bluuebunny/crossref_metadata_2025 huggingface dataset:
The MSA Certification Board: Practices and Visions 2010
Authors: Petrali John P.
Published: January 2010

The Microscopy Society of America (MSA) is the world's largest professional association of microscopists. The society presently provides the only forum for certification of technologists in the disciplines of biological transmission electron microscopy in the Americas. The certification program was initiated in 1978 to establish standards of technical skills required for ensuring proficiency in biological microscopy practices that could be recognized as leading to national certifications.
Net Notes
Authors: Phillips Thomas E.
Published: January 2010

Selected postings from the Microscopy Listserver from October 11, 2009 to November 30, 2009. Complete listings and subscription information can be obtained at http://www.microscopy.com. Postings may have been edited to conserve space or for clarity.
Microscopy & Microanalysis 2010 in Portland, Oregon
Authors: Mansfield John
Published: January 2010

The Microscopy & Microanalysis Meeting (M&M) is the premier meeting for biological scientists, materials scientists, and nanotechnologists who use microscopy or microanalysis in their professional activities. Microscopy & Microanalysis 2010 will be no exception!
Three-Dimensional Analysis of Optic Nerve Axons Using a Focused Ion Beam-Based Approach
Authors: Kidd Grahame J. , Avishai Amir , Yin Xinghua , Trapp Bruce D.
Published: January 2010

Neurons in the central nervous system (CNS) are extensively interconnected, and consequently almost half of the human brain is occupied by wiring in the form of the myelinated axons. Dysfunction and degeneration of these axons can result in profound and permanent disability. Axons are much more complex than simple wires, however. Signal propagation relies on elaborate ultrastructural specializations at the nodes of Ranvier, which are demarcated by gaps between myelin sheaths. As living extensions of neurons, axons also require constant replenishment of metabolites and organelles such as energy-generating mitochondria. Studies of pathogenesis of myelinated axons are often constrained by microscopic complexity that requires nanometer-scale resolution over substantial three-dimensional distances.
A Practical Guide to Deconvolution of Fluorescence Microscope Imagery
Authors: Biggs David S.C.
Published: January 2010

Over the past decade, deconvolution of 3D light optical microscopy data has advanced from an obscure technique employed by only a few dedicated souls to a routine method that is now available with all modern microscope systems. Dramatic increases in computer power, algorithm sophistication, and software ease of use have brought the power of deconvolution to the general microscope user, and processing large 3D datasets is no longer a rate-limiting step in the imaging process.
MMsPred: a bioactivity and toxicology predictive system
Authors: Masciocchi Joel , Pireddu Luca , Medda Ricardo , Palla Piergiorgio , Floris Matteo , Pani Luca , Rodriguez-Tome Patricia
Published: January 2010

In the last decade, the development and use of new methods in combinatorial chemistry and high-throughput screening has dramatically increased the number of known biologically active compounds. Paradoxically, the number of drugs reaching the market has not followed the same trend, often because many of the candidate drugs present poor qualities in absorption, distribution, metabolism, excretion, and toxicological properties (ADME-Tox). The ability to recognize and discard bad candidates early in the drug discovery steps would save lost investments in time and money. Machine learning techniques could provide solutions to this problem.The goal of my research is to develop classifiers that accurately discriminate between active and inactive molecules for a specific target. To this end, I am comparing the effectiveness of the application of different machine learning techniques to this problem. As a source of data we have selected a set of PubChem's public BioAssays1. In addition, with the objective of realizing a real-time query service with our predictors, we aim to keep the features describing the chemical compounds relatively simple.At the end of this process, we should better understand how to build statistical models that are able to recognize molecules active in a specific bioassay, including how to select the most appropriate classification technique, and how to describe compounds in such a way that is not excessively resource-consuming to generate, yet contains sufficient information for the classification. We see immediate applications of such technology to recognize compounds with high-risk of toxicity, and also to suggest likely metabolic pathways that would process it.
Myriocin-mediated up-regulation of hepatocyte apoA-I synthesis is associated with ERK inhibition
Authors: Glaros Elias N. , Kim Woojin S. , Garner Brett
Published: January 2010

Sphingolipids including sphingomyelin have been implicated as potential atherogenic lipids. Studies in apoE (apolipoprotein E)-null mice have revealed that the serine palmitoyltransferase inhibitor myriocin reduces plasma levels of sphingomyelin, ceramide, sphingosine-1-phosphate and glycosphingolipids and that this is associated with potent inhibition of atherosclerosis. Interestingly, hepatic apoA-I (apolipoprotein A-I) synthesis and plasma HDL (high-density lipoprotein)-cholesterol levels were also increased in apoE-null mice treated with myriocin. Since myriocin is a known inhibitor of ERK (extracellular-signal-related kinase) phosphorylation, we assessed the possibility that myriocin may be acting to increase hepatic apoA-I production via this pathway. To address this, HepG2 cells and primary mouse hepatocytes were treated with 200 μM myriocin for up to 48 h. Myriocin increased apoA-I mRNA and protein levels by approx. 3- and 2-fold respectively. Myriocin also increased apoA-I secretion up to 3.5-fold and decreased ERK phosphorylation by approx. 70%. Similar findings were obtained when primary hepatocytes were isolated from apoE-null mice that were treated with myriocin (intraperitoneal injection at a dose of 0.3 mg/kg body weight). Further experiments revealed that the MEK (mitogen-activated protein kinase/ERK kinase) inhibitor PD98059 potently inhibited ERK phosphorylation, as expected, and increased primary hepatocyte apoA-I production by 3-fold. These results indicate that ERK phosphorylation plays a role in regulating hepatic apoA-I expression and suggest that the anti-atherogenic mechanism of action for myriocin may be linked to this pathway.
Stable carbon and oxygen isotope ratios of otoliths differentiate juvenile winter flounder (Pseudopleuronectes americanus) habitats
Authors: Pruell Richard J. , Taplin Bryan K. , Karr Jonathan D.
Published: January 2010

