bluuebunny/crossref_metadata_2025 huggingface dataset:
PRIVATE AUTONOMY AND MARITAL PROPERTY AGREEMENTS
Authors: Sanders Anne
Published: August 2010

After the Court of Appeal decision in Radmacher v Granatino, the question whether English law should introduce enforceable pre-nuptial or marital property agreements came into focus again. Taking the decision as a starting point, the article argues in favour of introducing such agreements. Adopting a comparative approach, the article explains how such agreements are used in Germany and demonstrates that the idea of private autonomy, which has been regarded as the basis of pre-nuptial property agreements in Germany since the 19th century, can explain why couples should be allowed to make their own decisions with respect to the financial consequences of the breakdown of their relationship. Analysis of the different notions of contract in German and English law as well as comparing marriage with partnerships and other long-term contractual relationships illustrates not only the historical reasons why such agreements have not been allowed so far, but also helps to understand what safeguards the legislator and the judiciary could apply to ensure that parties do not abuse their freedom.
ELIMINATING TRADE REMEDIES FROM THE WTO: LESSONS FROM REGIONAL TRADE AGREEMENTS
Authors: Voon Tania
Published: August 2010

As the global financial crisis threatens to manifest in enhanced protectionism, the economic irrationality of dumping, countervailing, and global safeguard measures (so-called ‘trade remedies’) should be of increased concern to the Members of the World Trade Organization (‘WTO’). Long tolerated under the WTO agreements and perhaps a necessary evil to facilitate multilateral trade liberalization, elimination of trade remedies is far from the agenda of WTO negotiators. However, a small number of regional trade agreements offer a model for reducing the use of trade remedies among WTO Members in the longer term, consistent with WTO rules and broader public international law.
INCOHERENT AND INEFFECTIVE: THE CONCEPT OF PERSISTENT OBJECTOR REVISITED
Authors: Dumberry Patrick
Published: August 2010

A rule of customary international law is binding upon all States. One controversial question is whether a State should be permitted not to be bound by such a rule in the event that it objected to it in the early stage of its formation and did so constantly thereafter. This is the theory of the ‘persistent objector’. Articles recently published about the theory focus on its specific application in different areas of international law, including international investment law,1 international humanitarian law2 and human rights law.3 The present article intends to examine the concept of persistent objector in general international law.4
II. EUROPEAN COURT OF HUMAN RIGHTS MEDVEDYEV ET AL V FRANCE (GRAND CHAMBER, APPLICATION NO 3394/03) JUDGMENT OF 29 MARCH 2010
Authors: Papastavridis Efthymios
Published: August 2010

On 29 March 2010, the European Court of Human Rights (ECtHR), sitting as a Grand Chamber, delivered its Judgment in the Medvedyev v France case, which involved the interdiction and the exercise of enforcement jurisdiction over a drug smuggling vessel on the high seas. The case was referred by both the applicants and the Respondent State to the Grand Chamber, following the Judgment of a Chamber of the Fifth Section of the Court, on 10 July 2008. The Grand Chamber accepted this referral and the public hearing took place on 6 May 2009. This decision is of considerable importance as one of the very few decisions of the Strasbourg Court which has touched upon issues pertaining to the law of the sea, let alone to interdiction of vessels on the high seas, and the only case to have found a violation of the Convention on the part of the interdicting State, namely France.
III. THE MAKING AND UNMAKING OF THE COPENHAGEN ACCORD
Authors: Rajamani Lavanya
Published: August 2010

The last two years have witnessed a flurry of diplomatic activity on climate change. In addition to the 16 weeks of scheduled inter-governmental negotiations under the auspices of the UN Framework Convention on Climate Change (FCCC), meetings, many at a Ministerial level, were convened by the G-8, the Major Economies Forum, the UN Secretary General, and Denmark, the host of the 15th Conference of Parties (COP-15) to the FCCC. Notwithstanding regular and intense engagement at the highest-level many fundamental disagreements remained in the lead up to COP-15, including on the future (or lack thereof) of the Kyoto Protocol, the legal form and architecture of the future legal regime, and the nature and extent of differential treatment between developed and developing countries.
Population genetics of lichen-forming fungi – a review
Authors: WERTH Silke
Published: August 2010

Population genetics investigates the distribution of genetic variation in natural populations and the genetic differentiation among populations. Lichen-forming fungi are exciting subjects for population genetic studies due to their obligate symbiosis with a green-algal and/or cyanobacterial photobiont, and because their different reproductive strategies could influence fungal genetic structures in various ways. In this review, first, I briefly summarize the results from studies of chemotype variation in populations of lichen-forming fungi. Second, I compare and evaluate the DNA-based molecular tools available for population genetics of lichen-forming fungi. Third, I review the literature available on the genetic structure of lichen fungi to show general trends. I discuss some fascinating examples, and point out directions for future research.
Gloniella graphidoidea Rehm, another species of the Hysteriaceae associated with algae
Authors: MESSUTI María Inés , LORENZO Laura Emma
Published: August 2010

