bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoprene emission from terrestrial ecosystems in response to global change: minding the gap between models and observations
Authors: Monson Russell K , Trahan Nicole , Rosenstiel Todd N , Veres Patrick , Moore David , Wilkinson Michael , Norby Richard J , Volder Astrid , Tjoelker Mark G , Briske David D , Karnosky David F , Fall Ray
Published: May 2007

Coupled surface–atmosphere models are being used with increased frequency to make predictions of tropospheric chemistry on a ‘future’ earth characterized by a warmer climate and elevated atmospheric CO
2
concentration. One of the key inputs to these models is the emission of isoprene from forest ecosystems. Most models in current use rely on a scheme by which global change is coupled to changes in terrestrial net primary productivity (NPP) which, in turn, is coupled to changes in the magnitude of isoprene emissions. In this study, we conducted measurements of isoprene emissions at three prominent global change experiments in the United States. Our results showed that growth in an atmosphere of elevated CO
2
inhibited the emission of isoprene at levels that completely compensate for possible increases in emission due to increases in aboveground NPP. Exposure to a prolonged drought caused leaves to increase their isoprene emissions despite reductions in photosynthesis, and presumably NPP. Thus, the current generation of models intended to predict the response of isoprene emission to future global change probably contain large errors. A framework is offered as a foundation for constructing new isoprene emission models based on the responses of leaf biochemistry to future climate change and elevated atmospheric CO
2
concentrations.
Climate/chemistry feedbacks and biogenic emissions
Authors: Pyle John A , Warwick Nicola , Yang Xin , Young Paul J , Zeng Guang
Published: May 2007

The oxidizing capacity of the atmosphere is affected by anthropogenic emissions and is projected to change in the future. Model calculations indicate that the change in surface ozone at some locations could be large and have significant implications for human health. The calculations depend on the precise scenarios used for the anthropogenic emissions and on the details of the feedback processes included in the model. One important factor is how natural biogenic emissions will change in the future. We carry out a sensitivity calculation to address the possible increase in isoprene emissions consequent on increased surface temperature in a future climate. The changes in ozone are significant but depend crucially on the background chemical regime. In these calculations, we find that increased isoprene will increase ozone in the Northern Hemisphere but decrease ozone in the tropics. We also consider the role of bromine compounds in tropospheric chemistry and consider cases where, in a future climate, the impact of bromine could change.
Marine aerosol production: a review of the current knowledge
Authors: O'Dowd Colin D , de Leeuw Gerrit
Published: May 2007

The current knowledge in primary and secondary marine aerosol formation is reviewed. For primary marine aerosol source functions, recent source functions have demonstrated a significant flux of submicrometre particles down to radii of 20 nm. Moreover, the source functions derived from different techniques up to 10 μm have come within a factor of two of each other. For secondary marine aerosol formation, recent advances have identified iodine oxides and isoprene oxidation products, in addition to sulphuric acid, as contributing to formation and growth, although the exact roles remains to be determined. While a multistep process seems to be required, isoprene oxidation products are more likely to participate in growth and sulphuric acid is more likely to participate in nucleation. Iodine oxides are likely to participate in both nucleation and growth.
The Palaeocene–Eocene carbon isotope excursion: constraints from individual shell planktonic foraminifer records
Authors: Zachos James C , Bohaty Steven M , John Cedric M , McCarren Heather , Kelly Daniel C , Nielsen Tina
Published: May 2007

The Palaeocene–Eocene thermal maximum (PETM) is characterized by a global negative carbon isotope excursion (CIE) and widespread dissolution of seafloor carbonate sediments. The latter feature supports the hypothesis that the PETM and CIE were caused by the rapid release of a large mass (greater than 2000 Gt C) of
12
C-enriched carbon. The source of this carbon, however, remains a mystery. Possible sources include volcanically driven thermal combustion of organic-rich sediment, dissociation of seafloor methane hydrates and desiccation and oxidation of soil/sediment organics. A key constraint on the source(s) is the rate at which the carbon was released. Fast rates would be consistent with a catastrophic event, e.g. massive methane hydrate dissociation, whereas slower rates might implicate other processes. The PETM carbon flux is currently constrained by high-resolution marine and terrestrial records of the CIE. In pelagic bulk carbonate records, the onset of the CIE is often expressed as a single- or multiple-step excursion extending over 10
4
years. Individual planktonic shell records, in contrast, always show a single-step CIE, with either pre-excursion or excursion isotope values, but no transition values. Benthic foraminifera records, which are less complete owing to extinction and diminutive assemblages, show a delayed excursion. Here, we compile and evaluate the individual planktonic shell isotope data from several localities. We find that the most expanded records consistently show a bimodal isotope distribution pattern regardless of location, water depth or depositional facies. This suggests one of several possibilities: (i) the isotopic composition of the surface ocean/atmosphere declined in a geologic instant (<500 yr), (ii) that during the onset of the CIE, most shells of mixed-layer planktonic foraminifera were dissolved, or (iii) the abundances or shell production of these species temporarily declined, possibly due to initial pH changes.
The stability of the stratospheric ozone layer during the end-Permian eruption of the Siberian Traps
Authors: Beerling David J , Harfoot Michael , Lomax Barry , Pyle John A
Published: May 2007

