bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle
Authors: Protopopescu Xenia , Pan Hong , Altemus Margaret , Tuescher Oliver , Polanecsky Margaret , McEwen Bruce , Silbersweig David , Stern Emily
Published: October 2005

The orbitofrontal cortex (OFC) has been implicated in the representation of emotional stimuli, assignment of emotional valence/salience to stimuli, stimulus-reinforcement association learning, motivation, and socio-emotional control. Using functional magnetic resonance imaging in female subjects without premenstrual mood symptoms, we found that OFC activity to emotional linguistic stimuli varies depending on the menstrual cycle phase. Specifically, anterior-medial OFC activity for negative vs. neutral stimuli was increased premenstrually and decreased postmenstrually. The inverse pattern was seen in the lateral OFC. These findings suggest that specific subregional OFC activity to emotional stimuli is modulated across the menstrual cycle. The data also demonstrate that menstrual cycle phase is an important consideration in further studies attempting to elucidate the neural substrates of affective representation.
A hypervariable N-terminal region of
Yersinia
LcrV determines Toll-like receptor 2-mediated IL-10 induction and mouse virulence
Authors: Sing Andreas , Reithmeier-Rost Dagmar , Granfors Kaisa , Hill Jim , Roggenkamp Andreas , Heesemann Jürgen
Published: October 2005

The virulence antigen LcrV of
Yersinia enterocolitica
O:8 induces IL-10 in macrophages via Toll-like receptor 2 (TLR2). The TLR2-active region of LcrV is localized within its N-terminal amino acids (aa) 31-57. Sequencing of codons 25-92 of the
lcrV
gene from 59 strains of the three pathogenic
Yersinia
species revealed a hypervariable hotspot within aa 40-61. According to these sequence differences, seven LcrV groups were identified, with
Y. pestis
and
Y. pseudotuberculosis
represented in group I and the other six distributed within
Y. enterocolitica
. By testing LcrV sequence-derived synthetic oligopeptides of all seven LcrV groups in CD14/TLR2-transfected human embryonic kidney 293 cells, we found the highest TLR2 activity with a peptide derived from group IV comprising exclusively
Y. enterocolitica
O:8 strains. These findings were verified in murine peritoneal macrophages by using recombinant LcrV truncates representing aa 1-130 from different
Yersinia
spp. By systematically replacing charged aa residues by glutamine in synthetic oligopeptides, we show that the K42Q substitution leads to abrogation of TLR2 activity in both
in vitro
cell systems. This K42Q substitution was introduced in the
lcrV
gene from
Y. enterocolitica
O:8 WA-C(pYV), resulting in WA-C(pYVLcrV
K42Q
), which turned out to be less virulent for C57BL/6 mice than the parental strain. This difference in virulence was not observed in TLR2
-/-
or IL-10
-/-
mice, proving that LcrV contributes to virulence by TLR2-mediated IL-10 induction. LcrV is a defined bacterial virulence factor shown to target the TLR system for evasion of the host's immune response.
A structural model for maturation of the hepatitis B virus core
Authors: Roseman Alan M. , Berriman John A. , Wynne Samantha A. , Butler P. Jonathan G. , Crowther R. Anthony
Published: October 2005

Hepatitis B virus, a widespread and serious human pathogen, replicates by reverse transcription of an RNA intermediate. The virus consists of an inner nucleocapsid or core, surrounded by a lipid envelope containing virally encoded surface proteins. Using electron cryomicroscopy, we compare the structures of the bacterially expressed RNA-containing core particle and the mature DNA-containing core particle extracted from virions. We show that the mature core contains 240 subunits in a
T
= 4 arrangement similar to that in expressed core (
T
is the triangulation number and the icosahedral shell contains 60
T
subunits). During the infective cycle, the core assembles in an immature state around a complex of viral pregenomic RNA and polymerase. After reverse transcription with concomitant degradation of the RNA, the now mature core buds through a cellular membrane containing the surface proteins to become enveloped. Envelopment must not happen before reverse transcription is completed, so it has been hypothesized that a change in capsid structure may signal maturation. Our results show significant differences in structure between the RNA- and DNA-containing cores. One such difference is in a hydrophobic pocket, formed largely from residues that, on mutation, lead to abnormal secretion. We suggest that the changes we see are related to maturation and control of envelopment, and we propose a mechanism based on DNA synthesis for their triggering.
Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection
Authors: Wang Qing-Yin , Zhou Changhong , Johnson Karen E. , Colgrove Robert C. , Coen Donald M. , Knipe David M.
Published: October 2005

Herpes simplex virus (HSV) persists in its human host and evades the immune response by undergoing a latent infection in sensory neurons, from which it can reactivate periodically. HSV expresses >80 gene products during productive (“lytic”) infection, but only the latency-associated transcript (
LAT
) gene is expressed at abundant levels during latent infection. The
LAT
gene has been shown to repress lytic-gene expression in sensory neurons. In this study, we use chromatin immunoprecipitation to show that HSV lytic-gene promoters become complexed with modified histones associated with heterochromatin during the course of establishment of latent infection. Experiments comparing LAT-negative and LAT-positive viruses show that a function encoded by the
LAT
gene increases the amount of dimethyl lysine 9 form of histone H3 or heterochromatin and reduces the amount of dimethyl lysine 4 form of histone H3, a part of active chromatin, on viral lytic-gene promoters. Thus, HSV, and in particular the HSV
LAT
gene, may manipulate the cellular histone modification machinery to repress its lytic-gene expression and contribute to the persistence of its genome in a quiescent form in sensory neurons.
Regulation of
relB
in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter
Authors: Dong Xiangyang , Lutz Ward , Schroeder Tania M. , Bachman Lori A. , Westendorf Jennifer J. , Kumar Rajiv , Griffin Matthew D.
Published: October 2005

