bluuebunny/crossref_metadata_2025 huggingface dataset:
α-Farnesene: Isolation from the natural coating of apples
Authors: Murray KE
Published: May 2006

The isolation of a pure
sesquiterpene hydrocarbon from the natural coating of Granny Smith apples is
described. Evidence mainly from its ultraviolet, infrared, mass, and N.M.R.
spectra establish it as an α- farnesene stereoisomer (I) with a trans
configuration assigned to the 9,10 double bond and a likely trans configuration
of the 6,7 bond. Its infrared, mass, and N.M.R. spectra and those of
trans-β-farnesene (II) are reported.
The tropane alkaloids from three Western Australian Anthocercis species
Authors: Cannon JR , Joshi KR , Meehan GV , Williams JR
Published: May 2006

The major alkaloid of both
Anthocercis viscosa R. Br. and A. fasciculata F. Muell. has been identified as
(-)-hyoscyamine (I). A trace of the same partly racemic base has been isolated
from A. littorea Labill., together with meteloidine (II), but the major
alkaloid present in this species is littorine (III) which has been shown to be
R(-)-3α-(2-hydroxy-3-phenylpropionyloxy)tropane. ��� Rutin and ursolic acid have also been
isolated from A. viscosa.
Lewis-Base Adducts of Group 11 Metal(I) Complexes. XXXV. Complexes of the Asymmetric Bidentate Ligands (L) 2-Aminomethylpyridine and 2-Hydrazinopyridine With Copper(I) Halides: Syntheses and Structural Characterization of [CuL2]+X-, X = Cl, Br, I
Authors: Healy PC , Kildea JD , Skelton BW , White AH
Published: May 2006

The 1:2 adducts of the copper(I) halides (CuX ; X = Cl, Br, I) with the aliphatic/aromatic bidentate nitrogen bases 2-aminomethylpyridine, H2NCH2.C5H4N, and 2-hydrazinopyridine, H2N.NH.C5H4N, L, have been synthesized by recrystallization of stoichiometric copper(I) halide/base solutions from acetonitrile . In all cases, ionic complexes [CuL2]+ X- are obtained, copper being four-coordinated by a pair of bidentate ligands, and with widely varying distortions from ideal 2 symmetry. Cu-N (aromatic) in the 2-aminomethylpyridine adducts range from 1.979(8) to 2.037(5)Ǻ; while Cu-N(H2) are 2.102(9)-2.172(10)Ǻ, N( Ar )-Cu-N( Ar ) angles [130.7(2)-143.2(4)°] are larger than N(H2)-Cu-N(H2)[114.8(2)-116.3(4)°]. Comparable values for the 2-hydrazinopyridine complexes are 1.95(1)-2.036(5), 2.085(4)-2.214(7)Ǻ; 124.1(2)-140.8(4), 94.5(3)-128.0(3)°. In no case does the halide anion coordinate to the copper, displacing the aliphatic nitrogen donor group; rather it is stabilized in the crystal lattice by strong NH2…X hydrogen bonding.
Silylcuprate Routes to Cyclohex-2-enylsilanes
Authors: Laycock B , Maynard I , Wickham G , Kitching W
Published: May 2006

The efficacy of the dimethyl(phenyl)silylcuprate and (to a lesser extent) the methyl-diphenylsilylcuprate reagents in converting cyclohex-2-enyl chlorides into the corresponding allylsilanes has been investigated. The presence of copper(I) greatly suppresses formation of the coupled hydrocarbon, and promotes stereo- and regio-selective carbon-silicon bond formation, in a predominantly anti-SN2′ manner. Spectroscopic characterization of the diastereomeric silanes is presented. Grignard routes to some of these silanes are described.
Synthesis of a Cis-N2s2 Donor Macrocycle by Metal-Directed Condensation of Formaldehyde, Nitroethane and a Diaminodithiaalkane - Crystal-Structure of the (6-Methyl-6-Nitro-1,11-Dithia-4,8-Diazacyclotetradecane)-Copper(II) Perchlorate Product
Authors: Comba P , Lawrance GA , Rossignoli M , Skelton BW , White AH
Published: May 2006

Reaction of (3,7-dithianonane-1,9-diamine)copper(II)
ion with nitroethane and formaldehyde in basic
methanol gives the macrocyclic complex ion
(6-methyl-6-nitro-1,II-dithia-4,8- diazacyclotetradecane )copper(II)
in high yield. The complex as the perchlorate salt
crystallizes in the monoclinic space group P21/n, a 15.008(5), b
8.606(3), c 17.967(4)Ǻ, β 113.79(2)�. The copper ion lies in a square
plane of two nitrogen (average Cu-N 2.02 Ǻ) and two thioether
(average Cu-S 2.295 Ǻ) donors, with perchlorate oxygens (Cu-O 2.46 and 2.70 Ǻ) in axial sites.
Physical and structural properties of the CuIII
complexes of the 14-membered cis-N2S2 macrocycle
and the known analogous 14-membered N4-donor macrocycle
6-methyl-6-nitro-1,4,8,11- tetraazacyclotetradecane
are compared.
Synthesis of Heptacyclo[7.7.0.0/2,6/0/3,15/0/4,12/0/5,10/0/11,16]-Hexadeca-7,13-Diene - a Novel Dimer of Barrelene Possessing Perpendobiplanar D2d Symmetry
Authors: Barden TJ , Paddonrow MN
Published: May 2006

