bluuebunny/crossref_metadata_2025 huggingface dataset:
Response Latencies in Naming Objects
Authors: Oldfield R. C. , Wingfield A.
Published: March 2008

After some preliminary analysis of what is involved in naming objects, in which the possible role of classificatory systems in the memory store is discussed, it is shown experimentally that there are consistent differences between the times taken to respond to presented objects by uttering their names, variations between the performances of different individuals being outweighed by variations due to the different objects. Moreover, there is a high consistency between different individuals as to the ordering of objects in respect of their naming latencies. It is further shown that a high correlation exists between the time taken to name an object and the frequency with which its name occurs in the language as a whole, as estimated in the Thorndike-Lorge Word List. Some implications of these findings are discussed, especially with reference to possible mechanisms by which presented objects are visually identified, and the appropriate names retrieved from the “word-store.”
Three Estimates of the Word Span and their Stability over the Adult Years
Authors: Tallnd George A.
Published: March 2008

Three estimates of the immediate word span were compared in groups of men representing each decade between the ages of 20 and 69 years. No systematic change with age was found in free recall or in partial recall requiring the reproduction of the unrepeated word in lists of four to seven items. When the instruction was to report the entire list but leave the unrepeated word last, performance steadily deteriorated with age. Mean success in recall decreased on three criteria, and error by false terminal placement increased from each decade to the next. The results support the hypothesis that capacity to perform simultaneously two such operations as sub-vocal rehearsal of one item and vocal enumeration of the other items shrinks with the advancing years. This interpretation of the findings agrees with other observations about age-related changes in perceptual-motor skills and cognitive capacity, and indicates the manner in which an increased propensity to forgetfulness with the advancing years originates in immediate memory. It is also noted that in the general population the immediate word span is well below that determined in college students, even under the least exacting conditions of free recall, and that the additional requirement to search for, select and test a required item does not further restrict the word span below the age of 50.
The Common Value of Pausing Time in Spontaneous Speech
Authors: Henderson Alan , Goldman-Eisler Frieda , Skarbek Andrew
Published: March 2008

Experiments have shown that hesitation increases both before and during speech concerned with the solution of verbal tasks which involve an increasing degree of syntactic or semantic complexity. These experiments have been concerned with differences between tasks. An attempt is made to compare hesitation time between individuals who are set the same tasks, in terms of the quality of their responses to the tasks. Individual dispositions to a characteristic speech-silence ratio complicate such comparisons. Here a strong trend was found between the quality of the subjects' responses and the extra time they took over and above their characteristic speech-silence ratios.
Systematic kinetic analysis of mitotic dis- and reassembly of the nuclear pore in living cells
Authors: Dultz Elisa , Zanin Esther , Wurzenberger Claudia , Braun Marion , Rabut Gwénaël , Sironi Lucia , Ellenberg Jan
Published: March 2008

During mitosis in higher eukaryotes, nuclear pore complexes (NPCs) disassemble in prophase and are rebuilt in anaphase and telophase. NPC formation is hypothesized to occur by the interaction of mitotically stable subcomplexes that form defined structural intermediates. To determine the sequence of events that lead to breakdown and reformation of functional NPCs during mitosis, we present here our quantitative assay based on confocal time-lapse microscopy of single dividing cells. We use this assay to systematically investigate the kinetics of dis- and reassembly for eight nucleoporin subcomplexes relative to nuclear transport in NRK cells, linking the assembly state of the NPC with its function. Our data establish that NPC assembly is an ordered stepwise process that leads to import function already in a partially assembled state. We furthermore find that nucleoporin dissociation does not occur in the reverse order from binding during assembly, which may indicate a distinct mechanism.
The structural basis of actin filament branching by the Arp2/3 complex
Authors: Rouiller Isabelle , Xu Xiao-Ping , Amann Kurt J. , Egile Coumaran , Nickell Stephan , Nicastro Daniela , Li Rong , Pollard Thomas D. , Volkmann Niels , Hanein Dorit
Published: March 2008

The actin-related protein 2/3 (Arp2/3) complex mediates the formation of branched actin filaments at the leading edge of motile cells and in the comet tails moving certain intracellular pathogens. Crystal structures of the Arp2/3 complex are available, but the architecture of the junction formed by the Arp2/3 complex at the base of the branch was not known. In this study, we use electron tomography to reconstruct the branch junction with sufficient resolution to show how the Arp2/3 complex interacts with the mother filament. Our analysis reveals conformational changes in both the mother filament and Arp2/3 complex upon branch formation. The Arp2 and Arp3 subunits reorganize into a dimer, providing a short-pitch template for elongation of the daughter filament. Two subunits of the mother filament undergo conformational changes that increase stability of the branch. These data provide a rationale for why branch formation requires cooperative interactions among the Arp2/3 complex, nucleation-promoting factors, an actin monomer, and the mother filament.
PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25
Authors: Rivers David M. , Moreno Sergio , Abraham Mary , Ahringer Julie
Published: March 2008

