bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximating spectral invariants of Harper operators on graphs II
Authors: Mathai Varghese , Schick Thomas , Yates Stuart
Published: July 2005

We study Harper operators and the closely related discrete magnetic Laplacians (DML) on a graph with a free action of a discrete group, as defined by Sunada. The spectral density function of the DML is defined using the von Neumann trace associated with the free action of a discrete group on a graph. The main result in this paper states that when the group is amenable, the spectral density function is equal to the integrated density of states of the DML that is defined using either Dirichlet or Neumann boundary conditions. This establishes the main conjecture in a paper by Mathai and Yates. The result is generalized to other self adjoint operators with finite propagation speed.
André-Quillen homology via functor homology
Authors: Pirashvili Teimuraz
Published: July 2005

We obtain André-Quillen homology for commutative algebras using relative homological algebra in the category of functors on finite pointed sets.
A weak–type orthogonality principle
Authors: Barrionuevo Jose , Lacey Michael
Published: July 2005

We prove a weak type estimate for operators of the form

f
→

∑

s
∈

S

⟨
f
,
φ
s
⟩
φ
s

f \to \sum _{s\in \mathbf S}\langle f,\varphi s \rangle \varphi s

for certain collections of Schwartz functions

{
φ
s

}

s
∈

S

\{ \varphi s \}_{s\in \mathbf S}

. This extends some of the orthogonality issues involved in the study of the bilinear Hilbert transform by Lacey and Thiele.
cos𝜋𝜆 again
Authors: Fenton P.
Published: July 2005

It is shown that if, for an entire function,
\[

lim inf

r
→
∞

log
⁡
M
(
r
)

/

r

λ

=
0

\liminf _{r\to \infty } \log M(r)/r^{\lambda } = 0

\]
where

0
>
λ
>
1

0> \lambda >1

, then
\[

lim sup

r
→
∞

(
log
⁡
m
(
r
)
−
cos
⁡
π
λ
log
⁡
M
(
r
)
)

/

log
⁡
r
=
∞
.

\limsup _{r\to \infty }(\log m(r)-\cos \pi \lambda \log M(r))/\log r = \infty .

\]
In the proof, the zeros of the function are redistributed to minimize the large values of

log
⁡
m
(
r
)
−
cos
⁡
π
λ
log
⁡
M
(
r
)

\log m(r) -\cos \pi \lambda \log M(r)

.
On the greatest prime factor of (𝑎𝑏+1)(𝑎𝑐+1)
Authors: Corvaja P. , Zannier U.
Published: July 2005

We prove that for integers

a
>
b
>
c
>
0

a>b>c>0

, the greatest prime factor of

(
a
b
+
1
)
(
a
c
+
1
)

(ab+1)(ac+1)

tends to infinity with

a
a

. In particular, this settles a conjecture raised by Györy, Sarkozy and Stewart, predicting the same conclusion for the product

(
a
b
+
1
)
(
a
c
+
1
)
(
b
c
+
1
)

(ab+1)(ac+1)(bc+1)

.
Local automorphisms of operator algebras on Banach spaces
Authors: Molnár Lajos
Published: July 2005

In this paper we extend a result of Šemrl stating that every 2-local automorphism of the full operator algebra on a separable infinite dimensional Hilbert space is an automorphism. In fact, besides separable Hilbert spaces, we obtain the same conclusion for the much larger class of Banach spaces with Schauder bases. The proof rests on an analogous statement concerning the 2-local automorphisms of matrix algebras for which we present a short proof. The need to get such a proof was formulated in Šemrl’s paper.
A cocycle formula for the quaternionic discrete series
Authors: Donley Robert
Published: July 2005

Schmid’s proof of the Kostant-Langlands conjecture for discrete series representations of a semisimple Lie group provides a Hilbert space realization of such representations in

L

2

L^{2}

-cohomology. We give an explicit description of these harmonic forms for the quaternionic discrete series.
Volume preserving embeddings of open subsets of ℝⁿ into manifolds
Authors: Schlenk Felix
Published: July 2005

We consider a connected smooth

n
n

-dimensional manifold

M
M

endowed with a volume form

Ω
\Omega

, and we show that an open subset

U
U

of

R

n

{\mathbb R}^n

of Lebesgue measure

Vol

(
U
)

\operatorname {Vol}\;\! (U)

embeds into

M
M

by a smooth volume preserving embedding whenever the volume condition

Vol

(
U
)
≤
Vol

(
M
,
Ω
)

\operatorname {Vol}\;\! (U) \le \operatorname {Vol}\;\!(M, \Omega )

is met.
Two 𝐹_{𝜎𝛿} ideals
Authors: Farah Ilijas , Solecki Sławomir
Published: July 2005

We find two

F

σ
δ

F_{\sigma \delta }

ideals on

N

\mathbb N

neither of which is

F
σ

F_\sigma

whose quotient Boolean algebras are homogeneous but nonisomorphic. This solves a problem of Just and Krawczyk (1984).
Random Menshov spectra
Authors: Kozma Gady , Olevskiǐ Alexander
Published: July 2005

We show that the spectra

Λ
\Lambda

of frequencies

λ
\lambda

obtained by random perturbations of the integers allows one to represent any measurable function

f
f

on

R

\mathbb {R}

by an almost everywhere converging sum of harmonics:
\[

f
=

∑

Λ

c

λ

e

i
λ
t

.

f=\sum _{\Lambda }c_{\lambda }e^{i\lambda t}.

