bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying fertiliser management strategies to maximise nitrogen and phosphorus acquisition by wheat in two contrasting soils from Victoria, Australia
Authors: Dunbabin V. M. , Armstrong R. D. , Officer S. J. , Norton R. M.
Published: February 2009

Crop yield and profitability in the dryland production systems of southern Australia are directly affected by the application of nitrogen (N) and phosphorus (P) fertilisers. How efficiently a crop utilises applied fertiliser is affected by several factors that interact in a complex way, including: nutrient mobility, soil type and soil physicochemical and biological factors, season (including rainfall amount and distribution), and crop physiology. In addition, nutrient supply and crop demand need to synchronise both temporally and spatially if nutrient use efficiency is to be optimised. In this study, the mechanistic simulation model, ROOTMAP, was used to investigate and generate hypotheses about the implications of a range of fertiliser management strategies on the nutrient utilisation of wheat. A range of seasons and 2 commercially important soil types (a Wimmera Vertosol and a Mallee Sodosol) were considered. Simulation results showed a strong interaction between the timing and placement of N and P fertiliser, soil type, seasonal conditions, root growth, and nutrient uptake by wheat. This suggests that region-specific recommendations for fertiliser management may be superior to the ‘one size fits all’ approach typically adopted over the Wimmera/Mallee region. Fertiliser use efficiency differed between the 2 soil types, primarily because physicochemical subsoil constraints were present in the Sodosol, but not the Vertosol. These affected rooting depth, total root system size, and root distribution—notably root growth and hence foraging in the topsoil layer. The root growth response to fertiliser management strategies and seasonal rainfall was also reduced on the Sodosol compared with the Vertosol. Simulated fertiliser uptake was responsive to the placement strategy in a dry year characterised by small rainfall events, typical for the Wimmera and Mallee regions. Shallow placement (0.05 or 0.025 m) of N and P in the topsoil utilised topsoil moisture from these small rainfall events, improving crop N and P uptake. The degree of benefit differed between the 2 soil types, and placement of fertiliser was more effective than topdressing. The simulation approach used here provides a preliminary assessment of a range of fertiliser strategies for different soil type and seasonal conditions. However, because ROOTMAP does not provide direct predictions of grain yield response, simulation results need subsequent validation under field conditions before they can be used by growers.
Fire intensity, fire severity and burn severity: a brief review and suggested usage
Authors: Keeley Jon E.
Published: February 2009

Several recent papers have suggested replacing the terminology of fire intensity and fire severity. Part of the problem with fire intensity is that it is sometimes used incorrectly to describe fire effects, when in fact it is justifiably restricted to measures of energy output. Increasingly, the term has created confusion because some authors have restricted its usage to a single measure of energy output referred to as fireline intensity. This metric is most useful in understanding fire behavior in forests, but is too narrow to fully capture the multitude of ways fire energy affects ecosystems. Fire intensity represents the energy released during various phases of a fire, and different metrics such as reaction intensity, fireline intensity, temperature, heating duration and radiant energy are useful for different purposes. Fire severity, and the related term burn severity, have created considerable confusion because of recent changes in their usage. Some authors have justified this by contending that fire severity is defined broadly as ecosystem impacts from fire and thus is open to individual interpretation. However, empirical studies have defined fire severity operationally as the loss of or change in organic matter aboveground and belowground, although the precise metric varies with management needs. Confusion arises because fire or burn severity is sometimes defined so that it also includes ecosystem responses. Ecosystem responses include soil erosion, vegetation regeneration, restoration of community structure, faunal recolonization, and a plethora of related response variables. Although some ecosystem responses are correlated with measures of fire or burn severity, many important ecosystem processes have either not been demonstrated to be predicted by severity indices or have been shown in some vegetation types to be unrelated to severity. This is a critical issue because fire or burn severity are readily measurable parameters, both on the ground and with remote sensing, yet ecosystem responses are of most interest to resource managers.
Aldosterone activates endothelial exocytosis
Authors: Jeong Youngtae , Chaupin Damian F. , Matsushita Kenji , Yamakuchi Munekazu , Cameron Scott J. , Morrell Craig N. , Lowenstein Charles J.
Published: February 2009

Although elevated levels of aldosterone are associated with vascular inflammation, the proinflammatory pathways of aldosterone are not completely defined. We now show that aldosterone triggers endothelial cell exocytosis, the first step in leukocyte trafficking. Exogenous aldosterone stimulates endothelial exocytosis of Weibel-Palade bodies, externalizing P-selectin and releasing von Willebrand factor. Spironolactone, a nonselective mineralocorticoid receptor (MR) blocker, antagonizes aldosterone-induced endothelial exocytosis. Knockdown of the MR also decreases exocytosis, suggesting that the MR mediates exocytosis. Aldosterone triggers exocytosis within minutes, and this effect is not inhibited by actinomycin D, suggesting a nongenomic effect of aldosterone. Aldosterone treatment of endothelial cells increases leukocyte adherence to endothelial cells in culture. Taken together, our data suggest that aldosterone activates vascular inflammation in part through nongenomic, MR-mediated pathways. Aldosterone antagonism may decrease vascular inflammation and cardiac fibrosis in part by blocking endothelial exocytosis.
Nanometric chemical clocks
Authors: McEwen Jean-Sabin , Gaspard Pierre , de Bocarmé Thierry Visart , Kruse Norbert
Published: February 2009