Cell cycle lengths vary widely among different cells within an animal, yet mechanisms of cell cycle length regulation are poorly understood. In the Caenorhabditis elegans embryo, the first cell division produces two cells with different cell cycle lengths, which are dependent on the conserved partitioning-defective (PAR) polarity proteins. We show that two key cell cycle regulators, the Polo-like kinase PLK-1 and the cyclin-dependent kinase phosphatase CDC-25.1, are asymmetrically distributed in early embryos. PLK-1 shows anterior cytoplasmic enrichment and CDC-25.1 shows PLK-1–dependent enrichment in the anterior nucleus. Both proteins are required for normal mitotic progression. Furthermore, these asymmetries are controlled by PAR proteins and the muscle excess (MEX) proteins MEX-5/MEX-6, and the latter is linked to protein degradation. Our results support a model whereby the PAR and MEX-5/MEX-6 proteins asymmetrically control PLK-1 levels, which asymmetrically regulates CDC-25.1 to promote differences in cell cycle lengths. We suggest that control of Plk1 and Cdc25 may be relevant to regulation of cell cycle length in other developmental contexts.
Genetic Basis of Resistance to Systemic Infection by Xanthomonas axonopodis pv. dieffenbachiae in Anthurium
Authors: Elibox W. , Umaharan P.
Published: March 2008

The genetic basis of systemic resistance to bacterial blight disease (blight) of anthurium (Anthurium andraeanum) caused by Xanthomonas axonopodis pv. dieffenbachiae was investigated in progenies of 53 crosses involving 31 parent cultivars using segregation analysis. Inoculation of parents and progenies was achieved by injecting the petiole base of the most recent fully expanded leaf with 100 μl of 109 colony forming units per ml of the blight pathogen (strain X4gfp) transformed with the green fluorescent protein (GFP) gene. The time to death and the presence or absence of GFP fluorescence on newly emerging leaves was monitored over a period of 30 weeks after inoculation (WAI), on an individual plant basis. The expected resistance to susceptible ratios based on a digenic model involving two dominant genes, designated A and B, interacting according to a duplicate recessive epistasis model fitted the observed segregation ratios in the crosses. Based on the segregation ratios obtained, the parental cultivars were assigned plausible genotypes. There were significant differences (P < 0.001) in time to death following inoculation between the various genotypic designations. Cultivars with genotypes AABB, AABb, AaBB, and AaBb died within 10 WAI and designated as susceptible; AAbb and aaBB died from 18.8 to 25.6 WAI and were designated as moderately resistant; and Aabb, aaBb, and aabb produced resistant phenotypes. There was also some evidence for dosage effect especially in the highly resistant category. Hence, (AABb = AaBB = AaBb) < (aaBB = AAbb) < Aabb = aaBb = aabb). An approach to fixing resistance to blight in anthurium is discussed.
Influence of epidermal hydration on the friction of human skin against textiles
Authors: Gerhardt L.-C , Strässle V , Lenz A , Spencer N.D , Derler S
Published: March 2008

Friction and shear forces, as well as moisture between the human skin and textiles are critical factors in the formation of skin injuries such as blisters, abrasions and decubitus. This study investigated how epidermal hydration affects the friction between skin and textiles.

The friction between the inner forearm and a hospital fabric was measured in the natural skin condition and in different hydration states using a force plate. Eleven males and eleven females rubbed their forearm against the textile on the force plate using defined normal loads and friction movements. Skin hydration and viscoelasticity were assessed by corneometry and the suction chamber method, respectively.

In each individual, a highly positive linear correlation was found between skin moisture and friction coefficient (COF). No correlation was observed between moisture and elasticity, as well as between elasticity and friction. Skin viscoelasticity was comparable for women and men. The friction of female skin showed significantly higher moisture sensitivity. COFs increased typically by 43% (women) and 26% (men) when skin hydration varied between very dry and normally moist skin. The COFs between skin and completely wet fabric were more than twofold higher than the values for natural skin rubbed on a dry textile surface.

Increasing skin hydration seems to cause gender-specific changes in the mechanical properties and/or surface topography of human skin, leading to skin softening and increased real contact area and adhesion.
Comparing the strength of behavioural plasticity and consistency across situations: animal personalities in the hermit crab
Pagurus bernhardus
Authors: Briffa Mark , Rundle Simon D , Fryer Adam
Published: March 2008

Many phenotypic traits show plasticity but behaviour is often considered the ‘most plastic’ aspect of phenotype as it is likely to show the quickest response to temporal changes in conditions or ‘situation’. However, it has also been noted that constraints on sensory acuity, cognitive structure and physiological capacities place limits on behavioural plasticity. Such limits to plasticity may generate consistent differences in behaviour between individuals from the same population. It has recently been suggested that these consistent differences in individual behaviour may be adaptive and the term ‘animal personalities’ has been used to describe them. In many cases, however, a degree of both behavioural plasticity and relative consistency is probable. To understand the possible functions of animal personalities, it is necessary to determine the relative strength of each tendency and this may be achieved by comparison of statistical effect sizes for tests of difference and concordance. Here, we describe a new statistical framework for making such comparisons and investigate cross-situational plasticity and consistency in the duration of startle responses in the European hermit crab
Pagurus bernhardus
, in the field and the laboratory. The effect sizes of tests for behavioural consistency were greater than for tests of behavioural plasticity, indicating for the first time the presence of animal personalities in a crustacean model.
Strategic adjustment of begging effort by banded mongoose pups
Authors: Bell Matthew B.V
Published: March 2008