\]
An algebraic property of joinings
Authors: Ahn Young-Ho , Lemańczyk Mariusz
Published: July 2005

We show that an ergodic automorphism is semisimple if and only if the set of ergodic self-joinings is a subsemigroup of the semigroup of self-joinings.
Leafwise holomorphic functions
Authors: Feres R. , Zeghib A.
Published: July 2005

It is a well-known and elementary fact that a holomorphic function on a compact complex manifold is necessarily constant. The purpose of the present article is to investigate whether, or to what extent, a similar property holds in the setting of holomorphically foliated spaces.
Automorphisms of the endomorphism semigroup of a free monoid or a free semigroup
Authors: Mashevitzky G. , Schein Boris
Published: July 2005

We determine all isomorphisms between the endomorphism semigroups of free monoids or free semigroups and prove that automorphisms of the endomorphism semigroup of a free monoid or a free semigroup are inner or “mirror inner". In particular, we answer a question of B. I. Plotkin.
Existence of Gibbs measures for countable Markov shifts
Authors: Sarig Omri
Published: July 2005

We prove that a potential with summable variations and finite pressure on a topologically mixing countable Markov shift has a Gibbs measure iff the transition matrix satisfies the big images and preimages property. This strengthens a result of D. Mauldin and M. Urbański (2001) who showed that this condition is sufficient.
Convergence rates of cascade algorithms
Authors: Jia Rong-Qing
Published: July 2005

We consider solutions of a refinement equation of the form
\[

ϕ
=

∑

γ
∈

Z

s

a
(
γ
)
ϕ
(

M
⋅

−
γ
)
,

\phi = \sum _{\gamma \in \mathbb {Z}^s} a(\gamma ) \phi ({M\cdot }-\gamma ),

\]
where

a
a

is a finitely supported sequence called the refinement mask. Associated with the mask

a
a

is a linear operator

Q
a

Q_a

defined on

L
p

(

R

s

)

L_p(\mathbb {R}^s)

by
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper Q Subscript a Baseline psi colon equals sigma-summation Underscript gamma element-of double-struck upper Z Superscript s Endscripts a left-parenthesis gamma right-parenthesis psi left-parenthesis upper M dot minus gamma right-parenthesis">

Q
a

ψ
:=

∑

γ
∈

Z

s

a
(
γ
)
ψ
(

M
⋅

−
γ
)

Q_a \psi := \sum _{\gamma \in \mathbb {Z}^s} a(\gamma ) \psi ({M\cdot }-\gamma )

. This paper is concerned with the convergence of the cascade algorithm associated with

a
a

, i.e., the convergence of the sequence

(

Q
a
n

ψ

)

n
=
1
,
2
,
…

(Q_a^n\psi )_{n=1,2,\ldots }

in the

L
p

L_p

-norm. Our main result gives estimates for the convergence rate of the cascade algorithm. Let

ϕ
\phi

be the normalized solution of the above refinement equation with the dilation matrix

M
M

being isotropic. Suppose

ϕ
\phi

lies in the Lipschitz space

Lip
⁡
(
μ
,

L
p

(

R

s

)
)

\operatorname {Lip} (\mu ,L_p(\mathbb {R}^s))

, where

μ
>
0

\mu >0

and

1
≤
p
≤
∞

1 \le p \le \infty

. Under appropriate conditions on

ψ
\psi

, the following estimate will be established:
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar upper Q Subscript a Superscript n Baseline psi minus phi double-vertical-bar Subscript p Baseline less-than-or-equal-to upper C left-parenthesis m Superscript negative 1 slash s Baseline right-parenthesis Superscript mu n Baseline for-all n element-of double-struck upper N comma">

‖

Q
a
n

ψ
−
ϕ

‖

p

≤
C
(

m

−
1

/

s

)

μ
n

∀

n
∈

N

,

\bigl \| Q_a^n\psi - \phi \bigr \|_p \le C (m^{-1/s})^{\mu n}\quad \forall \, n \in \mathbb {N},

\]
where

m
:=

|

det
M

|

m:=|\det M|

and

C
C

is a constant. In particular, we confirm a conjecture of A. Ron on convergence of cascade algorithms.
Multi-dimensional versions of a theorem of Fine and Wilf and a formula of Sylvester
Authors: Simpson R. , Tijdeman R.
Published: July 2005

Let

v
0

→

,
.
.
.
,

v
k

→

{\vec {v_0},..., \vec {v_k}}

be vectors in

Z

k

\mathbf {Z}^k

which generate

Z

k

\mathbf {Z}^k

. We show that a body

V
⊂

Z

k

V \subset \mathbf {Z}^k

with the vectors

v
0

→

,
.
.
.
,

v
k

→

{\vec {v_0},..., \vec {v_k}}

as edge vectors is an almost minimal set with the property that every function

f
:
V
→

R

f: V \rightarrow \mathbf {R}

with periods

v
0

→

,
.
.
.
,

v
k

→

{\vec {v_0},..., \vec {v_k}}

is constant. For

k
=
1

k=1

the result reduces to the theorem of Fine and Wilf, which is a refinement of the famous Periodicity Lemma. Suppose

0
→

\vec {0}

is not a non-trivial linear combination of

v
0

→

,
.
.
.
,

v
k

→

{\vec {v_0},..., \vec {v_k}}

with non-negative coefficients. Then we describe the sector such that every interior integer point of the sector is a linear combination of

v
0

→

,
.
.
.
,

v
k

→

{\vec {v_0},..., \vec {v_k}}

over

Z

≥
0

\mathbf {Z}_{\geq 0}

, but infinitely many points on each of its hyperfaces are not. For

k
=
1

k=1

the result reduces to a formula of Sylvester corresponding to Frobenius’ Coin-changing Problem in the case of coins of two denominations.
Hypercyclic operators on non-locally convex spaces
Authors: Wengenroth Jochen
Published: July 2005

We transfer a number of fundamental results about hypercyclic operators on locally convex spaces (due to Ansari, Bès, Bourdon, Costakis, Feldman, and Peris) to the non-locally convex situation. This answers a problem posed by A. Peris [Multi-hypercyclic operators are hypercyclic, Math. Z. 236 (2001), 779-786].
Nonautonomous Kato classes of measures and Feynman-Kac propagators
Authors: Gulisashvili Archil
Published: July 2005

The behavior of the Feynman-Kac propagator corresponding to a time-dependent measure on

