bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 2007
Authors: Ljungman Gustaf , Jakobson Åke , Behrendtz Mikael , Ek Torben , Friberg Lars‐Göran , Hjalmars Ulf , Hjorth Lars , Lindh Jack , Pal Niklas , Sandstedt Bengt , Österlundh Gustaf , Gustafsson Göran ,   for the Swedish Childhood Solid Tumour Working Group (VSTB)
Published: December 2010

Aim:  Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival.

Methods:  We used the new WHO ICCC‐3 for reclassification of the patients. Incidence and survival analyses were performed in the study population.

Results:  Two thousand four hundred and eighty‐seven children (<15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow‐up have improved significantly when comparing the two time periods, 1983–1995 and 1995–2007 (76 vs. 82%; p < 0.01).

Conclusions:  The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow‐up were 80, 79 and 76%, respectively.
Congenital self‐healing reticulohistiocytosis – an important diagnostic challenge
Authors: Slott Jensen Marie Louise , Bygum Anette , Clemmensen Ole , Fenger‐Gron Jesper
Published: December 2010

Aim:  To present current and new knowledge on congenital self‐healing reticulohistiocytosis, a benign variant of cutaneous Langerhans cell histiocytosis presenting with skin lesions in the neonatal period.

Methods:  We describe and photo document two cases of this rare disease and review the literature.

Results:  Only few newborns have acute access to a neonatal dermatologist, and we demonstrate how the spontaneous cutaneous involution may happen even prior to the first dermatological assessment. As no sole criterion can reliably distinguish the self‐healing form from disseminated disease, multidisciplinary assessment and follow‐up are essential.

Conclusion:  Our data document how easily the diagnosis congenital self‐healing reticulocytosis may be missed and emphasize the importance and value of instant clinical photographing at the neonatal unit and the use of teledermatology whenever congenital self‐healing reticulohistiocytosis is suspected.
Noble gases and nitrogen in the Almahata Sitta ureilite
Authors: MURTY Sripada V. S. , MAHAJAN Ramakant R. , JENNISKENS Peter , SHADDAD Muawia H. , ELDIEN Beder
Published: December 2010

Abstract– A bulk sample (split from Almahata Sitta #36) and an acid resistant residue (from #44) have been analyzed for noble gases and nitrogen by step‐wise combustion/pyrolysis. In the bulk sample, He and Ne are a mixture of cosmogenic and trapped components. Cosmic‐ ray exposure ages of 13.8 and 16.0 Ma are calculated based on 3He, and 21Ne, respectively. Except for a small amount of cosmogenic 3He, He, and Ne in the acid‐resistant residue are not significantly above blank level. Ar, Kr, and Xe in both the bulk and residue are dominated by a trapped component, but the elemental ratios are different. While the ratios of 36Ar/132Xe and 84Kr/132Xe are about 400 and 1, respectively, in all the combustion steps of the residue, the bulk sample has about an order of magnitude more 132Xe in the corresponding combustion steps. It seems, an acid soluble phase is the host of this Xe‐rich carrier and is different from a similar phase observed in the ureilite Allan Hills 82130. Nitrogen in the bulk sample and acid residue are 21.1 ppm (−36.8‰), and 249.5 ppm (−74.3‰), respectively. Peak release of C (monitored as CO + CO2), N, Ar, Kr, and Xe occurred at the 700 °C combustion step of the residue, confirming diamond as the principal carrier for these gases. In the residue, the isotopic ratio 38Ar/36Ar shows a monotonic increase with release temperature.
Microarray-based enzyme profiling: Recent advances and applications (Review)
Authors: Uttamchandani M. , Moochhala S.
Published: December 2010

Enzymes are an integral part of biological systems. They constitute a significant majority of all proteins expressed (an estimated 18%–29%) within eukaryotic genomes. It thus comes as no major surprise that enzymes have been implicated in many diseases and form the second largest group of drug targets, after receptors. Despite their involvement in a multitude of physiological processes, only a limited number of enzymes have thus far been well-characterized. Consequently, little is understood about the physiological roles, substrate specificity, and downstream targets of the vast majority of these important proteins. In order to facilitate the biological characterization of enzymes, as well as their adoption as drug targets, there is a need for global “-omics” solutions that bridge the gap in understanding these proteins and their interactions. Herein the authors showcase how microarray methods can be adopted to facilitate investigations into enzymes and their properties, in a high-throughput manner. They will focus on several major classes of enzymes, including kinases, phosphatases, and proteases. As a result of research efforts over the last decade, these groups of enzymes have become readily amenable to microarray-based profiling methods. The authors will also describe the specific design considerations that are required to develop the appropriate chemical tools and libraries to characterize each enzyme class. These include peptide substrates, activity-based probes, and chemical compound libraries, which may be rapidly assembled using efficient combinatorial synthesis or “click chemistry” strategies. Taken together, microarrays offer a powerful means to study, profile, and also discover potent small molecules with which to modulate enzyme activity.
Iron-based ferritin nanocore as a contrast agent
Authors: Sana Barindra , Johnson Eric , Sheah Kenneth , Poh Chueh Loo , Lim Sierin
Published: December 2010

