bluuebunny/crossref_metadata_2025 huggingface dataset:
A geometric construction determines all permissible strand arrangements of sandwich proteins
Authors: Fokas A. S. , Papatheodorou T. S. , Kister A. E. , Gelfand I. M.
Published: October 2005

For a large class of proteins called sandwich-like proteins (SPs), the secondary structures consist of two β-sheets packed face-to-face, with each β-sheet consisting typically of three to five β-strands. An important step in the prediction of the three-dimensional structure of a SP is the prediction of its supersecondary structure, namely the prediction of the arrangement of the β-strands in the two β-sheets. Recently, significant progress in this direction was made, where it was shown that 91% of observed SPs form what we here call “canonical motifs.” Here, we show that all canonical motifs can be constructed in a simple manner that is based on thermodynamic considerations and uses certain geometric structures. The number of these structures is much smaller than the number of possible strand arrangements. For instance, whereas for SPs consisting of six strands there exist
a priori
900 possible strand arrangements, there exist only five geometric structures. Furthermore, the few motifs that are noncanonial can be constructed from canonical motifs by a simple procedure.
Pore conformations and gating mechanism of a Cys-loop receptor
Authors: Paas Yoav , Gibor Gilad , Grailhe Regis , Savatier-Duclert Nathalie , Dufresne Virginie , Sunesen Morten , de Carvalho Lia Prado , Changeux Jean-Pierre , Attali Bernard
Published: October 2005

Neurons regulate the propagation of chemoelectric signals throughout the nervous system by opening and closing ion channels, a process known as gating. Here, histidine-based metal-binding sites were engineered along the intrinsic pore of a chimeric Cys-loop receptor to probe state-dependent Zn
2+
-channel interactions. Patterns of Zn
2+
ion binding within the pore reveal that, in the closed state, the five pore-lining segments adopt an oblique orientation relative to the axis of ion conduction and constrict into a physical gate at their intracellular end. The interactions of Zn
2+
with the open state indicate that the five pore-lining segments should rigidly tilt to enable the movement of their intracellular ends away from the axis of ion conduction, so as to open the constriction (i.e., the gate). Alignment of the functional results with the 3D structure of an acetylcholine receptor allowed us to generate structural models accounting for the closed and open pore conformations and for a gating mechanism of a Cys-loop receptor.
Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa
Authors: Ramachandran Sohini , Deshpande Omkar , Roseman Charles C. , Rosenberg Noah A. , Feldman Marcus W. , Cavalli-Sforza L. Luca
Published: October 2005

Equilibrium models of isolation by distance predict an increase in genetic differentiation with geographic distance. Here we find a linear relationship between genetic and geographic distance in a worldwide sample of human populations, with major deviations from the fitted line explicable by admixture or extreme isolation. A close relationship is shown to exist between the correlation of geographic distance and genetic differentiation (as measured by
F
ST
) and the geographic pattern of heterozygosity across populations. Considering a worldwide set of geographic locations as possible sources of the human expansion, we find that heterozygosities in the globally distributed populations of the data set are best explained by an expansion originating in Africa and that no geographic origin outside of Africa accounts as well for the observed patterns of genetic diversity. Although the relationship between
F
ST
and geographic distance has been interpreted in the past as the result of an equilibrium model of drift and dispersal, simulation shows that the geographic pattern of heterozygosities in this data set is consistent with a model of a serial founder effect starting at a single origin. Given this serial-founder scenario, the relationship between genetic and geographic distance allows us to derive bounds for the effects of drift and natural selection on human genetic variation.
Structure of the metal-independent restriction enzyme BfiI reveals fusion of a specific DNA-binding domain with a nonspecific nuclease
Authors: Grazulis Saulius , Manakova Elena , Roessle Manfred , Bochtler Matthias , Tamulaitiene Giedre , Huber Robert , Siksnys Virginijus
Published: October 2005