R
n

R^n

is studied. We prove the boundedness of the propagator in various function spaces on

R
n

R^n

, and obtain a uniqueness theorem for an exponentially bounded distributional solution to a nonautonomous heat equation.
Irregular hypergeometric systems associated with a singular monomial curve
Authors: Hartillo-Hermoso María
Published: July 2005

In this paper we study irregular hypergeometric systems defined by one row. Specifically, we calculate slopes of such systems. In the case of reduced semigroups, we generalize the case studied by Castro and Takayama. In all the cases we find that there always exists a slope with respect to a hyperplane of this system. Only in the case of an irregular system defined by a

1
×
2

1\times 2

integer matrix we might need a change of coordinates to study slopes at infinity. In the other cases slopes are always at the origin, defined with respect to a hyperplane. We also compute all the

L
L

-characteristic varieties of the system, so we have a section of the Gröbner fan of the module defined by the hypergeometric system.
Canonical varieties with no canonical axiomatisation
Authors: Hodkinson Ian , Venema Yde
Published: July 2005

We give a simple example of a varietyV\mathbf {V}of modal algebras that is canonical but cannot be axiomatised by canonical equations or first-order sentences. We then show that the varietyRRA\mathbf {RRA}of representable relation algebras, although canonical, has no canonical axiomatisation. Indeed, we show that every axiomatisation of these varieties involves infinitely many non-canonical sentences. Using probabilistic methods of Erdős, we construct an infinite sequenceG0,G1,…G_0,G_1,\ldotsof finite graphs with arbitrarily large chromatic number, such that eachGnG_nis a bounded morphic image ofGn+1G_{n+1}and has no odd cycles of length at mostnn. The inverse limit of the sequence is a graph with no odd cycles, and hence is 2-colourable. It follows that a modal algebra (respectively, a relation algebra) obtained from theGnG_nsatisfies arbitrarily many axioms from a certain axiomatisation ofV (RRA)\mathbf {V}\ (\mathbf {RRA}), while its canonical extension satisfies only a bounded number of them. First-order compactness will now establish thatV (RRA)\mathbf {V}\ (\mathbf {RRA})has no canonical axiomatisation. A variant of this argument shows that all axiomatisations of these classes have infinitely many non-canonical sentences.
Towers of 2-covers of hyperelliptic curves
Authors: Bruin Nils , Flynn E.
Published: July 2005

In this article, we give a way of constructing an unramified Galois-cover of a hyperelliptic curve. The geometric Galois-group is an elementary abelian

2
2

-group. The construction does not make use of the embedding of the curve in its Jacobian, and it readily displays all subcovers. We show that the cover we construct is isomorphic to the pullback along the multiplication-by-

2
2

map of an embedding of the curve in its Jacobian. We show that the constructed cover has an abundance of elliptic and hyperelliptic subcovers. This makes this cover especially suited for covering techniques employed for determining the rational points on curves. In particular the hyperelliptic subcovers give a chance for applying the method iteratively, thus creating towers of elementary abelian 2-covers of hyperelliptic curves. As an application, we determine the rational points on the genus

2
2

curve arising from the question of whether the sum of the first

n
n

fourth powers can ever be a square. For this curve, a simple covering step fails, but a second step succeeds.
Classification problems in continuum theory
Authors: Camerlo Riccardo , Darji Udayan , Marcone Alberto
Published: July 2005

We study several natural classes and relations occurring in continuum theory from the viewpoint of descriptive set theory and infinite combinatorics. We provide useful characterizations for the relation of likeness among dendrites and show that it is a bqo with countably many equivalence classes. For dendrites with finitely many branch points the homeomorphism and quasi-homeomorphism classes coincide, and the minimal quasi-homeomorphism classes among dendrites with infinitely many branch points are identified. In contrast, we prove that the homeomorphism relation between dendrites is

S
∞

S_\infty

-universal. It is shown that the classes of trees and graphs are both

D

2

(

Σ

3

0

)

\mathrm {D}_{2}({{\boldsymbol \Sigma _{3}^{0}}})

-complete, the class of dendrites is

Π

3

0

{{\boldsymbol \Pi _{3}^{0}}}

-complete, and the class of all continua homeomorphic to a graph or dendrite with finitely many branch points is

Π

3

0

{{\boldsymbol \Pi _{3}^{0}}}

-complete. We also show that if

G
G

is a nondegenerate finitely triangulable continuum, then the class of

G
G

-like continua is

Π

2

0

{\boldsymbol \Pi _{2}^{0}}

-complete.
On the absolutely continuous spectrum of one-dimensional quasi-periodic Schrödinger operators in the adiabatic limit
Authors: Fedotov Alexander , Klopp Frédéric
Published: July 2005

In this paper we study the spectral properties of families of quasi-periodic Schrödinger operators on the real line in the adiabatic limit in the case when the adiabatic iso-energetic curves are extended along the position direction. We prove that, in energy intervals where this is the case, most of the spectrum is purely absolutely continuous in the adiabatic limit, and that the associated generalized eigenfunctions are Bloch-Floquet solutions.

Résumé.Cet article est consacré à l’étude du spectre de certaines familles d’équations de Schrödinger quasi-périodiques sur l’axe réel lorsque les variétés iso-énergetiques adiabatiques sont étendues dans la direction des positions. Nous démontrons que, dans un intervalle d’énergie où ceci est le cas, le spectre est dans sa majeure partie purement absolument continu et que les fonctions propres généralisées correspondantes sont des fonctions de Bloch-Floquet.
Free and semi-inert cell attachments
Authors: Bubenik Peter
Published: July 2005

Let

Y
Y

be the space obtained by attaching a finite-type wedge of cells to a simply-connected, finite-type CW-complex. We introduce the free and semi-inert conditions on the attaching map which broadly generalize the previously-studied inert condition. Under these conditions we determine

H
∗

(
Ω
Y
;
R
)

H_*(\Omega Y;R)

as an

R
R

-module and as an

R
R

-algebra, respectively. Under a further condition we show that

H
∗

(
Ω
Y
;
R
)