Self-assembling protein cages have been exploited as templates for nanoparticle synthesis. The ferritin molecule, a protein cage present in most living systems, stores excess soluble ferrous iron in the form of an insoluble ferric complex within its cavity. Magnetic nanocores formed by loading excess iron within an engineered ferritin from Archaeoglobus fulgidus (AfFtn-AA) were studied as a potential magnetic resonance (MR) imaging contrast agent. The self-assembly characteristics of the AfFtn-AA were investigated using dynamic light scattering technique and size exclusion chromatography. Homogeneous size distribution of the assembled nanoparticles was observed using transmission electron microscopy. The magnetic properties of iron-loaded AfFtn-AA were studied using vibrating sample magnetometry. Images obtained from a 3.0 T whole-body MRI scanner showed significant brightening of T1 images and signal loss of T2 images with increased concentrations of iron-loaded AfFtn-AA. The analysis of the MR image intensities showed extremely high R2 values (5300 mM−1 s−1) for the iron-loaded AfFtn-AA confirming its potential as a T2 contrast agent.
Bio-inspired track-walking molecular motors (Perspective)
Authors: Wang Zhisong
Published: December 2010

The emerging field of artificial track-walking molecular motors is reviewed. The author attempted to clarify the scientific and technological challenges that face the field. A comprehensive mechanistic diagram for molecular walkers was introduced, thereby the directions and possible routes for future development were suggested.
Current development of bioreactors for extracorporeal bioartificial liver (Review)
Authors: Wang Yan , Susando Thomas , Lei Xia , Anene-Nzelu Chukwuemeka , Zhou Huancheng , Liang Leo Hwa , Yu Hanry
Published: December 2010

The research and development of extracorporeal bioartificial liver is gaining pace in recent years with the introduction of a myriad of optimally designed bioreactors with the ability to maintain long-term viability and liver-specific functions of hepatocytes. The design considerations for bioartificial liver are not trivial; it needs to consider factors such as the types of cell to be cultured in the bioreactor, the bioreactor configuration, the magnitude of fluid-induced shear stress, nutrients' supply, and wastes' removal, and other relevant issues before the bioreactor is ready for testing. This review discusses the exciting development of bioartificial liver devices, particularly the various types of cell used in current reactor designs, the state-of-the-art culturing and cryopreservation techniques, and the comparison among many today's bioreactor configurations. This review will also discuss in depth the importance of maintaining optimal mass transfer of nutrients and oxygen partial pressure in the bioreactor system. Finally, this review will discuss the commercially available bioreactors that are currently undergoing preclinical and clinical trials.
Genetic Correction of PSA Values Using Sequence Variants Associated with PSA Levels
Authors: Gudmundsson Julius , Besenbacher Soren , Sulem Patrick , Gudbjartsson Daniel F. , Olafsson Isleifur , Arinbjarnarson Sturla , Agnarsson Bjarni A. , Benediktsdottir Kristrun R. , Isaksson Helgi J. , Kostic Jelena P. , Gudjonsson Sigurjon A. , Stacey Simon N. , Gylfason Arnaldur , Sigurdsson Asgeir , Holm Hilma , Bjornsdottir Unnur S. , Eyjolfsson Gudmundur I. , Navarrete Sebastian , Fuertes Fernando , Garcia-Prats Maria D. , Polo Eduardo , Checherita Ionel A. , Jinga Mariana , Badea Paula , Aben Katja K. , Schalken Jack A. , van Oort Inge M. , Sweep Fred C. , Helfand Brian T. , Davis Michael , Donovan Jenny L. , Hamdy Freddie C. , Kristjansson Kristleifur , Gulcher Jeffrey R. , Masson Gisli , Kong Augustine , Catalona William J. , Mayordomo Jose I. , Geirsson Gudmundur , Einarsson Gudmundur V. , Barkardottir Rosa B. , Jonsson Eirikur , Jinga Viorel , Mates Dana , Kiemeney Lambertus A. , Neal David E. , Thorsteinsdottir Unnur , Rafnar Thorunn , Stefansson Kari
Published: December 2010

Sequence variants in the human genome are associated with serum levels of prostate-specific antigen.
The Haze Clears: Second-Hand Tobacco Smoke a Risk for Bladder Cancer
Authors: Hansel Donna E.
Published: December 2010

Environmental tobacco exposure is associated with an increased risk for bladder cancer in lifelong nonsmokers.
The Hyb Hydrogenase Permits Hydrogen-Dependent Respiratory Growth of Salmonella enterica Serovar Typhimurium
Authors: Lamichhane-Khadka Reena , Kwiatkowski Andrea , Maier Robert J.
Published: December 2010

