bluuebunny/crossref_metadata_2025 huggingface dataset:
An approach to designing a national climate service
Authors: Miles E. L. , Snover A. K. , Whitely Binder L. C. , Sarachik E. S. , Mote P. W. , Mantua N.
Published: December 2006

Climate variability and change are considerably important for a wide range of human activities and natural ecosystems. Climate science has made major advances during the last two decades, yet climate information is neither routinely useful for nor used in planning. What is needed is a mechanism, a national climate service (NCS), to connect climate science to decision-relevant questions and support building capacity to anticipate, plan for, and adapt to climate fluctuations. This article contributes to the national debate for an NCS by describing the rationale for building an NCS, the functions and services it would provide, and how it should be designed and evaluated. The NCS is most effectively achieved as a federal interagency partnership with critically important participation by regional climate centers, state climatologists, the emerging National Integrated Drought Information System, and the National Oceanic and Atmospheric Administration (NOAA) Regional Integrated Sciences Assessment (RISA) teams in a sustained relationship with a wide variety of stakeholders. Because the NCS is a service, and because evidence indicates that the regional spatial scale is most important for delivering climate services, given subnational geographical/geophysical complexity, attention is focused on lessons learned from the University of Washington Climate Impacts Group's 10 years of experience, the first of the NOAA RISA teams.
Becoming what you want to be
Authors: Batchelor Denise
Published: December 2006

Challenges to become what you want to be permeate higher education recruitment literature, inviting students to realize their dreams. Students do not interpret this invitation only in vocational terms. Other aspects of meaning for being and becoming are important for them: self-realization,
and becoming who as well as what they want to be. A student voice for being and becoming is less valued and validated in contemporary higher education, and more vulnerable, than voices for knowing and doing. Yet if voices for being and becoming are unsupported, voices for knowing and doing
also become vulnerable. Integrity of voice is undermined.
Public–private convergence and the special case of voucher-receiving schools
Authors: Loomis Steven R. , Rodriguez Jacob P. , Honeycutt Jared , Arellano Manuel
Published: December 2006

Many arguments in favour of school voucher programs are based upon libertarian free agency principles. Viewed at the organizational level, allowing persons to exercise choice in education would seem to offer incentives for all educational organizations within that framework to improve
overall product quality and thus more effectively obtain the education good for both individual and society. However, analysis from the transcending institutional level shows that supra-organizational forces will progressively reduce choice and quality as both private and public organizations
relinquish their distinctive curricula and philosophies as a de facto requirement for participation within the broader educational institution or 'market'. Acknowledging the costs of, and designing policy to maintain, particular information are both essential to effectively producing
the education good within a competitive institutional structure.
Promoting thinking skills in education
Authors: Glevey Kwame E.
Published: December 2006

How children are guided in the development of their thinking is now crucial in the twenty-first century. Over the past decades special thinking skills programmes have been developed to enhance thinking but these programmes have so far been unable to produce clear evidence to support
their effectiveness. This article argues that due to the complex nature of thinking some fundamental changes in education must be tackled if all children are to be encouraged to develop and enhance their own particular ways of thinking.
Scientific Research in Homeopathic Medicine: Validation, Methodology and Perspectives
Authors: Pitari Giuseppina
Published: December 2006

Verona′s School of Homeopathic Medicine (www.omeopatia.org) organized a day of full immersion in the field of homeopathy, focusing on the validity of this much‐debated discipline. There is widespread consensus in the medical community that evidence‐based medicine is the best standard for assessing efficacy and safety of healthcare practices, and systematic reviews with strict protocols are essential to establish proof for various therapies. Students, homeopathic practitioners, academic and business representatives, who are interested in or curious about homeopathic practices attended the conference.
The cancer epigenome—components and functional correlates
Authors: Ting Angela H. , McGarvey Kelly M. , Baylin Stephen B.
Published: December 2006

It is increasingly apparent that cancer development not only depends on genetic alterations but on an abnormal cellular memory, or epigenetic changes, which convey heritable gene expression patterns critical for neoplastic initiation and progression. These aberrant epigenetic mechanisms are manifest in both global changes in chromatin packaging and in localized gene promoter changes that influence the transcription of genes important to the cancer process. An exciting emerging theme is that an understanding of stem cell chromatin control of gene expression, including relationships between histone modifications and DNA methylation, may hold a key to understanding the origins of cancer epigenetic changes. This possibility, coupled with the reversible nature of epigenetics, has enormous significance for the prevention and control of cancer.
The role of protein arginine methylation in the formation of silent chromatin
Authors: Yu Michael C. , Lamming Dudley W. , Eskin Julian A. , Sinclair David A. , Silver Pamela A.
Published: December 2006

Establishment and maintenance of silent chromatin in the Saccharomyces cerevisiae involves a step-wise assembly of the SIR complex. Here we demonstrate a role for the protein arginine methyltransferase Hmt1 in this process. In the absence of catalytically active Hmt1, yeast cells display increased transcription from silent chromatin regions and increased mitotic recombination within tandem repeats of rDNA. At the molecular level, loss of Hmt1’s catalytic activity results in decreased Sir2 and dimethylated Arg-3 histone H4 occupancy across silent chromatin regions. These data suggest a model whereby protein arginine methylation affects the establishment and maintenance of silent chromatin.
A dynamic, mitotic-like mechanism for bacterial chromosome segregation
Authors: Fogel Michael A. , Waldor Matthew K.
Published: December 2006