The use of natural tags for identifying the source locations of individuals recruited to fish populations has become an important area of research in fisheries science. We used stable carbon (δ13C) and oxygen (δ18O) isotope ratios in otoliths to differentiate juvenile winter flounder (Pseudopleuronectes americanus) collected from locations along the coast of Rhode Island, USA. Sagittal otoliths from the flounder were analysed for δ13C and δ18O using isotope ratio mass spectrometry. Plots of δ13C v. δ18O and discriminant function analysis (DFA) indicated differences among samples from Narragansett Bay, the coastal ponds and the Narrow River. Separations were observed among fish from the upper, middle and lower portions of Narragansett Bay and along the salinity gradient in Narrow River. Otoliths from sites grouped on the basis of low, medium and high salinities also showed differences according to DFA. Correlation analysis indicated a significant negative relationship (r = –0.60, P = 0.009) between seawater temperature and δ18O, and a significant positive relationship (r = 0.93, P < 0.001) between salinity and δ18O for the combined dataset. These results indicate that δ13C and δ18O values of juvenile winter flounder otoliths may prove useful for differentiating individuals from various juvenile habitats.
Response and recovery of fish and invertebrate assemblages following flooding in five tributaries of a sub-tropical river
Authors: Kroon F. J. , Ludwig J. A.
Published: January 2010

The response and recovery of aquatic ecosystems to major flooding is directly associated with the resistance and resilience of the perturbed ecosystem. In this 2-year study, we document the response of taxa assemblages in five tributary creeks of the Clarence River, Australia, following two sequential floods. Prior to the floods, we observed clear differences of taxa assemblages among tributaries, and clear but relatively small seasonal changes in all creeks. Flooding triggered large shifts in taxa assemblages in all creeks; however, only a few species out of the 106 taxa analysed were contributing to this pulse response. Combinations of specific water quality variables were significantly associated with the observed patterns in taxa assemblages in all but one creek. After an initial rapid recovery period, taxa compositions in all tributaries more slowly returned to resemble those before the floods. This strong resilience to major floods is most likely associated with high flushing rates, spatial and temporal refugia and life history characteristics of key biota. Overall, the results suggest that the current state of the Clarence floodplain has achieved a strong resilience to major flood disturbances, and that a shift to an alternate, potentially more desirable state may be difficult to achieve.
Climate-driven mobilisation of acid and metals from acid sulfate soils
Authors: Simpson Stuart L. , Fitzpatrick Rob W. , Shand Paul , Angel Brad M. , Spadaro David A. , Mosley Luke
Published: January 2010

The recent drought in south-eastern Australia has exposed to air, large areas of acid sulfate soils within the River Murray system. Oxidation of these soils has the potential to release acidity, nutrients and metals. The present study investigated the mobilisation of these substances following the rewetting of dried soils with River Murray water. Trace metal concentrations were at background levels in most soils. During 24-h mobilisation tests, the water pH was effectively buffered to the pH of the soil. The release of nutrients was low. Metal release was rapid and the dissolved concentrations of many metals exceeded the Australian water quality guidelines (WQGs) in most tests. The concentrations of dissolved Al, Cu and Zn were often greater than 100× the WQGs and strong relationships existed between dissolved metal release and soil pH. Attenuation of dissolved metal concentrations through co-precipitation and adsorption to Al and Fe precipitates was an important process during mixing of acidic, metal-rich waters with River Murray water. The study demonstrated that the rewetting of dried acid sulfate soils may release significant quantities of metals and a high level of land and water management is required to counter the effects of such climate change events.
Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments
Authors: Busse Dorothea , de la Rosa Maurus , Hobiger Kirstin , Thurley Kevin , Flossdorf Michael , Scheffold Alexander , Höfer Thomas
Published: January 2010