Salmonella entericaserovar Typhimurium contains three distinct respiratory hydrogenases, all of which contribute to virulence. Addition of H2significantly enhanced the growth rate and yield ofS. Typhimurium in an amino acid-containing medium; this occurred with three different terminal respiratory electron acceptors. Based on studies with site-specific double-hydrogenase mutant strains, most of this H2-dependent growth increase was attributed to the Hyb hydrogenase, rather than to the Hya or Hyd respiratory H2-oxidizing enzymes. The wild type strain with H2had 4.0-fold greater uptake of14C-labeled amino acids over a period of minutes than did cells incubated without H2. The double-uptake hydrogenase mutant containing only the Hyb hydrogenase transported amino acids H2dependently like the wild type. The Hyb-only-containing strain produced a membrane potential comparable to that of the wild type. The H2-stimulated amino acid uptake of the wild type and the Hyb-only strain was inhibited by the protonophore carbonyl cyanidem-chlorophenylhydrazone but was less affected by the ATP synthase inhibitor sodium orthovanadate. In the wild type, proteins TonB and ExbD, which are known to couple proton motive force (PMF) to transport processes, were induced by H2exposure, as were the genes corresponding to these periplasmic PMF-coupling factors. However, studies ontonBandexbDsingle mutant strains could not confirm a major role for these proteins in amino acid transport. The results link H2oxidation via the Hyb enzyme to growth, amino acid transport, and expression of periplasmic proteins that facilitate PMF-mediated transport across the outer membrane.

IMPORTANCEComplex carbohydrates consumed by animals are fermented by intestinal microflora, and this leads to molecular hydrogen production.Salmonella entericaserovar Typhimurium can utilize this gas via three distinct respiratory hydrogenases, all of which contribute to virulence. Since H2oxidation can be used to conserve energy, we predicted that its use may augment bacterial growth in nutrient-poor media or in competitive environments within H2-containing host tissues. We thus investigated the effect of added H2on the growth ofSalmonellaTyphimurium in carbon-poor media with various terminal respiratory electron acceptors. The positive effects of H2on growth led to the realization thatSalmonellahas mechanisms to increase carbon acquisition when oxidizing H2. We found that H2oxidation via one of the respiration-linked enzymes, the Hyb hydrogenase, led to increased growth, amino acid transport, and expression of periplasmic proteins that facilitate proton motive force-mediated transport across the outer membrane.
Cellulase-Xylanase Synergy in Designer Cellulosomes for Enhanced Degradation of a Complex Cellulosic Substrate
Authors: Moraïs Sarah , Barak Yoav , Caspi Jonathan , Hadar Yitzhak , Lamed Raphael , Shoham Yuval , Wilson David B. , Bayer Edward A.
Published: December 2010

Designer cellulosomes are precision-engineered multienzyme complexes in which the molecular architecture and enzyme content are exquisitely controlled. This system was used to examine enzyme cooperation for improved synergy among
Thermobifida fusca
glycoside hydrolases. Two
T. fusca
cellulases, Cel48A exoglucanase and Cel5A endoglucanase, and two
T. fusca
xylanases, endoxylanases Xyn10B and Xyn11A, were selected as enzymatic components of a mixed cellulase/xylanase-containing designer cellulosome. The resultant mixed multienzyme complex was fabricated on a single scaffoldin subunit bearing all four enzymes. Conversion of
T. fusca
enzymes to the cellulosomal mode followed by their subsequent incorporation into a tetravalent cellulosome led to assemblies with enhanced activity (~2.4-fold) on wheat straw as a complex cellulosic substrate. The enhanced synergy was caused by the proximity of the enzymes on the complex compared to the free-enzyme systems. The hydrolytic properties of the tetravalent designer cellulosome were compared with the combined action of two separate divalent cellulase- and xylanase-containing cellulosomes. Significantly, the tetravalent designer cellulosome system exhibited an ~2-fold enhancement in enzymatic activity compared to the activity of the mixture of two distinct divalent scaffoldin-borne enzymes. These results provide additional evidence that close proximity between cellulases and xylanases is key to the observed concerted degradation of the complex cellulosic substrate in which the integrated enzymes complement each other by promoting access to the relevant polysaccharide components of the substrate. The data demonstrate that cooperation among xylanases and cellulases can be augmented by their integration into a single designer cellulosome.

IMPORTANCE
Global efforts towards alternative energy programs are highlighted by processes for converting plant-derived carbohydrates to biofuels. The major barrier in such processes is the inherent recalcitrance to enzymatic degradation of cellulose combined with related associated polysaccharides. The multienzyme cellulosome complexes, produced by anaerobic bacteria, are considered to be the most efficient systems for degradation of plant cell wall biomass. In the present work, we have employed a synthetic biology approach by producing artificial designer cellulosomes of predefined enzyme composition and architecture. The engineered tetravalent cellulosome complexes contain two different types of cellulases and two distinct xylanases. Using this approach, enhanced synergistic activity was observed on wheat straw, a natural recalcitrant substrate. The present work strives to gain insight into the combined action of cellulosomal enzyme components towards the development of advanced systems for improved degradation of cellulosic material.
Musculoskeletal ultrasound education for sports medicine fellows: a suggested/potential curriculum by the American Medical Society for Sports Medicine
Authors: Finnoff Jonathan , Lavallee Mark E , Smith Jay
Published: December 2010