Variation in the intensity of conspicuous displays raises three basic questions: (i) the relationship between internal state and display intensity, (ii) the relationship between display intensity and receiver response, and (iii) the effect of variation in receiver responsiveness on signaller behaviour. Here, I investigate the interaction between pups and helpers in the communally breeding banded mongoose (
Mungos mungo
), where each pup forms an exclusive relationship with a single adult helper (termed its ‘escort’). By experimentally manipulating pup need, I demonstrate that changes in begging rate correspond to changes in short-term need. The data then suggest that escorts in good condition may be more responsive to increased begging and that pups associating with them increase their begging more than do pups paired with escorts in poor condition. Escorts also appear more responsive to increased begging by female pups, and female pups increase their begging more than do male pups. These results suggest that banded mongoose pups may strategically adjust their investment in begging in relation to variation in the expected pay-off. I argue that such adjustment is likely to be a general phenomenon: wherever there is variation in responsiveness to signals, signallers will be selected to identify different categories of receiver and adjust their signals in order to maximize the pay-offs. Therefore, differences in signal intensity may be as much a product of context as an indication of variation in individual phenotypic or genotypic state.
Attacker–defender models and road network vulnerability
Authors: Bell M.G.H , Kanturska U , Schmöcker J.-D , Fonzone A
Published: March 2008

The reliability of road networks depends directly on their vulnerability to disruptive incidents, ranging in severity from minor disruptions to terrorist attacks. This paper presents a game theoretic approach to the analysis of road network vulnerability. The approach posits predefined disruption, attack or failure scenarios and then considers how to use the road network so as to minimize the maximum expected loss in the event of one of these scenarios coming to fruition. A mixed route strategy is adopted, meaning that the use of the road network is determined by the worst scenario probabilities. This is equivalent to risk-averse route choice. A solution algorithm suitable for use with standard traffic assignment software is presented, thereby enabling the use of electronic road navigation networks. A variant of this algorithm suitable for risk-averse assignment is developed. A numerical example relating to the central London road network is presented. The results highlight points of vulnerability in the road network. Applications of this form of network vulnerability analysis together with improved solution methods are discussed.
Comprehensive high-throughput arrays for relative methylation (CHARM)
Authors: Irizarry Rafael A. , Ladd-Acosta Christine , Carvalho Benilton , Wu Hao , Brandenburg Sheri A. , Jeddeloh Jeffrey A. , Wen Bo , Feinberg Andrew P.
Published: March 2008

This study was originally conceived to test in a rigorous way the specificity of three major approaches to high-throughput array-based DNA methylation analysis: (1) MeDIP, or methylated DNA immunoprecipitation, an example of antibody-mediated methyl-specific fractionation; (2) HELP, or HpaII tiny fragment enrichment by ligation-mediated PCR, an example of differential amplification of methylated DNA; and (3) fractionation by McrBC, an enzyme that cuts most methylated DNA. These results were validated using 1466 Illumina methylation probes on the GoldenGate methylation assay and further resolved discrepancies among the methods through quantitative methylation pyrosequencing analysis. While all three methods provide useful information, there were significant limitations to each, specifically bias toward CpG islands in MeDIP, relatively incomplete coverage in HELP, and location imprecision in McrBC. However, we found that with an original array design strategy using tiling arrays and statistical procedures that average information from neighboring genomic locations, much improved specificity and sensitivity could be achieved, e.g., ∼100% sensitivity at 90% specificity with McrBC. We term this approach “comprehensive high-throughput arrays for relative methylation” (CHARM). While this approach was applied to McrBC analysis, the array design and computational algorithms are fractionation method-independent and make this a simple, general, relatively inexpensive tool suitable for genome-wide analysis, and in which individual samples can be assayed reliably at very high density, allowing locus-level genome-wide epigenetic discrimination of individuals, not just groups of samples. Furthermore, unlike the other approaches, CHARM is highly quantitative, a substantial advantage in application to the study of human disease.
What is PACT really?
Authors: Arias J. Salvador , Garzón‐Orduña Ivonne J. , López‐Osorio Federico , Parada‐Vargas Erika , Miranda‐Esquivel Daniel Rafael
Published: March 2008

“Phylogenetic Analysis for Comparing Trees” (PACT) has been presented as a “new algorithm” for the study of biogeography and coevolution. However, an exploration of this algorithm revealed some important problems missed in the original description. First, PACT is not new, rather it is an extension of Tree Mapping under Maximum Codivergence (TM‐MC). Second, as was described, PACT lacks an optimality criterion, and like secondary BPA, it does not offer a solution for handling incongruent elements. We found that PACT and TM‐MC differ only in the way the final answer is presented, and in the absence of an explicit algorithm of historical reconstruction under PACT. Given the equivalence between TM‐MC and PACT in their aims and assumptions, the criticism to TM‐MC as “orthogenetic” is not well founded.

© The Willi Hennig Society 2008.

