bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells
Authors: Coffinier Catherine , Hudon Sarah E. , Farber Emily A. , Chang Sandy Y. , Hrycyna Christine A. , Young Stephen G. , Fong Loren G.
Published: July 2007

HIV protease inhibitors (HIV-PIs) target the HIV aspartyl protease, which cleaves the HIV gag-pol polyprotein into shorter proteins required for the production of new virions. HIV-PIs are a cornerstone of treatment for HIV but have been associated with lipodystrophy and other side effects. In both human and mouse fibroblasts, we show that HIV-PIs caused an accumulation of prelamin A. The prelamin A in HIV-PI-treated fibroblasts migrated more rapidly than nonfarnesylated prelamin A, comigrating with the farnesylated form of prelamin A that accumulates in ZMPSTE24-deficient fibroblasts. The accumulation of farnesyl-prelamin A in response to HIV-PI treatment was exaggerated in fibroblasts heterozygous forZmpste24deficiency. HIV-PIs inhibited the endoproteolytic processing of a GFP-prelamin A fusion protein. The HIV-PIs did not affect the farnesylation of HDJ-2, nor did they inhibit protein farnesyltransferasein vitro. HIV-PIs also did not inhibit the activities of the isoprenyl-cysteine carboxyl methyltransferase ICMT or the prenylprotein endoprotease RCE1in vitro, but they did inhibit ZMPSTE24 (IC50: lopinavir, 18.4 ± 4.6 μM; tipranavir, 1.2 ± 0.4 μM). We conclude that the HIV-PIs inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A. The inhibition of ZMPSTE24 by HIV-PIs could play a role in the side effects of these drugs.
Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia
Authors: Giangrande Paloma H. , Zhang JianXin , Tanner Alice , Eckhart Andrea D. , Rempel Rachel E. , Andrechek Eran R. , Layzer Juliana M. , Keys Janelle R. , Hagen Per-Otto , Nevins Joseph R. , Koch Walter J. , Sullenger Bruce A.
Published: July 2007

Intimal hyperplasia (IH) and restenosis limit the long-term utility of bypass surgery and angioplasty due to pathological proliferation and migration of vascular smooth muscle cells (VSMCs) into the intima of treated vessels. Consequently, much attention has been focused on developing inhibitory agents that reduce this pathogenic process. The E2F transcription factors are key cell cycle regulators that play important roles in modulating cell proliferation and cell fate. Nonselective E2F inhibitors have thus been extensively evaluated for this purpose. Surprisingly, these E2F inhibitors have failed to reduce IH. These findings prompted us to evaluate the roles of different E2Fs during IH to determine how selective targeting of E2F isoforms impacts VSMC proliferation. Importantly, we show that E2F3 promotes proliferation of VSMCs leading to increased IH, whereas E2F4 inhibits this pathological response. Furthermore, we use RNA probes to show that selective inhibition of E2F3, not global inhibition of E2F activity, significantly reduces VSMC proliferation and limits IH in murine bypass grafts.
Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression
Authors: Schulz David J. , Goaillard Jean-Marc , Marder Eve E.
Published: July 2007

The postdevelopmental basis of cellular identity and the unique cellular output of a particular neuron type are of particular interest in the nervous system because a detailed understanding of circuits responsible for complex processes in the brain is impeded by the often ambiguous classification of neurons in these circuits. Neurons have been classified by morphological, electrophysiological, and neurochemical techniques. More recently, molecular approaches, particularly microarray, have been applied to the question of neuronal identity. With the realization that proteins expressed exclusively in only one type of neuron are rare, expression profiles obtained from neuronal subtypes are analyzed to search for diagnostic patterns of gene expression. However, this expression profiling hinges on one critical and implicit assumption: that neurons of the same type in different animals achieve their conserved functional output via conserved levels and quantitative relationships of gene expression. Here we exploit the unambiguously identifiable neurons in the crab stomatogastric ganglion to investigate the precise quantitative expression profiling of neurons at the level of single-cell ion channel expression. By measuring absolute mRNA levels of six different channels in the same individually identified neurons, we demonstrate that not only do individual cell types possess highly variable levels of channel expression but that this variability is constrained by unique patterns of correlated channel expression.
Emerging Role of Nrf2 in Protecting Against Hepatic and Gastrointestinal Disease
Authors: Aleksunes Lauren M. , Manautou José E.
Published: July 2007

Transcription factor NF-E2-related factor 2 (Nrf2) belongs to the basic region-leucine zipper family and is activated in response to electrophiles and reactive oxygen species. Nrf2 coordinately regulates the constitutive and inducible transcription of a wide array of genes involved in drug metabolism, detoxification, and antioxidant defenses. During periods of oxidative stress, Nrf2 is released from sequestration in the cytoplasm and translocates to the nucleus. Nrf2 binds antioxidant response elements (AREs) in the regulatory regions of target genes and activates transcription. Genetically modified mice lacking Nrf2 serve as a useful tool for identifying new ARE-regulated genes and assessing the ability of Nrf2 to confer protection against a variety of pathologies in numerous organs including the liver, intestine, lung, skin, and nervous system. With regards to the liver and gastrointestinal tract, Nrf2 knockout mice are more susceptible to acetaminophen-induced hepatocellular injury, benzo[a]pyrene-induced tumor formation and Fas-and TNFα-mediated hepatocellular apoptosis. The higher sensitivity of Nrf2 knockout mice to chemical toxicity is due in part to reduced basal and inducible expression of detoxification enzymes. Nrf2 may also be important in protecting against liver fibrosis, gallstone development, and formation of aberrant crypt foci. Research of Nrf2 has opened up new opportunities in understanding how antioxidant defense pathways are regulated, how oxidative stress contributes to disease progression and may serve as a novel target for designing therapies to prevent and treat diseases in which oxidative stress is implicated.
Apoptosis: A Review of Programmed Cell Death
Authors: Elmore Susan
Published: July 2007