The NF-κB component RelB is essential for dendritic cell (DC) differentiation and maturation. The vitamin D receptor (VDR) is a nuclear receptor that mediates inhibition of DC maturation and transcriptional repression of
relB
after engagement of its ligand, 1α,25-dihydroxyvitamin D
3
, or related analogs (D
3
analogs). Ligand-dependent
relB
suppression was abolished by a histone deacetylase (HDAC) inhibitor. Constitutive association of VDR with the
relB
promoter was demonstrated in DCs by chromatin immunoprecipitation. Promoter binding by VDR was enhanced by ligand and reduced by LPS. Association of HDAC3 and HDAC1 with the
relB
VDR-binding site was observed, but only HDAC3 was reciprocally modulated by D
3
analog and LPS. Overexpression of HDAC3 caused
relB
promoter suppression, increased sensitivity to D
3
analog, and resistance to LPS. Depletion of HDAC3 attenuated
relB
suppression by D
3
analog.
In vivo
, D
3
analog resulted in reduced RelB in DCs from VDR WT mice but not VDR knockout mice. Other NF-lation of RelB and c-Rel in control animals. We conclude that vitamin D-regulated
relB
transcription in DCs is controlled by chromatin remodeling by means of recruitment of complexes including HDAC3.
Scientific issues in the design of metrics for inclusion of oxides of nitrogen in global climate agreements
Authors: Shine K. P. , Berntsen T. K. , Fuglestvedt J. S. , Sausen R.
Published: October 2005

The Kyoto Protocol seeks to limit emissions of various greenhouse gases but excludes short-lived species and their precursors even though they cause a significant climate forcing. We explore the difficulties that are faced when designing metrics to compare the climate impact of emissions of oxides of nitrogen (NO
x
) with other emissions. There are two dimensions to this difficulty. The first concerns the definition of a metric that satisfactorily accounts for its climate impact. NO
x
emissions increase tropospheric ozone, but this increase and the resulting climate forcing depend strongly on the location of the emissions, with low-latitude emissions having a larger impact. NO
x
emissions also decrease methane concentrations, causing a global-mean radiative forcing similar in size but opposite in sign to the ozone forcing. The second dimension of difficulty concerns the intermodel differences in the values of computed metrics. We explore the use of indicators that could lead to metrics that, instead of using global-mean inputs, are computed locally and then averaged globally. These local metrics may depend less on cancellation in the global mean; the possibilities presented here seem more robust to model uncertainty, although their applicability depends on the poorly known relationship between local climate change and its societal/ecological impact. If it becomes a political imperative to include NO
x
emissions in future climate agreements, policy makers will be faced with difficult choices in selecting an appropriate metric.
Multiple modes of interaction of the deglycosylation enzyme, mouse peptide
N
-glycanase, with the proteasome
Authors: Li Guangtao , Zhou Xiaoke , Zhao Gang , Schindelin Hermann , Lennarz William J.
Published: October 2005

Peptide
N
-glycanase (PNGase) is involved in the cleavage of oligosaccharide chains from misfolded glycoproteins that are destined for degradation by the proteasome. Earlier, a number of potential binding partners of mouse PNGase (mPNGase) were detected by using the yeast two-hybrid system. In the current study, an
in vitro
system was set up to investigate direct interactions between mPNGase and these candidate proteins. Although the yeast two-hybrid system suggested an interaction of six different proteins with mPNGase, only mHR23B and the proteasome subunit mS4 were found to interact with mPNGase. In fact, mS4 competes with mHR23B for binding to mPNGase. These results suggested two possible pathways for the interaction between mPNGase and the proteasome. In one pathway, mHR23B mediates the interaction between mPNGase and the proteasome. In an alternative pathway, mPNGase directly binds to the proteasome subunit, mS4. In either case, it is clear that PNGase is located in close proximity to the proteasome and is available for deglycosylation of glycoproteins destined for degradation. Surprisingly, mPNGase also was found to mediate binding of the cytoplasmic protein, p97, to the proteasome through the formation of a ternary complex made up of mHR23B, mPNGase, and p97. Because p97 is known to bind to the endoplasmic reticulum membrane protein AMFR (gp78), an E3 ligase, we propose a model in which p97, mPNGase, and mHR23B mediate interaction of the endoplasmic reticulum with the proteasome.
Breath sulfides and pulmonary function in cystic fibrosis
Authors: Kamboures M. A. , Blake D. R. , Cooper D. M. , Newcomb R. L. , Barker M. , Larson J. K. , Meinardi S. , Nussbaum E. , Rowland F. S.
Published: October 2005