The synthesis of heptacyclo [7.7.0.02,6.03,15.04,12.05,10.011,16]hexadeca-7,13-
diene (9) is described. The diene
(9) was obtained in three steps from the known diketone
heptacyclo -[6.6.0.02,6.03,13.04,11.05,9.010,14] tetradecane - 7,12-dione (5). Double ring expansion of (5)
(with diazomethane) gave (12). Conversion of (12) into-the bis ( tosylhydrazone ), followed by double Bamford -Stevens
rearrangement, gave the diene (9).
A Novel Tertiary Amine-Sodium Iodide Complex - Crystallographic Characterization of Di-Mu-Iodo-Bis[(N,N,N',N',N'-Pentamethyl-Diethylenetriamine-N,N',N')S Odium(I)] Bis[Aqua(N,N,N',N',N'-Pentamethyldiethylene-Triamine-N,N',N')Lithium( I) Iodide]
Authors: Raston CL , Whitaker CR , White AH
Published: May 2006

No Abstract Available.
Complex genetic networks underlying the defensive system of rice (
Oryza sativa
L.) to
Xanthomonas oryzae
pv.
oryzae
Authors: Li Z. K. , Arif M. , Zhong D. B. , Fu B. Y. , Xu J. L. , Domingo-Rey J. , Ali J. , Vijayakumar C. H. M. , Yu S. B. , Khush G. S.
Published: May 2006

Complete resistance (CR) and partial resistance (PR) of rice (
Oryza sativa
L.) to its bacterial pathogen,
Xanthomonas oryzae
pv.
oryzae
(
Xoo
), was genetically dissected by using 2 mapping populations and 10
Xoo
races. Two CR genes, 50 quantitative resistance loci, and 60 digenic interactions were identified, which showed various degrees of race specificity to the
Xoo
races. The complex epistasis between these loci led us to the discovery of complex genetic networks underlying the rice defensive system to
Xoo
. The networks consisted of two major components: one representing interactions between alleles at the R loci of rice and alleles at the corresponding avirulence loci of
Xoo
for CR and the other comprising interactions between quantitative resistance loci in rice and their corresponding aggressiveness loci in
Xoo
for PR. The race specificity of PR and its strong genetic overlap with CR indicate that PR is essentially “weaker” CR. The genetic networks discovered are expected to maintain a high level of the allelic diversity at avirulent loci in the pathogen by stabilizing selection, which may maintain a high allelic diversity at R loci in the host by the frequency-dependent selection.
Brain response to putative pheromones in lesbian women
Authors: Berglund Hans , Lindström Per , Savic Ivanka
Published: May 2006

The progesterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(
10
),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. In previous positron emission tomography studies, we found that smelling AND and EST activated regions primarily incorporating the sexually dimorphic nuclei of the anterior hypothalamus, that this activation was differentiated with respect to sex and compound, and that homosexual men processed AND congruently with heterosexual women rather than heterosexual men. These observations indicate involvement of the anterior hypothalamus in physiological processes related to sexual orientation in humans. We expand the information on this issue in the present study by performing identical positron emission tomography experiments on 12 lesbian women. In contrast to heterosexual women, lesbian women processed AND stimuli by the olfactory networks and not the anterior hypothalamus. Furthermore, when smelling EST, they partly shared activation of the anterior hypothalamus with heterosexual men. These data support our previous results about differentiated processing of pheromone-like stimuli in humans and further strengthen the notion of a coupling between hypothalamic neuronal circuits and sexual preferences.
The positioning of cytoplasmic protein clusters in bacteria
Authors: Thompson Stephen R. , Wadhams George H. , Armitage Judith P.
Published: May 2006

Cell division is a carefully orchestrated procedure. Bacterial cells have intricate mechanisms to ensure that genetic material is copied, proofread, and accurately partitioned into daughter cells. Partitioning now appears to also occur for some cytoplasmic proteins. Previously, using chromosomal fluorescent protein fusions, we demonstrated that a subset of
Rhodobacter sphaeroides
chemotaxis proteins colocalize to a discrete region within the bacterial cytoplasm. Using TlpT-yellow fluorescent protein as a marker for the position of the cytoplasmic protein clusters, we show most cells contain either one cluster localized at mid-cell or two clusters at the one-fourth and three-fourths positions of cell length. The number and positioning of these protein clusters depend on a previously unrecognized bacterial protein positioning factor, PpfA, which has homology to bacterial type I DNA partitioning factors. These data suggest that there is a mechanism involved in partitioning some cytoplasmic proteins upon cell division that is analogous to a mechanism seen for plasmid and chromosomal DNA.
Velocity of vortices in inhomogeneous Bose–Einstein condensates
Authors: Nilsen Halvor M. , Baym Gordon , Pethick C. J.
Published: May 2006

We derive, from the Gross–Pitaevskii equation, an exact expression for the velocity of any vortex in a Bose–Einstein condensate, in equilibrium or not, in terms of the condensate wave function at the center of the vortex. In general, the vortex velocity is a sum of the local superfluid velocity, plus a correction related to the density gradient near the vortex. A consequence is that in rapidly rotating, harmonically trapped Bose–Einstein condensates, unlike in the usual situation in slowly rotating condensates and in hydrodynamics, vortices do not move with the local fluid velocity. We indicate how Kelvin’s conservation of circulation theorem is compatible with the velocity of the vortex center being different from the local fluid velocity. Finally, we derive an exact wave function for a single vortex near the rotation axis in a weakly interacting system, from which we derive the vortex precession rate.
High-resolution video monitoring of hematopoietic stem cells cultured in single-cell arrays identifies new features of self-renewal
Authors: Dykstra Brad , Ramunas John , Kent David , McCaffrey Lindsay , Szumsky Erin , Kelly Liam , Farn Kristen , Blaylock April , Eaves Connie , Jervis Eric
Published: May 2006

