bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymer particles that switch shape in response to a stimulus
Authors: Yoo Jin-Wook , Mitragotri Samir
Published: June 2010

Particle engineering for biomedical applications has unfolded the roles of attributes such as size, surface chemistry, and shape for modulating particle interactions with cells. Recently, dynamic manipulation of such key properties has gained attention in view of the need to precisely control particle interaction with cells. With increasing recognition of the pivotal role of particle shape in determining their biomedical applications, we report on polymeric particles that are able to switch their shape in real time in a stimulus-responsive manner. The shape-switching behavior was driven by a subtle balance between polymer viscosity and interfacial tension. The balance between the two forces was modulated by application of an external stimulus chosen from temperature, pH, or chemical additives. The dynamics of shape switch was precisely controlled over minutes to days under physiological conditions. Shape-switching particles exhibited unique interactions with cells. Elliptical disk-shaped particles that are not phagocytosed by macrophages were made to internalize through shape switch, demonstrating the ability of shape-switchable particles in modulating interaction with cells.
A type III-like restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical
Staphylococcus aureus
strains
Authors: Corvaglia Anna R. , François Patrice , Hernandez David , Perron Karl , Linder Patrick , Schrenzel Jacques
Published: June 2010

Staphylococcus aureus
is an versatile pathogen that can cause life-threatening infections. Depending on the clinical setting, up to 50% of
S. aureus
infections are caused by methicillin-resistant strains (MRSA) that in most cases are resistant to many other antibiotics, making treatment difficult. The emergence of community-acquired MRSA drastically changed the picture by increasing the risk of MRSA infections. Horizontal transfer of genes encoding for antibiotic resistance or virulence factors is a major concern of multidrug-resistant
S. aureus
infections and epidemiology. We identified and characterized a type III-like restriction system present in clinical
S. aureus
strains that prevents transformation with DNA from other bacterial species. Interestingly, our analysis revealed that some clinical MRSA strains are deficient in this restriction system, and thus are hypersusceptible to the horizontal transfer of DNA from other species, such as
Escherichia coli
, and could easily acquire a vancomycin-resistance gene from enterococci. Inactivation of this restriction system dramatically increases the transformation efficiency of clinical
S. aureus
strains, opening the field of molecular genetic manipulation of these strains using DNA of exogenous origin.
Bacteria dispersal by hitchhiking on zooplankton
Authors: Grossart Hans-Peter , Dziallas Claudia , Leunert Franziska , Tang Kam W.
Published: June 2010

Microorganisms and zooplankton are both important components of aquatic food webs. Although both inhabit the same environment, they are often regarded as separate functional units that are indirectly connected through nutrient cycling and trophic cascade. However, research on pathogenic and nonpathogenic bacteria has shown that direct association with zooplankton has significant influences on the bacteria's physiology and ecology. We used stratified migration columns to study vertical dispersal of hitchhiking bacteria through migrating zooplankton across a density gradient that was otherwise impenetrable for bacteria in both upward and downward directions (conveyor-belt hypothesis). The strength of our experiments is to permit quantitative estimation of transport and release of associated bacteria: vertical migration of
Daphnia magna
yielded an average dispersal rate of 1.3 × 10
5
·cells·
Daphnia
−1
·migration cycle
−1
for the lake bacterium
Brevundimonas
sp. Bidirectional vertical dispersal by migrating
D. magna
was also shown for two other bacterial species, albeit at lower rates. The prediction that diurnally migrating zooplankton acquire different attached bacterial communities from hypolimnion and epilimnion between day and night was subsequently confirmed in our field study. In mesotrophic Lake Nehmitz,
D. hyalina
showed pronounced diel vertical migration along with significant diurnal changes in attached bacterial community composition. These results confirm that hitchhiking on migrating animals can be an important mechanism for rapidly relocating microorganisms, including pathogens, allowing them to access otherwise inaccessible resources.
The acute effect of local homicides on children's cognitive performance
Authors: Sharkey Patrick
Published: June 2010

This study estimates the acute effect of exposure to a local homicide on the cognitive performance of children across a community. Data are from a sample of children age 5–17 y in the Project on Human Development in Chicago Neighborhoods. The effect of local homicides on vocabulary and reading assessments is identified by exploiting exogenous variation in the relative timing of homicides and interview assessments among children in the same neighborhood but assessed at different times. Among African-Americans, the strongest results show that exposure to a homicide in the block group that occurs less than a week before the assessment reduces performance on vocabulary and reading assessments by between ∼0.5 and ∼0.66 SD, respectively. Main results are replicated using a second independent dataset from Chicago. Findings suggest the need for broader recognition of the impact that extreme acts of violence have on children across a neighborhood, regardless of whether the violence is witnessed directly.
A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release
Authors: Yang Huan , Hreggvidsdottir Hulda S. , Palmblad Karin , Wang Haichao , Ochani Mahendar , Li Jianhua , Lu Ben , Chavan Sangeeta , Rosas-Ballina Mauricio , Al-Abed Yousef , Akira Shizuo , Bierhaus Angelika , Erlandsson-Harris Helena , Andersson Ulf , Tracey Kevin J.
Published: June 2010

