bluuebunny/crossref_metadata_2025 huggingface dataset:
Crossed Cerebellar Diaschisis in Patients With Cortical Infarction
Authors: Komaba Yuichi , Mishina Masahiro , Utsumi Kouichi , Katayama Yasuo , Kobayashi Shiro , Mori Osamu
Published: January 2004

Background and Purpose—

Crossed cerebellar diaschisis (CCD) refers to reduced metabolism and blood flow in the cerebellar hemisphere contralateral to a cerebral lesion. Many cortical areas have been reported to cause CCD without consideration of confounding factors. We performed single-photon emission computed tomography (SPECT) in patients with cortical infarction to identify regions independently related to CCD, controlling for possible confounding effects.

Methods—

Patients with unilateral cortical infarction (n=113; 75 male, 38 female; mean±SD age, 66±13 years) underwent SPECT of the brain with
N
-isopropyl-p-[
123
I]iodoamphetamine (
123
I-IMP). Regional cerebral blood flow was measured autoradiographically. Asymmetry indices (AIs) were calculated on the basis of ratios representing symmetrical regional cerebral blood flow in the cerebellum and 16 cerebral regions. CCD was defined as AI for cerebellum >0.1. AIs for 16 cortical regions were considered for both dichotomous and continuous variables for analysis of CCD occurrence by means of backward logistic regression.

Results—

For dichotomized variables, hypoperfusion of postcentral (odds ratio [OR]=7.607; 95% CI, 2.299 to 25.174) and supramarginal (OR=3.916; 95% CI, 1.394 to 11.003) regions independently influenced CCD. For continuous variables, hypoperfusion of postcentral (OR=1.044; 95% CI, 1.019 to 1.068) and supramarginal (OR=1.021; 95% CI, 1.001 to 1.041) regions (and, as a negative factor, medial occipital regions; OR=0.942; 95% CI, 0.895 to 0.991) independently influenced CCD.

Conclusions—

Many cortical areas apparently do not contribute to CCD. Correspondence of CCD between dichotomized and continuous analyses suggests that location of a lesion, not severity, is the main determinant of CCD.
Noninvasive Quantification of Brain Edema and the Space-Occupying Effect in Rat Stroke Models Using Magnetic Resonance Imaging
Authors: Gerriets T. , Stolz E. , Walberer M. , Müller C. , Kluge A. , Bachmann A. , Fisher M. , Kaps M. , Bachmann G.
Published: January 2004

Background and Purpose—

Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema?

Methods—

Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared.

Results—

Interobserver and intraobserver agreements for MRI measurements were excellent (
r
≥0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (
r
≥0.95). Corrected lesion volumes correlated with
r
=0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia.

Conclusions—

Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.
Acute Basilar Artery Occlusion
Authors: Ostrem Jill L. , Saver Jeffrey L. , Alger Jeffry R. , Starkman Sidney , Leary Megan C. , Duckwiler Gary , Jahan Reza , Vespa Paul , Villablanca J. Pablo , Gobin Y. Pierre , Vinuela Fernando , Kidwell Chelsea S.
Published: January 2004

Background and Purpose—

Diffusion-perfusion MRI in patients with anterior circulation occlusions has demonstrated salvage of threatened tissue after thrombolytic therapy. Similar studies have not been reported with posterior circulation occlusions.

Methods—

Patients with acute basilar artery occlusion treated with intra-arterial thrombolytics were studied with multimodal MRI before treatment, several hours after treatment, and at day 7.

Results—

Ten patients were studied (9 men, 1 woman). Mean age was 70 years, and median pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 14. In 6 patients imaged before treatment and at day 7, mean pretreatment diffusion-weighted imaging (DWI) lesion volume was 11 cm
3
, and day 7, lesion volume was 2.6 cm
3
. Significant mismatch was visualized in all 5 patients with pretreatment perfusion-diffusion imaging (mean, 73%; range, 49% to 99%). Late imaging obtained in 4 of these 5 patients demonstrated that mean posttreatment DWI lesion volume (21 cm
3
) was less than the mean initial perfusion lesion volume (62 cm
3
). Although there was no direct correlation between pretreatment DWI volume and initial NIHSS (
r
=−0.113), there was good correlation between pretreatment perfusion-weighted imaging volume and initial NIHSS (
r
=0.72).

Conclusions—

In this first report of diffusion-perfusion MRI in patients with acute basilar artery occlusions treated with intra-arterial thrombolysis, significant mismatch was visualized on pretreatment studies, suggesting that large volumes of salvageable tissue were present. Final infarct volumes were smaller than pretreatment perfusion volumes, suggesting that substantial volumes of tissue were salvaged by thrombolytic reperfusion.
Absolute Bioavailability of Imatinib (Glivec®) Orally versus Intravenous Infusion
Authors: Peng Bin , Dutreix Catherine , Mehring Gunther , Hayes Michael J. , Ben‐Am Monique , Seiberling Michael , Pokorny Rolf , Capdeville Renaud , Lloyd Peter
Published: January 2004