The mechanisms that mediate chromosome segregation in bacteria are poorly understood. Despite evidence of dynamic movement of chromosome regions, to date, mitotic-like mechanisms that act on the bacterial chromosome have not been demonstrated. Here we provide evidence that the Vibrio cholerae ParAI and ParBI proteins are components of an apparatus that pulls the origin region of the large V. cholerae chromosome to the cell pole and anchors it there. ParBI interacts with a conserved origin-proximal, centromere-like site (parSI) that, following chromosome replication, segregates asymmetrically from one pole to the other. While segregating, parSI stretches far away from neighboring chromosomal loci. ParAI forms a dynamic band that extends from the pole to the segregating ParBI/parSI complex. Movement of ParBI/parSI across the cell occurs in concert with ParAI retraction. Deletion of parAI disrupts proper origin localization and segregation dynamics, and parSI no longer separates from nearby regions. These data suggest that ParAI forms a dynamic structure that pulls the ParBI-bound chromosome to the pole in a process analogous to anaphase of eukaryotic mitosis.
MDC1 accelerates nonhomologous end-joining of dysfunctional telomeres
Authors: Dimitrova Nadya , de Lange Titia
Published: December 2006

Here we document the role of MDC1 (mediator of DNA damage checkpoint 1) in the detection and repair of human and mouse telomeres rendered dysfunctional through inhibition of TRF2. Consistent with its role in promoting DNA damage foci, MDC1 knockdown affected the formation of telomere dysfunction-induced foci (TIFs), diminishing the accumulation of phosphorylated ATM, 53BP1, Nbs1, and to a lesser extent, γ-H2AX. In addition to this effect on TIFs, the rate of nonhomologous end-joining (NHEJ) of dysfunctional telomeres was significantly decreased when MDC1 itself or its recruitment to chromatin was inhibited. MDC1 appeared to promote a step in the NHEJ pathway after the removal of the 3′ telomeric overhang. The acceleration of NHEJ was unlikely to be due to increased presence of 53BP1 and Mre11 in TIFs, since knockdown of neither factor affected telomere fusions. Furthermore, relevant cell cycle effectors (Chk2, p53, and p21) of the ATM kinase pathway were unaffected and there was no change in the rate of cell cycle progression. We propose that the binding of MDC1 to γ-H2AX directly affects NHEJ in a manner that is independent of the ATM-dependent cell cycle arrest pathway.
The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity
Authors: Ouararhni Khalid , Hadj-Slimane Réda , Ait-Si-Ali Slimane , Robin Philippe , Mietton Flore , Harel-Bellan Annick , Dimitrov Stefan , Hamiche Ali
Published: December 2006

The histone variant mH2A is believed to be involved in transcriptional repression, but how it exerts its function remains elusive. By using chromatin immunoprecipitation and tandem affinity immunopurification of the mH2A1.1 nucleosome complex, we identified numerous genes with promoters containing mH2A1.1 nucleosomes. In particular, the promoters of the inducible Hsp70.1 and Hsp70.2 genes, but not that of the constitutively expressed Hsp70.8, were highly enriched in mH2A1.1. PARP-1 was identified as a part of the mH2A1.1 nucleosome complex and was found to be associated with the Hsp70.1 promoter. A specific interaction between mH2A1.1 and PARP-1 was demonstrated and found to be associated with inactivation of PARP-1 enzymatic activity. Heat shock released both mH2A1.1 and PARP-1 from the Hsp70.1 promoter and activated PARP-1 automodification activity. The data we present point to a novel mechanism for control of Hsp70.1 gene transcription. mH2A1.1 recruits PARP-1 to the promoter, thereby inactivating it. Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins.
Validation of daily increment deposition in otoliths of juvenile Limnothrissa miodon (Clupeidae)
Authors: Meisfjord J. , Midtøy F. , Folkvord A.
Published: December 2006

Daily deposition of otolith increments was validated for juvenile Limnothrissa miodon in the Cahora Bassa reservoir, Mozambique, by the means of two successive chemical immersion markings.
Ultraviolet absorbance of the mucus of a tropical damselfish: effects of ontogeny, captivity and disease
Authors: Zamzow J. P. , Siebeck U. E.
Published: December 2006

The ultraviolet (UV) absorbance of the mucus of a Great Barrier Reef damselfish Pomacentrus amboinensis was investigated with regard to ontogeny and time spent in captivity. The UV absorbance of P. amboinensis mucus increased with fish size and decreased with time spent in captivity. The wavelength of maximum absorbance of the mucus did not change with fish size, but shifted towards shorter wavelengths with increasing time spent in captivity. The UV absorbance of the mucus of fish with ‘fin rot’ was compared to that of similar healthy individuals, and a significant decrease in UV absorbance of unhealthy fish mucus was detected; no wavelength shifting occurred. Pomacentrus amboinensis appears to sequester mycosporine‐like amino acids from the diet in order to protect epithelial tissues from UV damage, and decreases in UV absorbance in captive fish were probably due to insufficient dietary availability.
Gait transition and oxygen consumption in swimming striped surfperch Embiotoca lateralis Agassiz
Authors: Cannas M. , Schaefer J. , Domenici P. , Steffensen J. F.
Published: December 2006

