esthétique et les objectifs du traitement orthodontique.
Infrared emissivity of tin upon release of a 25 GPa shock into a lithium fluoride window
Authors: Turley W. D. , Holtkamp D. B. , Veeser L. R. , Stevens G. D. , Marshall B. R. , Seifter A. , Corrow R. B. , Stone J. B. , Young J. A. , Grover M.
Published: November 2011

We measured the emissivity of a tin sample at its interface with a lithium-fluoride window upon release of a 25 GPa shock wave from the tin into the window. Measurements were made over four wavelength bands between 1.2 and 5.4 μm. Thermal emission backgrounds from the tin, glue, and lithium fluoride were successfully removed from the reflectance signals. Emissivity changes for the sample, which was initially nearly specular, were small except for the longest wavelength band, where uncertainties were high because of poor signal-to-noise ratio at that wavelength. A thin glue layer, which bonds the sample to the window, was found to heat from reverberations of the shock wave between the tin and the lithium fluoride. At approximately 3.4 μm, the thermal emission from the glue was large compared to the tin, allowing a good estimate of the glue temperature from the thermal radiance. The glue appears to remain slightly colder than the tin, thereby minimizing heat conduction into or out of the tin immediately after the shock passage.
A laser system for the parametric amplification of electromagnetic fields in a microwave cavity
Authors: Agnesi A. , Braggio C. , Carugno G. , Valle F. Della , Galeazzi G. , Messineo G. , Pirzio F. , Reali G. , Ruoso G.
Published: November 2011

We describe recent improvements in the development of the high power laser system used in the motion induced radiation (MIR) experiment to amplify electromagnetic fields inside a microwave cavity. The improvements made on the oscillator stabilization, the pulse train shaping device, and the spatial beam uniformity are reported.
Dispersion interactions in density-functional theory: An adiabatic-connection analysis
Authors: Strømsheim Marie D. , Kumar Naveen , Coriani Sonia , Sagvolden Espen , Teale Andrew M. , Helgaker Trygve
Published: November 2011

We present an analysis of the dispersion interaction energy and forces in density-functional theory from the point of view of the adiabatic connection between the Kohn–Sham non-interacting and fully interacting systems. Accurate coupled-cluster singles-doubles-perturbative-triples [CCSD(T)] densities are computed for the helium dimer and used to construct the exchange-correlation potential of Kohn–Sham theory, showing agreement with earlier results presented for the Hartree–Fock–Kohn–Sham method [M. Allen and D. J. Tozer, J. Chem. Phys. 117, 11113 (2002)10.1063/1.1522715]. The accuracy of the methodology utilized to determine these solutions is checked by calculation of the Hellmann–Feynman forces based on the Kohn–Sham densities, which are compared with analytic CCSD(T) forces. To ensure that this comparison is valid in a finite atomic-orbital basis set, we employ floating Gaussian basis functions throughout and all results are counterpoise corrected. The subtle charge-rearrangement effects associated with the dispersion interaction are highlighted as the origin of a large part of the dispersion force. To recover the exchange-correlation components of the interaction energy, adiabatic connections are constructed for the supermolecular system and for its constituent atoms; subtraction of the resulting adiabatic-connection curves followed by integration over the interaction strength recovers the exchange-correlation contribution relevant to the density-functional description of the dispersion interaction. The results emphasize the long-ranged, dynamically correlated nature of the dispersion interaction between closed-shell species. An alternative adiabatic-connection path is also explored, where the electronic interactions are introduced in a manner that emphasizes the range of the electronic interactions, highlighting their purely long-ranged nature, consistent with the success of range-separated hybrid approaches in this context.
Orientational prewetting of planar solid substrates by a model liquid crystal
Authors: Greschek Manuel , Schoen Martin
Published: November 2011