H_*(\Omega Y;R)

is generated by Hurewicz images. As an example we study an infinite family of spaces constructed using only semi-inert cell attachments.
Uniform properties of rigid subanalytic sets
Authors: Lipshitz Leonard , Robinson Zachary
Published: July 2005

In the context of rigid analytic spaces over a non-Archimedean valued field, a rigid subanalytic set is a Boolean combination of images of rigid analytic maps. We give an analytic quantifier elimination theorem for (complete) algebraically closed valued fields that is independent of the field; in particular, the analytic quantifier elimination is independent of the valued field’s characteristic, residue field and value group, in close analogy to the algebraic case. This provides uniformity results about rigid subanalytic sets. We obtain uniform versions of smooth stratification for subanalytic sets and the Łojasiewicz inequalities, as well as a unfiorm description of the closure of a rigid semianalytic set.
First countable, countably compact spaces and the continuum hypothesis
Authors: Eisworth Todd , Nyikos Peter
Published: July 2005

We build a model of ZFC+CH in which every first countable, countably compact space is either compact or contains a homeomorphic copy ofω1\omega _1with the order topology. The majority of the paper consists of developing forcing technology that allows us to conclude that our iteration adds no reals. Our results generalize Saharon Shelah’s iteration theorems appearing in Chapters V and VIII ofProper and improper forcing(1998), as well as Eisworth and Roitman’s (1999) iteration theorem. We close the paper with a ZFC example (constructed using Shelah’s club–guessing sequences) that shows similar results do not hold for closed pre–images ofω2\omega _2.
ATM-dependent DNA Damage-independent Mitotic Phosphorylation of H2AX in Normally Growing Mammalian Cells
Authors: McManus Kirk J. , Hendzel Michael J.
Published: July 2005

H2AX is a core histone H2A variant that contains an absolutely conserved serine/glutamine (SQ) motif within an extended carboxy-terminal tail. H2AX phosphorylation at the SQ motif (γ-H2AX) has been shown to increase dramatically upon exogenously introduced DNA double-strand breaks (DSBs). In this study, we use quantitative in situ approaches to investigate the spatial patterning and cell cycle dynamics of γ-H2AX in a panel of normally growing (unirradiated) mammalian cell lines and cultures. We provide the first evidence for the existence of two distinct yet highly discernible γ-H2AX focal populations: a small population of large amorphous foci that colocalize with numerous DNA DSB repair proteins and previously undescribed but much more abundant small foci. These small foci do not recruit proteins involved in DNA DSB repair. Cell cycle analyses reveal unexpected dynamics for γ-H2AX in unirradiated mammalian cells that include an ATM-dependent phosphorylation that is maximal during M phase. Based upon similarities drawn from other histone posttranslational modifications and previous observations in haploinsufficient (H2AX-/+) and null mice (H2AX-/-), γ-H2AX may contribute to the fidelity of the mitotic process, even in the absence of DNA damage, thereby ensuring the faithful transmission of genetic information from one generation to the next.
The Golgi Ca2+-ATPase KlPmr1p Function Is Required for Oxidative Stress Response by Controlling the Expression of the Heat-Shock ElementHSP60inKluyveromyces lactis
Authors: Uccelletti Daniela , Farina Francesca , Pinton Paolo , Goffrini Paola , Mancini Patrizia , Talora Claudio , Rizzuto Rosario , Palleschi Claudio
Published: July 2005

The Golgi P-type Ca2+-ATPase, Pmr1p, is the major player for calcium homeostasis in yeast. The inactivation of KlPMR1 in Kluyveromyces lactis leads to high pleiotropic phenotypes that include reduced glycosylation, cell wall defects, and alterations of mitochondrial metabolism. In this article we found that cells lacking KlPmr1p have a morphologically altered mitochondrial network and that mitochondria (m) from Klpmr1Δ cells accumulate Ca2+more slowly and reach a lower [Ca2+]mlevel, when exposed to [Ca2+] < 5 μM, than wild-type cells. The Klpmr1Δ cells also exhibit traits of ongoing oxidative stress and present hyperphosphorylation of KlHog1p, the hallmark for the activation of stress response pathways. The mitochondrial chaperone KlHsp60 acts as a multicopy suppressor of phenotypes that occur in cells lacking the Ca2+-ATPase, including relief from oxidative stress and recovery of cell wall thickness and functionality. Inhibition of KlPMR1 function decreases KlHSP60 expression at both mRNA and protein levels. Moreover, KlPRM1 loss of function correlates with both decreases in HSF DNA binding activity and KlHSP60 expression. We suggest a role for KlPMR1 in HSF DNA binding activity, which is required for proper KlHSP60 expression, a key step in oxidative stress response.
SCAMP2 Interacts with Arf6 and Phospholipase D1 and Links Their Function to Exocytotic Fusion Pore Formation in PC12 Cells
Authors: Liu Lixia , Liao Haini , Castle Anna , Zhang Jie , Casanova James , Szabo Gabor , Castle David
Published: July 2005

SNAP receptor (SNARE)-mediated fusion is regarded as a core event in exocytosis. Exocytosis is supported by other proteins that set up SNARE interactions between secretory vesicle and plasma membranes or facilitate fusion pore formation. Secretory carrier membrane proteins (SCAMPs) are candidate proteins for functioning in these events. In neuroendocrine PC12 cells, SCAMP2 colocalizes on the cell surface with three other proteins required for dense-core vesicle exocytosis: phospholipase D1 (PLD1), the small GTPase Arf6, and Arf6 guanine nucleotide exchange protein ARNO. Arf6 and PLD1 coimmunoprecipitate (coIP) with SCAMP2. These associations have been implicated in exocytosis by observing enhanced coIP of Arf6 with SCAMP2 after cell depolarization and in the presence of guanosine 5′-O-(3-thio)triphosphate and by inhibition of coIP by a SCAMP-derived peptide that inhibits exocytosis. The peptide also suppresses PLD activity associated with exocytosis. Using amperometry to analyze exocytosis, we show that expression of a point mutant of SCAMP2 that exhibits decreased association with Arf6 and of mutant Arf6 deficient in activating PLD1 have the same inhibitory effects on early events in membrane fusion. However, mutant SCAMP2 also uniquely inhibits fusion pore dilation. Thus, SCAMP2 couples Arf6-stimulated PLD activity to exocytosis and links this process to formation of fusion pores.
Molecular Interactions Position Mso1p, a Novel PTB Domain Homologue, in the Interface of the Exocyst Complex and the Exocytic SNARE Machinery in Yeast
Authors: Knop Michael , Miller K. Juha , Mazza Massimiliano , Feng DeJiang , Weber Marion , Keränen Sirkka , Jäntti Jussi
Published: July 2005

