bluuebunny/crossref_metadata_2025 huggingface dataset:
Topical tacrolimus (FK506) for the treatment of feline idiopathic facial dermatitis
Authors: Chung T‐H , Ryu M‐H , Kim D‐Y , Yoon H‐Y , Hwang C‐Y
Published: September 2009

A 3‐year‐old, neutered male Persian cat with chronic ulcerative facial dermatitis was diagnosed with feline idiopathic facial dermatitis based on signalment, clinical history and diagnostic test results, including dermatohistopathological evaluation. Initial treatment started with 4 weeks of oral antifungal/antibiotic medication for severe secondary infectious dermatitis of Malassezia and bacteria. As the lesions gradually improved, the oral medication was withdrawn, leaving only 0.1% topical FK506 (tacrolimus) ointment for the remaining lesions. Topical treatment was administered just in case any new lesions developed. The patient has been managed effectively with topical tacrolimus and no side‐effects were observed during treatment. Feline idiopathic facial dermatitis is known as a difficult dermatosis to manage successfully, but our experience suggests that it may respond to topical tacrolimus.
Temperate marine reserves: global ecological effects and guidelines for future networks
Authors: Stewart Gavin B. , Kaiser Michel J. , Côté Isabelle M. , Halpern Benjamin S. , Lester Sarah E. , Bayliss Helen R. , Pullin Andrew S.
Published: September 2009

Marine reserves, areas closed to all fishing and other extractive activities, provide a refuge for species of commercial and conservation importance. Given the considerable resources committed to designing temperate reserve networks, we synthesized data from temperate reserves worldwide to determine their ecological effects. In common with other studies, we found higher density, biomass, and species richness in temperate marine reserves compared to adjacent exploited areas. However, there was considerable heterogeneity in magnitude of effect among reserves, variability which was largely unexplained by species or reserve characteristics. Our analytical approach allowed for formal power analyses, indicating that detection of large reserve effects in temperate systems globally requires monitoring at least 37 reserves. These results must be qualified by the limitations of data available and will undoubtedly vary at different spatio‐temporal scales and for different focal species, but provide guidance for the design and monitoring of future marine conservations plans. International commitments toward establishment of multiple reserves offer a unique opportunity to assess reserve effectiveness; this opportunity can only be realized if reserves are designed to achieve clear and quantifiable objectives and are adequately monitored before and after establishment, based on appropriate power analyses, to assess how well those objectives are achieved.
Fenretinide stimulates the apoptosis of hepatic stellate cells and ameliorates hepatic fibrosis in mice
Authors: Qian Jin , Zhang Jin Sheng , Wang Xue Qing , Ji Ju Ling , Mei Shuang
Published: September 2009

Aim: To investigate whether fenretinide, a clinically proved apoptosis‐inducing chemopreventive agent in tumor cells, can induce apoptosis in hepatic stellate cells (HSCs) and resolve hepatic fibrosis.

Methods: CCl4‐induced liver fibrosis in mice and rat activated hepatic stellate cells (HSC‐T6) as well as hepatocytes (BRL‐3A) were studied.

Results: The duplex staining of proliferating cell nuclear antigen and α‐ smooth muscle actin or terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling and α‐ smooth muscle actin demonstrated that fenretinide executed its anti‐fibrosis effect in liver by inducing apoptosis rather than inhibiting proliferation of HSCs, while it had no apparently apoptotic effect on hepatocytes. Fenretinide could elicit apoptosis of HSC‐T6in vitroat the concentration range from 0.5 to 5 µM, but at higher concentrations ≥5 µM was required to induce apoptosis in hepatocytes (BRL‐3A).

Conclusion: Further studies using malondialdehyde measurement, Western blot, antioxidant, inhibitors for p53, caspase 8 and 9 – as well as anti‐Fas neutralizing antibody – have shown that in HSC‐T6, fenretinide‐induced apoptosis involves a reactive oxygen species (ROS)‐generated, P53‐independent, mitochondria‐associated intrinsic pathway, whereas in hepatocytes (BRL‐3A), a ROS‐generated, P53‐dependent, Fas‐related extrinsic pathway is triggered only at high concentration.
Altered regulation of extrinsic apoptosis pathway in HCV‐infected HCC cells enhances susceptibility to mapatumumab‐induced apoptosis
Authors: Zhang Xiaozhen , Frank Astrid C. , Gille Christine M. , Daucher Marybeth , Kabat Juraj , Becker Steven , Lempicki Richard A. , Cortez Karoll J. , Polis Michael A. , Subramanian G. Mani , Kottilil Shyam
Published: September 2009

Background:  Hepatitis C virus (HCV)‐infected patients, including those co‐infected with human immunodeficiency virus (HIV), are at increased risk of developing hepatocellular carcinoma (HCC). We evaluated the ability of agonistic human monoclonal antibodies to tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) receptors, mapatumumab and lexatumumab, respectively, to induce TRAIL‐receptor mediated apoptosis (TRMA) in HCC (HCV‐infected and ‐uninfected) cells and in peripheral blood cells (HIV‐infected and ‐uninfected).

Methods:  Susceptibility to antibody‐mediated TRMA was measured by caspase 3/7 activity and by confocal microscopy. Surface expression of receptors on HCV‐uninfected and ‐infected Huh7.5 cells was measured by flow cytometry and confocal microscopy. Inhibitor of Apoptosis Protein (IAP) RNA levels were quantified by RT‐PCR. DNA Microarray was performed using RNA isolated from Huh7.5 cells (HCV‐infected and uninfected) using Affymetrix U133A chips.

