bluuebunny/crossref_metadata_2025 huggingface dataset:
Variational formulation for weakly nonlinear perturbations of ideal magnetohydrodynamics
Authors: HIROTA M.
Published: January 2011

A new equation of motion that governs weakly nonlinear phenomena in ideal magnetohydrodynamics (MHDs) is derived as a natural extension of the well-known linearized equation of motion for the displacement field. This derivation is made possible by expanding the MHD Lagrangian explicitly up to third order with respect to the displacement of plasma, which necessitates an efficient use of the Lie series expansion. The resultant equation of motion (i.e. the Euler–Lagrange equation) includes a new quadratic force term which is responsible for various mode–mode coupling due to the MHD nonlinearity. The third-order potential energy serves to quantify the coupling coefficient among resonant three modes and its cubic symmetry proves the Manley–Rowe relations. In contrast to earlier works, the coupling coefficient is expressed only by the displacement vector field, which is already familiar in the linear MHD theory, and both the fixed and free boundary cases are treated systematically.
Reworked late Neogene Austrochlamys anderssoni (Mollusca: Bivalvia) from northern James Ross Island, Antarctica
Authors: Pirrie D. , Jonkers H.A. , Smellie J.L. , Crame J.A. , McArthur J.M.
Published: January 2011

We report on the discovery of a new outcrop of fossiliferous Neogene sediments on northern James Ross Island, northern Antarctic Peninsula. Approximately 100 specimens of the pectinid bivalve Austrochlamys anderssoni (Hennig, 1911) were collected from the permafrost active layer. This bivalve species has a late Miocene to late Pliocene range and has previously been reported from both the glaciomarine Hobbs Glacier Formation and the interglacial Cockburn Island Formation in the James Ross Island area. The localized presence of abundant A. anderssoni within the permafrost suggests that the fossils have been frost heaved from an outcrop of either the Cockburn Island or the Hobbs Glacier formations, originally deposited on northern James Ross Island. The overall shell form, general absence of associated Antarctic Peninsula-derived clasts in the host sediment, and the measured 87Sr/86Sr isotope ratio of the shells (0.709050) which is indistinguishable from that for pectinid bivalves from the Cockburn Island Formation on Cockburn Island (0.709047) suggest that the shells were derived from a unit similar in age to the Cockburn Island Formation. This suggests that the Cockburn Island Formation was originally more laterally extensive than was previously known.
Teaching and learning geriatric medicine
Authors: Singh Inder , Hubbard Ruth E
Published: January 2011

Populations throughout the world are ageing, with the oldest old the most rapidly growing segment of society. Caring for this ageing population, some of whom have multiple chronic and disabling diseases, will be challenging to healthcare systems. Current training programmes are generating relatively low numbers of geriatricians, largely because students and residents lack interest in a career in geriatric medicine. Therefore, specialists in geriatric medicine cannot directly provide care for all older people. There is a responsibility to ensure that successful practices and essential skills are shared.

Here we explore negative attitudes towards geriatric medicine and contrast these with factors motivating change. Educational theories are discussed to investigate how processes of learning and the personal development of students can be optimized. An understanding of geriatric medicine is important for undergraduates, postgraduate trainees in geriatric medicine, general practitioners and allied health professionals. The different challenges presented by each group are reviewed, accompanied by recommendations to enhance learning and examples of effective teaching practices.
VOTE-BUYING AND GROWTH
Authors: Gersbach Hans , Mühe Felix
Published: January 2011

Vote-buying is widely used by parties in developing countries to influence the outcome of elections. We examine the impact of vote-buying on growth. We consider a model with a poverty trap where redistribution can promote growth. We show that vote-buying contributes to the persistence of poverty as taxed wealthy people buy votes from poor people. We then show that there exists a democratic constitution that breaks vote-buying and promotes growth. Such a constitution involves rotating agenda setting, a taxpayer-protection rule, and repeated voting. The latter rule makes vote-buying prohibitively costly.
Genetic diversity in Anatolian wild grapes (Vitis viniferasubsp.sylvestris) estimated by SSR markers
Authors: Ergül Ali , Perez-Rivera Gemma , Söylemezoğlu Gökhan , Kazan Kemal , Arroyo-Garcia Rosa
Published: January 2011

Anatolia (Asia Minor) is considered to be the cradle of viticulture, but wild grape accessions from this region have not been subjected to any genetic analysis. We present the first genetic characterization of wild grapes (Vitis viniferasubsp.sylvestris) from this region. Using 15 nuclear microsatellites, we genotyped 84 wild grape accessions collected from three Anatolian locations. The unweighted pair group method with arithmetic mean analysis revealed four genetic clusters that partially separated Anatolian wild grape populations. In general, accessions from geographically closer locations showed higher genetic similarities than those from more distant locations. In some cases, accessions from one population showed close genetic relationships to accessions from a different population. The genetic diversity between natural populations from both ends of the Mediterranean basin has shown higher genetic diversity in the Anatolian Peninsula than peripheral populations, suggesting that this area could be one centre of diversity of the species. The genetic relationship between wild and cultivated grapevine from Anatolian Peninsula indicated a clear separation between them. However, we cannot discarded a local genetic contribution. Overall, this study reveals useful information for management and potential utilization of Anatolian wild grape germplasm.
Risk adjustment and risk equalization: what needs to be done?
Authors: Van de Ven Wynand P. M. M.
Published: January 2011