During infection, vertebrates develop “sickness syndrome,” characterized by fever, anorexia, behavioral withdrawal, acute-phase protein responses, and inflammation. These pathophysiological responses are mediated by cytokines, including TNF and IL-1, released during the innate immune response to invasion. Even in the absence of infection, qualitatively similar physiological syndromes occur following sterile injury, ischemia reperfusion, crush injury, and autoimmune-mediated tissue damage. Recent advances implicate high-mobility group box 1 (HMGB1), a nuclear protein with inflammatory cytokine activities, in stimulating cytokine release. HMGB1 is passively released during cell injury and necrosis, or actively secreted during immune cell activation, positioning it at the intersection of sterile and infection-associated inflammation. To date, eight candidate receptors have been implicated in mediating the biological responses to HMGB1, but the mechanism of HMGB1-dependent cytokine release is unknown. Here we show that Toll-like receptor 4 (TLR4), a pivotal receptor for activation of innate immunity and cytokine release, is required for HMGB1-dependent activation of macrophage TNF release. Surface plasmon resonance studies indicate that HMGB1 binds specifically to TLR4, and that this binding requires a cysteine in position 106. A wholly synthetic 20-mer peptide containing cysteine 106 from within the cytokine-stimulating B box mediates TLR4-dependent activation of macrophage TNF release. Inhibition of TLR4 binding with neutralizing anti-HMGB1 mAb or by mutating cysteine 106 prevents HMGB1 activation of cytokine release. These results have implications for rationale, design, and development of experimental therapeutics for use in sterile and infectious inflammation.
Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis
Authors: Sheftel Alex D. , Stehling Oliver , Pierik Antonio J. , Elsässer Hans-Peter , Mühlenhoff Ulrich , Webert Holger , Hobler Anna , Hannemann Frank , Bernhardt Rita , Lill Roland
Published: June 2010

Mammalian adrenodoxin (ferredoxin 1; Fdx1) is essential for the synthesis of various steroid hormones in adrenal glands. As a member of the [2Fe-2S] cluster-containing ferredoxin family, Fdx1 reduces mitochondrial cytochrome P450 enzymes, which then catalyze; e.g., the conversion of cholesterol to pregnenolone, aldosterone, and cortisol. The high protein sequence similarity between Fdx1 and its yeast adrenodoxin homologue (Yah1) suggested that Fdx1, like Yah1, may be involved in the biosynthesis of heme A and Fe/S clusters, two versatile and essential protein cofactors. Our study, employing RNAi technology to deplete human Fdx1, did not confirm this expectation. Instead, we identified a Fdx1-related mitochondrial protein, designated ferredoxin 2 (Fdx2) and found it to be essential for heme A and Fe/S protein biosynthesis. Unlike Fdx1, Fdx2 was unable to efficiently reduce mitochondrial cytochromes P450 and convert steroids, indicating that the two ferredoxin isoforms are highly specific for their substrates in distinct biochemical pathways. Moreover, Fdx2 deficiency had a severe impact, via impaired Fe/S protein biogenesis, on cellular iron homeostasis, leading to increased cellular iron uptake and iron accumulation in mitochondria. We conclude that mammals depend on two distinct mitochondrial ferredoxins for the specific production of either steroid hormones or heme A and Fe/S proteins.
Drosophila
Orb2 targets genes involved in neuronal growth, synapse formation, and protein turnover
Authors: Mastushita-Sakai Tomoko , White-Grindley Erica , Samuelson Jessica , Seidel Chris , Si Kausik
Published: June 2010

In the study of long-term memory, how memory persists is a fundamental and unresolved question. What are the molecular components of the long-lasting memory trace? Previous studies in
Aplysia
and
Drosophila
have found that a neuronal variant of a RNA-binding protein with a self-perpetuating prion-like property, cytoplasmic polyadenylation element binding protein, is required for the persistence of long-term synaptic facilitation in the snail and long-term memory in the fly. In this study, we have identified the mRNA targets of the
Drosophila
neuronal cytoplasmic polyadenylation element binding protein,
Orb2
. These
Orb2
targets include genes involved in neuronal growth, synapse formation, and intriguingly, protein turnover. These targets suggest that the persistent form of the memory trace might be comprised of molecules that maintain a sustained, permissive environment for synaptic growth in an activated synapse.
BCL6promoter interacts with far upstream sequences with greatly enhanced activating histone modifications in germinal center B cells
Authors: Ramachandrareddy Himabindu , Bouska Alyssa , Shen Yulei , Ji Ming , Rizzino Angie , Chan Wing C. , McKeithan Timothy W.
Published: June 2010