The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.
Book review
Authors: Williams Gavin
Published: July 2007

Doctrines of Development(1996) by M P Cowen & R W Shenton, Routledge, 554pp.
Reviews
Authors: Iyenda Guillaume , Brittain Victoria
Published: July 2007

The Congo: From Leopold to Kabila. A People's Historyby Georges Nzongola‐Ntalaja, Zed Books, London, 2002. ISBN: 1 84277 053 5.

King Congo
Reviews
Authors: Coulson Andrew , Beckman Björn
Published: July 2007

Ecology Control and Economic Development in East African Historyby Helge Kjekshus. (Heinemann, London, 1977) 215pp. £2.80 (paper)

Nigeria: Economy and Society,edited by Gavin Williams (Rex Collings, London, 1976)
Reviews
Authors: Cobbe James
Published: July 2007

Books of the 1976 Revolt by Baruch Hirson

An Introduction to Political Economy by Michael Sefali (Morija Printing Works, Morija, Lesotho, 1977), no price.
Reviews
Authors: Nolutshungu Sam , Nolutshungu Sam , Freund Bill , Schröder Hans
Published: July 2007

Black Politics in South Africa since 1945 by Tom Lodge, (Longman, London, 1983), 389pp, pbk £5.95.

Volkskapitalisme: Class, Capital and Ideology in the Development of Afrikaner Nationalism, 1934–48 by Dan O'Meara, (Cambridge University Press, Cambridge, 1983), £22.50.

Also: Walvis Bay: Namibia's Port, by Richard Moorsom, International Defence and Aid Fund, 1984.
Reviews
Authors: Crisp Jeff , Olukoshi Adebayo
Published: July 2007

Imperialism and Fascism in Ugandaby Mahmood Mamdani, Heineman, London, 1983.

Imperialism and Underdevelopment in Nigeria: The Dialectics of MassPoverty by Bade Onimode (London, Zed Press, 1982), 258pp, £6.50.
Reviews
Authors: Wield David , Green Andrew , Egerö Bertil , Lindsay Jennie , Blaikie Piers , Pitcher Anne
Published: July 2007

Mozambique — Towards a People's Health Serviceby G. Walt and A. Melamed (Eds), Zed Press, London, 1983; Mozambique— the Revolution under Fireby Joe Hanlon, Zed Press, London, 1984; A Difficult Road — the Transition to Socialism in Mozambiqueby John S. Saul (Ed), Monthly Review Press, New York, 1985.

Crippling a Nationby Aziza Seedat, published by International Defence and Aid Fund (IDAF), London, 1986; and The South African Diseaseby Cedric de Beer published by Catholic Institute for International Relations (CIIR) London and AWP (US) autumn 1986. Originally published in 1984 by the Southern African Research Services, Johannesburg, South Africa.

Population and Development Projects in Africaedited by Clarke, Khogali and Kosinski, Cambridge University Press, 1985.

Health Sector Policy Options for Independent Namibiaby Neil Andersson. United Nations Institute for Namibia, Lusaka, 1984.

RESPONSE TO REVIEW BY KATE SHOWERS

The Third Portuguese Empire, 1825–1975: A Study in Economic Imperialismby Gervase Clarence‐Smith, Manchester University Press, 1985, 256pp.
Reviews
Authors: Markakis John , Markovitz Irving
                      Leonard
Published: July 2007

Recent Publications on the Horn of African from the Scandinavian Institute of African Studies, Uppsala.

Italian Colonialism in Eritrea, 1882–1941
by Tekeste Negash Uppsala: Uppsala University Press, 1987, xi + 217 pp.

The African Poor: A History
by John Iliffe, Cambridge & New York: Cambridge University Press, 1988.
Book reviews
Authors: Ericsson Magnus , McGregor Duncan , Jochelson Karen , Simon David
Published: July 2007

Mining in Africa Today – Strategies and Prospects by Faysal Yachir,Zed Books 1988.

No Timber Without Trees: Sustain‐ability in the Tropical Forest by Duncan Poore,London, Earthscan Publications, 1989.

Economics, Natural Resource Scarcity and Development by Edward B. Barbier, Earthscan, London 1989.
Book reviews
Authors: Bush Ray , Roberts Penelope , Powell Mike
Published: July 2007

Hunger and Public Actionby J. Dreze and A. Sen, Clarendon Press, Oxford, 1989.

Forced Labour and Migration: Patterns of Movement within Africaedited by Abebe Zegeye and Shubi Ishemo; Hans Zell Publishers, London, Munich and New York, 1989, ISBN 0–905450–36–1.