In this paper, we first deal with the rationale of risk adjustment and risk equalization in health insurance markets. Then we discuss the state of the art concerning the application of risk adjustment and risk equalization in practice. Finally, we focus on: What needs to be done?
The politics of health-care reform in the Netherlands since 2006
Authors: Maarse Hans , Paulus Aggie
Published: January 2011

This article comments on Schut and van de Ven's overview of the results of purchaser competition in Dutch health care, which concludes that the glass can be seen as half full or half empty. Although it is true that results have been achieved, we believe that the evidence is incomplete and in some respects flimsy. More importantly, however, Schut and van de Ven neglect the political context of the market reform introduced in 2006. The reform is far from finished and there has been a constant need for political compromise. Optimism about the market's potential also seems to be on the wane. Several insurer and provider initiatives have provoked political resistance. As a result, there are good reasons to argue that the reform's future is uncertain.
Effects of purchaser competition in the Dutch health system: is the glass half full or half empty?
Authors: Schut Frederik T. , van de Ven Wynand P. M. M.
Published: January 2011

In 2006, the Dutch health insurance system was radically reformed to strengthen competition among health insurers as purchasers of health services. This article considers whether purchaser competition has improved efficiency in health-care provision. Although supply and price regulation still dominates the allocation of health services, purchaser competition has already significantly affected the provision of hospital care, pharmaceuticals and primary care, as well as efforts to gather and disseminate information about quality of care. From this perspective, the glass is half full. However, based on the crude performance indicators available, the reforms have not yet demonstrated significant effects on the performance of the Dutch health system. From this perspective the glass is half empty. The article concludes that the effectiveness of purchaser competition depends crucially on the success of ongoing efforts to improve performance indicators, product classification and the risk equalisation scheme.
Diastolische Herzinsuffizienz – Diagnostik und Therapie
Authors: Schaefer Hans-Hendrik , Dieterle Thomas
Published: January 2011

Die diastolische Herzinsuffizienz, auch als Herzinsuffizienz mit normaler bzw. erhaltener Ejektionsfraktion bezeichnet, hat weltweit eine hohe Prävalenz und Mortalität. Klinisch manifestiert sie sich mit typischen Symptomen und Zeichen einer Herzinsuffizienz bei normaler bzw. nur leicht eingeschränkter Auswurffraktion des linken Ventrikels. Die Ursachen der diastolischen Herzinsuffizienz sind noch nicht vollständig verstanden. Funktionelle und strukturelle Veränderungen der Kardiomyozyten, der extrazellulären Matrix wie auch der Funktion des dem Herzen nachgeschalteten Gefäßbettes werden als Auslöser diskutiert. Die Diagnose erfolgt über herzinsuffizienz-typische Symptome und klinische Zeichen sowie dem – meist echokardiographischen – Nachweis einer diastolischen Dysfunktion und eines erhöhten Füllungsdruckes des linken Ventrikels. Erhöhte natriuretische Peptide unterstützen die Diagnose einer diastolischen Herzinsuffizienz. Katheteruntersuchungen und die Magnet-Resonanz-Tomographie helfen bei der Sicherung der Diagnose. Bisher existiert keine Therapie, die eine Reduktion von Morbidität und Mortalität zeigen konnte. Die aktuellen Therapieempfehlungen betonen daher die Wichtigkeit einer adäquaten Behandlung der Risikofaktoren und der Ursachen einer diastolischen Herzinsuffizienz.
Device-Therapie der chronischen Herzinsuffizienz
Authors: Schaer Beat A. , Sticherling Christian
Published: January 2011

Neben der medikamentösen Therapie steht mit der kardialen Resynchronisationstherapie bei ausgewählten Herzinsuffizienz-Patienten eine weitere Therapieoption zur Verfügung. Zur Verhinderung des plötzlichen Herztodes sollte zudem bei ihnen auch eine allfällige ICD-Implantation evaluiert werden.
Chirurgische Therapieoptionen bei terminaler Herzinsuffizienz
Authors: Grapow Martin T. R. , Carrel Thierry P. , Eckstein Friedrich S.
Published: January 2011

Trotz deutlicher Fortschritte in der pharmakologischen Therapie bleibt die terminale Herzinsuffizienz eine der Haupttodesursachen in der westlichen Welt. Der Goldstandard in der Therapie ist immer noch die Herztransplantation, es stehen den vielen potentiellen Empfängern jedoch signifikant weniger Spenderorgane zur Verfügung. Innerhalb der letzten 20 Jahre wurden parallel zur medikamentösen und rhythmologischen Herzinsuffizienztherapie zunehmend chirurgische, organerhaltende Strategien und Therapien eingeführt, um eine anstehende Herztransplantation hinauszuzögern oder zu vermeiden. Bei Patienten mit terminaler Herzinsuffizienz mit ausgereizter pharmakologischer Therapie sollte zeitnah die Möglichkeit einer individuell konfektionierten, chirurgischen Therapie als Alternative geprüft werden. Das vorliegende Manuskript soll einen Überblick geben über derzeitige und in Zukunft mögliche chirurgisch-therapeutische Optionen in der Behandlung der terminalen Herzinsuffizienz.
Herzinsuffizienz und Komorbiditäten
Authors: Widmer Fritz
Published: January 2011