BCL6encodes a transcriptional repressor that is essential for the germinal center (GC) reaction and important in lymphomagenesis. Although its promoter has been well studied, little is known concerning its possible regulation by more distal elements. To gain such information, we mapped critical histone modifications associated with active transcription withinBCL6as well as far upstream sequences at nucleosomal resolution in B-cell lines and in normal naive and GC B cells. Promoter-associated and intronic CpG islands (CGIs) inBCL6showed a reciprocal pattern of histone modifications. Gene expression correlated with a paradoxical loss from the intronic CGI of histone H3 lysine-4 trimethylation, normally associated with transcription, suggesting that the intronic CGI may interfere with transcription. In an ∼110-kb region extending 150–260 kb upstream ofBCL6, highly active histone modifications were present only in normal GC B cells and a GC B-cell line; this region overlaps with an alternative breakpoint region for chromosomal translocations and contains a GC-specific noncoding RNA gene. By chromosome conformation capture, we determined that theBCL6promoter interacts with this distant upstream region. It is likely that transcriptional enhancers in this region activateBCL6and overcome strong autorepression in GC B cells.
Conservation of progesterone hormone function in invertebrate reproduction
Authors: Stout E. Paige , La Clair James J. , Snell Terry W. , Shearer Tonya L. , Kubanek Julia
Published: June 2010

Steroids play fundamental roles regulating mammalian reproduction and development. Although sex steroids and their receptors are well characterized in vertebrates and several arthropod invertebrates, little is known about the hormones and receptors regulating reproduction in other invertebrate species. Evolutionary insights into ancient endocrine pathways can be gained by elucidating the hormones and receptors functioning in invertebrate reproduction. Using a combination of genomic analyses, receptor imaging, ligand identification, target elucidation, and exploration of function through receptor knockdown, we now show that comparable progesterone chemoreception exists in the invertebrate monogonont rotifer
Brachionus manjavacas
, suggesting an ancient origin of the signal transduction systems commonly associated with the development and integration of sexual behavior in mammals.
Proteomic identification of phosphatidylinositol (3,4,5) triphosphate-binding proteins in
Dictyostelium discoideum
Authors: Zhang Pingbo , Wang Yu , Sesaki Hiromi , Iijima Miho
Published: June 2010

Phosphatidylinositol (3,4,5)-triphosphate (PtdInsP
3
) mediates intracellular signaling for directional sensing and pseudopod extension at the leading edge of migrating cells during chemotaxis. How this PtdInsP
3
signal is translated into remodeling of the actin cytoskeleton is poorly understood. Here, using a proteomics approach, we identified multiple PtdInsP
3
-binding proteins in
Dictyostelium discoideum
, including five pleckstrin homology (PH) domain-containing proteins. Two of these, the serine/threonine kinase Akt/protein kinase B and the PH domain-containing protein PhdA, were previously characterized as PtdInsP
3
-binding proteins. In addition, PhdB, PhdG, and PhdI were identified as previously undescribed PH domain-containing proteins. Specific PtdInsP
3
interactions with PhdB, PhdG, and PhdI were confirmed using an in vitro lipid-binding assay. In cells, PhdI associated with the plasma membrane in a manner dependent on both the PH domain and PtdInsP
3
. Consistent with this finding, PhdI located to the leading edge in migrating cells. In contrast, PhdG was found in the cytosol in WT cells. However, when PtdInsP
3
was overproduced in
pten
−
cells, PhdG located to the plasma membrane, suggesting its weak affinity for PtdInsP
3
. PhdB was found to bind to the plasma membrane via both PtdInsP
3
-dependent and -independent mechanisms. The PtdInsP
3
-independent interaction was mediated by the middle domain, independent of the PH domain. In migrating cells, the majority of PhdB was found at the lagging edge. Finally, we deleted the genes encoding PhdB and PhdG and demonstrated that both proteins are required for efficient chemotaxis. Thus, this study advances our understanding of the PtdInsP
3
-mediated signaling mechanisms that control directed cell migration in chemotaxis.
Interference with Sin3 function induces epigenetic reprogramming and differentiation in breast cancer cells
Authors: Farias Eduardo F. , Petrie Kevin , Leibovitch Boris , Murtagh Janice , Chornet Manuel Boix , Schenk Tino , Zelent Arthur , Waxman Samuel
Published: June 2010

Sin3A/B is a master transcriptional scaffold and corepressor that plays an essential role in the regulation of gene transcription and maintenance of chromatin structure, and its inappropriate recruitment has been associated with aberrant gene silencing in cancer. Sin3A/B are highly related, large, multidomian proteins that interact with a wide variety of transcription factors and corepressor components, and we examined whether disruption of the function of a specific domain could lead to epigenetic reprogramming and derepression of specific subsets of genes. To this end, we selected the Sin3A/B-paired amphipathic α-helices (PAH2) domain based on its established role in mediating the effects of a relatively small number of transcription factors containing a PAH2-binding motif known as the Sin3 interaction domain (SID). Here, we show that in both human and mouse breast cancer cells, the targeted disruption of Sin3 function by introduction of a SID decoy that interferes with PAH2 binding to SID-containing partner proteins reverted the silencing of genes involved in cell growth and differentiation. In particular, the SID decoy led to epigenetic reprogramming and reexpression of the important breast cancer-associated silenced genes encoding E-cadherin, estrogen receptor α, and retinoic acid receptor β and impaired tumor growth in vivo. Interestingly, the SID decoy was effective in the triple-negative M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cell line, restoring sensitivity to 17β-estradiol, tamoxifen, and retinoids. Therefore, the development of small molecules that can block interactions between PAH2 and SID-containing proteins offers a targeted epigenetic approach for treating this type of breast cancer that may also have wider therapeutic implications.
Mapping of cerebral oxidative metabolism with MRI
Authors: Mellon Eric A. , Beesam R. Shashank , Elliott Mark A. , Reddy Ravinder
Published: June 2010