Cytokines are pleiotropic and readily diffusible messenger molecules, raising the question of how their action can be confined to specific target cells. The T cell cytokine interleukin-2 (IL-2) is essential for the homeostasis of regulatory T (Treg) cells that suppress (auto)immunity and stimulates immune responses mediated by conventional T cells. We combined mathematical modeling and experiments to dissect the dynamics of the IL-2 signaling network that links the prototypical IL-2 producers, conventional T helper (Th) cells, and Treg cells. We show how the IL-2-induced upregulation of high-affinity IL-2 receptors (IL-2R) establishes a positive feedback loop of IL-2 signaling. This feedback mediates a digital switch for the proliferation of Th cells and functions as an analog amplifier for the IL-2 uptake capacity of Treg cells. Unlike other positive feedbacks in cell signaling that augment signal propagation, the IL-2/IL-2R loop enhances the capture of the signal molecule and its degradation. Thus Treg and Th cells can compete for IL-2 and restrict its range of action through efficient cellular uptake. Depending on activation status and spatial localization of the cells, IL-2 may be consumed exclusively by Treg or Th cells, or be shared between them. In particular, a Treg cell can deprive a stimulated Th cell of its IL-2, but only when the cells are located in close proximity, within a few tens of micrometers. The present findings explain how IL-2 can play two disctinct roles in immune regulation and point to a hitherto largely unexplored spatiotemporal complexity of cytokine signaling.
Three major output pathways from the KaiABC-based oscillator cooperate to generate robust circadian
kaiBC
expression in cyanobacteria
Authors: Taniguchi Yasuhito , Takai Naoki , Katayama Mitsunori , Kondo Takao , Oyama Tokitaka
Published: January 2010

Circadian
kaiBC
expression in the cyanobacterium
Synechococcus elongatus
PCC 7942 is generated by temporal information transmission from the KaiABC-based circadian oscillator to RpaA, a putative transcriptional factor, via the SasA-dependent positive pathway and the LabA-dependent negative pathway which is responsible for feedback regulation of KaiC. However, the
labA
/
sasA
double mutant has a circadian
kaiBC
expression rhythm, suggesting that there is an additional circadian output pathway. Here we describe a third circadian output pathway, which is CikA-dependent. The
cikA
mutation attenuates KaiC overexpression-induced
kaiBC
repression and exacerbates the low-amplitude phenotype of the
labA
mutant, suggesting that
cikA
acts as a negative regulator of
kaiBC
expression independent of the LabA-dependent pathway. In the
labA
/
sasA
/
cikA
triple mutant,
kaiBC
promoter activity becomes almost arrhythmic, despite preservation of the circadian KaiC phosphorylation rhythm, suggesting that CikA largely accounts for the residual
kaiBC
expression rhythm observed in the
labA
/
sasA
double mutant. These results also strongly suggest that transcriptional regulation in the
labA
/
sasA
/
cikA
triple mutant is insulated from the circadian signals of the KaiABC-based oscillator. Based on these observations, we propose a model in which temporal information from the KaiABC-based circadian oscillator is transmitted to gene expression through three separate output pathways.
Ambient temperature response establishes ELF3 as a required component of the core
Arabidopsis
circadian clock
Authors: Thines Bryan , Harmon Frank G.
Published: January 2010

Circadian clocks synchronize internal processes with environmental cycles to ensure optimal timing of biological events on daily and seasonal time scales. External light and temperature cues set the core molecular oscillator to local conditions. In
Arabidopsis
, EARLY FLOWERING 3 (ELF3) is thought to act as an evening-specific repressor of light signals to the clock, thus serving a zeitnehmer function. Circadian rhythms were examined in completely dark-grown, or etiolated, null
elf3-1
seedlings, with the clock entrained by thermocycles, to evaluate whether the
elf3
mutant phenotype was light-dependent. Circadian rhythms were absent from etiolated
elf3-1
seedlings after exposure to temperature cycles, and this mutant failed to exhibit classic indicators of entrainment by temperature cues, consistent with global clock dysfunction or strong perturbation of temperature signaling in this background. Warm temperature pulses failed to elicit acute induction of temperature-responsive genes in
elf3-1
. In fact, warm temperature-responsive genes remained in a constitutively “ON” state because of clock dysfunction and, therefore, were insensitive to temperature signals in the normal time of day-specific manner. These results show ELF3 is broadly required for circadian clock function regardless of light conditions, where ELF3 activity is needed by the core oscillator to allow progression from day to night during either light or temperature entrainment. Furthermore, robust circadian rhythms appear to be a prerequisite for etiolated seedlings to respond correctly to temperature signals.
Analysis of CD161 expression on human CD8+T cells defines a distinct functional subset with tissue-homing properties
Authors: Billerbeck Eva , Kang Yu-Hoi , Walker Lucy , Lockstone Helen , Grafmueller Stefanie , Fleming Vicki , Flint Jonathan , Willberg Chris B. , Bengsch Bertram , Seigel Bianca , Ramamurthy Narayan , Zitzmann Nicole , Barnes Eleanor J. , Thevanayagam Jonarthan , Bhagwanani Anisha , Leslie Alasdair , Oo Ye H. , Kollnberger Simon , Bowness Paul , Drognitz Oliver , Adams David H. , Blum Hubert E. , Thimme Robert , Klenerman Paul
Published: January 2010

CD8+T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined. We have previously observed that CD8+T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8+CD161+T cells in healthy donors and those with hepatitis C virus and defined a population of CD8+T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor γ-t,P= 6 × 10−9; RUNX2,P= 0.004), cytokine receptors (e.g., IL-23R,P= 2 × 10−7; IL-18 receptor,P= 4 × 10−6), and chemokine receptors (e.g., CCR6,P= 3 × 10−8; CXCR6,P= 3 × 10−7; CCR2,P= 4 × 10−7). CD161+CD8+T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-γ and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P= 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8+T cells in normal humans and a substantial fraction of tissue-infiltrating CD8+T cells in chronic inflammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.
Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
Authors: Ma Nan , Tulu U. S. , Ferenz Nick P. , Fagerstrom Carey , Wilde Andrew , Wadsworth Patricia
Published: January 2010