The discovery of mutated palynomorphs in end-Permian rocks led to the hypothesis that the eruption of the Siberian Traps through older organic-rich sediments synthesized and released massive quantities of organohalogens, which caused widespread O
3
depletion and allowed increased terrestrial incidence of harmful ultraviolet-B radiation (UV-B, 280–315 nm; Visscher
et al
. 2004
Proc. Natl Acad. Sci. USA
101
, 12 952–12 956). Here, we use an extended version of the Cambridge two-dimensional chemistry–transport model to evaluate quantitatively this possibility along with two other potential causes of O
3
loss at this time: (i) direct effects of HCl release by the Siberian Traps and (ii) the indirect release of organohalogens from dispersed organic matter. According to our simulations, CH
3
Cl released from the heating of coals alone caused comparatively minor O
3
depletion (5–20% maximum) because this mechanism fails to deliver sufficiently large amounts of Cl into the stratosphere. The unusual explosive nature of the Siberian Traps, combined with the direct release of large quantities of HCl, depleted the model O
3
layer in the high northern latitudes by 33–55%, given a main eruptive phase of less than or equal to 200 kyr. Nevertheless, O
3
depletion was most extensive when HCl release from the Siberian Traps was combined with massive CH
3
Cl release synthesized from a large reservoir of dispersed organic matter in Siberian rocks. This suite of model experiments produced column O
3
depletion of 70–85% and 55–80% in the high northern and southern latitudes, respectively, given eruption durations of 100–200 kyr. On longer eruption time scales of 400–600 kyr, corresponding O
3
depletion was 30–40% and 20–30%, respectively. Calculated year-round increases in total near-surface biologically effective (BE) UV-B radiation following these reductions in O
3
layer range from 30–60 (kJ m
−2
 d
−1
)
BE
up to 50–100 (kJ m
−2
 d
−1
)
BE
. These ranges of daily UV-B doses appear sufficient to exert mutagenic effects on plants, especially if sustained over tens of thousands of years, unlike either rising temperatures or SO
2
concentrations.
Anaerobic methanotrophy and the rise of atmospheric oxygen
Authors: Catling D.C , Claire M.W , Zahnle K.J
Published: May 2007

In modern marine sediments, the anoxic decomposition of organic matter generates a significant flux of methane that is oxidized microbially with sulphate under the seafloor and never reaches the atmosphere. In contrast, prior to
ca
2.4 Gyr ago, the ocean had little sulphate to support anaerobic oxidation of methane (AOM) and the ocean should have been an important methane source. As atmospheric O
2
and seawater sulphate levels rose on the early Earth, AOM would have increasingly throttled the release of methane. We use a biogeochemical model to simulate the response of early atmospheric O
2
and CH
4
to changes in marine AOM as sulphate levels increased. Semi-empirical relationships are used to parameterize global AOM rates and the evolution of sulphate levels. Despite broad uncertainties in these relationships, atmospheric O
2
concentrations generally rise more rapidly and to higher levels (of order approx. 10
−3
 bar versus approx. 10
−4
 bar) as a result of including AOM in the model. Methane levels collapse prior to any significant rise in O
2
, but counter-intuitively, methane re-rises after O
2
rises to higher levels when AOM is included. As O
2
concentrations increase, shielding of the troposphere by stratospheric ozone slows the effective reaction rate between oxygen and methane. This effect dominates over the decrease in the methane source associated with AOM. Thus, even with the inclusion of AOM, the simulated Late Palaeoproterozoic atmosphere has a climatologically significant level of methane of approximately 50 ppmv.
Climate change and trace gases
Authors: Hansen James , Sato Makiko , Kharecha Pushker , Russell Gary , Lea David W , Siddall Mark
Published: May 2007

Palaeoclimate data show that the Earth's climate is remarkably sensitive to global forcings. Positive feedbacks predominate. This allows the entire planet to be whipsawed between climate states. One feedback, the ‘albedo flip’ property of ice/water, provides a powerful trigger mechanism. A climate forcing that ‘flips’ the albedo of a sufficient portion of an ice sheet can spark a cataclysm. Inertia of ice sheet and ocean provides only moderate delay to ice sheet disintegration and a burst of added global warming. Recent greenhouse gas (GHG) emissions place the Earth perilously close to dramatic climate change that could run out of our control, with great dangers for humans and other creatures. Carbon dioxide (CO
2
) is the largest human-made climate forcing, but other trace constituents are also important. Only intense simultaneous efforts to slow CO
2
emissions and reduce non-CO
2
forcings can keep climate within or near the range of the past million years. The most important of the non-CO
2
forcings is methane (CH
4
), as it causes the second largest human-made GHG climate forcing and is the principal cause of increased tropospheric ozone (O
3
), which is the third largest GHG forcing. Nitrous oxide (N
2
O) should also be a focus of climate mitigation efforts. Black carbon (‘black soot’) has a high global warming potential (approx. 2000, 500 and 200 for 20, 100 and 500 years, respectively) and deserves greater attention. Some forcings are especially effective at high latitudes, so concerted efforts to reduce their emissions could preserve Arctic ice, while also having major benefits for human health, agricultural productivity and the global environment.
The biodiversity and ecology of Antarctic lakes: models for evolution
Authors: Laybourn-Parry Johanna , Pearce David A
Published: May 2007

