bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphisms and evolutionary history of retrotransposon insertions in rice promoters
Authors: Xu Z. , Rafi S. , Ramakrishna W.
Published: August 2011

Retrotransposons are ubiquitous in higher plant genomes. The presence or absence of retrotransposons in whole genome and high throughput genomic sequence (HTGS) from cultivated and wild rice was investigated to understand the organization and evolution of retrotransposon insertions in promoter regions. Approximately half of the Oryza sativa subsp. japonica ‘Nipponbare’ promoters with retrotransposons conserved in Oryza sativa subsp. indica ‘93-11’ and four wild rice species showed higher sequence conservation in retrotransposon than nonretrotransposon regions. We further investigated, in detail, the evolutionary dynamics of five retrotransposons in the promoter regions of 95 rice genotypes. Our data suggest that four of five insertions (Rp2–Rp5) occurred in the ancestor of AA genome, while the other insertion (Rp1) predates the ancestral divergence of Oryza officinalis (CC genome). Four retrotransposons (Rp2–Rp5) were present in 52% (Rp2), 29% (Rp3), 53% (Rp4), and 43% (Rp5) of the rice genotypes with AA genome type, and the fifth retrotransposon (Rp1) was present in 95% of the rice genotypes with AA, BBCC, or CC genome types. Furthermore, most of these retrotransposons were found to evolve slower than flanking promoter regions, suggesting a role in promoter function for regulating downstream genes.
An analysis of selection on candidate genes for regulation, mobilization, uptake, and transport of iron in maize
Authors: Benke Andreas , Stich Benjamin
Published: August 2011

Insufficient iron (Fe) availability, which frequently occurs in soils with high pH levels, can lead to leaf chlorosis, a reduced Fe content in harvest products, and yield reduction in maize. The objectives of this study were (i) to describe patterns of sequence variation of 14 candidate genes for mobilization, uptake, and transport of Fe in maize, as well as regulatory function on these processes; (ii) to examine whether Fe-efficiency is an adaptive trait by determining if these genes were targets of selection during domestication; and (iii) to test if the allele distribution at these candidate genes is different for the different subpopulations of maize. The nucleotide diversity of Mtk was reduced by 78% in maize compared with teosinte. The results of our study revealed for the genes Naat1, Nas1, Nramp3, Mtk, and Ys1 a selective sweep, which suggests that these genes might be important for the fast adaptation of maize to new environments with different Fe availabilities.
Development of EST–SSR markers in castor bean (Ricinus communisL.) and their utilization for genetic purity testing of hybrids
Authors: Pranavi B. , Sitaram G. , Yamini K.N. , Dinesh Kumar V.
Published: August 2011

Expressed sequence tag (EST) databases offer opportunity for the rapid development of simple sequence repeat (SSR) markers in crops. Sequence assembly and clustering of 57 895 ESTs of castor bean resulted in the identification of 10 960 unigenes (6459 singletons and 4501 contigs) having 7429 SSRs. On an average, the unigenes contained 1 SSR for every 1.23 kb of unigene sequence. The identified SSRs mostly consisted of dinucleotide (62.4%) and trinucleotide (33.5%) repeats. The AG class was the most common among the dinucleotide motifs (68.9%), whereas the AAG class (25.9%) was predominant among the trinucleotide motifs. A total of 611 primer pairs were designed for the SSRs, having repeat length more than or equal to 20 nucleotides, of which a set of 130 markers were tested and 92 of these yielding robust amplicons were analyzed for their utility in genetic purity assessment of castor bean hybrids. Nine markers were able to detect polymorphism between the parental lines of nine commercial castor bean hybrids (DCH-32, DCH-177, DCH-519, GCH-2, GCH-4, GCH-5, GCH-6, GCH-7, and RHC-1), and their utility in genetic purity testing was demonstrated. These novel EST–SSR markers would be a valuable addition to the growing molecular marker resources that could be used in genetic improvement programmes of castor bean.
Origin of the H genome in StH-genomic Elymus species based on the single-copy nuclear gene DMC1
Authors: Sun Genlou , Zhang Xiaodi
Published: August 2011

Previous studies have suggested that the H haplome in Elymus could originate from different diploid Hordeum species, however, which diploid species best represent the parental species remains unanswered. The focus of this study seeks to pinpoint the origin of the H genome in Elymus. Allopolyploid Elymus species that contain the StH genome were analyzed together with diploid Hordeum species and a broad sample of diploid genera in the tribe Triticeae using DMC1 sequences. Both parsimony and maximum likelihood analyses well separated the American Hordeum species, except Hordeum brachyantherum subsp. californicum, from the H genome of polyploid Elymus species. The Elymus H-genomic sequences were formed into different groups. Our data suggested that the American Horedeum species, except H. brachyantherum subsp. californicum, are not the H-genomic donor to the Elymus species. Hordeum brevisubulatum subsp. violaceum was the progenitor species to Elymus virescens, Elymus confusus, Elymus lanceolatus, Elymus wawawaiensis, and Elymus caninus. Furthermore, North American H. brachyantherum subsp. californicum was a progenitor of the H genome to Elymus hystrix and Elymus cordilleranus. The H genomes in Elymus canadensis, Elymus sibiricus, and Elymus multisetus were highly differentiated from the H genome in Hordeum and other Elymus species. The H genome in both North American and Eurasian Elymus species was contributed by different Hordeum species.
NON-PROPERLY EMBEDDED MINIMAL PLANES IN HYPERBOLIC 3-SPACE
Authors: COSKUNUZER BARIS
Published: August 2011