Field ion microscopy combined with video techniques and chemical probing reveals the existence of catalytic oscillatory patterns at the nanoscale. This is the case when a rhodium nanosized crystal—conditioned as a field emitter tip—is exposed to hydrogen and oxygen. Here, we show that these nonequilibrium oscillatory patterns find their origin in the different catalytic properties of all of the nanofacets that are simultaneously exposed at the tip's surface. These results suggest that the underlying surface anisotropy, rather than a standard reaction–diffusion mechanism, plays a major role in determining the self-organizational behavior of multifaceted nanostructured surfaces. Surprisingly, this nanoreactor, composed of the tip crystal and a constant molecular flow of reactants, is large enough for the emergence of regular oscillations from the molecular fluctuations.
Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow
Authors: Tsao Gabriel J. , Allen Jessica A. , Logronio Kathryn A. , Lazzeroni Laura C. , Shizuru Judith A.
Published: February 2009

Antigen-specific immune responses are impaired after allogeneic hematopoietic cell transplantation (HCT). The events contributing to this impairment include host hematolymphoid ablation and donor cell regeneration, which is altered by pharmacologic immune suppression to prevent graft-versus-host disease (GVHD). A generally accepted concept is that graft T cell depletion performed to avoid GVHD yields poorer immune recovery because mature donor T cells are thought to be the major mediators of protective immunity early post-HCT. Our findings contradict the idea that removal of mature donor cells worsens immune recovery post-HCT. By transplantation of purified hematopoietic stem cells (HSC) compared with bone marrow (BM) across donor and recipient pairs of increasing genetic disparity, we show that grafts composed of the purified progenitor population give uniformly superior lymphoid reconstitution, both qualitatively and quantitatively. Subclinical GVHD by T cells in donor BM likely caused this lympho-depleting GVHD. We further determined in the major histocompatibility complex (MHC)-mismatched pairs, that T cell restricted proliferative responses were dictated by donor rather than host elements. We interpret these latter findings to show the importance of peripheral antigen presentation in the selection and maintenance of the T cell repertoire.
Rosid radiation and the rapid rise of angiosperm-dominated forests
Authors: Wang Hengchang , Moore Michael J. , Soltis Pamela S. , Bell Charles D. , Brockington Samuel F. , Alexandre Roolse , Davis Charles C. , Latvis Maribeth , Manchester Steven R. , Soltis Douglas E.
Published: February 2009

The rosid clade (70,000 species) contains more than one-fourth of all angiosperm species and includes most lineages of extant temperate and tropical forest trees. Despite progress in elucidating relationships within the angiosperms, rosids remain the largest poorly resolved major clade; deep relationships within the rosids are particularly enigmatic. Based on parsimony and maximum likelihood (ML) analyses of separate and combined 12-gene (10 plastid genes, 2 nuclear; >18,000 bp) and plastid inverted repeat (IR; 24 genes and intervening spacers; >25,000 bp) datasets for >100 rosid species, we provide a greatly improved understanding of rosid phylogeny. Vitaceae are sister to all other rosids, which in turn form 2 large clades, each with a ML bootstrap value of 100%: (i) eurosids I (Fabidae) include the nitrogen-fixing clade, Celastrales, Huaceae, Zygophyllales, Malpighiales, and Oxalidales; and (ii) eurosids II (Malvidae) include Tapisciaceae, Brassicales, Malvales, Sapindales, Geraniales, Myrtales, Crossosomatales, and Picramniaceae. The rosid clade diversified rapidly into these major lineages, possibly over a period of <15 million years, and perhaps in as little as 4 to 5 million years. The timing of the inferred rapid radiation of rosids [108 to 91 million years ago (Mya) and 107–83 Mya for Fabidae and Malvidae, respectively] corresponds with the rapid rise of angiosperm-dominated forests and the concomitant diversification of other clades that inhabit these forests, including amphibians, ants, placental mammals, and ferns.
New twist on the regulation of NKG2D ligand expression
Authors: Cerwenka Adelheid
Published: February 2009

The NK cell–activating receptor NKG2D plays a prominent role in antitumor immune responses. Expression of the multiple NKG2D ligands must be tightly controlled to guarantee that NK cells attack tumors but not healthy cells. New data reveal a novel mechanism of posttranslational regulation of the mouse NKG2D ligand MULT1, in which MULT1 is ubiquitinated and degraded in healthy cells. In response to UV stress or heat shock, ubiquitination of MULT1 decreases and cell surface expression increases. Thus, targeting the ubiquitination machinery in cancer cells might increase the susceptibility of tumors to NK cell–mediated killing.
David Artis: Fear no worm
Authors: Maxmen Amy
Published: February 2009

As the incidence of inflammatory disease and food allergies increases in the industrialized world, David Artis wonders if something is wrong with the little friends in our guts.
New results on the least common multiple of consecutive integers
Authors: Farhi Bakir , Kane Daniel
Published: February 2009

When studying the least common multiple of some finite sequences of integers, the first author introduced the interesting arithmetic functions

g
k

g_k

(
k
∈

N

)