Results:  Mapatumumab preferentially induces TRMA of HCV‐infected Huh7.5 cells by binding to TRAIL‐R1. Higher basal expression of TRAIL‐R2 compared to that of TRAIL‐R1 on HCV‐uninfected Huh7.5 cells were observed. Lexatumumab induces TRMA of both HCV‐infected and ‐uninfected cells by binding to TRAIL‐R2. IFN‐α has minimal effect on mapatumumab‐ and lexatumumab‐induced TRMA. HCV infection of Huh7.5 cells up‐regulates TRAIL‐R1 expression and X‐linked Inhibitor of apoptosis protein and survivin gene expression. Neither antibody had a pro‐apoptotic effect on PBMCs from patients with HIV infection ex vivo.

Conclusion:  Both mapatumumab and lexatumumab are excellent candidates for therapy of HCC. HCV infection of Huh7.5 cells selectively up‐regulates TRAIL‐R1 receptor, associated with increased susceptibility to mapatumumab‐mediated TRMA. HCV infection up‐regulated IAP genes, offering promise for future combination therapy using TRAIL agonists and IAP inhibitors.
Interstitial chemotherapy using thermosensitive gel‐coated ricin in nude mice bearing a human hepatoma
Authors: Chen Zhi‐kui , Lin Li‐wu , Yang Yinghong , Zhang Zhi‐qiang , Cai Huajing , Cai Min‐xian
Published: September 2009

Aim:  To investigate the anti‐tumor effects and mechanisms of interstitial chemotherapy using intra‐tumor injection of thermosensitive gel‐coated ricin in nude mice bearing a human hepatoma.

Methods:  In a subcutaneous mouse model of hepatoma, saline, blank gel, ricin, or thermosensitive gel‐coated ricin (TGR) was injected directly into tumors. Fourteen days later, eight mice in each group were sacrificed. The tumors were removed and weighed for calculating tumor growth inhibition rate. Serum alpha‐fetoprotein levels, as well as hepatic and renal functions, were measured. Tumor tissue was analyzed under an optical microscope. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling was used to detect the apoptotic index. Moreover, caspase‐3 activity and protein expression in tumor tissue were examined. The survival time of the tumor bearing mice was determined.

Results:  Following interstitial chemotherapy by intra‐tumor injection of TGR in nude mice, serum alpha‐fetoprotein levels were significantly reduced with no significant impact on hepatic or renal functions. The rate of tumor growth inhibition was 58.5% following a single, local injection. Histological analysis revealed abundant necrosis. The apoptotic index was 45.96 ± 7.41%. Caspase‐3 activity was increased, and caspase‐3 protein was significantly activated in tumor cells. Compared to the saline group, the survival time of mice in the TGR group was significantly extended. At the observation terminal time, day 120, two mice were still alive and fully recovered.

Conclusion:  Interstitial chemotherapy by intra‐tumor injection of TGR was highly efficient and safe for the treatment of nude mice bearing a human hepatoma. Interstitial chemotherapy exhibits inhibitory effects by inducing apoptosis and directly killing tumor cells.
Role of Kupffer cells in the outgrowth of colorectal cancer liver metastases
Authors: Paschos Konstantinos A. , Majeed Ali W. , Bird Nigel C.
Published: September 2009

Colorectal cancer is one of the commonest malignancies in the “developed” world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines. Subsequently, colorectal metastasising cells are destroyed either by KC‐performed phagocytosis or via the stimulation of other immune cells which migrate into the sinusoids and act accordingly. On the contrary, KC products, including cytokines, growth factors and matrix‐degrading enzymes may promote liver metastasis, supporting tumour cell extravasation, motility and invasion. Current research aims to exploit the antineoplastic properties of KCs in new therapeutic approaches of colorectal cancer liver metastasis. Numerous agents, such as the granulocyte macrophage‐colony stimulating factor, interferon gamma, muramyl peptide analogues and various antibody based treatments, have been tested in experimental models with promising results. Future trials may investigate their use in everyday clinical practice and compare their therapeutic value with current treatment of the disease.
Comment on “Infants’ Perseverative Search Errors Are Induced by Pragmatic Misinterpretation”
Authors: Spencer John P. , Dineva Evelina , Smith Linda B.
Published: September 2009

Topál
et al
. (Reports, 26 September 2008, p. 1831) proposed that infants’ perseverative search errors can be explained by ostensive cues from the experimenter. We use the dynamic field theory to test the proposal that infants encode locations more weakly when social cues are present. Quantitative simulations show that this account explains infants’ performance without recourse to the theory of natural pedagogy.
Response to Comment on “Infants’ Perseverative Search Errors Are Induced by Pragmatic Misinterpretation”
Authors: Topál József , Tóth Mária , Gergely György , Csibra Gergely
Published: September 2009

Spencer
et al
. argue that infants’ perseverative search errors cannot be ascribed to an interpretive bias induced by communicative cues as we proposed. We argue that their model leads to different predictions about infant behavior from those derived from natural pedagogy in certain situations and therefore fails to provide a viable alternative to ours.
On Universality in Human Correspondence Activity
Authors: Malmgren R. Dean , Stouffer Daniel B. , Campanharo Andriana S. L. O. , Amaral Luís A. Nunes
Published: September 2009

