bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome mobility during meiotic prophase in
Saccharomyces cerevisiae
Authors: Scherthan Harry , Wang Hailin , Adelfalk Caroline , White Eric J. , Cowan Carrie , Cande W. Zacheus , Kaback David B.
Published: October 2007

In many organisms, a synaptonemal complex (SC) intimately connects each pair of homologous chromosomes during much of the first meiotic prophase and is thought to play a role in regulating recombination. In the yeast
Saccharomyces cerevisiae
, the central element of each SC contains Zip1, a protein orthologous to mammalian SYCP1. To study the dynamics of SCs in living meiotic cells, a functional
ZIP1
::
GFP
fusion was introduced into yeast and analyzed by fluorescence video microscopy. During pachytene, SCs exhibited dramatic and continuous movement throughout the nucleus, traversing relatively large distances while twisting, folding, and unfolding. Chromosomal movements were accompanied by changes in the shape of the nucleus, and all movements were reversibly inhibited by the actin antagonist Latrunculin B. Normal movement required the
NDJ1
gene, which encodes a meiosis-specific telomere protein needed for the attachment of telomeres to the nuclear periphery and for normal kinetics of recombination and meiosis. These results show that SC movements involve telomere attachment to the nuclear periphery and are actin-dependent and suggest these movements could facilitate completion of meiotic recombination.
The basic helix–loop–helix domain of maize R links transcriptional regulation and histone modifications by recruitment of an EMSY-related factor
Authors: Hernandez J. Marcela , Feller Antje , Morohashi Kengo , Frame Kenneth , Grotewold Erich
Published: October 2007

The control of anthocyanin accumulation in maize by the cooperation of the basic helix–loop–helix (bHLH) protein R with the MYB transcription factor C1 provides one of the best examples of plant combinatorial transcriptional control. Establishing the function of the bHLH domain of R has remained elusive, and so far no proteins that interact with this conserved domain have been identified. We show here that the bHLH domain of R is dispensable for the activation of transiently expressed genes yet is essential for the activation of the endogenous genes in their normal chromatin environment. The activation of
A1
, one of the anthocyanin biosynthetic genes, is associated with increased acetylation of histone 3 (H3) at K9/K14 in the promoter region to which the C1/R complex binds. We identified R-interacting factor 1 (RIF1) as a nuclear, AGENET domain-containing EMSY-like protein that specifically interacts with the bHLH region of R. Knockdown experiments show that RIF1 is necessary for the activation of the endogenous promoters but not of transiently expressed genes. ChIP experiments established that RIF1 is tethered to the regulatory region of the
A1
promoter by the C1/R complex. Together, these findings describe a function for the bHLH domain of R in linking transcriptional regulation with chromatin functions by the recruitment of an EMSY-related factor.
Hydrogen sulfide mediates the vasoactivity of garlic
Authors: Benavides Gloria A. , Squadrito Giuseppe L. , Mills Robert W. , Patel Hetal D. , Isbell T. Scott , Patel Rakesh P. , Darley-Usmar Victor M. , Doeller Jeannette E. , Kraus David W.
Published: October 2007

The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H
2
S), an endogenous cardioprotective vascular cell signaling molecule. This H
2
S production, measured in real time by a novel polarographic H
2
S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H
2
S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the α carbon of the allyl substituent, thereby forming a hydropolysulfide (RS
n
H), a key intermediate during the formation of H
2
S. Organic polysulfides (R-S
n
-R′;
n
> 2) also undergo nucleophilic substitution at a sulfur atom, yielding RS
n
H and H
2
S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H
2
S. The vasoactivity of garlic compounds is synchronous with H
2
S production, and their potency to mediate relaxation increases with H
2
S yield, strongly supporting our hypothesis that H
2
S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H
2
S can be used to standardize garlic dietary supplements.
Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis
Authors: Samuel Melanie A. , Wang Hong , Siddharthan Venkatraman , Morrey John D. , Diamond Michael S.
Published: October 2007

West Nile virus (WNV) has emerged as a significant cause of epidemic viral encephalitis and flaccid limb paralysis, yet the mechanism by which it enters the CNS remains uncertain. We used compartmentalized neuron cultures to demonstrate that WNV spreads in both retrograde and anterograde directions via axonal transport. Transneuronal spread of WNV required axonal release of viral particles and was blocked by addition of a therapeutic neutralizing antibody. To test the physiologic significance of axonal transport
in vivo
, we directly inoculated the sciatic nerve of hamsters with WNV. Intrasciatic infection resulted in paralysis of the hind limb ipsilateral but not contralateral to the injection site. Limb paralysis was blocked either by surgical transection of the sciatic nerve or treatment with the therapeutic neutralizing antibody. Collectively, these studies establish that WNV undergoes bidirectional spread in neurons and that axonal transport promotes viral entry into the CNS and acute limb paralysis. Moreover, antibody therapeutics directly inhibit transneuronal spread of WNV infection and prevent the development of paralysis
in vivo
.
Efficient production of [
n
]rotaxanes by using template-directed clipping reactions
Authors: Wu Jishan , Leung Ken Cham-Fai , Stoddart J. Fraser
Published: October 2007