To search for new indicators of self-renewing hematopoietic stem cells (HSCs), highly purified populations were isolated from adult mouse marrow, micromanipulated into a specially designed microscopic array, and cultured for 4 days in 300 ng/ml Steel factor, 20 ng/ml IL-11, and 1 ng/ml flt3-ligand. During this period, each cell and its progeny were imaged at 3-min intervals by using digital time-lapse photography. Individual clones were then harvested and assayed for HSCs in mice by using a 4-month multilineage repopulation endpoint (>1% contribution to lymphoid and myeloid lineages). In a first experiment, 6 of 14 initial cells (43%) and 17 of 61 clones (28%) had HSC activity, demonstrating that HSC self-renewal divisions had occurredin vitro. Characteristics associated with HSC activity included longer cell-cycle times and the absence of uropodia on a majority of cells within the clone during the final 12 h of culture. Combining these criteria maximized the distinction of clones with HSC activity from those without and identified a subset of 27 of the 61 clones. These 27 clones included all 17 clones that had HSC activity; a detection efficiency of 63% (2.26 times more frequently than in the original group). The utility of these characteristics for discriminating HSC-containing clones was confirmed in two independent experiments where all HSC-containing clones were identified at a similar 2- to 3-fold-greater efficiency. These studies illustrate the potential of this monitoring system to detect new features of proliferating HSCs that are predictive of self-renewal divisions.
Genetic variants ofTgfb1act as context-dependent modifiers of mouse skin tumor susceptibility
Authors: Mao Jian-Hua , Saunier Elise F. , de Koning John P. , McKinnon Margaret M. , Higgins Mamie Nakijama , Nicklas Kathy , Yang Hai-Tao , Balmain Allan , Akhurst Rosemary J.
Published: May 2006

The humanTGFB1gene is polymorphic, and genetic variants are associated with altered cancer risk. However, human genetic association studies have had variable outcomes because TGFβ1 action is context-dependent. We used the murine skin model of chemical carcinogenesis in genetic linkage analysis of three independentMus musculusNIH/Ola × (Mus spretus×M. musculusNIH/Ola)F1backcrosses, to identify a skin tumor susceptibility locus,Skts14, on proximal chromosome 7.Tgfb1maps at the peak of linkage. The mouseTgfb1gene is polymorphic, resulting in cis-regulated differential allelic mRNA expression betweenM. spretusandM. musculusin F1mouse skin. This phenomenon is reflected in differential phospho-SMAD2 levels, downstream of TGFβ signaling, between these two mouse species. In normal F1mouse skin, theTgfb1SPRallele is expressed at higher levels than theTgfb1NIHallele, and this differential is accentuated by phorbol 12-myristate 13-acetate treatment. In benign F1papillomas, this imbalance is reversed, possibly by selection against expression of a hyperactiveTgfb1SPRallele in TGFβ growth-responsive tumors. We demonstrate that skin tumor susceptibility is altered byTgfb1gene dosage, but that manifestation ofTgfb1-linked skin tumor susceptibility inM. musculusNIH/Ola × (M. spretus×M. musculusNIH/Ola)F1backcross mice depends on interactions with another unlinked tumor modifying locus,Skts15, that overlapsTgfbm3on chromosome 12. These findings illustrate the power of complex genetic interactions in determining disease outcome and have major implications to the assessment of disease risk in individuals harboring variantTGFB1alleles.
A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons
Authors: Rush Anthony M. , Dib-Hajj Sulayman D. , Liu Shujun , Cummins Theodore R. , Black Joel A. , Waxman Stephen G.
Published: May 2006

Disease-producing mutations of ion channels are usually characterized as producing hyperexcitability or hypoexcitability. We show here that a single mutation can produce hyperexcitability in one neuronal cell type and hypoexcitability in another neuronal cell type. We studied the functional effects of a mutation of sodium channel Na
v
1.7 associated with a neuropathic pain syndrome, erythermalgia, within sensory and sympathetic ganglion neurons, two cell types where Na
v
1.7 is normally expressed. Although this mutation depolarizes resting membrane potential in both types of neurons, it renders sensory neurons hyperexcitable and sympathetic neurons hypoexcitable. The selective presence, in sensory but not sympathetic neurons, of the Na
v
1.8 channel, which remains available for activation at depolarized membrane potentials, is a major determinant of these opposing effects. These results provide a molecular basis for the sympathetic dysfunction that has been observed in erythermalgia. Moreover, these findings show that a single ion channel mutation can produce opposing phenotypes (hyperexcitability or hypoexcitability) in the different cell types in which the channel is expressed.
Understanding the bacterial polysaccharide antigenicity ofStreptococcus agalactiaeversusStreptococcus pneumoniae
Authors: Kadirvelraj Renuka , Gonzalez-Outeiriño Jorge , Foley B. Lachele , Beckham Meredith L. , Jennings Harold J. , Foote Simon , Ford Michael G. , Woods Robert J.
Published: May 2006