In this paper, we show that there are non-properly embedded minimal surfaces with finite topology in a simply connected Riemannian 3-manifold with non-positive curvature. We show this result by constructing a non-properly embedded minimal plane in H3. Hence, this gives a counterexample to Calabi–Yau conjecture for embedded minimal surfaces in negative curvature case.
SMALL ENERGY COMPACTNESS FOR APPROXIMATE HARMONIC MAPPINGS
Authors: LI JIAYU , ZHU XIANGRONG
Published: August 2011

In this paper, we consider the elliptic systems [Formula: see text] where u ∈ W1, 2(R2, RK) and f ∈ L ln+L, and Ω belongs to L2(R2, MK(R)⊗R2) which is antisymmetric. In the first part we prove a compactness theorem for this system. As a corollary, we obtain the compactness theorem for a sequence of mappings from a Riemannian surface to a compact Riemannian manifold with tension fields bounded in L ln+L. In the second part we prove the energy identity for a sequence of mappings from a surface to a sphere with tension fields bounded in L ln+L. In the last section we construct a blow-up sequence of mappings from B1to S2with tension fields bounded in L ln+L but there exists a neck with positive length during blowing up.
THE KHOVANOV HOMOLOGY OF A FAMILY OF THREE-COLUMN PRETZEL LINKS
Authors: QAZAQZEH KHALED
Published: August 2011

We give recursive relations to compute the rational Khovanov bigraded homology groups of three infinite families of non-quasi-alternating 3-column pretzel links. Based on this computations, we obtain an infinite family of homologically thin but not quasi-alternating knots.
ON THE EQUATION OF BARENBLATT–SOBOLEV
Authors: ADIMURTHI  , SEAM NGONN , VALLET GUY
Published: August 2011

In this paper, we are interested in the following pseudoparabolic problem, known as the Barenblatt–Sobolev problem: f(∂ut) - Δu - ϵΔ∂ut = g with u(0, ⋅) = u0 where f is a non-monotone Lipschitz-continuous function, ϵ > 0 and [Formula: see text]. We show the existence of a critical value ϵ0 >0 such that: if ϵ > ϵ0, then the problem admits a unique solution; if ϵ = ϵ0, the solution is unique and it exists under an additional assumption on f; if ϵ < ϵ0, then the solution is not unique in general. Passing to the limit with ϵ to 0+, we prove the existence (and uniqueness) of the solution of the Barenblatt differential inclusion Δu + g ∈ f(∂ut) for a class of maximal monotone operators f. Next, we give an extension of the main result for a stochastic perturbation of the problem and we give some numerical illustrations of the Barenblatt and the Barenblatt–Sobolev equation.
THE GINZBURG–LANDAU FUNCTIONAL WITH A DISCONTINUOUS AND RAPIDLY OSCILLATING PINNING TERM. PART I: THE ZERO DEGREE CASE
Authors: DOS SANTOS MICKAËL , MIRONESCU PETRU , MISIATS OLEKSANDR
Published: August 2011

We consider minimizers of the Ginzburg–Landau energy with pinning term and zero degree Dirichlet boundary condition. Without any assumptions on the pinning term, we prove that these minimizers do not develop vortices in the limit ε → 0. We next consider the specific case of a periodic discontinuous pinning term taking two values. In this setting, we determine the asymptotic behavior of the minimizers as ε → 0.
FINITE ZASSENHAUS MOUFANG SETS WITH ROOT GROUPS OF EVEN ORDER
Authors: BAUMEISTER BARBARA , GRÜNINGER MATTHIAS
Published: August 2011

In [On a class of doubly transitive groups, Ann. of Math.75 (1962) 104–145] Suzuki classified all Zassenhaus groups of finite odd degree. He showed that such a group is either isomorphic to a Suzuki group or to PSL (2, q) with q a power of 2. In this paper we give another proof of this result using the language of Moufang sets. More precisely, we show that every Zassenhaus Moufang set having root groups of finite even order is either special and thus isomorphic to the projective line over a finite field of even order or is isomorphic to a Suzuki Moufang set. In the final section we discuss generalized Suzuki Moufang sets and see that some properties such as that all involutions in a root group are conjugate hold only in the "ordinary" Suzuki Moufang sets.
MULTI-BUBBLE SOLUTIONS FOR EQUATIONS OF CAFFARELLI–KOHN–NIRENBERG TYPE
Authors: LIN LISHAN , LIU ZHAOLI
Published: August 2011

Multi-bubble solutions are constructed for the elliptic equations of Caffarelli–Kohn–Nirenberg type [Formula: see text] where N ≥ 3, [Formula: see text], [Formula: see text], [Formula: see text], a ≤ b < a + 1, K ∈ C(ℝN), K(x) > 0 for x ∈ ℝN, K(x) → 0 as |x| → 0 and |x| → ∞, and ϵ > 0 is a parameter.
SUBCRITICAL QUADRATIC NONLINEAR SCHRÖDINGER EQUATION
Authors: HAYASHI NAKAO , NAUMKIN PAVEL I.
Published: August 2011

We study the initial value problem for the quadratic nonlinear Schrödinger equation [Formula: see text] where γ > 0. Suppose that the Fourier transform [Formula: see text] of the initial data u1satisfies estimates [Formula: see text], where ε > 0 is sufficiently small. Also suppose that [Formula: see text] for |ξ| ≤ 1. Assume that γ > 0 is small: [Formula: see text]. Then we prove that there exists a unique solution u ∈ C([1, ∞);L2) of the Cauchy problem (*). Moreover, the solution u approaches for large time t → +∞ a self-similar solution of the quadratic nonlinear Schrödinger equation (*).
L2ESTIMATES FOR THE EIGENFUNCTIONS CORRESPONDING TO REAL EIGENVALUES OF THE TRICOMI OPERATOR
Authors: FAVARON ALBERTO
Published: August 2011