In this article, we report on the efficient synthesis of well defined, homogeneous [
n
]rotaxanes (
n
up to 11) by a template-directed thermodynamic clipping approach. By employing dynamic covalent chemistry in the form of reversible imine bond formation, [
n
]rotaxanes with dialkylammonium ion (–CH
2
NH
2
+
CH
2
–) recognition sites, encircled by [24]crown-8 rings, were prepared by a thermodynamically controlled, template-directed clipping procedure, that is, by mixing together a dumbbell compound containing a discrete number of

CH
2
NH
2
+
CH
2
– ion centers with appropriate amounts of a dialdehyde and a diamine to facilitate the [
n
]rotaxane formation. A 21-component self-assembly process is operative during the formation of the [11]rotaxane. The oligomeric dumbbells containing

CH
2
NH
2
+
CH
2
– ion recognition sites were prepared by a stepwise protocol. Several of the dynamic [
n
]rotaxanes were converted into their kinetically stable counterparts, first by reduction (“fixing”) of imine bonds with the BH
3
·THF complex, then by protonation of the complex by addition of acid.
Active root-inhabiting microbes identified by rapid incorporation of plant-derived carbon into RNA
Authors: Vandenkoornhuyse Philippe , Mahé Stéphane , Ineson Philip , Staddon Phil , Ostle Nick , Cliquet Jean-Bernard , Francez André-Jean , Fitter Alastair H. , Young J. Peter W.
Published: October 2007

Plant roots harbor a large diversity of microorganisms that have an essential role in ecosystem functioning. To better understand the level of intimacy of root-inhabiting microbes such as arbuscular mycorrhizal fungi and bacteria, we provided
13
CO
2
to plants at atmospheric concentration during a 5-h pulse. We expected microbes dependent on a carbon flux from their host plant to become rapidly labeled. We showed that a wide variety of microbes occurred in roots, mostly previously unknown. Strikingly, the greatest part of this unsuspected diversity corresponded to active primary consumers. We found 17 bacterial phylotypes co-occurring within roots of a single plant, including five potentially new phylotypes. Fourteen phylotypes were heavily labeled with the
13
C. Eight were phylogenetically close to Burkholderiales, which encompass known symbionts; the others were potentially new bacterial root symbionts. By analyzing unlabeled and
13
C-enriched RNAs, we demonstrated differential activity in C consumption among these root-inhabiting microbes. Arbuscular mycorrhizal fungal RNAs were heavily labeled, confirming the high carbon flux from the plant to the fungal compartment, but some of the fungi present appeared to be much more active than others. The results presented here reveal the possibility of uncharacterized root symbioses.
A role for IκB kinase 2 in bipolar spindle assembly
Authors: Irelan Jeffrey T. , Murphy Thomas J. , DeJesus Paul D. , Teo Hsiangling , Xu DingYue , Gomez-Ferreria Maria A. , Zhou Yingyao , Miraglia Loren J. , Rines Daniel R. , Verma Inder M. , Sharp David J. , Tergaonkar Vinay , Chanda Sumit K.
Published: October 2007

IκB kinase 2 (IKK2 or IKKβ) is a component of the IKK complex that coordinates the cellular response to a diverse set of extracellular stimuli, including cytokines, microbial infection, and stress. In response to an external stimulus, the complex is activated, resulting in the phosphorylation and subsequent proteasome-mediated degradation of IκB proteins. This event triggers the nuclear import of the NF-κB transcription factor, which activates the transcription of genes that regulate a variety of fundamental biological processes, including immune response, cell survival, and development. Here, we define an essential role for IKK2 in normal mitotic progression and the maintenance of spindle bipolarity. Chemical and genetic perturbation of IKK2 promotes the formation of multipolar spindles and chromosome missegregation. Depletion of IKK2 results in the deregulation of Aurora A protein stability and coincident hyperactivation of a putative Aurora A substrate, the mitotic motor KIF11. These data support a function for IKK2 as an antagonist of Aurora A signaling during mitosis. Additionally, our results indicate a direct role for IKK2 in the maintenance of genome stability and underscore the potential for oncogenic consequences in targeting this kinase for therapeutic intervention.
Proteomic identification of tmRNA substrates
Authors: Hong Sue-Jean , Lessner Faith H. , Mahen Elisabeth M. , Keiler Kenneth C.
Published: October 2007

The tmRNA–SmpB system releases ribosomes stalled on truncated mRNAs and tags the nascent polypeptides to target them for proteolysis. In many species, mutations that disrupt tmRNA activity cause defects in growth or development. In
Caulobacter crescentus
cells lacking tmRNA activity there is a delay in the initiation of DNA replication, which disrupts the cell cycle. To understand the molecular basis for this phenotype, 73
C. crescentus
proteins were identified that are tagged by tmRNA under normal growth conditions. Among these substrates, proteins involved in DNA replication, recombination, and repair were overrepresented, suggesting that misregulation of these factors in the absence of tmRNA activity might be responsible for the delay in initiation of DNA replication. Analysis of the tagging sites within these substrates revealed a conserved nucleotide motif 5′ of the tagging site, which is required for wild-type tmRNA tagging.
Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy
Authors: Tan Heneu O. , Reid Christopher A. , Single Frank N. , Davies Philip J. , Chiu Cindy , Murphy Susan , Clarke Alison L. , Dibbens Leanne , Krestel Heinz , Mulley John C. , Jones Mathew V. , Seeburg Peter H. , Sakmann Bert , Berkovic Samuel F. , Sprengel Rolf , Petrou Steven
Published: October 2007