Die Anzahl herzinsuffizienter Patienten mit nichtkardialen Komorbiditäten wächst stetig an und stellt eine immer größere medizinische und personelle Herausforderung dar. Niereninsuffizienz, Diabetes mellitus, COPD, Schlafstörungen und die Anämie sind die wichtigsten Prädiktoren für schlechten outcome und Mortalität sowie für verminderte Quality of Life. Das Erfassen der Komorbiditäten braucht internistisches Interesse, die Behandlung stellt eine ärztliche Herausforderung dar und die Betreuung dieser chronisch Kranken ist zeitintensiv. Gerade hier wären wir Ärzte auf die Unterstützung durch Herzinsuffizienz-Beraterinnen dringend angewiesen.
Rehabilitation bei Herzinsuffizienz – gibt es eine Behandlung jenseits von Pharmakologie, Chirurgie und Device-Therapie?
Authors: Lefkovits Michael
Published: January 2011

Bei Patienten mit chronischer Herzinsuffizienz kann die Leistungsintoleranz nicht alleine durch die kardiale Dysfunktion erklärt werden. Im Rahmen der Progression der Erkrankung nimmt die Bedeutung von peripheren Faktoren zu. Eine chronische Minderperfusion der Skelettmuskulatur, Inaktivität sowie die schädliche neurohumorale Aktivierung führen zu einer Myopathie mit Verlust an Mitochondrien, Kapillaren und zunehmender Fibrosierung. Ein systematisches, kontrolliertes und dosiertes Training verbessert bei Patienten mit einer Herzinsuffizienz die kardinalen Symptome wie Dyspnoe und Leistungsintoleranz. Zusätzlich wird eine Verbesserung der Lebensqualität, der linksventrikulären Pumpfunktion, eine Abnahme der enddiastolischen Dimensionen des linken Ventrikel, eine Verbesserung der Atemeffizienz sowie eine Reduktion der Rehospitalisation erreicht. In den europäischen Richtlinien besteht daher für das Herzinsuffizienztraining eine Empfehlung der Klasse I, welche somit gleich stark ausfällt wie diejenige für eine pharmakologische Standardtherapie. Der genaue Wirkungsmechanismus des Herzinsuffizienztrainings ist im Detail unklar. Bei ischämischer Herzinsuffizienz verbessert das Training die myokardiale Perfusion initial durch eine Verbesserung der Endothelfunktion und sekundär durch intermittierende ischämische Reize, welche eine Kollateralisation fördern. Das Training wirkt auf muskulärer Ebene der peripheren Myopathie entgegen und kann das Auftreten einer kardialen Kachexie verlangsamen oder umkehren. Im Vergleich zur Prävalenz der Herzinsuffizienz sowie der Bedeutung des Trainings ist die Zuweisung mit weniger als 500 Patienten pro Jahr in sämtliche Schweizer-Rehabilitationszentren sehr gering. Ein Herzinsuffizienztraining sollte in einem Zentrum strukturiert und kontrolliert eingeleitet werden und kann danach zuhause lebenslänglich weitergeführt werden.
Coccolithophore estimates of paleotemperature and paleoproductivity changes in the southeast Pacific over the past ∼27 kyr
Authors: Saavedra‐Pellitero M. , Flores J. A. , Lamy F. , Sierro F. J. , Cortina A.
Published: January 2011

We provide high‐resolution sea surface temperature (SST) and paleoproductivity data focusing on Termination 1. We describe a new method for estimating SSTs based on multivariate statistical analyses performed on modern coccolithophore census data, and we present the first downcore reconstructions derived from coccolithophore assemblages at Ocean Drilling Project (ODP) Site 1233 located offshore Chile. We compare our coccolithophore SST record to alkenone‐based SSTs as well as SST reconstructions based on dinoflagellates and radiolaria. All reconstructions generally show a remarkable concordance. As in the alkenone SST record, the Last Glacial Maximum (LGM, 19–23 kyr B.P.) is not clearly defined in our SST reconstruction. After the onset of deglaciation, three major warming steps are recorded: from 18.6 to 18 kyr B.P. (∼2.6°C), from 15.7 to 15.3 kyr B.P. (∼2.5°C), and from 13 to 11.4 kyr B.P. (∼3.4°C). Consistent with the other records from Site 1233 and Antarctic ice core records, we observed a clear Holocene Climatic Optimum (HCO) from ∼8–12 kyr B.P. Combining the SST reconstruction with coccolith absolute abundances and accumulation rates, we show that colder temperatures during the LGM are linked to higher coccolithophore productivity offshore Chile and warmer SSTs during the HCO to lower coccolithophore productivity, with indications of weak coastal upwelling. We interpret our data in terms of latitudinal displacements of the Southern Westerlies and the northern margin of the Antarctic Circumpolar Current system over the deglaciation and the Holocene.
Structural evolution of a composite middle to lower crustal section: The Sierra de Pie de Palo, northwest Argentina
Authors: Mulcahy S. R. , Roeske S. M. , McClelland W. C. , Jourdan F. , Iriondo A. , Renne P. R. , Vervoort J. D. , Vujovich G. I.
Published: January 2011