Using a T

1
ρ

MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of

gas. The study was performed by

inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9%+/-2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T

1
ρ

MRI following administration of

gas. Metabolism was calculated from the change in the T

1
ρ

weighted MRI signal due to H
2
17
O generated from

inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H
2
17
O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive

gas. Given the demonstrated high efficiency in use of

and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.
Understanding phase behavior of plant cell cortex microtubule organization
Authors: Shi Xia-qing , Ma Yu-qiang
Published: June 2010

Plant microtubules are found to be strongly associated with the cell cortex and to experience polymerization/depolymerization processes that are responsible for the organization of microtubule cortical array. Here we propose a minimal model that incorporates the basic assembly dynamics and intermicrotubule interaction to understand the unexplored phase behavior of such a system. Through kinetic Monte Carlo simulations and theoretical calculations, we show that the self-organized patterns of plant cell cortical microtubules can be regulated by controlling single microtubule assembly dynamics. Biologically, this means that the structural reorganization can be regulated by microtubule-associated proteins via changing microtubule dynamic instability parameters, such as the microtubule plus-end growing rate, GTP-tubulin hydrolysis rate, etc. Such regulation is indirectly confirmed by various in vivo experiments. For the physical aspects, we not only construct the phase diagram that determines under what parameters ordered microtubule arrays form, but also predict that the essentially different ordered structures may appear through continuous and discontinuous transitions. The present study will play a central role in our understanding of the basic mechanism of plant cell noncentrosomal microtubule arrays.
Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T
Authors: Iovannisci David , Illek Beate , Fischer Horst
Published: June 2010

Airways secrete considerable amounts of acid. In this study, we investigated the identity and the pH-dependent function of the apical H+ channel in the airway epithelium. In pH stat recordings of confluent JME airway epithelia in Ussing chambers, Zn-sensitive acid secretion was activated at a mucosal threshold pH of ∼7, above which it increased pH-dependently at a rate of 339 ± 34 nmol × h−1 × cm−2 per pH unit. Similarly, H+ currents measured in JME cells in patch clamp recordings were readily blocked by Zn and activated by an alkaline outside pH. Small interfering RNA–mediated knockdown of HVCN1 mRNA expression in JME cells resulted in a loss of H+ currents in patch clamp recordings. Cloning of the open reading frame of HVCN1 from primary human airway epithelia resulted in a wild-type clone and a clone characterized by two sequential base exchanges (452T>C and 453G>A) resulting in a novel missense mutation, M91T HVCN1. Out of 95 human genomic DNA samples that were tested, we found one HVCN1 allele that was heterozygous for the M91T mutation. The activation of acid secretion in epithelia that natively expressed M91T HVCN1 required ∼0.5 pH units more alkaline mucosal pH values compared with wild-type epithelia. Similarly, activation of H+ currents across recombinantly expressed M91T HVCN1 required significantly larger pH gradients compared with wild-type HVCN1. This study provides both functional and molecular indications that the HVCN1 H+ channel mediates pH-regulated acid secretion by the airway epithelium. These data indicate that apical HVCN1 represents a mechanism to acidify an alkaline airway surface liquid.
Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating
Authors: Zahradníková Alexandra , Valent Ivan , Zahradník Ivan
Published: June 2010

Cytosolic calcium concentration in resting cardiac myocytes locally fluctuates as a result of spontaneous microscopic Ca2+ releases or abruptly rises as a result of an external trigger. These processes, observed as calcium sparks, are fundamental for proper function of cardiac muscle. In this study, we analyze how the characteristics of spontaneous and triggered calcium sparks are related to cardiac ryanodine receptor (RYR) gating. We show that the frequency of spontaneous sparks and the probability distribution of calcium release flux quanta of triggered sparks correspond quantitatively to predictions of an allosteric homotetrameric model of RYR gating. This model includes competitive binding of Ca2+ and Mg2+ ions to the RYR activation sites and allosteric interaction between divalent ion binding and channel opening. It turns out that at rest, RYRs are almost fully occupied by Mg2+. Therefore, spontaneous sparks are most frequently evoked by random openings of the highly populated but rarely opening Mg4RYR and CaMg3RYR forms, whereas triggered sparks are most frequently evoked by random openings of the less populated but much more readily opening Ca2Mg2RYR and Ca3MgRYR forms. In both the spontaneous and the triggered sparks, only a small fraction of RYRs in the calcium release unit manages to open during the spark because of the limited rate of Mg2+ unbinding. This mechanism clarifies the unexpectedly low calcium release flux during elementary release events and unifies the theory of calcium signaling in resting and contracting cardiac myocytes.
“Regenten” (Gentlemanly) Capitalism: Saint-Simonian Technocracy and the Emergence of the “Industrialist Great Club” in the Mid-nineteenth Century Netherlands
Authors: Schrauwers Albert
Published: June 2010