We introduce a family [Formula: see text] of normal Tricomi domains Ωα,β, α > 0 > β, and we show that its elements are D-star-shaped with respect to the vector field D = -3x∂x- 2y∂yif and only if α ≥ 1/2. Provided that the underlying domain Ω belongs to [Formula: see text] for some α ≥ 1/2, we then establish L2estimates for the eigenfunctions corresponding to real eigenvalues of the Tricomi operator. In particular, our result highlights a dependency of these estimates on the values of α and β and the parabolic diameter of Ω.
ASYMPTOTIC BEHAVIOR OF THE PRINCIPAL EIGENVALUE FOR A CLASS OF NON-LOCAL ELLIPTIC OPERATORS RELATED TO BROWNIAN MOTION WITH SPATIALLY DEPENDENT RANDOM JUMPS
Authors: ARCUSIN NITAY , PINSKY ROSS G.
Published: August 2011

Let D ⊂ Rd be a bounded domain and let [Formula: see text] denote the space of probability measures on D. Consider a Brownian motion in D which is killed at the boundary and which, while alive, jumps instantaneously according to a spatially dependent exponential clock with intensity γV to a new point, according to a distribution [Formula: see text]. From its new position after the jump, the process repeats the above behavior independently of what has transpired previously. The generator of this process is an extension of the operator -Lγ,μ, defined by [Formula: see text] with the Dirichlet boundary condition, where Cμ is the "μ-centering" operator defined by [Formula: see text] The principal eigenvalue, λ0(γ, μ), of Lγ, μ governs the exponential rate of decay of the probability of not exiting D for large time. We study the asymptotic behavior of λ0(γ, μ) as γ → ∞. In particular, if μ possesses a density in a neighborhood of the boundary, which we call μ, then [Formula: see text] If μ and all its derivatives up to order k - 1 vanish on the boundary, but the kth derivative does not vanish identically on the boundary, then λ0(γ, μ) behaves asymptotically like [Formula: see text], for an explicit constant ck.
INFLUENCE OF STRAIN HARDENING ON THE BEHAVIOR AND DESIGN OF STEEL STRUCTURES
Authors: GARDNER LEROY , WANG FACHENG , LIEW ANDREW
Published: August 2011

The present generation of international structural steel design codes treats material nonlinearity through simplified elastic-plastic or rigid-plastic material models. However, the actual stress–strain response of structural steel is more complex than this and features, in particular, strain hardening. Strain hardening refers to the increase in strength beyond yield because of plastic deformation. The influence of strain hardening on the behavior and design of steel structures is examined in this study through both the experimentation and the analysis of existing data, and a method to exploit the additional capacity that arises is outlined. Both determinate and indeterminate structures are considered. The proposed design method, referred to as the continuous strength method (CSM), is a deformation-based design approach employing a continuous relationship between cross-sectional slenderness and cross-sectional deformation capacity, together with a material model that allows for strain hardening. Comparisons are made between test results generated as part of the present study and collected from existing studies, and the predictions from the CSM and Eurocode 3 (EC3). For all cases considered, the CSM, through a rational exploitation of strain hardening, offers a more accurate prediction of observed physical behavior.
LOCAL/DISTORTIONAL/GLOBAL MODE INTERACTION IN SIMPLY SUPPORTED COLD-FORMED STEEL LIPPED CHANNEL COLUMNS
Authors: DINIS P. B. , CAMOTIM D.
Published: August 2011

This paper reports the results of a numerical investigation concerning the elastic and elastic-plastic post-buckling behavior of cold-formed steel-lipped channel columns affected by local/distortional/global (flexural-torsional) buckling mode interaction. The results presented and discussed are obtained by means of analyses performed in the code ABAQUS and adopting column discretizations into fine four-node isoparametric shell element meshes. The columns analysed (i) are simply supported (locally/globally pinned end sections with free warping), (ii) have cross-section dimensions and lengths ensuring equal local, distortional, and global (flexural-torsional) critical buckling loads, thus maximizing the mode interaction phenomenon under scrutiny, and (iii) contain critical-mode initial geometrical imperfections exhibiting different configurations, all corresponding to linear combination of the three "competing" critical buckling modes. After briefly addressing the lipped channel column "pure" global post-buckling behavior, one presents and discusses in detail numerical results concerning the post-buckling behavior of similar columns experiencing strong local/distortional/global mode interaction effects. These results consist of (i) elastic (mostly) and elastic-plastic equilibrium paths, (ii) curves and figures providing the evolution of the deformed configurations of several columns (expressed as linear combinations of their local, distortional, and global components) and, for the elastic-plastic columns, (iii) figures enabling a clear visualization of (iii1) the location and growth of the plastic strains, and (iii2) the characteristics of the failure mechanisms more often detected in this work.
ANALYSIS-BASED 2D DESIGN OF STEEL STORAGE RACKS
Authors: RASMUSSEN K. J. R. , GILBERT B. P.
Published: August 2011