We present grand canonical ensemble Monte Carlo simulations of prewetting transitions in a model liquid crystal at structureless solid substrates. Molecules of the liquid crystal interact via anisometric Lennard-Jones potentials and can be anchored planar or homeotropically at the substrates. Fluid-substrate attraction is modeled by a Yukawa potential of variable range. By monitoring the grand-potential density and the nematic order parameter as functions of the chemical potential μ, several discontinuous prewetting, wetting, and isotropic-nematic phase transitions are observed. These transitions depend on both the range of the fluid-substrate attraction and the specific anchoring at the substrate. Our results show that at substrates characterized by degenerate anchoring prewetting occurs at lower μ compared with cases in which the anchoring is monostable. This indicates that prewetting transitions are driven by orientational entropy because degenerate anchoring allows for more orientationally distinct configurations of molecules compared with monostable anchoring. In addition, by analyzing local density and various local order parameters, a detailed picture of the structure of various phases emerges from our simulations.
Statistical analysis of high power microwave surface flashover delay times in nitrogen with metallic field enhancements
Authors: Foster Jonathan , Krompholz Hermann , Neuber Andreas
Published: November 2011

The physical mechanisms that contribute to atmospheric breakdown induced by high power microwaves (HPMs) are of particular interest for the further development of high power microwave systems and related technologies. For a system in which HPM is produced in a vacuum environment for the purpose of radiating into atmosphere, it is necessary to separate the atmospheric environment from the vacuum environment with a dielectric interface. Breakdown across this interface on the atmospheric side and plasma development to densities prohibiting further microwave propagation are of special interest. In this paper, the delay time between microwave application and plasma emergence is investigated. Various external parameters, such as UV illumination or the presence of small metallic points on the surface, provide sources for electron field emission and influence the delay time which yields crucial information on the breakdown mechanisms involved. Due to the inherent statistical appearance of initial electrons and the statistics of the charge carrier amplification mechanisms, the flashover delay times deviate by as much as ±50% from the average, for the investigated case of discharges in N2 at pressures of 60–140 Torr and a microwave frequency of 2.85 GHz with 3 μs pulse duration, 50 ns pulse risetime, and MW/cm2 power densities. The statistical model described in this paper demonstrates how delay times for HPM surface flashover events can be effectively predicted for various conditions given sufficient knowledge about ionization rate coefficients as well as the production rate for breakdown initiating electrons.
Angle dependence of the switching field of recording media at finite temperatures
Authors: Saharan L. , Morrison C. , Miles J. J. , Thomson T. , Schrefl T. , Hrkac G.
Published: November 2011

A combined micromagnetic and nudged elastic band method was used to investigate the utility of a one-grain model in describing the switching field of CoCrPt perpendicular recording media as a function of applied field angle at finite temperatures of 150 K, 292 K and 350 K. The effect of grain diameter, attempt frequency, and thermal activation on the switching field were investigated. The results of the simulations show good agreement with vector vibrating sample magnetometer measurements on well segregated, single layer CoCrPt-SiOx recording media and demonstrate that thermal activation modifies the Stoner-Wohlfarth angle dependency of the switching field by reducing the depth of the minimum that occurs at 45°.
Temperature dependent optical properties of pentacene films on zinc oxide
Authors: Helzel J. , Jankowski S. , El Helou M. , Witte G. , Heimbrodt W.
Published: November 2011

The optical transitions of pentacene films deposited on ZnO have been studied by absorption spectroscopy as a function of temperature in the range of room temperature down to 10 K. The pentacene films were prepared with thicknesses of 10 nm, 20 nm, and 100 nm on the ZnO-O(000-1) surface by molecular beam deposition. A unique temperature dependence has been observed for the two Davydov components of the excitons for different film thicknesses. At room temperature, the energetic positions of the respective absorption bands are the same for all films, whereas the positions differ more than 20 meV at 10 K caused by the very different expansion coefficients of pentacene and ZnO. Although the pentacene is just bonded via van der Waals interaction to the ZnO substrate, the very first pentacene monolayer (adlayer) is forced to keep the initial position on the ZnO surface and suffering, therefore, a substantial tensile strain. For all the subsequent pentacene monolayers, the strain is reduced step by step resulting electronically in a strong potential gradient at the interface.
Non-resonant parametric amplification in biomimetic hair flow sensors: Selective gain and tunable filtering
Authors: Droogendijk H. , Bruinink C. M. , Sanders R. G. P. , Krijnen G. J. M.
Published: November 2011