Bacterial surface capsular polysaccharides (CPS) that are similar in carbohydrate sequence may differ markedly in immunogenicity and antigenicity. The structural origin of these phenomena is poorly understood. Such a case is presented by the Gram-positive bacteriaStreptococcus agalactiae(Group BStreptococcus; GBS) type III (GBSIII) andStreptococcus pneumoniae(Pn) type 14 (Pn14), which share closely related CPS sequences. Nevertheless, antibodies (Abs) against GBSIII rarely cross-react with the CPS from Pn14. To establish the origin for the variation in CPS antigenicity, models for the immune complexes of CPS fragments from GBSIII and Pn14, with the variable fragment (Fv) of a GBS-specific mAb (mAb 1B1), are presented. The complexes are generated through a combination of comparative Ab modeling and automated ligand docking, followed by explicitly solvated 10-ns molecular dynamics simulations. The relationship between carbohydrate sequence and antigenicity is further quantified through the computation of interaction energies using the Molecular Mechanics–Generalized Born Surface Area (MM-GBSA) method, augmented by conformational entropy estimates. Despite the electrostatic differences between Pn14 and GBSIII CPS, analysis indicates that entropic penalties are primarily responsible for the loss of affinity of the highly flexible Pn14 CPS for mAb 1B1. The similarity of the solution conformation of the relatively rigid GBSIII CPS with that in the immune complex characterizes the previously undescribed 3D structure of the conformational epitope. The analysis provides a comprehensive interpretation for a large body of biochemical and immunological data related to Ab recognition of bacterial polysaccharides and should be applicable to other Ab–carbohydrate interactions.
Neutron activation analysis for development of mercury sorbent based on blue–green alga Spirulina platensis
Authors: Frontasyeva M.V. , Kirkesali E.I. , Aksenova N.G. , Mosulishvili L.M. , Belokobylsky A.I. , Khizanishvili A.I.
Published: May 2006

Epithermal neutron activation analysis (ENAA) was used to study the interaction of blue–green alga Spirulina platensis with toxic metal mercury. Various concentrations of Hg(II) were introduced into a nutrient medium during the process of Spirulina biomass cultivation. The dynamics of Hg accumulation by Spirulina biomass was investigated over several days. The process of Hg adsorption by Spirulina biomass was studied in short-time experiments. The isotherm of adsorption based on the results obtained was calculated. It was shown that live Spirulina biomass has the potential to be used for sorption of mercury from solutions at concentrations of ∼100–500 μg/l.
WORK–LIFE BALANCE IN EUROPE: A RESPONSE TO THE BABY BUST OR REWARD FOR THE BABY BOOMERS?
Authors: MacInnes John
Published: May 2006

The academic analysis of work–life balance (WLB) has too often followed the public policy debate without sufficient reflection on its origins, the accuracy of the assumptions it tends to make, or the analytical adequacy of the concepts it uses. This paper suggests that what are usually assumed to be the causes of the debate (longer hours and greater stress at work, along with the collapse of the male breadwinner division of parenting and employment responsibilities within couples) are nothing of the sort. Rather the debate's origins lie in states’ concerns about demographic trends, especially low and falling fertility, which they fear threatens the future of the labour supply and viable dependency ratios between those in work and those dependent upon them. The WLB debate can thus be seen as part of a specifically liberal discourse about ‘population ageing’ that seeks to legitimate the rolling back of a welfare state by arguing that current levels of support cannot be sustained in a globalising world. This analysis reveals two new features of WLB policies. First, most are quite contradictory. What makes them popular (such as enabling the ‘baby boomer’ generation to withdraw from work on favourable terms) also makes them unlikely to address their goal of specifically supporting parenting and avoiding a ‘baby bust’. Conversely effective support for parenting may require far more fundamental change than most WLB policies envisage. Second, demographic change has heightened the importance of the inter-generational transfer of resources between those now retired from employment, those currently in it, and those yet to enter it. This reveals a key feature of WLB policies to be how far these transfers are socialised or left to the family.
BALANCE BETWEEN WORK AND LIFE – NEW CORPORATE IMPOSITIONS THROUGH FLEXIBLE WORKING TIME OR OPPORTUNITY FOR TIME SOVEREIGNTY?
Authors: Hildebrandt Eckart
Published: May 2006

Working time is once again on the agenda. Actors in industry and politics are demanding the extension of working time and greater, market-oriented flexibilisation in the interest of cutting costs. At the present time the advocates of further reductions in working time and greater time sovereignty for employees have little say. At the same time, the compatibility of work and life has become an increasingly important issue, not only as a problem for working mothers but for corporate human resources policy as a whole. Forms of regulating flexible working time that promise to balance various time interests are therefore particularly important. One option of major interest is the institution of working time accounts, which permit flexible overtime as well as the use of ‘banked’ time to meet personal needs without generally extending working time. The study provides insight into corporate working time arrangements in various sectors and employee time choices in reconciling company requirements and private interests. Neither side has yet made adequate progress in creating the preconditions for a successful balance.
WORK–LIFE BALANCE AND INDUSTRIAL RELATIONS IN ITALY
Authors: Ponzellini Anna M.
Published: May 2006

