bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocytosis and degradation of BOR1, a boron transporter ofArabidopsis thaliana, regulated by boron availability
Authors: Takano Junpei , Miwa Kyoko , Yuan Lixing , von Wirén Nicolaus , Fujiwara Toru
Published: August 2005

Boron (B) is essential for plants but toxic when present in excess.Arabidopsis thalianaBOR1 is a B exporter for xylem loading and is essential for efficient B translocation from roots to shoots under B limitation. B translocation to shoots was enhanced under B limitation in WT but not inbor1-1mutant plants. The enhanced translocation was suppressed upon resupply of high levels of B within several hours. Unlike a number of transporters for essential mineral nutrients,BOR1mRNA accumulation was not strongly affected by B conditions. However, accumulation of a constitutively expressed BOR1-GFP fusion protein was elevated under conditions of limited B supply. Upon resupply of high levels of B, BOR1-GFP was degraded within several hours. These findings demonstrate that posttranscriptional mechanisms play a major role in regulation of BOR1 accumulation. Confocal laser scanning microscopy of root tip cells showed that BOR1-GFP is localized to the plasma membrane under B limitation. Shortly after B application, the protein was observed in dot-like structures in the cytoplasm before degradation. Colocalization studies of the fusion protein with an endocytic tracer FM4-64 and an endosomal Rab-GTPase Ara7 fused to monomeric red fluorescent protein suggested that BOR1 is transferred from the plasma membrane via the endosomes to the vacuole for degradation. These results establish that endocytosis and degradation of BOR1 are regulated by B availability, to avoid accumulation of toxic levels of B in shoots under high-B supply, while protecting the shoot from B deficiency under B limitation.
Amelioration of laminin-α2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin
Authors: Qiao Chunping , Li Jianbin , Zhu Tong , Draviam Romesh , Watkins Simon , Ye Xiaojing , Chen Chunlian , Li Juan , Xiao Xiao
Published: August 2005

Congenital muscular dystrophy (CMD) is characterized by severe muscle wasting, premature death in early childhood, and lack of effective treatment. Most of the CMD cases are caused by genetic mutations of laminin-α2, which is essential for the structural integrity of muscle extracellular matrix. Here, we report that somatic gene delivery of a structurally unrelated protein, a miniature version of agrin, functionally compensates for laminin-α2 deficiency in the murine models of CMD. Adeno-associated virus-mediated overexpression of miniagrin restored the structural integrity of myofiber basal lamina, inhibited interstitial fibrosis, and ameliorated dystrophic pathology. Furthermore, systemic gene delivery of miniagrin into multiple vital muscles significantly improved whole body growth and motility and quadrupled the lifespan (50% survival) of the dystrophic mice. Thus, our study demonstrated the efficacy of somatic gene therapy in a mouse model of CMD.
Alleles of the
NRAMP1
gene are risk factors for pediatric tuberculosis disease
Authors: Malik Suneil , Abel Laurent , Tooker Heather , Poon Audrey , Simkin Leah , Girard Manon , Adams Gerald J. , Starke Jeffrey R. , Smith Kimberly C. , Graviss Edward A. , Musser James M. , Schurr Erwin
Published: August 2005

Relatively little is known about the human genetics of susceptibility to common diseases caused by bacterial pathogens. Tuberculosis, caused by
Mycobacterium tuberculosis
, is a major cause of morbidity and mortality worldwide. So far, genetic studies of tuberculosis susceptibility have largely been focused on adult patients despite the fact that tuberculosis is highly prevalent among children. To study the host genetic component of pediatric tuberculosis susceptibility, we enrolled 184 ethnically diverse families from the Greater Houston area with at least one child affected by pediatric tuberculosis disease. Using a family-based control design, we found allelic variants of the natural resistance-associated macrophage protein gene 1 (
NRAMP1
) (alias
SLC11A1
) significantly associated with tuberculosis disease in this pediatric patient population [
P
= 0.01; odds ratio = 1.75 (95% confidence interval, 1.10-2.77)]. The association of
NRAMP1
with pediatric tuberculosis disease was significantly heterogeneous (
P
= 0.01) between simplex [
P
<0.0008; odds ratio = 3.13 (1.54-6.25)] and multiplex families (
P
= 1), suggesting an interplay between mechanisms of genetic control and exposure intensities. In striking contrast to previous studies in the adult population, we observed that the common alleles of
NRAMP1
polymorphisms were risk factors for pediatric tuberculosis disease. To explain the different direction of allelic association between adult and pediatric disease, we hypothesize that
NRAMP1
influences the speed of progression from infection to tuberculosis disease.
Quality assessment of maize assembled genomic islands (MAGIs) and large-scale experimental verification of predicted genes
Authors: Fu Yan , Emrich Scott J. , Guo Ling , Wen Tsui-Jung , Ashlock Daniel A. , Aluru Srinivas , Schnable Patrick S.
Published: August 2005