Mozambique: Who Calls the Shotsby Joseph Hanlon, James Currey/Indiana University “Press, 1991.
Book reviews
Authors: Seddon David , Crawford Gordon
Published: July 2007

Human Rights and Reform: Changing the Face of North African Politics
by Susan E Waltz, University of California Press, Berkeley, Los Angeles & London, 1995.
Review article
Authors: Markakis John
Published: July 2007

I M Lewis(1994), Blood and Bone: The Call of Kinship in Somali Society,Lawrenceville, N.J: The Red Sea Press, xii‐256.

Ahmed I Samatar(ed.) (1994), The Somali Challenge: From Catastrophe to Renewal,London: Lynne Rienner Publishers, xiii‐297.

Jama Mohamed Ghalib(1995), The Cost of Dictatorship: The Somali Experience.New York: Lilian Barber Press, xv‐267.

Ali Jimale Ahmed(ed.) (1995), The Invention of Somalia.Lawrenceville, N.J.: Red Sea Press, ix‐265.
From knowledge to wisdom: the need for an academic revolution
Authors: Maxwell Nicholas
Published: July 2007

At present the basic intellectual aim of academic inquiry is to improve knowledge. Much of the structure, the whole character, of academic inquiry, in universities all over the world, is shaped by the adoption of this as the basic intellectual aim. But, judged from the standpoint of
making a contribution to human welfare, academic inquiry of this type is irrational. Three of four of the most elementary rules of rational problem-solving are violated. A revolution in the aims and methods of academic inquiry is needed so that the basic aim becomes to promote wisdom, conceived
of as the capacity to realize what is of value, for oneself and others, thus including knowledge and technological know-how, but much else besides. This urgently needed revolution would affect every branch and aspect of the academic enterprise.
From knowledge-inquiry to wisdom-inquiry: is the revolution underway?
Authors: Iredale Mathew
Published: July 2007

In the final paragraph of his 1984 book From knowledge to wisdom, a revolution in the aims and methods of science, the philosopher Nicholas Maxwell boldly declared that an intellectual revolution was underway in the aims and methods of science, and academic inquiry in
general, from what he termed knowledge-inquiry to wisdom-inquiry. Twenty years later, this article discusses to what extent this revolution has taken place.
Wisdom remembered: recovering a theological vision of wisdom for the academe
Authors: Deane-Drummond Celia
Published: July 2007

In considering issues of public and global importance, social scientists are coming to an increasing recognition of the importance of religious belief in motivating particular attitudes and actions. If one of the tasks of academe is to articulate those values that are important in the
public sphere, it must necessarily include careful discussion of the religious dimension of human existence. This paper addresses the issue of what a theological vision of wisdom might look like and its relevance in serving the public good in the context of a university. John Henry Newman's
The idea of a university, proposed in the nineteenth century, gives some insights into what wisdom informed by theology might look like when applied to higher education. Prudence, or practical wisdom, as found in the medieval theologian Thomas Aquinas offers a mediating strategy between
philosophical and theological approaches to wisdom. An argument will be put forward for a recovery of prudence as relevant for shaping the ethos of universities. In this, universities can also serve the public good and promote human welfare in contested areas such as environmental decision-making
or new reproductive technologies.
Shakespeare on wisdom
Authors: Nordstrom Alan
Published: July 2007

In universities and elsewhere, might we study Shakespeare to learn about wisdom and how to grow wiser? Assuming with Nicholas Maxwell that wisdom is the capacity to realize what is of value in life, for oneself and others, then I say yes. The testimony is long and strong that being
wise goes against our grain, and that even if we can agree that this or that decision produces the most value, we may still fail to execute it well and faithfully. Though I wish things otherwise and hope for better, I still must register this long-respected 'wisdom' of our master bard in finding
us committed more to folly than its opposite. But what about wisdom, folly's opposite—does Shakespeare show us that and give us any clues about living wisely? Though he's never didactic, can we nonetheless deduce from his writing whether we mortals have any hope of escaping our innate
proclivity to foolish error and of following a path toward wisdom? I think so, if only in flashes and glimpses easily missed by those with no eyes to see nor ears to hear. In each of his plays elements of wisdom may be detected, often ironically in those characters who appear most foolish.
Functional Properties of Neuroglobin and Cytoglobin. Insights into the Ancestral Physiological Roles of Globins
Authors: Fago Angela , Hundahl Christian , Malte Hans , Weber Roy E.
Published: July 2007

Neuroglobin and cytoglobin are two recently discovered vertebrate globins, which are expressed at low levels in neuronal tissues and in all tissues investigated so far, respectively. Based on their amino acid sequences, these globins appear to be phylogenetically ancient and to have mutated less during evolution in comparison to the other vertebrate globins, myoglobin and hemoglobin. As with some plant and bacterial globins, neuroglobin and cytoglobin hemes are hexacoordinate in the absence of external ligands, in that the heme iron atom coordinates both a proximal and a distal His residue. While the physiological role of hexacoordinate globins is still largely unclear, neuroglobin appears to participate in the cellular defence against hypoxia. We present the current knowledge on the functional properties of neuroglobin and cytoglobin, and describe a mathematical model to evaluate the role of mammalian retinal neuroglobin in supplying O2 supply to the mitochondria. As shown, the model argues against a significant such role for neuroglobin, that more likely plays a role to scavenge reactive oxygen and nitrogen species that are generated following brain hypoxia. The O2 binding properties of cytoglobin, which is upregulated upon hypoxia, are consistent with a role for this protein in O2‐requiring reactions, such as those catalysed by hydroxylases.
IUBMB Life, 56: 689‐696, 2004
The 33rd Sir Frederick Bartlett Lecture Cognitive neuropsychiatry and delusional belief
Authors: Coltheart Max
Published: July 2007