A flow‐through respirometer and swim tunnel was used to estimate the gait transition speed (Up‐c) of striped surfperch Embiotoca lateralis, a labriform swimmer, and to investigate metabolic costs associated with gait transition. The Up‐c was defined as the lowest speed at which fish decrease the use of pectoral fins significantly. While the tail was first recruited for manoeuvring at relatively low swimming speeds, the use of the tail at these low speeds [as low as 0·75 body (fork) lengths s−1, LF s−1) was rare (<10% of the total time). Tail movements at these low speeds appeared to be associated with occasional slow manoeuvres rather than providing power. As speed was increased beyond Up‐c, pectoral fin (PF) frequencies kept increasing when the tail was not used, while they did not when PF locomotion was aided by the tail. At these high speeds, the tail was employed for 40–50% of the time, either in addition to pectoral fins or during burst‐and‐coast mode. Oxygen consumption increased exponentially with swimming speeds up to gait transition, and then levelled off. Similarly, cost of transport (CT) decreased with increasing speed, and then levelled off near Up‐c. When speeds ≥Up‐c are considered, CT is higher than the theoretical curve extrapolated for PF swimming, suggesting that PF swimming appears to be higher energetically less costly than undulatory swimming using the tail.
The effects of preservation on fish tissue stable isotope signatures
Authors: Kelly B. , Dempson J. B. , Power M.
Published: December 2006

The effects of formalin and ethanol preservation on the δ13C and δ15N isotope signatures of Arctic charr Salvelinus alpinus muscle tissue were examined. The lipid content of the tissue samples studied ranged from 3·6 to 6·1% and was not correlated with the magnitude of observed isotopic shifts in preserved samples. Ethanol and formalin significantly depleted and enriched, respectively, the δ13C isotope signatures of preserved tissues when compared to control samples. Ethanol did not significantly enrich δ15N signatures in comparison to controls, whereas formalin did. A meta‐analysis of multiple species effects further demonstrated significant preservation effects in fish tissue. Statistical analysis of data obtained by correcting preserved tissue isotope signatures with literature, bootstrapped or meta‐analysis derived correction factors demonstrated significant differences between corrected and control sample isotope signatures or failure to produce a unity slope when the data sets were regressed against one another. Species‐specific, bootstrapped linear correction models resulted in no such errors. Results suggest that species‐specific correction methods should be used for fishes because of the known wide variation in fish tissue lipid content and composition. Accordingly, the use of pilot studies will be required to develop correction factors that properly adjust for preservation effects when interpreting temporal patterns in historic analyses of food webs.
Effects of surgically implanted acoustic transmitters >2% of body mass on the swimming performance, survival and growth of juvenile sockeye and Chinook salmon
Authors: Brown R. S. , Geist D. R. , Deters K. A. , Grassell A.
Published: December 2006

The influence of surgical implantation of an acoustic transmitter on the swimming performance, growth and survival of juvenile sockeye salmon Oncorhynchus nerka and Chinook salmon Oncorhynchus tshawytscha was examined. The transmitter had a mass of 0·7 g in air while sockeye salmon had a mass of 7·0–16·0 g and Chinook salmon had a mass of 6·7–23·1 g (a transmitter burden of 4·5–10·3% for sockeye salmon and 3·1–10·7% for Chinook salmon). Mean critical swimming speeds (Ucrit) for Chinook salmon ranged from 47·5 to 51·2 cm s−1 [4·34–4·69 body lengths (fork length, LF) s−1] and did not differ among tagged, untagged and sham‐tagged groups. Tagged sockeye salmon, however, did have lower Ucrit than control or sham fish. The mean Ucrit for tagged sockeye salmon was 46·1 cm s−1 (4·1 LF s−1), which was c. 5% less than the mean Ucrit for control and sham fish (both groups were 48·6 cm s−1 or 4·3 LF s−1). A laboratory evaluation determined that there was no difference in LF or mass among treatments (control, sham or tag) either at the start or at the end of the test period, suggesting that implantation did not negatively influence the growth of either species. None of the sockeye salmon held under laboratory conditions died from the influence of surgical implantation of transmitters. In contrast, this study found that the 21 day survival differed between tagged and control groups of Chinook salmon, although this result may have been confounded by the poor health of Chinook salmon treatment groups.
A case of mistaken identity: skin filaments are unreliable for identifying Hippocampus guttulatus and Hippocampus hippocampus
Authors: Curtis J. M. R.
Published: December 2006

The presence or absence of skin filaments is an unreliable character for identifying European seahorses. Growth of skin filaments on Hippocampus guttulatus coincides with maturation, while presence on Hippocampus hippocampus is highly variable. Multiple morphological traits including snout, head and trunk shape should be used for identification.
Reproductive behaviour of the black‐striped pipefish Syngnathus abaster (Pisces; Syngnathidae)
Authors: Silva K. , Monteiro N. M. , Vieira M. N. , Almada V. C.
Published: December 2006