Recent sequencing efforts have targeted the gene-rich regions of the maize (
Zea mays
L.) genome. We report the release of an improved assembly of maize assembled genomic islands (MAGIs). The 114,173 resulting contigs have been subjected to computational and physical quality assessments. Comparisons to the sequences of maize bacterial artificial chromosomes suggest that at least 97% (160 of 165) of MAGIs are correctly assembled. Because the rates at which junction-testing PCR primers for genomic survey sequences (90-92%) amplify genomic DNA are not significantly different from those of control primers (≈91%), we conclude that a very high percentage of genic MAGIs accurately reflect the structure of the maize genome. EST alignments,
ab initio
gene prediction, and sequence similarity searches of the MAGIs are available at the Iowa State University MAGI web site. This assembly contains 46,688
ab initio
predicted genes. The expression of almost half (628 of 1,369) of a sample of the predicted genes that lack expression evidence was validated by RT-PCR. Our analyses suggest that the maize genome contains between ≈33,000 and ≈54,000 expressed genes. Approximately 5% (32 of 628) of the maize transcripts discovered do not have detectable paralogs among maize ESTs or detectable homologs from other species in the GenBank NR nucleotide/protein database. Analyses therefore suggest that this assembly of the maize genome contains approximately 350 previously uncharacterized expressed genes. We hypothesize that these “orphans” evolved quickly during maize evolution and/or domestication.
An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation
Authors: Chen Zhiqiang , Foster Matthew W. , Zhang Jian , Mao Lan , Rockman Howard A. , Kawamoto Toshihiro , Kitagawa Kyoko , Nakayama Keiichi I. , Hess Douglas T. , Stamler Jonathan S.
Published: August 2005

The identity of the cellular mechanisms through which nitroglycerin (glyceryl trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood vessels remains one of the longest standing foci of investigation and sources of controversy in cardiovascular biology. Recent evidence suggests an unexpected role for mitochondria. We show here that bioconversion by mitochondria of clinically relevant concentrations of GTN results in activation of guanylate cyclase, production of cGMP, vasodilation
in vitro
, and lowered blood pressure
in vivo
, which are eliminated by genetic deletion of the mitochondrial aldehyde dehydrogenase (mtALDH). In contrast, generation of vasoactivity from alternative nitro(so)-vasodilators is unaffected. In
mtALDH
-/-
mice and their isolated vascular tissue, GTN bioactivity can still be generated, but only at substantially higher concentrations of GTN and by a mechanism that does not exhibit tolerance. Thus, mtALDH is necessary and sufficient for vasoactivity derived from therapeutic levels of GTN, and, more generally, mitochondria can serve as a source of NO-based cellular signals that may originate independently of NO synthase activity.
Coupled biophysical global ocean model and molecular genetic analyses identify multiple introductions of cryptogenic species
Authors: Dawson Michael N , Gupta Alex Sen , England Matthew H.
Published: August 2005

The anthropogenic introduction of exotic species is one of the greatest modern threats to marine biodiversity. Yet exotic species introductions remain difficult to predict and are easily misunderstood because knowledge of natural dispersal patterns, species diversity, and biogeography is often insufficient to distinguish between a broadly dispersed natural population and an exotic one. Here we compare a global molecular phylogeny of a representative marine meroplanktonic taxon, the moon-jellyfish
Aurelia
, with natural dispersion patterns predicted by a global biophysical ocean model. Despite assumed high dispersal ability, the phylogeny reveals many cryptic species and predominantly regional structure with one notable exception: the globally distributed
Aurelia
sp.1, which, molecular data suggest, may occasionally traverse the Pacific unaided. This possibility is refuted by the ocean model, which shows much more limited dispersion and patterns of distribution broadly consistent with modern biogeographic zones, thus identifying multiple introductions worldwide of this cryptogenic species. This approach also supports existing evidence that (
i
) the occurrence in Hawaii of
Aurelia
sp. 4 and other native Indo-West Pacific species with similar life histories is most likely due to anthropogenic translocation, and (
ii
) there may be a route for rare natural colonization of northeast North America by the European marine snail
Littorina littorea
, whose status as endemic or exotic is unclear.
Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma
Authors: Huang Wei , Fileta John B. , Dobberfuhl Adam , Filippopolous Theodoros , Guo Yan , Kwon Gina , Grosskreutz Cynthia L.
Published: August 2005