We demonstrate that the responsivity of flow sensors for harmonic flows can be improved significantly by non-resonant parametric amplification. Using electrostatic spring softening by AC-bias voltages, increased responsivity and sharp filtering are achieved in our biomimetic flow sensors. Tunable filtering is obtained for non-resonant electromechanical parametric amplification, applicable at a wide range of non-resonant frequencies while achieving highly selective gain of up to 20 dB.
Nutrition × reproduction interaction in pasture-based systems: is nutrition a factor in reproductive failure?
Authors: Roche J. R. , Burke C. R. , Meier S. , Walker C. G.
Published: November 2011

Dairy cow fertility has declined in recent decades, coincidental with large increases in milk production. Cows take longer to return to oestrus, display poorer signs of oestrus, have greater early embryo loss, and may have poorer conception rates. The problem is often considered to be nutritional, at least in part, and, therefore, can be corrected through dietary adjustment. Although acknowledged as highly digestible, high quality pastured forages tend to be low in non-structural carbohydrates (NSC), high in rumen degradable protein and the temporal supply may not be adequate for cow demand at key times; diet adjustment is often recommended to overcome these limitations. The interaction between nutrition and reproduction is poorly defined, however, and study results are often contradictory. Hypothesised limitations to pastured forages within a grazing system will be discussed, and the likely impact of nutritional adjustment on pre- and post-ovulatory reproductive processes examined. The effect of energy balance, carbohydrate type, protein and fat on reproductive outcomes will be considered. Nutrition is an important component of successful reproduction, but dietary adjustment to improve pregnancy rates is complicated, and merely offering pastured cows a supplement is unlikely to result in large effects. Conclusions indicate that care must be taken in interpreting associative analyses and in applying results from different farming systems.
Hormonal induction of spermatozoa from amphibians with Rana temporaria and Bufo bufo as anuran models
Authors: Uteshev V. K. , Shishova N. V. , Kaurova S. A. , Browne R. K. , Gakhova E. N.
Published: November 2011

The use of hormonally induced spermatozoa expressed in urine (HISu) is a valuable component of reproduction technologies for amphibians. Five protocols for sampling HISu from the European common frog (Rana temporaria) were compared: (1) pituitary extracts, (2) 0.12 µg g–1 luteinising hormone-releasing hormone analogue (LHRHa), (3) 1.20 µg g–1 LHRHa, (4) 11.7 IU g–1 human chorionic gonadotrophin (hCG) and (5) 23.4 IU g–1 hCG (g–1 = per gram bodyweight). From 1 to 24 h after administration we assessed the number and concentration of spermatozoa in spermic urine and in holding water, and in urine the percentage of motile spermatozoa and their progressive motility. The protocol using 1.20 µg g–1 LHRHa gave the highest total sperm numbers (650 × 106) and the highest percentage (40%) of samples with sperm concentrations above 200 × 106 mL–1. The percentage motility and progressive motility was similar from all protocols. Considerable amounts of spermatozoa were expressed by R. temporaria into their holding water. We tested hormonal priming and spermiation in the common toad (Bufo bufo) using 0.13 µg g–1 LHRHa administered 24 h before a final spermiating dose of 12.8 IU g–1 hCG. No spermatozoa were expressed in holding water. Priming resulted in 35% more spermatozoa than without; however, there were no differences in sperm concentrations. Primed B. bufo produced spermatozoa with significantly higher percentage motility, but not progressive motility, membrane integrity, or abnormal spermatozoa than unprimed males.
Brain network local interconnectivity loss in agingAPOE-4 allele carriers
Authors: Brown Jesse A. , Terashima Kevin H. , Burggren Alison C. , Ercoli Linda M. , Miller Karen J. , Small Gary W. , Bookheimer Susan Y.
Published: November 2011