Correspondence Communications

Statistical physicists and social scientists have attempted to describe human activities, in terms of physical models, and look for universal principles. Correspondence patterns are thought to be driven primarily by the need to respond to other individuals with both e-mail and letter correspondence showing power-law distributions. Because there are different exponents for the two modes of correspondence, it has been suggested that human correspondence falls into one of two universality classes and that e-mail and letter correspondence are fundamentally different activities. NowMalmgrenet al.(p.1696) tested whether human correspondence patterns are instead driven by mechanisms such as circadian cycles, task repetition, and changing communication needs. Letter correspondence, like e-mail correspondence, was accurately modeled as a cascading nonhomogeneous Poisson process giving rise to non-Gaussian statistics, but not to power-law statistics. Instead, the correspondence patterns of each individual could be uniquely characterized by the parameters of the model; that is, the process was shown to be universal, but the parameters were not. Thus, an individual's affinity toward a particular life-style will affect communication patterns, which can be modeled as a complex system.
Why Capture CO
2
from the Atmosphere?
Authors: Keith David W.
Published: September 2009

Air capture is an industrial process for capturing CO
2
from ambient air; it is one of an emerging set of technologies for CO
2
removal that includes geological storage of biotic carbon and the acceleration of geochemical weathering. Although air capture will cost more than capture from power plants when both are operated under the same economic conditions, air capture allows one to apply industrial economies of scale to small and mobile emission sources and enables a partial decoupling of carbon capture from the energy infrastructure, advantages that may compensate for the intrinsic difficulty of capturing carbon from the air.
Doing Magic with DNA
Untangling the Double Helix
DNA Entanglement and the Action of the DNA Topoisomerases

by James C. Wang

Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2009. 245 pp. $79. ISBN 9780879698638. Paper, $45. ISBN 9780879698799.
Authors: Mondragón Alfonso
Published: September 2009

After providing a historical perspective on the problem of DNA entanglement, Wang discusses structural, functional, and clinical aspects of topoisomerases.
A New Departure in Fluorination Chemistry
Authors: Gouverneur Véronique
Published: September 2009

A method for fluorinating a wide range of aromatic molecules will find immediate application in pharmaceutical research and may facilitate access to medical imaging reagents.
A Lunar Waterworld
Authors: Lucey Paul G.
Published: September 2009

Space-based spectroscopic measurements provide strong evidence for water on the surface of the Moon.
Scoping Out Unseen Forces Shaping North America
Authors: Kerr Richard A.
Published: September 2009

As it sweeps across America, the USArray network of seismometers is revealing an impressive but often befuddling subsurface menagerie of slabs, drips, and plumes.
Do Scientists Like Green Porno?
Authors: Bohannon John
Published: September 2009

The Gonzo Scientist introduces a group of researchers to Green Porno, a series of cartoonlike vignettes about the sex life of animals, and asks them what they think of seeing their discoveries transformed into sexy art.
Loss of ALX4 expression in epithelial cells and adjacent stromal cells in breast cancer
Authors: Chang H , Mohabir N , Done S , Hamel P A
Published: September 2009

Background:

Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.

Aims:

To begin to define the role of ALX4 in the human breast and in breast cancer, the expression pattern of ALX4 in the normal human breast and changes in expression in breast cancer were determined.

Methods:

Cells expressing ALX4 in the human breast were identified by co-immunofluorescence using α-ALX4 antibodies and markers of specific mammary cell types. ALX4 expression in breast cancer was then determined by immunohistochemistry on tumour sections that also harboured regions of normal breast tissue. Using criteria that required ALX4 staining in both stromal and epithelial cells, changes in ALX4 expression in tumours on a tissue microarray were determined.

Results:

ALX4 was expressed in both stromal and luminal epithelial cells in the human breast. Scoring tissue sections of duct carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) that also harboured regions of normal breast tissue, a loss of ALX4 (p<0.001) in stromal and epithelial cells in breast tumours was observed. Analysis of ALX4 expression in 123 sections on a tissue microarray confirmed a highly significant loss (p<0.001) of ALX4 in breast cancer in the tumours themselves and in adjacent stromal cells.

Conclusions:

These data show a distinct pattern of expression of ALX4 in the human breast relative to the murine mammary gland. Furthermore, characterisation of ALX4 in breast cancer showed that loss of ALX4 in tumours and the surrounding untransformed stroma is a basic characteristic of DCIS and IDC.
Utilisation of laboratory services by health workers in a district hospital in Malawi
Authors: Mepham S O , Squire S Bertel , Chisuwo L , Kandulu J , Bates I
Published: September 2009

Aims:

To identify priorities for improving effective use of laboratory services in a district hospital in Malawi.

Methods:

A prospective observational study of clinician–patient interactions to analyse laboratory test requesting practices and utilisation of laboratory results. The proportion of tests that was appropriately ordered, processed and ultimately influenced clinical management was used to assess effectiveness of utilisation.

Results:

420 clinical consultations between health professionals and patients were observed. 92% of tests were ordered appropriately, 84% were processed by the laboratory and 64% of results influenced patient management. 73–79% of high-volume tests (haemoglobin, microscopy for malaria and tuberculosis) and 32% of low-volume tests influenced management.