Hysterium graphideum Speg. is proposed as a synonym of Gloniella graphidoidea Rehm. During the study of the types of both names, the presence of algae associated with the fungal hyphae was found. The main morphological and anatomical characters, and the ecology of the species are presented.
Grazing damage in the old forest lichenLobaria pulmonariaincreases with gastropod abundance in deciduous forests
Authors: VATNE Steinar , SOLHØY Torstein , ASPLUND Johan , GAUSLAA Yngvar
Published: August 2010

Gastropod abundance was quantified in forest litter around 33 trees harbouringLobaria pulmonariain southern Norway. In total, 1709 snails representing 28 species were found, and the number of snail species strongly increased with the total number of specimens found. Number of snail species, as well as snail abundance, was highest around trees on high pH soils. There was a positive relationship between number of snail specimens and cover of grazing traces onL. pulmonaria, presumably because calcareous soils facilitate both litter dwelling and climbing gastropods. The results suggest that gastropods may limit the distribution ofL. pulmonariain calcareous broad-leaved forests.
The question of evidence: current worldviews in environmental design research and practice
Authors: Moore Keith Diaz , Geboy Lyn
Published: August 2010

The popularity of the concept of evidence-based design (EBD) has exploded over the past five years, picking up speed as a topic of attention in environmental design conferences, papers and articles, and books. Rooted in the healthcare environment, the EBD concept has now bridged out to design of long-term care settings, housing and workplaces, as well as facilities management. While evidence-based design is indeed a seductive term for those of us interested in advancing research-informed design – portending linkages between research-derived evidence and environmental design – we cautiously note that, as of this writing, in its current conceptualisation, its clout is stronger than its clarity. This paper is a clarion invitation to the environmental design research community to consider the concept of evidence-based design as emergent, warranting careful, critical examination regarding its meaning and underlying assumptions.
Environmental retrofit: building integrated passive cooling in housing
Authors: Schiano-Phan Rosa
Published: August 2010

As the existing housing stock ages throughout Europe, retrofitting offers many opportunities for the substantial improvement of the energy performance of residential buildings and the provision of sustainable alternatives to conventional heating and cooling. The effect of global warming is leading to a widespread use of air conditioning in existing and new residential buildings. This potentially implies an increase in cooling energy and adverse environmental effects on an unprecedented scale. In the hot and dry climate of many south European cities, this could be avoided with the use of an innovative wall integrated passive evaporative cooling system, which harnesses air, water and porous ceramic to provide comfortable indoor conditions. Dr Rosa Schiano-Phan discusses the applicability of such a system to the urban context of Seville in the light of the current Spanish regulatory framework and recent developments of European energy performance standards.
Pc5 geomagnetic pulsations, pulsating particle precipitation, and VLF chorus: Case study on 24 November 2006
Authors: Manninen J. , Kleimenova N. G. , Kozyreva O. V. , Turunen T.
Published: August 2010

The event (24 November 2006, ∼0400–0500 UT) of the simultaneous observations of Pc5 ULF geomagnetic pulsations, electron precipitation (CNA riometer absorption), and whistler‐mode chorus, as well as solar wind (SW) and IMF parameters have been analyzed based on the data from IMAGE magnetometers, Finnish riometer array, and temporal VLF station. The visible correlation between the simultaneous occurrence of several minutes scale patches of chorus and pulsating CNA enhancements was found. The dynamic spectra of the riometer data showed a maximum at ∼3.5 mHz in the first half‐hour interval and at ∼2.0 mHz in the second one, while the ULF pulsation spectra exhibit these two maxima in both intervals simultaneously. In the first time interval, the Pc5 pulsations at ∼3.5 mHz demonstrated the typical FLR feature. The SW dynamic pressure fluctuations showed a broad (1.5–3.5 mHz) spectral maximum in the first interval; however, in the second one, the simultaneous oscillations at ∼2.0 mHz were observed in SW pressure and in IMF Bz. The similar ∼2.0 mHz peak has been found in the spectra of Pc5 pulsations from auroral zone to the equator, in riometer absorption, and in VLF chorus power. We suggest that the modulation of particle precipitation and whistler‐mode chorus patches was caused by the 2.0 mHz compressional component of Pc5 poloidal geomagnetic pulsations driven in the magnetosphere by SW dynamic pressure and IMF Bz disturbances.
Toward improved identification of hydrological models: A diagnostic evaluation of the “abcd” monthly water balance model for the conterminous United States
Authors: Martinez Guillermo F. , Gupta Hoshin V.
Published: August 2010