The paper presents a study of the capacities of steel rack frames based on linear analysis (LA), geometric nonlinear analysis (GNA), and geometric and material nonlinear analysis (GMNIA). In the case of linear and geometric nonlinear analyses, the design is carried out to the Australian cold-formed steel structures AS/NZS4600. The study includes braced, unbraced, and semi-braced frames, and compact and noncompact cross sections. The paper shows axial force and bending moment paths for geometric and geometric and material nonlinear analyses, and explains the differences observed in the design capacities obtained using the different types of analysis based on these paths. The paper provides evidence to support the use of advanced GMNIA for the direct design of steel rack frames without the need for checking section or member capacities to a structural design standard.
GENERALIZED BEAM THEORY REVISITED: FROM THE KINEMATICAL ASSUMPTIONS TO THE DEFORMATION MODE DETERMINATION
Authors: SILVESTRE N. , CAMOTIM D. , SILVA N. F.
Published: August 2011

This work is part of an ongoing investigation aimed at comparing the mechanics underlying the application of generalized beam theory (GBT) and the constrained finite strip method (cFSM), two alternative modal approaches to analyze the elastic buckling behavior of open-sectional unbranched thin-walled members. Previous work included an overall comparison between the numerical results yielded by the two approaches for lipped channel columns and beams, which were shown to be essentially identical — the few minor discrepancies were fully explained. The next step consists of revisiting the kinematical assumptions and procedures adopted by GBT to identify and characterize the cross-sectional deformations modes, presenting, explaining, and interpreting them from a novel perspective, deemed more suitable for a true comparison with the displacement field constraints employed in cFSM — the main objective of this paper. The starting point is the derivation of the conventional finite strip method (FSM), intended to show that some of the corresponding matrices also appear in GBT. Indeed, it is demonstrated that the determination of the GBT deformation modes involves a set of particular FSM matrices, termed "cross-sectional matrices." After a brief comparison between the GBT and cFSM assumptions and procedures, an illustrative example is presented and discussed, in order to provide a better grasp of the concepts and procedures involved in the new approach to the GBT deformation mode determination. Finally, the paper closes with a few concluding remarks that also address the work to be carried out in the near future.
Geochemical responses in peat groundwater over Attawapiskat kimberlites, James Bay Lowlands, Canada and their application to diamond exploration
Authors: Sader Jamil A. , Hattori Keiko H. , Kong Julie M. , Hamilton Stewart M. , Brauneder Kerstin
Published: August 2011

Peat groundwater compositions at depths of 0.4 and 1.1 m below ground surface in the Attawapiskat region of the James Bay Lowlands are evaluated for diamond exploration applications. Samples were collected along transects that typically extended at least 200 m beyond the margins of Yankee, Zulu, and Golf kimberlites. Locations of upwelling groundwater usually occur at or near kimberlite margins based on hydrogeological measurements and variations in peat groundwater geochemical parameters (pH and EC are high, and the Eh is low relative to ombrotrophic peat groundwaters). Concentrations of the kimberlite pathfinder metals Ni, Cr, light rare earth elements (LREEs), Ba, Mg/Ca, and alkalis are commonly elevated at sample sites at or near kimberlite margins and where groundwaters are upwelling. The presence of elevated kimberlite pathfinders at these sites suggests that fractures along the boundaries between kimberlites and limestone formed during kimberlite emplacement provide dilation for upward movement of groundwater with elevated kimberlite pathfinder metals. Typically, Ni, Cr, LREE, and Ba behave similarly and thus high concentrations of these metals are found at similar locations along transects. On the other hand, locations of elevated alkalis and Mg/Ca vary. The spatial variations among pathfinder metals in peat groundwaters are possibly due to geochemical processes in the peat, such as metal binding to dissolved organic material, adsorption to insoluble organics or Fe-oxyhydroxides, and incorporation into secondary mineral precipitates, which can act to increase or decrease metal solubility. The findings of this study are readily applicable in diamond exploration in wetlands elsewhere.

Supplementary material:
Krigged water table data for Yankee and Zulu locations are available at
http://www.geolsoc.org.uk/SUP18488
.
Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals
Authors: Jadcherla Sudarshan R. , Parks Vanessa N. , Peng Juan , Dzodzomenyo Samuel , Fernandez Soledad , Shaker Reza , Splaingard Mark
Published: August 2011

Electrocortical arousal (ECA) as an effect of visceral provocation or of its temporal relationships with aerodigestive reflexes in premature neonates is not known. We tested the hypothesis that esophageal provocation results in both esophageal reflex responses and ECAs during sleep and that ECAs are dependent on the frequency characteristics of esophageal neuromotor responses. We defined the spatiotemporal relationship of ECAs in relation to 1) spontaneous pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and 2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy premature neonates born at 27.9 ± 3.4 wk were tested at 36.8 ± 1.9 wk postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in sleep during concurrent manometry and videopolysomnography. With stimulus onset as reference point, we scored the response latency, frequency occurrence and duration of arousals, peristaltic reflex, and upper esophageal sphincter contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and esophageal sensory-motor parameters were scored by blinded observers. Significantly (for each characteristic listed, P < 0.05), swallow sequences were associated with arousals and sleep state changes, and arousals were associated with incomplete peristalsis, response delays to lower esophageal sphincter relaxation, and prolonged esophageal clearance. GER events (73.5%) provoked arousals, and arousals were associated with response delays to peristaltic reflexes or clearance, sleep state modification, and prolonged respiratory arousal. Midesophageal stimuli (54%) provoked arousals and were associated with increased frequency, prolonged latency, prolonged response duration of peristaltic reflexes and UESCR, and increased frequency of sleep state changes and respiratory arousals. In human neonates, ECAs are provoked upon esophageal stimulation; the sensory-motor characteristics of esophageal reflexes are distinct when accompanied by arousals. Aerodigestive homeostasis is defended by multiple tiers of aerodigestive safety mechanisms, and when esophageal reflexes are delayed, cortical hypervigilance (ECAs) occurs.
Secretin is not necessary for exocrine pancreatic development and growth in mice
Authors: Sans Maria Dolors , Sabbatini Maria Eugenia , Ernst Stephen A. , D'Alecy Louis G. , Nishijima Ichiko , Williams John A.
Published: August 2011