Conclusions:

25% of commonly requested laboratory tests were not utilised effectively; because of the high volume, interventions to improve their use are likely to be cost effective. Although 68% of low-volume tests were not used efficiently, the cost of providing support for these tests in a resource-poor setting needs to be balanced against their clinical usefulness. In contrast to published information, this study shows significant under-requesting of laboratory tests that were available. Measures to increase appropriate test requests will have implications for clinician education as well as laboratory space, budgets and staffing levels.
ATTRACTOR SOLUTION IN COUPLED YANG–MILLS FIELD DARK ENERGY MODELS
Authors: ZHAO WEN
Published: September 2009

We investigate the attractor solution in the coupled Yang–Mills field dark energy models with the general interaction term, and obtain the constraint equations for the interaction if the attractor solution exists. The research also shows that, if the attractor solution exists, the equation of state of dark energy must evolve from wy > 0 to wy ≤ -1, which is slightly suggested by the observation. At the same time, the total equation of state in the attractor solution is w tot = -1, the universe is a de Sitter expansion, and the cosmic big rip is naturally avoided. These features are all independent of the interacting forms.
PRICING AND HEDGING OF CDO-SQUARED TRANCHES BY USING A ONE FACTOR LÉVY MODEL
Authors: GUILLAUME FLORENCE , JACOBS PHILIPPE , SCHOUTENS WIM
Published: September 2009

This paper provides a comparison of the exponential copula Lévy model with the classical Gaussian copula model for the pricing of CDO-squared tranches. Several approximations of the recursive approach are considered: a full Monte Carlo approximation, a multivariate Normal approximation of the joint inner CDO loss distribution and a multivariate Poisson approximation of the joint number of defaults affecting the inner CDOs. More particularly, a sensitivity analysis is carried out for three particular days characterized by a low, medium and high value of the quoted iTraxx and CDX index spreads. Moreover, this paper features a comparison of the exponential Lévy and Gaussian Deltas under the multivariate Normal approximation for a period extended from 20 September 2007 until 13 February 2008. The Deltas are computed with respect to a weighted and unweighted version of the CDS pool as well as with respect to another CDO-squared tranche.
A NOVEL COHERENCE MEASURE FOR DISCOVERING SCALING BICLUSTERS FROM GENE EXPRESSION DATA
Authors: MUKHOPADHYAY ANIRBAN , MAULIK UJJWAL , BANDYOPADHYAY SANGHAMITRA
Published: September 2009

Biclustering methods are used to identify a subset of genes that are co-regulated in a subset of experimental conditions in microarray gene expression data. Many biclustering algorithms rely on optimizing mean squared residue to discover biclusters from a gene expression dataset. Recently it has been proved that mean squared residue is only good in capturing constant and shifting biclusters. However, scaling biclusters cannot be detected using this metric. In this article, a new coherence measure called scaling mean squared residue (SMSR) is proposed. Theoretically it has been proved that the proposed new measure is able to detect the scaling patterns effectively and it is invariant to local or global scaling of the input dataset. The effectiveness of the proposed coherence measure in detecting scaling patterns has been demonstrated experimentally on artificial and real-life benchmark gene expression datasets. Moreover, biological significance tests have been conducted to show that the biclusters identified using the proposed measure are composed of functionally enriched sets of genes.
PROBABILITY DENSITY EVOLUTION EQUATIONS — A HISTORICAL INVESTIGATION
Authors: JIE LI , JIANBING CHEN
Published: September 2009

The paper aims at clarifying the essential relationship between traditional probability density evolution equations and the generalized probability density evolution equation which is developed by the authors in recent years. Using the principle of preservation of probability as a uniform fundamental, the probability density evolution equations, including the Liouville equation, Fokker–Planck equation and the Dostupov–Pugachev equation, are derived from the physical point of view. It is pointed out that combining with Eulerian or Lagrangian description of the associated dynamical system will lead to different probability density evolution equations. Particularly, when both the principle and dynamical systems are viewed from Lagrangian description, we are led to the generalized probability density evolution equation.
Pebble population dating as an additional tool for provenance studies - examples from the Eastern Alps
Authors: Dunkl I. , Frisch W. , Kuhlemann J. , Brügel A.
Published: September 2009

Detrital fission-track (FT) dating can be successfully used in provenance studies of siliciclastic sediments to define the characteristic cooling ages of the source regions during erosion and sedimentation. In order to obtain more specific information about potential source regions we have developed the pebble population dating (PPD) method in which pebbles of specific lithotype are merged and dated. Dating of both zircon and apatite crystals from such pebble populations yields age distributions, which reflect the cooling ages of the given lithotype in the source area at the time of sedimentation. By this technique it is possible to define ‘FT litho-terrains’ in the source regions and thus outline palaeogeological maps.