Mutations in the GABAAreceptor γ2 subunit are associated with childhood absence epilepsy and febrile seizures. To understand better the molecular basis of absence epilepsy in man, we developed a mouse model harboring a γ2 subunit point mutation (R43Q) found in a large Australian family. Mice heterozygous for the mutation demonstrated behavioral arrest associated with 6-to 7-Hz spike-and-wave discharges, which are blocked by ethosuximide, a first-line treatment for absence epilepsy in man. Seizures in the mouse showed an abrupt onset at around age 20 days corresponding to the childhood nature of this disease. Reduced cell surface expression of γ2(R43Q) was seen in heterozygous mice in the absence of any change in α1 subunit surface expression, ruling out a dominant-negative effect. GABAA-mediated synaptic currents recorded from cortical pyramidal neurons revealed a small but significant reduction that was not seen in the reticular or ventrobasal thalamic nuclei. We hypothesize that a subtle reduction in cortical inhibition underlies childhood absence epilepsy seen in humans harboring the R43Q mutation.
Plasma membrane domain organization regulates EGFR signaling in tumor cells
Authors: Lajoie Patrick , Partridge Emily A. , Guay Ginette , Goetz Jacky G. , Pawling Judy , Lagana Annick , Joshi Bharat , Dennis James W. , Nabi Ivan R.
Published: October 2007

Macromolecular complexes exhibit reduced diffusion in biological membranes; however, the physiological consequences of this characteristic of plasma membrane domain organization remain elusive. We report that competition between the galectin lattice and oligomerized caveolin-1 microdomains for epidermal growth factor (EGF) receptor (EGFR) recruitment regulates EGFR signaling in tumor cells. In mammary tumor cells deficient for Golgi β1,6N-acetylglucosaminyltransferase V (Mgat5), a reduction in EGFR binding to the galectin lattice allows an increased association with stable caveolin-1 cell surface microdomains that suppresses EGFR signaling. Depletion of caveolin-1 enhances EGFR diffusion, responsiveness to EGF, and relieves Mgat5 deficiency–imposed restrictions on tumor cell growth. In Mgat5+/+ tumor cells, EGFR association with the galectin lattice reduces first-order EGFR diffusion rates and promotes receptor interaction with the actin cytoskeleton. Importantly, EGFR association with the lattice opposes sequestration by caveolin-1, overriding its negative regulation of EGFR diffusion and signaling. Therefore, caveolin-1 is a conditional tumor suppressor whose loss is advantageous when β1,6GlcNAc-branched N-glycans are below a threshold for optimal galectin lattice formation.
Splicing- and cleavage-independent requirement of RNA polymerase II CTD for mRNA release from the transcription site
Authors: Custódio Noélia , Vivo Maria , Antoniou Michael , Carmo-Fonseca Maria
Published: October 2007

Eukaryotic cells have a surveillance mechanism that identifies aberrantly processed pre-mRNAs and prevents their flow to the cytoplasm by tethering them near the site of transcription. Here we provide evidence that mRNA release from the transcription site requires the heptad repeat structure of the C-terminal domain (CTD) of RNA polymerase II. The mammalian CTD, which is essential for normal co-transcriptional maturation of mRNA precursors, comprises 52 heptad repeats. We show that a truncated CTD containing 31 repeats (heptads 1–23, 36–38, and 48–52) is sufficient to support transcription, splicing, cleavage, and polyadenylation. Yet, the resulting mRNAs are mostly retained in the vicinity of the gene after transcriptional shutoff. The retained mRNAs maintain the ability to recruit components of the exon junction complex and the nuclear exosome subunit Rrp6p, suggesting that binding of these proteins is not sufficient for RNA release. We propose that the missing heptads in the truncated CTD mutant are required for binding of proteins implicated in a final co-transcriptional maturation of spliced and 3′ end cleaved and polyadenylated mRNAs into export-competent ribonucleoprotein particles.
Bod1, a novel kinetochore protein required for chromosome biorientation
Authors: Porter Iain M. , McClelland Sarah E. , Khoudoli Guennadi A. , Hunter Christopher J. , Andersen Jens S. , McAinsh Andrew D. , Blow J. Julian , Swedlow Jason R.
Published: October 2007

We have combined the proteomic analysis of Xenopus laevis in vitro–assembled chromosomes with RNA interference and live cell imaging in HeLa cells to identify novel factors required for proper chromosome segregation. The first of these is Bod1, a protein conserved throughout metazoans that associates with a large macromolecular complex and localizes with kinetochores and spindle poles during mitosis. Small interfering RNA depletion of Bod1 in HeLa cells produces elongated mitotic spindles with severe biorientation defects. Bod1-depleted cells form syntelic attachments that can oscillate and generate enough force to separate sister kinetochores, suggesting that microtubule–kinetochore interactions were intact. Releasing Bod1-depleted cells from a monastrol block increases the frequency of syntelic attachments and the number of cells displaying biorientation defects. Bod1 depletion does not affect the activity or localization of Aurora B but does cause mislocalization of the microtubule depolymerase mitotic centromere- associated kinesin and prevents its efficient phosphorylation by Aurora B. Therefore, Bod1 is a novel kinetochore protein that is required for the detection or resolution of syntelic attachments in mitotic spindles.
DNA-dependent protein kinase in nonhomologous end joining: a lock with multiple keys?
Authors: Weterings Eric , Chen David J.
Published: October 2007