The reproductive behaviour of Syngnathus abaster is described and compared with those of other syngnathids. The need for standardized behavioural data is discussed in light of the actual theories of evolution of mating patterns and sex‐role reversal within this family.
Within‐population heterogeneity of habitat use by lake trout Salvelinus namaycush
Authors: Morbey Y. E. , Addison P. , Shuter B. J. , Vascotto K.
Published: December 2006

To learn more about the degree of individual variation in resource use by lake trout Salvelinus namaycush, ultrasonic telemetry was used to study their habitat use in a lake without pelagic schooling fish prey. Individuals spent most of their time within the metalimnion in favourable water temperatures. They also made frequent excursions, however, into lake temperatures exceeding their optimum for physiological performance at all temporal scales considered. Their frequent use of nearshore habitats suggested that feeding in littoral areas may be common. Habitat use was highly variable among individuals, but spatial habitat use by individuals showed remarkable consistency between years. In particular, some lake trout exhibited high site fidelity to shallow, nearshore areas, whereas others used deep areas extensively. This level of between‐individual variation indicated niche partitioning by depth and the possibility of alternative foraging strategies.
Comparison of various potential fecundity models for north‐east Arctic cod Gadus morhua, L. using oocyte diameter as a standardizing factor
Authors: Thorsen A. , Marshall C. T. , Kjesbu O. S.
Published: December 2006

To build a better data foundation for recruitment models of north‐east Arctic cod Gadus morhua the construction of fecundity models reflecting variation in the nutritional status of the fish was attempted. The models were based on fecundity time series covering 9 years within the period 1986–2004 and included both general and year‐specific approaches. Initial data analysis revealed that the potential fecundity (FP) (standing stock of vitellogenic oocytes) was significantly reduced as the vitellogenic oocytes increased in size towards the start of spawning. Histological examination strongly indicated that this seasonal reduction was caused by atresia. Regression analysis showed that the FP was positively correlated to fish total length (LT) and the Fulton’s condition factor (K). A multiple regression including data for all years using fish LT, K and mean oocyte diameter (DO) as independent predictors described the FP with an r2= 0·94. This was considerably higher than comparable univariate LT or mass‐based regressions. These univariate regressions had fairly high r2 values when split by years, but not as high as found for year‐specific multiple regressions. An important application for individual‐based fecundity models may be to generate outputs that can be fed into stock level fecundity and recruitment models. Overall, the multivariate models seemed to be the most accurate. The multivariate model including mean DO, however, also had the potential to correct for maturity and thus provide unbiased fecundity comparisons between years, stocks and locations.
Growth of larval Pacific anchovy Engraulis japonicus in the Yellow Sea as indicated by otolith microstructure analysis
Authors: Hwang S.‐D. , Song M.‐H. , Lee T.‐W. , McFarlane G. A. , King J. R.
Published: December 2006

Larval Pacific anchovy Engraulis japonicus were sampled from coastal waters off the central west coast of Korea from June to November 1996. Using otolith microstructure analysis (daily growth increments), three cohorts (spring, early summer and late summer) were distinguished based on backcalculated spawning dates. Growth rates differed between cohorts, with higher growth rates for late‐summer cohorts than either the spring or early‐summer cohorts. Growth rate was positively related to surface water temperature, with an optimum temperature range of between 20 and 26° C occurring during the late summer (late July through to mid‐September). The study highlights that early growth rates of Pacific anchovy are dependent on ecosystem (particularly water temperature) attributes during early life.
Seasonal variation of sound production in the Lusitanian toadfish Halobatrachus didactylus
Authors: Amorim M. C. P. , Vasconcelos R. O. , Marques J. F. , Almada F.
Published: December 2006

Seasonal variation of sound production, which includes boatwhistles, grunts, croaks and double croaks, was studied in the Lusitanian toadfish Halobatrachus didactylus. Boatwhistles were emitted during the mating season in contrast with the other sound types, which were emitted all year round.
The Fas/FasL system is a possible regulator of germ cell apoptosis in the testis of Torpedo marmorata
Authors: Ricchiari L. , Liguoro A. , Andreuccetti P. , Angelini F. , Prisco M.
Published: December 2006

The role played by the Fas/FasL system in the activation of apoptosis during the spermatogenesis of the spotted ray Torpedo marmorata was investigated. By immunohistochemical and western blot techniques it was demonstrated that the Fas/FasL system is amply represented during spermatogenesis of T. marmorata and it could act both via a paracrine and autocrine route: paracrine at the level of immature and mature cysts, autocrine only in mature cysts.
Influence of seasonal changes in relative liver size, condition, relative gonad size and variability in ovarian development in multiple spawning fish species used in environmental monitoring programmes
Authors: Galloway B. J. , Munkittrick K. R.
Published: December 2006

Basic biological information was collected to assist in understanding the biology of selected small‐bodied fishes for use in environmental monitoring programmes. Gonado‐somatic index (IG) and hepato‐somatic index (IH) profiles of female blacknose dace Rhinichthys atratulus, mummichog Fundulus heteroclitus and golden shiner Notemigonus crysoleucas were similar, decreasing gradually during the spawning season. IG and IH profiles of female northern redbelly dace Phoxinus eos peaked twice suggesting oocyte recruitment was continuous throughout the spawning season. Regressions of ovary mass to adjusted body mass (MA) were more variable in dace relative to the other fish species. For female blacknose dace, variability in the relationship between ovary mass and MA was minimized by selecting either 2 year‐old fish and fish that weighed 2–4 g.
Effects of alternative prey on predation intensity from herring Clupea harengus and sandeel Ammodytes marinus on capelin Mallotus villosus larvae in the Barents Sea
Authors: Godiksen J. A. , Hallfredsson E. H. , Pedersen T.
Published: December 2006