Increased intraocular pressure (IOP) leads, by an unknown mechanism, to apoptotic retinal ganglion cell (RGC) death in glaucoma. We now report cleavage of the autoinhibitory domain of the protein phosphatase calcineurin (CaN) in two rodent models of increased IOP. Cleaved CaN was not detected in rat or mouse eyes with normal IOP. In
in vitro
systems, this constitutively active cleaved form of CaN has been reported to lead to apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member, Bad. In a rat model of glaucoma, we similarly detect increased Bad dephosphorylation, increased cytoplasmic cytochrome
c
(cyt
c
), and RGC death. Oral treatment of rats with increased IOP with the CaN inhibitor FK506 led to a reduction in Bad dephosphorylation and cyt
c
release. In accord with these biochemical results, we observed a marked increase in both RGC survival and optic nerve preservation. These data are consistent with a CaN-mediated mechanism of increased IOP toxicity. CaN cleavage was not observed at any time after optic nerve crush, suggesting that axon damage alone is insufficient to trigger cleavage. These findings implicate this mechanism of CaN activation in a chronic neurodegenerative disease. These data demonstrate that increased IOP leads to the initiation of a CaN-mediated mitochondrial apoptotic pathway in glaucoma and support neuroprotective strategies for this blinding disease.
X-ray damage to the Mn
4
Ca complex in single crystals of photosystem II: A case study for metalloprotein crystallography
Authors: Yano Junko , Kern Jan , Irrgang Klaus-Dieter , Latimer Matthew J. , Bergmann Uwe , Glatzel Pieter , Pushkar Yulia , Biesiadka Jacek , Loll Bernhard , Sauer Kenneth , Messinger Johannes , Zouni Athina , Yachandra Vittal K.
Published: August 2005

X-ray absorption spectroscopy was used to measure the damage caused by exposure to x-rays to the Mn
4
Ca active site in single crystals of photosystem II as a function of dose and energy of x-rays, temperature, and time. These studies reveal that the conditions used for structure determination by x-ray crystallography cause serious damage specifically to the metal-site structure. The x-ray absorption spectra show that the structure changes from one that is characteristic of a high-valent Mn
4
(III
2
,IV
2
) oxo-bridged Mn
4
Ca cluster to that of Mn(II) in aqueous solution. This damage to the metal site occurs at a dose that is more than one order of magnitude lower than the dose that results in loss of diffractivity and is commonly considered safe for protein crystallography. These results establish quantitative x-ray dose parameters that are applicable to redox-active metalloproteins. This case study shows that a careful evaluation of the structural intactness of the active site(s) by spectroscopic techniques can validate structures derived from crystallography and that it can be a valuable complementary method before structure–function correlations of metalloproteins can be made on the basis of high-resolution x-ray crystal structures.
Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia
Authors: Schinzel Anna C. , Takeuchi Osamu , Huang Zhihong , Fisher Jill K. , Zhou Zhipeng , Rubens Jeffery , Hetz Claudio , Danial Nika N. , Moskowitz Michael A. , Korsmeyer Stanley J.
Published: August 2005

Mitochondrial permeability transition (PT) is a phenomenon induced by high levels of matrix calcium and is characterized by the opening of the PT pore (PTP). Activation of the PTP results in loss of mitochondrial membrane potential, expansion of the matrix, and rupture of the mitochondrial outer membrane. Consequently, PT has been implicated in both apoptotic and necrotic cell death. Cyclophilin D (CypD) appears to be a critical component of the PTP. To investigate the role of CypD in cell death, we created a CypD-deficient mouse.
In vitro
, CypD-deficient mitochondria showed an increased capacity to retain calcium and were no longer susceptible to PT induced by the addition of calcium. CypD-deficient primary mouse embryonic fibroblasts (MEFs) were as susceptible to classical apoptotic stimuli as the WT, suggesting that CypD is not a central component of cell death in response to these specific death stimuli. However, CypD-deficient MEFs were significantly less susceptible than their WT counterparts to cell death induced by hydrogen peroxide, implicating CypD in oxidative stress-induced cell death. Importantly, CypD-deficient mice displayed a dramatic reduction in brain infarct size after acute middle cerebral artery occlusion and reperfusion, strongly supporting an essential role for CypD in an ischemic injury model in which calcium overload and oxidative stress have been implicated.
Pungent products from garlic activate the sensory ion channel TRPA1
Authors: Bautista Diana M. , Movahed Pouya , Hinman Andrew , Axelsson Helena E. , Sterner Olov , Högestätt Edward D. , Julius David , Jordt Sven-Eric , Zygmunt Peter M.
Published: August 2005

Garlic belongs to the
Allium
family of plants that produce organosulfur compounds, such as allicin and diallyl disulfide (DADS), which account for their pungency and spicy aroma. Many health benefits have been ascribed to
Allium
extracts, including hypotensive and vasorelaxant activities. However, the molecular mechanisms underlying these effects remain unknown. Intriguingly, allicin and DADS share structural similarities with allyl isothiocyanate, the pungent ingredient in wasabi and other mustard plants that induces pain and inflammation by activating TRPA1, an excitatory ion channel on primary sensory neurons of the pain pathway. Here we show that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of sensory neurons and induce vasodilation by activating capsaicin-sensitive perivascular sensory nerve endings. Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems. These and other results suggest that garlic excites sensory neurons primarily through activation of TRPA1. Thus different plant genera, including
Allium
and
Brassica
, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence.
Sequence optimization and designability of enzyme active sites
Authors: Chakrabarti Raj , Klibanov Alexander M. , Friesner Richard A.
Published: August 2005