© The Willi Hennig Society 2008.
A genetic linkage map for coho salmon (Oncorhynchus kisutch)
Authors: McClelland E. K. , Naish K. A.
Published: March 2008

Construction of genetic linkage maps is an important first step for a variety of genomic applications, such as selective breeding in aquaculture, comparative studies of chromosomal evolution and identification of loci that have played key roles in the evolution of a species. Here we present a sex‐specific linkage map for coho salmon. The map was constructed using 148 AFLP markers, 133 microsatellite loci and the phenotypic locus SEX. Twenty‐four linkage groups spanning 287.4 cM were mapped in males, and 33 linkage groups spanning 429.7 cM were mapped in females. Several male linkage groups corresponded to two female linkage groups. The combination of linkage groups across both sexes appeared to characterize regions of 26 chromosomes. Two homeologous chromosomes were identified based on information from duplicated loci. Homologies between the coho and rainbow trout maps were examined. Eighty‐six loci were found to form common linkage relationships between the two maps; these relationships provided evidence for whole‐arm fissions, fusions and conservation of chromosomal regions in the evolution of these two species.
Identification of polymorphisms influencing feed intake and efficiency in beef cattle
Authors: Sherman E. L. , Nkrumah J. D. , Murdoch B. M. , Moore S. S.
Published: March 2008

Feed efficiency is an economically important trait in beef cattle. Net feed efficiency, measured as residual feed intake (RFI), is the difference between actual feed intake and the predicted feed intake required for maintenance and gain of the animal. SNPs that show associations with RFI may be useful quantitative trait nucleotides for marker‐assisted selection. This study identified associations between SNPs underlying five RFI QTL on five bovine chromosomes (BTA2, 5, 10, 20 and 29) with measures of dry matter intake (DMI), RFI and feed conversion ratio (FCR) in beef cattle. Six SNPs were found to have effects on RFI (P < 0.05). The largest single SNP allele substitution effect for RFI was −0.25 kg/day located on BTA2. The combined effects of the SNPs found significant in this experiment explained 6.9% of the phenotypic variation of RFI. Not all the RFI SNPs showed associations with DMI and FCR even though these traits are highly correlated with RFI (r = 0.77 and r = 0.62 respectively). This shows that these SNPs may be affecting the underlying biological mechanisms of feed efficiency beyond feed intake control and weight gain efficiency. These SNPs can be used in marker‐assisted selection but first it will be important to verify these effects in independent populations of cattle.
Double‐negative regulatory T cells induce allotolerance when expanded after allogeneic haematopoietic stem cell transplantation
Authors: McIver Z. , Serio B. , Dunbar A. , O’Keefe C. L. , Powers J. , Wlodarski M. , Jin T. , Sobecks R. , Bolwell B. , Maciejewski J. P.
Published: March 2008

Double‐negative (DN) regulatory T cells (Tregs) are specialized T lymphocytes involved in the down‐modulation of immune responses, resulting in allotolerance after allogeneic haematopoietic stem cell transplantation (HSCT). Most of the properties of DN Tregs were identified in murine models, including the unique ability to suppress alloreactive syngeneic effector T cells in an antigen‐specific manner via Fas/Fas‐ligand interactions. We investigated the behaviour of DN Tregs following human allogeneic HSCT with regard to occurrence of graft‐versus‐host disease (GvHD) and restoration of T‐cell receptor repertoire in a cohort of 40 patients. The frequency of DN Tregs and CD4/CD8 TCR repertoire was measured serially and at the time of diagnosis of GvHD by flow cytometry. Analysis demonstrated a positive correlation between degree of alloreactivity, as measured by grade of GvHD, and the number of variable beta chain (Vβ) family expansions in both T‐cell populations. We also found that a deficiency of DN Tregs was associated with an increased number of Vβ family expansions, and most importantly, with the occurrence of GvHD. All individuals who demonstrated more than 1% DN Tregs did not develop GvHD, providing evidence that DN Tregs participate in peripheral tolerance to prevent GvHD when expanded after allogeneic HSCT.
Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia
Authors: Kumkhaek Chutima , Taylor James G. , Zhu Jianqiong , Hoppe Carolyn , Kato Gregory J. , Rodgers Griffin P.
Published: March 2008

The hydroxycarbamide (HC)‐inducible small guanosine triphosphate (GTP)‐binding protein, secretion‐associated and RAS‐related (SAR) protein has recently been shown to play a pivotal role in HBG induction and erythroid maturation by causing cell apoptosis and G1/S‐phase arrest. Our preliminary analysis indicated that HC inducibility is transcriptionally regulated by elements within the SAR1A promoter. This study aimed to assess whether polymorphisms in the SAR1A promoter are associated with differences Hb F levels or HC therapeutic responses among sickle cell disease (SCD) patients. We studied 386 individuals with SCD comprised of 269 adults treated with or without HC and 117 newborns with SCD identified from a newborn screening program. Three previously unknown single nucleotide polymorphisms (SNPs) in the upstream 5′UTR (−809 C>T, −502 G>T and −385 C>A) were significantly associated with the fetal haemoglobin (HbF) response in Hb SS patients treated with HC (P < 0·05). In addition, four SNPs (rs2310991, −809 C>T, −385 C>A and rs4282891) were significantly associated with the change in absolute HbF after 2 years of treatment with HC. These data suggest that variation within SAR1A regulatory elements might contribute to inter‐individual differences in regulation of HbF expression and patient responses to HC in SCD.
Rituximab in the treatment of autoimmune haematological disorders
Authors: Garvey Bernadette
Published: March 2008

