bluuebunny/crossref_metadata_2025 huggingface dataset:
Scottish Missionaries and African Healers: Perceptions and Relations in The Livingstonia Mission, 1875-1930
Authors: Hokkanen Markku
Published: August 2004

This paper examines Scottish missionary perceptions of African healers, and the relationships between the missionaries and local healers in what is now Northern Malawi during the late nineteenth and early twentieth centuries. Analysing the Livingstonia missionary writings from the missionary doctor Walter Elmslie to the popular missionary author Donald Fraser and the amateur anthropologist T. Cullen Young, it is argued that, despite major differences and changes in the missionaries' perceptions regarding African healers, there were also important continuities. The paper also examines in detail the relationships between Elmslie and the family of African healer Kalengo Tembo. It is argued that the careful study of missionary writings, even blatant missionary propaganda, can offer novel insights not only into missionary discourse, but also into the historical interaction between Africans and missionaries in the field of medicine and healing.
The Interface of Christianity and Conservation in Colonial Malawi, C. 1850-1930
Authors: Mulwafu Wapulumuka
Published: August 2004

The study of the relationship between religion and the environment in Malawi has only recently begun to be appreciated. Christian missionaries in general did not actively promote the campaign for conservation of resources but some early missionaries frequently evoked biblical images and ideas that had a strong bearing on the perception and management of the environment. Later, certain religious groups were vocal in their support for or opposition to state-sponsored conservation schemes in the colonial period. This paper demonstrates that African religious beliefs and customs equally played a critical role in creating a set of ideas about conservation and the environment. The study is part of an effort to recover some early voices promoting conservation of natural resources in the country. It thus addresses the issues of religion and conservation as critical in the initial encounter between Europeans and Africans.
'Sekukuni, Listen!, Banna!, and to The Children of Frederick the Great and Our Kaiser Wilhelm': Documents in The Social and Religious History Of The Transvaal, 1860-1890
Authors: Rüther Kirsten
Published: August 2004

Encountering colonialism and Christianity, African people became intertwined with the development of a documentary culture in the Northern Transvaal. In the second half of the nineteenth century Africans, missionaries and settlers produced and read Bibles, codes of law, newspaper articles, translations of religious texts and church declarations. As a result of multifaceted social interaction, African people's attitudes were never an exclusively African business. The article shows how certain peoples cherished the technical skills of reading and writing, while others defined literacy as a subordinate instrument employable only for the attainment of religious goals. It argues that especially missionaries' and Africans' attitudes towards documents changed as a response to the broader economic and social transformations in the area. It also points out how the new Christian elite tried to use literacy as a window to the European reading public and how they produced documents of their own in which they ixed important parameters of African Christianity.
Crossing Boundaries and Building Bridges: The Anglican Women's Fellowship In Post-apartheid South Africa
Authors: Gaitskell Deborah
Published: August 2004

In the late 1960s, the South African Anglican Church set up a new women's organisation, the Anglican Women's Fellowship (AWF). With strong roots in the Cape and Natal, the AWF aimed to be more inclusive of all churchwomen than the international Mothers' Union (MU) where, at that time, membership was still closed to divorcees and unmarried mothers. MU locally had also become an African stronghold, which may have reinforced the qualms of white and Coloured women about joining. Based on some documentary sources and participation in the fourday AWF Provincial Council of October 2002, this paper explores the changing composition, goals and ethos of AWF over its 35-year history. Comparisons with other churchwomen's organisations—the (black) Methodist Manyano and (white) Women's Auxiliary as well as the MU—will be drawn to highlight what is distinctive about AWF and its response to social change in contemporary South Africa. While the article concludes by providing a brief snapshot of theology and practice within the movement, the striking current role of Coloured women leaders as bridge-builders is particularly emphasised and the effective crossing of racial, social, language and age boundaries evaluated.
Max Yergan Encounters South Africa: Theological Perspectives On Race
Authors: Anthony David Henry
Published: August 2004

While scholarship on the missionary encounter with Southern Africa has grown ever more sophisticated over the last decade, with a few notable exceptions scholars have tended to ignore religious traditions other than those of the 'historic' European churches. This paper sheds light upon one such overlooked tradition, that of the African-American sojourner Max Yergan (1892-1975), who worked in South Africa between 1922 and 1936 under the auspices of the North American YMCA. While he is known generally as a public figure who subsequently exerted influence upon a surprisingly broad range of political actors and events in and beyond South Africa, little has been written about a body of texts that help to reveal the evolution of his social thought and practice in South Africa. For nearly fifteen years Yergan left behind a trail of writings (which hitherto have not been explored) in local and overseas publications, together with numerous rich caches of correspondence, and inspired reportage in YMCA, Student Christian Association (SCA), African training school and mission periodicals. Much of this work was religiously inspired, and theological or missiological in content. Representative examples of this oeuvre are here deployed to provide a sense of Yergan's worldview, its relationship to his South African mission and his later career outside of it.
Themes and Methods in the Study Of Conversion in Ethiopia: a Review Essay
Authors: Kaplan Steven
Published: August 2004