We recently found that many residues in enzyme active sites can be computationally predicted by the optimization of scoring functions based on substrate binding affinity, subject to constraints on the geometry of catalytic residues and protein stability. Here, we explore the generality of this surprising observation. First, the impact of hydrogen-bonding networks necessary for catalysis on the accuracy of sequence optimization is assessed; incorporation of these networks, where relevant, into the set of catalytic constraints is found to be essential. Next, the impact of multiple substrate selectivity on sequence optimization is probed by carrying out independent calculations for complexes of deoxyribonucleoside kinases with various cognate ligands, revealing how simultaneous selection pressures determined active-site sequences of these enzymes. Including previous calculations on simpler enzymes, computational sequence optimization correctly predicts 76% of all active-site residues tested (86% correct, with 93% similar, for naturally conserved residues). In these studies, the ligand is fixed in its native conformation. To assess the applicability of these methods tode novoactive-site design, the effect of small ligand motions around the native pose is also examined. Robustness of sequence accuracy for topologically similar poses is demonstrated for selected kinases, but not for a model peptidase. Based on these observations, we introduce the notion of the designability of an enzyme active site, a metric that may be used to guide the search for protein scaffolds suitable for the introduction ofde novoactivity for a desired chemical reaction.
Ancestral antibiotic resistance in
Mycobacterium tuberculosis
Authors: Morris Rowan P. , Nguyen Liem , Gatfield John , Visconti Kevin , Nguyen Kien , Schnappinger Dirk , Ehrt Sabine , Liu Yang , Heifets Leonid , Pieters Jean , Schoolnik Gary , Thompson Charles J.
Published: August 2005

Chemotherapeutic options to treat tuberculosis are severely restricted by the intrinsic resistance of
Mycobacterium tuberculosis
to the majority of clinically applied antibiotics. Such resistance is partially provided by the low permeability of their unique cell envelope. Here we describe a complementary system that coordinates resistance to drugs that have penetrated the envelope, allowing mycobacteria to tolerate diverse classes of antibiotics that inhibit cytoplasmic targets. This system depends on
whiB7
, a gene that pathogenic
Mycobacterium
shares with
Streptomyces
, a phylogenetically related genus known as the source of diverse antibiotics. In
M. tuberculosis
,
whiB7
is induced by subinhibitory concentrations of antibiotics (erythromycin, tetracycline, and streptomycin) and
whiB7
null mutants (
Streptomyces
and
Mycobacterium
) are hypersusceptible to antibiotics
in vitro
.
M. tuberculosis
is also antibiotic sensitive within a monocyte model system. In addition to antibiotics,
whiB7
is induced by exposure to fatty acids that pathogenic
Mycobacterium
species may accumulate internally or encounter within eukaryotic hosts during infection. Gene expression profiling analyses demonstrate that
whiB7
transcription determines drug resistance by activating expression of a regulon including genes involved in ribosomal protection and antibiotic efflux. Components of the
whiB7
system may serve as attractive targets for the identification of inhibitors that render
M. tuberculosis
or multidrug-resistant derivatives more antibiotic-sensitive.
Microoxen: Microorganisms to move microscale loads
Authors: Weibel Douglas B. , Garstecki Piotr , Ryan Declan , DiLuzio Willow R. , Mayer Michael , Seto Jennifer E. , Whitesides George M.
Published: August 2005

It is difficult to harness the power generated by biological motors to carry out mechanical work in systems outside the cell. Efforts to capture the mechanical energy of nanomotors
ex vivo
require
in vitro
reconstitution of motor proteins and, often, protein engineering. This study presents a method for harnessing the power produced by biological motors that uses intact cells. The unicellular, biflagellated algae
Chlamydomonas reinhardtii
serve as “microoxen.” This method uses surface chemistry to attach loads (1- to 6-μm-diameter polystyrene beads) to cells, phototaxis to steer swimming cells, and photochemistry to release loads. These motile microorganisms can transport microscale loads (3-μm-diameter beads) at velocities of ≈100–200 μm·sec
–1
and over distances as large as 20 cm.
Methanococcus vannieliiselenium-binding protein (SeBP): Chemical reactivity of recombinant SeBP produced inEscherichia coli
Authors: Patteson Kemberly G. , Trivedi Neel , Stadtman Thressa C.
Published: August 2005

A selenium-binding protein (SeBP) fromMethanococcus vannieliiwas recently identified, and its gene was isolated and overexpressed inEscherichia coli[Self, W. T., Pierce, R. & Stadtman, T. C. (2004)IUBMB Life56, 501–507]. SeBP and recombinant SeBP (rSeBP) migrated as ≈42-kDa species on native gels and as ≈33-kDa species on SDS gels. rSeBP consists of identical 8.8-kDa subunits, each containing a single cysteine residue. rSeBP isolated in the absence of reducing agents contained oxidized cysteine (89%) and very little bound selenium (0.05 eq or less per subunit). Complete reduction of the oxidized cysteine residues in rSeBP with Tris(2-carboxyethyl)phosphine required addition of a denaturant, such as 1 M guanidine-hydrochloride. With selenite as the selenium source and the isolated reduced protein as sole reductant, binding of one selenium per tetramer under anaerobic conditions required four cysteine thiol groups, one on each subunit. In the corresponding reaction, with reduced glutathione (GSH), equimolar amounts of selenodiglutathione (GSSeSG) and glutathione disulfide are formed from selenite and 4 GSH. At GSH-to-selenite ratios >4:1, conversion of GSSeSG to a perselenide derivative, GSSe–, occurs. However, with the reduced rSeBP as sole electron donor in the reaction with selenite, further conversion of the R-SSeS-R product apparently did not occur. Prior alkylation of the cysteine thiol groups in reduced rSeBP prevented selenite reduction and selenium binding under comparable conditions.
Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal
Authors: Abu-Elheiga Lutfi , Matzuk Martin M. , Kordari Parichher , Oh WonKeun , Shaikenov Tattym , Gu Ziwei , Wakil Salih J.
Published: August 2005