We have determined the concentrations of carbonyl sulfide (OCS), dimethylsulfide, and carbon disulfide (CS2) in the breath of a group of cystic fibrosis (CF) patients and one of healthy controls. At the detection sensitivity in these experiments, room air always contained measurable quantities of these three gases. For each subject the inhaled room concentrations were subtracted from the time-coincident concentrations in exhaled breath air. The most significant differences between the CF and control cohorts in these breath-minus-room values were found for OCS. The control group demonstrated a net uptake of 250 ± 20 parts-per-trillion-by-volume (pptv), whereas the CF cohort had a net uptake of 110 ± 60 pptv (P= 0.00003). Three CF patients exhaled more OCS than they inhaled from the room. The OCS concentrations in the CF cohort were strongly correlated with pulmonary function. The dimethylsulfide concentrations in breath were greatly enhanced over ambient, but no significant difference was observed between the CF and healthy control groups. The net (breath minus room) CS2concentrations for individuals ranged between +180 and -100 pptv. They were slightly greater in the CF cohort (+26 ± 38 pptv) vs. the control group (-17 ± 15 pptv;P= 0.04). Lung disease in CF is accompanied by the subsistence of chronic bacterial infections. Sulfides are known to be produced by bacteria in various systems and were therefore the special target for this investigation. Our results suggest that breath sulfide content deserves attention as a noninvasive marker of respiratory colonization.
Identification of 14-3-3σ mutation causing cutaneous abnormality in repeated-epilation mutant mouse
Authors: Li Qiutang , Lu Qingxian , Estepa Gabriela , Verma Inder M.
Published: October 2005

Repeated-epilation (
Er
) mutation in the mouse is inherited as an autosomal and semidominant mutation. Major defects in heterozygous adults and homozygous fetuses were associated with skin and were caused by abnormal ectodermal differentiation. Heterozygous mice are characterized by repeated hair loss and regrowth, and homozygous fetuses die at birth with severe abnormality in skin, limb, tail, and face. To identify the gene causing
Er
mutation, we have performed gene-expression profiles of skins and mouse embryonic fibroblasts from WT and mutant
Er
mice by using Affymetrix (Santa Clara, CA) chip analysis. By analyzing the candidate genes generated from gene-expression profiling, we identified a
Sfn
mutation in
Er
mice. A single nucleotide insertion in the
Sfn
(Stratifin, also called 14-3-3σ) coding region results in a truncated protein lacking 40 amino acid residues at the C terminus. The mutation is linked with phenotypes of
Er
-heterozygous and -homozygous mice. Ectopic overexpression of WT 14-3-3σ in
Er/Er
keratinocytes rescues defects in keratinocyte differentiation. Our study demonstrates that 14-3-3σ is a crucial regulator for skin proliferation and differentiation.
Cultural determinism, Western hegemony & the efficacy of defective states
Authors: Jacoby Tim
Published: October 2005

This paper argues that the notion of a defective state, including those designated as ‘weak’, ‘failed’ or ‘collapsed’, has a number of obvious advantages for the West. First and most obviously, it offers an explanation for the faults of the state in question that does not implicate outside forces. Second, it justifies external action to intervene in the internal affairs of domestic regimes and, finally, it implies that such action can only reliably remove the inherent threat posed by defective states if intervention produces a project of political transformation. This suggests three questions (which make up the focus of the paper as a whole). First, if outside forces are not to blame, what is there within defective states that explains their failings? Second, what form should an external response to these problems take and, third, what sort of political transformation should that external response seek to enact within the target state?
Six months on: What shift is there in the EU approach to EPA negotiations?
Authors: Goodison Paul
Published: October 2005

With the UK presidency of the EU Council of Ministers pending (July 2005), EU Trade Commissioner Peter Mandelson is coming under increased pressure to modify the European Commission’s approach to Economic Partnership Agreement (EPA) negotiations with African, Caribbean and Pacific (ACP) countries. Criticism and pressure for change is not only coming from an increasingly vocal and active campaign by non-governmental development agencies in the UK, Europe and Africa (see http://www.stopepa.org/ for details of the campaign), but also from several more official sources. These include the Africa Commission established by prime minister Tony Blair, the inquiry by the House of Commons Select Committee on International Development into EU-ACP EPA negotiations1 and the joint position paper adopted by the UK Department of Trade and Industry and Department for International Development.2

Commissioner Mandelson has responded to this criticism by modifying and extending the rhetoric on the centrality of development concerns to the EC’s approach to EPA negotiations. However it is still unclear to what extent the Commissioner’s rhetoric is being taken up in practice by EC trade negotiators and EC aid officials. As the Zambian trade minister, Dipak Patel, has recently declared:

what Peter has said in his speech to the LSE [London School of Economics] was excellent, but perhaps his negotiators need to read it more than we do.
3
The Status of Likelihood Claims in International Relations and Peace Science
Authors: Dacey Raymond
Published: October 2005