Old age and possession of theAPOE-4 allele are the two main risk factors for developing later onset Alzheimer's Disease (AD). Carriers of theAPOE-4 allele have known differences in intrinsic functional brain network activity across the life span. These individuals also demonstrate specific regional differences in gray and white matter gross structure. However, the relationship of these variations to whole brain structural network connectivity remains unclear. We performed diffusion tensor imaging (DTI), T1 structural imaging, and cognitive testing on agingAPOE-4 noncarriers (n= 30; mean age = 63.8±8.3) andAPOE-4 carriers (n= 25; mean age = 60.8 ±9.7). Fiber tractography was used to derive whole brain structural graphs, and graph theory was applied to assess structural network properties. Network communication efficiency was determined for each network by quantifying local interconnectivity, global integration, and the balance between these, the small worldness. Relative to noncarriers,APOE-4 carriers demonstrated an accelerated age-related loss of mean local interconnectivity (r= −0.64,P≤ 0.01) and regional local interconnectivity decreases in the precuneus (r= −0.64), medial orbitofrontal cortex (r= −0.5), and lateral parietal cortex (r= −0.54).APOE-4 carriers also showed significant age-related loss in mean cortical thickness (r= −0.52,P< 0.05). Cognitively,APOE-4 carriers had significant negative correlations of age and performance on two episodic memory tasks (P< 0.05). This genotype-specific pattern of structural connectivity change with age thus appears related to changes in gross cortical structure and cognition, potentially affecting the rate and/or spatial distribution of AD-related pathology.
Molecular architecture of the Spire–actin nucleus and its implication for actin filament assembly
Authors: Sitar Tomasz , Gallinger Julia , Ducka Anna M. , Ikonen Teemu P. , Wohlhoefler Michael , Schmoller Kurt M. , Bausch Andreas R. , Joel Peteranne , Trybus Kathleen M. , Noegel Angelika A. , Schleicher Michael , Huber Robert , Holak Tad A.
Published: November 2011

The Spire protein is a multifunctional regulator of actin assembly. We studied the structures and properties of Spire–actin complexes by X-ray scattering, X-ray crystallography, total internal reflection fluorescence microscopy, and actin polymerization assays. We show that Spire–actin complexes in solution assume a unique, longitudinal-like shape, in which Wiskott–Aldrich syndrome protein homology 2 domains (WH2), in an extended configuration, line up actins along the long axis of the core of the Spire–actin particle. In the complex, the kinase noncatalytic C-lobe domain is positioned at the side of the first N-terminal Spire–actin module. In addition, we find that preformed, isolated Spire–actin complexes are very efficient nucleators of polymerization and afterward dissociate from the growing filament. However, under certain conditions, all Spire constructs—even a single WH2 repeat—sequester actin and disrupt existing filaments. This molecular and structural mechanism of actin polymerization by Spire should apply to other actin-binding proteins that contain WH2 domains in tandem.
Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway
Authors: Magalhaes Marco A. O. , Larson Daniel R. , Mader Christopher C. , Bravo-Cordero Jose Javier , Gil-Henn Hava , Oser Matthew , Chen Xiaoming , Koleske Anthony J. , Condeelis John
Published: November 2011