The DNA-dependent protein kinase (DNA-PK) is one of the central enzymes involved in DNA double-strand break (DSB) repair. It facilitates proper alignment of the two ends of the broken DNA molecule and coordinates access of other factors to the repair complex. We discuss the latest findings on DNA-PK phosphorylation and offer a working model for the regulation of DNA-PK during DSB repair.
Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis
Authors: Jeganathan Karthik , Malureanu Liviu , Baker Darren J. , Abraham Susan C. , van Deursen Jan M.
Published: October 2007

The physiological role of the mitotic checkpoint protein Bub1 is unknown. To study this role, we generated a series of mutant mice with a gradient of reduced Bub1 expression using wild-type, hypomorphic, and knockout alleles. Bub1 hypomorphic mice are viable, fertile, and overtly normal despite weakened mitotic checkpoint activity and high percentages of aneuploid cells. Bub1 haploinsufficient mice, which have a milder reduction in Bub1 protein than Bub1 hypomorphic mice, also exhibit reduced checkpoint activity and increased aneuploidy, but to a lesser extent. Although cells from Bub1 hypomorphic and haploinsufficient mice have similar rates of chromosome missegregation, cell death after an aberrant separation decreases dramatically with declining Bub1 levels. Importantly, Bub1 hypomorphic mice are highly susceptible to spontaneous tumors, whereas Bub1 haploinsufficient mice are not. These findings demonstrate that loss of Bub1 below a critical threshold drives spontaneous tumorigenesis and suggest that in addition to ensuring proper chromosome segregation, Bub1 is important for mediating cell death when chromosomes missegregate.
A constant affinity threshold for T cell tolerance
Authors: Naeher Dieter , Daniels Mark A. , Hausmann Barbara , Guillaume Philippe , Luescher Immanuel , Palmer Ed
Published: October 2007

T cell tolerance depends on the T cell receptor's affinity for peptide/major histocompatibility complex (MHC) ligand; this critical parameter determines whether a thymocyte will be included (positive selection) or excluded (negative selection) from the T cell repertoire. A quantitative analysis of ligand binding was performed using an experimental system permitting receptor–coreceptor interactions on live cells under physiological conditions. Using three transgenic mouse strains expressing distinct class I MHC–restricted T cell receptors, we determined the affinity that defines the threshold for negative selection. The affinity threshold for self-tolerance appears to be a constant for cytotoxic T lymphocytes.
Germinal centers in human lymph nodes contain reactivated memory B cells
Authors: Bende Richard J. , van Maldegem Febe , Triesscheijn Martijn , Wormhoudt Thera A.M. , Guijt Richard , van Noesel Carel J.M.
Published: October 2007

To reveal migration trails of antigen-responsive B cells in lymphoid tissue, we analyzed immunoglobulin (Ig)M-VH and IgG-VH transcripts of germinal center (GC) samples microdissected from three reactive human lymph nodes. Single B cell clones were found in multiple GCs, one clone even in as many as 19 GCs. In several GCs, IgM and IgG variants of the same clonal origin were identified. The offspring of individual hypermutated IgG memory clones were traced in multiple GCs, indicating repeated engagement of memory B cells in GC reactions. These findings imply that recurring somatic hypermutation progressively drives the Ig repertoire of memory B cells to higher affinities and infer that transforming genetic hits in non-Ig genes during lymphomagenesis do not have to arise during a single GC passage, but can be collected during successive recall responses.
Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes
Authors: Shi Guixiu , Partida-Sánchez Santiago , Misra Ravi S. , Tighe Michael , Borchers Michael T. , Lee James J. , Simon Melvin I. , Lund Frances E.
Published: October 2007

CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the basis for this signaling heterogeneity, we examined the chemokine receptors that signal in a CD38-dependent manner and identified a novel “alternative” chemokine receptor signaling pathway. Similar to the “classical” signaling pathway, the alternative chemokine receptor pathway is activated by Gαi2-containing Gi proteins. However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins. We show that Gαq-deficient neutrophils and dendritic cells (DCs) make defective calcium and chemotactic responses upon stimulation with N-formyl methionyl leucyl phenylalanine and CC chemokine ligand (CCL) 3 (neutrophils), or upon stimulation with CCL2, CCL19, CCL21, and CXC chemokine ligand (CXCL) 12 (DCs). In contrast, Gαq-deficient T cell responses to CXCL12 and CCL19 remain intact. Thus, the alternative chemokine receptor pathway controls the migration of only a subset of cells. Regardless, the novel alternative chemokine receptor signaling pathway appears to be critically important for the initiation of inflammatory responses, as Gαq is required for the migration of DCs from the skin to draining lymph nodes after fluorescein isothiocyanate sensitization and the emigration of monocytes from the bone marrow into inflamed skin after contact sensitization.
Zinc Modulation of Water Permeability Reveals that Aquaporin 0 Functions as a Cooperative Tetramer
Authors: Németh-Cahalan Karin L. , Kalman Katalin , Froger Alexandrine , Hall James E.
Published: October 2007