Many of the best scholars working in International Relations and Peace Science have employed statistical (e.g., logit/probit) and theoretical models to buttress claims of causally increased or decreased probabilities. The purpose of this paper is two-fold: to display the applicability of the tools of probabilistic causality and statistical explanation to assessing analyses in International Relations and Peace Science, and to assess the status of the claims of causally changed probabilities made in these disciplines. The paper displays the applicability of the relevant tools of probabilistic causality and statistical explanation by examining two remarkably interesting analyses due to Russell Leng and Patrick Regan. The paper concludes that claims of causally changed probabilities commonly made in the International Relations and Peace Science literatures are suspect.
Psychosocial Analysis of the Collective Processes in the United States After September 11
Authors: Rodriguez-Carballeira Alvaro , Javaloy Federico
Published: October 2005

This article studies alterations in the values, attitudes, and behaviors that emerged among U.S. citizens as a consequence of, and as a response to, the attacks of September 11, 2001. The study briefly examines the immediate reaction to the attack, before focusing on the collective reactions that characterized the behavior of the majority of the population between the events of 9/11 and the response to it in the form of intervention in Afghanistan. In studying this period an eight-phase sequential model (Botcharova, 2001) is used, where the initial phases center on the nation as the ingroup and the latter focus on the enemy who carried out the attack as the outgroup.

The study is conducted from a psychosocial perspective and uses “social identity theory” (Tajfel & Turner, 1979, 1986) as the basic framework for interpreting and accounting for the collective reactions recorded. The main purpose of this paper is to show that the interpretation of these collective reactions is consistent with the postulates of social identity theory. The application of this theory provides a different and specific analysis of events. The study is based on data obtained from a variety of rigorous academic studies and opinion polls conducted in relation to the events of 9/11.

In line with social identity theory, 9/11 had a marked impact on the importance attached by the majority of U.S. citizens to their identity as members of a nation. This in turn accentuated group differentiation and activated ingroup favoritism and outgroup discrimination (Tajfel & Turner, 1979, 1986). Ingroup favoritism strengthened group cohesion, feelings of solidarity, and identification with the most emblematic values of the U.S. nation, while outgroup discrimination induced U.S. citizens to conceive the enemy (al-Qaeda and its protectors) as the incarnation of evil, depersonalizing the group and venting their anger on it, and to give their backing to a military response, the eventual intervention in Afghanistan. Finally, and also in line with the postulates of social identity theory, as an alternative to the virtual bipolarization of the conflict (U.S. vs al-Qaeda), the activation of a higher level of identity in the ingroup is proposed, a group that includes the United States and the largest possible number of countries— including Islamic states—in the search for a common, more legitimate and effective solution.
Mistaken Identity: A Reply to Hegre
Authors: Gartzke Erik , Quan Li
Published: October 2005

Hegre (2005) offers an interesting example of cumulative science. By relaxing a restrictive assumption in Gartzke and Li (2003a), Hegre shows formally that the relationship between trade share and trade dependence need not be negative. Still, Hegre's assumptions are also in tension with his basic insight. We apply his logic in a more thorough manner to demonstrate that our original theoretical argument and empirical results are robust to the critique. Hegre (2005) also suggests that the pacifying effect of trade openness is likely an artifact of our failure to control for the size of the national economy. We re-estimate the effect of trade openness while controlling for the economic size of both states in the dyad and show that trade openness continues to reduce the likelihood of military conflict between countries.
Short article: Inferring causality assessments from predictive responses: Cue interaction without cue competition
Authors: Winman Anders , Gredebäck Gustaf
Published: October 2005

The authors criticize the use of participants’ predictive responses during a learning phase as a measure of causal assessments (J. M. Tangen & L. G. Allan, 2003, 2004). Simulations demonstrate that a general aim to minimize error as required in the prediction task will produce results in accordance with those observed, in particular apparent cue interaction effects. It is argued that measures estimated from prediction responses do not reflect causal ratings, but are side-effects of learning explained by adaptation in strategy to changes in presented cell frequencies. The results are reinterpreted to be in line with a causal model view, not requiring dual processes or cue competition of lower level associative processes.
Mechanisms for focusing mitotic spindle poles by minus end–directed motor proteins
Authors: Goshima Gohta , Nédélec François , Vale Ronald D.
Published: October 2005

During the formation of the metaphase spindle in animal somatic cells, kinetochore microtubule bundles (K fibers) are often disconnected from centrosomes, because they are released from centrosomes or directly generated from chromosomes. To create the tightly focused, diamond-shaped appearance of the bipolar spindle, K fibers need to be interconnected with centrosomal microtubules (C-MTs) by minus end–directed motor proteins. Here, we have characterized the roles of two minus end–directed motors, dynein and Ncd, in such processes in Drosophila S2 cells using RNA interference and high resolution microscopy. Even though these two motors have overlapping functions, we show that Ncd is primarily responsible for focusing K fibers, whereas dynein has a dominant function in transporting K fibers to the centrosomes. We also report a novel localization of Ncd to the growing tips of C-MTs, which we show is mediated by the plus end–tracking protein, EB1. Computer modeling of the K fiber focusing process suggests that the plus end localization of Ncd could facilitate the capture and transport of K fibers along C-MTs. From these results and simulations, we propose a model on how two minus end–directed motors cooperate to ensure spindle pole coalescence during mitosis.
Imaging sunspots using helioseismic methods
Authors: Tong C.H
Published: October 2005