The Sierra de Pie de Palo of northwest Argentina preserves middle to lower crustal metamorphic rocks that were penetratively deformed during Ordovician accretion of the Precordillera terrane to the Gondwana margin. New structural, petrologic, and geochronologic data from a 40 km structural transect reveals that the Sierra de Pie de Palo preserves a middle to lower crustal ductile thrust complex consisting of individual structural units and not an intact ophiolite and cover sequence. Top‐to‐the‐west thrusting occurred intermittently on discrete ductile shear zones from ∼515 to ∼417 Ma and generally propagated toward the foreland with progressive deformation. Ordovician crustal shortening and peak metamorphic temperatures in the central portion of the Sierra de Pie de Palo were synchronous with retro‐arc shortening and magmatic flare‐up within the Famatina arc. Accretion of the Precordillera terrane resulted in the end of arc flare‐up and the onset of synconvergent extension by ∼439 Ma. Continued synextensional to postextensional convergence was accommodated along progressively lower grade shear zones following terrane accretion and the establishment of a new plate margin west of the Precordillera terrane. The results support models of Cordilleran orogens that link voluminous arc magmatism to periods of regional shortening. The deformation, metamorphic, and magmatic history within the Sierra de Pie de Palo is consistent with models placing the region adjacent to the Famatina margin in the middle Cambrian and not as basement to the Precordillera terrane.
Performance of IRI‐based ionospheric critical frequency calculations with reference to forecasting
Authors: Ünal İbrahim , Şenalp Erdem Türker , Yeşil Ali , Tulunay Ersin , Tulunay Yurdanur
Published: January 2011

Ionospheric critical frequency (foF2) is an important ionospheric parameter in telecommunication. Ionospheric processes are highly nonlinear and time varying. Thus, mathematical modeling based on physical principles is extremely difficult if not impossible. The authors forecast foF2 values by using neural networks and, in parallel, they calculate foF2 values based on the IRI model. The foF2 values were forecast 1 h in advance by using the Middle East Technical University Neural Network model (METU‐NN) and the work was reported previously. Since then, the METU‐NN has been improved. In this paper, 1 h in advance forecast foF2 values and the calculated foF2 values have been compared with the observed values considering the Slough (51.5°N, 0.6°W), Uppsala (59.8°N, 17.6°E), and Rome (41.8°N, 12.5°E) station foF2 data. The authors have considered the models alternative to each other. The performance results of the models are promising. The METU‐NN foF2 forecast errors are smaller than the calculated foF2 errors. The models may be used in parallel employing the METU‐NN as the primary source for the foF2 forecasting.
Comparative sensitivity analysis of four distributed erosion models
Authors: Cheviron B. , Le Bissonnais Y. , Desprats J. F. , Couturier A. , Gumiere S. J. , Cerdan O. , Darboux F. , Raclot D.
Published: January 2011

Using a previously defined framework, we performed a comparative sensitivity analysis of four very different distributed erosion models (MHYDAS, STREAM, PESERA, and MESALES). We investigated their sensitivities to input fluxes, hydrological submodels, and specific erosion parameters gathered into equivalent slope and equivalent erodibility for each model, thus allowing explicit comparisons between models. Tests involved multiple combinations of rain intensities and runoff conditions for selected screenings of the equivalent parameter space, resorting to one‐at‐a‐time displacements and Latin hypercube samples. Sensitivity to spatial distributions of erosion parameters was calculated as a normalized index of numerical spread of soil loss results, obtained at the outlet of a nine‐cell virtual catchment endowed with a fixed flow pattern. Spatially homogeneous or distributed parameterizations yielded responses of comparable magnitudes. Equivalent erodibility was often the key parameter, while sensitivity trends depended on input fluxes and the propensity of soils for runoff, affecting continuous and discrete models in clearly dissimilar ways.
The metabolomic profile during isoflurane anesthesia differs from propofol anesthesia in the live rodent brain
Authors: Makaryus Rany , Lee Hedok , Yu Mei , Zhang Shaonan , Smith S David , Rebecchi Mario , Glass Peter S , Benveniste Helene
Published: January 2011

Development of noninvasive techniques to discover new biomarkers in the live brain is important to further understand the underlying metabolic pathways of significance for processes such as anesthesia-induced apoptosis and cognitive dysfunction observed in the undeveloped brain. We used in vivo proton magnetic resonance spectroscopy and two different signal processing approaches to test the hypothesis that volatile (isoflurane) and intravenous (propofol) anesthetics at equipotent doses produce distinct metabolomic profiles in the hippocampus and parietal cortex of the live rodent. For both brain regions, prolonged isoflurane anesthesia was characterized by higher levels of lactate (Lac) and glutamate compared with long-lasting propofol. In contrast, propofol anesthesia was characterized by very low concentrations of Lac ([lac]) as well as glucose. Quantitative analysis revealed that the [lac] was fivefold higher with isoflurane compared with propofol anesthesia and independent of [lac] in blood. The metabolomic profiling further demonstrated that for both brain regions, Lac was the most important metabolite for the observed differences, suggesting activation of distinct metabolic pathways that may impact mechanisms of action, background cellular functions, and possible agent-specific neurotoxicity.
High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke
Authors: Campos Francisco , Sobrino Tomás , Ramos-Cabrer Pedro , Castellanos Mar , Blanco Miguel , Rodríguez-Yáñez Manuel , Serena Joaquín , Leira Rogelio , Castillo José
Published: January 2011