(k \in \mathbb {N})

, defined by
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="g Subscript k Baseline left-parenthesis n right-parenthesis colon equals StartFraction n left-parenthesis n plus 1 right-parenthesis ellipsis left-parenthesis n plus k right-parenthesis Over l c m left-parenthesis n comma n plus 1 comma ellipsis comma n plus k right-parenthesis EndFraction">

g
k

(
n
)
:=

n
(
n
+
1
)
…
(
n
+
k
)

lcm
⁡
(
n
,
n
+
1
,
…
,
n
+
k
)

g_k(n) := \frac {n (n + 1) \dots (n + k)} {\operatorname {lcm}(n, n+1, \dots , n + k)}

(
∀
n
∈

N

∖
{
0
}
)

(\forall n \in \mathbb {N} \setminus \{0\})

. He proved that for each

k
∈

N

k \in \mathbb {N}

,

g
k

g_k

is periodic and

k
!

k!

is a period of

g
k

g_k

. He raised the open problem of determining the smallest positive period

P
k

P_k

of

g
k

g_k

. Very recently, S. Hong and Y. Yang improved the period

k
!

k!

of

g
k

g_k

to

lcm
⁡
(
1
,
2
,
…
,
k
)

\operatorname {lcm}(1 , 2, \dots , k)

. In addition, they conjectured that

P
k

P_k

is always a multiple of the positive integer

lcm
⁡
(
1
,
2
,
…
,
k
,
k
+
1
)

k
+
1

\frac {\operatorname {lcm}(1 , 2 , \dots , k , k + 1)}{k + 1}

. An immediate consequence of this conjecture is that if

(
k
+
1
)

(k + 1)

is prime, then the exact period of

g
k

g_k

is precisely equal to

lcm
⁡
(
1
,
2
,
…
,
k
)

\operatorname {lcm}(1 , 2 , \dots , k)

.

In this paper, we first prove the conjecture of S. Hong and Y. Yang and then we give the exact value of

P
k

P_k

(
k
∈

N

)

(k \in \mathbb {N})

. We deduce, as a corollary, that

P
k

P_k

is equal to the part of

lcm
⁡
(
1
,
2
,
…
,
k
)

\operatorname {lcm}(1 , 2 , \dots , k)

not divisible by some prime.
Average behavior of Fourier coefficients of cusp forms
Authors: Lü Guangshi
Published: February 2009

Let

a
0

(
n
)

a_0(n)

and

b
0

(
n
)

b_0(n)

be the normalized Fourier coefficients of the two holomorphic Hecke eigenforms

f
(
z
)
∈

S

2
k

(
Γ
)

f(z)\in S_{2k}(\Gamma )

and

φ
(
z
)
∈

S

2
l

(
Γ
)

\varphi (z)\in S_{2l}(\Gamma )

respectively. In 1999, Fomenko studied the following average sums of

a
0

(
n
)

a_0(n)

and

b
0

(
n
)

b_0(n)

:
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="sigma-summation Underscript n less-than-or-equal-to x Endscripts a 0 left-parenthesis n right-parenthesis cubed comma sigma-summation Underscript n less-than-or-equal-to x Endscripts a 0 left-parenthesis n right-parenthesis squared b 0 left-parenthesis n right-parenthesis comma sigma-summation Underscript n less-than-or-equal-to x Endscripts a 0 left-parenthesis n right-parenthesis squared b 0 left-parenthesis n right-parenthesis squared comma sigma-summation Underscript n less-than-or-equal-to x Endscripts a 0 left-parenthesis n right-parenthesis Superscript 4 Baseline period">

∑

n
≤
x

a
0

(
n

)
3

,

∑

n
≤
x

a
0

(
n

)
2

b
0

(
n
)
,

∑

n
≤
x

a
0

(
n

)
2

b
0

(
n

)
2

,

∑

n
≤
x

a
0

(
n

)
4

.

\sum _{n \leq x}a_0(n)^3, \quad \sum _{n \leq x}a_0(n)^2b_0(n), \quad \sum _{n \leq x}a_0(n)^2b_0(n)^2, \quad \sum _{n \leq x}a_0(n)^4.

\]
In this paper, we are able to improve on Fomenko’s results.
A study of counts of Bernoulli strings via conditional Poisson processes
Authors: Huffer Fred , Sethuraman Jayaram , Sethuraman Sunder
Published: February 2009

A sequence of random variables, each taking values

0
0

or

1
1

, is called a Bernoulli sequence. We say that a string of length

d
d

occurs in a Bernoulli sequence if a success is followed by exactly

(
d
−
1
)

(d-1)

failures before the next success. The counts of such

d
d

-strings are of interest, and in specific independent Bernoulli sequences are known to correspond to asymptotic

d
d

-cycle counts in random permutations.