Antarctic lakes are characterised by simplified, truncated food webs. The lakes range from freshwater to hypersaline with a continuum of physical and chemical conditions that offer a natural laboratory in which to study evolution. Molecular studies on Antarctic lake communities are still in their infancy, but there is clear evidence from some taxonomic groups, for example the Cyanobacteria, that there is endemicity. Moreover, many of the bacteria have considerable potential as sources of novel biochemicals such as low temperature enzymes and anti-freeze proteins. Among the eukaryotic organisms survival strategies have evolved, among which dependence on mixotrophy in phytoflagellates and some ciliates is common. There is also some evidence of evolution of new species of flagellate in the marine derived saline lakes of the Vestfold Hills. Recent work on viruses in polar lakes demonstrates high abundance and high rates of infection, implying that they may play an important role in genetic exchange in these extreme environments.
Introduction. Antarctic ecology: from genes to ecosystems. Part 2. Evolution, diversity and functional ecology
Authors: Rogers Alex D , Murphy Eugene J , Johnston Nadine M , Clarke Andrew
Published: May 2007

The Antarctic biota has evolved over the last 100 million years in increasingly isolated and cold conditions. As a result, Antarctic species, from micro-organisms to vertebrates, have adapted to life at extremely low temperatures, including changes in the genome, physiology and ecological traits such as life history. Coupled with cycles of glaciation that have promoted speciation in the Antarctic, this has led to a unique biota in terms of biogeography, patterns of species distribution and endemism. Specialization in the Antarctic biota has led to trade-offs in many ecologically important functions and Antarctic species may have a limited capacity to adapt to present climate change. These include the direct effects of changes in environmental parameters and indirect effects of increased competition and predation resulting from altered life histories of Antarctic species and the impacts of invasive species. Ultimately, climate change may alter the responses of Antarctic ecosystems to harvesting from humans. The unique adaptations of Antarctic species mean that they provide unique models of molecular evolution in natural populations. The simplicity of Antarctic communities, especially from terrestrial systems, makes them ideal to investigate the ecological implications of climate change, which are difficult to identify in more complex systems.
Genome sequence of a proteolytic (Group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes
Authors: Sebaihia Mohammed , Peck Michael W. , Minton Nigel P. , Thomson Nicholas R. , Holden Matthew T.G. , Mitchell Wilfrid J. , Carter Andrew T. , Bentley Stephen D. , Mason David R. , Crossman Lisa , Paul Catherine J. , Ivens Alasdair , Wells-Bennik Marjon H.J. , Davis Ian J. , Cerdeño-Tárraga Ana M. , Churcher Carol , Quail Michael A. , Chillingworth Tracey , Feltwell Theresa , Fraser Audrey , Goodhead Ian , Hance Zahra , Jagels Kay , Larke Natasha , Maddison Mark , Moule Sharon , Mungall Karen , Norbertczak Halina , Rabbinowitsch Ester , Sanders Mandy , Simmonds Mark , White Brian , Whithead Sally , Parkhill Julian
Published: May 2007

Clostridium botulinum is a heterogeneous Gram-positive species that comprises four genetically and physiologically distinct groups of bacteria that share the ability to produce botulinum neurotoxin, the most poisonous toxin known to man, and the causative agent of botulism, a severe disease of humans and animals. We report here the complete genome sequence of a representative of Group I (proteolytic) C. botulinum (strain Hall A, ATCC 3502). The genome consists of a chromosome (3,886,916 bp) and a plasmid (16,344 bp), which carry 3650 and 19 predicted genes, respectively. Consistent with the proteolytic phenotype of this strain, the genome harbors a large number of genes encoding secreted proteases and enzymes involved in uptake and metabolism of amino acids. The genome also reveals a hitherto unknown ability of C. botulinum to degrade chitin. There is a significant lack of recently acquired DNA, indicating a stable genomic content, in strong contrast to the fluid genome of Clostridium difficile, which can form longer-term relationships with its host. Overall, the genome indicates that C. botulinum is adapted to a saprophytic lifestyle both in soil and aquatic environments. This pathogen relies on its toxin to rapidly kill a wide range of prey species, and to gain access to nutrient sources, it releases a large number of extracellular enzymes to soften and destroy rotting or decayed tissues.
Effect of Angiotensin‐Converting Enzyme Inhibitors on Arterial Stiffness in Hypertension: Systematic Review and Meta‐Analysis
Authors: Mallareddy Madhavi , Parikh Chirag R. , Peixoto Aldo J.
Published: May 2007

Arterial stiffness is an independent cardiovascular prognostic factor and is modulated by angiotensin‐converting enzyme inhibitors (ACEIs). The authors performed a meta‐analysis of clinical trials investigating the effects of ACEIs on pulse wave velocity (PWV) or augmentation index. The search included randomized clinical trials as well as uncontrolled studies that measured in‐treatment changes in arterial stiffness. The authors performed separate analyses for carotid‐femoral PWV, brachioradial PWV, and augmentation index. Average absolute and relative reduction in mean arterial pressure and PWV were −15.4 mm Hg and −13.04% and −1.15 mis and ‐9.74% for carotid‐femoral PWV studies; and −11.2 mm Hg and ‐9.3% and −1.9 mis and −16.7% for brachioradial PWV studies. There was a greater reduction in augmentation index by ACEIs when compared with controls (—1.0% to −5.3%). The authors conclude that ACEIs have modest beneficial effects on arterial stiffness measured as PWV and augmentation index, and this effect is at least partly independent of changes in blood pressure.
Involvement of reactive oxygen species in multidrug resistance of a vincristine‐selected lymphoblastoma
Authors: Tsai Shih‐Ying , Sun Nian‐Kang , Lu Hsing‐Pang , Cheng Mei‐ling , Chao Chuck C.‐K.
Published: May 2007