Current treatment regimens for haematological autoimmune diseases are relatively non‐selective and are often associated with considerable toxicity. Recently, it has become clear that B cells play a key role in both the development and perpetuation of autoimmunity, suggesting that B‐cell depletion could be a valuable treatment approach for patients with autoimmune diseases. This article reviews data supporting the use of rituximab – an anti‐CD20 monoclonal antibody that specifically depletes B cells – in four key autoimmune haematological disorders: idiopathic thrombocytopenic purpura (ITP); autoimmune haemolytic anaemia (AIHA); acquired haemophilia; and thrombotic thrombocytopenic purpura (TTP). Although treatment of ITP, AIHA, acquired haemophilia and TTP with rituximab is still relatively uncommon, results from case series and small phase II trials indicate that patients of all ages can respond to rituximab, irrespective of the number or type of prior treatments that they have received. Moreover, patients with these diseases receiving rituximab experienced predominantly mild adverse events, with only a few serious adverse events reported. These data suggest that rituximab provides an effective and well‐tolerated alternative treatment option for patients with ITP, AIHA, acquired haemophilia and TTP, many of whom have limited treatment choices.
Outcome after autologous stem cell transplantation for multiple myeloma in patients with preceding plasma cell disorders
Authors: Kumar Shaji K. , Dingli David , Lacy Martha Q. , Dispenzieri Angela , Hayman Suzanne R. , Buadi Francis K. , Rajkumar S. Vincent , Litzow Mark R. , Gertz Morie A.
Published: March 2008

A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27·5 months vs. 17·2 months, P = 0·01), and longer overall survival (OS) from transplant (80·2 months vs. 48·3 months, P = 0·03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post‐transplant relapse independent of other known risk factors. Patients with pre‐existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma.
Effect of deferasirox (ICL670) on arterial function in patients with beta‐thalassaemia major
Authors: Cheung Y. F. , Chan Godfrey C. F. , Ha S. Y.
Published: March 2008

Deferasirox (ICL670) has been shown to have rapid accessibility to intracellular labile iron. We tested the hypothesis that oral deferasirox improves arterial dysfunction in patients with beta‐thalassaemia major. Nineteen thalassaemia patients, aged 23 ± 7 years, with normal left ventricular (LV) function were treated with deferasirox at 25–35 mg/kg/d for 12 months. LV function, brachial arterial flow‐mediated dilation (FMD), carotid arterial stiffness, and serum ferritin levels were determined at baseline prior to initiation, after 6 months and after 12 months of therapy. The baseline cardiovascular indices were compared with those of 17 age‐matched controls. Longitudinal changes in patients during the treatment period were also determined. Compared with controls, patients had similar echocardiographic indices of LV function (all P > 0·05), while their baseline brachial FMD was reduced (P < 0·001) and carotid stiffness increased (P = 0·019). An increase in FMD (P < 0·001) and a decrease in carotid stiffness (P = 0·007) were found at 6 and 12 months follow‐up. The stiffness index correlated inversely with FMD (r = −0·42, P = 0·001). Although there was an increase in ferritin level at 12 months (3303 ± 1185 ng/ml vs. 2714 ± 780 ng/ml at baseline, P = 0·006), no significant correlation existed between ferritin level and FMD or carotid stiffness. In conclusion, deferasirox therapy in thalassaemia patients is associated with improved arterial function.
Collagens, stromal cell‐derived factor‐1α and basic fibroblast growth factor increase cancer cell invasiveness in a hyaluronan hydrogel
Authors: David L. , Dulong V. , Coquerel B. , Le Cerf D. , Cazin L. , Lamacz M. , Vannier J.‐P.
Published: March 2008

Abstract.  Objective: Beyond to control of cell migration, differentiation and proliferation, the extracellular matrix (ECM) also contributes to invasiveness of human cancers. As the roles of hyaluronan (HA) and collagens in this process are still controversial, we have investigated their involvement in cancer pathogenesis. Materials and methods: With this aim in view, we developed a three‐dimensional matrix, as reticulate HA hydrogel alone or coated with different collagens, in which cells could invade and grow. Results: We show that cancer cells, which were non‐invasive in a single HA hydrogel, acquired this capacity in the concomitant presence of type I or III collagens. Both types of ECM compound, HA and collagens, possess the capacity to stimulate production of metalloprotease‐2, recognized otherwise as a factor for poor cancer prognosis. HA‐provoked cellular invasiveness resulted from CD44‐mediated increase in cytosolic [Ca2+] and its subsequent hydrolysis due to ADAM (a disintegrin and metalloprotease) proteolytic activity. Interestingly, this mechanism seemed to be absent in non‐invasive cancer cell lines. Conclusion: Furthermore, using basic fibroblast growth factor and stromal cell‐derived factor‐1α, we also show that this three‐dimensional reticulate matrix may be considered as a valuable model to study chemokinetic and chemotactic potentials of factors present in tumour stroma.
Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma
Authors: Seitz G. , Warmann S. W. , Fuchs J. , Heitmann H. , Mahrt J. , Busse A.‐C. , Ruck P. , Hoffman R. M. , Wessels J. T.
Published: March 2008