Acetyl-CoA carboxylases (ACC1 and ACC2) catalyze the carboxylation of acetyl-CoA to form malonyl-CoA, an intermediate metabolite that plays a pivotal role in the regulation of fatty acid metabolism. We previously reported that ACC2 null mice are viable, and that ACC2 plays an important role in the regulation of fatty acid oxidation through the inhibition of carnitine palmitoyltransferase I, a mitochondrial component of the fatty-acyl shuttle system. Herein, we used gene targeting to knock out the ACC1 gene. The heterozygous mutant mice (
Acc
1
+/–
) had normal fertility and lifespans and maintained a similar body weight to that of their wild-type cohorts. The mRNA level of ACC1 in the tissues of Acc1
+/–
mice was half that of the wild type; however, the protein level of ACC1 and the total malonyl-CoA level were similar. In addition, there was no difference in the acetate incorporation into fatty acids nor in the fatty acid oxidation between the hepatocytes of Acc1
+/–
mice and those of the wild type. In contrast to Acc2
–/–
mice, Acc1
–/–
mice were not detected after mating. Timed pregnancies of heterozygotes revealed that Acc
–/–
embryos are already undeveloped at embryonic day (E)7.5, they die by E8.5, and are completely resorbed at E11.5. Our previous results of the ACC2 knockout mice and current studies of ACC1 knockout mice further confirm our hypotheses that malonyl-CoA exists in two independent pools, and that ACC1 and ACC2 have distinct roles in fatty acid metabolism.
Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension
Authors: Mizuno Seiichi , Matsuura Keiichi , Gotou Takanobu , Nishimura Shingo , Kajimoto Osami , Yabune Mitsuharu , Kajimoto Yoshitaka , Yamamoto Naoyuki
Published: August 2005

We describe a clinical trial to study the efficacy of a casein hydrolysate, prepared using an Aspergillus oryzae protease, containing the major angiotensin-I-converting enzyme inhibitory peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) in a single-blind, placebo-controlled study. A total of 131 volunteers with high-normal blood pressure and mild hypertension were randomly divided into four groups (n 32 or 33 in each group). Each volunteer was given two tablets containing four different dosages of VPP and IPP (VPP+IPP: 0, 1·8, 2·5 and 3·6 mg), daily for 6 weeks. A significant decrease in systolic blood pressure was observed at 6 weeks in the active group receiving 1·8 mg (P<0·01) VPP and IPP; in the active groups receiving either 2·5 mg or 3·6 mg, systolic blood pressure was decreased at both 3 weeks (P<0·05 and P<0·05) and 6 weeks (P<0·001 and P<0·0001) compared with systolic blood pressure measured before treatment. Changes in the systolic blood pressure after 6 weeks of treatment in the four groups were −1·7, −6·3, −6·7 and −10·1 mmHg, and these effects were dose dependent. In addition, a significant difference in systolic blood pressure between the placebo group and the VPP and IPP group receiving 3·6 mg was observed (P<0·001) by two-way ANOVA. The antihypertensive effect was greater in mildly hypertensive subjects (n 20 or 21 in each group) than in any of the other subjects. No significant change of diastolic blood pressure was observed for all the test groups, and no differences in diastolic blood pressure in the test sample groups compared with the placebo group were observed during the test period.
Changes in arterial blood pressure in hypertensive rats caused by long-term intake of milk fermented by Enterococcus faecalis CECT 5728
Authors: Miguel M. , Muguerza B. , Sánchez E. , Delgado M. A. , Recio I. , Ramos M. , Aleixandre M. A.
Published: August 2005