The following musculoskeletal ultrasound (MSK US) curriculum was developed by the American Medical Society for Sports Medicine (AMSSM) to provide a pathway by which a sports medicine fellow can obtain adequate MSK US training during their fellowship to meet the requirements of competency outlined by the American Institute of Ultrasound in Medicine (AIUM) Training Guidelines for the Performance of MSK US Examination. Many fellowship programmes may not be able to follow all of the recommendations outlined by this document owing to their available resources. However, this curriculum can be used as a suggested/potential guideline for MSK US training within a sports medicine fellowship, and may assist programmes in developing or modifying their own internal training methods.
The match day use of ultrasound during professional football finals matches
Authors: James Phillip , Barbour Tim , Stone Ian
Published: December 2010

Objectives

To describe the use of ultrasound by a professional Australian rules football team in the immediate pregame period to guide local anaesthetic injections, during game time to assess injuries and to guide local anaesthetic injections, and postmatch to assess injuries and to guide therapeutic injections.

Methods

The use of match day ultrasound was documented during four finals matches. Local anaesthetic injections were considered effective if players played without pain and experienced no complication from the injection. The results of the diagnostic scans were assessed against subsequent clinical progress and correlation with any follow-up imaging. Therapeutic injections were considered effective if there was clinical improvement and the player was able to play in subsequent weeks without restriction.

Results

Pregame, a total of 11 ultrasound guided local anaesthetic injections were performed on eight players, with a further local anaesthetic during a game. All injections achieved good pain relief without any complication. A single diagnostic scan on one player during a game showed no acute muscle tear, the player successfully completed the game. Postgame, a total of four ultrasound guided steroid injections were performed on three players and all players played in the next match. The injections achieved good therapeutic results. The therapeutic injections given immediately postgame, maximised the recovery period available to the players.

Conclusions

Ultrasound proved useful in guiding local anaesthetic before and during matches and also therapeutic injections after matches. Ultrasound had a limited role in the assessment of injuries during a game.
GENERALIZED BRST TRANSFORMATION IN ABELIAN RANK-2 ANTISYMMETRIC TENSOR FIELD THEORY
Authors: UPADHYAY SUDHAKER , MANDAL BHABANI PRASAD
Published: December 2010

We generalize the BRST transformations in Abelian rank-2 tensor field theory by allowing the parameter to be finite and field-dependent and show that such transformations play crucial role in studying the Abelian 2-form gauge theory in noncovariant gauges. The generating functionals in different effective theories are connected through these generalized BRST transformations with different choice of finite parameter. We further consider the generalization of the anti-BRST transformations and show that even anti-BRST transformations with the finite field dependent parameter relate the generating functional for different effective theories. Such generalized BRST/anti-BRST transformations are useful in connecting generating functionals corresponding to different effective theories. Field/antifield formulation of this Abelian 2-form gauge theory is also studied in the context of generalized BRST transformations. We show that generalized BRST transformation connects the generating functional corresponding to the different solutions of quantum master equation in field/antifield formulation.
THE COMPLEX VOLUMES OF TWIST KNOTS VIA COLORED JONES POLYNOMIALS
Authors: CHO JINSEOK , MURAKAMI JUN
Published: December 2010

For a hyperbolic knot, an ideal triangulation of the knot complement corresponding to the colored Jones polynomial was introduced by Thurston. Considering this triangulation of a twist knot, we find a function which gives the hyperbolicity equations and the complex volume of the knot complement, using Zickert's theory of the extended Bloch group and the complex volume.

We also consider a formal approximation of the colored Jones polynomial. Following Ohnuki's theory of 2-bridge knots, we define another function which comes from the approximation. We show that this function is essentially the same as the previous function, and therefore it also gives the same hyperbolicity equations and the complex volume.

Finally we compare this result with our previous one which dealt with Yokota theory, and, as an application to Yokota theory, present a refined formula of the complex volumes for any twist knots.
LINKING IN STRAIGHT-EDGE EMBEDDINGS OF K7
Authors: LUDWIG LEWIS D. , ARBISI PAMELA
Published: December 2010

In 1983 Conway and Gordon and Sachs proved that every embedding of the complete graph on six vertices, K6, is intrinsically linked. In 2004 it was shown that all straight-edge embeddings of K6 have either one or three linked triangle pairs. We expand this work to characterize the straight-edge embeddings of K7 and determine the number and types of links in every embedding which forms a convex polyhedron of seven vertices.
ON UNIVERSAL KLEINIAN GROUPS GENERATED BY 180° ROTATIONS
Authors: HILDEN HUGH M. , RAMÍREZ-LOSADA ENRIQUE
Published: December 2010

A 2-universal knot is a universal knot having all branching indices 1 or 2. Here we construct the first example of a 2-universal knot which could be a hyperbolic knot (SnapPea). Hence, we could have an example of a universal group generated by 180° rotations.
ON CONJECTURES ABOUT POSITIVE BRAID KNOTS AND ALMOST ALTERNATING TORUS KNOTS
Authors: STOŠIĆ MARKO
Published: December 2010