Invadopodia are invasive protrusions with proteolytic activity uniquely found in tumor cells. Cortactin phosphorylation is a key step during invadopodia maturation, regulating Nck1 binding and cofilin activity. The precise mechanism of cortactin-dependent cofilin regulation and the roles of this pathway in invadopodia maturation and cell invasion are not fully understood. We provide evidence that cortactin–cofilin binding is regulated by local pH changes at invadopodia that are mediated by the sodium–hydrogen exchanger NHE1. Furthermore, cortactin tyrosine phosphorylation mediates the recruitment of NHE1 to the invadopodium compartment, where it locally increases the pH to cause the release of cofilin from cortactin. We show that this mechanism involving cortactin phosphorylation, local pH increase, and cofilin activation regulates the dynamic cycles of invadopodium protrusion and retraction and is essential for cell invasion in 3D. Together, these findings identify a novel pH-dependent regulation of cell invasion.
Mesoscale β diversity and spatial nestedness of crustacean larvae in the coastal zone off central southern Chile: population and community implications
Authors: Díaz-Cabrera Ernesto , Hernández-Miranda Eduardo , Hernández Cristián E. , Quiñones Renato A.
Published: November 2011

Díaz-Cabrera, E., Hernández-Miranda, E., Hernández, C. E., and Quiñones, R. A. 2012. Mesoscale β diversity and spatial nestedness of crustacean larvae in the coastal zone off central southern Chile: population and community implications. – ICES Journal of Marine Science, 69: 429–438. Spatial connectivity among populations is one of the central themes in marine ecology. This study evaluates the presence of mesoscale spatial patterns in meroplanktonic stages of decapods and stomatopods. The hypothesis is that β diversity increases with geographic distance at a mesoscale level. Seven oceanographic cruises were conducted in central southern Chile between May 2006 and February 2008. Samples were collected using a bongo net (300 µm) towed through the top 15 m of the water column. To test the hypothesis, (i) the β diversity of early stages of decapods and stomatopods was quantified, (ii) a linear model was fitted between β diversity and the geographic distance among all possible pairs of sampling sites, and (iii) a nestedness analysis of species richness was performed to evaluate the effect of local transport on species diversity. There was a positive relationship between β diversity and geographic distance, and a nestedness pattern in most sampling periods, suggesting that a source–sink dynamic dominates between nearby sites and that larval dispersion is limited, inducing low levels of population connectivity.
Predictors of Clinically Significant Upper Gastrointestinal Hemorrhage Among Children With Hematemesis
Authors: Freedman Stephen B. , Stewart Charles , Rumantir Maggie , Thull‐Freedman Jennifer D.
Published: November 2011

Objectives:

The aim of the study was to determine the proportion of children with hematemesis who experience a clinically significant upper gastrointestinal hemorrhage (UGIH) and to identify variables predicting their occurrence.

Methods:

A retrospective cohort study was conducted. All of the emergency department visits by children ages 0 to 18 years who presented with hematemesis between 2000 and 2007 were reviewed. The primary aim of the study was to determine the proportion of children who developed a clinically significant UGIH; the secondary aim was to identify risk factors predictive of a clinically significant UGIH. A significant UGIH was defined by any of the following: hemoglobin drop >20 g/L, blood transfusion, or emergent endoscopy or surgical procedure.

Results:

Twenty‐seven of 613 eligible children (4%; 95% confidence interval 3%–6%) had a clinically significant UGIH. Clinically significant hemorrhages were associated with older age (9.7 vs 2.9 years; P < 0.001), vomiting moderate to large amounts of fresh blood (58% vs 20%; P < 0.001), melena (37% vs 5%; P < 0.001), significant medical history (63% vs 24%; P < 0.001), unwell appearance (44% vs 6%; P < 0.001), and tachycardia (41% vs 10%; P < 0.001). The frequency of laboratory investigations increased with age (P < 0.001). The hemoglobin level was the only laboratory investigation whose results differed between those with and without significant bleeds. The presence of any one of the following characteristics identified all of the children with a clinically significant hemorrhage: melena, hematochezia, unwell appearance, or a moderate to large volume of fresh blood in the vomitus, sensitivity 100% (95% confidence interval 85%–100%).