The capacity of the blood enzyme glutamate oxaloacetate transaminase (GOT) to remove glutamate from the brain by means of blood glutamate degradation has been shown in experimental models to be an efficient and novel neuroprotective tool against ischemic stroke; however, the beneficial effects of this enzyme should be tested in patients with stroke to validate these results. This study aims to investigate the association of GOT levels in blood with clinical outcome in patients with acute ischemic stroke. In two clinical independent studies, we found that patients with poor outcome show higher glutamate and lower GOT levels in blood at the time of admission. Lower GOT levels and higher glutamate levels were independently associated with poorer functional outcome at 3 months and higher infarct volume. These findings show a clear association between high blood glutamate levels and worse outcome and vice versa for GOT, presumably explained by the capacity of this enzyme to metabolize blood glutamate.
The Simulation Experiment Description Markup Language - Update
Authors: Bergmann Frank
Published: January 2011

This presentation gives a brief overview of the Simulation Experiment Description Markup Language L1V1 as well as an introduction to LibSedML (http://libsedml.sf.net) a library for reading and writing SED-ML documents.
AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer
Authors: Hardie D. Grahame
Published: January 2011

It is essential to life that a balance is maintained between processes that produce ATP and those that consume it. An obvious way to do this would be to have systems that monitor the levels of ATP and ADP, although because of the adenylate kinase reaction (2ADP↔ATP+AMP), AMP is actually a more sensitive indicator of energy stress than ADP. Following the discoveries that glycogen phosphorylase and phosphofructokinase were regulated by AMP and ATP, Daniel Atkinson proposed that all enzymes at branch points between biosynthesis and degradation would be regulated by adenine nucleotides. This turned out to be correct, but what Atkinson did not anticipate was that sensing of nucleotides would, in most cases, be performed not by the metabolic enzymes themselves, but by a signalling protein, AMPK (AMP-activated protein kinase). AMPK occurs in essentially all eukaryotes and consists of heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits, of which the latter carries the nucleotide-binding sites. Once activated by a metabolic stress, it phosphorylates numerous targets that alter enzyme activity and gene expression to initiate corrective responses. In lower eukaryotes, it is critically involved in the responses to starvation for a carbon source. Because of its ability to switch cellular metabolism from anabolic to catabolic mode, AMPK has become a key drug target to combat metabolic disorders associated with overnutrition such as Type 2 diabetes, and some existing anti-diabetic drugs (e.g. metformin) and many ‘nutraceuticals’ work by activating AMPK, usually via inhibition of mitochondrial ATP production. AMPK activators also potentially have anticancer effects, and there is already evidence that metformin provides protection against the initiation of cancer. Whether AMPK activators can be used to treat existing cancer is less clear, because many tumour cells appear to have been selected for mutations that inactivate the AMPK system. However, if we can identify the various mechanisms by which this occurs, we may be able to find ways of overcoming it.
Homologous recombination in the archaea: the means justify the ends
Authors: White Malcolm F.
Published: January 2011

The process of information exchange between two homologous DNA duplexes is known as homologous recombination (HR) or double-strand break repair (DSBR), depending on the context. HR is the fundamental process underlying the genome shuffling that expands genetic diversity (for example during meiosis in eukaryotes). DSBR is an essential repair pathway in all three domains of life, and plays a major role in the rescue of stalled or collapsed replication forks, a phenomenon known as recombination-dependent replication (RDR). The process of HR in the archaea is gradually being elucidated, initially from structural and biochemical studies, but increasingly using new genetic systems. The present review focuses on our current understanding of the structures, functions and interactions of archaeal HR proteins, with an emphasis on recent advances. There are still many unknown aspects of archaeal HR, most notably the mechanism of branch migration of Holliday junctions, which is also an open question in eukarya.
The archaeal PCNA proteins
Authors: Pan Miao , Kelman Lori M. , Kelman Zvi
Published: January 2011

PCNA (proliferating-cell nuclear antigen) is a ring-shaped protein that encircles duplex DNA and plays an essential role in many DNA metabolic processes. The PCNA protein interacts with a large number of cellular factors and modulates their enzymatic activities. In the present paper, we summarize the structures, functions and interactions of the archaeal PCNA proteins.
Plasmids, viruses and virus-like membrane vesicles from Thermococcales
Authors: Soler Nicolas , Gaudin Marie , Marguet Evelyne , Forterre Patrick
Published: January 2011

Several families of plasmids and viruses (PVs) have now been described in hyperthermophilic archaea of the order Thermococcales. One family of plasmids replicates by the rolling circle mechanism, whereas most other PVs probably replicate by the θ mode. PVs from Thermococcales encode novel families of DNA replication proteins that have only detectable homologues in other archaeal PVs. PVs from different families share a common gene pool and co-evolve with their hosts. Most Thermococcales also produce virus-like membrane vesicles similar to eukaryotic microparticles (ectosomes). Some membrane vesicles of Thermococcus nautilus harbour the plasmid pTN1, suggesting that vesicles can be involved in plasmid transfer between species.
Assembling the archaeal ribosome: roles for translation-factor-related GTPases
Authors: Blombach Fabian , Brouns Stan J.J. , van der Oost John
Published: January 2011