Cognitive neuropsychiatry is a new field of cognitive psychology which seeks to learn more about the normal operation of high-level aspects of cognition such as belief formation, reasoning, decision making, theory of mind, and pragmatics by studying people in whom such processes are abnormal. So far, the high-level cognitive process most widely studied in cognitive neuropsychiatry has been belief formation, investigated by examining people with delusional beliefs. This paper describes some of the forms of delusional belief that have been examined from this perspective and offers a general two-deficit cognitive-neuropsychiatric account of delusional belief.
Tumor Cell Apoptosis Polarizes Macrophages—Role of Sphingosine-1-Phosphate
Authors: Weigert Andreas , Tzieply Nico , von Knethen Andreas , Johann Axel M. , Schmidt Helmut , Geisslinger Gerd , Brüne Bernhard
Published: July 2007

Macrophage polarization contributes to a number of human pathologies. This is exemplified for tumor-associated macrophages (TAMs), which display a polarized M2 phenotype, closely associated with promotion of angiogenesis and suppression of innate immune responses. We present evidence that induction of apoptosis in tumor cells and subsequent recognition of apoptotic debris by macrophages participates in the macrophage phenotype shift. During coculture of human primary macrophages with human breast cancer carcinoma cells (MCF-7) the latter ones were killed, while macrophages acquired an alternatively activated phenotype. This was characterized by decreased tumor necrosis factor (TNF)-α and interleukin (IL) 12-p70 production, but increased formation of IL-8 and -10. Alternative macrophage activation required tumor cell death because a coculture with apoptosis-resistant colon carcinoma cells (RKO) or Bcl-2–overexpressing MCF-7 cells failed to induce phenotype alterations. Interestingly, phenotype alterations were achieved with conditioned media from apoptotic tumor cells, arguing for a soluble factor. Knockdown of sphingosine kinase (Sphk) 2, but not Sphk1, to attenuate S1P formation in MCF-7 cells, restored classical macrophage responses during coculture. Furthermore, macrophage polarization achieved by tumor cell apoptosis or substitution of authentic S1P suppressed nuclear factor (NF)-κB signaling. These findings suggest that tumor cell apoptosis-derived S1P contributes to macrophage polarization.
Role of the V-ATPase in Regulation of the Vacuolar Fission–Fusion Equilibrium
Authors: Baars Tonie L. , Petri Sebastian , Peters Christopher , Mayer Andreas
Published: July 2007

Like numerous other eukaryotic organelles, the vacuole of the yeast Saccharomyces cerevisiae undergoes coordinated cycles of membrane fission and fusion in the course of the cell cycle and in adaptation to environmental conditions. Organelle fission and fusion processes must be balanced to ensure organelle integrity. Coordination of vacuole fission and fusion depends on the interactions of vacuolar SNARE proteins and the dynamin-like GTPase Vps1p. Here, we identify a novel factor that impinges on the fusion–fission equilibrium: the vacuolar H+-ATPase (V-ATPase) performs two distinct roles in vacuole fission and fusion. Fusion requires the physical presence of the membrane sector of the vacuolar H+-ATPase sector, but not its pump activity. Vacuole fission, in contrast, depends on proton translocation by the V-ATPase. Eliminating proton pumping by the V-ATPase either pharmacologically or by conditional or constitutive V-ATPase mutations blocked salt-induced vacuole fragmentation in vivo. In living cells, fission defects are epistatic to fusion defects. Therefore, mutants lacking the V-ATPase display large single vacuoles instead of multiple smaller vacuoles, the phenotype that is generally seen in mutants having defects only in vacuolar fusion. Its dual involvement in vacuole fission and fusion suggests the V-ATPase as a potential regulator of vacuolar morphology and membrane dynamics.
Expansion of Chromosome Territories with Chromatin Decompaction in BAF53-depleted Interphase Cells
Authors: Lee Kiwon , Kang Mi Jin , Kwon Su Jin , Kwon Yunhee Kim , Kim Ki Woo , Lim Jae-Hwan , Kwon Hyockman
Published: July 2007

Chromosomes are compartmentalized into discrete chromosome territories during interphase in mammalian cells. A chromosome territory is generated by the tendency of chromatin to occupy the smallest shell volume, which is determined by the polymeric properties and interactions of the internal meshwork of the chromatin fiber. Here, we show that BAF53 knockdown by small interfering RNA interference led to the expansion of chromosome territories. This was accompanied by a reduction in chromatin compaction, an increase in the micrococcal nuclease sensitivity of the chromatin, and an alteration in H3-K9 and H3-K79 dimethylation. Interestingly, the BAF53 knockdown cells suffer a cell cycle defect. Despite the significant irregularity and decompaction of the polynucleosomes isolated from the BAF53 knockdown cells, the chromatin loading of H1 and core histones remained unaltered, as did the nucleosome spacing. The histone hyperacetylation and down-regulation of BRG-1, mBrm, and Tip49, the catalytic components of the SWI/SNF complex and the TIP60 complex, respectively, did not expand chromosome territories. These results indicate that BAF53 contributes to the polymeric properties and/or the internal meshwork interactions of the chromatin fiber probably via a novel mechanism.
Mrc1 and Tof1 Regulate DNA Replication Forks in Different Ways during Normal S Phase
Authors: Hodgson Ben , Calzada Arturo , Labib Karim
Published: July 2007