The purpose of this study was to investigate the absolute bioavailability of a single oral dose of imatinib (Glivec®), 400 mg (capsules vs. oral solution), compared with imatinib, 100 mg (intravenous [i.v.] infusion), in healthy subjects. Twelve subjects received a single treatment in each treatment period: a 400‐mg oral dose of imatinib in capsule form or as a solution or a 100‐mg i.v. infusion of imatinib. Plasma imatinib concentrations were measured following each treatment; pharmacokinetic parameters and absolute bioavailability were determined. Absolute bioavailability values (compared with i.v. infusion) for the imatinib capsule and oral solution were 98.3% and 97.2%, respectively. Both the rate and extent of imatinib absorption, as measured by Cmax, partial AUC, and total AUC, were similar for the oral solution and the imatinib capsule intended for the market. The 400‐mg oral dose of imatinib, as a capsule or a solution, was completely absorbed and was almost completely bioavailable (> 97%).
Questioning a Class Effect: Does ACE Inhibitor Tissue Penetration Influence the Degree of Fibrinolytic Balance Alteration following an Acute Myocardial Infarction?
Authors: Tsikouris James P. , Suarez Jose A. , Meyerrose Gary E. , Ziska Martin , Fike David , Smith Jack
Published: January 2004

There is a common belief in a class effect among angiotensin‐converting enzyme (ACE) inhibitors. This is unsubstantiated for acute myocardial infarction (AMI). Because vascular tissue is a source of the endogenous fibrinolytic markers, and ACE inhibition in vascular tissue favorably influences the fibrinolytic system, the authors hypothesized that a high‐tissue‐penetrating ACE inhibitor would provide a more favorable reduction in plasminogen activator inhibitor‐1 (PAI‐1) and an increase in tissue plasminogen activator (t‐PA) after AMI compared to a low‐tissue‐penetrating ACE inhibitor. In a randomized open‐label trial, patients received the high‐tissue‐penetrating quinapril (n = 15) or low‐tissue‐penetrating enalapril (n = 15) immediately following an AMI. PAI‐1 and t‐PA antigen (ng/mL) were measured at baseline and through 14 days of treatment. There was no difference in baseline PAI‐1 or t‐PA antigen between treatments. PAI‐1 antigen trended toward being lower with quinapril versus enalapril on day 1 (24.44 ± 14.96 vs. 36.94 ± 19.49, respectively, p = 0.059) and was significantly lower on day 3 (17.32 ±9.57 vs. 27.49 ± 9.61, respectively, p = 0.009). Analysis of PAI‐1 antigen over time by two‐factor ANOVA with replication found significantly lower concentrations of PAI‐1 antigen over the entire treatment period with quinapril versus enalapril (p < 0.003). This investigation of ACE inhibitor tissue‐penetrating influence on markers of reinfarction risk suggests there may be a greater early reduction in PAI‐1 with a more highly tissue‐penetrating ACE inhibitor.
Tacrolimus Dosing in Adult Lung Transplant Patients Is Related to Cytochrome P4503A5 Gene Polymorphism
Authors: Zheng HongXia , Zeevi Adriana , Schuetz Erin , Lamba Jatinder , McCurry Kenneth , Griffith Bartley P. , Webber Steven , Ristich Julianne , Dauber James , Iacono Aldo , Grgurich Wayne , Zaldonis Diana , McDade Kevin , Zhang Jiong , Burckart Gilbert J.
Published: January 2004

Tacrolimus is a potent immunosuppressive agent used in lung transplantation and is a substrate for both P‐glycoprotein (P‐gp, encoded by the gene MDR1) and cytochrome (CYP) P4503A. A previous study by the authors identified a correlation between the tacrolimus blood level per dose with CYP3A5 and MDR1 gene polymorphisms in pediatric heart transplant patients. The objective of this study was to confirm the influence of these polymorphisms on tacrolimus dosing in adult lung transplant patients. Adult lung transplant patients who had been followed for at least 1 year after lung transplantation were studied. Tacrolimus blood level (ng/mL) per dose (mg/day) at 1, 3, 6, 9, and 12 months after transplantation was calculated as [L/D]. DNA was extracted from blood. MDR1 3435 CC, CT, and TT; MDR1 2677 GG, GT, and TT; and CYP3A5*1 (expressor) and *3 (nonexpressor) genotypes were determined by PCR amplification, direct sequencing, and sequence evaluation. Eightythree patients were studied. At 1, 3, 6, 9, and 12 months after the transplant, a significant difference in [L/D] was found between the CYP3A5 expressor versus nonexpressor genotypes (mean ± SD of 1.49 ± 0.88 vs. 3.11 ± 4.27, p = 0.01; 1.23 ± 0.82 vs. 3.44 ± 8.97, p = 0.05; 1.32 ± 0.96 vs. 3.81 ± 6.66, p = 0.005; 0.95 ±1.19 vs. 3.74 ±5.98, p = 0.0015; and 0.45 ± 0.2 vs. 3.76 ± 6.75, p = 0.0001, respectively). MDR1 G2677T and C3435T genotypes had only minimal effects on [L/D] at 1 and 3 months after transplantation. This study confirms the relationship of CYP3A5 polymorphisms to tacrolimus dosing in organ transplant patients. CYP3A5 expressor genotypes required a larger tacrolimus dose to achieve the same blood levels than the CYP3A5 nonexpressors at all time points during the first posttransplant year. This was not uniformly true for MDR1. The authors therefore conclude that tacrolimus dosing in adult lung transplant patients is associated with CYP3A5 gene polymorphisms.
Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol
Authors: Horn Peter A. , Keyser Kirsten A. , Peterson Laura J. , Neff Tobias , Thomasson Bobbie M. , Thompson Jesse , Kiem Hans-Peter
Published: January 2004