Although conversion is one of the major themes in the religious and cultural history of Ethiopia, it has yet to benefit from extensive and systematic comparative discussion. For generations, scholars have worked to deepen our understanding of conversion to both Orthodox Christianity and Islam in the Ethiopian highlands. Recent works, moreover, are noteworthy for their efforts to expand our knowledge of both regions and groups hitherto neglected. Modern Islam, Evangelical Christianity and the religious histories of the peoples of Southern Ethiopia are only a few of the topics that have benefited from scholarship during the past decade. We are, therefore, in an unprecedented position to offer a review of research which, while by no means comprehensive, at least offers broader coverage than was previously possible.
Microstructures and properties of laser/arc hybrid welds and autogenous laser welds in pipeline steels
Authors: Moore P.L. , Howse D.S. , Wallach E.R.
Published: August 2004

Lasers are capable of producing welds with deep penetration, low distortion and faster travel speeds, compared to arc welding. More recently, laser/arc hybrid welding processes have also been generating interest for industrial fabrication. In this paper, six carbon–manganese, mainly pipeline, steels were welded using both autogenous Nd:YAG laser welding, and Nd:YAG laser/MAG hybrid welding. The improvements in weld microstructures and weld metal toughness that are possible when using the hybrid process are described and illustrated. Laser/arc hybrid welding is shown to be a process that can generate good quality welds in commercially available pipeline steels. It also has the potential to complete girth welds in these steels with significantly fewer welding passes than are currently required for arc welded pipelines, reducing the joint completion time.
Viscoplastic behaviour of steels during welding
Authors: Bergheau J.-M. , Vincent Y. , Leblond J.-B. , Jullien J.-F.
Published: August 2004

In most numerical simulations of welding, viscoplastic phenomena are neglected, because of shortness of the process. The aim of this paper is to accurately assess the effect of such phenomena upon predicted residual stresses and distortions, through comparison of simulations using both elastic–plastic and elastic–viscoplastic constitutive laws, and experiments. These experiments are performed on a mock-up developed at INSA Lyon and especially designed for the study of the material behaviour in the heat affected zone of a welded component; this mock-up is sufficiently simple to allow for cheap 2D axisymmetric simulations, but nevertheless complex enough to represent a real welded structure, albeit in a schematic way. It is found that incorporation of viscous effects into the description of the material behaviour has a marginal influence upon predicted residual stresses but a significant one upon predicted residual distortions, which agree much better with measured ones when viscous effects are accounted for.
Transient liquid phase bonding
Authors: Gale W.F. , Butts D.A.
Published: August 2004

A review of the transient liquid phase (TLP) bonding process is presented in this paper. This review concentrates on the mechanisms of the TLP process, including both microstructural development and wettability aspects. However, design related issues and engineering applications are also considered. The paper explains how the TLP bonding process offers the potential for producing joints with microstructures and hence mechanical properties that are similar to those of the parent materials. The process of isothermal solidification is discussed at some length. The paper considers the ways in which specific microstructural features of the substrate material–interlayer material combination influence microstructural development. A distinction is drawn between cases where the progression of isothermal solidification dominates the final microstructure and those where events occurring after the completion of isothermal solidification are paramount. The paper describes the practical limitations on the production of parent-metal-like microstructures and the complexity of microstructural development in real materials, especially where dissimilar substrates are involved. Modification of the TLP bonding process to accommodate cases of limited solid solubility and/or low diffusion coefficients is discussed.
Expression of SMRTβ promotes ligand-induced activation of mutated and wild-type retinoid receptors
Authors: Côté Sylvie , McNamara Suzan , Brambilla Daria , Bianchini Andrea , Rizzo Giovanni , del Rincón Sonia Victoria , Grignani Francesco , Nervi Clara , Miller Wilson H.
Published: August 2004