The assembly of ribosomal subunits from their individual components (rRNA and ribosomal proteins) requires the assistance of a multitude of factors in order to control and increase the efficiency of the assembly process. GTPases of the TRAFAC (translation-factor-related) class constitute a major type of ribosome-assembly factor in Eukaryota and Bacteria. They are thought to aid the stepwise assembly of ribosomal subunits through a ‘molecular switch’ mechanism that involves conformational changes in response to GTP hydrolysis. Most conserved TRAFAC GTPases are involved in ribosome assembly or other translation-associated processes. They typically interact with ribosomal subunits, but in many cases, the exact role that these GTPases play remains unclear. Previous studies almost exclusively focused on the systems of Bacteria and Eukaryota. Archaea possess several conserved TRAFAC GTPases as well, with some GTPase families being present only in the archaeo–eukaryotic lineage. In the present paper, we review the occurrence of TRAFAC GTPases with translation-associated functions in Archaea.
CRISPR-based immune systems of the Sulfolobales: complexity and diversity
Authors: Garrett Roger A. , Shah Shiraz A. , Vestergaard Gisle , Deng Ling , Gudbergsdottir Soley , Kenchappa Chandra S. , Erdmann Susanne , She Qunxin
Published: January 2011

CRISPR (cluster of regularly interspaced palindromic repeats)/Cas and CRISPR/Cmr systems of Sulfolobus, targeting DNA and RNA respectively of invading viruses or plasmids are complex and diverse. We address their classification and functional diversity, and the wide sequence diversity of RAMP (repeat-associated mysterious protein)-motif containing proteins encoded in Cmr modules. Factors influencing maintenance of partially impaired CRISPR-based systems are discussed. The capacity for whole CRISPR transcripts to be generated despite the uptake of transcription signals within spacer sequences is considered. Targeting of protospacer regions of invading elements by Cas protein–crRNA (CRISPR RNA) complexes exhibit relatively low sequence stringency, but the integrity of protospacer-associated motifs appears to be important. Different mechanisms for circumventing or inactivating the immune systems are presented.
Positive supercoiling in thermophiles and mesophiles: of the good and evil
Authors: Valenti Anna , Perugino Giuseppe , Rossi Mosè , Ciaramella Maria
Published: January 2011

DNA supercoiling plays essential role in maintaining proper chromosome structure, as well as the equilibrium between genome dynamics and stability under specific physicochemical and physiological conditions. In mesophilic organisms, DNA is negatively supercoiled and, until recently, positive supercoiling was considered a peculiar mark of (hyper)thermophilic archaea needed to survive high temperatures. However, several lines of evidence suggest that negative and positive supercoiling might coexist in both (hyper)thermophilic and mesophilic organisms, raising the possibility that positive supercoiling might serve as a regulator of various cellular events, such as chromosome condensation, gene expression, mitosis, sister chromatid cohesion, centromere identity and telomere homoeostasis.
Assembly and function of the archaeal flagellum
Authors: Ghosh Abhrajyoti , Albers Sonja-Verena
Published: January 2011

Motility is a common behaviour in prokaryotes. Both bacteria and archaea use flagella for swimming motility, but it has been well documented that structures of the flagellum from these two domains of life are completely different, although they contribute to a similar function. Interestingly, information available to date has revealed that structurally archaeal flagella are more similar to bacterial type IV pili rather than to bacterial flagella. With the increasing genome sequence information and advancement in genetic tools for archaea, identification of the components involved in the assembly of the archaeal flagellum is possible. A subset of these components shows similarities to components from type IV pilus-assembly systems. Whereas the molecular players involved in assembly of the archaeal flagellum are being identified, the mechanics and dynamics of the assembly of the archaeal flagellum have yet to be established. Recent computational analysis in our laboratory has identified conserved highly charged loop regions within one of the core proteins of the flagellum, the membrane integral protein FlaJ, and predicted that these are involved in the interaction with the assembly ATPase FlaI. Interestingly, considerable variation was found among the loops of FlaJ from the two major subkingdoms of archaea, the Euryarchaeota and the Crenarchaeota. Understanding the assembly pathway and creating an interaction map of the molecular players in the archaeal flagellum will shed light on the details of the assembly and also the evolutionary relationship to the bacterial type IV pili-assembly systems.
The role of the DNA sliding clamp in Okazaki fragment maturation in archaea and eukaryotes
Authors: Beattie Thomas R. , Bell Stephen D.
Published: January 2011

Efficient processing of Okazaki fragments generated during discontinuous lagging-strand DNA replication is critical for the maintenance of genome integrity. In eukaryotes, a number of enzymes co-ordinate to ensure the removal of initiating primers from the 5′-end of each fragment and the generation of a covalently linked daughter strand. Studies in eukaryotic systems have revealed that the co-ordination of DNA polymerase δ and FEN-1 (Flap Endonuclease 1) is sufficient to remove the majority of primers. Other pathways such as that involving Dna2 also operate under certain conditions, although, notably, Dna2 is not universally conserved between eukaryotes and archaea, unlike the other core factors. In addition to the catalytic components, the DNA sliding clamp, PCNA (proliferating-cell nuclear antigen), plays a pivotal role in binding and co-ordinating these enzymes at sites of lagging-strand replication. Structural studies in eukaryotic and archaeal systems have revealed that PCNA-binding proteins can adopt different conformations when binding PCNA. This conformational malleability may be key to the co-ordination of these enzymes' activities.
An additional glucose dehydrogenase from Sulfolobus solfataricus: fine-tuning of sugar degradation?
Authors: Haferkamp Patrick , Kutschki Simone , Treichel Jenny , Hemeda Hatim , Sewczyk Karsten , Hoffmann Daniel , Zaparty Melanie , Siebers Bettina
Published: January 2011