The use of lentiviral vectors for the transduction of hematopoietic stem cells has evoked much interest owing to their ability to stably integrate into the genome of nondividing cells. However, published large animal studies have reported highly variable gene transfer rates of typically less than 1%. Here we report the use of lentiviral vectors for the transduction of canine CD34+ hematopoietic repopulating cells using a very short, 18-hour transduction protocol. We compared lentiviral transduction of hematopoietic repopulating cells from either stem cell factor (SCF)– and granulocyte-colony stimulating factor (G-CSF)–primed marrow or mobilized peripheral blood in a competitive repopulation assay in 3 dogs. All dogs engrafted rapidly within 9 days. Transgene expression was detected in all lineages (B cells, T cells, granulocytes, and red blood cells as well as platelets) indicating multilineage engraftment of transduced cells, with overall long-term marking levels of up to 12%. Gene transfer levels in mobilized peripheral blood cells were slightly higher than in primed marrow cells. In conclusion, we show efficient lentiviral transduction of canine repopulating cells using an overnight transduction protocol. These results have important implications for the design of stem cell gene therapy protocols, especially for those diseases in which the maintenance of stem cells in culture is a major limitation.
Autoimmune anemia in macaques following erythropoietin gene therapy
Authors: Chenuaud Pierre , Larcher Thibaut , Rabinowitz Joseph E. , Provost Nathalie , Cherel Yan , Casadevall Nicole , Samulski Richard J. , Moullier Philippe
Published: January 2004

We delivered the homologous erythropoietin (Epo) cDNA driven from a doxycycline-regulated promoter via recombinant adeno-associated virus in skeletal muscle of 9 cynomolgus macaques. Upon induction, rapid supraphysiologic levels of Epo were obtained. Unexpectedly, some individuals developed a profound anemia that correlated with the appearance of neutralizing antibodies against the endogenous Epo. Both the endogenous erythropoietin and vector sequences were identical. This is the first example of the inadvertent development of an autoimmune disease in primates as a result of gene transfer of a gene expressing a self-antigen. It raises some concerns when a therapeutic protein is produced at high levels from an ectopic site. (Blood. 2004;103:3303-3304)
Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma
Authors: Kewalramani Tarun , Zelenetz Andrew D. , Nimer Stephen D. , Portlock Carol , Straus David , Noy Ariela , O'Connor Owen , Filippa Daniel A. , Teruya-Feldstein Julie , Gencarelli Alison , Qin Jing , Waxman Alyson , Yahalom Joachim , Moskowitz Craig H.
Published: January 2004

Patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) who achieve complete response (CR) before autologous stem cell transplantation (ASCT) generally have better outcomes than those who achieve only partial response (PR). We investigated whether adding rituximab to the ifosfamide-carboplatin-etoposide (ICE) chemotherapy regimen (RICE) could increase the CR rate of patients with DLBCL under consideration for ASCT. Thirty-six eligible patients were treated with RICE, and 34 received all 3 planned cycles. The CR rate was 53%, significantly better than the 27% CR rate (P = .01) achieved among 147 similar consecutive historical control patients with DLBCL treated with ICE; the PR rate was 25%. Febrile neutropenia was the most frequent grade 3 or 4 nonhematologic toxicity; it occurred in 7.5% of delivered cycles. No patient had RICE-related toxicity that precluded ASCT. The median number of CD34+ cells per kilogram mobilized was 6.3 × 106. Progression-free survival rates of patients who underwent transplantation after RICE were marginally better than those of 95 consecutive historical control patients who underwent transplantation after ICE (54% vs 43% at 2 years; P = .25). RICE appears to induce very high CR rates in patients with relapsed and refractory DLBCL; however, further studies are necessary to determine whether this treatment regimen will improve outcomes after ASCT.
A fungal multicopper oxidase restores iron homeostasis in aceruloplasminemia
Authors: Harris Z. Leah , Davis-Kaplan Sandra R. , Gitlin Jonathan D. , Kaplan Jerry
Published: January 2004

Mutations that lead to a loss of the copper-containing plasma enzyme ceruloplasmin disrupt mammalian iron homeostasis. The mechanism by which ceruloplasmin mobilizes iron from cell stores has been controversial. We demonstrate that injection of a soluble copper-containing yeast protein Fet3p can restore iron homeostasis in phlebotomized mice with a deletion of the ceruloplasmin gene. These results show the conservation of function of copper-containing proteins in eukaryotic iron metabolism. (Blood. 2004;103:4672-4673)
PU.1 determines the self-renewal capacity of erythroid progenitor cells
Authors: Back Jonathan , Dierich Andrée , Bronn Corinne , Kastner Philippe , Chan Susan
Published: January 2004

PU.1 is a hematopoietic-specific transcriptional activator that is absolutely required for the differentiation of B lymphocytes and myeloid-lineage cells. Although PU.1 is also expressed by early erythroid progenitor cells, its role in erythropoiesis, if any, is unknown. To investigate the relevance of PU.1 in erythropoiesis, we produced a line of PU.1-deficient mice carrying a green fluorescent protein reporter at this locus. We report here that PU.1 is tightly regulated during differentiation—it is expressed at low levels in erythroid progenitor cells and down-regulated upon terminal differentiation. Strikingly, PU.1-deficient fetal erythroid progenitors lose their self-renewal capacity and undergo proliferation arrest, premature differentiation, and apoptosis. In adult mice lacking one PU.1 allele, similar defects are detected following stress-induced erythropoiesis. These studies identify PU.1 as a novel and critical regulator of erythropoiesis and highlight the versatility of this transcription factor in promoting or preventing differentiation depending on the hematopoietic lineage.
Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder
Authors: Gris Jean-Christophe , Mercier Eric , Quéré Isabelle , Lavigne-Lissalde Géraldine , Cochery-Nouvellon Eva , Hoffet Médéric , Ripart-Neveu Sylvie , Tailland Marie-Laure , Dauzat Michel , Marès Pierre
Published: January 2004