The Mrc1 and Tof1 proteins are conserved throughout evolution, and in budding yeast they are known to associate with the MCM helicase and regulate the progression of DNA replication forks. Previous work has shown that Mrc1 is important for the activation of checkpoint kinases in responses to defects in S phase, but both Mrc1 and Tof1 also regulate the normal process of chromosome replication. Here, we show that these two important factors control the normal progression of DNA replication forks in distinct ways. The rate of progression of DNA replication forks is greatly reduced in the absence of Mrc1 but much less affected by loss of Tof1. In contrast, Tof1 is critical for DNA replication forks to pause at diverse chromosomal sites where nonnucleosomal proteins bind very tightly to DNA, and this role is not shared with Mrc1.
Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure
Authors: Marcello Lucio , Barry J. David
Published: July 2007

Trypanosoma brucei evades host acquired immunity through differential activation of its large archive of silent variant surface glycoprotein (VSG) genes, most of which are pseudogenes in subtelomeric arrays. We have analyzed 940 VSGs, representing one half to two thirds of the arrays. Sequence types A and B of the VSG N-terminal domains were confirmed, while type C was found to be a constituent of type A. Two new C-terminal domain types were found. Nearly all combinations of domain types occurred, with some bias to particular combinations. One-third of encoded N-terminal domains, but only 13% of C-terminal domains, are intact, indicating a particular need for silent VSGs to gain a functional C-terminal domain to be expressed. About 60% of VSGs are unique, the rest occurring in subfamilies of two to four close homologs (>50%–52% peptide identity). We found a subset of VSG-related genes, differing from VSGs in genomic environment and expression patterns, and predict they have distinct function. Almost all (92%) full-length array VSGs have the partially conserved flanks associated with the duplication mechanism that activates silent genes, and these sequences have also contributed to archive evolution, mediating most of the conversions of segments, containing ≥1 VSG, within and between arrays. During infection, intact array genes became activated by duplication after two weeks, and mosaic VSGs assembled from pseudogenes became expressed by week three and predominated by week four. The small subfamily structure of the archive appears to be fundamental in providing the interacting donors for mosaic formation.
Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation with lifespan in the red cell
Authors: Manning Lois R. , Russell J. Eric , Padovan Julio C. , Chait Brian T. , Popowicz Anthony , Manning Robert S. , Manning James M.
Published: July 2007

The different types of naturally occurring, normal human hemoglobins vary in their tetramer–dimer subunit interface strengths (stabilities) by three orders of magnitude in the liganded (CO or oxy) state. The presence of embryonic ζ‐subunits leads to an average 20‐fold weakening of tetramer–dimer interfaces compared to corresponding hemoglobins containing adult α‐subunits. The dimer–monomer interfaces of these hemoglobins differ by at least 500‐fold in their strengths; such interfaces are weak if they contain ζ‐subunits and exchange with added β‐subunits in the form of β4 (HbH) significantly faster than do those with α‐subunits. Subunit exchange occurs at the level of the dimer, although tetramer formation reciprocally influences the amount of dimer available for exchange. Competition between subunit types occurs so that pairs of weak embryonic hemoglobins can exchange subunits to form the stronger fetal and adult hemoglobins. The dimer strengths increase in the order Hb Portland‐2 (ζ2β2) < Hb Portland‐1 (ζ2γ2) ≅ Hb Gower‐1 (ζ2ε2) < Hb Gower‐2 (α2ε2) < HbF1 < HbF (α2γ2) < HbA2 (α2δ2), i.e., from embryonic to fetal to adult types, representing maturation from weaker to stronger monomer–monomer subunit contacts. This increasing order recapitulates the developmental order in which globins are expressed (embryonic → fetal → adult), suggesting that the intrinsic binding properties of the subunits themselves regarding the strengths of interfaces they form with competing subunits play an important role in the dynamics of protein assemblies and networks.
Structure in an extreme environment: NMR at high salt
Authors: Binbuga Bulent , Boroujerdi Arezue F.B. , Young John K.
Published: July 2007

Proteins from halophiles have adapted to challenging environmental conditions and require salt for their structure and function. How halophilic proteins adapted to a hypersaline environment is still an intriguing question. It is important to mimic the physiological conditions of the archae extreme halophiles when characterizing their enzymes, including structural characterization. The NMR derived structure of Haloferax volcanii dihydrofolate reductase in 3.5 M NaCl is presented, and represents the first high salt structure calculated using NMR data. Structure calculations show that this protein has a solution structure which is similar to the previously determined crystal structure with a difference at the N terminus of β3 and the type of β‐turn connection β7 and β8.
Building native protein conformation from NMR backbone chemical shifts using Monte Carlo fragment assembly
Authors: Gong Haipeng , Shen Yang , Rose George D.
Published: July 2007