This article examines the work–life balance system in Italy, with particular regard to the role played by extra-statutory arrangements and provision – extra leave, benefits and allowances for parents provided by employers, in-company crèches, family-friendly working hours, etc. – originated from collective bargaining and industrial relations at company-level. The Italian pattern of welfare state and women's employment is characterised by weak state support, a relevant role of intergenerational solidarity, one of the lowest fertility rates and still low women's activity rates. As for human resource management and industrial relations’ contribution to work–life balance, empirical evidence shows that a certain number of extra-statutory arrangements and provision has been implemented at company level. Though, they are not enough to fill the gap with countries where state social protection is higher. The articles argue that industrial relations may play an important role in fostering a better work–life balance, on condition that a priority is given to decentralised collective bargaining and new ‘territorial pacts’ involving a wider range of social actors – not only unions and the companies, but also families, local governments, caregivers and the cared-for. Particularly for unions, this could be a possible response to unionisation decline.
WELFARE STATES AND WORK–LIFE BALANCE
Authors: Leitner Andrea , Wroblewski Angela
Published: May 2006

Within the European Employment Strategy benchmarking and learning from good practices are main mechanisms to improve national performance. This is also the case for WLB strategies which are reinforced because of economic reasons to increase employment and population growth. The paper asks for the main criteria for public policies to promote WLB and whether or under which conditions such policies are transferable between the successful Nordic countries and the less successful conservative countries like Austria and Germany. Denmark and Finland are used as ‘good practice’ examples. The analysis shows that childcare leave regulations are an important instrument to encourage mothers for continuous working careers. But the consequences of these regulations concerning employment turn out to be quite different, even in measures with similar orientation. What we can learn from the Nordic countries is that the consistency of welfare state regulations and institutions are an important precondition for a successful WLB. This calls for an interplay of different fields and means that the imbalance of family and work and family reconciliation can hardly be solved by flexible working contracts or longer parental leave possibilities.
THE ORGANISATION OF TIME OVER THE LIFE COURSE: EUROPEAN TRENDS
Authors: Anxo Dominique , Boulin Jean-Yves
Published: May 2006

Over the last decades, the life course approach has developed into a major research paradigm. The notion of life course provides a common field of research and a heuristic conceptual device aiming at studying individuals trajectories over time. In its modern version, the life course approach can be said to represent a major innovation in our understanding of complex social phenomena, making time, context and process core theoretical dimensions of social behaviour. Most of the research using this approach has stressed the extent to which social structures and individual factors shape the life course of individuals and has focused on the developmental consequences of alternative life trajectories. One of the main features of the life course approach is therefore to recognize the crucial role time plays in our understanding of individual behaviour and structural changes in society. The second important dimension of the life course approach is its attempt to take a holistic view, in that the analysis no longer focuses on isolated specific events, phases or demographic groups as being discrete and fixed but considers the entire life as the basic framework for empirical analysis and policy evaluation. The link between individual trajectories on one hand and historical period, social structures, as well as human agency on the other is also at the core of the life course paradigm. The notion of life course posits therefore that life trajectories are constituted by a palette of sequences of events that are both individually and socially constructed. The main objective of this cross-country comparative paper is to analyse to which extent the design of national welfare state regimes shape households’ patterns of labour market integration over the life course. An analysis of the various national regulatory frameworks, with special focus on institutional opportunities and/or barriers to combine paid work with other social activities, is provided. Special attention is also given to companies’ human resource and time management and whether human resource strategies encompass a life course perspective. By linking the specificity of the various regulatory and social protection systems to the country's current patterns of labour market integration the authors not only examine the impact of the overall institutional framework on time allocation over the life course but, also the extent to which the current working time options actually affect the sustainability of the social protection systems. Finally, in the conclusion, some policy implications are suggested with a special focus on the needs of finding new forms of time organisation and distribution of income over the life course. According to the authors these new forms of time management might contribute to a better work life balance for employees and might favour positive compromises between firms’ productive efficiency and employees’ needs for a larger control on their time structures over their life course.
Semaphorin 4D/Plexin-B1–mediated R-Ras GAP activity inhibits cell migration by regulating β1 integrin activity
Authors: Oinuma Izumi , Katoh Hironori , Negishi Manabu
Published: May 2006

Plexins are cell surface receptors for semaphorins and regulate cell migration in many cell types. We recently reported that the semaphorin 4D (Sema4D) receptor Plexin-B1 functions as a GTPase-activating protein (GAP) for R-Ras, a member of Ras family GTPases implicated in regulation of integrin activity and cell migration (Oinuma, I., Y. Ishikawa, H. Katoh, and M. Negishi. 2004. Science. 305:862–865). We characterized the role of R-Ras downstream of Sema4D/Plexin-B1 in cell migration. Activation of Plexin-B1 by Sema4D suppressed the ECM-dependent R-Ras activation, R-Ras–mediated phosphatydylinositol 3-kinase activation, and β1 integrin activation through its R-Ras GAP domain, leading to inhibition of cell migration. In addition, inactivation of R-Ras by overexpression of the R-Ras–specific GAP or knockdown of R-Ras by RNA interference was sufficient for suppressing β1 integrin activation and cell migration in response to the ECM stimulation. Thus, we conclude that R-Ras activity is critical for ECM-mediated β1 integrin activation and cell migration and that inactivation of R-Ras by Sema4D/Plexin-B1–mediated R-Ras GAP activity controls cell migration by modulating the activity of β1 integrins.
Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells
Authors: Stavru Fabrizia , Nautrup-Pedersen Gitte , Cordes Volker C. , Görlich Dirk
Published: May 2006