Continental‐scale water balance (WB) assessments are important for characterizing hydrologic systems and understanding regional‐scale dynamics and for identifying hydroclimatic trends and systematic data biases. However, it is not clear whether existing models can reproduce the catchment dynamics observed in nature. Nor has our ability to evaluate model results kept pace with computational and data processing abilities. Consequently, methods for diagnostic model evaluation and improvement remain weak. There is a need for well‐conceived, systematic strategies to guide model selection, establish data requirements, estimate parameters, and evaluate and track model performance. We examine these challenges in the context of monthly WB modeling for the conterminous United States by applying the “abcd” model to 764 catchments selected for their comprehensive coverage of hydrogeological conditions. By examining diagnostically relevant components of model error, we evaluate the details of its spatial variability across the continental United States. Model performance, parameters, and structures are found to be correlated with hydroclimatic variables. However, our results indicate a need for the conventional identification approach to be improved. Because they do not constrain models to reproduce important hydrological behaviors, reported values of NSE or r2 performance can be misleading. Further, we must establish suitable model hypotheses with appropriate spatiotemporal scale for each hydroclimatic region. Until these issues are resolved, such models cannot reliably be used to infer the spatiotemporal dynamics of continental‐scale water balance or to regionalize model structures and parameters to ungaged locations.
Prime‐boost vaccinations using recombinant flavivirus replicon and vaccinia virus vaccines: an ELISPOT analysis
Authors: Rattanasena Paweena , Anraku Itaru , Gardner Joy , Le Thuy T , Wang Xiang Ju , Khromykh Alexander A , Suhrbier Andreas
Published: August 2010

Recombinant Kunjin replicon virus‐like particle (VLP), vaccinia virus (rVV) and DNA vaccines were tested in a large series of prime‐boost vaccinations using interferon (IFN)γ ELISPOT assays that reflected effector (E), effector memory (EM) and central memory (CM) responses. All vaccine constructs encoded the murine polytope immunogen and responses to four CD8 T‐cell epitopes (TYQRTRALV, SYIPSAEKI, YPHFMPTNL and RPQASGVYM) were measured. VLP/rVV out performed (by 14‐ to 20‐fold) DNA/rVV for induction of CM responses, whereas EM responses were only marginally increased. DNA/VLP induced more EM, but not CM responses, than VLP alone, illustrating that DNA priming is not universally beneficial. rVV/VLP gave comparable results to VLP/rVV combinations, although the former induced approximately threefold more E responses, illustrating the utility of poxvirus priming in this setting. Although higher doses of VLP and rVV increased responses after single immunizations, such dose increases provided only marginal benefit in heterologous prime‐boost settings. Triple combinations also provided no benefit over two vaccinations. DNA vaccination was associated with broad CM, but not EM responses, and the breadth of EM and E responses was significantly improved by increasing viral vector dose. VLP/rVV, rather than DNA priming, induced T cells with consistently high IFNγ secretion profiles across all ELISPOT measures. Vector‐specific CD8 T‐cell responses generally correlated well with immunogen‐specific responses, although, as expected, single use of each vector reduced the relative levels of vector‐specific responses. These experiments illustrate the utility of replicons in heterologous prime‐boost vaccinations, and illustrate the diversity of data that can be obtained from ELISPOT analyses.
A canine
Arylsulfatase G
(
ARSG
) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis
Authors: Abitbol Marie , Thibaud Jean-Laurent , Olby Natasha J. , Hitte Christophe , Puech Jean-Philippe , Maurer Marie , Pilot-Storck Fanny , Hédan Benoit , Dréano Stéphane , Brahimi Sandra , Delattre Delphine , André Catherine , Gray Françoise , Delisle Françoise , Caillaud Catherine , Bernex Florence , Panthier Jean-Jacques , Aubin-Houzelstein Geneviève , Blot Stéphane , Tiret Laurent
Published: August 2010

Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the
Arylsulfatase G
(
ARSG
) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.
Predictable waves of sequential forest degradation and biodiversity loss spreading from an African city
Authors: Ahrends Antje , Burgess Neil D. , Milledge Simon A. H. , Bulling Mark T. , Fisher Brendan , Smart James C. R. , Clarke G. Philip , Mhoro Boniface E. , Lewis Simon L.
Published: August 2010