The origin of sunspots is one of the most fundamental and yet poorly understood areas in solar physics. Imaging local anomalous features in the solar interior offers a direct way to unravel the underlying physical processes of sunspots and the mechanisms behind their formation. The advent of local helioseismology in the last few years has, for the first time, made it possible to image local internal solar structures. High-resolution satellite and ground telescope data which reveal the details of the vibrations of the visible solar surface are essential in the development of local helioseismology. We are now in a position to transfer the seismic methods that have traditionally been used to study the Earth's interior to solar investigations. This interdisciplinary approach to developing seismic imaging techniques is opening up new ways of understanding the flow and other structural characteristics beneath sunspots. In this article, I review recent progress in the imaging of sunspots and the surrounding solar active regions. By highlighting the strengths of seismic methods and the challenges facing local helioseismology, I discuss some of the new research directions and possibilities that have arisen from this novel type of seismic imaging.
Planetary heat flow measurements
Authors: Hagermann Axel
Published: October 2005

The year 2005 marks the 35th anniversary of the Apollo 13 mission, probably the most successful failure in the history of manned spaceflight. Naturally, Apollo 13's scientific payload is far less known than the spectacular accident and subsequent rescue of its crew. Among other instruments, it carried the first instrument designed to measure the flux of heat on a planetary body other than Earth. The year 2005 also should have marked the launch of the Japanese LUNAR-A mission, and ESA's Rosetta mission is slowly approaching comet Churyumov-Gerasimenko. Both missions carry penetrators to study the heat flow from their target bodies. What is so interesting about planetary heat flow? What can we learn from it and how do we measure it?

Not only the Sun, but all planets in the Solar System are essentially heat engines. Various heat sources or heat reservoirs drive intrinsic and surface processes, causing ‘dead balls of rock, ice or gas’ to evolve dynamically over time, driving convection that powers tectonic processes and spawns magnetic fields. The heat flow constrains models of the thermal evolution of a planet and also its composition because it provides an upper limit for the bulk abundance of radioactive elements. On Earth, the global variation of heat flow also reflects the tectonic activity: heat flow increases towards the young ocean ridges, whereas it is rather low on the old continental shields.

It is not surprising that surface heat flow measurements, or even estimates, where performed, contributed greatly to our understanding of what happens inside the planets. In this article, I will review the results and the methods used in past heat flow measurements and speculate on the targets and design of future experiments.
Focused fluid flow in passive continental margins
Authors: Berndt Christian
Published: October 2005

Passive continental margins such as the Atlantic seaboard of Europe are important for society as they contain large energy resources, and they sustain ecosystems that are the basis for the commercial fish stock. The margin sediments are very dynamic environments. Fluids are expelled from compacting sediments, bottom water temperature changes cause gas hydrate systems to change their locations and occasionally large magmatic intrusions boil the pore water within the sedimentary basins, which is then expelled to the surface. The fluids that seep through the seabed at the tops of focused fluid flow systems have a crucial role for seabed ecology, and study of such fluid flow systems can also help in predicting the distribution of hydrocarbons in the subsurface and deciphering the climate record. Therefore, the study of focused fluid flow will become one of the most important fields in marine geology in the future.
Peatland hydrology and carbon release: why small-scale process matters
Authors: Holden Joseph
Published: October 2005

Peatlands cover over 400 million hectares of the Earth's surface and store between one-third and one-half of the world's soil carbon pool. The long-term ability of peatlands to absorb carbon dioxide from the atmosphere means that they play a major role in moderating global climate. Peatlands can also either attenuate or accentuate flooding. Changing climate or management can alter peatland hydrological processes and pathways for water movement across and below the peat surface. It is the movement of water in peats that drives carbon storage and flux. These small-scale processes can have global impacts through exacerbated terrestrial carbon release. This paper will describe advances in understanding environmental processes operating in peatlands. Recent (and future) advances in high-resolution topographic data collection and hydrological modelling provide an insight into the spatial impacts of land management and climate change in peatlands. Nevertheless, there are still some major challenges for future research. These include the problem that impacts of disturbance in peat can be irreversible, at least on human time-scales. This has implications for the perceived success and understanding of peatland restoration strategies. In some circumstances, peatland restoration may lead to exacerbated carbon loss. This will also be important if we decide to start to create peatlands in order to counter the threat from enhanced atmospheric carbon.
The impact rate on Earth
Authors: Bland Philip A
Published: October 2005

Recent data, and modelling of the interaction between asteroids and the atmosphere, has defined a complete size-frequency distribution for terrestrial impactors, from meteorite-sized objects up to kilometre-sized asteroids, for both the upper atmosphere and the Earth's surface. Although there remain significant uncertainties in the incidence of specific size-fractions of impactors, these estimates allow us to constrain the threat posed by impacts to human populations. It is clear that impacts remain a significant natural hazard, but uniquely, they are a threat that we can accurately predict, and take steps to avoid.
Weather patterns, food security and humanitarian response in sub-Saharan Africa
Authors: Haile Menghestab
Published: October 2005

Although considerable achievements in the global reduction of hunger and poverty have been made, progress in Africa so far has been very limited. At present, a third of the African population faces widespread hunger and chronic malnutrition and is exposed to a constant threat of acute food crisis and famine. The most affected are rural households whose livelihood is heavily dependent on traditional rainfed agriculture. Rainfall plays a major role in determining agricultural production and hence the economic and social well being of rural communities. The rainfall pattern in sub-Saharan Africa is influenced by large-scale intra-seasonal and inter-annual climate variability including occasional El Niño events in the tropical Pacific resulting in frequent extreme weather event such as droughts and floods that reduce agricultural outputs resulting in severe food shortages. Households and communities facing acute food shortages are forced to adopt coping strategies to meet the immediate food requirements of their families. These extreme responses may have adverse long-term impacts on households' ability to have sustainable access to food as well as the environment. The HIV/AIDS crisis has also had adverse impacts on food production activities on the continent.