Nuclear receptors are ligand-modulated transcription factors regulated by interactions with corepressors and coactivators, whose functions are not fully understood. Acute promyelocytic leukemia (APL) is characterized by a translocation, t(15;17), that produces a PML/RARα fusion oncoprotein, whose abnormal transcriptional function is successfully targeted by pharmacologic levels of all-trans-retinoic acid (ATRA). Mutations in the ligand-binding domain of PML/RARα that confer resistance to ATRA have been studied by expression in nonhematopoietic cells, such as Cos-1. Here, we show that ATRA binding and transcriptional activation by the same PML/RARα mutant differ markedly between nonhematopoietic and leukemic cell lines. Differential expression of the corepressor isoform silencing mediator for retinoid and thyroid receptors β (SMRTβ) correlates with increased ligand binding and transcription by the mutant PML/RARα. Transient and stable overexpression of SMRTβ in hematopoietic cells that only express SMRTα increased ATRA binding, ligand-induced transcription, and ATRA-induced cell differentiation. This effect may not be limited to abnormal nuclear receptors, because overexpression of SMRTβ increased ATRA-induced binding and transcriptional activation of wild-type receptors PML/RARα and RARα. Our results suggest a novel role for the SMRTβ isoform whereby its cell-specific expression may influence the binding and transcriptional capacities of nuclear receptors, thus providing new evidence of distinct functions of corepressor isoforms and adding complexity to transcriptional regulation.
Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- γc-/- mice: functional inactivation of p53 in developing T cells
Authors: Gimeno Ramon , Weijer Kees , Voordouw Arie , Uittenbogaart Christel H. , Legrand Nicolas , Alves Nuno L. , Wijnands Erwin , Blom Bianca , Spits Hergen
Published: August 2004

Tumor suppressor p53 plays an important role in regulating cell cycle progression and apoptosis. Here we applied RNA interference to study the role of p53 in human hematopoietic development in vivo. An siRNA construct specifically targeting the human tumor-suppressor gene p53 was introduced into human CD34+ progenitor cells by lentivirus-mediated gene transfer, which resulted in more than 95% knockdown of p53. We adapted the human-SCID mouse model to optimize the development of hematopoietic cells, particularly of T cells. This was achieved by the intraperitoneal injection of CD34+ precursor cells into newborn Rag2-/- γc-/- mice that lack T, B, and NK cells. Robust development of T cells was observed in these mice, with peripheral T-cell repopulation 8 weeks after injection of the precursor cells. Other lymphocyte and myeloid subsets also developed in these mice. Injecting p53 siRNA-transduced CD34+ cells resulted in stable expression and down-modulation of p53 in the mature T-cell offspring. Inactivating p53 did not affect the development of CD34+ cells into various mature leukocyte subsets, including T cells, but it conferred resistance to γ-irradiation and other p53-dependent apoptotic stimuli to the T cells. (Blood. 2004;104:3886-3893)
Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice
Authors: Delfino Domenico Vittorio , Agostini Massimiliano , Spinicelli Stefania , Vito Pasquale , Riccardi Carlo
Published: August 2004

Glucocorticoids promote thymocyte apoptosis and modulate transcription of numerous genes. GILZ (glucocorticoid-induced leucine zipper), being one of them, is strongly up-regulated in the thymus. To elucidate its function we generated transgenic mice overexpressing it specifically in the T-cell lineage and characterized its influence on thymus function. In young adult transgenic mice CD4+CD8+ thymocyte number was significantly decreased and ex vivo thymocyte apoptosis was increased. Apoptotic pathway analysis detected reduced antiapoptotic B-cell leukemia XL (Bcl-xL) expression and increased activation of caspase-8 and caspase-3. Time-course experiments showed that in wild-type (WT) thymocytes GILZ up-regulation was followed by sequential Bcl-xL decreased expression and activation of caspase-8 and of caspase-3. Moreover, GILZ delivered inside WT thymocytes by a fusion protein with the transactivator of transcription (TAT) peptide decreased Bcl-xL and promoted their apoptosis. In aged mice perturbation of thymic subset numbers was amplified over time, as demonstrated by a further decrease in CD4+CD8+ cells and increases in CD4+CD8-, CD4-CD8-, and CD8+CD4- cell counts. These results support the hypothesis that GILZ participates in the regulation of thymocyte apoptosis by glucocorticoids. (Blood. 2004;104:4134-4141)
Functional and structural correlations of individual αIIbβ3 molecules
Authors: Litvinov Rustem I. , Nagaswami Chandrasekaran , Vilaire Gaston , Shuman Henry , Bennett Joel S. , Weisel John W.
Published: August 2004