The geometric pattern of Amsterdam's canals was iconic of its nineteenth-century social order. The spider's web of canals fanned out along the Amstel river in concentric rings, its barge traffic linking the city to its hinterland, the province of Holland, and to the wider Netherlands of which it is the nominal capital. These canals divided the “Venice of the North” into ninety islands linked by more than a thousand bridges. Imposing aristocratic and merchant houses stretched along the innermost canal ring, theGolden Curveof theGentleman's Canal. At the center of the web lay de Dam, the 200 m long market square built on the first medieval dike protecting the city from the encroaching sea. The three pillars of the Dutch state framed the market square: the Royal Palace of the Merchant King, the Dutch Reformed New Church, and in the nineteenth century, the Amsterdam stock market, the world's oldest exchange.
Social enhancement can create adaptive, arbitrary and maladaptive cultural traditions
Authors: Franz Mathias , Matthews Luke J.
Published: June 2010

Many animals are known to learn socially, i.e. they are able to acquire new behaviours by using information from other individuals. Researchers distinguish between a number of different social-learning mechanisms such as imitation and social enhancement. Social enhancement is a simple form of social learning that is among the most widespread in animals. However, unlike imitation, it is debated whether social enhancement can create cultural traditions. Based on a recent study on capuchin monkeys, we developed an agent-based model to test the hypotheses that (i) social enhancement can create and maintain stable traditions and (ii) social enhancement can create cultural conformity. Our results supported both hypotheses. A key factor that led to the creation of cultural conformity and traditions was the repeated interaction of individual reinforcement and social enhancement learning. This result emphasizes that the emergence of cultural conformity does not necessarily require cognitively complex mechanisms such as ‘copying the majority’ or group norms. In addition, we observed that social enhancement can create learning dynamics similar to a ‘copy when uncertain’ learning strategy. Results from additional analyses also point to situations that should favour the evolution of learning mechanisms more sophisticated than social enhancement.
Flexible phase adjustment of circadian albumin D site-binding protein (Dbp) gene expression by CRYPTOCHROME1
Authors: Stratmann Markus , Stadler Frédéric , Tamanini Filippo , van der Horst Gijsbertus T.J. , Ripperger Jürgen A.
Published: June 2010

The albumin D site-binding protein (DBP) governs circadian transcription of a number of hepatic detoxification and metabolic enzymes prior to the activity phase and subsequent food intake of mice. However, the behavior of mice is drastically affected by the photoperiod. Therefore, continuous adjustment of the phase of circadian Dbp expression is required in the liver. Here we describe a direct impact of CRYPTOCHROME1 (CRY1) on the phase of Dbp expression. Dbp and the nuclear receptor Rev-Erbα are circadian target genes of BMAL1 and CLOCK. Surprisingly, dynamic CRY1 binding to the Dbp promoter region delayed BMAL1 and CLOCK-mediated transcription of Dbp compared with Rev-Erbα. Extended presence of CRY1 in the nucleus enabled continuous uncoupling of the phase of Dbp from Rev-Erbα expression upon change from short to longer photoperiods. CRY1 thus maintained the peak of DBP accumulation close to the activity phase. In contrast, Rev-Erbα expression was phase-locked to the circadian oscillator and shaped by accumulation of its own gene product. Our data indicate that fine-tuning of circadian transcription in the liver is even more sophisticated than expected.
Size‐dependent reproductive success of wild zebrafishDanio rerioin the laboratory
Authors: Uusi‐Heikkilä S. , Wolter C. , Meinelt T. , Arlinghaus R.
Published: June 2010

Size‐dependent reproductive success of wild zebrafishDanio reriowas studied under controlled conditions in the laboratory to further understand the influence of spawner body size on reproductive output and egg and larval traits. Three different spawner size categories attained by size‐selective harvesting of the F1‐offspring of wildD. reriowere established and their reproductive performance compared during a 5 day period. As to be expected, large females spawned more frequently and had significantly greater clutch sizes than small females. Contrary to expectations, small females produced larger eggs when measured as egg diameter with similar amounts of yolk compared to eggs spawned by large spawners. Eggs from small fish, however, suffered from higher egg mortality than the eggs of large individuals. Embryos from small‐sized spawners also hatched later than offspring from eggs laid by large females. Larval standard length (LS)‐at‐hatch did not differ between the size categories, but the offspring of the large fish had significantly larger area‐at‐hatch and greater yolk‐sac volume indicating better condition. Offspring growth rates were generally similar between offspring from all size categories, but they were significantly higher for offspring spawned by small females in terms ofLSbetween days 60 and 90 post‐fertilization. Despite temporarily higher growth rates among the small fish offspring, the smaller energy reserves at hatching translated into lower condition later in ontogeny. It appeared that the influence of spawner body size on egg and larval traits was relatively pronounced early in development and seemed to remain in terms of condition, but not in growth, after the onset of exogenous feeding. Further studies are needed to explore the mechanisms behind the differences in offspring quality between large‐ and small‐sized spawners by disentangling size‐dependent maternal and paternal effects on reproductive variables inD. rerio.
The impact of HLA genotyping on survival following unrelated donor haematopoietic stem cell transplantation
Authors: Shaw Bronwen E. , Arguello Rafael , Garcia‐Sepulveda Christian A. , Madrigal J. Alejandro
Published: June 2010