We previously showed that the water permeability of AQP0, the water channel of the lens, increases with acid pH and that His40 is required (Németh-Cahalan, K.L., and J.E. Hall. 2000. J. Biol. Chem. 275:6777–6782; Németh-Cahalan, K.L., K. Kalman, and J.E. Hall. 2004. J. Gen. Physiol. 123:573–580). We have now investigated the effect of zinc (and other transition metals) on the water permeability of AQP0 expressed in Xenopus oocytes and determined the amino acid residues that facilitate zinc modulation. Zinc (1 mM) increased AQP0 water permeability by a factor of two and prevented any additional increase induced by acid pH. Zinc had no effect on water permeability of AQP1, AQP4 or MIPfun (AQP0 from killifish), or on mutants of AQP1 and MIPfun with added external histidines. Nickel, but not copper, had the same effect on AQP0 water permeability as zinc. A fit of the concentration dependence of the zinc effect to the Hill equation gives a coefficient greater than three, suggesting that binding of more than one zinc ion is necessary to enhance water permeability. His40 and His122 are necessary for zinc modulation of AQP0 water permeability, implying structural constraints for zinc binding and functional modulation. The change in water permeability was highly sensitive to a coinjected zinc-insensitive mutant and a single insensitive monomer completely abolished zinc modulation. Our results suggest a model in which positive cooperativity among subunits of the AQP0 tetramer is required for zinc modulation, implying that the tetramer is the functional unit. The results also offer the possibility of a pharmacological approach to manipulate the water permeability and transparency of the lens.
A Quantitative Description of KcsA Gating II: Single-Channel Currents
Authors: Chakrapani Sudha , Cordero-Morales Julio F , Perozo Eduardo
Published: October 2007

The kinetic transitions of proton-activated WT KcsA and the noninactivating E71A mutant were studied at the single-channel level in purified, liposome-reconstituted preparations. Single-channel currents were recorded using patch-clamp techniques under nonstationary and steady-state conditions. Maximum-likelihood analyses reveal that the key influence of acidic pH is to increase the frequency of bursting without an effect on the intraburst open and closed dwell times, consistent with the finding from macroscopic currents that protons promote activation without a significant effect on inactivation. However, in steady-conditions of pH, voltage not only alters the burst frequency but also affects their properties, such as the frequency of the flickers and the dwell times of the closed and open states. This is to be expected if voltage modulates pathways connecting open and inactivated states. Upon opening, KcsA can enter at least two closed states that are not part of the activation pathway. The frequency and duration of these closed states was found to be voltage dependent and therefore these are likely to represent short-lived inactivated states. Single-channel recordings of WT KcsA also show varying propensity for the presence of subconductance states. The probability of occurrence of these states did not show clear modulation by voltage or pH and their origin remains unclear and a focus for further investigation. A kinetic model is proposed to describe the gating events in KcsA that recapitulates its macroscopic and single-channel behavior. The model has been constrained by the single-channel analyses presented in this work along with data from macroscopic currents in the preceding paper.
Bertrand's Paradox and the Principle of Indifference
Authors: Shackel Nicholas
Published: October 2007

The principle of indifference is supposed to suffice for the rational assignation of probabilities to possibilities. Bertrand advances a probability problem, now known as his paradox, to which the principle is supposed to apply; yet, just because the problem is ill-posed in a technical sense, applying it leads to a contradiction. Examining an ambiguity in the notion of an ill-posed problem shows that there are precisely two strategies for resolving the paradox: thedistinction strategyand thewell-posing strategy. The main contenders for resolving the paradox, Marinoff and Jaynes, offer solutions which exemplify these two strategies. I show that Marinoff's attempt at the distinction strategy fails, and I offer a general refutation of this strategy. The situation for the well-posing strategy is more complex. Careful formulation of the paradox within measure theory shows that one of Bertrand's original three options can be ruled out but also shows that piecemeal attempts at the well-posing strategy will not succeed. What is required is an appeal to general principle. I show that Jaynes's use of such a principle, the symmetry requirement, fails to resolve the paradox; that a notion of metaindifference also fails; and that, while the well-posing strategy may not be conclusively refutable, there is no reason to think that it can succeed. So the current situation is this. The failure of Marinoff's and Jaynes's solutions means that the paradox remains unresolved, and of the only two strategies for resolution, one is refuted and we have no reason to think the other will succeed. Consequently, Bertrand's paradox continues to stand in refutation of the principle of indifference.
Determinants of Good Adherence to Hand Hygiene Among Healthcare Workers Who Have Extensive Exposure to Hand Hygiene Campaigns
Authors: Sax Hugo , Uçkay Ilker , Richet Hervé , Allegranzi Benedetta , Pittet Didier
Published: October 2007

Objective.

To quantify the different behavioral components of healthcare workers' motivation to comply with hand hygiene in a healthcare institution with a 10-year history of hand hygiene campaigning.

Design.

Cross-sectional study, by use of an anonymous, self-administered questionnaire.

Setting.

A 2,200-bed university teaching hospital.

Participants.

A stratified random sample of 2,961 medical and nursing staff.

Results.