The divalent cation Mn2+ and the reducing agent dithiothreitol directly shift integrins from their inactive to their active states. We used transmission electron microscopy and laser tweezers-based force spectroscopy to determine whether structural rearrangements induced by these agents in the integrin αIIbβ3 correlate with its ability to bind fibrinogen. Mn2+ increased the probability of specific fibrinogen-αIIbβ3 interactions nearly 20-fold in platelets, and both Mn2+ and dithiothreitol increased the probability more than 2-fold using purified proteins. Of 3 αIIbβ3 conformations, closed with stalks touching, open with stalks separated, and globular without visible stalks, Mn2+ and dithiothreitol induced a significant increase in the proportion of open structures, as well as structural changes in the αIIbβ3 headpiece. Mn2+ also increased the number of complexes between fibrinogen and purified αIIbβ3 molecules, all of which were in the open conformation. Finally, Mn2+ induced the formation of αIIbβ3 clusters that resulted from interactions exclusively involving the distal ends of the stalks. These results indicate that there is a direct correlation between αIIbβ3 activation and the overall conformation of the molecule. Further, they are consistent with the presence of a linked equilibrium between single inactive and single active αIIbβ3 molecules and active αIIbβ3 clusters. (Blood. 2004;104:3979-3985)
Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufficiency
Authors: Marrone Anna , Stevens David , Vulliamy Tom , Dokal Inderjeet , Mason Philip J.
Published: August 2004

Mutations in TERC, encoding the RNA component of telomerase, have been found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia (AA). Several polymorphisms also exist in the TERC gene, making functional testing of potential pathogenic mutations essential. Here, we have tested normal and mutant TERC molecules in 2 telomerase reconstitution assays, 1 in vitro and 1 in transfected telomerase-negative cells. We find that 2 polymorphic mutations G58A and G228A have no effect on telomerase activity in these assays, whereas 6 mutations found in DC and AA cause reduction or abolition of telomerase activity. Mutations in the pseudoknot region of the TERC molecule, C72G, 96-7ΔCT, GC107-8AG and 110-3ΔGACT reduce the catalytic activity of reconstituted telomerase, whereas mutations in the 3′ portion of the molecule C408G and a deletion of the 3′ 74 bases have normal activity in vitro but reduced intracellular activity. By analyzing second site mutations that recreate regions of secondary structure but retain the pathogenic mutations we show that mutations C72G, GC107-8AG, and C408G act by disrupting the secondary structure or folding of TERC. Finally, experiments reconstituting telomerase with both normal and mutant TERC molecules suggest the mutations act via haploinsufficiency rather than by a dominant-negative mechanism. (Blood. 2004;104:3936-3942)
Core 2 branching β1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes
Authors: Gauguet Jean-Marc , Rosen Steven D. , Marth Jamey D. , von Andrian Ulrich H.
Published: August 2004

Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I-/- and HEC-GlcNAc6ST-/- mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST-/- HEVs, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin+/- T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. (Blood. 2004;104:4104-4112)
Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes
Authors: Alkhalil Abdulnaser , Cohn Jamieson V. , Wagner Marissa A. , Cabrera Jennifer S. , Rajapandi Thavamani , Desai Sanjay A.
Published: August 2004

Invasion by the human malaria parasite, Plasmodium falciparum, is associated with marked yet selective increases in red blood cell (RBC) membrane permeability. We previously identified an unusual voltage-dependent ion channel, the plasmodial surface anion channel (PSAC), which may account for these increases. Since then, controversy has arisen about whether there are additional parasite-induced anion channels on the RBC membrane and whether these channels are parasite-encoded proteins or the result of modifications of an endogenous host protein. Here, we used genetically divergent parasite isolates and quantitative transport measurements to examine these questions. Our studies indicate that PSAC alone can adequately account for the increased permeability of infected RBCs to key solutes. Two distinct parasite isolates, grown in RBCs from a single donor, exhibit channel activity with measurably different voltage-dependent gating, a finding difficult to reconcile with simple activation or modification of a host protein. Instead, this difference in channel gating can be conservatively explained by a small number of polymorphisms in a parasite gene that encodes PSAC. The absence of known eukaryotic ion channel homologues in the completed P falciparum genome suggests a novel channel gene, and substantiates PSAC as a target for antimalarial development.
Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism
Authors: Eltzschig Holger K. , Thompson Linda F. , Karhausen Jorn , Cotta Richard J. , Ibla Juan C. , Robson Simon C. , Colgan Sean P.
Published: August 2004