Our previous study identified a vincristine‐selected multidrug resistance (MDR) cell line, HOB1/VCR, derived from a lymphoblastoma HOB1. The HOB1/VCR cells are resistant to typical MDR drugs and are cross‐resistant to P‐glycoprotein‐independent drugs such as cisplatin (cis‐diamminedichloroplatinum [II]). The mechanism of this atypical MDR phenotype is uncertain. The present study provides evidence regarding the contribution of reactive oxygen species (ROS) to the resistance of cells in response to treatments (vincristine, cisplatin and H2O2). Notably, the HOB1/VCR cells were cross‐resistant to H2O2. High levels of ROS formed in both sensitive and HOB1/VCR cells by H2O2, and moderate levels of ROS were generated by treatment with cisplatin and vincristine. The ROS level in HOB1/VCR cells was lower than that in sensitive cells following treatments. The ROS level was reduced markedly by a non‐toxic concentration of N‐acetyl‐l‐cysteine, a ROS scavenger, in drug‐treated cells, and was correlated with reduced cytotoxicity. Furthermore, concentrations of glutathione and glutathione peroxidase, but not superoxide dismutase and catalase, increased in HOB/VCR cells. The dl‐buthionine‐[S,R]‐sulfoximine inhibited formation of glutathione and sensitized both cell types to treatments. Therefore, overexpression of an H2O2‐reducing system, glutathione–glutathione peroxidase, has a role in resistance. Experimental results further demonstrate that ROS is likely a primary signal in the acquisition of the MDR phenotype and therefore a potential target when designing drugs for chemoresistance. (Cancer Sci 2007; 98: 1206–1214)
Alcohol dehydrogenase and aldehyde dehydrogenase polymorphisms and colorectal cancer: The Fukuoka Colorectal Cancer Study
Authors: Yin Guang , Kono Suminori , Toyomura Kengo , Moore Malcolm A. , Nagano June , Mizoue Tetsuya , Mibu Ryuichi , Tanaka Masao , Kakeji Yoshihiro , Maehara Yoshihiko , Okamura Takeshi , Ikejiri Koji , Futami Kitaroh , Yasunami Yohichi , Maekawa Takafumi , Takenaka Kenji , Ichimiya Hitoshi , Imaizumi Nobutoshi
Published: May 2007

Alcohol dehydrogenase and aldehyde dehydrogenase are key enzymes in alcohol metabolism and therefore may be of importance to colorectal cancer development. The present case–control study was conducted to determine the influence of ADH2, ADH3 and ALDH2 polymorphisms in Fukuoka, Japan, with 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly from the study area. Alcohol use was ascertained by in‐person interview. Statistical adjustment was made for sex, age class, area, and alcohol use. Individuals with the allele 47Arg of the ADH2 polymorphism (slow metabolizers) had a statistically significant increase in risk, with an adjusted OR of 1.32 (95% CI = 1.07–1.63), compared with those having the ADH2*47His/His genotype. This association was not affected by the level of alcohol consumption. The ADH3 polymorphism showed no measurable association with the risk of colorectal cancer on either overall analysis or stratified analysis with alcohol use. The heterozygous ALDH2*487Glu/Lys genotype was not associated with an increase in the risk of colorectal cancer (adjusted OR 0.89, 95% CI = 0.71–1.13) compared with the ALDH2*487Glu/Glu genotype. Rather unexpectedly, the homozygous ALDH2*487Lys/Lys genotype was related to a statistically significantly decreased risk of colorectal cancer (adjusted OR 0.55, 95% CI = 0.33–0.93). It is unlikely that acetaldehyde metabolism determined by ALDH2 polymorphism contributes to the risk of colorectal cancer, whereas the role of ADH2 polymorphism deserves further investigation. (Cancer Sci 2007; 98: 1248–1253)
Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions
Authors: Akatsuka Yoshiki , Morishima Yasuo , Kuzushima Kiyotaka , Kodera Yoshihisa , Takahashi Toshitada
Published: May 2007

Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft‐versus‐host disease in human leukocyte antigen (HLA)‐matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)‐bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non‐self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft‐versus‐leukemia/lymphoma (GVL) effects without increasing the risk of life‐threatening graft‐versus‐host disease (GVHD). Accumulating evidence suggests that T‐cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL‐directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed self‐proteins, mHag‐based immunotherapy may lead to a new treatment modality for high‐risk malignancies following allogeneic HCT. (Cancer Sci 2007; 98: 1139–1146)
A vision of the next generation of behavioral therapies research in the addictions*
Authors: Carroll Kathleen M. , Rounsaville Bruce J.
Published: May 2007