TPX2 is a Ran-regulated spindle assembly factor that is required for kinetochore fiber formation and activation of the mitotic kinase Aurora A. TPX2 is enriched near spindle poles and is required near kinetochores, suggesting that it undergoes dynamic relocalization throughout mitosis. Using photoactivation, we measured the movement of PA-GFP-TPX2 in the mitotic spindle. TPX2 moves poleward in the half-spindle and is static in the interzone and near spindle poles. Poleward transport of TPX2 is sensitive to inhibition of dynein or Eg5 and to suppression of microtubule flux with nocodazole or antibodies to Kif2a. Poleward transport requires the C terminus of TPX2, a domain that interacts with Eg5. Overexpression of TPX2 lacking this domain induced excessive microtubule formation near kinetochores, defects in spindle assembly and blocked mitotic progression. Our data support a model in which poleward transport of TPX2 down-regulates its microtubule nucleating activity near kinetochores and links microtubules generated at kinetochores to dynein for incorporation into the spindle.
Marine habitat use of Peruvian boobies: a geographic and oceanographic comparison between inshore and offshore islands
Authors: Zavalaga Carlos B. , Halls Joanne , Dell'Omo Giacomo
Published: January 2010

Zavalaga, C. B., Halls, J., and Dell'Omo, G. 2010. Marine habitat use of Peruvian boobies: a geographic and oceanographic comparison between inshore and offshore islands. – ICES Journal of Marine Science, 67: 940–951. Foraging areas of Peruvian boobies (Sula variegata) from Isla Lobos de Tierra (LT, inshore) and Isla Lobos de Afuera (LA, offshore) were overlaid with concurrent data on wind patterns and remotely sensed hydrographic features to identify the main abiotic factors that affect booby distribution and to compare habitat use between birds from inshore and offshore islands. Birds used across winds and across headwinds when commuting to their feeding grounds and across tailwinds when returning to their colonies. This strategy increased flight speeds by 38–53% in relation to headwinds, probably resulting in a reduction in energy costs when birds returned to their nests with heavy loads of food. Sea surface temperature of the foraged and the available areas were similar around LT and LA. Boobies from LT fed over the continental shelf and alongshore in areas with chlorophyll a (Chl a) concentration higher than expected from a random distribution. Conversely, birds from LA never came inshore, feeding over the shelf break and in waters with concentrations of Chl a similar to those in the available area. Remote-sensing measurements of primary productivity predicted the distribution of Peruvian boobies only for LT. Plumes of enriched water alongshore are formed during the austral summer, favouring the aggregation of anchoveta (Engraulis ringens), the main prey of Peruvian boobies. Boobies from LA may have potentially foraged inshore in an area also used by birds from LT, but it is likely that competition for food and energy constraints to raise three-chick broods restricted foraging range to waters far from the mainland.
Adhesion to and invasion of pulmonary epithelial cells by the F15/LAM4/KZN and Beijing strains of Mycobacterium tuberculosis
Authors: Ashiru Olubisi T. , Pillay Manormoney , Sturm A. Willem
Published: January 2010

Globally, specific genotypes of Mycobacterium tuberculosis have been shown to dominate in patients, suggesting that these are more successful pathogens. One such genotype, the F15/LAM4/KZN (KZN) family of M. tuberculosis, has predominated in KwaZulu-Natal, South Africa, since the early 1990s. This strain recently evolved from multidrug-resistant to extensively drug-resistant (XDR). The ability of M. tuberculosis strains belonging to the Beijing family, the KZN family, strains with unique DNA fingerprint patterns and laboratory strains (H37Rv and H37Ra) to adhere to and invade a human alveolar (A549) and a human bronchial (BBM) epithelial cell line was investigated. All strains displayed greater adhesion to and invasion of A549 cells as compared to BBM cells. The Beijing and KZN strains combined showed greater adhesion (28 %) than the unique strains (5 %) (P <0.05). The XDR variant of KZN invaded A549 cells more effectively than the other isolates. These results suggest that the successful spread of the Beijing and KZN strains might be related to their interaction with alveolar epithelium.
Acquisition of multidrug resistance transposon Tn6061 and IS6100-mediated large chromosomal inversions in Pseudomonas aeruginosa clinical isolates
Authors: Coyne Sébastien , Courvalin Patrice , Galimand Marc
Published: January 2010

Pseudomonas aeruginosa is a major human opportunistic pathogen, especially for patients in intensive care units or with cystic fibrosis. Multidrug resistance is a common feature of this species. In a previous study we detected the ant(4′)-IIb gene in six multiresistant clinical isolates of P. aeruginosa, and determination of the environment of the gene led to characterization of Tn6061. This 26 586 bp element, a member of the Tn3 family of transposons, carried 10 genes conferring resistance to six drug classes. The ant(4′)-IIb sequence was flanked by directly repeated copies of ISCR6 in all but one of the strains studied, consistent with ISCR6-mediated gene acquisition. Tn6061 was chromosomally located in six strains and plasmid-borne in the remaining isolate, suggesting horizontal acquisition. Duplication-insertion of IS6100, that ended Tn6061, was responsible for large chromosomal inversions. Acquisition of Tn6061 and chromosomal inversions are further examples of intricate mechanisms that contribute to the genome plasticity of P. aeruginosa.
The enigmatic lack of glucose utilization in Streptomyces clavuligerus is due to inefficient expression of the glucose permease gene
Authors: Pérez-Redondo Rosario , Santamarta Irene , Bovenberg Roel , Martín Juan F. , Liras Paloma
Published: January 2010