Stomach contents from lesser sandeel Ammodytes marinus and herring Clupea harengus caught at one and three stations, respectively, were analysed to investigate predation intensity on capelin Mallotus villosus larvae. Most capelin larvae were found in the anterior sections of the stomachs close to the oesophagus, indicating that rapid digestion rates of larvae reduced the abundance in the posterior sections. The anterior sections of the stomachs had alternating layers of either copepods or capelin larvae and krill. This shows that the individual predators switched between feeding on either copepods or on krill and capelin larvae. A total of 549 capelin larvae was found in 440 fish stomachs. Capelin larvae were found in 20% of the sandeel stomachs, and 24, 34 and 62% of the stomachs from the three herring stations, respectively. Many of the predator stomachs contained more than five larvae, and up to 28 larvae were found in one herring stomach. The herring appeared to prey selectively on the largest capelin larvae, and the number of larvae per stomach was much higher in stomachs where krill had recently been eaten than where copepods were dominant. The predation intensity measured in this study is much higher than reported in earlier studies, and it is suggested that the predators were feeding using a searching image, and that the concentrations of alternative prey (copepods and krill) varied around a switching threshold.
Efficient immortalization of primary human cells by p16INK4a‐specific short hairpin RNA or Bmi‐1, combined with introduction of hTERT
Authors: Haga Kei , Ohno Shin‐ichi , Yugawa Takashi , Narisawa‐Saito Mako , Fujita Masatoshi , Sakamoto Michiie , Galloway Denise A. , Kiyono Tohru
Published: December 2006

Activation of telomerase is sufficient for immortalization of some types of human cells but additional factors may also be essential. It has been proposed that stress imposed by inadequate culture conditions induces senescence due to accumulation of p16INK4a. Here, we present evidence that many human cell types undergo senescence by activation of the p16INK4a/Rb pathway, and that introduction of Bmi‐1 can inhibit p16INK4a expression and extend the life span of human epithelial cells derived from skin, mammary gland and lung. Introduction of p16INK4a‐specific short hairpin RNA, as well as Bmi‐1, suppressed p16INK4a expression in human mammary epithelial cells without promoter methylation, and extended their life span. Subsequent introduction of hTERT, the telomerase catalytic subunit, into cells with low p16INK4a levels resulted in efficient immortalization of three cell types without crisis or growth arrest. The majority of the human mammary epithelial cells thus immortalized showed almost normal ploidy as judged by G‐banding and spectral karyotyping analysis. Our data suggest that inhibition of p16INK4a and introduction of hTERT can immortalize many human cell types with little chromosomal instability. (Cancer Sci 2007; 98: 147–154)
Growth factor‐independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate
Authors: Elmaagacli Ahmet H. , Koldehoff Michael , Zakrzewski Johannes L. , Steckel Nina K. , Ottinger Hellmut , Beelen Dietrich W.
Published: December 2006

Growth factor‐independent 1B (GFI1B) is a transcription factor essential for the development and differentiation of erythroid and megakaryocytic lineages. We evaluated the GFI1B expression in erythroleukaemia and megakaryocytic leukaemia, as well as in patients with other subtypes of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), myelodysplastic syndrome (MDS), severe aplastic anaemia (SAA), myelofibrosis with myeloid metaplasia (MMM) and in healthy volunteers. GFI1B expression was increased at least threefold in patients with erythroleukaemia (P < 0·01 compared with controls) and megakaryocytic leukaemia (P < 0·05) as well as in their corresponding leukaemic cell lines HEL, K562, CMK and M‐07e. Patients with undifferentiated or monocytic AML, ALL, MMM, MDS and CML had no significantly altered GFI1B expression, whereas GFI1B expression was decreased 10‐fold in patients with SAA (P < 0·0001 compared with controls). Silencing GFI1B by transfection with small interfering RNA (siRNA) markedly reduced the proliferation rate in the leukaemic cell lines HEL, K562 and NB4 (P < 0·01). Concomitantly, we observed a two‐ to threefold increase in the apoptosis rate in these cells after transfection with siRNA towards GFI1B. Our data indicate that GFI1B plays a major role in AML‐M6 and AML‐M7 and qualifies as a target for anti‐leukaemic strategies in these malignancies.
Severity of pulmonary hypertension during vaso‐occlusive pain crisis and exercise in patients with sickle cell disease
Authors: Machado Roberto F. , Kyle Mack A. , Martyr Sabrina , Barnett Christopher , MacArthur Peter , Sachdev Vandana , Ernst Inez , Hunter Lori A. , Coles Wynona A. , Nichols James P. , Kato Gregory J. , Gladwin Mark T.
Published: December 2006