Among all restriction endonucleases known to date, BfiI is unique in cleaving DNA in the absence of metal ions. BfiI represents a different evolutionary lineage of restriction enzymes, as shown by its crystal structure at 1.9-Å resolution. The protein consists of two structural domains. The N-terminal catalytic domain is similar to Nuc, an EDTA-resistant nuclease from the phospholipase D superfamily. The C-terminal DNA-binding domain of BfiI exhibits a β-barrel-like structure very similar to the effector DNA-binding domain of the Mg
2+
-dependent restriction enzyme EcoRII and to the B3-like DNA-binding domain of plant transcription factors. BfiI presumably evolved through domain fusion of a DNA-recognition element to a nonspecific nuclease akin to Nuc and elaborated a mechanism to limit DNA cleavage to a single double-strand break near the specific recognition sequence. The crystal structure suggests that the interdomain linker may act as an autoinhibitor controlling BfiI catalytic activity in the absence of a specific DNA sequence. A
psi-blast
search identified a BfiI homologue in a
Mesorhizobium
sp. BNC1 bacteria strain, a plant symbiont isolated from an EDTA-rich environment.
Essential role of Shp2-binding sites on FRS2α for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells
Authors: Yamamoto S. , Yoshino I. , Shimazaki T. , Murohashi M. , Hevner R. F. , Lax I. , Okano H. , Shibuya M. , Schlessinger J. , Gotoh N.
Published: October 2005

Mammalian corticogenesis occurs through a complex process that includes neurogenesis, in which neural progenitor cells proliferate, differentiate, and migrate. It has been reported recently that neurogenesis occurs in the subventricular zone (SVZ), a region previously thought to be the primary site of gliogenesis. It has been recognized that in the SVZ, intermediate progenitor cells, derived from radial glial cells that are multipotent neural stem cells, produce only neurons. However, the molecular mechanisms underlying the regulation of neural stem cells and intermediate progenitor cells as well as their contribution to overall corticogenesis remain unknown. The docking protein FRS2α is a major mediator of signaling by means of FGFs and neurotrophins. FRS2α mediates many of its pleiotropic cellular responses by recruiting the adaptor protein Grb2 and the protein tyrosine phosphatase Shp2 upon ligand stimulation. Here, we report that targeted disruption of Shp2-binding sites in FRS2α leads to severe impairment in cerebral cortex development in mutant mice. The defect in corticogenesis appears to be due at least in part to abnormalities in intermediate progenitor cells. Genetic evidence is provided that FRS2α plays critical roles in the maintenance of intermediate progenitor cells and in neurogenesis in the cerebral cortex. Moreover, FGF2-responsive neurospheres, which are cell aggregates derived from neural stem/progenitor cells (NSPCs), from FRS2α mutant mice were smaller than those of WT mice. However, mutant NSPCs were able to self-renew, demonstrating that Shp2-binding sites on FRS2α play an important role in NSPC proliferation but are dispensable for NSPC self-renewing capacity after FGF2 stimulation.
Regulation of the
Caenorhabditis elegans
oxidative stress defense protein SKN-1 by glycogen synthase kinase-3
Authors: An Jae Hyung , Vranas Kelly , Lucke Michael , Inoue Hideki , Hisamoto Naoki , Matsumoto Kunihiro , Blackwell T. Keith
Published: October 2005

Oxidative stress plays a central role in many human diseases and in aging. In
Caenorhabditis elegans
the SKN-1 protein induces phase II detoxification gene transcription, a conserved oxidative stress response, and is required for oxidative stress resistance and longevity. Oxidative stress induces SKN-1 to accumulate in intestinal nuclei, depending on p38 mitogen-activated protein kinase signaling. Here we show that, in the absence of stress, phosphorylation by glycogen synthase kinase-3 (GSK-3) prevents SKN-1 from accumulating in nuclei and functioning constitutively in the intestine. GSK-3 sites are conserved in mammalian SKN-1 orthologs, indicating that this level of regulation may be conserved. If inhibition by GSK-3 is blocked, background levels of p38 signaling are still required for SKN-1 function. WT and constitutively nuclear SKN-1 comparably rescue the
skn-1
oxidative stress sensitivity, suggesting that an inducible phase II response may provide optimal stress protection. We conclude that (
i
) GSK-3 inhibits SKN-1 activity in the intestine, (
ii
) the phase II response integrates multiple regulatory signals, and (
iii
), by inhibiting this response, GSK-3 may influence redox conditions.
The role of TNF-α in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: Analysis of dendritic cell maturation
Authors: Lee Li-Fen , Xu Baohui , Michie Sara A. , Beilhack Georg F. , Warganich Tibor , Turley Shannon , McDevitt Hugh O.
Published: October 2005