Adaptive exocrine pancreatic growth is mediated primarily by dietary protein and the gastrointestinal hormone cholecystokinin (CCK). Feeding trypsin inhibitors such as camostat (FOY-305) is known to induce CCK release and stimulate pancreatic growth. However, camostat has also been reported to stimulate secretin release and, because secretin often potentiates the action of CCK, it could participate in the growth response. Our aim was to test the role of secretin in pancreatic development and adaptive growth through the use of C57BL/6 mice with genetic deletion of secretin or secretin receptor. The lack of secretin in the intestine or the secretin receptor in the pancreas was confirmed by RT-PCR. Other related components, such as vasoactive intestinal polypeptide (VIP) receptors (VPAC1and VPAC2), were not affected. Secretin increased cAMP levels in acini from wild-type (WT) mice but had no effect on acini from secretin receptor-deleted mice, whereas VIP and forskolin still induced a normal response. Secretin in vivo failed to induce fluid secretion in receptor-deficient mice. The pancreas of secretin or secretin receptor-deficient mice was of normal size and histology, indicating that secretin is not necessary for normal pancreatic differentiation or maintenance. When WT mice were fed 0.1% camostat in powdered chow, the pancreas doubled in size in 1 wk, accompanied by parallel increases in protein and DNA. Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK.
Exploration of the copper-related compensatory response in the Belgrade rat model of genetic iron deficiency
Authors: Jiang Lingli , Ranganathan Perungavur , Lu Yan , Kim Changae , Collins James F.
Published: August 2011

The Menkes copper ATPase (Atp7a) and metallothionein (Mt1a) are induced in the duodenum of iron-deficient rats, and serum and hepatic copper levels increase. Induction of a multi-copper ferroxidase (ceruloplasmin; Cp) has also been documented. These findings hint at an important role for Cu during iron deficiency. The intestinal divalent metal transporter 1 (Dmt1) is also induced during iron deficiency. The hypothesis that Dmt1 is involved in the copper-related compensatory response during iron deficiency was tested, utilizing a mutant Dmt1 rat model, namely the Belgrade ( b/ b) rat. Data from b/ b rats were compared with phenotypically normal, heterozygous +/ b rats. Intestinal Atp7a and Dmt1 expression was increased in b/ b rats, whereas Mt1a expression was unchanged. Serum and liver copper levels did not increase in the Belgrades nor did Cp protein or activity. The lack of fully functional Dmt1 may thus partially blunt the compensatory response to iron deficiency by 1) decreasing copper levels in enterocytes, as exemplified by a lack of Mt1a induction and a lesser induction of Atp7a, 2) abolishing the frequently described increase in liver and serum copper, and 3) attenuating the documented increase in Cp expression and activity.
Assessment of the protective effects of oral tocotrienols in arginine chronic-like pancreatitis
Authors: González Ana María , Garcia Tània , Samper Esther , Rickmann Mariana , Vaquero Eva Cristina , Molero Xavier
Published: August 2011

Tocotrienols exhibit anti-inflammatory properties over macrophages and promote cytotoxicity in activated pancreatic stellate cells, suggesting that they may limit chronic pancreatitis progression. We aimed to quantitate the effect of oral tocotrienols on a rat model of chronic pancreatic injury. Chronic-like pancreatitis was induced by repeated arginine pancreatitis. Palm oil tocotrienol-rich fraction (TRF) was given by gavage before and after pancreatitis inductions. Amylase and hydroxyproline were determined in pancreatic homogenates; collagen, fibronectin, α-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and phosphorylated Smad3 were assessed by Western blotting. Transforming growth factor (TGF)-β1 was measured in plasma. Morphological assessment included light microscopy, fibrosis area fraction, and collagen network fractal analysis. Arginine pancreatitis induced pancreatic atrophy and increased hydroxyproline that ameliorated after TRF. Arginine increased TGF-β1 (185 ± 40 vs. 15 ± 2 ng/ml; P <0.01) that was blunted by TRF (53 ± 19; P < 0.01). TRF reduced protease and Smad3 activation, collagen, and fibronectin. α-SMA increased and GFAP diminished in arginine pancreatitis, consistent with long-term stellate cell activation, and TRF reverted these changes to basal. Arginine pancreatitis increased fibrosis area fraction (4.5 ± 0.3% vs. 0.2 ± 0.2%), collagen network complexity (fractal dimension 1.52 ± 0.03 vs. 1.42 ± 0.01; P < 0.001), and inhomogeneity (lacunarity 0.63 ± 0.03 vs. 0.40 ± 0.02; P < 0.001), which were all reduced by TRF (1.3 ± 0.4%, 1.43 ± 0.02%, and 0.51 ± 0.03%, respectively; P < 0.01). Best correlation coefficients were obtained when comparing fibrosis area fraction with lacunarity ( r = 0.88) and both parameters with pancreatic weight ( r = −0.91 and −0.79, respectively). TRF administered only before pancreatitis best, but not fully, recapitulated the beneficial effects of TRF. Tocotrienols improve quantitative measures of chronic pancreatic damage. They may be of benefit in human chronic pancreatitis.
Gastric electrical stimulation parameter dependently alters ventral medial hypothalamic activity and feeding in obese rats
Authors: Zhang Jing , Maude-Griffin Roland , Zhu Hongbing , Sun Yan , Starkebaum Warren , Firestone Elizabeth , Chen Jiande D. Z.
Published: August 2011