So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several nucleoporins, such as Nup62 or Nup358, to ectopic assembly sites. It thus appears to act as a nucleation site for the assembly of NPC substructures. Nonetheless, we observed functional NPCs and intact NEs in severely POM121-depleted cells. Double knockdowns of gp210 and POM121 in HeLa cells, as well as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein–protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane-integral nucleoporins for anchorage within the lipid bilayer of the NE. In Stavru et al. (on p. 509 of this issue), we describe such an additional transmembrane nucleoporin as the metazoan orthologue of yeast Ndc1p.
Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system
Authors: Voehringer David , Reese Tiffany A. , Huang Xiaozhu , Shinkai Kanade , Locksley Richard M.
Published: May 2006

Nippostrongylus brasiliensis infection and ovalbumin-induced allergic lung pathology are highly interleukin (IL)-4/IL-13 dependent, but the contributions of IL-4/IL-13 from adaptive (T helper [Th]2 cells) and innate (eosinophil, basophils, and mast cells) immune cells remain unknown. Although required for immunoglobulin (Ig)E induction, IL-4/IL-13 from Th2 cells was not required for worm expulsion, tissue inflammation, or airway hyperreactivity. In contrast, innate hematopoietic cell–derived IL-4/IL-13 was dispensable for Th2 cell differentiation in lymph nodes but required for effector cell recruitment and tissue responses. Eosinophils were not required for primary immune responses. Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell–dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity.
Singapore's multibillion dollar gamble
Authors: Van Epps Heather L.
Published: May 2006

Biopolis, Singapore's futuristic research hub. How does a country one-fourth the size of Rhode Island with little history in biomedical science become one of the world's biomedical research giants? The answer: with a pile of money and a large dose of chutzpah. Since 2000, Singapore has dumped more than US$2 billion into developing a biomedical research industry—from scratch. Is the gamble paying off?
Ignoring endotoxin
Authors: Van Epps Heather L.
Published: May 2006

In 1947, Paul Beeson showed that rabbits repeatedly injected with certain bacteria eventually become resistant to the bacteria's fever-provoking effects—a phenomenon known as endotoxin tolerance.
FCP: functional coverage of the proteome by structures
Authors: García-Serna Ricard , Opatowski Lulla , Mestres Jordi
Published: May 2006

Motivation: Tools and resources for translating the remarkable growth witnessed in recent years in the number of protein structures determined experimentally into actual gain in the functional coverage of the proteome are becoming increasingly necessary. We introduce FCP, a publicly accessible web tool dedicated to analyzing the current state and trends of the population of structures within protein families. FCP offers both graphical and quantitative data on the degree of functional coverage of enzymes and nuclear receptors by existing structures, as well as on the bias observed in the distribution of structures along their respective functional classification schemes.

Availability:  

Contact:  jmestres@imim.es
Developing a move-set for protein model refinement
Authors: Offman Marc N. , Fitzjohn Paul W. , Bates Paul A.
Published: May 2006

Motivation: A wide variety of methods for the construction of an atomic model for a given amino acid sequence are known, the more accurate being those that use experimentally determined structures as templates. However, far fewer methods are aimed at refining these models. The approach presented here carefully blends models created by several different means, in an attempt to combine the good quality regions from each into a final, more refined, model.

Results: We describe here a number of refinement operators (collectively, ‘move-set’) that enable a relatively large region of conformational space to be searched. This is used within a genetic algorithm that reshuffles and repacks structural components. The utility of the move-set is demonstrated by introducing a cost function, containing both physical and other components guiding the input structures towards the target structure. We show that our move-set has the potential to improve the conformation of models and that this improvement can be beyond even the best template for some comparative modelling targets.

Availability: The populus software package and the source code are available at

Contact:  paul.bates@cancer.org.uk
Diagnostic Tests in Hirschsprung Disease
Authors: de Lorijn F. , Kremer L.C.M. , Reitsma J.B. , Benninga M.A.
Published: May 2006

Objective:

We conducted a systematic review to determine and compare the diagnostic accuracy of contrast enema (CE), anorectal manometry (ARM) and rectal suction biopsy (RSB) in infants suspected of Hirschsprung disease.

Design:

This is a systematic review.

Data Sources:

Articles were identified through electronic searches in Medline, EMBASE.com and Cochrane Controlled Trials Register. Searches were limited to articles published after 1966 in PubMed and after 1980 in EMBASE.com.

Study Selection:

Studies were included if infants underwent at least one of the following tests: CE, ARM or RSB, followed by full‐thickness biopsy and/or clinical follow‐up as the reference standard.

Data Extraction:

Two reviewers independently assessed the methods of data collection, patient selection, blinding and prevention of verification bias and description of the test protocol and reference standard. Data to construct 2 × 2 tables were abstracted for each test.

Results:

Twenty‐four studies met our inclusion criteria, but 2 studies were subsequently excluded for statistical analysis because data was missing to construct the 2 × 2 table. RSB (14 studies for a total of 993 patients) was the most accurate test, having both the highest mean sensitivity (93%; 95% confidence interval [CI], 88%‐95%) and mean specificity (98%; 95% CI, 95%‐99%). Sensitivity and specificity of ARM (9 studies for a total of 400 patients) were similar to those of RSB (91% vs 93%, P = 0.73 and 94% vs 98%, P = 0.08, respectively). Sensitivity and specificity of CE (12 studies for a total of 425 patients) were significantly lower than those of RSB and ARM, with mean sensitivity and mean specificity of 70% and 83%, respectively.