Whither, or wither, empirically supported therapies? Increasingly rigorous research in behavioral therapies has yielded a large number of effective therapies, but comparatively little work, demonstrating that integrating empirically supported therapies (ESTs) into standard practice results in meaningful improvements in patient outcomes. Methodology and strategies for evaluating ESTs and their effectiveness in clinical practice is a fairly recent innovation, and a host of unanswered questions remain regarding issues such as selection among different ESTs and what type of ESTs should be emphasized in dissemination efforts, what type of clinicians should be trained in what type of ESTs, the most effective training strategies for various types of clinicians, the need for ongoing supervision to maintain minimum levels of treatment fidelity and skill. In this review, we call for broader use of new research strategies and methods relevant to dissemination of ESTs; these may include adaptive designs, identification of mechanisms of action to foster greater emphasis on effective change principles, training and adoption trials, as well as novel implementation strategies including computer‐assisted therapy and computer‐assisted training.
Factor and item‐response analysis DSM‐IV criteria for abuse of and dependence on cannabis, cocaine, hallucinogens, sedatives, stimulants and opioids
Authors: Gillespie Nathan A. , Neale Michael C. , Prescott Carol A. , Aggen Steven H. , Kendler Kenneth S.
Published: May 2007

Aims  This paper explored, in a population‐based sample of males, the factorial structure of criteria for substance abuse and dependence, and compared qualitatively the performance of these criteria across drug categories using item–response theory (IRT).

Design  Marginal maximum likelihood was used to explore the factor structure of criteria within drug classes, and a two‐parameter IRT model was used to determine how the difficulty and discrimination of individual criteria differ across drug classes.

Participants  A total of 4234 males born from 1940 to 1974 from the population‐based Virginia Twin Registry were approached to participate.

Measurements  DSM‐IV drug use, abuse and dependence criteria for cannabis, sedatives, stimulants, cocaine and opiates.

Findings  For each drug class, the pattern of endorsement of individual criteria for abuse and dependence, conditioned on initiation and use, could be best explained by a single factor. There were large differences in individual item performance across substances in terms of item difficulty and discrimination. Cocaine users were more likely to have encountered legal, social, physical and psychological consequences.

Conclusions  The DSM‐IV abuse and dependence criteria, within each drug class, are not distinct but best described in terms of a single underlying continuum of risk. Because individual criteria performed very differently across substances in IRT analyses, the assumption that these items are measuring equivalent levels of severity or liability with the same discrimination across different substances is unsustainable. Compared to other drugs, cocaine usage is associated with more detrimental effects and negative consequences, whereas the effects of cannabis and hallucinogens appear to be less harmful. Implications for other drug classes are discussed.
Alcoholics Anonymous in Ireland: AA's first European experience
Authors: Butler Shane , Jordan Tony
Published: May 2007

Aims  To trace the evolution of Alcoholics Anonymous in Ireland from its establishment there in 1946, focusing on the efforts of early members to publicize the fellowship and negotiate a role for themselves in relation to existing religious and healthcare institutions.

Methods  Archival research, drawing mainly on primary sources in AA archives in New York and Dublin.

Results  Anticipated tensions between this fellowship, which had its roots in Evangelical Protestantism, and the politically powerful Roman Catholic Church in Ireland were skillfully avoided; initial hostility from the medical profession quickly dissipated; and AA distanced itself from policy debate on the wider topic of alcoholism as disease.

Conclusions  The relatively smooth introduction of AA to Ireland, the first European country in which it was established, may be attributed to the essentially pragmatic nature of the fellowship and the strategic abilities of its early members.
The spatial ecology of alcohol problems: niche theory and assortative drinking
Authors: Gruenewald Paul J.
Published: May 2007

Aims This paper summarizes several theoretical perspectives that serve to explain observed associations between concentrations of alcohol outlets and alcohol‐related problems. A critique of each perspective discusses how each addresses the social etiology of these problems; that is, how, where and why these problems arise in association with alcohol outlets?

Methods This theoretical work is based upon mathematical and computational models of the ecology of alcohol‐related problems developed in the ‘Ecosystems Modeling Project’, an advanced research project of the National Institute on Alcohol Abuse and Alcoholism, United States.

Results Associations between outlets and problems are thought to arise from the concentration of individuals in drinking places (‘flow models’), the attraction of some places for people at risk for problems (‘gravity models’), or because outlets are located in high‐risk neighborhoods and have negative social normative effects (‘social contextual models’). None of these approaches explain how some outlets come to have more problems than others (e.g. violent outlets). An alternative social ecological model is introduced which asserts that the complementary processes of niche marketing and assortative drinking form the social dynamic that explains these relationships. Alcohol sellers ‘niche market’ to select social strata, drinkers return to establishments at which they find people like themselves, and consequent social stratification of the market‐place increases the levels of related problems in some outlets.