We have been analyzing the extent to which protein secondary structure determines protein tertiary structure in simple protein folds. An earlier paper demonstrated that three‐dimensional structure can be obtained successfully using only highly approximate backbone torsion angles for every residue. Here, the initial information is further diluted by introducing a realistic degree of experimental uncertainty into this process. In particular, we tackle the practical problem of determining three‐dimensional structure solely from backbone chemical shifts, which can be measured directly by NMR and are known to be correlated with a protein's backbone torsion angles. Extending our previous algorithm to incorporate these experimentally determined data, clusters of structures compatible with the experimentally determined chemical shifts were generated by fragment assembly Monte Carlo. The cluster that corresponds to the native conformation was then identified based on four energy terms: steric clash, solvent‐squeezing, hydrogen‐bonding, and hydrophobic contact. Currently, the method has been applied successfully to five small proteins with simple topology. Although still under development, this approach offers promise for high‐throughput NMR structure determination.
A novel technique for estimating the compact myocardium in fishes reveals surprising results for an athletic air‐breathing fish, the Pacific tarpon
Authors: Farrell A. P. , Simonot D. L. , Seymour R. S. , Clark T. D.
Published: July 2007

A method for quickly assessing the relative proportion of compact myocardium in the ventricle of teleosts is introduced and used in juvenile Pacific tarpon Megalops cyprinoides, a member of the only air‐breathing elopomorph teleost genus. The proportion of compact myocardium increased with body mass, reaching up to 60% of the ventricular mass. The finding for tarpon was a surprising discovery since recent literature has suggested that air breathing evolved primarily as means of supplying oxygen to the fish heart during activity. The present data, which represent the first quantitative assessment of the compact myocardium for any air‐breathing fish, suggest that myocardial oxygen supply in the tarpon is supplemented by the coronary circulation associated with compact myocardium during exercise, while air breathing is important during aquatic hypoxia. Compact myocardium was also measured as a point of reference in an extant representative from a more ancient fish lineage than the elopomorphs, the water‐breathing spiny dogfish Squalus acanthias and found to be only 9% of ventricular mass. In conclusion, the presence of a coronary circulation in extant elasmobranchs may mean that the coronary circulation evolved well before air breathing in fishes and, for tarpon at least, the coronary oxygen supply to the ventricular myocardium has not necessarily been superseded by air breathing.
Geographic variation in life‐history traits of the endemic kite skate Dipturus chilensis (Batoidea: Rajidae), along its distribution in the fjords and channels of southern Chile
Authors: Licandeo R. , Cerna F. T.
Published: July 2007

Life‐history traits of kite skates Dipturus chilensis were examined from two regions (c. 2286 km apart) in the sheltered fjords and channels of southern Chile. A total of 482 and 403 specimens were collected from the southern fjords (c. 42–46° S) and the fjords of Chilean Patagonia (c. 51–54° S), from September 2003 to 2004, respectively. Vertebra marginal increment analysis indicated an annual deposition of growth rings which was completed during the winter months. For each region, von Bertalanffy growth parameters showed that females attained a larger asymptotic size, L∞, had a lower growth coefficient, K, and lived longer than males. Growth analysis indicated that D. chilensis from the Patagonian fjords had a longer life span (females: 22 v. 21 years; males 19 v. 17 years), attained a larger L∞ (females: 150 v. 136 cm; males: 122 v. 118 cm total length, LT) and had a lower K value (females: 0·087 v. 0·104; males: 0·110 v. 0·116) than their counterparts in the southern fjords. Comparisons with previous studies indicated that D. chilensis from both southern and Patagonian sheltered fjords had larger L∞, and grew more slowly than their counterparts from central‐southern Chile (L∞= 119–123 cm, K= 0·123–0·127), suggesting latitudinal variations in growth. Females attained sexual maturity later than males in both regions. For both sexes, lengths at 50% maturity (L50%) between regions were similar (females: c. 103 cm; males: c. 87 cm LT); however, D. chilensis from Patagonia appeared to mature 1 year earlier (females: 13 v. 14 years; males: 10 v. 11 years). Specimens from Patagonia had a lower ovarian fecundity than those from the southern fjords. An increase in the proportion of mature females and males during summer, suggests that the reproductive peak occurs in this season, and no regional differences were found. The size of the egg cases increased with maternal LT and these were longer in Patagonia. The information provided here represents the first evidence of regional variations in life‐history traits for elasmobranchs in the south‐eastern Pacific.
First record of Cephalopholis taeniops (Valenciennes) in the Mediterranean Sea
Authors: Ben Abdallah A. , Ben Souissi J. , Méjri H. , Capapé C. , Golani D.
Published: July 2007

Two specimens of African hind Cephalopholis taeniops (Valenciennes, 1828) are recorded for the first time in the Mediterranean Sea, in the coastal area of Gulf of Syrte, Libya. This finding represents an additional case of a tropical species of fish of West African origin in the Mediterranean Sea.
Larval development of the Ambon damselfish Pomacentrus amboinensis, with a summary of pomacentrid development
Authors: Murphy B. F. , Leis J. M. , Kavanagh K. D.
Published: July 2007