One of the major factors that have contributed to improving the outcomes of Stem Cell Transplantation is progress made in the field of human leucocyte antigen(s) (HLA). This is evident not only in developing techniques for rapid and accurate tissue typing, but also in the greatly improved understanding of the HLA system and the impact of HLA matching on transplant complications. It is now accepted that high‐resolution HLA matching for transplant recipients and unrelated donors is associated with the best clinical outcomes. The most important HLA determinants are the six ‘classical’ polymorphic HLA loci: HLA‐A, ‐B, ‐C, ‐DRB1,‐DQB1, ‐DPB1. For several years, based on the outcome of numerous studies, a 10/10 matched donor (HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1) was considered the ideal. The impact of HLA‐DPB1 has been less clear, in view of reduced likelihood of patient/donor matching for this locus. More recently, several large studies have questioned the importance of HLA‐DQB1 matching on outcome. Based on the findings of recent studies, the current gold standard unrelated donor is believed to be one matched for 8/8 alleles at high resolution i.e. matched for HLA‐A, ‐B, ‐C, ‐DRB1, however, in certain circumstances, mismatches may be tolerated and/or permissive.
Assessment of liver stiffness in subjects affected by familial combined hyperlipidaemia with hepatic steatosis
Authors: Riggio Stefania , Mamone Federica , Mandraffino Giuseppe , Maimone Sergio , Alibrandi Angela , Manti Lauretta , Saitta Carlo , Tripodi Pier Francesco , Sardo Maria Adriana , Squadrito Giovanni , Saitta Antonino
Published: June 2010

Eur J Clin Invest 2010; 40 (8): 722–728

Background  Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and is associated with familial combined hyperlipidaemia (FCHL). Currently, the invasive liver biopsy is considered as the gold standard for evaluating liver fibrosis (LF); however, liver stiffness measurement (LSM) by transient elastography (TE) trough FibroScan device may be employed to estimate LF noninvasively. The aim of this study was to evaluate the prevalence of NAFLD in FCHL subjects and to analyse LSM with TE to better identify those individuals with a potential risk of liver disease progression.

Materials and methods  Sixty subjects with FCHL (38 men, 22 women, mean age 46·4 ± 10·9 years) were included in the study. We studied biochemical parameters including lipid profile, glucose, transaminase and insulin; blood pressure and waist circumference (WC) were measured; BMI and HOMA‐index were calculated. Ultrasonography was performed to assess liver steatosis and carotid intima‐media thickness (IMT). Liver fibrosis was measured by FibroScan.

Results  Patients were classified according to have no (group 0: 19%), mild (group 1: 32%) or moderate–severe (group 2: 49%) steatosis. No difference was found between group 0 and 1 concerning all study parameters. WC (P < 0·05), BMI (P < 0·05), glucose (P < 0·05), insulin (P < 0·001), HOMA‐index (P < 0·001) and LSM (6·03 ± 1·9 Kpa vs. 4·2 ± 0·5 Kpa, P < 0·001) were significantly higher in group 2 than groups 1 and 0. Furthermore, LSM correlated with insulin (P < 0·05), glucose (P < 0·05), HOMA‐index (P < 0·001), transaminase (P < 0·01) and liver steatosis (P < 0·001). Regression analysis showed that LSM (P < 0·001) and NAFLD (P < 0·01) is associated with HOMA‐index; NAFLD is also associated with WC (P < 0·05).

Conclusion  Our results suggest that in FCHL subjects, HOMA‐index, an insulin resistance index, is strongly associated with liver steatosis and its progression. Furthermore, in these subjects, we propose the transient elastography to identify and follow up patients for the progression of hepatic disease.
White clover selected for enhanced competitive ability widens the compatibility with grasses and favours the optimization of legume content and forage yield in mown clover‐grass mixtures
Authors: Annicchiarico P. , Proietti S.
Published: June 2010

White clover‐grass mixtures should provide swards with a high dry matter (DM) yield with a clover proportion of at least 0·30. This study assessed the compatibility of one white clover variety selected for competitive ability (Giga) and four other large‐leaved clover varieties (Aran, Espanso, Fantastico and Regal) in mown binary mixtures with each of four grass companions (cocksfoot cv. Padania, hybrid ryegrass cv. AberExcel, Italian ryegrass cv. Crema, and tall fescue cv. Magno) over 3 years in northern Italy. On average, the mixtures including Giga had at least a two‐fold greater clover proportion in the total harvested DM (P < 0·01) and contained fewer weeds (P < 0·10) than those with other clover varieties, and also tended to have the highest total DM yields. On average, mixtures containing AberExcel had clover proportions of >0·25 but gave the lowest total DM yields, whereas those of Magno maximized total DM and had a higher proportion of clover than Padania or Crema. No clover × grass interaction was detected (P > 0·05). The association with Giga allowed the tall fescue‐based mixture to attain a clover proportion 0·331 along with a top‐yielding total DM. This mixture, compared with the only one without Giga that displayed a near‐sufficient clover proportion (Espanso with AberExcel), exhibited a 21·7% higher total DM (P < 0·05) and had far fewer weeds.
Topical 1,25‐dihydroxyvitamin D3 subverts the priming ability of draining lymph node dendritic cells
Authors: Gorman Shelley , Judge Melinda A. , Hart Prue H.
Published: June 2010