Conclusions:

RSB and ARM are the most accurate tests in the diagnostic workup of Hirschsprung disease.
Breast‐feeding Duration and Childhood Acute Leukemia and Lymphomas in a Sample of Turkish Children
Authors: Altinkaynak Sevin , Selimoglu Mukadder Ayse , Turgut Ahmet , Kilicaslan Buket , Ertekin Vildan
Published: May 2006

Objectives:

Whether breast‐feeding is associated with decreased incidence of the lymphoid malignancies in children is uncertain. We evaluated childhood acute leukemia and lymphoma in relation to duration of breast‐feeding.

Methods:

We investigated this issue in a case‐control study comprising 137 patients, aged 1 to 16 years, with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin or non‐Hodgkin lymphoma, in addition to 146 controls matched for age and sex.

Results:

The median duration of breast‐feeding among patients was shorter than that of controls (10 vs 12 months). Patients with ALL and AML had shorter mean breast‐feeding duration compared with healthy children (P = 0.001 and P < 0.001, respectively). The shortest mean breast‐feeding duration was noted in the children with AML.

Breast‐feeding for a duration of 0 to 6 months, when compared with feeding of longer than 6 months, was associated with increased odds ratios (ORs) for ALL [OR = 2.44, 95% confidence interval (CI) = 1.17‐5.10], AML (OR = 6.67, 95% CI = 1.32‐33.69), Hodgkin lymphoma (OR = 3.33, 95% CI = 0.60‐18.54), non‐Hodgkin lymphoma (OR = 1.90, 95% CI = 0.68‐5.34) and overall (OR = 2.54, 95% CI = 1.51‐4.26).

Conclusions:

Our findings suggest that breast‐feeding of more than 6 months is protective against childhood lymphoid malignancies, especially for AML and ALL. JPGN 42:568‐572, 2006.
Bifidogenic Effects of Solid Weaning Foods With Added Prebiotic Oligosaccharides
Authors: Scholtens Petra A.M.J. , Alles Martine S. , Bindels Jacques G. , van der Linde Esmeralda G.M. , Tolboom Jules J.M. , Knol Jan
Published: May 2006

Objectives:

Breast‐fed infants have relatively high proportions of faecal bifidobacteria. This bifidogenic microbiota is at least partly explained by the high levels of prebiotic oligosaccharides in human milk. The present study aimed at testing the effect of solid foods with added prebiotic galacto‐ and fructo‐oligosaccharides (GOS/FOS) on the composition of the intestinal microbiota of fully formula‐fed infants during the weaning period.

Methods:

The study was a double‐blind, randomised trial with an intervention period of 6 weeks. Infants aged 4 to 6 months who were about to start consuming solid foods were randomised to receive either weaning products with a mixture of GOS/FOS or control weaning products with maltodextrin. After an adjustment period, the presented daily dose of GOS/FOS was 4.5 g. Total numbers of bacteria and bifidobacteria in faecal samples were analysed with fluorescent in situ hybridization.

Results:

Thirty‐five infants were included in the study, and 20 infants were included in a per‐protocol analysis. In the GOS/FOS group, the faecal percentage of bifidobacteria significantly increased from 43% to 57% (P = 0.031) from week 0 to week 6, but did not significantly change in the control group (36% and 32%, respectively; P = 0.387). The change in the percentage of bifidobacteria between week 0 and week 6 in the GOS/FOS was significantly different from this change in the control group (P = 0.026).

Conclusions:

We conclude that addition of GOS/FOS to solid foods induces an increase in the faecal proportion of bifidobacteria in the intestinal microbiota of fully formula‐fed infants with an established, mixed‐type microbiota in the weaning period.
The “Red Umbilicus”
Authors: Iacono Giuseppe , Di Prima Lidia , D'Amico Domenico , Scalici Calogero , Geraci Girolamo , Carroccio Antonio
Published: May 2006

Introduction:

Red umbilicus is considered to be an infectious disease typical of neonates. In our experience, umbilical erythema could be due to cow's milk protein intolerance (CMPI).

Aims:

To evaluate the frequency and clinical significance of umbilical erythema in a series of consecutive children referred for suspected CMPI.

Patients and Methods:

Seven hundred ninety‐six consecutive patients (median age, 18 months) referred for suspected CMPI diagnosis were studied. CMPI diagnosis was based on the disappearance of symptoms on elimination diet and their subsequent reappearance on double‐blind placebo‐controlled cow's milk challenge.

Results:

CMPI was diagnosed in 384 patients: 120 with respiratory, 75 dermatologic and 198 gastroenterological symptoms. Although some patients showed more than 1 type of symptom, whether gastroenterological, dermatologic or respiratory, they were classified in 1 category only according to the main reason for referral to the outpatients clinic. Umbilical erythema was observed in 36 patients (median age, 10 months): 16 (8%) with gastroenterological symptoms, 9 (7.5%) with recurrent asthma and 11 (15%) with atopic dermatitis. None of the symptomatic controls without CMPI had umbilical erythema. On elimination diet, the erythema disappeared within the second week. On CMPI challenge, it reappeared within 24 hours.

Conclusions:

Umbilical erythema can be a sign of food intolerance and can be a useful diagnostic tool for CMPI.
Allergic Eosinophilic Gastroenteritis With Protein‐losing Enteropathy
Authors: Chehade Mirna , Magid Margret S. , Mofidi Shideh , Nowak‐Wegrzyn Anna , Sampson Hugh A. , Sicherer Scott H.
Published: May 2006

Objectives:

A subset of patients with allergic eosinophilic gastroenteritis (AEG) has anemia and hypoalbuminemia caused by protein‐losing enteropathy (PLE). Our goals were to describe the response to therapy and the long‐term outcome of patients in this subgroup and to evaluate their gastric and intestinal biopsies for distinguishing features that might explain their protein and blood loss.