Within the SulfoSYS (Sulfolobus Systems Biology) project, the effect of temperature on a metabolic network is investigated at the systems level. Sulfolobus solfataricus utilizes an unusual branched ED (Entner–Doudoroff) pathway for sugar degradation that is promiscuous for glucose and galactose. In the course of metabolic pathway reconstruction, a glucose dehydrogenase isoenzyme (GDH-2, SSO3204) was identified. GDH-2 exhibits high similarity to the previously characterized GDH-1 (SSO3003, 61% amino acid identity), but possesses different enzymatic properties, particularly regarding substrate specificity and catalytic efficiency. In contrast with GDH-1, which exhibits broad substrate specificity for C5 and C6 sugars, GDH-2 is absolutely specific for glucose. The comparison of kinetic parameters suggests that GDH-2 might represent the major player in glucose catabolism via the branched ED pathway, whereas GDH-1 might have a dominant role in galactose degradation via the same pathway as well as in different sugar-degradation pathways.
A thaumarchaeal provirus testifies for an ancient association of tailed viruses with archaea
Authors: Krupovic Mart , Spang Anja , Gribaldo Simonetta , Forterre Patrick , Schleper Christa
Published: January 2011

Archaeal viruses, or archaeoviruses, display a wide range of virion morphotypes. Whereas the majority of those morphotypes are unique to archaeal viruses, some are more widely distributed across different cellular domains. Tailed double-stranded DNA archaeoviruses are remarkably similar to viruses of the same morphology (order Caudovirales) that infect many bacterial hosts. They have, so far, only been found in one phylum of the archaea, the Euryarchaeota, which has led to controversial hypotheses about their origin. In the present paper, we describe the identification and analysis of a putative provirus present in the genome of a mesophilic thaumarchaeon. We show that the provirus is related to tailed bacterial and euryarchaeal viruses and encodes a full complement of proteins that are required to build a tailed virion. The recently discovered wide distribution of tailed viruses in Euryarchaeota and the identification of a related provirus in Thaumarchaeota, an archaeal phylum which might have branched off before the separation of Crenarchaeota and Euryarchaeota, suggest that an association of these viruses with Archaea might be more ancient than previously anticipated.
Translation initiation in Archaea: conserved and domain-specific features
Authors: Benelli Dario , Londei Paola
Published: January 2011

Initiation is a critical step in translation, during which the ribosome lands on the start codon and sets the correct reading frame for mRNA decoding. The rate and efficiency of translation are largely determined by initiation, which is therefore the preferred target of translation regulation mechanisms. Initiation has incurred an extensive evolutionary divergence among the primary domains of cell descent. The Archaea, albeit prokaryotes, have an initiation mechanism and apparatus more complex than those of the Bacteria; the molecular details of archaeal initiation are just beginning to be unravelled. The most notable aspects of archaeal initiation are the presence of two, perhaps three, distinct mechanisms for mRNA–ribosome interaction and the presence of a relatively large set of IFs (initiation factors), several of which are shared exclusively with the Eukarya. Among these, the protein termed a/eIF2 (archaeal/eukaryotic IF2) and aIF6 (archaeal IF6) are of special interest, since they appear to play key regulatory roles in the Eukarya. Studies of the function of these factors in Archaea have uncovered new features that will help to elucidate their conserved and domain-specific functions.
Insights into chaperonin function from studies on archaeal thermosomes
Authors: Lund Peter
Published: January 2011

It is now well understood that, although proteins fold spontaneously (in a thermodynamic sense), many nevertheless require the assistance of helpers called molecular chaperones to reach their correct and active folded state in living cells. This is because the pathways of protein folding are full of traps for the unwary: the forces that drive proteins into their folded states can also drive them into insoluble aggregates, and, particularly when cells are stressed, this can lead, without prevention or correction, to cell death. The chaperonins are a family of molecular chaperones, practically ubiquitous in all living organisms, which possess a remarkable structure and mechanism of action. They act as nanoboxes in which proteins can fold, isolated from their environment and from other partners with which they might, with potentially deleterious consequences, interact. The opening and closing of these boxes is timed by the binding and hydrolysis of ATP. The chaperonins which are found in bacteria are extremely well characterized, and, although those found in archaea (also known as thermosomes) and eukaryotes have received less attention, our understanding of these proteins is constantly improving. This short review will summarize what we know about chaperonin function in the cell from studies on the archaeal chaperonins, and show how recent work is improving our understanding of this essential class of molecular chaperones.
Structure and function of the primase domain of the replication protein from the archaeal plasmid pRN1
Authors: Lipps Georg
Published: January 2011

The replication protein of the archaeal plasmid pRN1 is a multifunctional enzyme which appears to carry out several steps at the plasmid replication initiation. We recently determined the structure of the minimal primase domain of the replication protein and found out that the primase domain consists of a catalytic primase/polymerase domain and an accessory helix-bundle domain. Structure-guided mutagenesis allowed us to identify amino acids which are important for template binding, dinucleotide formation and a step before primer extension. On the basis of functional and structural data, we propose a model of the catalytic cycle of primer synthesis by the pRN1 replication protein.
Nucleoid-associated proteins in Crenarchaea
Authors: Driessen Rosalie P.C. , Dame Remus Th.
Published: January 2011