Streptomyces clavuligerusATCC 27064 is unable to use glucose but has genes for a glucose permease (glcP) and a glucose kinase (glkA). Transformation ofS. clavuligerus27064 with theStreptomyces coelicolor glcP1gene with its own promoter results in a strain able to grow on glucose. TheglcPgene ofS. clavuligerusencodes a 475 amino acid glucose permease with 12 transmembrane segments. GlcP is a functional protein when expressed from theS. coelicolor glcP1promoter and complements two different glucose transport-negativeEscherichia colimutants. Transcription studies indicate that theglcPpromoter is very weak and does not allow growth on glucose. These results suggest thatS. clavuligerusinitially contained a functional glucose permease gene, like most otherStreptomycesspecies, and lost the expression of this gene by adaptation to glucose-poor habitats.
Activation of geminivirus V‐sense promoters in roots is restricted to nematode feeding sites
Authors: ESCOBAR CAROLINA , GARCÍA ALEJANDRA , ARISTIZÁBAL FABIO , PORTILLO MARY , HERREROS ESTHER , MUNOZ‐MARTÍN M. ANGELES , GRUNDLER FLORIAN , MULLINEAUX PHILLIP M. , FENOLL CARMEN
Published: January 2010

Obligate sedentary endoparasitic nematodes, such as the root‐knot and cyst nematodes, elicit the differentiation of specialized nematode nurse or feeding cells [nematode feeding sites (NFS), giant cells and syncytia, respectively]. During NFS differentiation, marked changes in cell cycle progression occur, partly similar to those induced by some geminiviruses. In this work, we describe the activation of V‐sense promoters from the Maize streak virus (MSV) and Wheat dwarf virus (WDV) in NFS formed by root‐knot and cyst nematodes. Both promoters were transiently active in microinjection experiments. In tobacco and Arabidopsis transgenic lines carrying promoter–β‐glucuronidase fusions, the MSV V‐sense promoter was activated in the vascular tissues of aerial plant parts, primarily leaf and cotyledon phloem tissue and some floral structures. Interestingly, in roots, promoter activation was restricted to syncytia and giant cells tested with four different nematode populations, but undetectable in the rest of the root system. As the activity of the promoter in transgenic rootstocks should be restricted to NFS only, the MSV promoter may have utility in engineering grafted crops for nematode control. Therefore, this study represents a step in the provision of some of the much needed additional data on promoters with restricted activation in NFS useful in biotechnological nematode control strategies.
Ultrasonographic guided axillary plexus blocks with low volumes of local anaesthetics: a crossover volunteer study
Authors: Marhofer P. , Eichenberger U. , Stöckli S. , Huber G. , Kapral S. , Curatolo M. , Kettner S.
Published: January 2010

Our study group recently evaluated an ED95 local anaesthetic volume of 0.11 ml.mm−2 cross‐sectional nerve area for the ulnar nerve. This prospective, randomised, double‐blind crossover study investigated whether this volume is sufficient for brachial plexus blocks at the axillary level. Ten volunteers received an ultrasonographic guided axillary brachial plexus block either with 0.11 (‘low’ volume) or 0.4 (‘high’ volume) ml.mm−2 cross‐sectional nerve area with mepivacaine 1%. The mean (SD) volume was in the low volume group 4.0 (1.0) and 14.8 (3.8) ml in the high volume group. The success rate for the individual nerve blocks was 27 out of 30 in the low volume group (90%) and 30 out of 30 in the high volume group (100%), resulting in 8 out of 10 (80%) vs 10 out of 10 (100%) complete blocks in the low vs the high volume groups, respectively (NS). The mean (SD) sensory onset time was 25.0 (14.8) min in the low volume group and 15.8 (6.8) min in the high volume group (p < 0.01). The mean (SD) duration of sensory block was 125 (38) min in the low volume group and 152 (70) min in the high volume group (NS). This study confirms our previous published ED95 volume for mepivacaine 1% to block peripheral nerves. The volume of local anaesthetic has some influence on the sensory onset time.
Modulation of immune responses through direct activation of Toll-like receptors to T cells
Authors: Liu G , Zhang L , Zhao Y
Published: January 2010

Toll-like receptors (TLRs), which are a family of pattern recognition receptors (PRRs), are involved critically in the generation and regulation of innate immunity as well as initiation of subsequent adaptive immune responses. However, recent research results showed that different subsets of T cells express certain types of TLRs during development and activation stages. Importantly, TLRs participate in the direct regulation of adaptive immune response, possibly as co-stimulatory molecules. In this review we summarize recent studies about the novel regulation of TLRs on the homeostasis and immunity of different T cell subtypes including CD4+CD25+T regulatory cells (Treg) and interleukin (IL)-17-producing CD4+T cells (T helper type 17). The direct involvement of TLRs in T cell-mediated immunity prompted us to reconsider the role of TLRs in the occurrence of autoimmune diseases, infectious diseases and graft rejection. The important effects of TLRs in T cell-intrinsic components also prompt us to explore novel vaccine adjuvants for modifying desired immune responses in an efficient way.
Thyroid fine needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results
Authors: Rossi E. D. , Morassi F. , Santeusanio G. , Zannoni G. F. , Fadda G.
Published: January 2010