Two examples are presented from the Eastern Alps. (i) Comparison of FT ages from a sandstone sample and a gneiss PPD sample from an Oligocene conglomerate of the Molasse Basin shows that the youngest age cluster is present only in the sand fraction and derived from the Oligocene volcanic activity along the Periadriatic zone. The lack of the youngest ages in the gneiss pebble assemblage excludes the Oligocene exhumation of the crystalline basement from mid-crustal level. (ii) Pebble assemblages of red Bunter sandstone, gneiss and quartzite were collected from an Upper Miocene conglomerate of the Molasse Foreland Basin and merged as PPD samples. Apatite and zircon FT grain age distributions of these PPD samples, representing the largest ancient East Alpine catchment, allow generating a new combination of palaeogeological and palaeo-FT-age maps of the Eastern Alps for the Late Miocene.
Late- and post-Variscan evolution of the Ardennes in France and Belgium: constraints from apatite fission-track data
Authors: Xu Changhai , Mansy Jean Louis , Van Den Haute Peter , Guillot Francois , Zhou Zuyi , Chen Jun , De Grave Johan
Published: September 2009

Apatite fission-track (AFT) analyses were performed on 13 Late Palaeozoic samples in order to unravel the late- to post-Variscan evolution of the Ardennes. The dated AFT ages cover a range from 290±33 Ma to 168±12 Ma, and the mean confined track lengths correspond to a unimodal distribution, with means varying between 13.1±0.1 µm and 11.7±0.3 µm. These ages for the sedimentary rocks are clearly younger than the respective stratigraphic ages, indicative of a cooling through the apatite partial annealing zone after post-depositional complete annealing. All available AFT data (290–146 Ma) from this region might be classified as three groups, that is 290–229 Ma, 218–198 Ma and 190–146 Ma, at least in correlation with three exhumation events. Using an inverse model, four major cooling episodes are identified from the modelled temperature–time (
T
–
t
) paths. The first rapid cooling (4.2–5.4 °C Ma
−1
, 320–300 Ma) corresponds to the late-Variscan rapid thrusting that ceased at about 300 Ma. The second cooling episode (0.2–4.0 °C Ma
−1
, up to 230 Ma) activated differentially, and was probably controlled by the post-Variscan transtension. The third cooling regime (0.1–0.3 °C Ma
−1
, 230–45 Ma) in the Ardennes Allochthon is slow, and represents a long-term and slow exhumation. In the Brabant Parautochthon, however, it is subdivided into 0.7 °C Ma
−1
(225–110 Ma) and 0.2 °C Ma
−1
(110–45 Ma). The last accelerated cooling (0.7–1.1 °C Ma
−1
, since 45 Ma) that affected the whole Ardennes is associated with a south–north compression during the Pyrenean phase.
A reappraisal of low-temperature thermochronology of the eastern Fennoscandia Shield and radiation-enhanced apatite fission-track annealing
Authors: Kohn Barry P. , Lorencak Matevz , Gleadow Andrew J. W. , Kohlmann Fabian , Raza Asaf , Osadetz Kirk G. , Sorjonen-Ward Peter
Published: September 2009

We assess the proposal of Hendriks & Redfield (
Earth and Planetary Science Letters
,
236
, 443–458, 2005) that cross-over of the predicted apatite fission track (AFT)>(U–Th–Sm)/He (AHe) age relationship in the southeastern Fennoscandian shield in southern Finland reflects α-radiation-enhanced annealing (REA) of fission tracks at low temperatures and that more robust estimates of the denudation history are recorded through reproducible AHe data. New AHe results from southern Finland showing variable dispersion of single-grain ages may be biased by different factors operating within grains, which tend to give a greater weighting towards older age outliers. AHe ages from mafic rocks show the least dispersion and tend to be consistently lower than their coexisting AFT ages. In general, it is at the younger end of the single-grain variation range from such lithologies where most meaningful AHe ages can be found. AHe data from multigrain aliquots are, therefore, of limited value for evaluating thermal histories in southern Finland, especially when compared against coexisting AFT data as supporting evidence for REA.

New, large datasets from the southern Canadian and Western Australian shields show the relationship between AFT age, single-grain age or mean track length as a function of U content (determined by the external detector method). These do not display the moderately strong inverse correlations previously reported from southern Finland in support of REA. Rather, the trends are inconsistent and generally exhibit weak positive or negative correlations. This is also the case for plots from both shields, as well as those from southern Finland, where AFT parameters are plotted against effective U concentration [eU] [based on U and Th content determined by inductively coupled plasma-mass spectroscopy (ICP-MS)], which weights decay of the parents more accurately in terms of their α‐productivity. Further, samples from southern Finland yield values of chi-square χ
2
>5%, indicating that there is no significant effect of the range of uranium content between grains within samples on the AFT ages, and that they are all consistent with a single population.

The oldest AFT ages in southern Finland apatites (amongst the oldest recorded from anywhere) are found in gabbros, which also have the highest Cl content of all samples studied. We suggest, that it is Cl content rather than REA that has influenced the annealing history of the apatites, which have experienced a history including reburial into the partial annealing zone by Caledonian Foreland basin sedimentation. The study of apatite from low U and Th rocks, with relatively low levels of α-radiation damage may provide the most practical approach for producing reliable results for AFT and AHe thermochronometry studies in cratonic environments.
Denudation along the Atlantic passive margin: new insights from apatite fission-track analysis on the western coast of South Africa
Authors: Kounov A. , Viola G. , de Wit M. , Andreoli M. A. G.
Published: September 2009