In the absence of safety nets and appropriate financial support mechanisms, humanitarian aid is required to enable households effectively cope with emergencies and manage their limited resources more efficiently. Timely and appropriate humanitarian aid will provide households with opportunities to engage in productive and
sustainable
livelihood strategies. Investments in poverty reduction efforts would have better impact if complemented with timely and predictable response mechanisms that would ensure the protection of livelihoods during crisis periods whether weather or conflict-related. With an improved understanding of climate variability including El Niño, the implications of weather patterns for the food security and vulnerability of rural communities have become more predictable and can be monitored effectively. The purpose of this paper is to investigate how current advances in the understanding of climate variability, weather patterns and food security could contribute to improved humanitarian decision-making. The paper will propose new approaches for triggering humanitarian responses to weather-induced food crises.
Probabilistic prediction of climate using multi-model ensembles: from basics to applications
Authors: Palmer T.N , Doblas-Reyes F.J , Hagedorn R , Weisheimer A
Published: October 2005

The development of multi-model ensembles for reliable predictions of inter-annual climate fluctuations and climate change, and their application to health, agronomy and water management, are discussed.
Calibrating a coalescent simulation of human genome sequence variation
Authors: Schaffner Stephen F. , Foo Catherine , Gabriel Stacey , Reich David , Daly Mark J. , Altshuler David
Published: October 2005

Population genetic models play an important role in human genetic research, connecting empirical observations about sequence variation with hypotheses about underlying historical and biological causes. More specifically, models are used to compare empirical measures of sequence variation, linkage disequilibrium (LD), and selection to expectations under a “null” distribution. In the absence of detailed information about human demographic history, and about variation in mutation and recombination rates, simulations have of necessity used arbitrary models, usually simple ones. With the advent of large empirical data sets, it is now possible to calibrate population genetic models with genome-wide data, permitting for the first time the generation of data that are consistent with empirical data across a wide range of characteristics. We present here the first such calibrated model and show that, while still arbitrary, it successfully generates simulated data (for three populations) that closely resemble empirical data in allele frequency, linkage disequilibrium, and population differentiation. No assertion is made about the accuracy of the proposed historical and recombination model, but its ability to generate realistic data meets a long-standing need among geneticists. We anticipate that this model, for which software is publicly available, and others like it will have numerous applications in empirical studies of human genetics.
Genomic scans for selective sweeps using SNP data
Authors: Nielsen Rasmus , Williamson Scott , Kim Yuseob , Hubisz Melissa J. , Clark Andrew G. , Bustamante Carlos
Published: October 2005

Detecting selective sweeps from genomic SNP data is complicated by the intricate ascertainment schemes used to discover SNPs, and by the confounding influence of the underlying complex demographics and varying mutation and recombination rates. Current methods for detecting selective sweeps have little or no robustness to the demographic assumptions and varying recombination rates, and provide no method for correcting for ascertainment biases. Here, we present several new tests aimed at detecting selective sweeps from genomic SNP data. Using extensive simulations, we show that a new parametric test, based on composite likelihood, has a high power to detect selective sweeps and is surprisingly robust to assumptions regarding recombination rates and demography (i.e., has low Type I error). Our new test also provides estimates of the location of the selective sweep(s) and the magnitude of the selection coefficient. To illustrate the method, we apply our approach to data from the Seattle SNP project and to Chromosome 2 data from the HapMap project. In Chromosome 2, the most extreme signal is found in the lactase gene, which previously has been shown to be undergoing positive selection. Evidence for selective sweeps is also found in many other regions, including genes known to be associated with disease risk such as DPP10 and COL4A3.
Genome-wide definitive haplotypes determined using a collection of complete hydatidiform moles
Authors: Kukita Yoji , Miyatake Katsuyuki , Stokowski Renee , Hinds David , Higasa Koichiro , Wake Norio , Hirakawa Toshio , Kato Hidenori , Matsuda Takao , Pant Krishna , Cox David , Tahira Tomoko , Hayashi Kenshi
Published: October 2005

We present genome-wide definitive haplotypes, determined using a collection of 74 Japanese complete hydatidiform moles, each carrying a genome derived from a single sperm. The haplotypes incorporate 281,439 common SNPs, genotyped with a high throughput array-based oligonucleotide hybridization technique. Comparison of haplotypes inferred from pseudoindividuals (constructed from randomized mole pairs) with those of moles showed some switch errors in resolution of phases by the computational inference method. The effects of these errors on local haplotype structure and selection of tag SNPs are discussed. We also show that definitive haplotypes of moles may be useful for elucidation of long-range haplotype structure, and should be more effective for detecting extended haplotype homozygosity indicative of positive selection.
Analysis of the cDNAs of Hypothetical Genes on Arabidopsis Chromosome 2 Reveals Numerous Transcript Variants
Authors: Xiao Yong-Li , Smith Shannon R. , Ishmael Nadeeza , Redman Julia C. , Kumar Nihkil , Monaghan Erin L. , Ayele Mulu , Haas Brian J. , Wu Hank C. , Town Christopher D.
Published: October 2005