In this paper we resolve some conjectures concerning positive braid knots and almost alternating torus knots. Namely, we prove that the first Khovanov homology group of positive braid knot is trivial, as conjectured by Khovanov. Also, we generalize this result to show that the same is true in the case of Khovanov–Rozansky homology (sl(n) link homology) for any positive integer n. Moreover, by using the Khovanov homology theory, we prove the classical knot theory conjecture by Adams, that the only almost alternating torus knots are T3, 4 and T3, 5.
Storage Ring Light Sources
Authors: Zhao Z. T.
Published: December 2010

This article outlines the development and evolution of storage ring light sources, focusing on the latest, third generation light sources. After making brief historical remarks, it describes the current status, the performance, and the technological advancements of third generation light sources. The future developments of the ultimate storage ring as the next generation light source are envisioned.
The Large Hadron Collider from Conception to Commissioning: A Personal Recollection
Authors: Evans Lyndon
Published: December 2010

It is generally accepted that the birth of the Large Hadron Collider (LHC) was in the Lausanne Workshop in 1984 [1], where machine builders and experimentalists first got together to discuss the next big project for CERN. In reality, the seeds were sown much earlier, with the construction of the Intersecting Storage Rings at CERN, followed by the proton–antiproton colliders at CERN and at Fermilab. In this article I try to give a historical perspective on how the LHC came to be, as well as my own account of some of the political, technical and financial challenges that had to be met in order to make it a reality.
Undulators and Other Insertion Devices
Authors: Levichev Eugene , Vinokurov Nikolay
Published: December 2010

This article reviews insertion devices (IDs) — wigglers and undulators — both for synchrotron radiation production and for machine parameter control. As there are many types of wigglers and undulators and it is impossible to describe them all in detail, here we particularly emphasize the design, characteristics and tolerances of undulators for free electron lasers and damping wigglers for controlling beam damping parameters. The influence of periodic IDs on beam parameters in cyclic accelerators is described in brief. A profound description of different ID types can be found in [1].
Compton Sources of Electromagnetic Radiation
Authors: Krafft Geoffrey A. , Priebe Gerd
Published: December 2010

When a relativistic electron beam interacts with a high-field laser beam, intense and highly collimated electromagnetic radiation will be generated through Compton scattering. Through relativistic upshifting and the relativistic Doppler effect, highly energetic polarized photons are radiated along the electron beam motion when the electrons interact with the laser light. For example, X-ray radiation can be obtained when optical lasers are scattered from electrons of tens-of-MeV beam energy. Because of the desirable properties of the radiation produced, many groups around the world have been designing, building, and utilizing Compton sources for a wide variety of purposes. In this review article, we discuss the generation and properties of the scattered radiation, the types of Compton source devices that have been constructed to date, and the prospects of radiation sources of this general type. Due to the possibilities of producing hard electromagnetic radiation in a device that is small compared to the alternative storage ring sources, it is foreseen that large numbers of such sources may be constructed in the future.
The Impact of Microbial Metabolism on Marine Dissolved Organic Matter
Authors: Kujawinski Elizabeth B.
Published: December 2010

Microbes mediate global biogeochemical cycles through their metabolism, and all metabolic processes begin with the interaction between the microbial cell wall or membrane and the external environment. For all heterotrophs and many autotrophs, critical growth substrates and factors are present within the dilute and heterogeneous mixture of compounds that constitutes dissolved organic matter (DOM). In short, the microbe–molecule interaction is one of the fundamental reactions within the global carbon cycle. Here, I summarize recent findings from studies that examine DOM–microbe interactions from either the DOM perspective (organic geochemistry) or the microbe perspective (microbial ecology). Gaps in our knowledge are highlighted and future integrative research directions are proposed.
Beyond the Calvin Cycle: Autotrophic Carbon Fixation in the Ocean
Authors: Hügler Michael , Sievert Stefan M.
Published: December 2010

Organisms capable of autotrophic metabolism assimilate inorganic carbon into organic carbon. They form an integral part of ecosystems by making an otherwise unavailable form of carbon available to other organisms, a central component of the global carbon cycle. For many years, the doctrine prevailed that the Calvin-Benson-Bassham (CBB) cycle is the only biochemical autotrophic CO2 fixation pathway of significance in the ocean. However, ecological, biochemical, and genomic studies carried out over the last decade have not only elucidated new pathways but also shown that autotrophic carbon fixation via pathways other than the CBB cycle can be significant. This has ramifications for our understanding of the carbon cycle and energy flow in the ocean. Here, we review the recent discoveries in the field of autotrophic carbon fixation, including the biochemistry and evolution of the different pathways, as well as their ecological relevance in various oceanic ecosystems.
Environmental Proteomics: Changes in the Proteome of Marine Organisms in Response to Environmental Stress, Pollutants, Infection, Symbiosis, and Development
Authors: Tomanek Lars
Published: December 2010