Conclusions The proposed mechanism is very general, and suggests that over‐concentrations of outlets will lead to stratification of drinking groups and intensification of problems related to those outlets.
Chromophore‐assisted light inactivation of pKi‐67 leads to inhibition of ribosomal RNA synthesis
Authors: Rahmanzadeh R. , Hüttmann G. , Gerdes J. , Scholzen T.
Published: May 2007

Abstract.  Objectives: Expression of the nuclear Ki‐67 protein (pKi‐67) is strongly associated with cell proliferation. For this reason, antibodies against this protein are widely used as prognostic tools for the assessment of cell proliferation in biopsies from cancer patients. Despite this broad application in histopathology, functional evidence for the physiological role of pKi‐67 is still missing. Recently, we proposed a function of pKi‐67 in the early steps of ribosomal RNA (rRNA) synthesis. Here, we have examined the involvement of pKi‐67 in this process by photochemical inhibition using chromophore‐assisted light inactivation (CALI). Materials and methods: Anti‐pKi‐67 antibodies were labelled with the fluorochrome fluorescein 5(6)‐isothiocyanate and were irradiated after binding to their target protein. Results: Performing CALI in vitro on cell lysates led to specific cross‐linking of pKi‐67. Moreover, the upstream binding factor (UBF) necessary for rRNA transcription was also partly subjected to cross‐link formation, indicating a close spatial proximity of UBF and pKi‐67. CALI in living cells, using micro‐injected antibody, caused a striking relocalization of UBF from foci within the nucleoli to spots located at the nucleolar rim or within the nucleoplasm. pKi‐67‐CALI resulted in dramatic inhibition of RNA polymerase I‐dependent nucleolar rRNA synthesis, whereas RNA polymerase II‐dependent nucleoplasmic RNA synthesis remained almost unaltered. Conclusions: Our data presented here argue for a crucial role of pKi‐67 in RNA polymerase I‐dependent nucleolar rRNA synthesis.
The influence of 3,3′,5‐triiodo‐l‐thyronine on human haematopoiesis
Authors: Grymuła K. , Paczkowska E. , Dziedziejko V. , Baśkiewicz‐Masiuk M. , Kawa M. , Baumert B. , Celewicz Z. , Gawrych E. , Machaliński B.
Published: May 2007

Abstract.  Objectives: Thyroid hormones mediate many physiological and developmental functions in humans. The role of the 3,3′,5‐triiodo‐l‐thyronine (T3) in normal human haematopoiesis at the cellular and molecular levels has not been determined. In this study, it was revealed that the human haematopoietic system might be directly depended on T3 influence. Materials and methods: We detected the TRα1 and TRβ1 gene expression at the mRNA level in human cord blood, peripheral blood and bone marrow CD34+‐enriched progenitor cells, using the RT‐PCR method. Furthermore, we performed Western blotting to prove TRα1 and TRβ1 expression occurs at the protein level in human cord blood, peripheral blood and bone marrow CD34+ cells. In addition, the examined populations of cells were exposed in serum‐free conditions to increasing doses of T3 and were subsequently investigated for clonogenic growth of granulocyte‐macrophage colony‐forming unit and erythrocyte burst‐forming unit in methylcellulose cultures, and for the level of apoptosis, by employing annexin V staining and the terminal deoxynucleotidyltransferase‐mediated dUTP nick‐end labelling method. We investigated expression levels of apoptosis‐related Bax and antiapoptotic Bcl‐2 and Bcl‐xL genes in the examined cells. Results: We found that exposure to higher and lower than normal concentration of thyroid hormone significantly influenced clonogenecity and induced apoptosis in human haematopoietic progenitor cells. Conclusions: This study expands the understanding of the role of thyroid disorders in normal human haematopoiesis and indicates a direct influence of T3 on this process.
Isothiocyanate E‐4IB induces MAPK activation, delayed cell cycle transition and apoptosis
Authors: Bodo J. , Duraj J. , Jakubikova J. , Sedlak J.
Published: May 2007

Abstract.  Introduction: Epidemiologic studies point towards a significant correlation between the dietary intake of isothiocyanate‐containing foods and the reduced risk for cancer. Methods and results: In the current investigation, we examined the consequence of activating of signalling pathways during the release the cells from the block at G1/S boundary by synthetic isothiocyanate E‐4IB. Using synchronized leukaemic HL60 cells, we show that activation of mitogen‐activated protein kinases ERK1/2, c‐Jun N‐terminal kinase and p38 signalling pathways by E‐4IB are coupled with delayed transition through the cell cycle and rapid cell cycle arrest resulted in diminished mitochondrial membrane potential culminating in apoptosis. These events were accompanied by histone deacetylase inhibition, increase of double strand DNA breaks detected by histone H2AX phosphorylation and up‐regulation of cell cycle regulatory protein p21 and phosphorylation of CDC25C phosphatase. Conclusion: These findings suggest that the activation of mitogen‐activated protein kinases signalling pathways, followed by the induction cell cycle arrest and apoptosis, might be responsible for anticancer activities of E‐4IB.
Deletion of a single allele of Cx43 is associated with a reduction in the gap junctional intercellular communication and increased cell proliferation of mouse lung pneumocytes type II
Authors: Avanzo J. L. , Mennecier G. , Mesnil M. , Hernandez‐Blazquez F. J. , Fukumasu H. , Da Silva T. C. , Rao K. V. K. , Dagli M. L. Z.
Published: May 2007