In the fully sequenced Arabidopsis (Arabidopsis thaliana) genome, many gene models are annotated as “hypothetical protein,” whose gene structures are predicted solely by computer algorithms with no support from either expressed sequence matches from Arabidopsis, or nucleic acid or protein homologs from other species. In order to confirm their existence and predicted gene structures, a high-throughput method of rapid amplification of cDNA ends (RACE) was used to obtain their cDNA sequences from 11 cDNA populations. Primers from all of the 797 hypothetical genes on chromosome 2 were designed, and, through 5′ and 3′ RACE, clones from 506 genes were sequenced and cDNA sequences from 399 target genes were recovered. The cDNA sequences were obtained by assembling their 5′ and 3′ RACE polymerase chain reaction products. These sequences revealed that (1) the structures of 151 hypothetical genes were different from their predictions; (2) 116 hypothetical genes had alternatively spliced transcripts and 187 genes displayed polyadenylation sites; and (3) there were transcripts arising from both strands, from the strand opposite to that of the prediction and possible dicistronic transcripts. Promoters from five randomly chosen hypothetical genes (At2g02540, At2g31270, At2g33640, At2g35550, and At2g36340) were cloned into report constructs, and their expressions are tissue or development stage specific. Our results indicate at least 50% of hypothetical genes on chromosome 2 are expressed in the cDNA populations with about 38% of the gene structures differing from their predictions. Thus, by using this targeted approach, high-throughput RACE, we revealed numerous transcripts including many uncharacterized variants from these hypothetical genes.
Increased Calcium Levels and Prolonged Shelf Life in Tomatoes Expressing Arabidopsis H+/Ca2+ Transporters
Authors: Park Sunghun , Cheng Ning Hui , Pittman Jon K. , Yoo Kil Sun , Park Jungeun , Smith Roberta H. , Hirschi Kendal D.
Published: October 2005

Here we demonstrate that fruit from tomato (Lycopersicon esculentum) plants expressing Arabidopsis (Arabidopsis thaliana) H+/cation exchangers (CAX) have more calcium (Ca2+) and prolonged shelf life when compared to controls. Previously, using the prototypical CAX1, it has been demonstrated that, in yeast (Saccharomyces cerevisiae) cells, CAX transporters are activated when the N-terminal autoinhibitory region is deleted, to give an N-terminally truncated CAX (sCAX), or altered through specific manipulations. To continue to understand the diversity of CAX function, we used yeast assays to characterize the putative transport properties of CAX4 and N-terminal variants of CAX4. CAX4 variants can suppress the Ca2+ hypersensitive yeast phenotypes and also appear to be more specific Ca2+ transporters than sCAX1. We then compared the phenotypes of sCAX1- and CAX4-expressing tomato lines. The sCAX1-expressing tomato lines demonstrate increased vacuolar H+/Ca2+ transport, when measured in root tissue, elevated fruit Ca2+ level, and prolonged shelf life but have severe alterations in plant development and morphology, including increased incidence of blossom-end rot. The CAX4-expressing plants demonstrate more modest increases in Ca2+ levels and shelf life but no deleterious effects on plant growth. These findings suggest that CAX expression may fortify plants with Ca2+ and may serve as an alternative to the application of CaCl2 used to extend the shelf life of numerous agriculturally important commodities. However, judicious regulation of CAX transport is required to assure optimal plant growth.
Sec22 and Memb11 Are v-SNAREs of the Anterograde Endoplasmic Reticulum-Golgi Pathway in Tobacco Leaf Epidermal Cells
Authors: Chatre Laurent , Brandizzi Federica , Hocquellet Agnès , Hawes Chris , Moreau Patrick
Published: October 2005

Distinct sets of soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) are distributed to specific intracellular compartments and catalyze membrane fusion events. Although the central role of these proteins in membrane fusion is established in nonplant systems, little is known about their role in the early secretory pathway of plant cells. Analysis of the Arabidopsis (Arabidopsis thaliana) genome reveals 54 genes encoding SNARE proteins, some of which are expected to be key regulators of membrane trafficking between the endoplasmic reticulum (ER) and the Golgi. To gain insights on the role of SNAREs of the early secretory pathway in plant cells, we have cloned the Arabidopsis v-SNAREs Sec22, Memb11, Bet11, and the t-SNARE Sed5, and analyzed their distribution in plant cells in vivo. By means of live cell imaging, we have determined that these SNAREs localize at the Golgi apparatus. In addition, Sec22 was also distributed at the ER. We have then focused on understanding the function of Sec22 and Memb11 in comparison to the other SNAREs. Overexpression of the v-SNAREs Sec22 and Memb11 but not of the other SNAREs induced collapse of Golgi membrane proteins into the ER, and the secretion of a soluble secretory marker was abrogated by all SNAREs. Our studies suggest that Sec22 and Memb11 are involved in anterograde protein trafficking at the ER-Golgi interface.
Suppression of Allene Oxide Cyclase in Hairy Roots of Medicago truncatula Reduces Jasmonate Levels and the Degree of Mycorrhization with Glomus intraradices
Authors: Isayenkov Stanislav , Mrosk Cornelia , Stenzel Irene , Strack Dieter , Hause Bettina
Published: October 2005