The prospective evaluation of the effect of thromboprophylaxis in women with one unexplained pregnancy loss from the 10th week of amenorrhea was performed. A total of 160 patients with heterozygous factor V Leiden mutation, prothrombin G20210A mutation, or protein S deficiency were given 5 mg folic acid daily before conception, to be continued during pregnancy, and low-dose aspirin 100 mg daily or low-molecular-weight heparin enoxaparin 40 mg was taken from the 8th week. Twenty-three of the 80 patients treated with low-dose aspirin and 69 of the 80 patients treated with enoxaparin had a healthy live birth (odds ratio [OR], 15.5; 95% confidence interval [CI], 7-34, P < .0001). Enoxaparin was superior to low-dose aspirin in each subgroup defined according to the underlying constitutional thrombophilic disorder. An associated protein Z deficiency and/or positive antiprotein Z antibodies were associated with poorer outcomes. The neonate weight was higher in the women successfully treated with enoxaparin, and neonates small for gestational age were more frequent in patients treated with low-dose aspirin. No significant side effects of the treatments could be evidenced in patients or newborns. As there is no argument to prove that low-dose aspirin may have been deleterious, these results support enoxaparin use during such at-risk pregnancies.
Activation of phosphatidylinositol 3-kinase and c-Jun-N-terminal kinase cascades enhances NF-κB-dependent gene transcription in BCG-stimulated macrophages through promotion of p65/p300 binding
Authors: Darieva Zoulfia , Lasunskaia Elena B , Campos Mariana N N , Kipnis Thereza L , da Silva Wilmar D
Published: January 2004

The proinflammatory response of infected macrophages is an important early host defense mechanism against mycobacterial infection. Mycobacteria have been demonstrated to induce proinflammatory gene transcription through the Toll-like receptors, (TLR)2 and TLR 4, which initiate signaling cascades leading to nuclear factor (NF)-κB activation. The main transduction pathway responsible for NF-κB activation has been established and involves the MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor-6, NF-κB-inducing kinase, and inhibitor of κB kinase complex. The role of other kinase cascades triggered by mycobacteria in the NF-κB activation is less clear. We herein examine the role of the mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI-3K) cascades in the expression of the bacillus Calmette-Guerin (BCG) mycobacteria-induced NF-κB-dependent genes, macrophage-inflammatory protein-2 (MIP-2) and inducible nitric oxide (NO) synthase. Specific pharmacological inhibition of the PI-3K, c-jun-N-terminal kinase (JNK), and to a smaller extent, p38 MAPK but not extracellular-regulated kinase (ERK), suppressed NF-κB-dependent reporter gene transcription and MIP-2 and NO secretion in BCG-induced RAW264.7 macrophages. A similar effect was obtained following molecular inhibition of JNK via JNK-interacting protein-1 overexpression. In addition, a kinase-dead mutant of MEK kinase-1, the up-stream regulator of JNK, also proved to be a potent inhibitor of NF-κB-reporter activity. The effect of inhibitors was mediated by the down-regulation of NF-κB transcription activity and without effecting its nuclear translocation. These data suggest an indirect mechanism of the NF-κB regulation by these kinases, probably through p65 phosphorylation and improved binding to the p300 transcription coactivator. The data obtained demonstrate that PI-3K, JNK, and p38 MAPK activation by mycobacteria enhance NF-κB-driven gene expression contributing to the proinflammatory macrophage response.
Soluble Jagged-1 is able to inhibit the function of its multivalent form to induce hematopoietic stem cell self-renewal in a surrogate in vitro assay
Authors: Vas Virág , Szilágyi László , Pálóczi Katalin , Uher Ferenc
Published: January 2004

Stem cells reside in customized microenvironments (niches) that contribute to their unique ability to divide asymmetrically to give rise to self and to a daughter cell with distinct properties. Notch receptors and their ligands are highly conserved and have been shown to regulate cell-fate decisions in multiple developmental systems through local cell interactions. To assess whether Notch signaling may regulate hematopoiesis to maintain cells in an immature state, we examined the functional role of the recombinant, secreted form of the Notch ligand Jagged-1 during mouse hematopoietic stem cell (HSC) and progenitor cell proliferation and maturation. We found that ligand immobilization on stromal layer or on Sepharose-4B beads is required for the induction of self-renewing divisions of days 28–35 cobblestone area-forming cell. The free, soluble Jagged-1, however, has a dominant-negative effect on self-renewal in the stem-cell compartment. In contrast, free as well as immobilized Jagged-1 promotes growth factor-induced colony formation of committed hematopoietic progenitor cells. Therefore, we propose that differences in Jagged-1 presentation and developmental stage of the Notch receptor-bearing cells influence Notch ligand-binding results toward activation or inhibition of downstream signaling. Moreover, these results suggest potential clinical use of recombinant Notch ligands for expanding human HSC populations in vitro.
Wavefield interpolation in the Fourier wavefield extrapolation
Authors: Fu Li‐Yun
Published: January 2004