In this paper, we give a new framework, in terms of conditional Poisson processes, which allows for a quick characterization of the joint distribution of the counts of all

d
d

-strings, in a general class of Bernoulli sequences, as certain mixtures of the product of Poisson measures. In particular, this general class includes all Bernoulli sequences considered in the literature, as well as a host of new sequences.
Torsion of the symmetric algebra and implicitization
Authors: Busé Laurent , Chardin Marc , Jouanolou Jean-Pierre
Published: February 2009

Recently, a method to compute the implicit equation of a parametrized hypersurface has been developed by the authors. We address here some questions related to this method. First, we prove that the degree estimate for the stabilization of the MacRae’s invariant of

Sym

A

⁡
(
I

)

ν

\operatorname {Sym}_{A}(I)_{\nu }

is optimal. Then, we show that the extraneous factor that may appear in the process splits into a product of linear forms in the algebraic closure of the base field, each linear form being associated to a non-complete intersection base point. Finally, we make a link between this method and a resultant computation for the case of rational plane curves and space surfaces.
Generic spectral simplicity of polygons
Authors: Hillairet Luc , Judge Chris
Published: February 2009

We study the Laplace operator with Dirichlet or Neumann boundary conditions on polygons in the Euclidean plane. We prove that almost every simply connected polygon with at least four vertices has a simple spectrum. We also address the more general case of geodesic polygons in a constant curvature space form.
Boundary points as limit functions of iterated holomorphic function systems
Authors: Tavakoli Kourosh
Published: February 2009

We show that if

c
c

is a boundary point of a non-relatively compact subdomain of the unit disk, there always exists an iterated holomorphic function system with the constant

c
c

as a limit function.
On gradient Ricci solitons with symmetry
Authors: Petersen Peter , Wylie William
Published: February 2009

We study gradient Ricci solitons with maximal symmetry. First we show that there are no nontrivial homogeneous gradient Ricci solitons. Thus, the most symmetry one can expect is an isometric cohomogeneity one group action. Many examples of cohomogeneity one gradient solitons have been constructed. However, we apply the main result in our paper “Rigidity of gradient Ricci solitons” to show that there are no noncompact cohomogeneity one shrinking gradient solitons with nonnegative curvature.
Remarks on the blow-up of solutions to a toy model for the Navier-Stokes equations
Authors: Gallagher Isabelle , Paicu Marius
Published: February 2009

In a 2001 paper, S. Montgomery-Smith provides a one-dimensional model for the three-dimensional, incompressible Navier-Stokes equations, for which he proves the blow-up of solutions associated with a class of large initial data, while the same global existence results as for the Navier-Stokes equations hold for small data. In this paper the model is adapted to the cases of two and three space dimensions, with the additional feature that the divergence-free condition is preserved. It is checked that a family of initial data constructed by Chemin and Gallagher, which is arbitrarily large yet generates a global solution to the Navier-Stokes equations in three space dimensions, actually causes blow-up for the toy model — meaning that the precise structure of the nonlinear term is crucial to understanding the dynamics of large solutions to the Navier-Stokes equations.
Regularity and Segre-Veronese embeddings
Authors: Cox David , Materov Evgeny
Published: February 2009

This paper studies the regularity of certain coherent sheaves that arise naturally from Segre-Veronese embeddings of a product of projective spaces. We give an explicit formula for the regularity of these sheaves and show that their regularity is subadditive. We then apply our results to study the Tate resolutions of these sheaves.
Minimal polynomial of an exponential automorphism of ℂⁿ
Authors: Zygadło Jakub
Published: February 2009

We show that the minimal polynomial of a polynomial exponential automorphism

F
F

of

C

n

\mathbb {C}^n

(i.e.

F
=
exp
⁡
(
D
)

F=\exp (D)

where

D
D

is a locally nilpotent derivation) is of the form

μ
F

(
T
)
=
(
T
−
1

)
d

\mu _F(T)=(T-1)^d

, with

d
=
min
{
m
∈

N

:

D

∘
m

(

X
i

)
=
0
 for 
i
=
1
,
…
,
n
}

d=\min \{m\in \mathbb {N}: D^{\circ m}(X_i)=0\text { for } i=1,\ldots ,n\}

.
Borg-type uniqueness theorems for periodic Jacobi operators with matrix-valued coefficients
Authors: Korotyaev Evgeny , Kutsenko Anton
Published: February 2009

We give a simple proof of Borg-type uniqueness theorems for periodic Jacobi operators with matrix-valued coefficients.
Equidistribution of dilations of polynomial curves in nilmanifolds
Authors: Björklund Michael , Fish Alexander
Published: February 2009

In this paper we study the asymptotic behaviour under dilations of probability measures supported on polynomial curves in nilmanifolds. We prove, under some mild conditions, the effective equidistribution of such measures to the Haar measure. We also formulate a mean ergodic theorem for

R

n

\mathbb {R}^n

-representations on Hilbert spaces, restricted to a moving phase of low dimension. Furthermore, we bound the necessary dilation of a given smooth curve in

R

n

\mathbb {R}^n

so that the canonical projection onto

T

n

\mathbb {T}^n

is

ε
\varepsilon

-dense.
Aurora B Kinase Regulates the Postmitotic Endoreduplication Checkpoint via Phosphorylation of the Retinoblastoma Protein at Serine 780
Authors: Nair Jayasree S. , Ho Alan L. , Tse Archie N. , Coward Jesse , Cheema Haider , Ambrosini Grazia , Keen Nicholas , Schwartz Gary K.
Published: February 2009