Abstract.  Objectives: Connexins (Cx) are proteins that form the gap junctional channels at neighbouring plasma membranes between adjacent cells. Cxs are involved in cell communication, which is reportedly correlated with cell proliferation and differentiation. Alterations in connexin expression and/or gap junctional intercellular communication (GJIC) capacity have long been postulated to be important in a number of pathological conditions including cancer. This study was performed to determine the consequences of the deletion of a single allele of Gja1 (Cx43 gene) in Alveolar Type II cells (APTIIs), and its impact on GJIC and cell proliferation. Material and methods: In order to do so, APTIIs from wild type (Cx43+/+) and heterozygous (Cx43+/–) mice were harvested and cultured for 4 days. The GJIC capacity was evaluated by scrape‐loading method, with the transfer of lucifer yellow dye. The expression of Cx43 was evaluated by immunofluorescence method and Western blotting. Cell proliferation was evaluated by 3‐(4,5‐dimethylthazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Results: It was observed that GJIC capacity was significantly reduced and cell proliferation index was significantly higher in Cx43+/– cells compared to Cx43+/+ cells. Conclusions: These results show that knocking out one allele of Cx43 leads to a lower cell to cell communication capacity, and consequently induces a higher cell proliferation. Because chemically induced lung adenomas in mice are known to originate from APTIIs, these alterations may play a critical role in their susceptibility to lung carcinogenesis.
Establishment of a tetraploid cell line from mouse H‐1 (ES) cells highly polyploidized with demecolcine
Authors: Fujikawa‐Yamamoto K. , Miyagoshi M. , Yamagishi H.
Published: May 2007

Abstract.  Objective: Establishment of tetraploid ES cells. Materials and methods: Mouse H‐1 (ES) cells were polyploidized by demecolcine and released from the drug. Results: A tetraploid cell line (4nH1 cells) was established from mouse H‐1 (ES) cells (2nH1 cells) highly polyploidized by treatment with demecolcine. Cell cycle parameters of 4nH1 cells were almost the same as those of 2nH1 cells, suggesting that the rate of DNA synthesis was about twice that of the diploid cells. Mode of chromosome number of 4nH1 cells was 76, about twice that of 2nH1 cells. Cell volume of 4nH1 cells was about twice of that of diploid cells, indicating that 4nH1 cells contained about twice as much total intracellular material as 2nH1 cells. Morphology of the 4nH1 cells was flagstone‐like, thus differing from that of the spindle‐shaped 2nH1 cells, suggesting that the transformation had occurred during the diploid–tetraploid transition. 4nH1 cells exhibited alkaline phosphatase activity and formed teratocarcinomas, implying that they would be pluripotent. Conclusion: A pluripotent tetraploid cell line (4nH1 cells) was established.
Role of c‐Fos/JunD in protecting stress‐induced cell death
Authors: Zhou H. , Gao J. , Lu Z. Y. , Lu L. , Dai W. , Xu M.
Published: May 2007

Abstract.  Objective: The exposure of mammalian cells to extracellular stress induces the expression of immediate early genes such as c‐fos and c‐jun and activates transcription factor activator protein‐1 (AP‐1). The purpose of the current study was to investigate the role of c‐Fos and JunD in stress‐induced cell death. Materials and methods: We exposed cultured primary mouse embryonic fibroblasts (MEF) to ultraviolet light (UV‐C) or hydrogen peroxide (H2O2). Induction of c‐Fos and JunD and activation of MAPK/ERK1/2 signalling in the presence or absence of a MAPK inhibitor were analyzed by western blotting. Activation of AP‐1 transcription factors was detected by the electrophoretic mobility shift assay and immunoprecipitation. Cell death was measured by changes in caspase 3 activities and nuclear morphology. Effects of c‐Fos and JunD expression on cell death were investigated by transfection. Results: We found that the exposure of cultured primary MEF cells to UV or H2O2 caused a significant increase in c‐Fos and JunD protein levels. In addition, these two proteins formed complexes with each other and contributed to activation of AP‐1 transcription complexes. More importantly, under both stress conditions, overexpression of JunD alone or overexpression of both c‐Fos and JunD reduced caspase 3 activity and cell death. At the same time, UV irradiation activated the MAPK/ERK1/2 signalling pathway. The suppression of MEK1/ERK1/2 activation inhibited UV‐induced expression of c‐Fos and JunD and increased caspase 3 activity and cell death. Conclusion: Our results suggest that both UV and H2O2 induce the activation of c‐Fos/JunD AP‐1 complexes resulting in the prevention of cell death. Moreover, UV irradiation‐induced increases in c‐Fos/JunD expression in primary MEF cells are mediated through the activation of the MAPK/ERK1/2 signalling pathway.
Susceptibility genes in Graves’ ophthalmopathy: searching for a needle in a haystack?
Authors: Bednarczuk Tomasz , Gopinath Bamini , Ploski Rafal , Wall Jack R.
Published: May 2007

The variety of clinical presentations of eye changes in patients with Graves’ disease suggests that complex interactions between genetic, environmental, endogenous and local factors influence the development/severity of Graves’ ophthalmopathy (GO). At present, the role of genetic factors in the development of GO remains unknown. Based on small case‐control association studies with candidate genes, several susceptibility loci in GO have been proposed. These are human leucocyte antigen (HLA, 6p21·3), cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4, 2q33), tumour necrosis factor (TNF, 6p21·3), interferon‐γ (IFN‐γ, 12q14), intercellular adhesion molecule‐1 (ICAM‐1, 19p13), and thyroid stimulating hormone receptor gene (TSH‐R, 14q31). Unfortunately, these results were either not confirmed or require replication in larger studies. There are many reasons for the lack of reproducibility of association studies in GO, including poor characterization of the studied groups and small sample sizes, which may result in both false positive and negative results. Thus, the genetic background of GO remains to be elucidated in future research. However, the possibility that GO may be a genetically heterogeneous disorder, or that the development of GO may be predominantly influenced by environmental factors such as cigarette smoking, can not be disregarded.
Eco‐evolutionary conservation biology: contemporary evolution and the dynamics of persistence
Authors: KINNISON MICHAEL T. , HAIRSTON NELSON G.
Published: May 2007

Natural and human mediated perturbations present challenges to the fate of populations but fuel contemporary evolution (evolution over humanly observable time‐scales). Here we ask if such evolution is sufficient to make the difference between population extinction and persistence.