Gastric electrical stimulation (GES) has been used to treat obesity with unclear mechanisms and limited parameter ranges. This study explores effects of GES parameters on ventral medial hypothalamic (VMH) activity, feeding, and body weight in diet-induced obese (DIO) rats. For experiment 1, discharge rates were recorded in 39 gastric distension-responsive (GD-R) neurons in 12 DIO rats. Basal rates were compared with rates under GES using varied pulse amplitudes, widths, frequencies, and train-on times. For experiment 2, a crossover experiment in 16 DIO rats measured food intake and weight effects of GES pulse width, the parameter with the steepest neuronal response gradient in experiment 1. Treatments were sham and 0.5-, 2.0-, and 5.0-ms pulse GES. In experiment 1, 11 of 13 GES parameter sets tested produced significantly ( P < 0.05) altered discharge rates of GD-R neurons. Increases in pulse amplitude ( P < 0.05) and width ( P < 0.0001) produced significant upward linear trends in response over the range tested, with the trend being strongest for pulse width. In experiment 2, over 4 days of 0.5-, 2.0-, and 5.0-ms GES treatment, food intake was 9.6% ( P < 0.05), 21.0% ( P < 0.0001), and 47.3% ( P < 0.0001) lower than under sham-GES, whereas body weight changes were 0.7 ( P = 0.48), 2.2 ( P < 0.05), and 3.5 ( P < 0.002) percentage points lower, respectively. We concluded that GES pulse width increases had the largest effect on VMH neuronal activity, and these effects were paralleled by pulse width-dependent reductions in food intake and body weight. Lengthening pulse width beyond the range used in prior clinical studies may be critical to making GES a viable obesity treatment.
Critical closing pressure during midazolam-induced sleep
Authors: Genta Pedro R. , Eckert Danny J. , Gregorio Marcelo G. , Danzi Naury J. , Moriya Henrique T. , Malhotra Atul , Lorenzi-Filho Geraldo
Published: August 2011

The critical closing pressure (Pcrit) is the airway pressure at which the airway collapses and reflects the anatomical contribution to the genesis of obstructive sleep apnea. Pcrit is usually determined during non-rapid eye movement sleep at night, but has been determined under midazolam sedation during the day in the absence of sleep stage monitoring. Indeed, little is known about the effects of midazolam on sleep architecture. Moreover, deeper sedation with midazolam can decrease upper airway muscle activity and increase collapsibility compared with natural sleep. Pcrit under sedation has not been systematically compared with the usual method performed during natural sleep. Therefore, this study aimed to test the hypothesis that Pcrit following low doses of midazolam during the day would be comparable to Pcrit measured during natural sleep in the same patient. Fifteen men (age 54 ± 10 yr, body mass index 30 ± 4 kg/m2) with obstructive sleep apnea underwent a baseline standard overnight polysomnogram (apnea-hypopnea index 38 ± 22 events/h, range: 8–66 events/h), and Pcrit was determined during natural sleep and following midazolam. Sleep induction was obtained with low doses of midazolam (2.4 mg, range 2.0–4.4 mg), and sleep architecture was comparable to natural sleep. Natural sleep and induced sleep Pcrit were similar (−0.82 ± −3.44 and −0.97 ± 3.21 cmH2O, P = 0.663) and closely associated (intraclass correlation coefficient = 0.92; 95% confidence interval, 0.78–0.97, P < 0.001). Natural and midazolam-induced Pcrit correlated with obstructive sleep apnea severity, indicating that both Pcrit measures provided meaningful physiological information. Pcrit determined during the day with sleep induction is similar to natural overnight sleep and is a valid alternative approach in which to determine Pcrit.
Microbubble detection following hyperbaric chamber dives using dual-frequency ultrasound
Authors: Swan J. G. , Bollinger B. D. , Donoghue T. G. , Wilbur J. C. , Phillips S. D. , Alvarenga D. L. , Knaus D. A. , Magari P. J. , Buckey J. C.
Published: August 2011

Venous gas emboli (VGE) can be readily detected in the bloodstream using existing ultrasound methods. No method currently exists to detect decompression-induced microbubbles in tissue. We hypothesized that dual-frequency ultrasound (DFU) could detect these microbubbles. With DFU, microbubbles are driven with two frequencies: a lower “pump” (set to the resonant frequency of the desired bubble size) and a higher “image” frequency. A bubble of the resonant size emits the sum and difference of the two transmitted frequencies. For this study we used a pump frequency of 2.25 MHz and an image frequency of 5.0 MHz, which detects bubbles of roughly 1–10 μm in diameter in a water tank. Four anesthetized swine were pressurized at 4.5 ATA for 2 h and decompressed over 5 min, inducing moderate to very severe VGE scores. Four sites on the thigh of each swine were monitored with DFU before and after the dives. A single mock dive was also performed. The number of sites returning signals consistent with microbubbles increased dramatically after the chamber dive ( P < 0.01), but did not change with the mock dive. The increase in DFU signal after the chamber dive was sustained and present at multiple sites in multiple swine. This research shows for the first time that decompression-induced tissue microbubbles can be detected using DFU and that DFU could be used to monitor decompression-induced microbubbles at multiple sites on the body. Additionally, DFU could be used to track the time course of microbubble formation and growth during decompression stress.
Noninvasive estimation of pharyngeal airway resistance and compliance in children based on volume-gated dynamic MRI and computational fluid dynamics
Authors: Persak Steven C. , Sin Sanghun , McDonough Joseph M. , Arens Raanan , Wootton David M.
Published: August 2011