Architectural proteins play an important role in compacting and organizing the chromosomal DNA in all three kingdoms of life (Eukarya, Bacteria and Archaea). These proteins are generally not conserved at the amino acid sequence level, but the mechanisms by which they modulate the genome do seem to be functionally conserved across kingdoms. On a generic level, architectural proteins can be classified based on their structural effect as DNA benders, DNA bridgers or DNA wrappers. Although chromatin organization in archaea has not been studied extensively, quite a number of architectural proteins have been identified. In the present paper, we summarize the knowledge currently available on these proteins in Crenarchaea. By the type of architectural proteins available, the crenarchaeal nucleoid shows similarities with that of Bacteria. It relies on the action of a large set of small, abundant and generally basic proteins to compact and organize their genome and to modulate its activity.
Studying biomolecular complexes with pulsed electron–electron double resonance spectroscopy
Authors: Reginsson Gunnar W. , Schiemann Olav
Published: January 2011

The function of biomolecules is intrinsically linked to their structure and the complexes they form during function. Techniques for the determination of structures and dynamics of these nanometre assemblies are therefore important for an understanding on the molecular level. PELDOR (pulsed electron–electron double resonance) is a pulsed EPR method that can be used to reliably and precisely measure distances in the range 1.5–8 nm, to unravel orientations and to determine the number of monomers in complexes. In conjunction with site-directed spin labelling, it can be applied to biomolecules of all sizes in aqueous solutions or membranes. PELDOR is therefore complementary to the methods of X-ray crystallography, NMR and FRET (fluorescence resonance energy transfer) and is becoming a powerful method for structural determination of biomolecules. In the present review, the methods of PELDOR are discussed and examples where PELDOR has been used to obtain structural information on biomolecules are summarized.
Structure and function of a novel endonuclease acting on branched DNA substrates
Authors: Creze Christophe , Lestini Roxane , Kühn Joelle , Ligabue Alessio , Becker Hubert F. , Czjzek Mirjam , Flament Didier , Myllykallio Hannu
Published: January 2011

Branched DNA structures that occur during DNA repair and recombination must be efficiently processed by structure-specific endonucleases in order to avoid cell death. In the present paper, we summarize our screen for new interaction partners for the archaeal replication clamp that led to the functional characterization of a novel endonuclease family, dubbed NucS. Structural analyses of Pyrococcus abyssi NucS revealed an unexpected binding site for ssDNA (single-stranded DNA) that directs, together with the replication clamp, the nuclease activity of this protein towards ssDNA–dsDNA (double-stranded DNA) junctions. Our studies suggest that understanding the detailed architecture and dynamic behaviour of the NucS (nuclease specific for ssDNA)–PCNA (proliferating-cell nuclear antigen) complex with DNA will be crucial for identification of its physiologically relevant activities.
Ploidy and gene conversion in Archaea
Authors: Soppa Jörg
Published: January 2011

The genome copy numbers of seven crenarchaeal species of four genera have been reported. All of them are monoploid and thus this seems to be a characteristic feature of Crenarchaeota. In stark contrast, none of six species representing six euryarchaeal genera is monoploid. Therefore Euryarchaea are typically oligoploid or polyploidy and their genome copy numbers are tightly regulated in response to growth phase and/or growth rate. A theoretical consideration called ‘Muller's ratchet’ predicts that asexually reproducing polyploid species should not be able to exist. An escape from Muller's ratchet would be a mechanism leading to the equalization of genome copies, such as gene conversion. Using two species of methanogenic and halophilic archaea, it was shown that heterozygous cells containing different genomes simultaneously can be selected, exemplifying gene redundancy as one possible evolutionary advantage of polyploidy. In both cases, the genomes were rapidly equalized in the absence of selection, showing that gene conversion operates at least in halophilic and methanogenic Euryarchaea.
Thermophilic archaeal enzymes and applications in biocatalysis
Authors: Littlechild Jennifer A.
Published: January 2011

Thermophilic enzymes have advantages for their use in commercial applications and particularly for the production of chiral compounds to produce optically pure pharmaceuticals. They can be used as biocatalysts in the application of ‘green chemistry’. The thermophilic archaea contain enzymes that have already been used in commercial applications such as the L-aminoacylase from Thermococcus litoralis for the resolution of amino acids and amino acid analogues. This enzyme differs from bacterial L-aminoacylases and has similarities to carboxypeptidases from other archaeal species. An amidase/γ-lactamase from Sulfolobus solfataricus has been used for the production of optically pure γ-lactam, the building block for antiviral carbocyclic nucleotides. This enzyme has similarities to the bacterial signature amidase family. An alcohol dehydrogenase from Aeropyrum pernix has been used for the production of optically pure alcohols and is related to the zinc-containing eukaryotic alcohol dehydrogenases. A transaminase and a dehalogenase from Sulfolobus species have also been studied. The archaeal transaminase is found in a pathway for serine synthesis which is found only in eukaryotes and not in bacteria. It can be used for the asymmetric synthesis of homochiral amines of high enantioselective purity. The L-2-haloacid dehalogenase has applications both in biocatalysis and in bioremediation. All of these enzymes have increased thermostability over their mesophilic counterparts.