Apatite fission-track (AFT) data from two traverses across the Great Escarpment of the western coast of South Africa are used to reconstruct the tectonic evolution and denudation history of this sector of the Atlantic passive margin. Fission-track ages range between 180 and 86 Ma. Modelling of this data identifies two distinct cooling events. The first event, between 160 and 138 Ma, is recorded only by the rocks above the escarpment in the Karoo area, and is tentatively linked to post-Karoo magmatism (
c.
180 Ma) thermal relaxation. The second, between 115 and 90 Ma, results instead from a tectonically induced denudation episode responsible for the removal of up to 2.5 km of crust across the coastal zone in front of the escarpment and less than 1 km on the elevated interior plateau. Based on these results, it is suggested that the Cretaceous is the time when most of the elevated topography of Southern Africa was generated, with only a minor Cenozoic contribution.
Coincidence mapping - a key strategy for the automatic counting of fission tracks in natural minerals
Authors: Gleadow Andrew J. W. , Gleadow Stewart J. , Belton David X. , Kohn Barry P. , Krochmal Michael S. , Brown Roderick W.
Published: September 2009

We report on new image-analysis techniques that, for the first time, provide a practical solution to the problem of fully automated counting of fission tracks in natural minerals, a long-desired goal in fission-track dating. Specific challenges to be overcome have been the discrimination of fission tracks from non-track defects, polishing scratches, etc.; resolving multiple track overlaps; and reliable identification of small tracks amongst a similarly sized background of surface defects, fluid inclusions, etc. Most previous attempts at automated image analysis have failed in one or more of these tasks. The central component of our system is called ‘coincidence mapping’ and utilizes two images of the same tracks obtained in transmitted and reflected light. The complementary nature of the information in these two images allows a powerful discrimination of true fission tracks from most non-track features. The much smaller average track size in the reflected light image allows the resolution of most track overlaps apparent in transmitted light. The discrimination is achieved by segmenting the two images using a custom-developed thresholding routine and extracting the coincidence of features in the two binary images. The analysis is computationally efficient and takes only a few seconds to complete the processing of images that may contain up to many hundreds of tracks. Preliminary indications are that error rates are about the same as, or better than, those achieved by a human operator using normal counting conditions in transmitted light. The performance is even better at high track densities (>10
7
cm
−2
) giving the potential for measuring track densities up to an order of magnitude greater than a human operator can count. Automated counting should significantly increase the speed and consistency of analysis and improve data quality in fission-track dating through better counting statistics, increased objectivity and measurement of additional track description parameters that are not currently determined.
Fission-track analysis of the Atotsugawa Fault (Hida Metamorphic Belt, central Japan): fault-related thermal anomaly and activation history
Authors: Yamada Ryuji , Ongirad Hasbaator , Matsuda Tatsuo , Omura Kentaro , Takeuchi Akira , Iwano Hideki
Published: September 2009

Fission-track (FT) thermochronology was applied to the Atotsugawa Fault in the Hida Metamorphic Belt, central Japan, to detect any ancient thermal anomaly associated with fault displacements. Apatite and zircon grains from gouges (
c
. 2 cm wide) and fractured rocks (
c
. 10 cm) at six fracture zones within a 15 m-wide fault zone were dated. Most of the zircon (120–150 Ma) and apatite (44–60 Ma) ages agree well with emplacement ages for the granites that intrude the Hida Belt. The discordance in zircon and apatite FT ages is interpreted to reflect cooling due to regional uplift and associated erosion. A thermal anomaly was identified at one of the gouge zones that showed an exceptionally young apatite age (
c
. 32 Ma) with an unimodal FT length distribution. It presumably indicates secondary heating induced by frictional slip during an earthquake, possibly giving a younger limit of the initiation of the activity in the Hida Belt.
Spontaneous oscillations in intracellular Ca2+ concentration via purinergic receptors elicit transient cell swelling in rat parotid ducts
Authors: Shitara Akiko , Tanimura Akihiko , Sato Atsuko , Tojyo Yosuke
Published: September 2009

Using multiphoton microscopy, we established that rat parotid ductal cells exhibit spontaneous oscillations in intracellular Ca2+ concentration ([Ca2+]i). These oscillatory Ca2+ responses were observed during continuous perfusion with a physiological salt solution at 37°C in the absence of calcium mobilizing agonist stimulation. The timing and patterns of these spontaneous Ca2+ oscillations varied among individual ductal cells, and the average number of Ca2+ responses in a single responding ductal cell was 2.1 in a 10-min recording period. High-speed scanning (0.6 s/image) revealed that most spontaneous elevations in [Ca2+]i were initiated at the luminal side of ductal cells and spread toward the basal side within 2 s. Electron microscopic analysis after Ca2+ imaging indicated that spontaneously oscillating ducts contained numerous granules at the luminal side, which is characteristic of granular ducts. These Ca2+ oscillations were completely blocked by the purinergic receptor inhibitors 4-[[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid (PPADS) and suramin but were not blocked by the muscarinic antagonist atropine or the α-adrenergic antagonist phentolamine. Simultaneous observation of fura-2 fluorescence and differential interference contrast (DIC) images showed that spontaneous elevations of [Ca2+]i were well correlated with changes in shape of ductal cells. Using a plasma membrane fluorescence probe, SynaptoGreen C4, we found that the changes in DIC images reflected spontaneous cell swelling of ductal cells. Our findings present the possibility that purinergic receptors mediate spontaneous Ca2+ oscillations in parotid ductal cells and regulate electrolyte reabsorption from the primary saliva in the resting state.
Human duodenum responses to vitamin D metabolites of TRPV6 and other genes involved in calcium absorption
Authors: Balesaria Sara , Sangha Sonia , Walters Julian R. F.
Published: September 2009