TNF-α has been linked to the development of type 1 diabetes (T1D). We previously reported that neonatal treatment of nonobese diabetic (NOD) mice with TNF-α accelerated the onset of T1D, whereas TNF-α blockade in the same time period resulted in a complete absence of diabetes. The mechanisms by which TNF-α modulates development of T1D in NOD mice remain unclear. Here we tested the effects of TNF-α on the maturation of dendritic cells (DCs) in the NOD mouse. We found that neonatal treatment with TNF-α caused an increase in expression of maturation markers on CD11c+CD11b+DC subpopulations, whereas treatment with anti-TNF-α resulted in a decrease in expression of maturation markers in the CD11c+CD11b+subset. Moreover, neonatal treatment with TNF-α resulted in skewed development of a CD8α+CD11b-CD11c+DC subset such that TNF-α decreases the CD8α+CD11c+DC subset, increases the CD11c+CD11b+subset, and causes an increase in the expression of CD40 and CD54 on mature DCs capable of inducing immunity. Anti-TNF-α-treated mice had an increase in the CD8α+CD11c+DCs. Notably, adoptively transferred naïve CD4+T cells from BDC2.5 T cell receptor transgenic mice proliferated in the pancreatic lymph nodes in TNF-α-treated NOD mice but not in anti-TNF-α-treated mice. Finally, we show that anti-TNF-α-treated mice showed immunological tolerance to islet cell proteins. We conclude that TNF-α plays an important role in the initiation of T1D in the NOD mouse by regulating the maturation of DCs and, thus, the activation of islet-specific pancreatic lymph node T cells.
A model of anthrax toxin lethal factor bound to protective antigen
Authors: Lacy D. Borden , Lin Henry C. , Melnyk Roman A. , Schueler-Furman Ora , Reither Laura , Cunningham Kristina , Baker David , Collier R. John
Published: October 2005

Anthrax toxin is made up of three proteins: the edema factor (EF), lethal factor (LF) enzymes, and the multifunctional protective antigen (PA). Proteolytically activated PA heptamerizes, binds the EF/LF enzymes, and forms a pore that allows for EF/LF passage into host cells. Using directed mutagenesis, we identified three LF-PA contact points defined by a specific disulfide crosslink and two pairs of complementary charge-reversal mutations. These contact points were consistent with the lowest energy LF-PA complex found by using Rosetta protein-protein docking. These results illustrate how biochemical and computational methods can be combined to produce reliable models of large complexes. The model shows that EF and LF bind through a highly electrostatic interface, with their flexible N-terminal region positioned at the entrance of the heptameric PA pore and thus poised to initiate translocation in an N- to C-terminal direction.
Poverty reduction strategy papers: Now who calls the shots?
Authors: Fraser Alastair
Published: October 2005

This paper argues that Poverty Reduction Strategy Papers (PRSPs) can be understood as a technology of ‘social control’, which seeks to shape domestic political space. Despite widespread recognition that the World Bank and the IMF continue to impose orthodox policy conditions on debt relief and loans to African countries, many suggest the requirement in PRSPs for civil society ‘participation’ introduces a progressive element that could, in time, subvert the logic of coercion. In contrast, this paper suggests that it is precisely through participation that international Non-Governmental Organisations (NGOs) and bilateral donors are working with the IFIs** to secure ever more intimate supervision of African political communities. Thus, if the answer to Hanlon's (1991) rhetorical question ‘who calls the shots?’ under structural adjustment was ‘the IFIs’, the answer under PRSPs is ‘an uneasy coalition of NGOs, donors and the IFIs’. These groups share an agenda of securing consent to liberal systems of political and economic management. Through the PRSP and related processes they divide the labour required to manufacture consent, seeking to build ‘reform coalitions’ by transforming the objectives and nature of states, bureaucracies, social and political movements and, at their most ambitious, populations. In the process they imperil African sovereignty, self-determination and hopes for substantive democracy.

** Editor's Note: International financial institutions (IFIs) are public banks, using taxpayer money to invest in countries outside their borders, often in the name of fostering economic development, at home or abroad. Many of these IFIs are also large backers of fossil fuel projects around the world. They include both multilateral and bilateral development banks and export credit agencies.
Development denied: Autocratic militarism in post-election Zimbabwe
Authors: Bracking Sarah
Published: October 2005

This article examines the recent ideological position of ‘Vote for Development’ which the ZANU-PF government in Zimbabwe pursued during the election campaign of March 2005, and the brief period of freer expression that accompanied the campaign. This strategy of power, the willingness to seemingly embrace democratic process, is then compared with the postelection situation in Zimbabwe, where despite having entrenched themselves in government, the ZANU-PF leadership is conducting a campaign to destroy the infrastructural, physical, economic and social assets of the urban poor. I review the ‘Operation Restore Order’ against informal traders, and the ‘Operation Murambatsvina’ (‘Operation Clear Away the Trash’ – or grime, rubbish, filth) of 25 May to early July 2005 against peoples homes, and ask how we can categorise the Zimbabwean state in its contemporary, seemingly contradictory, form.
Violence & social order beyond the state: Somalia & Angola
Authors: Bakonyi Jutta , Stuvøy Kirsti
Published: October 2005