E. D. Rossi, F. Morassi, G. Santeusanio, G. F. Zannoni and G. Fadda  Thyroid fine needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results

Background:  Fine needle aspiration cytology is the most accurate tool for diagnosing thyroid nodules. Its accuracy is related to the rate of inadequate samples, which can be minimized with the adoption of on‐site assessment of the adequacy of the material. The introduction of liquid‐based cytology (LBC) in the thyroid does not allow checking on the adequacy of the cellularity. The possibility of making a second LBC slide for decreasing the number of non‐diagnostic cases is studied.

Methods:  Out of 553 cases diagnosed in a single institution from January to March 2005, 166 consecutive cases with an LBC slide reviewed by the same pathologist were evaluated. The cases were classified in a five‐tiered category system (Thy1 to 5 according to the British Thyroid Association guidelines) and all but two (with cystic degeneration) were processed by LBC and stained with Papanicolaou stain. The above‐mentioned categories are defined as follows: Thy1 inadequate or haemorrhagic, Thy2 non‐neoplastic lesion; Thy3 follicular lesion/suspected follicular neoplasm; Thy4 suspicious for malignancy; Thy5 diagnostic of malignancy. For each case the cytological diagnosis was made on the LBC slide and the adequacy of the cellularity for a conclusive diagnosis was assessed.

Results:  Of the 166 cases, 39 were non‐diagnostic (Thy1—inadequate), ten presented features of cystic degeneration (Thy1—haemorrhagic), 90 were benign (Thy2), 22 were diagnosed as a follicular lesion (Thy3), one as suspicious of malignancy (Thy4) and four as papillary carcinoma (Thy5). Thirty‐nine cases had a second LBC for achieving a definitive diagnosis with eventual re‐classification. Of these cases, 23 (61.5%) led to a conclusive diagnosis (18 Thy2, five Thy3) with a 18.5% decrease of the inadequacy rate.

Conclusions:  The making of an additional LBC slide helps in achieving a diagnosis in cases classified as non‐diagnostic on the first standard slide (52.1% recovery rate). This procedure is particularly helpful for meeting the adequacy criteria in benign and indeterminate lesions and could also be used for refining the diagnosis of suspicious for a malignant thyroid neoplasm.
Differential gene expression in senescing leaves of two silver birch genotypes in response to elevated CO2 and tropospheric ozone
Authors: KONTUNEN‐SOPPELA SARI , RIIKONEN JOHANNA , RUHANEN HANNA , BROSCHÉ MIKAEL , SOMERVUO PANU , PELTONEN PETRI , KANGASJÄRVI JAAKKO , AUVINEN PETRI , PAULIN LARS , KEINÄNEN MARKKU , OKSANEN ELINA , VAPAAVUORI ELINA
Published: January 2010

Long‐term effects of elevated CO2 and O3 concentrations on gene expression in silver birch (Betula pendula Roth) leaves were studied during the end of the growing season. Two birch genotypes, clones 4 and 80, with different ozone growth responses, were exposed to 2× ambient CO2 and/or O3 in open‐top chambers (OTCs). Microarray analyses were performed after 2 years of exposure, and the transcriptional profiles were compared to key physiological characteristics during leaf senescence. There were genotypic differences in the responses to CO2 and O3. Clone 80 exhibited greater transcriptional response and capacity to alter metabolism, resulting in better stress tolerance. The gene expression patterns of birch leaves indicated contrasting responses of senescence‐related genes to elevated CO2 and O3. Elevated CO2 delayed leaf senescence and reduced associated transcriptional changes, whereas elevated O3 advanced leaf senescence because of increased oxidative stress. The combined treatment demonstrated that elevated CO2 only temporarily alleviated the negative effects of O3. Gene expression data alone were insufficient to explain the O3 response in birch, and additional physiological and biochemical data were required to understand the true O3 sensitivity of these clones.
Peyronie’s disease compromises the durability and component‐malfunction rates in patients implanted with an inflatable penile prosthesis
Authors: DiBlasio Christopher J. , Kurta Jordan M. , Botta Sisir , Malcolm John B. , Wan Jim Y. , Derweesh Ithaar H. , Aleman Michael A. , Wake Robert W.
Published: January 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To compare the durability and complication rates of surgery to implant an inflatable penile prosthesis (IPP) between patients with and without Peyronie’s disease (PD).

PATIENTS AND METHODS

We retrospectively reviewed all patients undergoing IPP surgery at one centre (Memphis) between July 1997 and May 2007. Variables included age at surgery, race, body mass index, presence of PD, brand/type of IPP (two vs three pieces), presence of diabetes mellitus (DM), active tobacco use, and complications. The result were assessed using t‐tests, chi‐square and regression analysis, with P < 0.05 considered to indicate significant differences.