Calcium absorption by the intestine is necessary for bone mineralization. Much has been learned about this process and the role of vitamin D metabolites in gene transcription from animal studies, but the molecular mechanisms in humans are less well understood. We have used samples of normal human duodenal mucosa, obtained at endoscopy, to investigate the effects of the vitamin D metabolites, 1α-dihydroxycholecalciferol [1,25(OH)2D3] and 25-hydroxycholecalciferol (25OHD), on transcripts on genes involved in calcium absorption and vitamin D metabolism. TRPV6 transcripts were significantly higher after incubation for 6 h with 1,25(OH)2D3 (10−9 mol/l) than after control incubations (median difference 3.1-fold, P < 0.001). Unexpectedly, TRPV6 expression was also higher (2.4-fold, P < 0.02) after incubation with 25OHD (10−7 mol/l). Transcripts for the calcium-ATPase, PMCA1, were significantly higher with 1,25(OH)2D3; CYP24 transcripts were reliably detected after incubation with either metabolite, but calbindin-D9k transcripts were unaffected. The response of TRPV6 to 25OHD and the expression of transcripts for CYP27B1, the 25OHD-1α-hydroxylase, were significantly correlated ( r = 0.82, P < 0.02). Basal duodenal expression of TRPV6 and CYP27B1 were significantly associated ( r = 0.72, P < 0.001) in a separate previously reported series of subjects. Multiple regression analysis of the associations with basal duodenal TRPV6 expression identified CYP27B1 expression and serum 1,25(OH)2D as major factors. Expression of the CYP27B1 protein was demonstrated immunohistochemically in duodenal mucosa. This study has shown that human duodenal TRPV6, PMCA1, and CYP24 transcripts respond rapidly to 1,25(OH)2D3 and provides evidence suggesting that local duodenal production of 1,25(OH)2D3 by 25OHD-1α-hydroxylase may have a role in human calcium absorption.
Cystitis increases colorectal afferent sensitivity in the mouse
Authors: Brumovsky Pablo Rodolfo , Feng Bin , Xu Linjing , McCarthy Carly Jane , Gebhart G. F.
Published: September 2009

Studies in humans and rodents suggest that colon inflammation promotes urinary bladder hypersensitivity and, conversely, that cystitis contributes to colon hypersensitivity, events referred to as cross-organ sensitization. To investigate a potential peripheral mechanism, we examined whether cystitis alters the sensitivity of pelvic nerve colorectal afferents. Male C57BL/6 mice were treated with cyclophosphamide (CYP) or saline, and the mechanosensitive properties of single afferent fibers innervating the colorectum were studied with an in vitro preparation. In addition, mechanosensitive receptive endings were exposed to an inflammatory soup (IS) to study sensitization. Urinary bladder mechanosensitive afferents were also tested. We found that baseline responses of stretch-sensitive colorectal afferents did not differ between treatment groups. Whereas IS excited a proportion of colorectal afferents CYP treatment did not alter the magnitude of this response. However, the number of stretch-sensitive fibers excited by IS was increased relative to saline-treated mice. Responses to IS were not altered by CYP treatment, but the proportion of IS-responsive fibers was increased relative to saline-treated mice. In bladder, IS application increased responses of muscular afferents to stretch, although no differences were detected between saline- and CYP-treated mice. In contrast, their chemosensitivity to IS was decreased in the CYP-treated group. Histological examination revealed no changes in colorectum and modest edema and infiltration in the urinary bladder of CYP-treated mice. In conclusion, CYP treatment increased mechanical sensitivity of colorectal muscular afferents and increased the proportion of chemosensitive colorectal afferents. These data support a peripheral contribution to cross-organ sensitization of pelvic organs.
Polysome trafficking of transcripts and microRNAs in regenerating liver after partial hepatectomy
Authors: Kren Betsy T. , Wong Phillip Y.-P. , Shiota Akira , Zhang Xiaoxiao , Zeng Yan , Steer Clifford J.
Published: September 2009

Liver regeneration after 70% partial hepatectomy (PH) in rats induces >95% of hepatocytes to undergo two rounds of semisynchronous cell replication. Gene expression is controlled primarily by posttranscriptional processing, including changes in mRNA stability. However, the translational activity of a specific mRNA can also be modulated after PH, resulting in significant uncoupling of protein and transcript levels relative to quiescent liver for many genes including c-myc and p53. Although the precise mechanism by which this uncoupling occurs is unknown, the polysomal association of mRNA and microRNA (miRNA) can significantly modulate rate of decay as well as translational activity. Thus we characterized the association of c-myc and p53 mRNAs and miRNAs in free and cytoskeleton- and membrane-bound polysome populations 3, 6, and 24 h after PH. The transcripts for c-myc and p53 were differentially distributed in the three discrete polysome populations, and this was dramatically modulated during liver regeneration. Nascent polysome-associated p53 and c-myc proteins were also differentially expressed in the free and cytoskeleton- and membrane-bound polysomes and significantly uncoupled from transcript levels relative to nonresected liver. At least 85 miRNAs were associated with the three polysome populations, and their abundance and distribution changed significantly during liver regeneration. These data suggest that posttranscriptional control of c-myc and p53 protein expression is associated with the translocation of transcripts between the different polyribosomes. The alteration of expression for the same transcript in different polysome populations may, in part, be due to the action of miRNAs.
Altered reactivity to norepinephrine through COX-2 induction by vascular injury in hypercholesterolemic rabbits
Authors: Foudi Nabil , Norel Xavier , Rienzo Mario , Louedec Liliane , Brink Charles , Michel Jean-Baptiste , Bäck Magnus
Published: September 2009