Conclusions:

The occurrence of a clinically significant UGIH was uncommon among children with hematemesis, especially in well‐appearing children without melena, hematochezia, or who had not vomited a moderate to large amount of fresh blood.
CCL5 mRNA is a marker for early fibrosis in chronic hepatitis C and is regulated by interferon‐α therapy and toll‐like receptor 3 signalling
Authors: Katsounas A. , Trippler M. , Wang B. , Polis M. , Lempicki R. A. , Kottilil S. , Gerken G. , Schlaak J. F.
Published: November 2011

Summary.  Mechanisms causing liver fibrosis during chronic hepatitis C virus infection (cHCV) are not sufficiently understood. This study was aimed to identify biomarkers for early fibrosis (EF) and to investigate their potential role in cHCV‐related fibrogenesis. To this end, peripheral whole blood (PB) samples from 36 patients with cHCV recruited from two independent cohorts were subjected to microarray analysis 12 h before initiation of peginterferon‐alpha (Peg‐IFN‐α) and ribavirin therapy. Liver biopsies were evaluated using the Batts‐Ludwig staging (BL‐S) classification system for fibrosis. We showed that gene expression profiles (N = 8) distinguished between EF (BL‐S: 0,1) and late fibrosis (LF; BL‐S: 2,3,4) with 88.9% accuracy. Fibrosis‐related functional annotations for chemokine‐’C‐C‐motif’’ ligand 5 (CCL5) provided foundation for focused investigation, and qRT‐PCR confirmed that CCL5 mRNA levels (PB) reliably discriminate EF from LF (accuracy: 86.7%). Positive correlations (P < 0.05) with CCL5 mRNA levels and EF discovered gene expression profiles (PB) reflecting stable expression of IFN‐α receptor 1, negative regulation of the MyD88‐dependent toll‐like receptor (TLR) pathway and decreased expression of TLR3 in vivo. Remarkably, Peg‐IFN‐α suppressed CCL5 mRNA levels (PB) in EF in vivo. These findings along with results from parallel in vitro investigation into the effect of IFN‐α or poly I:C (TLR3‐agonist) on CCL5 gene expression in hepatic stellate cells (HSC) attest to the multi‐site involvement of these pathways in regulating fibrogenesis. In conclusion, we identified novel, reliable biomarkers for EF and exposed functional properties of the molecular network regulating CCL5 biosynthesis in peripheral or hepatic cell types with key roles in cHCV‐related liver and/or immune pathogenesis.
Asthma, atopy and exhaled nitric oxide in a cohort of 6‐yr‐old New Zealand children
Authors: Crane Julian , Lampshire Philippa , Wickens Kristin , Epton Michael , Siebers Robert , Ingham Tristram , Pattemore Philip , Town Ian ,   The Year Six New Zealand Asthma and Allergy Cohort Study Group (NZAACS6)
Published: November 2011

To cite this article: Crane J, Lampshire P, Wickens K, Epton M, Siebers R, Ingham T, Pattemore P, Town GI and The Year Six New Zealand Asthma and Allergy Cohort Study Group (NZAACS6). Asthma, atopy and exhaled nitric oxide in a cohort of 6‐yr‐old New Zealand children. Pediatric Allergy Immunology 2012: 23: 59–64.

Background:  Exhaled nitric oxide has been promoted as a non‐invasive measure of airway inflammation, with clinical utility for the diagnosis and management of asthma.

Aim:  We studied associations between exhaled nitric oxide, asthma and atopy in a variety of clinically relevant phenotypes in a cohort of 6‐yr‐old children.

Method:  Asthma was defined using standard questionnaire criteria, atopy was measured using skin prick tests (SPT) and specific IgE to common allergens, and exhaled nitric oxide was measured using a chemiluminescence analyser according to American and European Thoracic Society criteria.