The computational cost for seismic migration relies heavily on the methods used for wavefield extrapolation. In general, seismic migration by current industry techniques extrapolates wavefields through a thick slab and then interpolates wavefields in small layers inside the slab. In this paper, I first optimize practical implementation of the Fourier wavefield extrapolation. I then design three interpolation algorithms: Fourier transform, Kirchhoff, and Born‐Kirchhoff for mild, moderate, and large to strong lateral heterogeneities, respectively. The Fourier transform interpolation simultaneously implements wavefield interpolation and imaging without needing to invoke the imaging principle by summing over all frequency components of the interpolated wavefield. The Kirchhoff interpolation is based on the traditional Kirchhoff migration formula and is performed by diffraction summation with a very limited aperture using the average velocity of a laterally heterogeneous slab. The Born‐Kirchhoff interpolation is based on the Lippmann‐Schwinger integral equation. It differs from the Kirchhoff interpolation in that it accounts not only for the obliquity, spherical spreading, and wavelet shaping factors but also for the relative slowness perturbation in a laterally heterogeneous slab. Recursive seismic migration usually accounts for a 20‐ to 40‐ms depth size for wavefield extrapolation in practical applications. Using the above interpolation techniques, Fourier depth migration methods are shown to tolerate a 40‐ to 60‐ms depth size with the SEG/EAGE salt model. Therefore, the Fourier depth migration techniques with thick‐slab extrapolation plus thin‐slab interpolation can be used to image structures with salt‐related complexes.
Holocene environmental change: contributions from the peatland archive
Authors: Chambers Frank M. , Charman Dan J.
Published: January 2004

Peatlands provide a widespread terrestrial archive of Holocene environmental change. The taphon omy of peat is relatively simple, the range of evidence and proxies is wide, and dating methods have become more accurate and precise, such that the potential temporal resolution of records is high. Although long estab lished, the use of peatlands as archives of Holocene change has undergone phases of decline and resurgence. Here, the variable exploitation of the peat archive is explored, and recent developments in peatland science as applied to Holocene records are reviewed with reference to the collection of papers in this Special Issue of The Holocene, which are arranged in four key themes: (1) records of Holocene climatic change; (2) peatland dynamics; (3) carbon accumulation; and (4) implications for conservation and management. The changing acceptance of peatlands as archives of Holocene climatic change is attributed to developments in understanding of the peatland system and geographical differences in the history of Holocene research. Recent developments in biological and geochemical proxies combined with improvements in chronological techniques have resulted in renewed interest in peatland palaeoclimate records. Peatlands are an important global carbon pool and it is clear that climate has influenced the efficiency of long-term carbon sequestration by these systems. Climate has also had an impact on the biodiversity and condition of peatlands, which creates problems in discerning cause and effect in sites affected by human activities, and in targeting remedial management. It is concluded that particular strengths of the archive are the current diversity of peat-based palaeoenvironmental research and the potential for multiproxy analyses to be applied to a range of research issues. Mire-based investigations can complement research in other realms, and are deserving of greater attention from researchers of other archives.
A Late-glacial and Holocene record of climatic change from a Swiss peat humification profile
Authors: Roos-Barraclough Fiona , van der Knaap W. O. , van Leeuwen J. F.N. , Shotyk W.
Published: January 2004

Colorimetric measurements of alkaline extracts from two Swiss peat cores have provided a complete 14500-year-long record of peat humification, a proxy of effective precipitation. Peat from the cold Younger Dryas (11050–9550 cal. bc) was well preserved despite low levels of precipitation. A particularly dry period, peaking at c. 7100 cal. bc, is indicated by well-decomposed peat. Peat from c. 6750–4250 cal. bc shows a low degree of decomposition, indicating a wet bog surface despite relatively warm temperatures and therefore indicating high levels of precipitation. A sharp transition to higher levels of decomposition c. 4450–3750 cal. bc indicates a major transition to a drier bog surface. Subsequently, peat humification generally decreases towards the end of the deeper profile (c. cal. ad 1050), indicating a gradual return to wetter conditions. This gradual decrease is punctuated by periods of particularly low humification which appear to be due to shifts to higher levels of effective precipitation from c. 2500 to 1350 cal. bc, c. 1050 to 550 cal. bc, centered around 150 cal. bc, and from c. cal. ad 550 onwards. Anthropogenic influences appear to have affected peat humification at the site at least since the Middle Ages. This study indicates that humification in colder regions/time periods could be more affected by temperature than precipitation and vice versa.
Snapshots in time: precise correlations of peat-based proxy climate records in Scotland using mid-Holocene tephras
Authors: Langdon P. G. , Barber K. E.
Published: January 2004