Tropical forest degradation emits carbon at a rate of ~0.5 Pg·y−1, reduces biodiversity, and facilitates forest clearance. Understanding degradation drivers and patterns is therefore crucial to managing forests to mitigate climate change and reduce biodiversity loss. Putative patterns of degradation affecting forest stocks, carbon, and biodiversity have variously been described previously, but these have not been quantitatively assessed together or tested systematically. Economic theory predicts a systematic allocation of land to its highest use value in response to distance from centers of demand. We tested this theory to see if forest exploitation would expand through time and space as concentric waves, with each wave targeting lower value products. We used forest data along a transect from 10 to 220 km from Dar es Salaam (DES), Tanzania, collected at two points in time (1991 and 2005). Our predictions were confirmed: high-value logging expanded 9 km·y−1, and an inner wave of lower value charcoal production 2 km·y−1. This resource utilization is shown to reduce the public goods of carbon storage and species richness, which significantly increased with each kilometer from DES [carbon, 0.2 Mg·ha−1; 0.1 species per sample area (0.4 ha)]. Our study suggests that tropical forest degradation can be modeled and predicted, with its attendant loss of some public goods. In sub-Saharan Africa, an area experiencing the highest rate of urban migration worldwide, coupled with a high dependence on forest-based resources, predicting the spatiotemporal patterns of degradation can inform policies designed to extract resources without unsustainably reducing carbon storage and biodiversity.
Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays
Authors: Saliba Antoine-Emmanuel , Saias Laure , Psychari Eleni , Minc Nicolas , Simon Damien , Bidard François-Clément , Mathiot Claire , Pierga Jean-Yves , Fraisier Vincent , Salamero Jean , Saada Véronique , Farace Françoise , Vielh Philippe , Malaquin Laurent , Viovy Jean-Louis
Published: August 2010

We propose a unique method for cell sorting, “Ephesia,” using columns of biofunctionalized superparamagnetic beads self-assembled in a microfluidic channel onto an array of magnetic traps prepared by microcontact printing. It combines the advantages of microfluidic cell sorting, notably the application of a well controlled, flow-activated interaction between cells and beads, and those of immunomagnetic sorting, notably the use of batch-prepared, well characterized antibody-bearing beads. On cell lines mixtures, we demonstrated a capture yield better than 94%, and the possibility to cultivate in situ the captured cells. A second series of experiments involved clinical samples—blood, pleural effusion, and fine needle aspirates— issued from healthy donors and patients with B-cell hematological malignant tumors (leukemia and lymphoma). The immunophenotype and morphology of B-lymphocytes were analyzed directly in the microfluidic chamber, and compared with conventional flow cytometry and visual cytology data, in a blind test. Immunophenotyping results using Ephesia were fully consistent with those obtained by flow cytometry. We obtained in situ high resolution confocal three-dimensional images of the cell nuclei, showing intranuclear details consistent with conventional cytological staining. Ephesia thus provides a powerful approach to cell capture and typing allowing fully automated high resolution and quantitative immunophenotyping and morphological analysis. It requires at least 10 times smaller sample volume and cell numbers than cytometry, potentially increasing the range of indications and the success rate of microbiopsy-based diagnosis, and reducing analysis time and cost.
Agricultural management explains historic changes in regional soil carbon stocks
Authors: van Wesemael Bas , Paustian Keith , Meersmans Jeroen , Goidts Esther , Barancikova Gabriela , Easter Mark
Published: August 2010

Agriculture is considered to be among the economic sectors having the greatest greenhouse gas mitigation potential, largely via soil organic carbon (SOC) sequestration. However, it remains a challenge to accurately quantify SOC stock changes at regional to national scales. SOC stock changes resulting from SOC inventory systems are only available for a few countries and the trends vary widely between studies. Process-based models can provide insight in the drivers of SOC changes, but accurate input data are currently not available at these spatial scales. Here we use measurements from a soil inventory dating from the 1960s and resampled in 2006 covering the major soil types and agricultural regions in Belgium together with region-specific land use and management data and a process-based model. The largest decreases in SOC stocks occurred in poorly drained grassland soils (clays and floodplain soils), consistent with drainage improvements since 1960. Large increases in SOC in well drained grassland soils appear to be a legacy effect of widespread conversion of cropland to grassland before 1960. SOC in cropland increased only in sandy lowland soils, driven by increasing manure additions. Modeled land use and management impacts accounted for more than 70% of the variation in observed SOC changes, and no bias could be demonstrated. There was no significant effect of climate trends since 1960 on observed SOC changes. SOC monitoring networks are being established in many countries. Our results demonstrate that detailed and long-term land management data are crucial to explain the observed SOC changes for such networks.
De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific
Authors: Majka Susan M. , Fox Keith E. , Psilas John C. , Helm Karen M. , Childs Christine R. , Acosta Alistaire S. , Janssen Rachel C. , Friedman Jacob E. , Woessner Brian T. , Shade Theodore R. , Varella-Garcia Marileila , Klemm Dwight J.
Published: August 2010