Computational fluid dynamics (CFD) analysis was used to model the effect of collapsing airway geometry on internal pressure and velocity in the pharyngeal airway of three sedated children with obstructive sleep apnea syndrome (OSAS) and three control subjects. Model geometry was reconstructed from volume-gated magnetic resonance images during normal tidal breathing at 10 increments of tidal volume through the respiratory cycle. Each geometry was meshed with an unstructured grid and solved using a low-Reynolds number k-ω turbulence model driven by flow data averaged over 12 consecutive breathing cycles. Combining gated imaging with CFD modeling created a dynamic three-dimensional view of airway anatomy and mechanics, including the evolution of airway collapse and flow resistance and estimates of the local effective compliance. The upper airways of subjects with OSAS were generally much more compliant during tidal breathing. Compliance curves (pressure vs. cross-section area), derived for different locations along the airway, quantified local differences along the pharynx and between OSAS subjects. In one subject, the distal oropharynx was more compliant than the nasopharynx (1.028 vs. 0.450 mm2/Pa) and had a lower theoretical limiting flow rate, confirming the distal oropharynx as the flow-limiting segment of the airway in this subject. Another subject had a more compliant nasopharynx (0.053 mm2/Pa) during inspiration and apparent stiffening of the distal oropharynx (C = 0.0058 mm2/Pa), and the theoretical limiting flow rate indicated the nasopharynx as the flow-limiting segment. This new method may help to differentiate anatomical and functional factors in airway collapse.
EGF Receptor Inhibition Radiosensitizes NSCLC Cells by Inducing Senescence in Cells Sustaining DNA Double-Strand Breaks
Authors: Wang Meng , Morsbach Fabian , Sander David , Gheorghiu Liliana , Nanda Akash , Benes Cyril , Kriegs Malte , Krause Mechthild , Dikomey Ekkehard , Baumann Michael , Dahm-Daphi Jochen , Settleman Jeffrey , Willers Henning
Published: August 2011

The mechanisms by which inhibition of the epidermal growth factor receptor (EGFR) sensitizes non–small cell lung cancer (NSCLC) cells to ionizing radiation remain poorly understood. We set out to characterize the radiosensitizing effects of the tyrosine kinase inhibitor erlotinib and the monoclonal antibody cetuximab in NSCLC cells that contain wild-type p53. Unexpectedly, EGFR inhibition led to pronounced cellular senescence but not apoptosis of irradiated cells, both in vitro and in vivo. Senescence was completely dependent on wild-type p53 and associated with a reduction in cell number as well as impaired clonogenic radiation survival. Study of ten additional NSCLC cell lines revealed that senescence is a prominent mechanism of radiosensitization in 45% of cell lines and occurs not only in cells with wild-type p53 but also in cells with mutant p53, where it is associated with an induction of p16. Interestingly, senescence and radiosensitization were linked to an increase in residual radiation-induced DNA double-strand breaks irrespective of p53/p16 status. This effect of EGFR inhibition was at least partially mediated by disruption of the MEK–ERK pathway. Thus, our data indicate a common mechanism of radiosensitization by erlotinib or cetuximab across diverse genetic backgrounds. Our findings also suggest that assays that are able to capture the initial proliferative delay that is associated with senescence should be useful for screening large cell line panels to identify genomic biomarkers of EGFR inhibitor–mediated radiosensitization. Cancer Res; 71(19); 6261–9. ©2011 AACR.
The C-Terminal Sequence of Several Human Serine Proteases Encodes Host Defense Functions
Authors: Kasetty Gopinath , Papareddy Praveen , Kalle Martina , Rydengård Victoria , Walse Björn , Svensson Bo , Mörgelin Matthias , Malmsten Martin , Schmidtchen Artur
Published: August 2011

Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest.
Social Status and Sex Effects on Neural Morphology in Damaraland Mole-Rats, Fukomys damarensis
Authors: Anyan Jeff J. , Seney Marianne L. , Holley Amanda , Bengston Lynn , Goldman Bruce D. , Forger Nancy G. , Holmes Melissa M.
Published: August 2011

We previously reported that in a eusocial rodent, the naked mole-rat (Heterocephalus glaber), traditional neural sex differences were absent; instead, neural dimorphisms were associated with breeding status. Here we examined the same neural regions previously studied in naked mole-rats in a second eusocial species, the Damaraland mole-rat (Fukomys damarensis). Damaraland mole-rats live in social groups with breeding restricted to a small number of animals. However, colony sizes are much smaller in Damaraland mole-rats than in naked mole-rats and there is consequently less reproductive skew. In this sense, Damaraland mole-rats may be considered intermediate in social organization between naked mole-rats and more traditional laboratory rodents. We report that, as in naked mole-rats, breeding Damaraland mole-rats have larger volumes of the principal nucleus of the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus than do subordinates, with no effect of sex on these measures. Thus, these structures may play special roles in breeders of eusocial species. However, in contrast to what was seen in naked mole-rats, we also found sex differences in Damaraland mole-rats: volume of the medial amygdala and motoneuron number in Onuf’s nucleus were both greater in males than in females, with no significant effect of breeding status. Thus, both sex and breeding status influence neural morphology in Damaraland mole-rats. These findings are in accord with the observed sex differences in body weight and genitalia in Damaraland but not naked mole-rats. We hypothesize that the increased sexual dimorphism in Damaraland mole-rats relative to naked mole-rats is related to reduced reproductive skew.
Self-Organization Phenomena in Embryonic Stem Cell-Derived Embryoid Bodies: Axis Formation and Breaking of Symmetry during Cardiomyogenesis
Authors: Fuchs Christiane , Scheinast Matthias , Pasteiner Waltraud , Lagger Sabine , Hofner Manuela , Hoellrigl Alexandra , Schultheis Martina , Weitzer Georg
Published: August 2011