To answer this question requires a shift from the usual focus on trait evolution to the emergent ‘eco‐evolutionary’ dynamics that arise through interactions of evolution, its fitness consequences and population abundance.

By combining theory, models and insights from empirical studies of contemporary evolution, we provide an assessment of three contexts: persistence of populationsin situ, persistence of colonising populations, and persistence under gene flow and in metapopulations.

Contemporary evolution can likely rescue some, but not all, populations facing environmental change. Populations may fail partly because of the demographic cost of selection.

Contemporary evolution that initiates positive population growth, such as selective founding processes, may create a ‘persistence vortex’ that overcomes the problems of small populations.

Complex, even shifting, relationships between gene flow and adaptation may aid the persistence of subpopulations as well as the persistence and expansion of metapopulations.

An eco‐evolutionary perspective suggests that we expand our focus beyond the acute problems of threatened populations and growing invasions, to consider how contemporary evolutionary mechanics contribute to such problems in the first place or affect their resolution.
The incidence and outcome of intracranial haemorrhage in newborns with haemophilia: analysis of the Nationwide Inpatient Sample database
Authors: TARANTINO M. D. , GUPTA S. L. , BRUSKY R. M.
Published: May 2007

Summary.  The incidence of intracranial haemorrhage (ICH) in newborns with haemophilia is unknown. Retrospective studies, estimate the incidence to be around 3%. Because of this uncertainty, we analysed the largest inpatient database in the USA, the Nationwide Inpatient Sample (NIS), to better approximate the incidence of ICH in these patients. ICD‐9 coding data were used to reference NIS entries of haemophilia (A, B or C) or von Willebrand’s disease (VWD), with intraventricular (IVH), subarachnoid (SAH), subdural (SDH) and/or intraparenchymal (IPH) haemorrhage. Of 9.2 × 107 hospitalizations from 1988 to 2001, 11% or 1 × 107 were newborns. Of these, 0.00527%, or 580 were diagnosed with haemophilia or VWD. Twenty of 580, or 3.4%, experienced an ICH. The ICH rate in non‐haemophilic newborns was 0.11% (P value: <0.0001). The rate of ICH among term haemophilic newborns without sepsis, respiratory distress syndrome (RDS) or congenital heart disease (CHD), delivered without vacuum assist was 1.9%. One death occurred on the day of birth in a term neonate with haemophilia C. The mean length of stay for ICH patients with haemophilia was 28 days (median 28, range: 6–143 days). The mean hospital charges for the group were $102 072 (median $67 551, range: $9624–467 132). These data add credence to the estimates of ICH in haemophilic newborns and may guide treatment strategies around the time of their birth. Further, uncomplicated delivery of term, otherwise healthy haemophilic newborns may carry a lesser risk of ICH.
Janus kinase 3‐deficient T lymphocytes have an intrinsic defect in CCR7‐mediated homing to peripheral lymphoid organs
Authors: García‐Zepeda Eduardo A. , Licona‐Limón Ileana , Jiménez‐Sólomon M. Fernanda , Soldevila Gloria
Published: May 2007

Chemokine‐mediated signalling involves the activation of a Janus kinase (Jak) pathway. We have previously shown that Jak3 mediates CCR9 and CXCR4 signalling in response to CCL25 and CXCL12 in BM progenitors and thymocytes. The lack of peripheral lymph nodes and Peyer's patches observed in Jak3–/– mice suggested a possible role of Jak3 in CCR7‐mediated homing to these organs. Here, we demonstrate phosphorylation of Jak3 in peripheral lymphocytes in response CCL19 and CCL21. In addition, Jak3–/– naïve T cells and pharmacologically inhibited Jak3+/+ T lymphocytes have impaired chemotactic responses towards these ligands. Interestingly, CCR7 expression was higher in Jak3–/– thymocytes compared to their Jak3+/– littermates, indicating that the impaired migration must be caused by impaired CCR7‐mediated signalling, in the absence of Jak3. In addition, adoptive transfer experiments showed that Jak3+/+ mice reconstituted with Jak3–/– green fluorescent protein (GFP)+ bone marrow progenitors had reduced T‐lymphocyte homing to peripheral and mesenteric lymph nodes, compared to reconstitution with Jak3+/+ GFP+ progenitors. Furthermore, reciprocal transfer experiments indicated that Jak3–/– stromal cells were not responsible for the deficient T‐cell homing. Finally, we performed direct competitive homing assays and demonstrated that Jak3–/– T lymphocytes have a clear defect in homing to peripheral and mesenteric lymph nodes, while migration to spleen was moderately impaired. Our data demonstrates that Jak3–/– T lymphocytes have an intrinsic defect in CCR7‐mediated homing to peripheral lymphoid organs.