Results:  Exhaled nitric oxide was strongly related to atopy and in particular to sensitization to house dust mites. Children with non‐allergic asthma had no increase in exhaled nitric oxide compared with non‐asthmatic children. Compared with children who never wheezed both late onset and persistent, wheezing was associated with increased FENO, while early transient wheezing was not. Elevated levels of exhaled nitric oxide amongst children with allergic asthma were almost entirely explained by their levels of specific IgE to aeroallergens, predominantly D pteronyssinus.

Conclusion:  Airway inflammation as measured by exhaled nitric oxide in young New Zealand children is related to their level of specific IgE to aeroallergens. This has implications for the utility of nitric oxide as a diagnostic and management tool in childhood asthma and for the importance of specific IgE as a marker of asthma severity.
Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study
Authors: Belderbos M. E. , Houben M. L. , van Bleek G. M. , Schuijff L. , van Uden N. O. P. , Bloemen‐Carlier E. M. , Kimpen J. L. L. , Eijkemans M. J. C. , Rovers M. , Bont L. J.
Published: November 2011

To cite this article: Belderbos ME, Houben ML, van Bleek GM, Schuijff L, van Uden NOP, Bloemen‐Carlier EM, Kimpen JLL, Eijkemans MJC, Rovers M, Bont LJ. Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study. Pediatric Allergy Immunology 2012: 23: 65–74.

Background:  Neonatal Toll‐like receptor (TLR) responses are biased toward Th2‐polarizing responses at birth and rapidly mature toward more balanced responses during the first month of life. Postnatal TLR maturation may be guided by environmental exposure.

Aims:  To determine the environmental determinants of neonatal TLR function.

Materials and Methods:  A prospective birth cohort study was performed in 291 healthy term neonates. Mode of delivery, breastfeeding, birth month, siblings, pets and parental smoking were analyzed in relation to neonatal innate immune parameters at the age of 1 month. Whole blood concentrations of innate immune cells were measured by flow cytometry. In vitro TLR‐mediated cytokine production was determined by ELISA.

Results:  Breastfeeding was the major determinant of neonatal innate immunity, associated with 5 (31%) of neonatal innate immune parameters, of which the association with TLR7‐mediated IL‐10 production was most significant (76 pg/ml in breastfed neonates vs. 293 pg/ml in formula‐fed neonates, p = 0.001). Of innate immune variables, TLR3‐mediated IL‐12p70 production was highly associated with environmental exposures (pets, breastfeeding and mode of delivery), whereas TLR9‐mediated cytokine responses were not associated with any environmental factor.

Conclusion:  Neonatal innate immune responses are differentially modulated by environmental exposure in the first month of life. The protective effect of breastfeeding against subsequent infections and atopy might be explained by its innate immune modulatory effects in the first month of life.
Energy requirements of puppies of two different breeds for ideal growth from weaning to 28 weeks of age
Authors: Dobenecker B. , Endres V. , Kienzle E.
Published: November 2011

To ensure an optimal growth is crucial in raising healthy dogs, especially in large and giant breeds. Dogs with a moderate growth velocity tend to have lesser problems with developmental orthopaedic diseases than those with forced or maximum weight gain. In this study, the energy needs of growing dogs from two different breeds (Beagles as a medium‐size breed and Foxhound crossbreds as a large‐size breed) to ensure a growth development as recommended by the National Research Council (NRC) were determined at the age of 6–28 weeks. After weaning at the age of 6 weeks, the food rations sufficient to meet the energy requirements of each individual puppy were adjusted every other day according to growth level, guaranteeing a development consistent with the recommended weight curve for the respective breed size. The food and therefore energy intake of the puppies was registered daily; it ranged from 0.72 to 2.34 times the maintenance requirements with little effect of age. During the whole period, however, there was a consistent breed difference: Foxhound‐Boxer‐Ingelheim Labrador crossbreds (FBIs) had higher energy intakes expressed as multiples of maintenance than Beagles, suggesting that during the major period of growth, the energy requirement is not a function of age. Adult Beagles and FBIs showed similar differences in energy requirements as already during growth as shown in this study. This indicates that breed differences in energy requirements have already to be taken into account during growth. On the other hand, the results showed clearly lower energy needs for growth in these two different breeds than recommended in the NRC.
Diet segregation between two colonies of little penguins Eudyptula minor in southeast Australia
Authors: CHIARADIA ANDRÉ , FORERO MANUELA G. , HOBSON KEITH A. , SWEARER STEPHEN E. , HUME FIONA , RENWICK LEANNE , DANN PETER
Published: November 2011