Morphological development of the larvae of the Ambon damselfish Pomacentrus amboinensis from the Great Barrier Reef, Australia, is described from 34 reared specimens (2·5–13·0 mm standard length), and two wild settlement‐stage larvae (10·8–11·3 mm) captured in light traps. Reared larvae emerged from demersal eggs at c. 2·5 mm, underwent notochord flexion at 4·0–4·5 mm, and settled at 11–13 mm at 19–21 days after hatching (within the known range for wild larvae). Reared larvae grew at 0·3 mm day−1 (preflexion) to 0·5 mm day−1 (postflexion). Development was direct with few specializations for pelagic existence and was typical of pomacentrids. Head spination consisted of very weak spines on the preopercle, opercle, interopercle, subopercle and supracleithrum. Development of the olfactory system and retina are also described. A summary of published descriptions of early life‐history stages of pomacentrid damselfishes is provided (n= 15% of known species). Larvae of several genera (e.g. Abudefduf, Chromis and Stegastes) are deeper‐bodied and more ‘hunchbacked’ than P. amboinensis. Larvae of other genera (e.g. Amblyglyphidodon, Chrysiptera and Neoglyphidodon) are similar to P. amboinensis. Larvae of only three other Pomacentrus species have been described, and they are similar to P. amboinensis in body morphology, pigmentation and head spination.
Pioglitazone shift circadian rhythm of blood pressure from non‐dipper to dipper type in type 2 diabetes mellitus
Authors: Anan F. , Masaki T. , Fukunaga N. , Teshima Y. , Iwao T. , Kaneda K. , Umeno Y. , Okada K. , Wakasugi K. , Yonemochi H. , Eshima N. , Saikawa T. , Yoshimatsu H.
Published: July 2007

Background  Insulin resistance significantly correlated with a non‐dipper type of essential hypertension. Thiazolidinediones (TZD), oral hypoglycaemic agents that act as insulin sensitizers, have been demonstrated in multiple in vivo and in vitro studies to possess antihypertensive properties. This study examined the efficacy of TZD therapy with pioglitazone at transforming the circadian rhythms of blood pressure from a non‐dipper to a dipper type.

Materials  We examined 31 patients with type 2 diabetes mellitus during both a baseline period and a period of treatment with pioglitazone. Patients received 15 mg day−1 pioglitazone for four weeks and 30 mg day−1 for 12 weeks. Twenty‐four hour ambulatory blood pressure monitoring (ABPM) and laboratory data (blood tests for cardiovascular risk factors) were obtained at the beginning and end of the study.

Results  In non‐dippers (n = 16), but not dippers (n = 15), we observed a significant interaction between pioglitazone therapy and nocturnal falls in systolic and diastolic blood pressure. This examination indicated that the magnitude of the nocturnal blood pressure fall was affected by pioglitazone therapy. In non‐dippers, but not dippers, a significant correlation was observed between the percent decrease in nocturnal BP and the homeostasis model assessment (HOMA) index (r = 0·774, P = 0·0007).

Conclusions  The present study demonstrated that pioglitazone can restore the nocturnal BP declines in parallel to reductions in the HOMA index, suggesting that insulin resistance may play an important role in the genesis of circadian BP rhythms. TZD‐based treatment may thus have the additional therapeutic advantage of reducing the risk of cardiovascular complications by transforming the circadian rhythm of BP.
Utility of computed tomography of the head following head trauma in boys with haemophilia
Authors: WITMER C. M. , RAFFINI L. J. , MANNO C. S.
Published: July 2007

Summary.  The most serious site of bleeding for patients with haemophilia is the central nervous system. Intracranial haemorrhage (ICH) in patients with haemophilia can occur spontaneously or following mild head trauma however no guidelines exist for the approach to these patients. The goal of this review was to determine the utility of screening computed tomography (CT) of the head for patients with haemophilia who experience head trauma and to determine if the use of clinical criteria could allow a selective approach to radiographic imaging. In a retrospective study we reviewed the management of head trauma in a cohort of paediatric patients with haemophilia in a single institution. The cohort included males, ages birth to 18 years with haemophilia A or B who were followed at the haemophilia treatment center at The Children’s Hospital of Philadelphia from 1994 to 2005. Between the years of 1994 and 2005, 97 patients were evaluated for head trauma for a total of 374 emergency department visits. There were 295 head CT scans performed to identify 9 (3%) episodes of intracranial bleeding. Fifty‐six per cent of the patients with intracranial bleeding had no clinical signs or symptoms. The clinical outcome was excellent in all cases with no deaths or reported morbidity. In this cohort, a lack of symptoms and a normal neurological exam did not exclude ICH, especially in patients with severe haemophilia who were evaluated soon after a mild head trauma event suggesting the utility of early head CT imaging.
Family dynamics in families of severe COPD patients
Authors: Kanervisto Merja , Paavilainen Eija , Heikkilä Johanna
Published: July 2007

Aim and objectives.  The purpose of this study was to describe family dynamics in families with severe chronic obstructive pulmonary disease (COPD) on the basis of Barnhill's framework for healthy family systems. The sample consisted of 35 severe COPD patients and 30 family members at Tampere University Hospital, Finland or in the neighbouring regions.

Background.  Chronic obstructive pulmonary disease is a public health problem worldwide. It is a slowly progressive airway disease, producing a decline in lung function which is not fully reversible.

Design.  The sample included the families of patients without oxygen therapy and the families of patients who had long‐term oxygen therapy (LTOT). The data were collected using the Family Dynamics Measure 2 (FDM2) and the Family Dynamics Questionnaire (FDQ).