RESULTS

In all, 79 men were analysed (mean age 59.8 years, range 38.1–81.5). Nine (11%) patients had PD and had a IPP implanted, with penile modelling. Overall, 43 (54%) patients had pre‐existing DM and 51 (65%) actively used tobacco. At a mean (range) follow‐up of 19.6 (0.1–115.3) months, six (8%) patients had component malfunctions. Of these, three had DM and four actively smoked. Of the nine patients with PD, three developed component malfunctions, vs three (4%) who did not have PD (P= 0.002). Both groups had similar infection rates (P= 0.98). The mean (range) time to component malfunction was 4.3 (0.1–9.6) months, which was longer (but not significantly) in the PD group, with a mean (median, range) of 10.9 (6.3, 1.1–9.6) months, than the 3.0 (1.0, 0.2–7.9) months in the group without PD (P= 0.4). Groups were matched for rates of DM (P= 0.1) and tobacco use (P= 0.2). PD was a significant predictor of component malfunction on both univariate (P= 0.001) and multivariate analysis (P= 0.002) when adjusting for age (P= 0.2), body mass index (P= 0.7), DM (P= 0.3) and tobacco use (P= 0.8).

CONCLUSION

Patients with PD implanted with a IPP, with penile modelling, had significantly higher component malfunction rates. Further, PD independently predicted component malfunction. These findings might be related to stress on the device at the time of surgery, during use, or both. Further study into this relationship is required.
PLAYING FOR KEEPS: PAY AND PERFORMANCE IN THE NBA
Authors: STIROH KEVIN J.
Published: January 2010

This paper examines contract‐related incentive effects using a unique dataset on individual performance and individual contracts. Evidence from professional basketball players in the 1980s and 1990s shows that individual performance improves significantly in the year before signing a multi‐year contract but declines after the contract is signed. One interpretation is that workers strategically increase effort to obtain the most lucrative, multi‐year contract but then reduce it once the contract is locked in. This highlights the double‐edged nature of long‐term contracts: good for employers when workers are fighting for them, but less so when workers have them. (JEL J22, J3)
NOMINAL WAGE CONTRACTS AND THE MONETARY TRANSMISSION MECHANISM
Authors: JANKO ZUZANA
Published: January 2010

We introduce staggered and synchronized nominal wage contracts into a one‐sector monetary dynamic general equilibrium model to analyze the importance of the monetary transmission mechanism. We find a stronger monetary propagation mechanism under a synchronized setting as compared to a staggered setting. This causes the economy under staggering to be less volatile, better matching the data, as well as bringing about lower welfare costs (measured in terms of consumption). However, our results are mixed when it comses to evaluating the contemporaneous correlations and cross‐correlations. We conclude that overall staggered contracts do better in matching the U.S. economy. (JEL E32, E51, J41)
OUTPUT EFFECTS OF INFLATION WITH FIXED PRICE– AND QUANTITY–ADJUSTMENT COSTS
Authors: DANZIGER LEIF
Published: January 2010

This article examines how the aggregate production varies with inflation when there are fixed price– and quantity–adjustment costs. It shows that such variation is determined by the elasticity of the firms’ marginal real revenue with respect to demand. The aggregate production decreases with inflation if this elasticity always exceeds minus unity, whereas the aggregate production increases with inflation if the elasticity is always less than minus unity. The aggregate production is independent of inflation in the special case that the elasticity always equals minus unity. The latter occurs if demand is derived from a log‐quadratic utility function. (JEL E31)
The Governance of the Multinational Enterprise: Insights from Internalization Theory
Authors: Buckley Peter J. , Strange Roger
Published: January 2010

abstract

The objectives of this paper are to outline the contribution of internalization theory to our understanding of the governance of the MNE, and to highlight aspects of the theory that we believe have received insufficient attention in the literature. In particular, we suggest two promising lines of future research. The first focuses on the internal transaction costs associated with the governance and organization of the activities within the MNE, and here we highlight the costs of information acquisition and transmission, the costs of coordination, and the costs of aligning the interests of different stakeholders within the MNE. The second addresses the implications of different assumptions about the risk propensity of the MNE.
Seventeen‐month‐olds appeal to false beliefs to interpret others’ referential communication
Authors: Southgate Victoria , Chevallier Coralie , Csibra Gergely
Published: January 2010

Recent studies have demonstrated infants’ pragmatic abilities for resolving the referential ambiguity of non‐verbal communicative gestures, and for inferring the intended meaning of a communicator’s utterances. These abilities are difficult to reconcile with the view that it is not until around 4 years that children can reason about the internal mental states of others. In the current study, we tested whether 17‐month‐old infants are able to track the status of a communicator’s epistemic state and use this to infer what she intends to refer to. Our results show that manipulating whether or not a communicator has a false belief leads infants to different interpretations of the same communicative act, and demonstrate early mental state attribution in a pragmatic context.
Late potentials and QT dispersion after high‐dose chemotherapy in patients with non‐Hodgkin lymphoma
Authors: Kuittinen Taru , Jantunen Esa , Vanninen Esko , Mussalo Hanna , Nousiainen Tapio , Hartikainen Juha
Published: January 2010