In this study, we have analyzed the association of the Sec1p interacting protein Mso1p with the membrane fusion machinery in yeast. We show that Mso1p is essential for vesicle fusion during prospore membrane formation. Green fluorescent protein-tagged Mso1p localizes to the sites of exocytosis and at the site of prospore membrane formation. In vivo and in vitro experiments identified a short amino-terminal sequence in Mso1p that mediates its interaction with Sec1p and is needed for vesicle fusion. A point mutation, T47A, within the Sec1p-binding domain abolishes Mso1p functionality in vivo, and mso1T47A mutant cells display specific genetic interactions with sec1 mutants. Mso1p coimmunoprecipitates with Sec1p, Sso1/2p, Snc1/2p, Sec9p, and the exocyst complex subunit Sec15p. In sec4-8 and SEC4I133 mutant cells, association of Mso1p with Sso1/2p, Snc1/2p, and Sec9p is affected, whereas interaction with Sec1p persists. Furthermore, in SEC4I133 cells the dominant negative Sec4I133p coimmunoprecipitates with Mso1p–Sec1p complex. Finally, we identify Mso1p as a homologue of the PTB binding domain of the mammalian Sec1p binding Mint proteins. These results position Mso1p in the interface of the exocyst complex, Sec4p, and the SNARE machinery, and reveal a novel layer of molecular conservation in the exocytosis machinery.
APC and EB1 Function Together in Mitosis to Regulate Spindle Dynamics and Chromosome Alignment
Authors: Green Rebecca A. , Wollman Roy , Kaplan Kenneth B.
Published: July 2005

Recently, we have shown that a cancer causing truncation in adenomatous polyposis coli (APC) (APC1–1450) dominantly interferes with mitotic spindle function, suggesting APC regulates microtubule dynamics during mitosis. Here, we examine the possibility that APC mutants interfere with the function of EB1, a plus-end microtubule-binding protein that interacts with APC and is required for normal microtubule dynamics. We show that siRNA-mediated inhibition of APC, EB1, or APC and EB1 together give rise to similar defects in mitotic spindles and chromosome alignment without arresting cells in mitosis; in contrast inhibition of CLIP170 or LIS1 cause distinct spindle defects and mitotic arrest. We show that APC1–1450acts as a dominant negative by forming a hetero-oligomer with the full-length APC and preventing it from interacting with EB1, which is consistent with a functional relationship between APC and EB1. Live-imaging of mitotic cells expressing EB1-GFP demonstrates that APC1–1450compromises the dynamics of EB1-comets, increasing the frequency of EB1-GFP pausing. Together these data provide novel insight into how APC may regulate mitotic spindle function and how errors in chromosome segregation are tolerated in tumor cells.
Regulation of Interleukin-6 Promoter Activation in Gastric Epithelial Cells Infected withHelicobacter pylori
Authors: Lu Hong , Wu Jeng Yih , Kudo Takahiko , Ohno Tomoyuki , Graham David Y. , Yamaoka Yoshio
Published: July 2005

The regulation of Helicobacter pylori induced interleukin (IL)-6 in the gastric epithelium remains unclear. Primary gastric epithelial cells and MKN28 cells were cocultured with H. pylori and its isogenic cag pathogenicity island (PAI) mutant and/or oipA mutants. H. pylori infection-induced IL-6 mRNA expression and IL-6 protein production, which was further enhanced by the cag PAI and OipA. Luciferase reporter gene assays and electrophoretic mobility shift assays showed that full IL-6 transcription required binding sites for nuclear factor-κB (NF-κB), cAMP response element (CRE), CCAAT/enhancer binding protein (C/EBP), and activator protein (AP)-1. The cag PAI and OipA were involved in binding to NF-κB, AP-1, CRE, and C/EBP sites. The cag PAI activated the extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) pathways; OipA activated the p38 pathway. Transfection of dominant negative G-protein confirmed roles for Raf, Rac1, and RhoA in IL-6 induction. Overall, the cag PAI-related IL-6 signal transduction pathway involved the Ras/Raf/MEK1/2/ERK/AP-1/CRE pathway and the JNK/AP-1/CRE pathway; the OipA-related pathway is p38/AP-1/CRE and both the cag PAI and OipA appear to be involved in the RhoA/Rac1/NF-κB pathway. Combination of different pathways by the cag PAI and OipA will lead to the maximum IL-6 induction.
Identification ofHistoplasma capsulatumTranscripts Induced in Response to Reactive Nitrogen Species
Authors: Nittler M. Paige , Hocking-Murray Davina , Foo Catherine K. , Sil Anita
Published: July 2005