We studied foraging segregation between two different sized colonies of little penguins Eudyptula minor with overlapping foraging areas in pre‐laying and incubation. We used stomach contents and stable isotope measurements of nitrogen (δ15N) and carbon (δ13C) in blood to examine differences in trophic position, prey‐size and nutritional values between the two colonies. Diet of little penguins at St Kilda (small colony) relied heavily on anchovy while at Phillip Island (large colony), the diet was more diverse and anchovies were larger than those consumed by St Kilda penguins. Higher δ15N values at St Kilda, differences in δ13C values and the prey composition provided further evidence of diet segregation between colonies. Penguins from each colony took anchovies from different cohorts and probably different stocks, although these sites are only 70 km apart. Differences in diet were not reflected in protein levels in the blood of penguins, suggesting that variation in prey between colonies was not related to differences in nutritional value of the diet. Anchovy is currently the only available prey to penguins throughout the year and its absence could have a negative impact on penguin food supply, particularly at St Kilda where the diet is dominated by this species. While it is difficult to establish whether diet segregation is caused by inter‐ or intra‐colony competition or spatial differences in foraging areas, we have shown that colonies with broadly overlapping foraging ranges could have significant differences in trophic position, diet composition and prey size while maintaining a diet of similar nutritional value.
Consequences of grazing on the vertical transmission of a fungal Neotyphodium symbiont in an annual grass population
Authors: GARCÍA PARISI PABLO A. , CASAS CECILIA , GUNDEL PEDRO E. , OMACINI MARINA
Published: November 2011

Symbiosis between cool‐season grasses and vertically transmitted fungal endophytes are common and significantly impact on ecosystem function. This makes the understanding of the underlying mechanisms to symbiotic individuals frequency in local populations much more interesting. Most studies have been focused on the differential fitness between symbiotic and non‐symbiotic counterparts (relative fitness), barely considering other mechanisms. We performed a microcosms experiment to evaluate whether grazing alters the dynamics of the endophyte Neotyphodium occultans in the annual grass Lolium multiflorum by simultaneously modifying the relative fitness and the endophyte efficiency to be transmitted from host plants to seeds. Grazing was simulated by means of clipping and trampling on symbiotic and non‐symbiotic plants growing separately, in soils obtained from paddocks, differing in their agronomic management history (natural grassland vs. ryegrass promotion). Seed production showed a complex pattern as it depended on the symbiotic status of the plants, the level of grazing and the agro‐ecological context. Grazed plants produced three times fewer seeds than ungrazed plants only in microcosms with endophyte‐symbiotic plants in soils from ryegrass promotion. Endophyte benefits on seed production were exclusively observed in ungrazed plants in the same soil. Symbiotic plants produced symbiotic and non‐symbiotic seeds in all the treatments. While the production of non‐symbiotic seeds by these plants was not affected by grazing and the soil, grazing reduced the production of symbiotic seeds in both contexts. Grazing negative effect on the density of fully infected spikes determined a significant increment in the transmission failures which were not modified by agro‐ecological contexts. Therefore, grazing can modulate symbiosis dynamics through reducing seed production and endophyte transmission efficiency. Transmission has been disregarded, but it is a context‐dependent process that could lead to a gradual reduction in the symbiotic plants frequency in a population if the mutualism effectiveness does not outweigh transmission failures.