During the symbiotic interaction between Medicago truncatula and the arbuscular mycorrhizal (AM) fungus Glomus intraradices, an endogenous increase in jasmonic acid (JA) occurs. Two full-length cDNAs coding for the JA-biosynthetic enzyme allene oxide cyclase (AOC) from M. truncatula, designated as MtAOC1 and MtAOC2, were cloned and characterized. The AOC protein was localized in plastids and found to occur constitutively in all vascular tissues of M. truncatula. In leaves and roots, MtAOCs are expressed upon JA application. Enhanced expression was also observed during mycorrhization with G. intraradices. A partial suppression of MtAOC expression was achieved in roots following transformation with Agrobacterium rhizogenes harboring the MtAOC1 cDNA in the antisense direction under control of the cauliflower mosaic virus 35S promoter. In comparison to samples transformed with 35S∷uidA, roots with suppressed MtAOC1 expression exhibited lower JA levels and a remarkable delay in the process of colonization with G. intraradices. Both the mycorrhization rate, quantified by fungal rRNA, and the arbuscule formation, analyzed by the expression level of the AM-specific gene MtPT4, were affected. Staining of fungal material in roots with suppressed MtAOC1 revealed a decreased number of arbuscules, but these did not exhibit an altered structure. Our results indicate a crucial role for JA in the establishment of AM symbiosis.
Why is the management of glucocorticoid deficiency still controversial: a review of the literature
Authors: Crown Anna , Lightman Stafford
Published: October 2005

All endocrinologists would like to make glucocorticoid replacement therapy for their hypoadrenal patients as physiological as possible. Many would like the reassurance of a method of monitoring such treatment to confirm that they are achieving this aim. Advances in our knowledge of the normal physiology are relevant to our attempts to do this. The cortisol production rate in normal subjects is lower than was previously believed. The normal pattern of glucocorticoid secretion includes both a diurnal rhythm and a pulsatile ultradian rhythm. Glucocorticoid access to nuclear receptors is ‘gated’ by the 11‐β‐hydroxysteroid dehydrogenase enzymes, which interconvert active cortisol and inactive cortisone. Such complexities make the target of physiological glucocorticoid replacement therapy hard to achieve. The available evidence suggests that conventional treatment of hypoadrenal patients may result in adverse effects on some surrogate markers of disease risk, such as a lower bone mineral density than age‐sex matched controls, and increases in postprandial glucose and insulin concentrations. Although the quality of life of hypoadrenal patients may be impaired, there is no evidence of an improvement on higher doses of steroids, although quality of life is better if the hydrocortisone dose is split up, with the highest dose taken in the morning. Thus the evidence suggests that most patients may safely be treated with a low dose of glucocorticoid (e.g. 15 mg hydrocortisone daily) in two or three divided doses, with education about the appropriate action to take in the event of intercurrent illnesses.
Serum osteoprotegerin levels are associated with inflammation and pulse wave velocity
Authors: Kim S. M. , Lee J. , Ryu O. H. , Lee K. W. , Kim H. Y. , Seo J. A. , Kim S. G. , Kim N. H. , Baik S. H. , Choi D. S. , Choi K. M.
Published: October 2005

Objective  We examined the association between serum osteoprotegerin (OPG) levels, systemic inflammation and arterial stiffness in normal and diabetic patients.

Patients and measurements  The study subjects comprised 49 newly diagnosed diabetic patients and 72 age‐ and sex‐matched normal glucose controls. Anthropometric parameters, blood pressure, fasting blood glucose (FBG), lipid profiles, serum OPG, high‐sensitive C‐reactive protein (hsCRP), interleukin‐6 (IL‐6) and brachial‐ankle pulse wave velocity (baPWV) were measured.

Results  Serum OPG levels (6·1 ± 1·4 vs. 5·4 ± 1·3 pmol/l, P = 0·011) and baPWV (1562 ± 354 vs. 1399 ± 257 cm/s, P = 0·004) were significantly higher in the diabetic group than in the normal glucose group. Serum OPG levels in normal and diabetic patients correlated significantly with systolic blood pressure (r = 0·20, P = 0·035), FBG (r = 0·30, P = 0·002), right baPWV (r = 0·22, P = 0·021), left baPWV (r = 0·26, P = 0·006), homeostasis model assessment insulin resistance (HOMA‐IR) (r = 0·19, P = 0·045), IL‐6 (r = 0·32, P = 0·001) and hsCRP (r = 0·21, P = 0·027) after adjusting for age and sex. Multiple regression analysis showed that serum OPG level was significantly associated with age, FBG, IL‐6, systolic blood pressure, triglyceride and hsCRP (R2 = 0·299).

Conclusions  In summary, serum OPG and baPWV levels are elevated in diabetic patients and serum OPG levels are significantly associated with inflammation and arterial stiffness.