We have evaluated the changes in arterial blood pressure caused in spontaneously hypertensive rats (SHR) by long-term intake of an Enterococcus faecalis CECT 5728-fermented milk with significant angiotensin-converting enzyme (ACE)-inhibitory activity. After being weaned, male 3-week-old SHR were randomized into five groups. Until the 20th week of life, rats in each group were given one of the following drinking fluids: tap water (negative control 1), a fermented milk without ACE-inhibitory activity (negative control 2), captopril (100 mg/kg) (positive control), the E. faecalis CECT 5728-fermented milk that had significant ACE-inhibitory activity, or Ca-enriched E. faecalis CECT 5728-fermented milk. Animals in the different groups were then given tap water as drinking fluid from the 20th to 25th week of life. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured weekly in the rats, from the 6th to 25th week of life, by the tail-cuff method. A definite decrease in SBP and DBP could be observed in the rats treated with captopril and also in the rats that received the E. faecalis CECT 5728-fermented milks. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the Ca-enriched fermented milk was slightly more accentuated and more constant than the effect of the E. faecalis CECT 5728-fermented milk that had not been enriched in Ca. SBP and DBP increased in the treated SHR when the corresponding antihypertensive treatment was removed. Fermentation of milk with E. faecalis CECT 5728 may therefore be a successful strategy to produce a functional food with antihypertensive activity.
Dietary patterns among older Europeans: the EPIC-Elderly study
Authors: Bamia Christina , Orfanos Philippos , Ferrari Pietro , Overvad Kim , Hundborg Heidi H. , Tjønneland Anne , Olsen Anja , Kesse Emmanuelle , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Nagel Gabriele , Boffetta Paolo , Boeing Heiner , Hoffmann Kurt , Trichopoulos Dimitrios , Baibas Nikos , Psaltopoulou Theodora , Norat Teresa , Slimani Nadia , Palli Domenico , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Sacerdote Carlotta , Bueno-de-Mesquita H. B. , Ocké Marga C. , Peeters Petra H. , van Rossum Caroline T. , Quirós José-Ramón , Sánchez Maria-José , Navarro Carmen , Barricarte Aurelio , Dorronsoro Miren , Berglund Göran , Wirfält Elisabet , Hallmans Göran , Johansson Ingegerd , Bingham Sheila , Khaw Kay-Tee , Spencer Elizabeth A. , Roddam Andrew W. , Riboli Elio , Trichopoulou Antonia
Published: August 2005

Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a ‘vegetable-based’ diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a ‘sweet- and fat-dominated’ diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. ‘Vegetable-based’ and a ‘sweet- and fat-dominated’ diets are prevalent among the elderly across Europe, and there is a north–south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.
Learning distributed leadership: part 2
Authors: Ross Lisa , Rix Mike , Gold Jeff
Published: August 2005

Purpose

The second paper in a two‐paper series, this article seeks to consider how the ideas of cultural historical activity theory were used in a learning programme for managers to examine and apply leadership as a collective phenomenon usually referred to as distributed leadership.

Design/methodology/approach

The main elements of the programme are presented along with examples of application by learners.

Findings

A key learning point that stood out is the identification of the social, historical and cultural context of leadership, rather than being focused on an individual. As learners move from actions of individuals to the activity system as a whole, distributed leadership is considered as the exertion of influence that can be inspired, distorted, subverted or ignored.

Practical implications

Activity systems are understood to be multi‐voiced and multi‐layered, subject to disturbances and flux that result in tension, contradiction and paradox which need to be understood and utilised to find ways of improving organisation performance.

Originality/value

A case study on the experience of learners attempting to consider distributed leadership is provided.
The 6Ds™
Authors: Terry Robert
Published: August 2005

Purpose

Today's executive education programmes must lend themselves to comprehensive evaluation and measurement, in order that return on investment can be clearly demonstrated in the boardroom. This requires a unique approach to programme design from the outset, providing scope to ensure that outcomes can be continually followed up, long after an event has taken place. This paper aims to examine proven methods used to achieve this objective, creating programmes that deliver proof of lasting results.

Design/methodology/approach

This is the 6DsTM approach pioneered by Calhoun Wick and Roy Pollock of the Fort Hill Company, on the basis of research undertaken amongst 30,000 learners. This method focuses on instigating behavioural change interventions over many months. It has been shown to significantly improve return on investment in executive education.

Findings

The paper states the evidence for the effectiveness of this technique but also highlights the fact that the majority of programmes are still not designed with the long‐term evaluation of performance and behavioural change in mind.

Originality/value

The paper challenges the paradigm of the traditional two‐day workshop where the trainer is centre‐stage. It instead concentrates on a new and innovative approach where the learner's line manager is pivotal, and success is measured in terms of measurable improvements in business performance. It will be of interest to educators and purchasers of executive education programmes.
Diversity in the spotlight
Authors: McDougall Adrian
Published: August 2005

Purpose

This paper aims to address the problems that diversity, by its nature, throws up for training professionals, and to highlight the various ways in which drama, as a learning tool, offers solutions to those problems.

Design/methodology/approach

The theory of experiential learning forms the back‐bone of the arguments proposed by the paper, and has many applications in the development and assessment of groups and individuals. While it focuses on a technique called “forum theatre”, all forms of drama‐based learning are founded on the theory of “learning by doing”.

Findings

The findings of the paper focus on the benefits of illustrating learning points through drama; encouraging creative thinking, risk‐taking, empathy and the use of conflict in a simulated environment to examine issues from all points of view.

Practical implications

These findings point to a need for an artistic and non‐directive approach to diversity training, one that is responsive to the sensitive and emotive nature of the subject. It also calls for organisations to encourage the embracing of differences within their workforces.