A total of 1,042 questionnaires (35.2%) were returned. Of the respondents, 271 (26.0%) were physicians, 629 (60.4%) were nurses, and 141 (13.5%) were nursing assistants. Overall, 1,008 respondents provided information about sex; 718 (71.2%) of these were women. Respondents provided demographic information and data about various behavioral, normative, and control beliefs that determined their intentions with respect to performing hand hygiene. Among behavioral beliefs, the perception that healthcare-associated infections are severe for patients was highly ranked as a determinant of behavior by 331 (32.1%) of the respondents, and the perception that hand hygiene is effective at preventing these infections was ranked highly by 891 respondents (86.0%). Among normative beliefs, perceived social pressure from patients to perform hand hygiene was ranked highly by 760 respondents (73.7%), pressure from superiors was ranked highly by 687 (66.8%), pressure from colleagues was ranked highly by 596 (57.9%), and pressure from the person perceived to be most influential was ranked highly by 687 (68.8%). Among control beliefs, the perception that hand hygiene is relatively easy to perform was rated highly by 670 respondents (65.1%). High self-reported rates of adherence to hand hygiene (defined as performance of proper hand hygiene during 80% or more of hand hygiene opportunities) was independently associated with female sex, receipt of training in hand hygiene, participation in a previous hand hygiene campaign, peer pressure from colleagues, perceived good adherence by colleagues, and the perception that hand hygiene is relatively easy to perform.

Conclusions.

In a setting with a long tradition of hand hygiene campaigns, behavioral beliefs are strongly in favor of hand hygiene, but adherence is driven by peer pressure and the perception of high self-efficacy, rather than by reasoning about the impact of hand hygiene on patient safety. Female sex, training, and campaign exposure increased the likelihood of compliance with hand hygiene. This additional insight can help to shape future promotional activity.
Influence of Honey on the Suppression of Human Low Density Lipoprotein (LDL) Peroxidation (In Vitro)
Authors: Hegazi Ahmed G. , Abd El-Hady Faten K.
Published: October 2007

The antioxidant activity of four honey samples from different floral sources (Acacia, Coriander, Sider and Palm) were evaluated with three different assays; DPPH free radical scavenging assay, superoxide anion generated in xanthine–xanthine oxidase (XOD) system and low density lipoprotein (LDL) peroxidation assay. The dark Palm and Sider honeys had the highest antioxidant activity in the DPPH assay. But all the honey samples exhibited more or less the same highly significant antioxidant activity within the concentration of 1mg honey/1 ml in XOD system and LDL peroxidation assays. The chemical composition of these samples was investigated by GC/MS and HPLC analysis, 11 compounds being new to honey. The GC/MS revealed the presence of 90 compounds, mainly aliphatic acids (37 compounds), which represent 54.73, 8.72, 22.87 and 64.10% and phenolic acids (15 compound) 2.3, 1.02, 2.07 and 11.68% for Acacia, Coriander, Sider and Palm honeys. In HPLC analysis, 19 flavonoids were identified. Coriander and Sider honeys were characterized by the presence of large amounts of flavonoids.
Novel Diagnosis of Lyme Disease: Potential for CAM Intervention
Authors: Vojdani Aristo , Hebroni Frank , Raphael Yaniv , Erde Jonathan , Raxlen Bernard
Published: October 2007

Lyme disease (LD) is the most common tick‐borne disease in the northern hemisphere, producing a wide range of disabling effects on multiple human targets, including the skin, the nervous system, the joints and the heart. Insufficient clinical diagnostic methods, the necessity for prompt antibiotic treatment along with the pervasive nature of infection impel the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity and specificity. The goal of this article is 4‐fold: (i) to detail LD infection and pathology, (ii) to review prevalent diagnostic methods, emphasizing inherent problems, (iii) to introduce the usage of in vivo induced antigen technology (IVIAT) in clinical diagnostics and (iv) to underscore the relevance of a novel comprehensive LD diagnostic approach to practitioners of Complementary and Alternative Medicine (CAM). Utilization of this analytical method will increase the accuracy of the diagnostic process and abridge the time to treatment, with antibiotics, herbal medicines and nutritional supplements, resulting in improved quality of care and disease prognosis.
On Formal Theory and Statistical Methods: A Response to Carrubba, Yuen, and Zorn
Authors: Signorino Curtis S.
Published: October 2007

The recent article by Carrubba, Yuen, and Zorn (2007) (CYZ) attempts to relate the strategic random utility models in Signorino (1999, 2002, 2003) and in Signorino and Yilmaz (2003) to existing game theory practice and to existing statistical techniques. It contributes to this literature by reminding us that comparative statics analysis can be applied to the equilibria of these models. There are a number of claims in CYZ, however, that require clarification. In particular, the article's primary claim is that comparative statics analysis, in combination with one of three proposed statistical estimators, provides a simpler alternative to methods previously advocated. This claim (or combination of claims) is incorrect. When one examines the procedure CYZ recommends, it is no simpler for substantive researchers than anything previously recommended. Moreover, none of the proposed estimators are new: they are exactly the same methods introduced in Signorino (1999, 2003), in Signorino and Yilmaz (2003), in Signorino, Walker, and Bas (2002), and in Bas, Signorino, and Walker (2007).
Transient tumbling chaos and damping identification for parametric pendulum
Authors: Horton Bryan , Wiercigroch Marian , Xu Xu
Published: October 2007