Abstract.  Objective: The aim of this study was to establish a preclinical mouse model to study metastases of paediatric rhabdomyosarcoma at the macroscopic and cellular levels, with different imaging methods. Experimental Design: The alveolar rhabdomyosarcoma cell line Rh30 was stably transfected with the red fluorescent protein (DsRed2) then was xenotransplanted (intravenous injection [n = 8], and footpad injection [n = 8]) into nude mice (NMRI nu/nu). Macroscopic imaging of metastases was performed using DsRed2‐fluorescence and flat‐panel volumetric computed tomography scan. In a further series of animals (n = 8), in vivo cell trafficking of rhabdomyosarcoma cells using cellular imaging with an Olympus OV100 variable‐magnification small‐animal imaging system was used. Results: Metastases in the pelvis, thoracic wall and skin were visualized by fluorescence imaging. Pelvic metastases were found after tail vein injection and at other metastatic sites after footpad injection. Flat‐panel volumetric computed tomography scan data allowed highly specific analysis of contrast between tumour and surrounding tissue. Correlation between fluorescence and flat‐panel volumetric computed tomography scan imaging data was observed. Single‐cell imaging visualized tumour cells in the vessels and demonstrated the arrest of tumour cells at vessel junctions followed by extravasation of the tumour cells. Conclusion: We established a model for visualization of experimental metastatic invasion and describe relevant tools for imaging childhood rhabdomyosarcoma metastases at the macroscopic and cellular levels. Imaging of cell trafficking visualized the behaviour of tumour cells and development of metastases by accumulation and extravasation of rhabdomyosarcoma cells.
Analysis of the PTPN11 gene in idiopathic short stature children and Noonan syndrome patients
Authors: Ferreira Lize V. , Souza Silvia C. A. L. , Montenegro Luciana R. , Malaquias Alexsandra C. , Arnhold Ivo J. P. , Mendonca Berenice B. , Jorge Alexander A. L.
Published: March 2008

Background  Mutations in the PTPN11 gene are the main cause of Noonan syndrome (NS). The presence of some NS features is a frequent finding in children with idiopathic short stature (ISS). These children can represent the milder end of the NS clinical spectrum and PTPN11 is a good candidate for involvement in the pathogenesis of ISS.

Objective  To evaluate the presence of mutations in PTPN11 in ISS children who presented NS‐related signs and in well‐characterized NS patients.

Patients and methods  We studied 50 ISS children who presented at least two NS‐associated signs but did not fulfil the criteria for NS diagnosis. Forty‐nine NS patients diagnosed by the criteria of van der Burgt et al.3 were used to assess the adequacy of these criteria to select patients for PTPN11 mutation screening. The coding region of PTPN11 was amplified by polymerase chain reaction (PCR), followed by direct sequencing.

Results  No mutations or polymorphisms were found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49 NS patients (39%) presented mutations in PTPN11. No single characteristic enabled us to distinguish between NS patients with or without PTPN11 mutations.

Conclusion  Considering that no mutations were found in the present cohort with NS‐related signs, it is unlikely that mutations would be found in unselected ISS children. The van der Burgt et al. criteria are adequate in attaining NS diagnosis and selecting patients for molecular studies. Mutations in the PTPN11 gene are commonly involved in the pathogenesis of NS but are not a common cause of ISS.
Percutaneous ethanol injection therapy: a surgery‐sparing treatment for primary hyperparathyroidism
Authors: Stratigis Spyros , Stylianou Kostas , Mamalaki Evangelia , Perakis Kostas , Vardaki Eleftheria , Tzenakis Nikolaos , Katsipi Irene , Papavasiliou Stathis , Yarmenitis Spyros , Kyriazis John , Daphnis Eugene
Published: March 2008

Objective  To describe our 3‐year experience in the long‐term efficacy and safety of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery for the management of patients with primary hyperparathyroidism (p‐HPT).

Design  Prospective study with a mean follow‐up of 19·6 ± 10·6 months.

Patients  Our study population included 19 consecutive high risk patients with p‐HPT, who met the criteria for surgery.

Measurements  Under ultrasonic guidance, ethanol (95%) was injected into parathyroid glands with a volume of ≥ 0·15 cm3. With the aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections were carried out, in an interval of 2 weeks, until normalization of iPTH was reached or until no residual blood supply was detected by ultrasound in the gland. Biochemical parameters were monitored throughout the study.

Results  At 6‐month follow‐up, normalization of iPTH levels (10–65 ng/l) was achieved in 11 (58%) patients (responders). Of the eight remaining patients (nonresponders), six patients had reduced (but not normalized) iPTH levels and two patients required parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19 patients (89·5%) became normocalcaemic (serum Ca ≤ 2·57 mmol/l) and remained so for a mean follow‐up of 21 months (8–39 months). The odds ratio (P < 0·05) of response vs. no response to PEIT was 16·7‐fold for pretreatment iPTH < 200 vs. > 200 ng/l. The only complication was a transient dysphonia noticed in three patients.