Mid-Holocene tephra layers have been located and geochemically analysed from seven ombrotrophic bogs in Scotland. The tephras found in these Scottish peats occur as stratigraphically discrete horizons, not visible to the naked eye, and originate from volcanic activity in Iceland. Identifying and geochemically typing the tephra layers can enable precise correlations between sites on regional scales, depending on the spatial extent of the airfall events. Dispersal of both the Glen Garry and Hekla-4 tephras is excellent over Scotland, enabling snapshot views of the past at the time of these tephra depositions. Palaeoecological analyses have also been undertaken on these bogs, providing detailed reconstructions of past changes in bog vegetation and surface wetness, a proxy for past climates. Correlations between the ombrotrophic bogs at the time of the Glen Garry tephra revealed significant differences between the proxy climate records in the north and the south of Scotland, suggesting asynchronous changes between northern Scotland and the rest of Great Britain.
Solar forcing of climatic change during the mid-Holocene: indications from raised bogs in The Netherlands
Authors: Blaauw Maarten , van Geel Bas , van der Plicht Johannes
Published: January 2004

Two cores of mid-Holocene raised-bog deposits from the Netherlands were 14C wiggle-match dated at high precision. Changes in local moisture conditions were inferred from the changing species composition of consecutive series of macrofossil samples. Several wet-shifts were inferred, and these were often coeval with major rises in the Δ14C archive (probably caused by major declines in solar activity). The use of Δ14C as a proxy for changes in solar activity is validated. This paper adds to the increasing body of evidence that solar variability forced climatic changes during the Holocene.
Changes in solar activity and Holocene climatic shifts derived from 14C wiggle-match dated peat deposits
Authors: Mauquoy Dmitri , van Geel Bas , Blaauw Maarten , Speranza Alessandra , van der Plicht Johannes
Published: January 2004

Closely spaced sequences of accelerator mass spectrometer (AMS) 14C dates of peat deposits display century-scale wiggles which can be fitted to the radiocarbon calibration curve. By wiggle-matching such sequences, high-precision calendar age chronologies can be generated which show that changes in mire surface wetness during the Bronze Age/Iron Age transition (c. 850 cal. BC) and the ‘Little Ice Age’ (Wolf, Spörer, Maunder and Dalton Minima) occurred during periods of suddenly increasing atmospheric concentration of 14C. Replicate evidence from peat-based proxy climate indicators in northwest Europe suggest these changes in climate may have been driven by temporary declines of solar activity. Carbon-accumulation rates of two raised peat bogs in the UK and Denmark record low values during the ‘Little Ice Age’ which reflects reduced primary productivity of the peat-forming vegetation during these periods of climatic deterioration.
Complex hydroseral vegetation succession and ‘dryland’ pollen signals: a case study from northwest Scotland
Authors: Bunting M. Jane , Tipping Richard
Published: January 2004

Pollen assemblages from sediment systems developed in response to changing sea level provide potentially valuable archives of local landscape dynamics in the coastal zone. Changes in wetland vegetation structure associated with the successional transition from saline to freshwater communities, and subsequent terrestrialization, however, will have marked effects on the palynological signal from surrounding dry land communities by altering the taphonomic properties of the pollen-recruiting system. We present data from one such system, a coastal wetland on the Coigach Peninsula in northwest Scotland, focusing here on reconstructing the hydroseral processes of wetland development, and how they affect the interpretation of the dry pollen signal. This contribution highlights the often-unacknowledged ambiguities inherent in reconstructing past environments from complex sedimentary systems, and outlines strategies for clarifying them.
Contrasting pathways to ombrotrophy in three raised bogs from Ireland and Cumbria, England
Authors: Hughes P. D. M. , Barber K. E.
Published: January 2004

The plant macrofossil records from three raised bogs from western and central Ireland and from Cumbria were compared to investigate variations in the character and timing of the fen-bog transition (FBT). Two modes of raised or ombrotrophic peat formation were recognized. In the first mode the transition develops through a sedge-fen stage directly to raised-bog lawn, maintaining a near surface water table throughout the FBT (Abbeyknockmoy Bog). The second mode is characterized by a switch from fen or reedswamp to a dry Eriophorum-dominated mire type, suggestive of low or unstable water tables (Mongan Bog and Bolton Fell Moss). Comparisons with the Holocene effective precipitation record suggest that the type of transition and its timing may be affected by the prevailing climate regime. All that is required for ombrotrophy is a separation of the growing peat surface from the influence of ground and surface waters. This separation may be achieved by rapid peat accumulation in a moist climate, the accumulation of decay-resistant Eriophorum vaginatum hummocks or by a lowering of the water table, leading to a ‘perched peat bed’. In the latter two cases, a ‘pseudo-raised bog’ community often persists, laying down highly humified peat, until increased oceanicity enables Sphagnum to dominate.
Mire ontogeny, environmental and climatic change inferred from fossil beetle successions from Hatfield Moors, eastern England
Authors: Whitehouse Nicki J.
Published: January 2004