Hypoxia is a well-documented inflammatory stimulus and results in tissue polymorphonuclear leukocyte (PMN) accumulation. Likewise, increased tissue adenosine levels are commonly associated with hypoxia, and given the anti-inflammatory properties of adenosine, we hypothesized that adenosine production via adenine nucleotide metabolism at the vascular surface triggers an endogenous anti-inflammatory response during hypoxia. Initial in vitro studies indicated that endogenously generated adenosine, through activation of PMN adenosine A2A and A2B receptors, functions as an antiadhesive signal for PMN binding to microvascular endothelia. Intravascular nucleotides released by inflammatory cells undergo phosphohydrolysis via hypoxia-induced CD39 ectoapyrase (CD39 converts adenosine triphosphate/adenosine diphosphate [ATP/ADP] to adenosine monophosphate [AMP]) and CD73 ecto-5′-nucleotidase (CD73 converts AMP to adenosine). Extensions of our in vitro findings using cd39- and cd73-null animals revealed that extracellular adenosine produced through adenine nucleotide metabolism during hypoxia is a potent anti-inflammatory signal for PMNs in vivo. These findings identify CD39 and CD73 as critical control points for endogenous adenosine generation and implicate this pathway as an innate mechanism to attenuate excessive tissue PMN accumulation. (Blood. 2004;104:3986-3992)
FTY720 suppresses humoral immunity by inhibiting germinal center reaction
Authors: Han Shuhua , Zhang Xuejun , Wang Gangdou , Guan Hui , Garcia Gabriela , Li Ping , Feng Lili , Zheng Biao
Published: August 2004

FTY720 is a novel immunosuppressant that is highly effective in inhibiting rejection of allografts and autoimmunity in various animal models. It has been shown that the sphingosine 1 phosphate (S1P) receptors are the direct molecular targets of FTY720. However, the mechanisms responsible for inhibiting specific immune responses by FTY720 are not well resolved. In particular, there is no available information on whether or how this compound affects humoral immunity. We have investigated the effect of FTY720 treatment on B-cell response during the immune response to a well-defined T-dependent antigen. Our data demonstrated that germinal center reaction was significantly reduced in peripheral lymphoid tissues of mice treated with FTY720. In addition, FTY720 treatment inhibited the production of high-affinity, class-switched antibodies, but not the production of low-affinity, immunoglobulin M (IgM) antibody. Consistently, FTY720 did not have a significant effect on antibody response to a T-independent antigen. Our results may have important implications in application of FTY720 in immune regulation. (Blood. 2004; 104:4129-4133)
Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma
Authors: Raje Noopur , Kumar Shaji , Hideshima Teru , Ishitsuka Kenji , Chauhan Dharminder , Mitsiades Constantine , Podar Klaus , Le Gouill Steven , Richardson Paul , Munshi Nikhil C. , Stirling David I. , Antin Joseph H. , Anderson Kenneth C.
Published: August 2004

Previous studies have demonstrated the in vitro and in vivo activity of CC-5013 (Revlimid), an immunomodulatory analog (IMiD) of thalidomide, in multiple myeloma (MM). In the present study, we have examined the anti-MM activity of rapamycin (Rapamune), a specific mTOR inhibitor, combined with CC-5013. Based on the Chou-Talalay method, combination indices of less than 1 were obtained for all dose ranges of CC-5013 when combined with rapamycin, suggesting strong synergism. Importantly, this combination was able to overcome drug resistance when tested against MM cell lines resistant to conventional chemotherapy. Moreover, the combination, but not rapamycin alone, was able to overcome the growth advantage conferred on MM cells by interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), or adherence to bone marrow stromal cells (BMSCs). Combining rapamycin and CC-5013 induced apoptosis of MM cells. Differential signaling cascades, including the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3′-kinase/Akt kinase (PI3K/Akt) pathways, were targeted by these drugs individually and in combination, suggesting the molecular mechanism by which they interfere with MM growth and survival. These studies, therefore, provide the framework for clinical evaluation of mTOR inhibitors combined with IMiDs to improve patient outcome in MM.
Diferric transferrin regulates transferrin receptor 2 protein stability
Authors: Johnson Martha B. , Enns Caroline A.
Published: August 2004