Conclusions  PEIT is a safe and effective nonsurgical treatment for patients with p‐HPT, who are unsuitable for surgical intervention.
In search of stable soil organic carbon fractions: a comparison of methods applied to soils labelled with 14C for 40 days or 40 years
Authors: Bruun S. , Thomsen I. K. , Christensen B. T. , Jensen L. S.
Published: March 2008

A reliable method for the isolation of a stable fraction of soil organic carbon (SOC) would be very helpful for improving our understanding of the mechanisms responsible for stabilization of SOC and the dynamics of SOC turnover. We tested acid hydrolysis, physical fractionation (particle density/size), photo‐oxidation, treatment with chemical oxidants (NaOCl and NaS2O8) and thermal treatment on two soils incubated with 14C‐labelled barley straw for either 40 days or 40 years. Different intensities of the treatments were included. Acid hydrolysis, photo‐oxidation and treatment with a chemical oxidant consistently removed more 40‐year‐old C than 40‐day‐old C, which suggests that the isolated fractions contained a large proportion of material with a relatively rapid turnover. The clay + silt associated SOC fraction contained a small proportion of 40‐day‐old C and a large proportion of 40‐year‐old C. This is consistent with a SOC fraction with medium turnover. The thermal treatment removed more 40‐year‐old C than 40‐day‐old C. At 400°C there was still a small proportion of the 40‐year‐old C remaining, whereas almost all the 40‐day‐old C was removed. This is consistent with a stable SOC fraction. However, because only 2–3% of the C remained after this treatment, the isolated SOC fraction may be of little quantitative importance. Furthermore, the thermally resistant fraction is likely to be heavily altered by the treatment, and therefore unsuitable for further studies of the chemical nature of stable SOC.
Do freeze‐thaw events enhance C and N losses from soils of different ecosystems? A review
Authors: Matzner E. , Borken W.
Published: March 2008

Freezing and thawing of soils may affect the turnover of soil organic matter and thus the losses of C and N from soils. Here we review the literature with special focus on: (i) the mechanisms involved, (ii) the effects of freezing temperature and frequency, (iii) the differences between arable soils and soils under natural vegetation, and (iv) the hypothesis that freeze‐thaw events lead to significant C and N losses from soils at the annual scale. Changes in microbial biomass and populations, root turnover and soil structure might explain increased gaseous and solute fluxes of C and N following freeze‐thaw events, but these mechanisms have seldom been addressed in detail. Effects of freeze‐thaw events appear to increase with colder frost temperatures below 0°C, but a threshold value for specific soils and processes cannot be defined. The pool of C and N susceptible to freeze‐thaw events is rather limited, as indicated by decreasing losses with short‐term repeated events. Elevated nitrate losses from soils under alpine and/or arctic and forest vegetation occurred only in the year following exceptional soil frost, with greatest reported losses of about 13 kg N ha−1. Nitrate losses are more likely caused by reduced root uptake rather than by increased N net mineralization. N2O emissions from forest soils often increased after thawing, but this lasted only for a relatively short time (days to 1–2 months), with the greatest reported cumulative N2O emissions of about 2 kg N2O‐N ha−1. The emissions of N2O after freeze‐thaw events were in some cases substantially greater from arable soils than from forest soils. Thus, freeze‐thaw events might induce gaseous and/or solute losses of N from soils that are relevant at the annual time scale. While a burst of CO2 after thawing of frozen soils is often found, there is strong evidence that, at the annual time scale, freeze‐thaw cycles either have little effect or will even reduce soil C losses as compared with unfrozen conditions. On the contrary, a milder winter climate with fewer periods of soil frost may result in greater losses of C from soils that are presently influenced by extended frost periods.
The turnover of organic carbon in subsoils. Part 1. Natural and bomb radiocarbon in soil profiles from the Rothamsted long‐term field experiments
Authors: Jenkinson D. S. , Poulton P. R. , Bryant C.
Published: March 2008

The Rothamsted long‐term field experiments, started more than 150 years ago, provide unique material for the study of carbon turnover in subsoils. Total organic C, 14C and 13C were measured on soil profiles taken from these experiments, before and after the thermonuclear bomb tests of the mid‐20th century. Four contrasting systems of land management were sampled: land cultivated every year for winter wheat; regenerating woodland on acid soil; regenerating woodland on calcareous soil; and old grassland. The mean radiocarbon ages of all the pre‐bomb samples from cultivated land were 1210 years (0–23 cm), 2040 years (23–46 cm), 3610 years (46–69 cm) and 5520 years (69–92 cm). Bomb radiocarbon derived from thermonuclear tests was present throughout the profile in all the post‐bomb samples, although below 23 cm the amounts were small and the pre‐ and post‐bomb radiocarbon measurements were often not significantly different. Values of δ13C increased down the profile, from −26.3‰ (0–23 cm layer, mean of all measurements) to −25.2‰ for the 69–92 cm layer. The C/N ratios decreased with depth in virtually all of the profiles sampled. Excluding the surface (0–23 cm) soils from the old grassland, the hyperbola m = 152.1 − 2341/(1 + 0.264n) gave a close fit to the radiocarbon data from all depths, all sampling times and all sites, where n is the organic C content of the soil, in t ha−1, and m is the radiocarbon content of the soil, in Δ14C units, corrected for expansion or contraction of soil layers with time. The aberrant grassland soils almost certainly contained coal: one of them was shown by 13C‐NMR to contain 0.82% coal C. In Part 2 (this issue) of this pair of papers, these radiocarbon and total C measurements are used to develop and test a new model for the turnover of organic C in subsoils.
The turnover of organic carbon in subsoils. Part 2. Modelling carbon turnover
Authors: Jenkinson D. S. , Coleman K.
Published: March 2008