Pulmonary hypertension is associated with sudden death and is a risk factor for mortality in adult patients with sickle cell disease. The high mortality despite only mild‐to‐moderate increases in pulmonary vascular resistance remains an unresolved paradox. Accordingly, little is known about the cardiovascular effects of stressors, such as vaso‐occlusive pain crisis (VOC) and exercise, which may acutely increase pulmonary pressures and impair right heart function. We therefore evaluated pulmonary artery pressures by echocardiogram in 25 patients with sickle cell disease in steady‐state and during VOC, and by right heart catheterisation with exercise in a second cohort of 21 patients to determine whether pulmonary hypertension worsens during acute cardiopulmonary stress. TRV increased during VOC (P < 0·001), and the increased pulmonary pressures during VOC were associated with decreases in haemoglobin levels (P < 0·001), and increases in lactate dehydrogenase (P < 0·001) and plasma haemoglobin levels (P = 0·03). During exercise stress performed during cardiac catheterisation, mean pulmonary artery pressures (P < 0·001) and pulmonary vascular resistance increased (P < 0·001) in all subjects. These data suggest that acute elevations in pulmonary pressures during VOC or exercise may contribute to morbidity and mortality in patients with sickle cell disease.
Advances in the management of alloimmune thrombocytopenia
Authors: Murphy Michael F. , Bussel James B.
Published: December 2006

There have been considerable advances in the clinical and laboratory diagnosis of alloimmune thrombocytopenia (AIT), and its postnatal and antenatal management. The antenatal management of AIT has been particularly problematic, because severe haemorrhage occurs as early as 16 weeks gestation and there is no non‐invasive investigation that reliably predicts the severity of AITin utero. The strategies for antenatal treatment have included the use of serial platelet transfusions that, while effective, are invasive and associated with significant morbidity and mortality. Maternal therapy involving the administration of intravenous immunoglobulin and/or steroids is also effective and associated with fewer risks to the fetus. Significant recent progress has involved refinement of maternal treatment, stratifying it according to the likely severity of AIT based on the history in previous pregnancies. However, the ideal antenatal treatment, which is effective without causing significant side‐effects to the mother or fetus, has yet to be determined, and further clinical trials are needed.
Gene expression profiles of erythroid precursors characterise several mechanisms of the action of hydroxycarbamide in sickle cell anaemia
Authors: Chagas Costa Flávia , Ferreira da Cunha Anderson , Fattori André , De Sousa Peres Tarcísio , Gilson Lacerda Costa Gustavo , Ferraz Machado Tiago , Martins de Albuquerque Dulcinéia , Gambero Sheley , Lanaro Carolina , Olala Saad Sara T. , Ferreira Costa Fernando
Published: December 2006

Hydroxycarbamide (HC) (or hydroxyurea) has been reported to increase fetal haemoglobin levels and improve clinical symptoms in sickle cell anaemia (SCA) patients. However, the complete pathway by which HC acts remains unclear. To study the mechanisms involved in the action of HC, global gene expression profiles were obtained from the bone marrow cells of a SCA patient before and after HC treatment using serial analysis of gene expression. In the comparison of both profiles, 147 differentially expressed transcripts were identified. The functional classification of these transcripts revealed a group of gene categories associated with transcriptional and translational regulation, e.g. EGR‐1, CENTB1, ARHGAP4 and RIN3, suggesting a possible role for these pathways in the improvement of clinical symptoms of SCA patients. The genes involved in these mechanisms may represent potential tools for the identification of new targets for SCA therapy.
The haematocrit and platelet target in polycythemia vera
Authors: Di Nisio Marcello , Barbui Tiziano , Di Gennaro Leonardo , Borrelli Giovanna , Finazzi Guido , Landolfi Raffaele , Leone Giuseppe , Marfisi RosaMaria , Porreca Ettore , Ruggeri Marco , Rutjes Anne W. S. , Tognoni Gianni , Vannucchi Alessandro M. , Marchioli Roberto ,   the European Collaboration on Low‐dose Aspirin in Polycythemia Vera (ECLAP) Investigators
Published: December 2006

Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events and progression to acute leukaemia or myelofibrosis. Whether the haematocrit and platelet count predict such complications remains unclear. The European Collaboration on Low‐dose Aspirin in Polycythemia Vera prospective study included 1638 PV patients. A total of 164 deaths (10%), 145 (8·85%) major thrombosis and 226 (13·8%) total thrombosis were encountered during 4393 person‐years follow‐up (median 2·8 years). In time‐dependent multivariable analysis, a haematocrit in the evaluable range of 40–55% was neither associated with the occurrence of thrombotic events, mortality nor with haematological progression in the studied population. The haematocrit of patients in the highest and lowest deciles at baseline was maintained within a narrow interval of haematocrit values ranging from 40% to 47% throughout follow‐up. High platelet count was associated with a lower progression rate to acute leukaemia/myelofibrosis, whereas it had no significant relationship with thrombotic events or mortality. Our findings do not suggest that the range of haematocrit (<55%) and platelet counts (<600 × 109/l) we encountered in our population had an impact on the outcome of PV patients treated by current therapeutic strategies.
Primary nodal marginal zone B‐cell lymphoma: clinical features and prognostic assessment of a rare disease
Authors: Arcaini Luca , Paulli Marco , Burcheri Sara , Rossi Andrea , Spina Michele , Passamonti Francesco , Lucioni Marco , Motta Teresio , Canzonieri Vincenzo , Montanari Mauro , Bonoldi Emanuela , Gallamini Andrea , Uziel Lilj , Crugnola Monica , Ramponi Antonio , Montanari Francesca , Pascutto Cristiana , Morra Enrica , Lazzarino Mario ,   Intergruppo Italiano Linfomi
Published: December 2006