Results of a fossil Coleoptera (beetle) fauna from a fen edge sequence from Hatfield Moors, Humber-head Levels, England, are presented. Mire ontogeny inferred from this location and others are discussed, particularly in the light of previous palynological and plant macrofossil investigations. Peat initiation across most of the site centres around 3000 cal. bc, characterized by a Calluna- Eriophorum heath with areas of PinusBetula woodland. The onset of peat accumulation on the southern margins of the site was delayed until 1520– 1390 cal. bc and appears to overlap closely with a recurrence surface at a pollen site (HAT 2) dated to 1610– 1440 cal. bc, suggesting that increased surface wetness may have caused mire expansion at this time. The faunas illustrate the transition from eutrophic and mesotrophic fen to ombrotrophic raised mire, although the significance of both Pinus- and Calluna-indicating species through the sequence suggests that heath habitats may have continued to be important. Elsewhere, this earlier phase of rich fen is lacking and mesotrophic mire developed immediately above nutrient-poor sands, with ombrotrophic conditions indicated soon after. Correspondence analysis of the faunas provides valuable insights into the importance of sandy heath habitats on Hatfield Moors. The continuing influence of the underlying coversands suggests these may have been instrumental in mire ontogeny. The research highlights the usefulness of using Coleoptera to assess mire ontogeny, fluctuations in site hydrology and vegetation cover, particularly when used in conjunction with other peatland proxies. The significance of a suite of extinct beetle species is discussed with reference to forest history and climatic change.
Mineral deficiency and the presence of Pinus sylvestris on mires during the mid- to late Holocene: palaeoecological data from Cadogan's Bog, Mizen Peninsula, Co. Cork, southwest Ireland
Authors: Mighall T. M. , Lageard J. G. A. , Chambers F. M. , Field M. H. , Mahi P.
Published: January 2004

Pollen records across parts of Ireland, England and northern Scotland show a dramatic collapse in Pinus pollen percentages at approximately 4000 radiocarbon years BP. This phenomenon has attracted much palaeoecological interest and several hypotheses have been put forward to account for this often synchronous and rapid reduction in pine from mid-Holocene woodland. Explanations for the ‘pine decline’ include prehistoric human activity, climatic change, in particular a substantial increase in precipitation resulting in increased mire wetness, and airborne pollution associated with the deposition of tephra. Hitherto, one largely untested hypothesis is that mineral deficiency could adversely affect pine growth and regeneration on mire surfaces. The discovery of pine-tree remains (wood pieces, stumps and trunks) within a peat located at Cadogan's Bog on the Mizen Peninsula, southwest Ireland, provided an opportunity to investigate the history of Pinus sylvestris and also to assess the importance of mineral nutrition in maintaining pine growth on mires. Pollen, plant macrofossils, microscopic charcoal and geochemical data are presented from a radiocarbon dated monolith extracted from this peat together with tree ring-width data and radiocarbon dated age estimates from subfossil wood. Analyses of these data suggest that peat accumulation commenced at the site around 6000 years BP when pine was the dominant local tree. Thereafter Pinus pollen percentages diminish in two stages, with the second decline taking place around 4160 6 50 years BP. Concomitant with this decline in Pinus pollen, there is a noticeable, short-lived increase in wet-loving mire taxa and a decrease in the concentration of phosphorus, potassium, magnesium, calcium, sodium, iron and zinc. These results suggest that increased mire surface wetness, possibly the result of a change in climate, created conditions unsuitable for pine growth c. 4000 years BP. Mire surface wetness, coupled with a period of associated nutrient deficiency, appears to be a possible explanation for a lack of subsequent pine-seedling establishment for most of the later Holocene.
Input rates, decay losses and accumulation rates of carbon in bogs during the last millennium: internal processes and environmental changes
Authors: Malmer Nils , Wallén Bo
Published: January 2004

In peatlands the balance between litter input and decay loss in the oxic acrotelm determines the rate of carbon input to the anoxic catotelm with carbon lost at very slow rate. In the acrotelm the C/N-quotient decreases with depth and indicates the loss of carbon from the acrotelm. On one boreo-nemoral and three subalpine ombrotrophic bogs in Sweden the carbon losses in the acrotelm plus the apparent carbon-accumu lation rates in the catotelm for the last millennium revealed a constant carbon-sequestering rate up to the end of the nineteenth century equalling that in recent Sphagnum-dominated communities. On the boreo-nemoral bog the carbon-accumulation rate in the catotelm decreased by 50% over the same period while it remained constant on the subalpine bogs. A catotelm with permafrost may have provided more constant conditions for the carbon accumulation than a rising water level creating anoxic conditions. Due to vegetation changes, the recent carbon sequestering in the peat-forming communities is lower than previously and only just enough to compensate for the integrated losses. It is argued that because of internal processes the bogs up to the end of the nineteenth century had obtained or were approaching a steady-state with regard to the carbon input to the catotelm and the supply of mineral nutrients. In contrast, an increased climatic humidity around 1000 cal. BP resulted in high carbon-accumulation rates in the boreo-nemoral bog. Climate could have triggered the recent vegetation changes, but an increased nitrogen deposition is also a probable reason.
Mud-bottom hollows: exceptional features in carbon-accumulating bogs?
Authors: Karofeld Edgar
Published: January 2004

Mud-bottom hollows are depressions on the bog surface where Sphagnum mosses have died and peat accumulation is retarded or even replaced with loss by oxidation. Results of measurements carried out at Männikjärve Bog, central Estonia, con” rmed that peat accumulation has stopped and that in 1999–2001 the uppermost 2–3 cm thick surface layer of mud-bottom hollows became thinner by 1.95 6 0.75 mm yr21 (n = 188). Different methods revealed the corresponding carbon loss from the mud-bottom hollows 25 mm thick surface layer as 50–60 g C m22 yr21. As a result, the surface of mud-bottom hollows becomes lower as compared to surroundings with peat accumulation c. 1.5 mm yr21, and they are likely to have an important role in the differentiation of bog microtopography. Owing to the combination of a cessation in peat accumu lation, carbon loss by oxidation and increased emission of decomposition gases, mud-bottom hollows could have an important in‘ uence on the carbon budget of bogs.
High-resolution peatland water-table changes for the past 200 years: the influence of climate and implications for management
Authors: Hendon Dawn , Charman Dan J.
Published: January 2004