Transferrin receptor 2 (TfR2) is a type 2 transmembrane protein expressed in hepatocytes that binds iron-bound transferrin (Tf). Mutations in TfR2 cause one form of hereditary hemochromatosis, a disease in which excessive absorption of dietary iron can lead to liver cirrhosis, diabetes, arthritis, and heart failure. The function of TfR2 in iron homeostasis is unknown. We have studied the regulation of TfR2 in HepG2 cells. Western blot analysis shows that TfR2 increases in a time- and dose-dependent manner after diferric Tf is added to the culture medium. In cells exposed to diferric Tf, the amount of TfR2 returns to control levels within 8 hours after the removal of diferric Tf from the medium. However, TfR2 does not increase when non–Tf-bound iron (FeNTA) or apo Tf is added to the medium. The response to diferric Tf appears to be hepatocyte specific. Real-time quantitative reverse transcription–polymerase chain reaction (qRT-PCR) analysis shows that TfR2 mRNA levels do not change in cells exposed to diferric Tf. Rather, the increase in TfR2 is attributed to an increase in the half-life of TfR2 protein in cells exposed to diferric Tf. Our results support a role for TfR2 in monitoring iron levels by sensing changes in the concentration of diferric Tf.
Periodicity of DNA in exons
Authors: Eskesen Stephen T , Eskesen Frank N , Kinghorn Brian , Ruvinsky Anatoly
Published: August 2004

Background

The periodic pattern of DNA in exons is a known phenomenon. It was suggested that one of the initial causes of periodicity could be the universal (RNY)
n
pattern (R = A or G, Y = C or U, N = any base) of ancient RNA. Two major questions were addressed in this paper. Firstly, the cause of DNA periodicity, which was investigated by comparisons between real and simulated coding sequences. Secondly, quantification of DNA periodicity was made using an evolutionary algorithm, which was not previously used for such purposes.

Results

We have shown that simulated coding sequences, which were composed using codon usage frequencies only, demonstrate DNA periodicity very similar to the observed in real exons. It was also found that DNA periodicity disappears in the simulated sequences, when the frequencies of codons become equal.

Frequencies of the nucleotides (and the dinucleotide AG) at each location along phase 0 exons were calculated for C. elegans, D. melanogaster and H. sapiens. Two models were used to fit these data, with the key objective of describing periodicity. Both of the models showed that the best-fit curves closely matched the actual data points. The first dynamic period determination model consistently generated a value, which was very close to the period equal to 3 nucleotides. The second fixed period model, as expected, kept the period exactly equal to 3 and did not detract from its goodness of fit.

Conclusions

Conclusion can be drawn that DNA periodicity in exons is determined by codon usage frequencies. It is essential to differentiate between DNA periodicity itself, and the length of the period equal to 3. Periodicity itself is a result of certain combinations of codons with different frequencies typical for a species. The length of period equal to 3, instead, is caused by the triplet nature of genetic code. The models and evolutionary algorithm used for characterising DNA periodicity are proven to be an effective tool for describing the periodicity pattern in a species, when a number of exons in the same phase are analysed.
Endotoxin leads to rapid subcellular re-localization of hepatic RXRα: A novel mechanism for reduced hepatic gene expression in inflammation
Authors: Ghose Romi , Zimmerman Tracy L , Thevananther Sundararajah , Karpen Saul J
Published: August 2004

Background

Lipopolysaccharide (LPS) treatment of animals down-regulates the expression of hepatic genes involved in a broad variety of physiological processes, collectively known as the negative hepatic acute phase response (APR). Retinoid X receptor α (RXRα), the most highly expressed RXR isoform in liver, plays a central role in regulating bile acid, cholesterol, fatty acid, steroid and xenobiotic metabolism and homeostasis. Many of the genes regulated by RXRα are repressed during the negative hepatic APR, although the underlying mechanism is not known. We hypothesized that inflammation-induced alteration of the subcellular location of RXRα was a common mechanism underlying the negative hepatic APR.

Results

Nuclear RXRα protein levels were significantly reduced (~50%) within 1–2 hours after low-dose LPS treatment and remained so for at least 16 hours. RXRα was never detected in cytosolic extracts from saline-treated mice, yet was rapidly and profoundly detectable in the cytosol from 1 hour, to at least 4 hours, after LPS administration. These effects were specific, since the subcellular localization of the RXRα partner, the retinoic acid receptor (RARα), was unaffected by LPS. A potential cell-signaling modulator of RXRα activity, c-Jun-N-terminal kinase (JNK) was maximally activated at 1–2 hours, coincident with maximal levels of cytoplasmic RXRα. RNA levels of RXRα were unchanged, while expression of 6 sentinel hepatic genes regulated by RXRα were all markedly repressed after LPS treatment. This is likely due to reduced nuclear binding activities of regulatory RXRα-containing heterodimer pairs.