It is generally assumed that white adipocytes arise from resident adipose tissue mesenchymal progenitor cells. We challenge this paradigm by defining a hematopoietic origin for both the de novo development of a subset of white adipocytes in adults and a previously uncharacterized adipose tissue resident mesenchymal progenitor population. Lineage and cytogenetic analysis revealed that bone marrow progenitor (BMP)-derived adipocytes and adipocyte progenitors arise from hematopoietic cells via the myeloid lineage in the absence of cell fusion. Global gene expression analysis indicated that the BMP-derived fat cells are bona fide adipocytes but differ from conventional white or brown adipocytes in decreased expression of genes involved in mitochondrial biogenesis and lipid oxidation, and increased inflammatory gene expression. The BMP-derived adipocytes accumulate with age, occur in higher numbers in visceral than in subcutaneous fat, and in female versus male mice. BMP-derived adipocytes may, therefore, account in part for adipose depot heterogeneity and detrimental changes in adipose metabolism and inflammation with aging and adiposity.
Direct inhibition of P/Q-type voltage-gated Ca
2+
channels by Gem does not require a direct Gem/Ca
v
β interaction
Authors: Fan Mingming , Buraei Zafir , Luo Huai-Rong , Levenson-Palmer Rose , Yang Jian
Published: August 2010

The Rem, Rem2, Rad, and Gem/Kir (RGK) family of small GTP-binding proteins potently inhibits high voltage-activated (HVA) Ca
2+
channels, providing a powerful means of modulating neural, endocrine, and muscle functions. The molecular mechanisms of this inhibition are controversial and remain largely unclear. RGK proteins associate directly with Ca
2+
channel β subunits (Ca
v
β), and this interaction is widely thought to be essential for their inhibitory action. In this study, we investigate the molecular underpinnings of Gem inhibition of P/Q-type Ca
2+
channels. We find that a purified Gem protein markedly and acutely suppresses P/Q channel activity in inside-out membrane patches, that this action requires Ca
v
β but not the Gem/Ca
v
β interaction, and that Gem coimmunoprecipitates with the P/Q channel α
1
subunit (Ca
v
α
1
) in a Ca
v
β-independent manner. By constructing chimeras between P/Q channels and Gem-insensitive low voltage-activated T-type channels, we identify a region encompassing transmembrane segments S1, S2, and S3 in the second homologous repeat of Ca
v
α
1
critical for Gem inhibition. Exchanging this region between P/Q and T channel Ca
v
α
1
abolishes Gem inhibition of P/Q channels and confers Ca
v
β-dependent Gem inhibition to a chimeric T channel that also carries the P/Q I-II loop (a cytoplasmic region of Ca
v
α
1
that binds Ca
v
β). Our results challenge the prevailing view regarding the role of Ca
v
β in RGK inhibition of high voltage-activated Ca
2+
channels and prompt a paradigm in which Gem directly binds and inhibits Ca
v
β-primed Ca
v
α
1
on the plasma membrane.
Prefrontal–striatal pathway underlies cognitive regulation of craving
Authors: Kober Hedy , Mende-Siedlecki Peter , Kross Ethan F. , Weber Jochen , Mischel Walter , Hart Carl L. , Ochsner Kevin N.
Published: August 2010

The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with (
i
) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and (
ii
) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.
Age-induced disruption of selective olfactory bulb synaptic circuits
Authors: Richard Marion B. , Taylor Seth R. , Greer Charles A.
Published: August 2010

Little is known about how normal aging affects the brain. Recent evidence suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle and still controversial, region- and layer-specific alterations of neuron morphology and synapses are reported during aging, leading to the notion that discrete changes in neural circuitry may underlie age-related cognitive deficits. Although deficits in sensory function suggest that primary sensory cortices are affected by aging, our understanding of the age-related cellular and molecular changes is sparse. To assess the effect of aging on the organization of olfactory bulb (OB) circuitry, we carried out quantitative morphometric analyses in the mouse OB at 2, 6, 12, 18, and 24 mo. Our data establish that the volumes of the major OB layers do not change during aging. Parallel to this, we are unique in demonstrating that the stereotypic glomerular convergence of M72-GFP OSN axons in the OB is preserved during aging. We then provide unique evidence of the stability of projection neurons and interneurons subpopulations in the aging mouse OB, arguing against the notion of an age-dependent widespread loss of neurons. Finally, we show ultrastructurally a significant layer-specific loss of synapses; synaptic density is reduced in the glomerular layer but not the external plexiform layer, leading to an imbalance in OB circuitry. These results suggest that reduction of afferent synaptic input and local modulatory circuit synapses in OB glomeruli may contribute to specific age-related alterations of the olfactory function.
Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development
Authors: Ueda Takeshi , Sasaki Masato , Elia Andrew J. , Chio Iok In Christine , Hamada Koichi , Fukunaga Rikiro , Mak Tak W.
Published: August 2010

MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) are protein-serine/threonine kinases that are activated by ERK or p38 and phosphorylate eIF4E, which is involved in cap-dependent translation initiation. However, Mnk1/2 double knockout (Mnk-DKO) mice show normal cell growth and development despite an absence of eIF4E phosphorylation. Here we show that the tumorigenesis occurring in the Lck-Pten mouse model (referred to here as tPten
−/−
mice) can be suppressed by the loss of Mnk1/2. Phosphorylation of eIF4E was greatly enhanced in lymphomas of parental tPten
−/−
mice compared with lymphoid tissues of wild-type mice, but was totally absent in lymphomas of tPten
−/−
; Mnk-DKO mice. Notably, stable knockdown of Mnk1 in the human glioma cell line U87MG resulted in dramatically decreased tumor formation when these cells were injected into athymic
nude
mice. Our data demonstrate an oncogenic role for Mnk1/2 in tumor development, and highlight these molecules as potential anticancer drug targets that could be inactivated with minimal side effects.
Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair
Authors: Lee J.-H. , Choy M. L. , Ngo L. , Foster S. S. , Marks Paul A.
Published: August 2010

Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and nonhistone proteins, which affect gene expression, cell cycle progression, cell migration, and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here, we show that the HDACi, vorinostat (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs) in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to cancer cells repair the DSBs despite continued culture with vorinostat. In transformed cells, phosphorylated H2AX (γH2AX), a marker of DNA DSBs, levels increased with continued culture with vorinostat, whereas in normal cells, this marker decreased with time. Vorinostat induced the accumulation of acetylated histones within 30 min, which could alter chromatin structure-exposing DNA to damage. After a 24-h culture of cells with vorinostat, and reculture without the HDACi, γH2AX was undetectable by 2 h in normal cells, while persisting in transformed cells for the duration of culture. Further, we found that vorinostat suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not cancer cells can repair. This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death.
Limited taste discrimination in
Drosophila
Authors: Masek Pavel , Scott Kristin
Published: August 2010

In the gustatory systems of mammals and flies, different populations of sensory cells recognize different taste modalities, such that there are cells that respond selectively to sugars and others to bitter compounds. This organization readily allows animals to distinguish compounds of different modalities but may limit the ability to distinguish compounds within one taste modality. Here, we developed a behavioral paradigm in
Drosophila melanogaster
to evaluate directly the tastes that a fly distinguishes. These studies reveal that flies do not discriminate among different sugars, or among different bitter compounds, based on chemical identity. Instead, flies show a limited ability to distinguish compounds within a modality based on intensity or palatability. Taste associative learning, similar to olfactory learning, requires the mushroom bodies, suggesting fundamental similarities in brain mechanisms underlying behavioral plasticity. Overall, these studies provide insight into the discriminative capacity of the
Drosophila
gustatory system and the modulation of taste behavior.
Structural basis for the glucan phosphatase activity of Starch Excess4
Authors: Vander Kooi Craig W. , Taylor Adam O. , Pace Rachel M. , Meekins David A. , Guo Hou-Fu , Kim Youngjun , Gentry Matthew S.
Published: August 2010

Living organisms utilize carbohydrates as essential energy storage molecules. Starch is the predominant carbohydrate storage molecule in plants while glycogen is utilized in animals. Starch is a water-insoluble polymer that requires the concerted activity of kinases and phosphatases to solubilize the outer surface of the glucan and mediate starch catabolism. All known plant genomes encode the glucan phosphatase Starch Excess4 (SEX4). SEX4 can dephosphorylate both the starch granule surface and soluble phosphoglucans and is necessary for processive starch metabolism. The physical basis for the function of SEX4 as a glucan phosphatase is currently unclear. Herein, we report the crystal structure of SEX4, containing phosphatase, carbohydrate-binding, and C-terminal domains. The three domains of SEX4 fold into a compact structure with extensive interdomain interactions. The C-terminal domain of SEX4 integrally folds into the core of the phosphatase domain and is essential for its stability. The phosphatase and carbohydrate-binding domains directly interact and position the phosphatase active site toward the carbohydrate-binding site in a single continuous pocket. Mutagenesis of the phosphatase domain residue F167, which forms the base of this pocket and bridges the two domains, selectively affects the ability of SEX4 to function as a glucan phosphatase. Together, these results reveal the unique tertiary architecture of SEX4 that provides the physical basis for its function as a glucan phosphatase.
Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in
Drosophila
Authors: Tanji Takahiro , Yun Eun-Young , Ip Y. Tony
Published: August 2010