This paper examines the activities of non-state actors in war in Somalia and Angola. Arguing that prolonged wars are characterised by the emergence of social orders of violence beyond the state, our analytical focus is on how actors establish and sustain these orders. A core influence is the insight from research on war economies that war is not equal to the breakdown of societal order, but represents an alternative form of social order. We therefore examine the economic activities of insurgents in regard to their embeddedness in social and political spheres. The central question in this paper is how economic, political and symbolic aspects interact and determine as well as transform social orders of violence. With the examples of Somalia and Angola, two rather distinct cases of non-state orders of violence are examined. It is argued that these orders represent forms of authority with fundamental structural aspects in common. We suggest that these orders can be systematised on a continuum between two poles of institutionalisation of authority beyond the state: a warlord system and a quasi-state system of violence.
Identifying How Trade Matters in Empirical Studies of Interstate Conflict
Authors: Hegre Havard
Published: October 2005

Gartzke and Li (2003b) formulate a mathematical relationship between “trade share,” “trade dependence,” and “trade openness,” and use this to argue that the disparity between the findings in studies by Barbieri and those of Oneal and Russett and others can partly be explained by features of variable construction. This article argues that although Gartzke and Li's formulation is very useful, the authors draw some conclusions from their analysis that only hold under very restrictive assumptions. “Trade share” does not in general measure a state's disconnectedness from the world trading system, and “trade share” is not associated with a high risk of interstate dispute if “trade dependence” is associated with a low risk. What Gartzke and Li attribute to “trade share” is rather an effect of trade substition from one partner to another. Finally, the trade openness variable may be a proxy for country size. The discussion also illustrates some problems involved in controlling for variables that are related by definition to a key explanatory variable.
Conflict Diamonds: A New Dataset
Authors: Gilmore Elisabeth , Gleditsch Nils Petter , Lujala Päivi , Ketil Rod Jan
Published: October 2005

Natural resources, and diamonds especially, are commonly believed to play a significant role in the onset and duration of armed civil conflict. Although there is ample case study evidence that diamonds and similar resources have been used by rebel groups to finance fighting, there are few systematic empirical studies assessing the role of lootable resources in civil conflict. This is largely due to lack of reliable data on production and location. In this article we discuss priorities for the collection of data on conflict-relevant resources and introduce a new dataset, DIADATA, that provides a comprehensive list of diamond deposits accompanied by geographic coordinates throughout the world. The dataset includes characteristics relevant to conflict such as production status and geological form of the deposit. Particularly important is the distinction between primary and secondary diamonds, because the latter are more easily lootable. The dataset incorporates a spatial as well as a temporal dimension.
A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans
Authors: Audhya Anjon , Hyndman Francie , McLeod Ian X. , Maddox Amy S. , Yates John R. , Desai Arshad , Oegema Karen
Published: October 2005

Cytokinesis completes cell division and partitions the contents of one cell to the two daughter cells. Here we characterize CAR-1, a predicted RNA binding protein that is implicated in cytokinesis. CAR-1 localizes to germline-specific RNA-containing particles and copurifies with the essential RNA helicase, CGH-1, in an RNA-dependent fashion. The atypical Sm domain of CAR-1, which directly binds RNA, is dispensable for CAR-1 localization, but is critical for its function. Inhibition of CAR-1 by RNA-mediated depletion or mutation results in a specific defect in embryonic cytokinesis. This cytokinesis failure likely results from an anaphase spindle defect in which interzonal microtubule bundles that recruit Aurora B kinase and the kinesin, ZEN-4, fail to form between the separating chromosomes. Depletion of CGH-1 results in sterility, but partially depleted worms produce embryos that exhibit the CAR-1–depletion phenotype. Cumulatively, our results suggest that CAR-1 functions with CGH-1 to regulate a specific set of maternally loaded RNAs that is required for anaphase spindle structure and cytokinesis.
The role of Fis1p–Mdv1p interactions in mitochondrial fission complex assembly
Authors: Karren Mary Anne , Coonrod Emily M. , Anderson Teresa K. , Shaw Janet M.
Published: October 2005