The most common cardiotoxic effects of high‐dose cyclophosphamide (CY) are electrocardiographic changes and transient arrhythmias. Therefore, we prospectively assessed serial electrocardiogram (ECG) and signal‐averaged electrocardiogram (SAECG) recordings in 30 adult patients with non‐Hodgkin lymphoma (NHL) receiving high‐dose CY as part of high‐dose chemotherapy (HDT) regimen. All patients were treated with anthracyclines earlier. Heart‐rate‐corrected QT interval and QT dispersion (QTc and QTc dispersion) were measured from ECG. QRS duration and late potentials (LPs) were analysed from SAECG. Both ECG and SAECG were recorded 1 day (d) prior to HDT (d−7) at baseline, and 1 day (d−2), 7 days (d+7), 12 days (+12) and 3 months (m+3) after HDT. Stem cells were infused on day 0 (d0). Cardiac systolic and diastolic function were assessed on (d−7), (d+12) and (m+3) by radionuclide ventriculography. At baseline, four patients presented with LPs. Cardiac systolic function decreased significantly (53 ± 2; 49 ± 2%, P = 0·009 versus baseline), whilst no patient developed acute heart failure. QRS duration prolonged and RMS40 reduced significantly versus baseline (104 ± 3; 107 ± 3 ms, P = 0·003; 41 ± 4; 38 ± 3 μV, P = 0·03), and six patients (21%) presented with LPs after CY treatment. Both QTc interval and QTc dispersion increased versus baseline (402 ± 5; 423 ± 5 ms, P<0·001; 32 ± 2; 44 ± 3 ms, P = 0·012), and six patients (20%) developed abnormal QT dispersion. In conclusion, high‐dose CY causes subclinical and transient electrical instability reflected by occurrence of LPs as well as increased QTc interval and QT dispersion. Thus, longer follow‐up is required to confirm the meaning of these adverse effects on cardiac function and quality of life.
Sensitization to dimethyl fumarate with multiple concurrent patch test reactions
Authors: Lammintausta Kaija , Zimerson Erik , Winhoven Sandra , Susitaival Päivikki , Hasan Taina , Gruvberger Birgitta , Williams Jason , Beck Michael , Bruze Magnus
Published: January 2010

Background: Chairs and sofas imported from China to Europe were shown to contain dimethyl fumarate (DMF), a sensitizing, volatile chemical. Many of the sensitized patients also had positive patch test reactions to acrylates.

Objectives: To analyse the occurrence and strength of DMF sensitization and the appearance of concomitant reactions.

Methods: Patch testing with DMF in concentrations of 0.1–0.00001% was carried out in 37 patients. Diethyl fumarate (DEF), diethyl maleate (DEM), dimethyl maleate (DMM), ethyl acrylate (EA), methyl acrylate (MA), and methyl methacrylate (MMA) were also tested with a dilution series at equimolar concentrations.

Results: The lowest concentration of DMF eliciting a reaction varied between 0.0001% and 0.1% and all but four patients reacted concurrently to DEF. DEM elicited positive patch test reactions in 21/37 patients and DMM reactions were seen in all 9 patients tested. EA elicited positive reactions in 13/37 patients and a positive MA reaction was seen in 7/37 patients, 2 of whom also reacted to MMA.

Conclusions: The strength of the sensitization to DMF showed variation and concurrent reactions were common. Concurrent reactions to (meth)acrylates were seen in patients, who reacted to lower (0.001% or less) DMF concentration probably elicited by cross‐reactivity.
Sheep genetic diversity in Bhutan using microsatellite markers
Authors: DORJI Tashi , JIANLIN Han , WAFULA Po , YAMAMOTO Yoshio , SASAZAKI Shinji , OYAMA Kenji , HANOTTE Oliver , LIN Bang‐Zhong , MANNEN Hideyuki
Published: January 2010

Genotype data from eight microsatellite markers were used to assess genetic diversity and relationships among five indigenous Bhutanese sheep populations, Sakten, Jakar, Sarpang, Sipsu and Tsirang. Estimates of mean observed and expected heterozygosities, mean number of alleles per locus/population were obtained. The highest observed heterozygosities were found in Jakar (0.657) and Sakten (0.647), while the lowest one was found in Tsirang (0.539). Genetic distances, pairwise proportion of different alleles, UPGMA tree, and principal component analysis indicate close relationship among Tsirang, Sipsu and Sarpang populations, while Jakar and Sakten populations are located in one cluster. These two clusters are separated geographically, and show distinct phenotypic as well as molecular characters. We therefore recommend that the Bhutanese native sheep populations be classified into at least two distinct breeds, Jakar‐Sakten sheep and Sipsu sheep. Since Jakar and Sakten sheep have different morphological phenotypes, further analyses will be required to understand the genetic differences between these two sheep populations.
Linking MODFLOW with an Agent‐Based Land‐Use Model to Support Decision Making
Authors: Reeves Howard W. , Zellner Moira L.
Published: January 2010

The U.S. Geological Survey numerical groundwater flow model, MODFLOW, was integrated with an agent‐based land‐use model to yield a simulator for environmental planning studies. Ultimately, this integrated simulator will be used as a means to organize information, illustrate potential system responses, and facilitate communication within a participatory modeling framework. Initial results show the potential system response to different zoning policy scenarios in terms of the spatial patterns of development, which is referred to as urban form, and consequent impacts on groundwater levels. These results illustrate how the integrated simulator is capable of representing the complexity of the system. From a groundwater modeling perspective, the most important aspect of the integration is that the simulator generates stresses on the groundwater system within the simulation in contrast to the traditional approach that requires the user to specify the stresses through time.