The innate immune response in
Drosophila
involves the inducible expression of antimicrobial peptide genes mediated by the Toll and IMD signaling pathways. Dorsal and DIF act downstream of Toll, whereas Relish acts downstream of IMD to regulate target gene expression. Dorsal, DIF, and Relish are NF-κB-related transcription factors and function as obligate dimers, but it is not clear how the various dimer combinations contribute to the innate immune response. We systematically examined the dimerization tendency of these proteins through the use of transgenic assays. The results show that all combinations of homo- and heterodimers are formed, but with varying degrees of efficiency. The formation of the DIF-Relish heterodimer is particularly interesting because it may mediate signaling for the seemingly independent Toll and IMD pathways. By incorporating a flexible peptide linker, we specifically tested the functions of the DIF^Relish (a ^ sign represents the peptide linker) linked heterodimer. Our results demonstrate that the linked heterodimer can activate target genes of both the Toll and IMD pathways. The DIF and Relish complex is detectable in whole animal extracts, suggesting that this heterodimer may function in vivo to increase the spectrum and level of antimicrobial peptide production in response to different infections.
Combining antiangiogenic therapy with immunotherapy exerts better therapeutical effects on large tumors in a woodchuck hepatoma model
Authors: Huang Kai-Wen , Wu Hui-Lin , Lin Hsiu-Lin , Liang Po-Chin , Chen Pei-Jer , Chen Shih-Hui , Lee Hsin-I , Su Pei-Yi , Wu Wen-Hsuan , Lee Po-Huang , Hwang Lih-Hwa , Chen Ding-Shinn
Published: August 2010

Cytokine and antiangiogenic gene therapies have proved effective in implanted hepatocellular carcinoma (HCC) models in which small tumor burdens were established in small rodents. These models, however, may not reflect human HCCs, which are frequently detected at a stage when tumors are large and multifocal. In addition, HCC in patients is often associated with viral hepatitis. To investigate the effectiveness of a mixture type of gene therapy strategy on large tumor burdens, we used the woodchuck model in which woodchuck hepatitis virus-induced HCCs are large and multifocal, simulating the conditions in humans. Adenoviruses encoding antiangiogenic factors (pigment epithelium-derived factor and endostatin) or cytokines (GM-CSF and IL-12) were delivered via the hepatic artery separately or in combination into woodchuck livers bearing HCCs. Our results showed that the mixture type of strategy, which contained two cytokines and two antiangiogenic factors, had better antitumor effects on large tumors as compared with monotherapy either with antiangiogenic or cytokine genes. The immunotherapy recruited significant levels of CD3+T cells that infiltrated the tumors, whereas the antiangiogenesis-based therapy significantly reduced tumor vasculature. The mixture type of gene therapy achieved both effects. In addition, it induced high levels of natural killer cells and apoptotic cells and reduced the levels of immunosuppressive effectors in the tumor regions. Hence, antiangiogenic therapy may provide the advantage of reducing immune tolerance in large tumors, making them more vulnerable to the immune reactions. Our study implies that in the future, the combination therapy may prove effective for the treatment of patients with advanced HCC.
NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain
Authors: Kim Donghoon , You Byunghyun , Jo Eun-Kyeong , Han Sang-Kyou , Simon Melvin I. , Lee Sung Joong
Published: August 2010

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain.
IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells
Authors: Grinberg-Bleyer Yenkel , Baeyens Audrey , You Sylvaine , Elhage Rima , Fourcade Gwladys , Gregoire Sylvie , Cagnard Nicolas , Carpentier Wassila , Tang Qizhi , Bluestone Jeffrey , Chatenoud Lucienne , Klatzmann David , Salomon Benoît L. , Piaggio Eliane
Published: August 2010

Regulatory T cells (T reg cells) play a major role in controlling the pathogenic autoimmune process in type 1 diabetes (T1D). Interleukin 2 (IL-2), a cytokine which promotes T reg cell survival and function, may thus have therapeutic efficacy in T1D. We show that 5 d of low-dose IL-2 administration starting at the time of T1D onset can reverse established disease in NOD (nonobese diabetic) mice, with long-lasting effects. Low-dose IL-2 increases the number of T reg cells in the pancreas and induces expression of T reg cell–associated proteins including Foxp3, CD25, CTLA-4, ICOS (inducible T cell costimulator), and GITR (glucocorticoid-induced TNF receptor) in these cells. Treatment also suppresses interferon γ production by pancreas-infiltrating T cells. Transcriptome analyses show that low-dose IL-2 exerts much greater influence on gene expression of T reg cells than effector T cells (T eff cells), suggesting that nonspecific activation of pathogenic T eff cells is less likely. We provide the first preclinical data showing that low-dose IL-2 can reverse established T1D, suggesting that this treatment merits evaluation in patients with T1D.
A retrobulbar meningioma as a cause of unilateral exophthalmos and blindness in a horse
Authors: Naylor R. J. , Dunkel B. , Dyson S. , Paz‐Penuelas M. P. , Dobson J.
Published: August 2010