Mitochondrial division requires coordinated interactions among Fis1p, Mdv1p, and the Dnm1p GTPase, which assemble into fission complexes on the outer mitochondrial membrane. The integral outer membrane protein Fis1p contains a cytoplasmic domain consisting of a tetratricopeptide repeat (TPR)–like fold and a short NH2-terminal helix. Although it is known that the cytoplasmic domain is necessary for assembly of Mdv1p and Dnm1p into fission complexes, the molecular details of this assembly are not clear. In this study, we provide new evidence that the Fis1p–Mdv1p interaction is direct. Furthermore, we show that conditional mutations in the Fis1p TPR-like domain cause fission complex assembly defects that are suppressed by mutations in the Mdv1p-predicted coiled coil. We also define separable functions for the Fis1p NH2-terminal arm and TPR-like fold. These studies suggest that the concave binding surface of the Fis1p TPR-like fold interacts with Mdv1p during mitochondrial fission and that Mdv1p facilitates Dnm1p recruitment into functional fission complexes.
Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors
Authors: Gerbino Andrea , Ruder Warren C. , Curci Silvana , Pozzan Tullio , Zaccolo Manuela , Hofer Aldebaran M.
Published: October 2005

Termination of cyclic adenosine monophosphate (cAMP) signaling via the extracellular Ca2+-sensing receptor (CaR) was visualized in single CaR-expressing human embryonic kidney (HEK) 293 cells using ratiometric fluorescence resonance energy transfer–dependent cAMP sensors based on protein kinase A and Epac. Stimulation of CaR rapidly reversed or prevented agonist-stimulated elevation of cAMP through a dual mechanism involving pertussis toxin–sensitive Gαi and the CaR-stimulated increase in intracellular [Ca2+]. In parallel measurements with fura-2, CaR activation elicited robust Ca2+ oscillations that increased in frequency in the presence of cAMP, eventually fusing into a sustained plateau. Considering the Ca2+ sensitivity of cAMP accumulation in these cells, lack of oscillations in [cAMP] during the initial phases of CaR stimulation was puzzling. Additional experiments showed that low-frequency, long-duration Ca2+ oscillations generated a dynamic staircase pattern in [cAMP], whereas higher frequency spiking had no effect. Our data suggest that the cAMP machinery in HEK cells acts as a low-pass filter disregarding the relatively rapid Ca2+ spiking stimulated by Ca2+-mobilizing agonists under physiological conditions.
Norms and essential norms of linear combinations of endomorphisms
Authors: Gorkin Pamela , Mortini Raymond
Published: October 2005

We compute norms and essential norms of linear combinations of endomorphisms on uniform algebras.
Equivariant Gysin maps and pulling back fixed points
Authors: Hanke Bernhard , Puppe Volker
Published: October 2005

We develop a new approach to the pulling back fixed points theorem of W. Browder and use it in order to prove various generalizations of this result.
Some quotient Hopf algebras of the dual Steenrod algebra
Authors: Palmieri J.
Published: October 2005

Fix a prime

p
p

, and let

A
A

be the polynomial part of the dual Steenrod algebra. The Frobenius map on

A
A

induces the Steenrod operation

P

~

0

\widetilde {\mathscr {P}}^{0}

on cohomology, and in this paper, we investigate this operation. We point out that if

p
=
2

p=2

, then for any element in the cohomology of

A
A

, if one applies

P

~

0

\widetilde {\mathscr {P}}^{0}

enough times, the resulting element is nilpotent. We conjecture that the same is true at odd primes, and that “enough times” should be “once.” The bulk of the paper is a study of some quotients of

A
A

in which the Frobenius is an isomorphism of order

n
n

. We show that these quotients are dual to group algebras, the resulting groups are torsion-free, and hence every element in Ext over these quotients is nilpotent. We also try to relate these results to the questions about

P

~

0

\widetilde {\mathscr {P}}^{0}

. The dual complete Steenrod algebra makes an appearance.
Newton polygons and local integrability of negative powers of smooth functions in the plane
Authors: Greenblatt Michael
Published: October 2005

Let

f
(
x
,
y
)

f(x,y)

be any smooth real-valued function with

f
(
0
,
0
)
=
0

f(0,0)=0

. For a sufficiently small neighborhood

U
U

of the origin, we study the number
\[

sup

{
ϵ
:

∫
U

|

f
(
x
,
y
)

|

−
ϵ

>
∞
}

.

\sup \left \{\epsilon :\int _U |f(x,y)|^{-\epsilon }>\infty \right \}.