Conclusion

The subcellular localization of native RXRα rapidly changes in response to LPS administration, correlating with induction of cell signaling pathways. This provides a novel and broad-ranging molecular mechanism for the suppression of RXRα-regulated genes in inflammation.
Bistability and hysteresis of the 'Secteur' differentiation are controlled by a two-gene locus in Nectria haematococca
Authors: Graziani Stéphane , Silar Philippe , Daboussi Marie-Josée
Published: August 2004

Background

Bistability and hysteresis are increasingly recognized as major properties of regulatory networks governing numerous biological phenomena, such as differentiation and cell cycle progression. The full scope of the underlying molecular mechanisms leading to bistability and hysteresis remains elusive. Nectria haemaotcocca, a saprophytic or pathogenic fungus with sexual reproduction, exhibits a bistable morphological modification characterized by a reduced growth rate and an intense pigmentation. Bistability is triggered by the presence or absence of σ, a cytoplasmic determinant. This determinant spreads in an infectious manner in the hyphae of the growing margin, insuring hysteresis of the differentiation.

Results

Seven mutants specifically affected in the generation of σ were selected through two different screening strategies. The s1 and s2 mutations completely abolish the generation of σ and of its morphological expression, the Secteur. The remaining five mutations promote its constitutive generation, which determines an intense pigmentation but not growth alteration. The seven mutations map at the same locus, Ses (for 'Secteur-specific'). The s2 mutant was obtained by an insertional mutagenesis strategy, which permitted the cloning of the Ses locus. Sequence and transcription analysis reveals that Ses is composed of two closely linked genes, SesA, mutated in the s1 and s2 mutant strains, and SesB, mutated in the s* mutant strains. SesB shares sequence similarity with animal and fungal putative proteins, with potential esterase/lipase/thioesterase activity, whereas SesA is similar to proteins of unknown function present only in the filamentous fungi Fusarium graminearum and Podospora anserina.

Conclusions

The cloning of Ses provides evidence that a system encoded by two linked genes directs a bistable and hysteretic switch in a eukaryote. Atypical regulatory relations between the two proteins may account for the hysteresis of Secteur differentiation.
We still fail to account for Mendel's observations
Authors: Porteous John W
Published: August 2004

Background

The present article corrects common textbook accounts of Mendel's experiments by re-establishing what he wrote and how he accounted for his observations. It notes the long-established tests for the validity of any explanations that purport to explain observations obtained by experiment. Application of these tests to Mendel's paper shows that the arguments he used to explain his observations were internally consistent but were, on one crucial issue, implausible. The same tests are applied to the currently accepted explanation for Mendel's observations.

Conclusions

The currently favoured explanation for Mendel's observations is untenable. It misrepresents Mendel, fails to distinguish between the parameters and the variables of any system of interacting components, its arguments are inconsistent, it repeats the implausibility in Mendel's paper, fails to give a rational explanation for his observed 3:1 trait ratio and cannot explain why this ratio is not always observed in experimental practice. A rational explanation for Mendel's observations is initiated. Readers are challenged to complete the process before a further article appears.
WHO systematic review of maternal morbidity and mortality: the prevalence of severe acute maternal morbidity (near miss)
Authors: Say Lale , Pattinson Robert C , Gülmezoglu A Metin
Published: August 2004

Aim

To determine the prevalence of severe acute maternal morbidity (SAMM) worldwide (near miss).

Method

Systematic review of all available data. The methodology followed a pre-defined protocol, an extensive search strategy of 10 electronic databases as well as other sources. Articles were evaluated according to specified inclusion criteria. Data were extracted using data extraction instrument which collects additional information on the quality of reporting including definitions and identification of cases. Data were entered into a specially constructed database and tabulated using SAS statistical management and analysis software.

Results

A total of 30 studies are included in the systematic review. Designs are mainly cross-sectional and 24 were conducted in hospital settings, mostly teaching hospitals. Fourteen studies report on a defined SAMM condition while the remainder use a response to an event such as admission to intensive care unit as a proxy for SAMM. Criteria for identification of cases vary widely across studies. Prevalences vary between 0.80% – 8.23% in studies that use disease-specific criteria while the range is 0.38% – 1.09% in the group that use organ-system based criteria and included unselected group of women. Rates are within the range of 0.01% and 2.99% in studies using management-based criteria. It is not possible to pool data together to provide summary estimates or comparisons between different settings due to variations in case-identification criteria. Nevertheless, there seems to be an inverse trend in prevalence with development status of a country.