Environmental proteomics, the study of changes in the abundance of proteins and their post-translational modifications, has become a powerful tool for generating hypotheses regarding how the environment affects the biology of marine organisms. Proteomics discovers hitherto unknown cellular effects of environmental stressors such as changes in thermal, osmotic, and anaerobic conditions. Proteomic analyses have advanced the characterization of the biological effects of pollutants and identified comprehensive and pollutant-specific sets of biomarkers, especially those highlighting post-translational modifications. Proteomic analyses of infected organisms have highlighted the broader changes occurring during immune responses and how the same pathways are attenuated during the maintenance of symbiotic relationships. Finally, proteomic changes occurring during the early life stages of marine organisms emphasize the importance of signaling events during development in a rapidly changing environment. Changes in proteins functioning in energy metabolism, cytoskeleton, protein stabilization and turnover, oxidative stress, and signaling are common responses to environmental change.
Microbial Metagenomics: Beyond the Genome
Authors: Gilbert Jack A. , Dupont Christopher L.
Published: December 2010

Metagenomics literally means “beyond the genome.” Marine microbial metagenomic databases presently comprise ∼400 billion base pairs of DNA, only ∼3% of that found in 1 ml of seawater. Very soon a trillion-base-pair sequence run will be feasible, so it is time to reflect on what we have learned from metagenomics. We review the impact of metagenomics on our understanding of marine microbial communities. We consider the studies facilitated by data generated through the Global Ocean Sampling expedition, as well as the revolution wrought at the individual laboratory level through next generation sequencing technologies. We review recent studies and discoveries since 2008, provide a discussion of bioinformatic analyses, including conceptual pipelines and sequence annotation and predict the future of metagenomics, with suggestions of collaborative community studies tailored toward answering some of the fundamental questions in marine microbial ecology.
Use of Flow Cytometry to Measure Biogeochemical Rates and Processes in the Ocean
Authors: Lomas Michael W. , Bronk Deborah A. , van den Engh Ger
Published: December 2010

An important goal of marine biogeochemists is to quantify the rates at which elements cycle through the ocean's diverse microbial assemblage, as well as to determine how these rates vary in time and space. The traditional view that phytoplankton are producers and bacteria are consumers has been found to be overly simplistic, and environmental metagenomics is discovering new and important microbial metabolisms at an accelerating rate. Many nutritional strategies previously attributed to one microorganism or functional group are also or instead carried out by other groups. To tease apart which organism is doing what will require new analytical approaches. Flow cytometry, when combined with other techniques, has great potential for expanding our understanding of microbial interactions because groups can be distinguished optically, sorted, and then collected for subsequent analyses. Herein, we review the advances in our understanding of marine biogeochemistry that have arisen from the use of flow cytometry.
Natural Processes in Delta Restoration: Application to the Mississippi Delta
Authors: Paola Chris , Twilley Robert R. , Edmonds Douglas A. , Kim Wonsuck , Mohrig David , Parker Gary , Viparelli Enrica , Voller Vaughan R.
Published: December 2010

Restoration of river deltas involves diverting sediment and water from major channels into adjoining drowned areas, where the sediment can build new land and provide a platform for regenerating wetland ecosystems. Except for local engineered structures at the points of diversion, restoration mainly relies on natural delta-building processes. Present understanding of such processes is sufficient to provide a basis for determining the feasibility of restoration projects through quantitative estimates of land-building rates and sustainable wetland area under different scenarios of sediment supply, subsidence, and sea-level rise. We are not yet to the point of being able to predict the evolution of a restored delta in detail. Predictions of delta evolution are based on field studies of active deltas, deltas in mine-tailings ponds, experimental deltas, and countless natural experiments contained in the stratigraphic record. These studies provide input for a variety of mechanistic delta models, ranging from radially averaged formulations to more detailed models that can resolve channels, topography, and ecosystem processes. Especially exciting areas for future research include understanding the mechanisms by which deltaic channel networks self-organize, grow, and distribute sediment and nutrients over the delta surface and coupling these to ecosystem processes, especially the interplay of topography, network geometry, and ecosystem dynamics.
Endoplasmic reticulum stress in glomerular epithelial cell injury
Authors: Cybulsky Andrey V. , Takano Tomoko , Papillon Joan , Kitzler Thomas M. , Bijian Krikor
Published: December 2010

Focal segmental glomerulosclerosis (FSGS) may be associated with glomerular epithelial cell (GEC; podocyte) apoptosis due to acquired injury or mutations in specific podocyte proteins. This study addresses mediation of GEC injury, focusing on endoplasmic reticulum (ER) stress. We studied signaling in cultured GECs in the presence or absence of the extracellular matrix (ECM). Adhesion to collagen supports cell survival, but adhesion to plastic (loss of contact with ECM) leads to apoptosis. Compared with collagen-adherent cells, GECs on plastic showed increased protein misfolding in the ER, and an adaptive-protective ER stress response, including increased expression of ER chaperones, increased phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), and a reduction in protein synthesis. Activation of these ER stress pathways counteracted apoptosis. However, tunicamycin (a potent stimulator of ER stress) changed the ER stress response from protective to cytotoxic, as tunicamycin induced the proapoptotic ER stress gene, C/EBP homologous protein-10, and exacerbated apoptosis in GECs adherent to plastic, but not collagen. In GECs adherent to plastic, adaptive ER stress was associated with an increase in polyubiquitinated proteins and “choking” of the proteasome. Furthermore, pharmacological inhibition of the proteasome induced ER stress in GECs. Finally, we show that ER stress (induction of ER chaperones and eIF2α phosphorylation) was evident in experimental FSGS in vivo. Thus interactions of GECs with ECM may regulate protein folding and induction of the ER stress response. FSGS is associated with induction of ER stress. Enhancing protective aspects of the ER stress response may reduce apoptosis and possibly glomerulosclerosis.
Pitfalls in target mRNA quantification for real-time quantitative RT-PCR in overload-induced skeletal muscle hypertrophy
Authors: Chaillou T. , Malgoyre A. , Banzet S. , Chapot R. , Koulmann N. , Pugnière P. , Beaudry M. , Bigard X. , Peinnequin A.
Published: December 2010