The aim of this study is to provide a simple, yet effective and generally applicable technique for determining damping for parametric pendula. The proposed model is more representative of system dynamics because the numerical results describe the qualitative features of experimentally exhibited transient tumbling chaotic motions well. The assumption made is that the system is accurately modelled by a combination of viscous and Coulomb dampings; a parameter identification procedure is developed from this basis. The results of numerical and experimental time histories of free oscillations are compared with the model produced from the parameters identified by the classic logarithmic decrement technique. The merits of the present method are discussed before the model is verified against experimental results. Finally, emphasis is placed on a close corroboration between the experimental and theoretical transient tumbling chaotic trajectories.
Experimental investigation on the avoidance of self-excited vibrations
Authors: Kröger Matthias , Neubauer Marcus , Popp Karl
Published: October 2007

Self-excited vibrations are observed in many technical applications. Frictional contacts are often involved in the mechanism which generates vibrations. Reasons for the excitation mechanisms are decreasing friction characteristics depending on the sliding velocity, fluctuating normal loads or different geometrical effects. First, the mechanisms are explained using simple examples. The practical relevance of self-excited, friction-induced vibrations is exemplified with three technical systems: a system with an axial seal; a tread block of a tyre; and a disc brake.

The knowledge of the excitation mechanism is necessary to introduce successfully design countermeasures. These measures to avoid self-excited vibrations are important to solve practical problems. They are the main focus of this work. Further, additional passive and active subsystems are described and validated experimentally. Therefore, a large range of design, active and passive solutions are given.
Distributed friction damping of travelling wave vibration in rods
Authors: Tangpong Xiangqing W , Wickert Jonathan A , Akay Adnan
Published: October 2007

A ring damper can be affixed to a rotating base structure such as a gear, an automotive brake rotor or a gas turbine's labyrinth air seal. Depending on the frequency range, wavenumber and level of preload, vibration of the base structure can be effectively and passively attenuated by friction that develops along the interface between it and the damper. The assembly is modelled as two rods that couple in longitudinal vibration through spatially distributed hysteretic friction, with each rod having periodic boundary conditions in a manner analogous to an unwrapped ring and disc. As is representative of rotating machinery applications, the system is driven by a travelling wave disturbance, and for that form of excitation, the base structure's and the damper's responses are determined without the need for computationally intensive simulation. The damper's performance can be optimized with respect to normal preload, and its effectiveness is insensitive to variations in preload or the excitation's magnitude when its natural frequency is substantially lower than the base structure's in the absence of contact.
Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases
Authors: Lemberg Marius K. , Freeman Matthew
Published: October 2007

Rhomboids are a recently discovered family of widely distributed intramembrane serine proteases. They have diverse biological functions, including the regulation of growth factor signaling, mitochondrial fusion, and parasite invasion. Despite their existence in all branches of life, the sequence identity between rhomboids is low. We have combined BLAST-based database mining with functional and structural data to generate a comprehensive genomic analysis of eukaryotic rhomboid-like proteins. We show that robust membrane topology models are necessary to classify active rhomboid proteases unambiguously, and we define rules for distinguishing predicted active proteases from the larger evolutionary group of rhomboid-like proteins. This leads to a revision of estimates of numbers of proteolytically active rhomboids. We identify three groups of eukaryotic rhomboid-like proteins: true active rhomboids, a tightly clustered group of novel inactive rhomboids that we name the iRhoms, and a small number of other inactive rhomboid-like proteins. The active proteases are themselves subdivided into secretase and PARL-type (mitochondrial) subfamilies; these have distinct transmembrane topologies. This enhanced genomic analysis leads to conclusions about rhomboid enzyme function. It suggests that a given rhomboid can only cleave a single orientation of substrate, and that both products of rhomboid catalyzed intramembrane cleavage can be released from the membrane. Our phylogeny predictions also have evolutionary implications: Despite the complex classification of rhomboids, our data suggest that a rhomboid-type intramembrane protease may have been present in the last eukaryotic common ancestor.
Reconstructing migrations of individual cod (Gadus morhuaL.) in the Baltic Sea by using electronic data storage tags
Authors: NEUENFELDT STEFAN , HINRICHSEN HANS‐HARALD , NIELSEN ANDERS , ANDERSEN KEN H.
Published: October 2007

A new methodology is presented to reconstruct migration pathways of individual fish inhabiting ecosystems with moderate‐to‐strong gradients in temperature or salinity. The method uses measurements of ambient pressure, temperature and salinity obtained from electronic data storage tags attached to individual fish and is particularly applicable in areas with negligible tides. We demonstrate the method with Baltic cod. Hydrographic fields obtained from hydrodynamic modelling were used as a geolocation database to identify daily positions of Baltic cod by comparison with the environmental data collected by the tags. Using randomly distributed individual parameter perturbations in the range of the instrument precision of the tag we simulated a cod migrating through the Baltic Sea. The distance between the prescribed and geolocated positions of this artificial cod was on average 2.9 ± 4.7 (SD) km. Subsequently, the method was used to reconstruct migration routes of 10 real cod tagged in the Bornholm Basin of the Baltic Sea in early spring 2003. Differences were compared between the tag data and the geolocation database. The uncertainty in geolocation at recapture day was on average 75 ± 23 (SD) km, as shown by comparison between geolocated position and recapture position.
Iron deficiency prevalence and dietary patterns by school district in Istanbul
Authors: Manios Y. , Moschonis G. , Kolotourou M. , Keskin Y. , Sur H. , Kocaoglu B. , Hayran O.
Published: October 2007

Introduction  The aim of this study was to record the prevalence of iron deficiency (serum ferritin concentration <15 μg L−1) among schoolchildren and identify possible factors related to the development of this medical condition.