The pathogenic fungus Histoplasma capsulatum escapes innate immune defenses and colonizes host macrophages during infection. After the onset of adaptive immunity, the production of the antimicrobial effector nitric oxide (.NO) restricts H. capsulatum replication. However, H. capsulatum can establish persistent infections, indicating that it survives in the host despite exposure to reactive nitrogen species (RNS). To understand how H. capsulatum responds to RNS, we determined the transcriptional profile of H. capsulatum to.NO-generating compounds using a shotgun genomic microarray. We identified 695 microarray clones that were induced ≥4-fold upon nitrosative stress. Because our microarray clones were generated from random fragments of genomic DNA, they did not necessarily correspond to H. capsulatum open reading frames. To identify induced genes, we used high-density oligonucleotide tiling arrays to determine the genomic boundaries and coding strand of 153 RNS-induced transcripts. Homologues of these genes in other organisms are involved in iron acquisition, energy production, stress response, protein folding/degradation, DNA repair, and.NO detoxification. Ectopic expression of one of these genes, a P450 nitric oxide reductase homologue, was sufficient to increase resistance of H. capsulatum to RNS in culture. We propose that H. capsulatum uses the pathways identified here to cope with RNS-induced damage during pathogenesis.
Transcriptional Response ofCandida albicansto Nitric Oxide and the Role of theYHB1Gene in Nitrosative Stress and Virulence
Authors: Hromatka Bethann S. , Noble Suzanne M. , Johnson Alexander D.
Published: July 2005

Here, we investigate how Candida albicans, the most prevalent human fungal pathogen, protects itself from nitric oxide (.NO), an antimicrobial compound produced by the innate immune system. We show that exposure of C. albicans to.NO elicits a reproducible and specific transcriptional response as determined by genome-wide microarray analysis. Many genes are transiently induced or repressed by.NO, whereas a set of nine genes remain at elevated levels during.NO exposure. The most highly induced gene in this latter category is YHB1, a flavohemoglobin that detoxifies.NO in C. albicans and other microbes. We show that C. albicans strains deleted for YHB1 have two phenotypes in vitro; they are hypersensitive to.NO and they are hyperfilamentous. In a mouse model of disseminated candidiasis, a YHB1 deleted C. albicans strain shows moderately attenuated virulence, but the virulence defect is not suppressed by deletion of the host NOS2 gene. These results suggest that.NO production is not a prime determinant of virulence in the mouse tail vein model of candidiasis and that the attenuated virulence of a yhb1Δ/yhb1Δ strain is attributable to a defect other than its reduced ability to detoxify.NO.
Transformation of an edible crop with the pagA gene of Bacillus anthracis
Authors: Aziz Mohd. Azhar , Sikriwal Deepa , Singh Samer , Jarugula Sridhar , Anand Kumar P. , Bhatnagar Rakesh
Published: July 2005

Vaccination against anthrax is the most important strategy to combat the disease. This study describes a generation of edible transgenic crop expressing, functional protective antigen (PA). In vitro studies showed that the plant‐expressed antigen is qualitatively similar to recombinant PA. Immunization studies in mouse animal models indicated the generation of PA‐specific neutralizing antibodies and stressed the need for improving expression levels to generate higher antibody titers. Genetic engineering of a plant organelle offers immense scope for increasing levels of antigen expression. An AT‐rich PA gene (pagA) coding for the 83‐kDa PA molecule was thus cloned and expressed in tobacco chloroplasts. Biolistics was used for the transformation of a chloroplast genome under a set of optimized conditions. The expression of the pagA gene with 69% AT content was highly favored by an AT‐rich chloroplast genome. A multifold expression level of functional PA was obtained as compared with the nuclear transgenic tobacco plants. This report describes for the first time a comprehensive study on generating transgenic plants expressing PA, which may serve as a source of an edible vaccine against anthrax. Two important achievements of expressing PA in an edible crop and use of chloroplast technology to enhance the expression levels are discussed here.
Characterization of the E-138 (Glu/Lys) mutation in Japanese encephalitis virus by using a stable, full-length, infectious cDNA clone
Authors: Zhao Zijiang , Date Tomoko , Li Yuhua , Kato Takanobu , Miyamoto Michiko , Yasui Kotaro , Wakita Takaji
Published: July 2005

A stable plasmid DNA, pMWJEAT, was constructed by using full-length Japanese encephalitis virus (JEV) cDNA isolated from the wild-type strain JEV AT31. Recombinant JEV was obtained by synthetic RNA transfection into Vero cells and designated rAT virus. JEV rAT exhibited similar large-plaque morphology and antigenicity to the parental AT31 strain. Mutant clone pMWJEAT-E138K, containing a single Glu-to-Lys mutation at aa 138 of the envelope (E) protein, was also constructed to analyse the mechanisms of viral attenuation arising from this mutation. Recombinant JEV rAT-E138K was also recovered and displayed a smaller-plaque morphology and lower neurovirulence and neuroinvasiveness than either AT31 virus or rAT virus. JEV rAT-E138K exhibited greater plaque formation than rAT virus in virus–cell interactions under acidic conditions. Heparin or heparinase III treatment inhibited binding to Vero cells more efficiently for JEV rAT-E138K than for rAT virus. Inhibition of virus–cell interactions by using wheatgerm agglutinin was more effective for JEV rAT than for rAT-E138K on Vero cells. About 20 % of macropinoendocytosis of JEV rAT for Vero cells was inhibited by cytochalasin D treatment, but no such inhibition occurred for rAT-E138K virus. Furthermore, JEV rAT was predominantly secreted from infected cells, whereas rAT-E138K was more likely to be retained in infected cells. This study demonstrates clearly that a single Glu-to-Lys mutation at aa 138 of the envelope protein affects multiple steps of the viral life cycle. These multiple changes may induce substantial attenuation of JEV.
Regulation of polymeric immunoglobulin receptor expression by reovirus
Authors: Pal Kasturi , Kaetzel Charlotte S. , Brundage Kathleen , Cunningham Cynthia A. , Cuff Christopher F.
Published: July 2005

Polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA and IgA-coated immune complexes from the lamina propria across epithelia and into secretions. The effect of reovirus infection on regulation of pIgR expression in the human intestinal epithelial cell line HT-29 was characterized in this report. Both replication-competent and UV-inactivated reovirus at m.o.i. equivalents of 1–100 p.f.u. per cell upregulated pIgR mRNA by 24 h post-infection and intracellular pIgR protein was increased at 48 h following exposure to UV-inactivated virus. Binding of virus to HT-29 cells was required, as pre-incubating virus with specific antiserum, but not non-immune serum, inhibited reovirus-mediated pIgR upregulation. Endosomal acidification leading to uncoating of virus is a required step for pIgR upregulation, as ammonium chloride or bafilomycin A1 pre-treatment inhibited virus-induced pIgR upregulation. Inhibition experiments using the calpain inhibitorN-acetyl-leucyl-leucyl-norleucinal suggested that calpains are involved in reovirus-mediated pIgR upregulation. Upregulation of pIgR following virus infection appears to be an innate immune response against invading pathogens that could help the host clear infection effectively. Signalling induced by microbes and their products may serve to augment pIgR-mediated transcytosis of IgA, linking the innate and acquired immune responses to viruses.
Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity
Authors: Bergmeier Lesley A. , Babaahmady Kaboutar , Wang Yufei , Lehner Thomas
Published: July 2005

The hypothesis was tested that mucosal stimulation with unmatched mononuclear cells would induce systemic alloimmune responses. Rectal or vaginal mucosal administration of 104–107 unmatched mononuclear cells induced significant dose-dependent T-cell proliferation stimulated by the allogeneic cells in rhesus macaques. This was associated with a significant upregulation of CD8+ T-cell-derived suppressor factor, as well as the CC chemokines CCL3, CCL4 and CCL5. In addition, there was a dose-dependent increase in antibodies to CCR5. These responses were associated with decreased in vitro simian immunodeficiency virus (SIV) infectivity of CD4+ T cells. A further investigation of SIV infectivity of CD4+ T cells separated from multiparous macaques also showed significant inhibition compared with male macaques. It is suggested that vaginal or rectal exposure to allogeneic stimulation by a partner's HLA antigens in seminal fluid, as occurs during sexual intercourse, or immunization by semi-allogeneic fetuses in multiparous females may elicit protection against SIV or human immunodeficiency virus infection.
Modifications of both selectivity factor and upstream binding factor contribute to poliovirus-mediated inhibition of RNA polymerase I transcription
Authors: Banerjee Rajeev , Weidman Mary K. , Navarro Sonia , Comai Lucio , Dasgupta Asim
Published: July 2005

Soon after infection, poliovirus (PV) shuts off host-cell transcription, which is catalysed by all three cellular RNA polymerases. rRNA constitutes more than 50 % of all cellular RNA and is transcribed from rDNA by RNA polymerase I (pol I). Here, evidence has been provided suggesting that both pol I transcription factors, SL-1 (selectivity factor) and UBF (upstream binding factor), are modified and inactivated in PV-infected cells. The viral protease 3Cproappeared to cleave the TATA-binding protein-associated factor 110 (TAF110), a subunit of the SL-1 complex, into four fragmentsin vitro.In vitroprotease-cleavage assays using various mutants of TAF110and purified 3Cproindicated that the Q265G266and Q805G806sites were cleaved by 3Cpro. Both SL-1 and UBF were depleted in PV-infected cells and their disappearance correlated with pol I transcription inhibition. rRNA synthesis from a template containing a human pol I promoter demonstrated that both SL-1 and UBF were necessary to restore pol I transcription fully in PV-infected cell extracts. These results suggested that both SL-1 and UBF are transcriptionally inactivated in PV-infected HeLa cells.
Intricate transmission routes and interactions between picorna-like viruses (Kashmir bee virus and sacbrood virus) with the honeybee host and the parasitic varroa mite
Authors: Shen Miaoqing , Cui Liwang , Ostiguy Nancy , Cox-Foster Diana
Published: July 2005

Viral diseases of honeybees are a major problem in apiculture, causing serious economic losses worldwide, especially in combination with varroa mites. To increase understanding of the relationship among viruses, mites and colony decline, the tripartite relationships among bees, viruses [Kashmir bee virus (KBV) and sacbrood virus (SBV)] and varroa mites have been investigated systematically. To develop an antibody-based test for KBV, two structural recombinant proteins were purified for polyclonal-antibody production. By using ELISA and RT-PCR, the presence of KBV and SBV was studied comparatively in different developmental stages and castes of bees. The results demonstrated that KBV may persist as a viral genome with extremely low levels of viral-capsid proteins and that KBV and SBV can co-infect honeybees. This study indicated the presence of KBV and SBV RNAs in both queens and eggs by RT-PCR, suggesting a route of transovarial transmission. Horizontal transmission is also very likely among adult bees and from adult workers to larvae through contaminated food resources, because both viruses have been detected in all developmental stages and food sources (brood food, honey, pollen and royal jelly). Furthermore, it was demonstrated that mites were another possible route of horizontal transmission, as both viruses were detected in mites and their saliva. This study, for the first time, detected co-occurrence of viruses in varroa, further underlining the importance of the mites in vectoring different bee viruses. Therefore, these results indicated that multiple infection routes exist for honeybee viral diseases.
Hepatitis C virus NS3 protein interacts with ELKS-δ and ELKS-α, members of a novel protein family involved in intracellular transport and secretory pathways
Authors: Hidajat Rachmat , Nagano-Fujii Motoko , Deng Lin , Tanaka Motofumi , Takigawa Yuki , Kitazawa Sohei , Hotta Hak
Published: July 2005