Aggregation of embryonic stem cells gives rise to embryoid bodies (EBs) which undergo developmental processes reminiscent of early eutherian embryonic development. Development of the three germ layers suggests that gastrulation takes place. In vivo, gastrulation is a highly ordered process but in EBs only few data support the hypothesis that self-organization of differentiating cells leads to morphology, reminiscent of the early gastrula. Here we demonstrate that a timely implantation-like process is a prerequisite for the breaking of the radial symmetry of suspended EBs. Attached to a surface, EBs develop a bilateral symmetry and presumptive mesodermal cells emerge between the center of the EBs and a horseshoe-shaped ridge of cells. The development of an epithelial sheet of cells on one side of the EBs allows us to define an ‘anterior’ and a ‘posterior’ end of the EBs. In the mesodermal area, first cardiomyocytes (CMCs) develop mainly next to this epithelial sheet of cells. Development of twice as many CMCs at the ‘left’ side of the EBs breaks the bilateral symmetry and suggests that cardiomyogenesis reflects a local or temporal asymmetry in EBs. The asymmetric appearance of CMCs but not the development of mesoderm can be disturbed by ectopic expression of the muscle-specific protein Desmin. Later, the bilateral morphology becomes blurred by an apparently chaotic differentiation of many cell types. The absence of comparable structures in aggregates of cardiovascular progenitor cells isolated from the heart demonstrates that the self-organization of cells during a gastrulation-like process is a unique feature of embryonic stem cells.
Immunobiology of Intestinal Eosinophils – A Dogma in the Changing?
Authors: Svensson-Frej Marcus
Published: August 2011

Infiltration of eosinophils into the intestinal mucosa is a typical hallmark of antiparasite immune responses and inflammatory disorders of the intestinal tract, and eosinophils are thought to contribute to these processes by release of their cytotoxic granule content. However, utilizing novel tools to study eosinophils, it has been recognized that eosinophils are constitutively present in the gastrointestinal tract. In addition, as the dogmatic antiparasite function of eosinophils has proven difficult to document experimentally, it has become increasingly clear that eosinophils are likely to have a more complex role than previously appreciated. Thus, the prevailing dogma of eosinophils merely as antiparasitic effector cells is changing. Instead, it has been suggested that eosinophils can contribute also to several other processes in the intestinal mucosa, e.g. local tissue homeostasis and adaptive immune responses. This review describes the current knowledge regarding the characteristics and functions of intestinal eosinophils, and the regulation of eosinophil trafficking to the intestinal mucosa during the steady state and inflammation. Finally, potential additional and new roles of intestinal eosinophils in the intestinal mucosal immune system are discussed.
Binocular Vision and Ipsilateral Retinal Projections in Relation to Eye and Forelimb Coordination
Authors: Larsson Matz
Published: August 2011

It is commonly proposed that the number of fibers that do not cross in the optic chiasm (OC) is proportional to the size of the binocular visual field, and that the major advantage of binocular vision is acute depth perception. I present an alternative, an ‘eye-forelimb’ (EF) hypothesis, suggesting that alterations in the OC influence the length of neural pathways that transmit visual information to motor nuclei and somatosensory areas involved in forelimb coordination. Evolutionary processes resulting in increased ipsilateral retinal projections (IRP) are of adaptive value in animals that regularly use the forelimbs in a frontal position, while evolutionary change towards reduced IRP is of value for animals that mainly use the forelimbs in lateral positions. Primates and cats, to a large extent, use visually guided forelimb maneuvers, and both groups have high proportions of IRP. The fact that vertebrates’ IRP arise exclusively from the temporal retina supports the hypothesis, since IRP from the nasal retina would increase the length of neural pathways involved in forelimb coordination. The EF hypothesis offers new perspectives on why a high proportion of IRP among early limbless vertebrates became reduced during the evolution of laterally situated limbs, and why reptiles that lost their limbs (snakes) evolved more IRP. Anatomical, neurophysiological, phylogenetic, ontogenetic and ecological data suggest that mutations changing the proportions of ipsilateral visual connections in the OC may have selective value for EF coordination.
Importance of Toll-Like Receptor 9 in Host Defense against M1T1 Group A Streptococcus Infections
Authors: Zinkernagel Annelies S. , Hruz Petr , Uchiyama Satoshi , von Köckritz-Blickwede Maren , Schuepbach Reto A. , Hayashi Tomoko , Carson Dennis A. , Nizet Victor
Published: August 2011

Timely recognition and elimination of invasive group A Streptococcus (GAS) by innate immunity is crucial to control infection. The intracellular pattern recognition receptor Toll-like receptor 9 (TLR9) promotes macrophage hypoxia-inducible factor-1α levels, oxidative burst and nitric oxide production in response to GAS. TLR9 contributes to GAS clearance in vivo in both localized cutaneous and systemic infection models.