The active form of vitamin D, 1,25‐hydroxyvitamin D3 [1,25(OH)2D3] is produced in skin following exposure to sunlight. It is also used topically to control inflammatory skin diseases by stimulating keratinocyte differentiation and suppressing immune responses. Administration of 1,25(OH)2D3 to the skin of mice increases the capacity of CD4+ CD25+ (Foxp3+) regulatory T cells residing in the skin‐draining lymph nodes (SDLN) to suppress immune responses. We hypothesized that dendritic cells (DC) may migrate from the skin to the lymph nodes to regulate T‐cell function. Increased proportions of skin‐derived DC (CD11c+ ClassII+ DEC‐205hi CD8lo) cells were detected in the SDLN 18 hr after topical 1,25(OH)2D3 treatment of mouse skin. The capacity of DC from the SDLN to take up, process and present antigen to co‐cultured T cells was not modified following topical 1,25(OH)2D3. However, CD11c+ cells from the SDLN of 1,25(OH)2D3‐treated mice induced a significantly smaller ear‐swelling response in a T helper type 1/17‐mediated model of contact hypersensitivity. CD4+ CD25+ cells isolated from the ear‐draining lymph nodes (EDLN) of mice that received ear injections of CD11c+ cells from donor mice topically treated with 1,25(OH)2D3 more potently suppressed effector cell proliferation. In addition, EDLN cells from recipients of CD11c+ cells from 1,25(OH)2D3‐treated mice produced increased interleukin‐4 levels. The CD11c+ cells from the SDLN of mice treated with topical 1,25(OH)2D3 expressed increased levels of indoleamine 2,3‐dioxygenase messenger RNA, a molecule by which topical 1,25(OH)2D3 may enhance the ability of DC to control the suppressive function of CD4+ CD25+ cells.
rSj16, a recombinant protein of Schistosoma japonicum‐derived molecule, reduces severity of the complete Freund’s adjuvant‐induced adjuvant arthritis in rats’ model
Authors: SUN X. , LIU Y. H. , LV Z. Y. , YANG L. L. , HU S. M. , ZHENG H. Q. , HU W. , CAO J. P. , FUNG M. Q. , WU Z. D.
Published: June 2010

Sj16, a 16‐kDa protein produced by Schistosoma japonicum, has been demonstrated to have anti‐inflammatory effect. However, the possible mechanism of these phenomena has not been discovered. Here, we tried to touch it with arthritis rats’ model induced by injection of complete Freund’s adjuvant (CFA). A set of pathogenic characters were observed in CFA‐treated rat, including local and systematic read‐out, which showed the model successfully set up. After administration of rSj16 (recombinant Sj16) in vivo, paw swelling reduced significantly and in a dose‐dependent manner, the level of TNF‐α, IL‐1β and NO decreased and IL‐10 in the serum increased. In vitro, rSj16 reversed the augmented surface expression of CD80, CD86, CD54 and OX6 induced by lipopolysaccharide (LPS) in bone marrow–derived DCs (BMDCs), whereas endocytotic capacity of rSj16‐treated dendritic cell (DC) was profoundly increased. IL‐12p70 released from rSj16‐treated BMDC was decreased but IL‐10 increased. Further, following incubation with rSj16 primed BMDCs, the sensitized T cells exhibited increased production of anti‐inflammatory IL‐10 and IL‐4 and decreased production of IL‐12p70 and IFN‐γ. Collectively, these results implied that rSj16 alleviated CFA‐induced arthritis, and the possible mechanisms may be its interruption of maturation and function of DCs. rSj16 could be a potential therapeutic agent against rheumatoid arthritis.
Evaluation of the vascular anatomy in potential living kidney donors with gadolinium‐enhanced magnetic resonance angiography: comparison with digital subtraction angiography and intraoperative findings
Authors: Asgari Majid A. , Dadkhah Farid , Ghadian Ali R. , Razzaghi Mohammad R. , Noorbala Mohammad H. , Amini Erfan
Published: June 2010

Asgari MA, Dadkhah F, Ghadian AR, Razzaghi MR, Noorbala MH, Amini E. Evaluation of the vascular anatomy in potential living kidney donors with gadolinium‐enhanced magnetic resonance angiography: comparison with digital subtraction angiography and intraoperative findings. Clin Transplant 2011: 25: 481–485. © 2010 John Wiley & Sons A/S.

Abstract:  Background:  X‐ray contrast arteriography has traditionally been used for pre‐operative evaluation in living kidney donors. However, magnetic resonance angiography (MRA) offers a non‐invasive alternative, which has been considered to be less accurate. This study was performed to determine whether MRA in the pre‐operative investigation of living kidney donors provides sufficient information.

Methods:  From December 2005 to December 2007, 173 potential live donors were evaluated in this study. Donors performed digital subtraction angiography (DSA) and those with one or more accessory arteries at least on one side recruited for further evaluation with three‐dimensional gadolinium‐enhanced MRA.