The phenotypic change characteristic of Aurora B inhibition is the induction of polyploidy. Utilizing specific siRNA duplexes and a selective small molecule inhibitor (AZD1152) to inhibit Aurora B activity in tumor cells, we sought to elucidate the mechanism by which Aurora B inhibition results in polyploidy. Cells treated with AZD1152 progressed through mitosis with misaligned chromosomes and exited without cytokinesis and subsequently underwent endoreduplication of DNA despite activation of a p53-dependent pseudo G1 checkpoint. Concomitant with polyploid cell formation, we observed the appearance of Rb hypophosphorylation, an event that occurred independently of cyclin-dependent kinase inhibition. We went on to discover that Aurora B directly phosphorylates Rb at serine 780 both in vitro and in vivo. This novel interaction plays a critical role in regulating the postmitotic checkpoint to prevent endoreduplication after an aberrant mitosis. Thus, we propose for the first time that Aurora B determines cellular fate after an aberrant mitosis by directly regulating the Rb tumor suppressor protein.
RAMI: a tool for identification and characterization of phylogenetic clusters in microbial communities
Authors: Pommier Thomas , Canbäck Björn , Lundberg Per , Hagström Åke , Tunlid Anders
Published: February 2009

Motivation: The most common approach to estimate microbial diversity is based on the analysis of DNA sequences of specific target genes including ribosomal genes. Commonly, the sequences are grouped into operational taxonomic units based on genetic distance (sequence similarity) instead of genetic change (patristic distance). This method may fail to adequately identify clusters of evolutionary related sequences and it provides no information on the phylogenetic structure of the community. An ease-of-use web application for this purpose has been missing.

Results: We have developed RAMI, which clusters related nodes in a phylogenetic tree based on the patristic distance. RAMI also produces indices of cluster properties and other indices used in population and community studies on-the-fly.

Availability: RAMI is licensed under GNU GPL and can be run or downloaded from http://www.acgt.se/online.html.

Contact:  tpommier@univ-montp2.fr; bcanback@acgt.se

Supplementary information:  http://www.acgt.se/RAMI/SuppInfo
Identification of differential gene pathways with principal component analysis
Authors: Ma Shuangge , Kosorok Michael R.
Published: February 2009

Motivation: Development of high-throughput technology makes it possible to measure expressions of thousands of genes simultaneously. Genes have the inherent pathway structure, where pathways are composed of multiple genes with coordinated biological functions. It is of great interest to identify differential gene pathways that are associated with the variations of phenotypes.

Results: We propose the following approach for detecting differential gene pathways. First, we construct gene pathways using databases such as KEGG or GO. Second, for each pathway, we extract a small number of representative features, which are linear combinations of gene expressions and/or their transformations. Specifically, we propose using (i) principal components (PCs) of gene expression sets, (ii) PCs of expanded gene expression sets and (iii) expanded sets of PCs of gene expressions, as the representative features. Third, we identify differential gene pathways as those with representative features significantly associated with the variations of phenotypes, particularly disease clinical outcomes, in regression models. The false discovery rate approach is used to adjust for multiple comparisons. Analysis of three gene expression datasets suggests that (i) the proposed approach can effectively identify differential gene pathways; (ii) PCs that explain only a small amount of variations of gene expressions may bear significant associations between gene pathways and phenotypes; (iii) including second-order terms of gene expressions may lead to identification of new differential gene pathways; (iv) the proposed approach is relatively insensitive to additional noises; and (v) the proposed approach can identify gene pathways missed by alternative approaches.

Contact:  shuangge.ma@yale.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning
Authors: Alexander Jon C. , McDermott Carmel M. , Tunur Tumay , Rands Vicky , Stelly Claire , Karhson Debra , Bowlby Mark R. , An W. Frank , Sweatt J. David , Schrader Laura A.
Published: February 2009

Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K+) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K+ channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.
The solution structure of the anti‐HIV chemokine vMIP‐II
Authors: Liwang Andy C. , Wang Zi‐Xuan , Sun Yi , Peiper Stephen C. , Liwang Patricia J.
Published: February 2009

We report the solution structure of the chemotactic cytokine (chemokine) vMIP‐II. This protein has unique biological activities in that it blocks infection by several different human immunodeficiency virus type 1 (HIV‐1) strains. This occurs because vMIP‐II binds to a wide range of chemokine receptors, some of which are used by HIV to gain cell entry. vMIP‐II is a monomeric protein, unlike most members of the chemokine family, and its structure consists of a disordered N‐terminus, followed by a helical turn (Gln25‐Leu27), which leads into the first strand of a three‐stranded antiparallel β‐sheet (Ser29‐Thr34; Gly42‐Thr47; Gln52‐Asp56). Following the sheet is a C‐terminal α‐helix, which extends from residue Asp60 until Gln68. The final five residues beyond the C‐terminal helix (Pro70‐Arg74) are in an extended conformation, but several of these C‐terminal residues contact the first β‐strand. The structure of vMIP‐II is compared to other chemokines that also block infection by HIV‐1, and the structural basis of its lack of ability to form a dimer is discussed.
A stable intermediate in the equilibrium unfolding of Escherichia coli citrate synthase
Authors: Ayed Ayeda , Duckworth Harry W.
Published: February 2009