This study defined the clinical features and assessed the prognosis of 47 patients (17 males, 30 females, median age 63 years) with primary nodal marginal zone B‐cell lymphoma. Forty‐five per cent had stage IV disease. Hepatitis C virus serology was positive in 24%. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 33% were classified as low‐risk, 34% as intermediate‐risk, and 33% as high‐risk. The 5‐year overall survival (OS) was 69%. In univariate analysis worse OS was associated with: FLIPI (P = 0·02), age > 60 years (P = 0·05) and raised lactate dehydrogenase (P = 0·05). In multivariate analysis, only FLIPI predicted a worse OS (P = 0·02).
Dose‐adjusted EPOCH plus rituximab is an effective regimen in patients with poor‐prognostic untreated diffuse large B‐cell lymphoma: results from a prospective observational study
Authors: García‐Suárez Julio , Bañas Helena , Arribas Ignacio , De Miguel Dunia , Pascual Teresa , Burgaleta Carmen
Published: December 2006

This study was designed to assess the efficacy and safety of an infusional DA‐EPOCH (dose‐adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) and rituximab (DA‐EPOCH‐R) regimen for patients with poor prognosis diffuse large B‐cell lymphoma (DLBCL). Thirty‐three patients, aged 21–76 years, with an age‐adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled, and 31/33 patients were evaluable for response. Consolidative radiation therapy was given to eight patients with bulky (≥10 cm) disease at presentation. Overall, 26 patients (83·8%) achieved a complete remission (CR), four patients (12·9%) achieved a partial remission, and one patient (3·2%) died during induction. Two patients relapsed (7·6%) within 15 months. Grade 3–4 neutropenia developed in 52% of cycles and neutropenic fever in 14% of cycles (51% of patients). The estimates for event‐free survival (EFS) and overall survival at 2 years were 68% and 75% respectively. The only factor related to poor EFS was the presence of three age‐adjusted IPI‐risk factors. We conclude that DA‐EPOCH‐R has clinically significant activity with a favourable toxicity profile for poor‐prognostic DLBCL patients. The administration of DA‐EPOCH‐R as an outpatient regimen by using a single portable infusion pump may be a feasible alternative to improve the compliance and to reduce the total cost of this very effective regimen.
Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years?
Authors: Ferrucci Pier Francesco , Zucca Emanuele
Published: December 2006

Primary gastric (PG) lymphomas are generally non‐Hodgkin lymphomas (NHL). They represent 5% of gastric malignancies and show an apparently increasing incidence worldwide. The most common histological subtypes are diffuse large B‐cell and marginal zone B‐cell NHL of the mucosa‐associated lymphoid tissue (MALT)‐type. Pathogenesis is often related to Helicobacter pylori infection (HPI). There is still no consensus on the optimal treatment for PG lymphoma. Nowadays surgery is limited to rare cases and radiotherapy – combined or not with chemotherapy – represents an effective therapeutic option ensuring long‐term, organ‐salvage benefits mainly in aggressive histological subtypes. Additionally, the description of MALT lymphomas has made the situation even more complex, because antibiotics alone can induce lasting remissions in those cases associated with HPI. Consequently, a global therapeutic approach to the cure of PG‐NHL has completely changed over the last 10 years: innovative, conservative options to reduce treatment toxicity, thus preventing systemic relapses, have made their appearance and are on the rise.
Bisphosphonate incadronate inhibits growth of human T‐cell leukaemia virus type I‐infected T‐cell lines and primary adult T‐cell leukaemia cells by interfering with the mevalonate pathway
Authors: Ishikawa Chie , Matsuda Takehiro , Okudaira Taeko , Tomita Mariko , Kawakami Hirochika , Tanaka Yuetsu , Masuda Masato , Ohshiro Kazuiku , Ohta Takao , Mori Naoki
Published: December 2006

Anti‐resorptive bisphosphonates are used for the treatment of hypercalcaemia and bone complications associated with malignancies and osteoporosis, but also have been shown to have anti‐tumour effects in various cancers. Adult T‐cell leukaemia (ATL) is a fatal T‐cell malignancy caused by infection with human T‐cell leukaemia virus type I (HTLV‐I), and remains incurable. ATL is associated with osteolytic bone lesions and hypercalcaemia, both of which are major factors in the morbidity of ATL. Thus, the search for anti‐ATL agents that have both anti‐tumour and anti‐resorptive activity is warranted. The bisphosphonate agent, incadronate, prevented cell growth of HTLV‐I‐infected T‐cell lines and primary ATL cells, but not of non‐infected T‐cell lines or normal peripheral blood mononuclear cells. Incadronate induced S‐phase cell cycle arrest and apoptosis in HTLV‐I‐infected T‐cell lines, and treatment of these cells with substrates of the mevalonate pathway blocked the incadronate‐mediated growth suppression. Incadronate also prevented the prenylation of Rap1A protein. These results demonstrated that incadronate‐induced growth suppression occurs by interfering with the mevalonate pathway. Importantly, treatment with incadronate reduced tumour formation from an HTLV‐I‐infected T‐cell line when these cells were inoculated subcutaneously into severe combined immunodeficient mice. These findings suggest that incadronate could be potentially useful for the treatment of ATL.
Leaf biomechanical properties and the densities of herbivorous insect guilds
Authors: PEETERS PAULA J. , SANSON GORDON , READ JENNIFER
Published: December 2006

This study investigated relationships between leaf biomechanical properties and the densities of their associated insect herbivores.