Method.  A quantitative research method was employed in the study. Frequency and percentage distributions, as well as cross‐tabulations, were used to describe the data. Mean values and standard deviations were calculated for the sum variables of six dimensions of the FDM2.

Results.  In the dimensions of individuation, mutuality and flexibility, dynamics in the families of patients with LTOT was significantly better than of the patients without oxygen therapy. Especially in the dimension of mutuality, the families of LTOT patients functioned very well, while in the dimensions of communication and roles, family dynamics in these families was notably worse, although still good.

Conclusion.  Poor self‐identity – enmeshment, isolation from others and lack of flexibility to varying conditions – in families with severe COPD can weaken the ability of the families to manage in everyday life.

Relevance to clinical practice.  Families need family nursing to adapt to alterations occurring when a family member has severe COPD. Nurses can give support and help for these families for their roles of patient and caregiver, as well as opportunities to speak with someone about their situation.
Preceptoring a student in the final clinical placement: reflections from nurses in a Canadian Hospital
Authors: Bourbonnais Frances Fothergill , Kerr Evelyn
Published: July 2007

Aim.  To capture personal reflections on being a preceptor and to identify the supports and challenges to enacting the role.

Background.  Prior to graduation from a nursing programme, students begin the transition in roles from student to practicing health‐care professional. To ease this transition, preceptorship programmes have been implemented to foster professional socialization and help students achieve confidence in their practice during their final clinical placement (consolidation experience). Preparation for the preceptor role is dependent upon the information offered by the agency as well as by the educational institution. Nursing staff are requested for much of the calendar year to work with increasing numbers of undergraduate students at various levels, function as preceptors in the final clinical experience (consolidation) as well as be involved in the orientation of newly hired nurses.

Methods.  This qualitative study used one‐on‐one tape recorded interviews with nurses who had previous experience as a preceptor. Thematic analysis of the transcribed data resulted in the emergence of an overall theme and categories.

Results.  Eight nurses were interviewed from a variety of units including medical surgical as well as critical care. The overriding theme from the analysis was ‘safe passage’. This safe passage was for the patient and the student and was accomplished through the process of teaching and a clear view of the preceptor role. Challenges to the role were lack of recognition by other nursing staff as well as limited support from some faculty advisors. Supports for the role were the visible presence and ongoing support by faculty advisors as well as the hospital workshop.

Conclusion.  This study highlighted the importance of support from nursing faculty as well as recognition by fellow nurses of the workload involved when being a preceptor.

Relevance to clinical practice.  Preceptors play an important role with students prior to graduation. Both the hospital and educational institutions need to ensure that nurses are given the necessary support, recognition and resources.
Resistance of Pseudoperonospora cubensis to flumorph on cucumber in plastic houses
Authors: Zhu S. S. , Liu X. L. , Wang Y. , Wu X. H. , Liu P. F. , Li J. Q. , Yuan S. K. , Si N. G.
Published: July 2007

Plastic‐house experiments were conducted over a 2‐year period (2004–05) to estimate the effects of successive applications of flumorph or a mixture of flumorph with mancozeb to cucumber plants on selection for flumorph resistance in the downy mildew oomycete, Pseudoperonospora cubensis. Application of flumorph alone favoured the selection of resistant isolates of Ps. cubensis. Resistant populations were detected at a frequency of 2·5% after six successive applications of flumorph alone in a plastic house in 2004. Resistant isolates were also detected (4·8%) after eight successive applications of the mixture of flumorph and mancozeb in 2004, although the mixture gave significantly better disease control than flumorph alone and produced a slight delay in the development of resistance. In a second cucumber crop in the same plastic houses in 2004, the frequency of resistant isolates increased to 100% after three successive applications of flumorph or four of flumorph + mancozeb. Under laboratory conditions, most flumorph‐resistant isolates showed high levels of resistance and their levels of pathogenicity and sporulation were as high as that of wild‐type isolates. Flumorph showed cross‐resistance with dimethomorph and iprovalicarb, but not with azoxystrobin, cyazofamid, cymoxanil or metalaxyl. These studies suggest a high risk for the occurrence of resistance to flumorph in Ps. cubensis in cucumber crops under plastic‐house conditions.
Diversity and detection of Korean Erwinia pyrifoliae strains as determined by plasmid profiling, phylogenetic analysis and PCR
Authors: Shrestha R. , Lee S. H. , Kim J. E. , Wilson C. , Choi S.‐G. , Park D. H. , Wang M. H. , Hur J. H. , Lim C. K.
Published: July 2007

Twenty‐five strains of Erwinia pyrifoliae were investigated for their plasmid profiles and genetic relatedness. Four types of plasmid profile were observed for the first time, suggesting intraspecific plasmid profile diversity in E. pyrifoliae. Moreover, BOX‐PCR and phylogenetic analysis based on the 16S‐23S intergenic transcribed spacer (ITS) region showed genetic variations among E. pyrifoliae strains, although all strains were clustered in one group and separated from E. amylovora. On the other hand, ERIC‐PCR and phylogenetic analysis based on partial groEL gene sequences revealed close genetic relatedness among the strains. Amplification with EpSPF and EpSPR primers of a fragment of approximately 0·65 kb from the genomic DNA of all E. pyrifoliae strains, but not from E. amylovora strains, suggested that this primer set is useful for identification of this pathogen.