Methods:

Patients with AEG + PLE were identified retrospectively and compared with controls and with patients with AEG only. Immunohistochemical staining for tryptase, a mast cell mediator, was performed on gastric and duodenal tissues. Eosinophils identified by hematoxylin/eosin stain and mast cells identified as tryptase‐positive cells were counted in one high‐power field area with maximal cell infiltration.

Results:

Although all patients had excellent response to therapy with amino acid‐based formula and tolerated gradual introduction of some foods with time, food‐responsive disease persisted in all patients over 2.5 to 5.5 years of follow‐up. Routine histological evaluation did not show any features differentiating AEG + PLE from AEG. When eosinophils and mast cells were counted in intestinal biopsies, however, significantly more mast cells were found in biopsies of the AEG + PLE group despite comparable numbers of eosinophils. In contrast, in gastric biopsies, eosinophils were more prominent in AEG + PLE, but mast cell numbers were similar in all groups.

Conclusions:

Patients with AEG + PLE responded well to therapy with amino acid‐based formula. Food hypersensitivities did not completely resolve over up to 5.5 years. Intestinal mast cells were significantly increased in maximally infiltrated areas of the intestine, possibly causing increased intestinal permeability and protein loss. JPGN 42:516‐521, 2006.
Lactobacillus rhamnosus GG Decreases Lipopolysaccharide‐induced Systemic Inflammation in a Gastrostomy‐fed Infant Rat Model
Authors: Zhang Liyan , Li Nan , des Robert Clotilde , Fang Maozhong , Liboni Kellym , McMahon Robert , Caicedo Ricardo A. , Neu Josef
Published: May 2006

Objectives:

A gastrostomy‐fed rat infant “pup‐in‐a‐cup” model was used to test the hypothesis that enterally administered Lactobacillus rhamnosus GG (LGG) decreases the proinflammatory response induced by Escherichia coli lipopolysaccharide (LPS) in the developing infant rat small intestine, plasma, lung and liver.

Methods:

Two groups of 6‐ to 7‐day‐old pups were fed a rat milk substitute with LPS added via the gastrostomy tube for 6 days. One of the rat milk substitute‐fed groups received supplemental LGG; another group received LPS without LGG. Age‐matched mother‐fed rat pups were used as controls.

Results:

LPS treatment blunted body growth, but LGG supplementation had no effect on weight increments. LGG decreased LPS‐induced inflammation in intestinal tissue; CINC‐1 (rodent IL‐8 equivalent) production in plasma, liver, lung and distal small intestine; and tumor necrosis factor alpha (TNF‐α) production in plasma and lung. Cytokine multiplex assay showed lung interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, growth‐related oncogene (GRO)/KC (rat CINC‐1) and TNF‐α were significantly higher in gastrostomy‐fed, LPS‐treated pups than in mother‐reared pups, and LGG significantly blunted the LPS‐induced elevation of IL‐1β, IL‐10, IL‐18, GRO/KC and TNF‐α; liver GRO/KC was significantly higher in gastrostomy‐fed, LPS‐treated pups than in mother‐reared pups, and LGG significantly blunted the LPS‐induced elevation of GRO/KC.

Conclusions:

LGG provided by the enteral route is able to downregulate LPS‐induced proinflammatory mediators. This effect is not only present in the splanchnic organs, that is, the intestine and the liver, but extends to the plasma and a distal organ, the lung. JPGN 42:545‐552, 2006.
Severity of Basal Cell Hyperplasia Differs in Reflux Versus Eosinophilic Esophagitis
Authors: Steiner Steven J. , Kernek Kevin M. , Fitzgerald Joseph F.
Published: May 2006

Objectives:

Basal cell hyperplasia of the esophageal epithelium is a frequent finding in children with histological evidence of esophagitis. The aim of this study was to compare the severity of basal cell hyperplasia in gastroesophageal reflux vs eosinophilic esophagitis.

Methods:

A cohort of pediatric patients who underwent same‐day endoscopy with esophageal biopsy and 24‐hour esophageal pH monitoring was divided into groups based on endoscopic and pH monitoring findings. Basal cell hyperplasia was defined as normal (≤25% of esophageal epithelial height), mild (26%‐50%), moderate (51%‐75%) or severe (>75%). The severity of basal cell hyperplasia in patients with abnormal pH monitoring studies, both with and without endoscopic abnormalities of the esophagus, was compared with the severity in patients with eosinophilic esophagitis.

Results:

Twenty‐seven children with abnormal pH monitoring were identified. Of these 27 children, 11 had endoscopic findings consistent with reflux esophagitis. Thirty patients with eosinophilic esophagitis were identified. Patients with eosinophilic esophagitis had significantly increased severity (P < 0.001) of basal cell hyperplasia (87% severe, 3% moderate, 3% mild, 7%, normal) than patients with abnormal esophageal pH monitoring alone (11% severe, 4% moderate, 15% mild, 70% normal) or in combination with endoscopic abnormalities (18% severe, 9% moderate, 18% mild, 55% normal).

Conclusions:

Basal cell hyperplasia is more severe in children with eosinophilic esophagitis than in those with reflux esophagitis. The finding of basal cell hyperplasia is a powerful clue into the underlying etiology of pediatric esophagitis and, along with epithelial eosinophil count, can be used as information to guide therapy.