The herbivorous insects associated with 18 co‐occurring plant species were sampled over 16 months. Biomechanical properties of new and mature leaves of each plant species were measured using punching, shearing and tearing tests.

Significant variation in leaf biomechanical properties was found among plant species, and between new and mature leaves.

Total insect density was significantly negatively correlated with work to tear (r = −0·43, P < 0·05) and work to shear (r = −0·70, P < 0·01).

Although chewing insect density was significantly correlated with punch strength of mature leaves, sucking insect density was not. While studies of herbivory often include measures of leaf punch strength, this mechanical trait may indicate resistance to chewing insects but not sucking insects.

We conclude that leaf biomechanical properties are influencing the functional composition of herbivorous insect assemblages in this system.
Plant trait responses to grazing – a global synthesis
Authors: DÍAZ SANDRA , LAVOREL SANDRA , McINTYRE SUE , FALCZUK VALERIA , CASANOVES FERNANDO , MILCHUNAS DANIEL G. , SKARPE CHRISTINA , RUSCH GRACIELA , STERNBERG MARCELO , NOY‐MEIR IMANUEL , LANDSBERG JILL , ZHANG WEI , CLARK HARRY , CAMPBELL BRUCE D.
Published: December 2006

Herbivory by domestic and wild ungulates is a major driver of global vegetation dynamics. However, grazing is not considered in dynamic global vegetation models, or more generally in studies of the effects of environmental change on ecosystems at regional to global scale. An obstacle to this is a lack of empirical tests of several hypotheses linking plant traits with grazing. We, therefore, set out to test whether some widely recognized trait responses to grazing are consistent at the global level. We conducted a meta‐analysis of plant trait responses to grazing, based on 197 studies from all major regions of the world, and using six major conceptual models of trait response to grazing as a framework. Data were available for seven plant traits: life history, canopy height, habit, architecture, growth form (forb, graminoid, herbaceous legume, woody), palatability, and geographic origin. Covariates were precipitation and evolutionary history of herbivory. Overall, grazing favoured annual over perennial plants, short plants over tall plants, prostrate over erect plants, and stoloniferous and rosette architecture over tussock architecture. There was no consistent effect of grazing on growth form. Some response patterns were modified by particular combinations of precipitation and history of herbivory. Climatic and historical contexts are therefore essential for understanding plant trait responses to grazing. Our study identifies some key traits to be incorporated into plant functional classifications for the explicit consideration of grazing into global vegetation models used in global change research. Importantly, our results suggest that plant functional type classifications and response rules need to be specific to regions with different climate and herbivory history.
The Colorado Haemophilia Paediatric Joint Physical Examination Scale: normal values and interrater reliability
Authors: HACKER M. R. , FUNK S. M. , MANCO‐JOHNSON M. J.
Published: December 2006

Summary.  Persons with haemophilia often experience their first joint haemorrhage in early childhood. Recurrent bleeding into a joint may lead to significant morbidity, specifically haemophilic arthropathy. Early identification of the onset and progression of joint damage is critical to preserving joint structure and function. Physical examination is the most feasible approach to monitor joint health. Our group developed the Colorado Haemophilia Paediatric Joint Physical Examination Scale to identify earlier signs of joint degeneration and incorporate developmentally appropriate tasks for assessing joint function in young children. This study's objectives were to establish normal ranges for this scale and assess interrater reliability. The ankles, knees and elbows of 72 healthy boys aged 1 through 7 years were evaluated by a physical therapist to establish normal ranges. Exactly 10 boys in each age category from 2 to 7 years were evaluated by a second physical therapist to determine interrater reliability. The original scale was modified to account for the finding that mild angulation in the weight‐bearing joints is developmentally normal. The interrater reliability of the scale ranged from fair to good, underscoring the need for physical therapists to have specific training in the orthopaedic assessment of very young children and the measurement error inherent in the goniometer. Modifications to axial alignment scoring will allow the scale to distinguish healthy joints from those suffering frequent haemarthroses.
Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation
Authors: SALVAGNO G. L. , ASTERMARK J. , EKMAN M. , FRANCHINI M. , GUIDI G. C. , LIPPI G. , POLI G. , BERNTORP E.
Published: December 2006

Summary.  In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma‐derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:C); Haemate‐P with a ratio of 2.5:1 and Hemofil‐M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil‐M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate‐P with intermediate titres needed for inhibition of Hemofil‐M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF‐containing concentrates Fanhdi and Haemate‐P, added to FVIII‐deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil‐M and Kogenate Bayer.