Quantifying target mRNA using real-time quantitative reverse transcription-polymerase chain reaction requires an accurate normalization method. Determination of normalization factors (NFs) based on validated reference genes according to their relative stability is currently the best standard method in most usual situations. This method controls for technical errors, but its physiological relevance requires constant NF values for a fixed weight of tissue. In the functional overload model, the increase in the total RNA concentration must be considered in determining the NF values. Here, we pointed out a limitation of the classical geNorm-derived normalization. geNorm software selected reference genes despite that the NF values extensively varied under experiment. Only the NF values calculated from four intentionally selected genes were constant between groups. However, a normalization based on these genes is questionable. Indeed, three out of four genes belong to the same functional class (negative regulator of muscle mass), and their use is physiological nonsense in a hypertrophic model. Thus, we proposed guidelines for optimizing target mRNA normalization and quantification, useful in models of muscle mass modulation. In our study, the normalization method by multiple reference genes was not appropriate to compare target mRNA levels between overloaded and control muscles. A solution should be to use an absolute quantification of target mRNAs per unit weight of tissue, without any internal normalization. Even if the technical variations will stay present as a part of the intergroup variations, leading to less statistical power, we consider this method acceptable because it will not generate misleading results.
Prone Positioning and Intravenous Zanamivir may Represent Effective Alternatives for Patients with Severe ARDS Virus A (H1N1) Related Pneumonia in Hospitals with no Access to ECMO
Authors: Gristina Giuseppe , Nardi Giuseppe , Orazi Daniela , Lauria Francesco Nicola , Valli Maria Beatrice , Lalle Eleonora , Menzo Stefano , Riccioni Luigi , Camporiondo Maria Pia
Published: December 2010

The first patient with influenza A/H1N1-related pneumonia was admitted to an Italian ICU at the end of August 2009. Until then, despite the international alarm, the level of awareness was low and very few Italian hospitals were equipped with ECMOs. Moreover the PCR test for A H1N1 virus was sporadically available and the emergency departments of even the largest institutions could rely only on the rapid test for the urgent screening of patients with pneumonia and respiratory failure. On September 5th, a young and “apparently” previously healthy man, was admitted to our ICU because of a severe ARDS caused by influenza A H1N1 virus. As there was no ECMO available, he was treated with prolonged cycles of prone positioning ventilation. Antiviral treatment was started with Oseltamivir, but as enteral absorption was impaired by paralytic ileus and tube feeding intolerance, Oseltamivir had to be discontinued. Intravenous Zanamivir 1200 mg/day for ten days was therefore prescribed as “off label” antiviral therapy. A bone marrow biopsy allowed the diagnosis of an initial stage of “hairy cells leukaemia.” ARDS related to A/H1N1 influenza was the first sign of the disease in our patient. He did well with complete clearance of the infection from the BAL after 10 days of Zanamivir, although the nasopharyngeal swabs remained positive for ten more days. Prone positioning ventilation may be a life-saver strategy in patients with severe ARDS when ECMO is not immediately available. However, prone positioning ventilation is often associated with severe impairment of the absorption of drugs that require enteral administration via the nasogastric tube. In these cases, intravenous Zanamivir may be an effective alternative strategy.
Oscillation Criteria of Solution for a Second Order Difference Equation with Forced Term
Authors: Huiqin Chen , Zhen Jin
Published: December 2010

We will consider oscillation criteria for the second order difference equation with forced term Δ(anΔ(xn + λxn−τ)) + qnxn−σ = rn (n ≥ 0). We establish sufficient conditions which guarantee that every solution is oscillatory or eventually positive solutions converge to zero.
Thoracic Radionecrosis Following Repeated Cardiac Catheterization
Authors: Banic Borut , Meier Bernhard , Banic Andrej , Weinand Christian
Published: December 2010

Radiodermatitis is a known complication in patients having undergone radiotherapy. It usually appears 2 to 5 years after irradiation. We are reporting on a case of radiodermatitis that occurred within months after coronary dilatation and stenting. It started with painful swelling, followed by a typical appearance on the skin surface. Histological finding confirmed the diagnosis. However, magnetic resonance imaging showed changes in the subcutaneous tissue extending into the ribs. A radical debridement was performed including removal of a partially necrotic 4th rib. The defect was closed with a latissimus dorsi transposition flap. Our findings are compared with the literature reports.
Liposomes for Use in Gene Delivery
Authors: Balazs Daniel A. , Godbey WT.
Published: December 2010

Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.
Basal Cell Carcinoma of the Head and Neck
Authors: Nakayama Masahiro , Tabuchi Keiji , Nakamura Yasuhiro , Hara Akira
Published: December 2010

Basal cell carcinoma (BCC) is a malignant neoplasm derived from nonkeratinizing cells that originate from the basal layer of the epidermis and is the most frequent type of skin cancer in humans, with cumulative exposure to ultraviolet radiation as an important risk factor. BCC occurs most frequently at sun-exposed sites, with the head and neck being common areas. Tumors can be classified as nodular, superficial, morpheaform, infiltrating, metatypic, and fibroepithelioma of Pinkus. Several treatment options such as surgical excision and nonsurgical procedures are available. The choice of treatment should be determined based on the histological subtype of a lesion, cost, its size and location, patient age, medical condition of the patient, treatment availability, and the patient's wishes. The aim of any therapy selected for BCC treatment involving the head and neck is to ensure complete removal, the preservation of function, and a good cosmetic outcome.
STOX1: Key Player in Trophoblast Dysfunction Underlying Early Onset Preeclampsia with Growth Retardation
Authors: van Dijk Marie , Oudejans Cees B. M.
Published: December 2010

Currently, only two preeclampsia susceptibility genes (ACVR2A,STOX1) have been identified within confirmed regions with significant genome-wide linkage, although many genetic screens in multiple populations have been performed. In this paper, we focus on theSTOX1gene. The epigenetic status of this gene is discussed explaining the maternal transmission of theSTOX1susceptibility allele observed in preeclamptic families. The known upstream regulation and downstream effector genes of the transcription factor STOX1 are described. Finally, we propose a model in which we combine the cell type-specific and allele-specific effects of STOX1. This includes intrinsic effects (differential CpG island methylation) and extrinsic effects (regulation of effector genes).
Regulation of the Embryonic Morphogen Nodal by Notch4 Facilitates Manifestation of the Aggressive Melanoma Phenotype
Authors: Hardy Katharine M. , Kirschmann Dawn A. , Seftor Elisabeth A. , Margaryan Naira V. , Postovit Lynne-Marie , Strizzi Luigi , Hendrix Mary J.C.
Published: December 2010

Metastatic melanoma is an aggressive skin cancer associated with poor prognosis. The reactivation of the embryonic morphogen Nodal in metastatic melanoma has previously been shown to regulate the aggressive behavior of these tumor cells. During the establishment of left-right asymmetry in early vertebrate development, Nodal expression is specifically regulated by a Notch signaling pathway. We hypothesize that a similar relationship between Notch and Nodal may be reestablished in melanoma. In this study, we investigate whether cross talk between the Notch and Nodal pathways can explain the reactivation of Nodal in aggressive metastatic melanoma cells. We show a molecular link between Notch and Nodal signaling in the aggressive melanoma cell line MV3 via the activity of an RBPJ-dependent Nodal enhancer element. We show a precise correlation between Notch4 and Nodal expression in multiple aggressive cell lines but not poorly aggressive cell lines. Surprisingly, Notch4 is specifically required for expression of Nodal in aggressive cells and plays a vital role both in the balance of cell growth and in the regulation of the aggressive phenotype. In addition, Notch4 function in vasculogenic mimicry and anchorage-independent growth in vitro is due in part to Notch4 regulation of Nodal. This study identifies an important role for cross talk between Notch4 and Nodal in metastatic melanoma, placing Notch4 upstream of Nodal, and offers a potential molecular target for melanoma therapy. Cancer Res; 70(24); 10340–50. ©2010 AACR.
Longitudinal, Noninvasive Imaging of T-Cell Effector Function and Proliferation in Living Subjects
Authors: Patel Manishkumar R. , Chang Ya-Fang , Chen Ian Y. , Bachmann Michael H. , Yan Xinrui , Contag Christopher H. , Gambhir Sanjiv S.
Published: December 2010

Adoptive immunotherapy is evolving to assume an increasing role in treating cancer. Most imaging studies in adoptive immunotherapy to date have focused primarily on locating tumor-specific T cells rather than understanding their effector functions. In this study, we report the development of a noninvasive imaging strategy to monitor T-cell activation in living subjects by linking a reporter gene to the Granzyme B promoter (pGB), whose transcriptional activity is known to increase during T-cell activation. Because pGB is relatively weak and does not lead to sufficient reporter gene expression for noninvasive imaging, we specifically employed 2 signal amplification strategies, namely the Two Step Transcription Amplification (TSTA) strategy and the cytomegalovirus enhancer (CMVe) strategy, to maximize firefly luciferase reporter gene expression. Although both amplification strategies were capable of increasing pGB activity in activated primary murine splenocytes, only the level of bioluminescence activity achieved with the CMVe strategy was adequate for noninvasive imaging in mice. Using T cells transduced with a reporter vector containing the hybrid pGB–CMVe promoter, we were able to optically image T-cell effector function longitudinally in response to tumor antigens in living mice. This methodology has the potential to accelerate the study of adoptive immunotherapy in preclinical cancer models. Cancer Res; 70(24); 10141–9. ©2010 AACR.