Originality/value

The learning points discussed offer a fresh perspective to diversity trainers. It suggests opportunities to address the root causes of prejudice without the risks that traditional training methods necessarily bring with them, and it is relevant to anyone involved in the design and delivery of diversity training.
Results of a survey into how people become managers and the management development implications
Authors: Rees W. David , Porter Christine
Published: August 2005

Purpose

To establish how people become managers.

Design/methodology/approach

A survey of 50 managers carried out at the end of 2004 by students on the BA in Business and Management course at the University of Westminster. A total of 25 students chose two managers each to interview. Of the managers, 38 were from the UK.

Findings

Out of 50 managers surveyed, 47 were specialists before they acquired management responsibilities. Only 12 received management training before becoming managers and that training was not always felt to be effective. The transition from specialist to becoming a manager of specialists was often stressful. Only two people became managers as a direct result of undertaking business studies degree programmes.

Research limitations/implications

Specialists often acquire managerial responsibilities, and often quite early in their career. Those aspiring to management have found that their entry route is via a specialist department. Consequently, it is appropriate to see that managers have the right blend of specialist and managerial skills and that they are given help in adjusting to managerial roles. The implications of the specialist route into management needs to be reflected in the structure of increasingly popular undergraduate programmes in business studies. There is a case for such courses having both specialist options and a managerial component.

Originality/value

There is little research about how people become managers. It is particularly important that the specialist route identified is understood by those wishing to become managers, by universities and colleges running both business and specialist courses and by employers.
Are graduates equipped with the right skills in the employability stakes?
Authors: Raybould Joanne , Sheedy Victoria
Published: August 2005

Purpose

To discuss employability and skills requirements for graduates from a graduate recruiter's point of view.

Design/methodology/approach

To look at key graduate recruitment organisations and explain what skills programmes are available to graduates. Also looks at continued development and what employers may be able to do in the future to improve skills?

Findings

There are transferable skills that employers like to see in a graduate and these can vary according to type of role; also, in general, graduates are keen to develop their skills further. There are organisations to help graduates improve these employability skills like Graduate Advantage and higher education institutions.

Originality/value

Of value to employers looking to recruit graduates, who need to be aware of what types of programmes are available to graduates. It is valuable to graduates, who need to look at their own skills and improve their employability.
How does dry contact occur in elastohydrodynamic lubrication?
Authors: Zhang Y.
Published: August 2005

Purpose

To form and develop a new mode of mixed elastohydrodynamic lubrication (mixed EHL) which is more realistic and of more application values to a practical elastohydrodynamic contact on gears, cams and roller bearings than the previous and current existing mixed EHL models.

Design/methodology/approach

The representative theoretical and experimental studies on elastohydrodynamic lubrication (EHL) and mixed EHL carried out in the previous and recent time, including those of the author, are reviewed. The obtained results on EHL and mixed EHL in those studies and the viewpoints on the mode of mixed EHL based on those results developed in those studies are compared and evaluated. Strong proves are formed on the new mode of mixed EHL proposed in the present paper based on these comparisons and evaluations.

Findings

Strong viewpoints are formed on the mode of the occurrence of dry contact in EHL in a practical concentrated contact. A new mode of mixed EHL is proposed by incorporating this mode of the occurrence of dry contact in EHL. Also, comments and evaluations on the previous researches on mixed EHL are made.

Practical implications

A very useful material for the engineers who are engaged in the design of EHL on gears, cams and roller bearings, and for the tribology scientists who thrust efforts in studying EHL and mixed EHL both by theoretical modeling and by experiments.

Originality/value

A new mode of mixed EHL is originally proposed by incorporating the finding of a more realistic mode of the occurrence of dry contact in EHL. This new mode of mixed EHL should become the direction of the theoretical research of mixed EHL in the future time. It provides a clearer way to this research.
Study into mechanical properties of TiN coating on Ti‐6Al‐4V alloy through three‐point bending tests
Authors: Yilbas B.S. , Sunar M. , Qasem Z. , Abdul Aleem B.J. , Zainaulabdeen S.
Published: August 2005

Purpose

To examine the mechanical properties of TiN PVD coated Ti‐6Al‐4V alloy through three‐point bending tests.

Design/methodology/approach

Ti‐6Al‐4V alloy is cut in size and polished and cleaned chemically before TiN PVD coating process. INSTRON three‐point bending equipment is used to conduct the bending tests for TiN coated and uncoated workpieces. During the tests, the load and displacement characteristics were recorded. The tests were terminated when the coating failed. Micrographs of surface and crack sites were obtained by SEM.

Findings

Coating failure occurs due to shearing effect on the tensile surface. The spalling and buckling of the coating on the compressive surface are observed. The compressive stress generated on the top surface (where the indent is in contact) did not cause adhesive failure of the coating. Moreover, cohesive cracks occur on the tensile surface of the coating. The crack ledge under the action of shear stress appears on the tensile surface of TiN coating and multi cracking of coating is resulted. The crack spacing is small indicating sliding and splitting separation between the adjacent columns in the coating.