A new model, RothPC‐1, is described for the turnover of organic C in the top metre of soil. RothPC‐1 is a version of RothC‐26.3, an earlier model for the turnover of C in topsoils. In RothPC‐1 two extra parameters are used to model turnover in the top metre of soil: one, p, which moves organic C down the profile by an advective process, and the other, s, which slows decomposition with depth. RothPC‐1 is parameterized and tested using measurements (described in Part 1, this issue) of total organic C and radiocarbon on soil profiles from the Rothamsted long‐term field experiments, collected over a period of more than 100 years. RothPC‐1 gives fits to measurements of organic C and radiocarbon in the 0–23, 23–46, 46–69 and 69–92 cm layers of soil that are almost all within (or close to) measurement error in two areas of regenerating woodland (Geescroft and Broadbalk Wildernesses) and an area of cultivated land from the Broadbalk Continuous Wheat Experiment. The fits to old grassland (the Park Grass Experiment) are less close. Two other sites that provide the requisite pre‐ and post‐bomb data are also fitted; a prairie Chernozem from Russia and an annual grassland from California. Roth‐PC‐1 gives a close fit to measurements of organic C and radiocarbon down the Chernozem profile, provided that allowance is made for soil age; with the annual grassland the fit is acceptable in the upper part of the profile, but not in the clay‐rich Bt horizon below. Calculations suggest that treating the top metre of soil as a homogeneous unit will greatly overestimate the effects of global warming in accelerating the decomposition of soil C and hence on the enhanced release of CO2 from soil organic matter; more realistic estimates will be obtained from multi‐layer models such as RothPC‐1.
The effect of landscape processes upon gene flow and genetic diversity in an Australian freshwater fish, Neosilurus hyrtlii
Authors: HUEY J. A. , BAKER A. M. , HUGHES J. M.
Published: March 2008

1. Flow regime and riverine architecture are two important landscape characteristics that influence genetic diversity and gene flow in riverine species.

2. Using population genetic markers (mtDNA, microsatellites and allozymes), this study aimed to investigate genetic diversity and gene flow in the freshwater fish, Neosilurus hyrtlii, across two major drainage divisions in northern and central Australia (the Gulf of Carpentaria and Lake Eyre basins). These basins lie adjacent to each other and differ in their hydrological inputs and riverine structure, providing an ideal opportunity to identify the impact of landscape processes upon population dynamics of freshwater fish.

3. Populations were strongly structured among basins, among catchments within basins and were weakly structured within catchments in the Lake Eyre Basin, providing support for the Stream Hierarchy Model.

4. Interestingly, mtDNA and microsatellite diversity was much higher in the Gulf of Carpentaria Basin compared to the Lake Eyre Basin. It was concluded that this difference was due to the extreme hydrological variability in this basin and boom‐bust population cycles resulting in smaller effective population sizes in the Lake Eyre Basin.
Upscaling leaf area index in an Arctic landscape through multiscale observations
Authors: WILLIAMS M. , BELL R. , SPADAVECCHIA L. , STREET L. E. , VAN WIJK M. T.
Published: March 2008

Monitoring and understanding global change requires a detailed focus on upscaling, the process for extrapolating from the site‐specific scale to the smallest scale resolved in regional or global models or earth observing systems. Leaf area index (LAI) is one of the most sensitive determinants of plant production and can vary by an order of magnitude over short distances. The landscape distribution of LAI is generally determined by remote sensing of surface reflectance (e.g. normalized difference vegetation index, NDVI) but the mismatch in scales between ground and satellite measurements complicates LAI upscaling. Here, we describe a series of measurements to quantify the spatial distribution of LAI in a sub‐Arctic landscape and then describe the upscaling process and its associated errors. Working from a fine‐scale harvest LAI–NDVI relationship, we collected NDVI data over a 500 m × 500 m catchment in the Swedish Arctic, at resolutions from 0.2 to 9.0 m in a nested sampling design. NDVI scaled linearly, so that NDVI at any scale was a simple average of multiple NDVI measurements taken at finer scales. The LAI–NDVI relationship was scale invariant from 1.5 to 9.0 m resolution. Thus, a single exponential LAI–NDVI relationship was valid at all these scales, with similar prediction errors. Vegetation patches were of a scale of ∼0.5 m and at measurement scales coarser than this, there was a sharp drop in LAI variance. Landsat NDVI data for the study catchment correlated significantly, but poorly, with ground‐based measurements. A variety of techniques were used to construct LAI maps, including interpolation by inverse distance weighting, ordinary Kriging, External Drift Kriging using Landsat data, and direct estimation from a Landsat NDVI–LAI calibration. All methods produced similar LAI estimates and overall errors. However, Kriging approaches also generated maps of LAI estimation error based on semivariograms. The spatial variability of this Arctic landscape was such that local measurements assimilated by Kriging approaches had a limited spatial influence. Over scales >50 m, interpolation error was of similar magnitude to the error in the Landsat NDVI calibration. The characterisation of LAI spatial error in this study is a key step towards developing spatio‐temporal data assimilation systems for assessing C cycling in terrestrial ecosystems by combining models with field and remotely sensed data.