The NS3 protein of hepatitis C virus (HCV) has a serine protease activity in its N-terminal region, which plays a crucial role in virus replication. This region has also been reported to interact not only with its viral cofactor NS4A, but also with a number of host-cell proteins, which suggests a multifunctional feature of NS3. By means of yeast two-hybrid screening using an N-terminal region of NS3 as bait, a human cDNA encoding a region of ELKS-δ, a member of a novel family of proteins involved in intracellular transport and secretory pathways, was molecularly cloned. Using co-immunoprecipitation, GST pull-down and confocal and immunoelectron microscopic analyses, it was shown that full-length NS3 interacted physically with full-length ELKS-δ and its splice variant, ELKS-α, both in the absence and presence of NS4A, in cultured human cells, including Huh-7 cells harbouring an HCV subgenomic RNA replicon. The degree of binding to ELKS-δ varied with different sequences of the N-terminal 180 residues of NS3. Interestingly, NS3, either full-length or N-terminal fragments, enhanced secretion of secreted alkaline phosphatase (SEAP) from the cells, and the increase in SEAP secretion correlated well with the degree of binding between NS3 and ELKS-δ. Taken together, these results suggest the possibility that NS3 plays a role in modulating host-cell functions such as intracellular transport and secretion through its binding to ELKS-δ and ELKS-α, which may facilitate the virus life cycle and/or mediate the pathogenesis of HCV.
Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2
Authors: Naas Turaya , Ghorbani Masoud , Alvarez-Maya Ikuri , Lapner Michael , Kothary Rashmi , De Repentigny Yves , Gomes Susantha , Babiuk Lorne , Giulivi Antonio , Soare Catalina , Azizi Ali , Diaz-Mitoma Francisco
Published: July 2005

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma worldwide. The purpose of this study was to determine how the HCV structural proteins affect the dynamic structural and functional properties of hepatocytes and measure the extra-hepatic manifestations induced by these viral proteins. A transgenic mouse model was established by expressing core, E1 and E2 proteins downstream of a CMV promoter. HCV RNA was detected using RT-PCR in transgenic mouse model tissues, such as liver, kidney, spleen and heart. Expression of the transgene was analysed by real-time PCR to quantify viral RNA in different tissues at different ages. Immunofluorescence analysis revealed the expression of core, E1 and E2 proteins predominantly in hepatocytes. Lower levels of protein expression were detected in spleen and kidneys. HCV RNA and viral protein expression increased in the liver with age. Histological analysis of liver cells demonstrated steatosis in transgenic mice older than 3 months, which was more progressed with age. Electron microscopy analysis revealed alterations in nuclei, mitochondria and endoplasmic reticulum. HCV structural proteins induce a severe hepatopathy in the transgenic mouse model. These mice became more prone to liver and lymphoid tumour development and hepatocellular carcinoma. In this model, the extra-hepatic effects of HCV, which included swelling of renal tubular cells, were mild. It is likely that the HCV structural proteins mediate some of the histological alterations in hepatocytes by interfering with lipid transport and liver metabolism.
Evidence for recombination in Crimean-Congo hemorrhagic fever virus
Authors: Lukashev Alexander N.
Published: July 2005

Crimean-Congo hemorrhagic fever (CCHF) virus has attracted considerable attention recently and a number of phylogenetic studies have been published, based mostly on partial sequences of S and M RNA segments. In this study, available full-length S, M and L segment sequences of CCHF virus were checked for recombination. Similarity plots and bootscan analysis of the S segment suggested multiple recombination events between southern European, Asian and African CCHF virus strains, with additional evidence provided by phylogenetic trees, the hidden Markov model and probabilistic divergence measures methods. No unambiguous signs of recombination were observed for M and L segments; however, the results did not exclude the possibility of this. These findings, coupled with a recent report on reassortment in CCHF virus, suggest caution when assessing CCHF virus phylogeny based on short sequence fragments.
Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells
Authors: Calvo E. , Escors D. , López J. A. , González J. M. , álvarez A. , Arza E. , Enjuanes L.
Published: July 2005

The nucleocapsid (N) protein is the only phosphorylated structural protein of the coronavirus Transmissible gastroenteritis virus (TGEV). The phosphorylation state and intracellular distribution of TGEV N protein in infected cells were characterized by a combination of techniques including: (i) subcellular fractionation and analysis of tryptic peptides by two-dimensional nano-liquid chromatography, coupled to ion-trap mass spectrometry; (ii) tandem mass-spectrometry analysis of N protein resolved by SDS-PAGE; (iii) Western blotting using two specific antisera for phosphoserine-containing motifs; and (iv) confocal microscopy. A total of four N protein-derived phosphopeptides were detected in mitochondria–Golgi–endoplasmic reticulum–Golgi intermediate compartment (ERGIC)-enriched fractions, including N-protein phosphoserines 9, 156, 254 and 256. Confocal microscopy showed that the N protein found in mitochondria–Golgi–ERGIC fractions localized within the Golgi–ERGIC compartments and not with mitochondria. Phosphorylated N protein was also present in purified virions, containing at least phosphoserines 156 and 256. Coronavirus N proteins showed a conserved pattern of secondary structural elements, including six β-strands and four α-helices. Whilst serine 9 was present in a non-conserved domain, serines 156, 254 and 256 were localized close to highly conserved secondary structural elements within the central domain of coronavirus N proteins. Serine 156 was highly conserved, whereas no clear homologous sites were found for serines 254 and 256 for other coronavirus N proteins.
Genomic RNA sequence of Feline coronavirus strain FIPV WSU-79/1146
Authors: Dye Charlotte , Siddell Stuart G.
Published: July 2005

A consensus sequence of the Feline coronavirus (FCoV) (strain FIPV WSU-79/1146) genome was determined from overlapping cDNA fragments produced by RT-PCR amplification of viral RNA. The genome was found to be 29 125 nt in length, excluding the poly(A) tail. Analysis of the sequence identified conserved open reading frames and revealed an overall genome organization similar to that of other coronaviruses. The genomic RNA was analysed for putative cis-acting elements and the pattern of subgenomic mRNA synthesis was analysed by Northern blotting. Comparative sequence analysis of the predicted FCoV proteins identified 16 replicase proteins (nsp1–nsp16) and four structural proteins (spike, membrane, envelope and nucleocapsid). Two mRNAs encoding putative accessory proteins were also detected. Phylogenetic analyses confirmed that FIPV WSU-79/1146 belongs to the coronavirus subgroup G1-1. These results confirm and extend previous findings from partial sequence analysis of FCoV genomes.