Materials and methods  The study population consisted of 504 schoolchildren attending three primary schools, located in two districts of Istanbul with higher and lower socio‐economic level (SEL) respectively. Certain biochemical and haematological indices of iron status were measured. Dietary intake was estimated using the 24‐h recall technique and a food frequency questionnaire.

Results  The prevalence of iron deficiency in the lower SEL school district was twice that of the higher SEL school district (42% and 21.2% respectively). Furthermore, the levels of serum ferritin, mean corpuscular volume, mean corpuscular haemoglobin (all P < 0.001) and mean corpuscular haemoglobin concentration (P = 0.016) were higher for students in the higher than in the lower SEL school district. Consumption of tea, cola beverages and dairy products was more frequent by children living in the lower than in the higher SEL school district. Furthermore, consumption of red meat and citrus fruits was less frequent by boys in the lower than in the higher SEL school district.

Conclusions  Iron deficiency was more prevalent among children from the lower SEL school district. Different patterns in the consumption of foods and beverages that inhibit or enhance intestinal iron absorption between children in the two school districts could provide some explanation for the observed differences in the prevalence of iron deficiency.
Nutritional status of patients who have fallen in an acute care setting
Authors: Bauer J. D. , Isenring E. , Torma J. , Horsley P. , Martineau J.
Published: October 2007

Background  Falls may result in injury, loss of independence and higher healthcare costs. The aim of this study was to examine the nutritional status of patients who had fallen in an acute care setting.

Methods  Forty‐nine patients who had experienced a fall while admitted at an Australian private hospital participated in the study (age: 71.2 (SD 14.1) years; 21 male: 28 female). Nutritional status was assessed using subjective global assessment. Protein and energy intake was determined by dietary history and analysed using Australian computerised food composition data.

Results  According to subjective global assessment, 27 patients were well nourished and 22 malnourished (21 moderately, one severely malnourished). Well nourished fallers had significantly higher BMI (mean difference 3.7 kg/m2, CI: 1.2‐6.2), dietary protein (mean difference 19.8 g, CI: 2.0‐37.5) and energy intake (mean difference 1751 kJ, CI: 332‐3170) compared to malnourished fallers. There was no difference in severity of falls based on nutritional status, weight or BMI.

Conclusions  There was a high prevalence of malnutrition and poor intake in this sample of patients who had fallen in hospital. Nutrition assessment and intervention for patients who have fallen in the acute care setting should be considered.
Extremely high levels of melanoma in Tauranga, New Zealand: Possible causes and comparisons with Australia and the northern hemisphere
Authors: Salmon Paul JM , Chan Weng Chen , Griffin Jenny , McKenzie Richard , Rademaker Marius
Published: October 2007

The objective of the study was to determine the incidence of melanoma in the Tauranga region of New Zealand, to compare these findings within Australasia and the northern hemisphere, and to understand the causes of the relatively high rates in Tauranga. Data were obtained from retrospective review of histology reports from the public and private health systems in greater Tauranga (Tauranga and Western Bay of Plenty Districts). Primary cutaneous melanomas (including both invasive and in situ melanomas) reported during 2003 were included. Age‐standardized melanoma rates were calculated for the entire population as well as for the non‐Maori population of the region, identified from the 2001 New Zealand Census. The age‐standardized incidence of invasive melanoma in the non‐Maori population of the greater Tauranga region was 79/100 000. The age‐standardized rate for the entire population was 70/100 000. The rate of in situ disease was 78/100 000 for non‐Maori and 72/100 000 for the entire population. The Tauranga region of New Zealand has an exceptionally high incidence of invasive and in situ melanomas. This is likely related to environmental, geographical and societal factors, including relatively high levels of UV exacerbated in recent times by ozone depletion, relatively cool summer temperatures which encourage outdoor exposure, and relatively fair skin colouring.
Reticulate keloidal purpura associated with transient antiphospholipid antibodies and hyperhomocysteinaemia
Authors: Fisher Jemima , Parsi Kurosh , Hannaford Rodney
Published: October 2007

A 66‐year‐old woman presented with a reticulate pattern of purpuric, keloidal scarring affecting her lower legs and necrosis of her left thumb and little finger as sequelae of an episode of staphylococcal septicaemia. Her premorbid past history includes three miscarriages, three episodes of pulmonary embolism and an internal iliac vein thrombosis. Skin biopsy specimens showed keloidal scar tissue in the dermis but no evidence of thrombosis or vasculitis. Blood tests demonstrated moderate hyperhomocysteinaemia. Elevated levels of anticardiolipin antibodies were found on one occasion but this was not detected on initial or repeat testing.