Research limitations/implications

The tests can be extended to include the duplex treated workpieces such as the heat treatment of surface prior to TiN coating. This enhances the interface properties of the coating and base alloy.

Practical implications

The results can be used to assess the TiN coating applications in cutting tools, particularly drill bits and punches.

Originality/value

This paper provides information on mechanical behavior of TiN coating when subjected to bending force and offers practical help for the researchers and scientists working in the coating area.
Future polyimide coatings used in high loaded bearings
Authors: Görlach B. , Holweger W.
Published: August 2005

Purpose

To prevent damages of machinery elements and enhancing life lubrication by using new surface engineering techniques.

Design/methodology/approach

A new “wet” coating technique offers an easy and promising route to modify steel surfaces. The design of surface coatings and the results of an official bearing test are presented.

Findings

Based on common bearing tests (e.g. DIN 51819), wear behaviour and tribological properties of modified surfaces are verified.

Research limitations/implications

Our actual research proves an enhanced tribological behaviour in the case of improving surface properties. In contrast, to the common vapour deposition techniques the “wet” coating method seems to offer an alternative route to get surfaces with enhanced tribological properties.

Practical implications

The technique of “wet” coating offers an easy route to modify steel surfaces of all kinds of bearings.

Originality/value

Pre‐polymer coating provides a promising future technique for surface engineering.
An investigation on the variation of surface areas in upsetting of cylindrical specimen
Authors: Erol Akata H. , Çetinarslan Cem S.
Published: August 2005

Purpose

The purpose of presented study is to investigate the development of the barreling obtaining the variation of the surface area during upsetting of cylindrical specimens for various metals and alloys.

Design/methodology/approach

Variations of the surface areas were first obtained analytically using mathematical equations for uniform and non‐uniform upsetting. Barreling contours were accepted as circular segments in the development of the equations. In the experimental part of the study, barreling radii and other related dimensions of upset specimens were measured and inserted into the developed equations in order to obtain the variations of total specimen surface areas.

Findings

As it is expected, barreling effects the variation of total surface areas of the specimen. It can be concluded that the total surface area first decreases at low upset ratios for all the test materials and then begins to increase as the upset ratios increases. Consequently, total surface areas for non‐uniform upsetting are always smaller that those of uniform upsetting.

Research limitations/implications

Five kinds of materials were used in the experimental part of the study. Specimens were also upset without lubrication. A relatively slow hydraulic press was used during the experiments with 5 mm/s ram speed.

Practical implications

Although the study has not direct implications for the practical purposes in forging area, results can be used as a very useful source of information for researchers in this field to plan their studies. Variation character of total surface area obtained in the study may give useful data in analyzing the deformation patterns in upsetting.

Originality/value

The effects of barreling on the material behavior in upsetting for non‐uniform conditions were analyzed with respect to variation of total specimen surface area. This point of view may be extended for different materials and friction conditions.
A study of lubrication mechanism of oil‐in‐water (O/W) emulsions in steel cold rolling
Authors: Dubey S.P. , Sharma G.K. , Shishodia K.S. , Sekhon G.S.
Published: August 2005

Purpose

Oil‐in‐water (O/W) emulsion has been used in industrial rolling mills for many decades, but its lubrication mechanism is still not adequately understood. There is a need to understand the role of chemical ingredients and emulsifier in lubrication and tribological characteristics of rolling oil. With this purpose, the authors selected three commercially available O/W emulsions of different generations and of known industrial performance. The aim is to understand the lubrication mechanism of these rolling oils and to correlate the laboratory findings with that of industrial rolling mills.

Design/methodology/approach

The lubrication mechanism has been studied with the help of an ultra thin film interferometry EHD test rig, an advanced experimental rolling mill and a Coulter LS 230 instrument. Film thickness, rolling parameters and droplet size were measured. The coefficient of friction was computed with the help of the measured values of rolling parameters. Emulsion stability and saponification value (SAP) of the selected emulsions were also determined. The results of film thickness, rolling parameters and droplet size have been presented. The lubrication mechanism of the emulsions has been explained on the basis of film thickness, droplet size, emulsion stability, SAP value and coefficient of friction.

Findings

Results of the present study reveal that chemistry of O/W emulsions plays an important role in their film forming and tribological behavior. Rolling emulsions of relatively low stability, higher droplet size and high SAP value are found to provide better lubrication and lower coefficient of friction. The results of the present study correlate well with the actual industrial experience except those obtained on EHD test rig.

Research limitations/implications

Coulter LS 230 instrument was available with M/s LUBRIZOL CORP., USA. Only limited study on droplet size was carried. Although the study carried out has given good information but it would have been more practical if the emulsion samples taken from the experimental mill stand would have been studied for droplet size.

Practical implications

From understanding point of view of lubrication mechanism of O/W emulsion, it will be useful for oil technologists, tribologists and rolling mill users.

Originality/value

The study is original in nature and gives information on lubrication mechanism of O/W emulsions in steel cold rolling of steel strips.