Results:  A total of 30 donors constituted the study population. When compared with DSA as the reference method, MRA detected 20 of 36 renal accessory arteries which indicates a sensitivity of 55.6%. The difference between MRA and DSA in identifying accessory renal arteries was significant (p‐value <0.001). Considering intraoperative findings as the standard of reference, MRA depicted correctly four of six (66.7%) accessory arteries on the transplanted kidneys.

Conclusions:  MRA has the advantage of avoiding exposure to ionizing radiation and is non‐invasive. These are important considerations in pre‐operative evaluation of a generally healthy donor population. However, MRA provides suboptimal accuracy in detecting small accessory arteries.
Passive smoking alters circulating naïve/memory lymphocyte T‐cell subpopulations in children
Authors: Vardavas Constantine I. , Plada Maria , Tzatzarakis Manolis , Marcos Ascension , Warnberg Julia , Gomez‐Martinez Sonia , Breidenassel Christina , Gonzalez‐Gross Marcela , Tsatsakis Aristeidis M. , Saris Wim H. , Moreno Luis A. , Kafatos Anthony G. ,   on behalf of the HELENA Heraklion Study Group
Published: June 2010

Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez‐Martinez S, Breidenassel C, Gonzalez‐Gross M, Tsatsakis AM, Saris WH., Moreno LA, Kafatos AG. Passive smoking alters circulating naïve/memory lymphocyte T‐cell subpopulations in children. Pediatr Allergy Immunol 2010: 21: 1171–1178. © 2010 John Wiley & Sons A/S

While it has been indicated that exposure to second‐hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population‐based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non‐smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose–response reduction in the percentages of memory CD4+CD45RO+ (p = 0.005) and CD3+CD45RO+ T‐cell subsets (p = 0.005 and p = 0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T‐cell subsets (p = 0.006 and p = 0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p = 0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T‐cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population‐based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.
Electron microscopic study of intercellular space: Correlation analysis of bronchial asthma and gastroesophageal reflux disease
Authors: Park Sanghoon , Lee Eun Joo , Chun Hoon Jai , Keum Bora , Seo Yeon Seok , Kim Yong Sik , Jeen Yoon‐Tae , Lee Hong Sik , Um Soon Ho , Kim Chang Duck , Ryu Ho Sang , In Kwang Ho , Uhm Chang‐Sub , Lee Sung Joon
Published: June 2010

Background and Aims:  Bronchial asthma (BA) is considered an extra‐esophageal syndrome of gastroesophageal reflux disease (GERD) with poor pathophysiological background. We analyzed the correlation between GERD and BA, examining esophageal epithelium with transmission electron microscopy (TEM), along with clinical findings.

Methods:  BA patients of controlled and partly‐controlled levels were enrolled in the study. A pulmonary and gastrointestinal (GI) questionnaire was given. Patients with no symptoms joined the control group. Esophageal mucosal tissue was taken by esophagogastroduodenoscopy from both groups and processed for TEM. Intercellular space (IS) was measured with an image analyzing program, 100 times for each patient.

Results:  The control (n = 20) and BA (n = 20) groups revealed no significant differences in baseline characteristics. All BA patients were using corticosteroid inhalers, with seven patients having a recent history of acute exacerbation. Patients with at least one GI symptom made up 70% (14/20) of the BA group, and heartburn and/or regurgitation were detected in 40% of patients. Endoscopic findings of GERD were mucosal breaks (n = 3). The IS of the control group was 0.389 ± 0.297 um, while the BA group was 0.806 ± 0.556 um (P = 0.001). The presence of GERD symptoms (P = 0.306) and a history of recent asthma attacks (P = 0.710) did not show significant differences.

Conclusions:  The BA group showed a significant difference in the dilatation of IS compared to the control group, suggesting a higher prevalence of GERD in BA patients and a close pathophysiological correlation.
Causes and consequences of variation in plant population growth rate: a synthesis of matrix population models in a phylogenetic context
Authors: Buckley Yvonne M. , Ramula Satu , Blomberg Simon P. , Burns Jean H. , Crone Elizabeth E. , Ehrlén Johan , Knight Tiffany M. , Pichancourt Jean‐Baptiste , Quested Helen , Wardle Glenda M.
Published: June 2010

Ecology Letters (2010) 13: 1182–1197

Explaining variation in population growth rates is fundamental to predicting population dynamics and population responses to environmental change. In this study, we used matrix population models, which link birth, growth and survival to population growth rate, to examine how and why population growth rates vary within and among 50 terrestrial plant species. Population growth rates were more similar within species than among species; with phylogeny having a minimal influence on among‐species variation. Most population growth rates decreased over the observation period and were negatively autocorrelated between years; that is, higher than average population growth rates tended to be followed by lower than average population growth rates. Population growth rates varied more through time than space; this temporal variation was due mostly to variation in post‐seedling survival and for a subset of species was partly explained by response to environmental factors, such as fire and herbivory. Stochastic population growth rates departed from mean matrix population growth rate for temporally autocorrelated environments. Our findings indicate that demographic data and models of closely related plant species cannot necessarily be used to make recommendations for conservation or control, and that post‐seedling survival and the sequence of environmental conditions are critical for determining plant population growth rate.