Urea‐induced unfolding of Escherichia coli citrate synthase occurs in two phases, as monitored by circular dichroism at 222 nm (measuring secondary structure) or by tryptophan fluorescence. In this paper we characterize the intermediate state, which retains about 40% of the ellipticity of the native state, and is stable between 2.5 M and 5.5 M urea, approximately. This intermediate binds significant amounts of the probe for hydrophobic surfaces, anilinonaphthalene sulfonate, but forms aggregates at least as high as an octamer, as shown by transverse urea gradient polyacrylamide electrophoresis. Thermal denaturation of E. coli citrate synthase also produces an intermediate at temperatures near 60 °C, which also retains about 40% of the native ellipticity and forms aggregates, as measured by electrosprayionization/time‐of‐flight mass spectrometry. We have used a collection of “cavity‐forming” mutant proteins, in which bulky buried hydrophobic residues are replaced by alanines, to explore the nature of the intermediate state further. A certain amount of these mutant proteins shows a destabilized intermediate, as measured by the urea concentration range in which the intermediate is observed. These mutants are found in parts of the citrate synthase sequence that, in a native state, form helices G, M, N, Q, R, and S. From this and other evidence, it is argued that the intermediate state is an aggregated state in which these six helices, or parts of them, remain folded, and that formation of this intermediate is also likely to be a key step in the folding of E. coli citrate synthase.
Analysis of long‐range interactions in a model denatured state of staphylococcal nuclease based on correlated changes in backbone dynamics
Authors: Sinclair James F. , Shortle David
Published: February 2009

An expanded, highly dynamic denatured state of staphylococcal nuclease exhibits a native‐like topology in the apparent absence of tight packing and fixed hydrogen bonds (Gillespie JR, Shortle D, 1997, J Mol Biol 268:158–169, 170–184). To address the physical basis of the long‐range spatial ordering of this molecule, we probe the effects of perturbations of the sequence and solution conditions on the local chain dynamics of a denatured 101‐residue fragment that is missing the first three beta strands. Structural interactions between chain segments are inferred from correlated changes in the motional behavior of residues monitored by 15N NMR relaxation measurements. Restoration of the sequence corresponding to the first three beta strands significantly increases the average order of all chain segments that form the five strand beta barrel including loops but has no effect on the carboxy terminal 30 residues. Addition of the denaturing salt sodium perchlorate enhances ordering over the entire sequence of this fragment. Analysis of seven different substitution mutants points to a complex set of interactions between the hydrophobic segment corresponding to beta strand 5 and the remainder of the chain. General patterns in the data suggest there is a hierarchy of native‐like interactions that occur transiently in the denatured state and are consistent with the overall topology of the denatured state ensemble being determined by many coupled local interactions rather than a few highly specific long‐range interactions.
Dual coenzyme specificity of Archaeoglobus fulgidus HMG‐CoA reductase
Authors: Kim Dong‐Yul , Stauffacher Cynthia V. , Rodwell Victor W.
Published: February 2009

Comparison of the inferred amino acid sequence of orf AF1736 of Archaeoglobus fulgidus to that of Pseudomonas mevalonii HMG‐CoA reductase suggested that AF1736 might encode a Class II HMG‐CoA reductase. Following polymerase chain reaction‐based cloning of AF1736 from A. fulgidus genomic DNA and expression in Escherichia coli, the encoded enzyme was purified to apparent homogeneity and its enzymic properties were determined. Activity was optimal at 85°C,ΔHa was 54 kJ/mol, and the statin drug mevinolin inhibited competitively with HMG‐CoA (Ki 180 μM). Protonated forms of His390 and Lys277, the apparent cognates of the active site histidine and lysine of the P. mevalonii enzyme, appear essential for activity. The mechanism proposed for catalysis of P. mevalonii HMG‐CoA reductase thus appears valid for A. fulgidus HMG‐CoA reductase. Unlike any other HMG‐CoA reductase, the A. fulgidus enzyme exhibits dual coenzyme specificity. pH‐activity profiles for all four reactions revealed that optimal activity using NADP(H) occurred at a pH from 1 to 3 units more acidic than that observed using NAD(H). Kinetic parameters were therefore determined for all substrates for all four catalyzed reactions using either NAD(H) or NADP(H). NADPH and NADH compete for occupancy of a common site. kcat[NAD(H)]/kcat[NADP(H)] varied from unity to under 70 for the four reactions, indicative of slight preference for NAD(H). The results indicate the importance of the protonated status of active site residues His390 and Lys277, shown by altered KM and kcat values, and indicate that NAD(H) and NADP(H) have comparable affinity for the same site.
Repeat Teenage Pregnancy in Two Cultures–The Meanings Ascribed by Teenagers
Authors: Clarke Jean
Published: February 2009