This report describes the unusual diagnosis of a retrobulbar syncytial meningioma in a 16‐year‐old Thoroughbred gelding. The horse initially presented with unilateral left sided exophthalmos and apparent blindness characterised by unilaterally absent menace and pupillary light responses. Magnetic resonance imaging (MRI) identified a well‐defined soft tissue mass intimately associated with the optic nerve. Based on the characteristic MRI appearance, a meningioma was suspected. The eye was enucleated under general anaesthesia and partial excision of the mass was achieved. Histopathology confirmed the diagnosis and the horse underwent a course of adjuvant radiotherapy. Twelve months following surgery the horse is back in work, no neurological abnormalities have been detected and follow‐up computed tomographic imaging of the skull has revealed mild bone sclerosis with no remnants of the mass identified.
Taking children's rights seriously
Authors: FREEMAN M. D. A.
Published: August 2010

SUMMARY. How are we to justify our criticisms of current policies in relation to children? This paper, delivered as the Fourth Brian Jackson Memorial Lecture at Huddersfield Polytechnic on 6 November 1987, argues that we need to address the questions of why we ought to take children's rights seriously and of how this can be done. The article examines the moral grounds for rights for children and concludes by suggesting some institutional changes including the establishment of a Children's Ombudsperson. The suggestion is also made that a ‘child impact statement’ should be attached to all new legislation and other major policy statements.
Residential care and education
Authors: JACKSON SONIA
Published: August 2010

SUMMARY. Children in care have a poor record of achievement in school. Those in residential care face particular difficulties, arising from changes of placement, inadequate liaison between children's homes and schools, low expectations among care and school staff, and an environment in which educational needs are not given priority. The experience of one voluntary children's home suggests some ways in which these disadvantages may be overcome.
Groupwork as a response to a structural analysis of child abuse
Authors: MULLENDER AUDREY
Published: August 2010

SUMMARY. This paper considers an appropriate form of intervention with parents accused of physically abusing their children where structural pressures are seen as the predominant problem. Traditional practice is regarded as too prone to individualised explanations and responses. Groupwork is therefore proposed as the method of choice and, within this, the self‐directed model is shown to offer particular advantages. An account of a particular group is given, showing both the groupworkers' and the group members' aims for the group. The results of the group are outlined, and are shown to have included important practical gains as well as increases in confidence and self‐esteem for the group members
The early history of Scottish child welfare
Authors: HILL MALCOLM , MURRAY KATHLEEN , RANKIN JUDITH
Published: August 2010

SUMMARY. There is a growing interest in the history of childhood and child care. This article brings together from disparate sources some of the details and themes concerning the emergence and development of public and voluntary child welfare in Scotland. Particular attention is given to residential and foster care arrangements under the Poor Law and to the influence of ‘philanthropic’ individuals and organisations. Comparative references are made to the contemporary situation in England and Wales and to present day practice.
The abuse of children in out of home care
Authors: NUNNO MICHAEL , RINDFLEISCH NOLAN
Published: August 2010

SUMMARY: One of the major paradoxes in child protective services in the United States is that children removed from their homes on protective orders and placed in foster and group care face continued abuse. These children are reported at two to three times the rates of children living with their families.

Investigations are performed by the very system that marks placements. In the US, some recommend resolving these problems by withdrawing from the active protection of children in care. Others hold that because children are in the care and custody of the state, and demand a higher standard of care, specialised prevention, identification. reporting and investigation initiatives are necessary to ensure their safety. This has important implications for other countries, especially the United Kingdom with its recent spate of inquiries into abuse in residential care.
Educational Attainment and Stability in Long‐Term Foster Care
Authors: Aldgate Jane , Colton Matthew , Ghate Deborah , Heath Anthony
Published: August 2010

SUMMARY. This paper explores the relationship between the reading attainment of a group of 8–14 year olds in long‐term foster care and factors in their histories and current home environments. The findings suggest that children's early histories before entry to care may have an effect on their educational attainment in middle childhood. Some amelioration of early childhood experience may be found in a stable foster home placement which has an expectation of permanence. The type of permanent placement seems less important than the expectation of stability. There was no difference in progress between children where the eventual outcome might be adoption or custodianship and those who would remain foster children. Of especial interest was the fact that the foster children's educational attainment was not related either positively or negatively to contact with their birth parents.