Management of peatlands for conservation purposes is often directed at mitigation of damaging impacts of past and present human activity. Assessment of such impacts is often based on perspectives from short-term ecological data. Here we test a series of hypotheses for the causes of changes in mire hydrology and vegetation on the Border Mires in northern England using palaeoecological data for the last 200 years. Ecological data suggest peatlands surrounded by plantation forestry have become drier over the last 40 years. This could be caused by direct hydrological impacts of the growing trees and associated drainage or indirectly by the cessation of grazing and burning. A third hypothesis is that hydrological changes are the result of recent climatic change. High-resolution water-table reconstructions from testate amoebae analysis supported by plant macrofossil analysis and dated by 210Pb, spheroidal carbonaceous particles (SCPs) and pollen data demonstrate that a site outside the direct in‘ uence of forestry has also become drier during the twentieth century. This suggests that forestry is not the main cause of changes observed on other sites. Water-table declines began earlier than the main phase of forest planting and the magnitude of change appears to be similar to that on a site within the forest. Subjective comparisons of reconstructed water tables with meteorological data suggest that hydrological changes on the mires are primarily driven by summer temperature changes. If future regional climatic change predictions are correct, further water-table decline will follow and current management activities are unlikely to restore mires to their former condition.
The conservation management value of testate amoebae as ‘restoration’ indicators: speculations based on two damaged raised mires in northwest England
Authors: Davis S. R. , Wilkinson D. M.
Published: January 2004

The ideas behind peatland restoration and the utility of testate amoebae in informing such schemes are brie‘ y reviewed and discussed in the context of two lowland raised-mire sites in northwest England (Astley Moss, part of the Chat Moss complex in Greater Manchester, and Danes Moss, Cheshire). Our study indicates a high degree of correspondence between the sites in their response to major documented climatic deteriorations during the last five millennia. In particular, the c. 2300 BP event appears to correspond with greatly increased water-table ‘ uctuation at both sites and pronounced declines in characteristic mire taxa of testate amoebae. These do not regain their former dominance save for a brief episode at c. 300 BP affecting both sites. Despite some restoration attempts at both sites, testate assemblages bear little resemblance to what might be considered a typical mire assemblage and do not appear to have done so with any degree of stability for c. 2500 years. This raises important issues regarding the practicability and suitability of such sites for large-scale restoration attempts and the range of conditions that can be considered natural for such sites; these questions should form the basis of future research.
Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a
Authors: Yoshitomi Hideyuki , Zaret Kenneth S.
Published: January 2004

Dorsal and ventral pancreatic bud development from the endoderm requires inductive interactions with diverse mesodermal cell types and the action of transcription factors expressed within the endoderm. Presently it is unclear which mesodermal interactions activate which pancreatic transcription factors,and whether such inductions are common for initiating dorsal and ventral pancreas development. Previous studies of Lammert et al. (Lammert, E.,Cleaver, O. and Melton, D. (2001) Science 294, 564-567) showed that signaling from embryonic blood vessel cells, derived from the mesoderm,promotes pancreatic bud development. Using a combination of mouse Flk1-/- embryos lacking endothelial cells and tissue recombination experiments, we discovered that the initial induction of dorsal endoderm cells positive for the pancreatic and duodenal transcription factor Pdx1 does not require aorta or endothelial cell interactions, but dorsal pancreatic bud emergence and the maintenance of Pdx1 expression does. Aortal endothelial cells induce the crucial pancreatic transcription factor Ptf1a in the dorsal pancreatic endoderm; whereas the vitelline veins, which are normally adjacent to the emerging ventral pancreatic bud, are unnecessary for ventral Ptf1a induction or for ventral pancreatic bud initiation. We find that the aorta cells themselves, apart from the blood supply, cause the induction of Ptf1a in dorsal endoderm explants. Thus, endothelial cell interactions specifically promote early dorsal pancreatic development, at least in part, by inducing Ptf1a+ pancreatic progenitors. Additionally, we find that endothelial cells are necessary for the induction of both the insulin and glucagon genes.
Mili, a mammalian member ofpiwifamily gene, is essential for spermatogenesis
Authors: Kuramochi-Miyagawa Satomi , Kimura Tohru , Ijiri Takashi W. , Isobe Taku , Asada Noriko , Fujita Yukiko , Ikawa Masahito , Iwai Naomi , Okabe Masaru , Deng Wei , Lin Haifan , Matsuda Yoichi , Nakano Toru
Published: January 2004

The piwi family genes, which are defined by conserved PAZ and Piwi domains, play important roles in stem cell self-renewal, RNA silencing, and translational regulation in various organisms. To reveal the function of the mammalian homolog of piwi, we produced and analyzed mice with targeted mutations in the Mili gene, which is one of three mouse homologs of piwi. Spermatogenesis in the MILI-null mice was blocked completely at the early prophase of the first meiosis, from the zygotene to early pachytene, and the mice were sterile. However, primordial germ cell development and female germ cell production were not disturbed. Furthermore,MILI bound to MVH, which is an essential factor during the early spermatocyte stage. The similarities in the phenotypes of the MILI- and MVH-deficient mice and in the physical binding properties of MILI and MVH indicate a functional association of these proteins in post-transcriptional regulation. These data indicate that MILI is essential for the differentiation of spermatocytes.