This qualitative study charts the views, feelings and experiences of two diverse, yet in many ways similar, groups of respondents from two cultures – one group of 26 respondents from the Caribbean islands of Jamaica and Barbados and the other group of 26 respondents from London, who have experienced repeat teenage pregnancies. The study uses a comparative approach to provide a psychosocial, emotional and economic understanding of the factors, which lead to repeat pregnancies. This study cautions against an over reliance on a mechanistic understanding and management of both single and repeat teenage pregnancies, and emphasises the fact that economic, social, psychological and emotional processes are also crucial to our understanding of repeat teenage pregnancies.
Phosphoinositide 3‐kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo
Authors: Teranishi Futoshi , Takahashi Naoko , Gao Nan , Akamo Yoshimi , Takeyama Hiromitsu , Manabe Tadao , Okamoto Takashi
Published: February 2009

In order to block peritoneal metastasis of pancreatic cancer cells, we have attempted to block the signal transduction pathway involving hyaluronan (HA), Src, phosphoinositide 3‐kinase (PI3K) and Akt. We examined the effects of Src, PI3K and Akt inhibitors on pancreatic cancer cell motility, invasion and metastasis. The pancreatic cancer cell line SW1990, known to cause peritoneal metastasis efficiently in nude mice, was used in this study. SW1990 cells were stimulated by HA to induce Akt phosphorylation. Then, the inhibitory effects of PI3K and Src kinase inhibitors were examined. Cell motility and cell migration assays were adopted to assess the cancer cell motility and its migration capability. We also examined the therapeutic efficacies of PI3K inhibitor wortmannin on peritoneal metastasis of SW1990 cells in the nude mouse model. Stimulation of SW1990 cells by HA markedly induced the Src‐PI3K‐Akt signaling, thus enhancing cancer cell motility and its migration. Significantly, we found that wortmannin could exert marked inhibition of the peritoneal metastasis of SW1990 in nude mice in vivo. These findings indicate that the PI3K‐Akt signaling pathway plays an essential role in peritoneal metastasis and PI3K inhibitors such as wortmannin can be novel modalities to prevent peritoneal metastasis of invasive cancers such as pancreatic cancer. (Cancer Sci 2009; 100: 770–777)
Preclinical and clinical studies of anticancer agent‐incorporating polymer micelles
Authors: Matsumura Yasuhiro , Kataoka Kazunori
Published: February 2009

The size of anticancer agent‐incorporating micelles can be controlled within the diameter range of 20–100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug‐induced side‐effects may be decreased owing to the reduced drug distribution in normal tissue. Micelle systems can also evade non‐specific capture by the reticuloendothelial system because the outer shell of a micelle is covered with polyethylene glycol. Consequently, a polymer micelle carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Moreover, a water‐insoluble drug can be incorporated into polymer micelles. Presently, several anticancer agent‐incorporating micelle carrier systems are under preclinical and clinical evaluation. Furthermore, nucleic acid‐incorporating micelle carrier systems are also being developed. (Cancer Sci2009; 100: 572–579)
C‐reactive protein and colorectal adenomas: Self Defense Forces Health Study
Authors: Otake Toshie , Uezono Kousaku , Takahashi Ryota , Fukumoto Jin , Tabata Shinji , Abe Hiroshi , Tajima Osamu , Mizoue Tetsuya , Ohnaka Keizo , Kono Suminori
Published: February 2009

Chronic inflammation has been implicated in colorectal carcinogenesis. Several studies have investigated the relationship between C‐reactive protein (CRP), a biomarker of inflammation, and colorectal cancer and adenomas, resulting in inconsistent findings. The present study examined the relationship between circulating levels of high‐sensitivity CRP and colorectal adenomas. The study subjects comprised 646 cases of colorectal adenoma and 635 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces. Statistical adjustment was made for cigarette smoking, alcohol use, body mass index, physical activity, and other potential confounders. The multivariate‐adjusted geometric means showed no measurable differences between adenoma cases and controls, but were higher among cases with larger adenomas (trend P = 0.03). Likewise, although the prevalence odds of colorectal adenomas did not differ according to CRP levels as categorized at the 30th, 60th, and 90th percentiles in the controls, higher levels of CRP were associated with a statistically significant increase in the prevalence odds of large adenomas (≥5 mm), but not of small adenomas (<5 mm). The multivariate‐adjusted odds ratios of large adenomas for the lowest to highest categories of CRP were 1.00 (referent), 1.81 (95% confidence interval 1.17–2.80), 1.61 (95% confidence interval 1.03–2.52), and 2.21 (95% confidence interval 1.28–3.84), respectively (trend P = 0.01). A positive association between CRP and prevalence odds of large adenomas was not modified by either smoking or overweight. These findings suggest that inflammation is linked to the growth of colorectal adenomas. (Cancer Sci 2009; 100: 709–711)
Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprine
Authors: SEKSIK P. , COSNES J. , SOKOL H. , NION‐LARMURIER I. , GENDRE J.‐P. , BEAUGERIE L.
Published: February 2009

Background  There are few data on the incidence of benign infections (upper respiratory tract infections, herpes lesions and viral warts) during exposure to azathioprine.

Aims  To determine the incidence of benign infections in IBD out‐patients receiving azathioprine (AZA+) and to look at the influence of leucocyte counts in the onset of these events.

Methods  A total of 230 patients were included in a prospective cohort and observed during 207 patient‐years. Episodes of benign infections were collected and incidences of benign infections were compared between the AZA+ group and patients without AZA (AZA−).