Conclusion

There is a clear need to set uniform criteria to classify patients as SAMM. This standardisation could be made for similar settings separately. An organ-system dysfunction/failure approach is the most epidemiologically sound as it is least open to bias, and thus could permit developing summary estimates.
What is Nutrition & Metabolism?
Authors: Feinman Richard D , Hussain M Mahmood
Published: August 2004

A new Open Access journal, Nutrition & Metabolism (N&M) will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.
Ketogenic diets and physical performance
Authors: Phinney Stephen D
Published: August 2004

Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.
Amino acids as regulators of gene expression
Authors: Kimball Scot R , Jefferson Leonard S
Published: August 2004

The role of amino acids as substrates for protein synthesis is well documented. However, a function for amino acids in modulating the signal transduction pathways that regulate mRNA translation has only recently been described. Interesting, some of the signaling pathways regulated by amino acids overlap with those classically associated with the cellular response to hormones such as insulin and insulin-like growth factors. The focus of this review is on the signaling pathways regulated by amino acids, with a particular emphasis on the branched-chain amino acid leucine, and the steps in mRNA translation controlled by the signaling pathways.
β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet
Authors: Darimont Christian , Turini Marco , Epitaux Micheline , Zbinden Irène , Richelle Myriam , Montell Eulàlia , Ferrer-Martinez Andreu , Macé Katherine
Published: August 2004

Background

Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.

Methods

Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.

Results

In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.

Conclusions

These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.
Diet induced thermogenesis
Authors: Westerterp Klaas R
Published: August 2004

Objective

Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet.

Methods

Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition.

Results

Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety.

In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.
Quantifying soil erosion by water in the UK: a review of monitoring and modelling approaches
Authors: Brazier Richard
Published: August 2004

The role of erosion by water in the UK is considered. A summary of available data describing water erosion is presented providing insights into rates of erosion from the hillslope scale to the large catchment scale. Evidence suggests that soil erosion rates in excess of acceptable thresholds occur on a wide range of soils and under a wide range of land uses throughout the country. Given the recent shift towards erosion modelling and away from erosion monitoring, discussion of the quality of existing available observed data in the context of model evaluation is made. Much quality data exist in the UK to describe erosion by water, but it is argued here that few datasets provide the necessary detail with which to evaluate model performance accurately, especially when the description of the spatial heterogeneity of soil loss is a goal. Furthermore, the paradox between data collection (to improve models) and erosion modelling (to replace data collection) is highlighted as an issue that must be addressed within the discipline if full use of datasets and improvement of models is to be made.
Wind erosion research in China: past, present and future
Authors: Shi Peijun , Yan Ping , Yuan Yi , Nearing Mark A.
Published: August 2004

Wind erosion is one of the most important processes associated with land degradation and desertification in the arid, semi-arid and portions of the subhumid regions of China. The total land area experiencing wind erosion is approximately 160.74 104 km2, which is 16.7% of the national territory. Wind erosion is recognized as a great threat to land utilization and sustainable social and economic development. Documentation of wind erosion and its negative impacts in China dates back over 2000 years. Since the 1950s Chinese scientists have carried out an integrated investigation of the principal lands susceptible to wind erosion, and have undertaken many laboratory tests and field observations with respect to the stabilization and utilization of soil in desert areas. Since the late 1970s there has been an increasing concern worldwide regarding land desertification caused by climatic changes and human activities. Hence, wind erosion, one of the main processes of desertification, has attracted the attention of Chinese scientists to an even greater extent. Studies have been conducted to investigate the mechanics, causes and control techniques related to wind erosion using wind tunnel simulation tests and field observations in typical areas. Some encouraging achievements have been made. In this paper we summarize the main research results on wind erosion that have come to light in China in recent decades, and put forward some perspectives and suggestions to deal with problems in both research into and control practices of wind erosion in China.
Climate and infectious disease in the southwestern United States
Authors: Kolivras Korine N. , Comrie ndrew C.
Published: August 2004

As in many parts of the world, climate variability has a strong impact on infectious diseases within the southwestern USA. Moisture and temperature conditions can either indirectly impact disease by providing an environment conducive to the growth of an animal host or reservoir, or directly through the survival and dispersal of an infectious agent. It is also expected that climate change will affect the number of cases and/or the spatial distribution of infectious diseases. Before the effects of climate change on diseases can be determined, an understanding of the basic relationship between incidence and climate variability should be established. A review of climate impacts on four infectious diseases (hantavirus, plague, dengue and coccidioidomycosis) currently found in southwestern USA (or potentially found in the southwest in the case of dengue) is followed by suggested future research to further understand the relationship between climate variability/change and disease.