Although long-term use of cyclooxygenase (COX)-2 inhibitors may be associated with increased cardiovascular risk, their effects on vascular reactivity in atherosclerosis has remained largely unexplored. The aim of the present study was to evaluate the role of COX-2 induced by an atherosclerotic process, in the local control of vascular tone. New Zealand White rabbits were fed 0.3% cholesterol and subjected to balloon injury of the abdominal aorta. After 2 wk, the aorta was removed and used for organ bath experiments and immunohistochemistry, and the prostaglandins released were measured using enzyme immunoassays. Hypercholesterolemia and vascular injury significantly increased the thickness of the intimal layer, which was associated with an induction of COX-2 immunoreactivity throughout the aortic wall. In these preparations, a significant decrease of the maximal contractions induced by norepinephrine was observed. The norepinephrine-induced contractions of atherosclerotic preparations were restored by the COX inhibitors DuP-697 (0.5 μmol/l) and indomethacin (1.7 μmol/l), to similar contractions as was observed in aortic preparations derived from healthy rabbits. Norepinephrine stimulation of the abdominal aorta was accompanied by increased levels of prostaglandin I2 but not of prostaglandin E2, prostaglandin D2, or thromboxane A2 in atherosclerotic compared with normal aorta. Selective COX-2 inhibition significantly decreased the prostaglandin I2 release from atherosclerotic aorta but had no effect on the prostaglandin release from aortic preparations derived from normal rabbits. These observations suggest that the local induction of COX-2 during atherosclerosis decreased the sensitivity to norepinephrine and that COX-2 inhibitors may increase vascular reactivity at sites of atherosclerotic lesions.
Doxorubicin acts through tumor necrosis factor receptor subtype 1 to cause dysfunction of murine skeletal muscle
Authors: Gilliam Laura A. A. , Ferreira Leonardo F. , Bruton Joseph D. , Moylan Jennifer S. , Westerblad Håkan , St. Clair Daret K. , Reid Michael B.
Published: September 2009

Cancer patients receiving doxorubicin chemotherapy experience both muscle weakness and fatigue. One postulated mediator of the muscle dysfunction is an increase in tumor necrosis factor-α (TNF), a proinflammatory cytokine that mediates limb muscle contractile dysfunction through the TNF receptor subtype 1 (TNFR1). Our main hypothesis was that systemic doxorubicin administration would cause muscle weakness and fatigue. Systemic doxorubicin administration (20 mg/kg) depressed maximal force of the extensor digitorum longus (EDL; P < 0.01), accelerated EDL fatigue ( P < 0.01), and elevated serum TNF levels ( P < 0.05) 72 h postinjection. Genetic TNFR1 deficiency prevented the fall in specific force caused by systemic doxorubicin, without protecting against fatigue ( P < 0.01). These results demonstrate that clinical doxorubicin concentrations disrupt limb muscle function in a TNFR1-dependent manner.
Should We Customize Fetal Growth Standards?
Authors: Figueras F. , Gardosi J.
Published: September 2009

Several maternal and fetal physiological characteristics account for a substantial proportion of the variation in birth weight. These characteristics can be used to calculate an individualized optimal birth weight and to adjust or ‘customize’ the birth weight standard. Customized birth weight standards improve the distinction between constitutional and pathological smallness, and there is evidence that this finding can be extrapolated into the fetal period to evaluate intrauterine growth, but further studies are required to evaluate and quantify the effectiveness of customized versus conventional charts in improving the diagnosis of pathological smallness before birth.
Maternal Serum Activin A at 11–13 Weeks of Gestation in Hypertensive Disorders of Pregnancy
Authors: Akolekar Ranjit , Etchegaray Adolfo , Zhou Yi , Maiz Nerea , Nicolaides Kypros H.
Published: September 2009

Objectives: To investigate whether the maternal serum concentration of activin A at 11–13 weeks of gestation in pregnancies that subsequently develop hypertensive disorders is different from those with a normal outcome and to examine whether any possible differences are related to uterine artery pulsatility index (PI), serum pregnancy-associated plasma protein A (PAPP-A) and serum tumor necrosis factor-α receptor-1 (TNF-R1). Material and Methods: Serum activin A, TNF-R1, PAPP-A and uterine artery PI were determined in a case-control study of 126 cases that developed preeclampsia, 88 that developed gestational hypertension and 214 controls. Results: In preeclampsia, compared to controls, uterine artery PI, serum activin A and serum TNF-R1 were higher and serum PAPP-A was lower. In gestational hypertension, compared to controls, serum activin A was higher but uterine artery PI, serum PAPP-A and serum TNF-R1 were not significantly different. There were no significant associations between serum activin A and either uterine artery PI or serum TNF-R1 in either the hypertensive groups or the controls. Discussion: The data do not support the hypothesis linking activin A with impaired trophoblastic invasion of the maternal spiral arteries, placental hypoxia and the release of cytokines which in turn cause endothelial dysfunction and the development of the clinical symptoms of the disease.