Results  The incidence of upper respiratory tract infections in the cohort was 2.1 ± 2.2 per observation‐year. There was no difference between the AZA+ (n = 169) and AZA− (n = 61) groups (2.2 ± 2.3 vs. 2.1 ± 2.1, P = 0.77). The incidence of herpes flares was significantly increased in the AZA+ group compared to the AZA− group (1.0 ± 2.6 vs. 0.2 ± 0.8 per year, P = 0.04). Similarly, there were significantly more patients with appearance or worsening viral warts in the AZA+ group (17.2% (AZA+) vs. 3.3% (AZA−), P = 0.004).

Conclusion  This study suggests that the incidence of herpes flares and the appearance or worsening of viral warts are increased in IBD patients receiving AZA.
Serum and monoclonal immunoglobulin E antibodies from NC/Nga mice with severe atopic‐like dermatitis recognize an auto‐antigen, histone H3
Authors: Matsubara T. , Aoki N. , Hino S. , Okajima T. , Nadano D. , Matsuda T.
Published: February 2009

Background
NC/Nga mice are known to show a spontaneous outbreak of atopic‐like dermatitis accompanied by a marked elevation in serum IgE levels when reared in a conventional environment. The specific effects of such a strong serum IgE response on the development of the dermatitis and specific antigens recognized by the IgE antibodies are still uncertain.

Objective and methods
To characterize the IgE of NC/Nga mice, we established IgE‐secreting hybridoma clones from spleen cells of NC/Nga mice spontaneously developing dermatitis and identified variable‐region genes and specific antigens of the IgE monoclonal antibodies (mAbs). Serum polyclonal IgE, as well as IgG1 and IgG2a, specific for the identified antigen were also analysed.

Results
Four IgE‐producing hybridoma clones were established. Variable‐region nucleotide sequences of the IgE mAbs showed that these clones did not necessarily share common germline gene segments (V, D or J) for each variable region, and several somatic mutations had occured in the V gene segments. Through antigen screening, histone H3 was identified to be an auto‐antigen recognized by three of the four IgE mAbs. Serum IgE as well as IgG1 specific for histone H3 were almost undetectable in 6‐week‐old mice, but rapidly increased by 10–12 weeks of age. This age‐dependent increase in the serum anti‐histone H3 IgE was roughly in parallel with the onset of dermatitis, and slightly preceding total IgE elevation. The serum‐specific IgE level correlated well with a dermatitis‐severity score of each mouse at 12–16 weeks of age, and weakly with the severity of ear erosion of each mouse over 28 weeks of age. Furthermore, immunologically detectable histone‐H3 antigens were observed in skin tissue sections from the dermatitis sites.

Conclusion
In NC/Nga mice, anti‐histone H3 auto‐antibodies may contribute, at least in part, to the considerably elevated serum IgE and might play some roles in the development and exacerbation of dermatitis.
Use of A‐type CpG oligodeoxynucleotides as an adjuvant in allergen‐specific immunotherapy in humans: a phase I/IIa clinical trial
Authors: Senti G. , Johansen P. , Haug S. , Bull C. , Gottschaller C. , Müller P. , Pfister T. , Maurer P. , Bachmann M. F. , Graf N. , Kündig T. M.
Published: February 2009

BackgroundB‐type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half–life, which is due to its phosphorothioate backbone. A‐type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus‐like particles (VLP) consisting of the bacteriophage Qβ coat protein, A‐type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A‐type CpGs in humans.

ObjectiveTo test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients.

MethodsA single centre, open‐label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty‐one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end‐points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen‐specific IgG and IgE.

ResultsQbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom‐free and this amelioration lasted for at least 38 weeks post‐treatment. Following injections of QbG10 and HDM allergen extract, allergen‐specific IgG increased, while there was a transient increase in allergen‐specific IgE titres. Skin reactivity to HDM was reduced.

ConclusionThe subcutaneous application of HDM allergen, together with A‐type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo‐controlled phase II studies.
Safety and efficacy of treatment using interleukin-2 in a patient with idiopathic CD4+ lymphopenia andMycobacterium avium-intracellulare
Authors: Trojan T , Collins R , Khan D A
Published: February 2009

We present the case of a 39-year-old white man with a Myobacterium avium-intracellulare pulmonary infection found to have a CD4+ count of 172 cells/mm3 and diagnosed subsequently with idiopathic CD4+ lymphopenia (ICL). After receiving clathromycin for 4 months with minimal improvement, the patient was started on pegylated subcutaneous interleukin (IL)-2 at 600 000 units daily. Later, he received incrementally higher pegylated IL-2 doses until he reached a maintenance dose 3 months later of 11 million units weekly divided into three equal doses. After 5 months of therapy, the patient’s chronic cough resolved completely, sputum cultures became negative for Myobacterium avium-intracellulare and the CD4+ T cell count increased to 553 cells/mm3. After 35 months of well-tolerated IL-2 treatments and no recurrence of any opportunistic infections, IL-2 treatment was stopped. CD4+ counts 6 and 9 months after discontinuing IL-2 treatment were 596 and 378 cells/mm3 respectively, and he remains asymptomatic. This report supports IL-2 treatment for ICL-associated opportunistic infections as a safe and potentially efficacious treatment option, especially when combined with more traditional treatment regimens.