\]
It is known that sometimes this number can be expressed in a natural way using the Newton polygon of

f
f

. We provide necessary and sufficient conditions for this Newton polygon characterization to hold. The behavior of the integral at the supremal

ϵ
\epsilon

is also analyzed.
Multi-scale Young measures
Authors: Pedregal Pablo
Published: October 2005

We introduce multi-scale Young measures to deal with problems where multi-scale phenomena are relevant. We prove some interesting representation results that allow the use of these families of measures in practice, and illustrate its applicability by treating, from this perspective, multi-scale convergence and homogenization of multiple integrals.
The general hyperplane section of a curve
Authors: Gorla Elisa
Published: October 2005

In this paper, we discuss some necessary and sufficient conditions for a curve to be arithmetically Cohen-Macaulay, in terms of its general hyperplane section. We obtain a characterization of the degree matrices that can occur for points in the plane that are the general plane section of a non-arithmetically Cohen-Macaulay curve of

P

3

\mathbf {P}^3

. We prove that almost all the degree matrices with positive subdiagonal that occur for the general plane section of a non-arithmetically Cohen-Macaulay curve of

P

3

\mathbf {P}^3

, arise also as degree matrices of some smooth, integral, non-arithmetically Cohen-Macaulay curve, and we characterize the exceptions. We give a necessary condition on the graded Betti numbers of the general plane section of an arithmetically Buchsbaum (non-arithmetically Cohen-Macaulay) curve in

P

n

\mathbf {P}^n

. For curves in

P

3

\mathbf {P}^3

, we show that any set of Betti numbers that satisfies that condition can be realized as the Betti numbers of the general plane section of an arithmetically Buchsbaum, non-arithmetically Cohen-Macaulay curve. We also show that the matrices that arise as a degree matrix of the general plane section of an arithmetically Buchsbaum, integral, (smooth) non-arithmetically Cohen-Macaulay space curve are exactly those that arise as a degree matrix of the general plane section of an arithmetically Buchsbaum, non-arithmetically Cohen-Macaulay space curve and have positive subdiagonal. We also prove some bounds on the dimension of the deficiency module of an arithmetically Buchsbaum space curve in terms of the degree matrix of the general plane section of the curve, and we prove that they are sharp.
Representation formulae and inequalities for solutions of a class of second order partial differential equations
Authors: D’Ambrosio Lorenzo , Mitidieri Enzo , Pohozaev Stanislav
Published: October 2005

LetLLbe a possibly degenerate second order differential operator and letΓη=d2−Q\Gamma _\eta =d^{2-Q}be its fundamental solution atη\eta; hereddis a suitable distance. In this paper we study necessary and sufficient conditions for the weak solutions of−Lu≥f(ξ,u)≥0-Lu\ge f(\xi ,u)\ge 0onRN{\mathbb {R}}^Nto satisfy the representation formula\[<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis upper R right-parenthesis u left-parenthesis eta right-parenthesis greater-than-or-equal-to integral Underscript double-struck upper R Superscript upper N Baseline Endscripts normal upper Gamma Subscript eta Baseline f left-parenthesis xi comma u right-parenthesis d xi period">(R)u(η)≥∫RNΓηf(ξ,u)dξ.(\mbox R)\qquad \qquad \qquad \qquad \qquad u(\eta )\ge \int _{\mathbb {R}^N} \Gamma _\eta f(\xi ,u) \,d\xi .\qquad \qquad \qquad \qquad \qquad \qquad\]We prove that (R) holds providedf(ξ,⋅)f(\xi ,\cdot )is superlinear, without any assumption on the behavior ofuuat infinity. On the other hand, ifuusatisfies the condition\[<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="limit inf minus integral Subscript upper R less-than-or-equal-to d left-parenthesis xi right-parenthesis less-than-or-equal-to 2 upper R Baseline StartAbsoluteValue u left-parenthesis xi right-parenthesis EndAbsoluteValue d xi equals 0 comma">lim infR→∞−∫R≤d(ξ)≤2R|u(ξ)|dξ=0,\liminf _{R\rightarrow \infty } {-\!\!\!\!\!\!\int }_{R\le d(\xi )\le 2R}|u(\xi )|d\xi =0,\]then (R) holds with no growth assumptions onf(ξ,⋅)f(\xi ,\cdot ).
Lagrangian submanifolds and moment convexity
Authors: Krötz Bernhard , Otto Michael
Published: October 2005

We consider a Hamiltonian torus action

T
×
M
→
M

T\times M \rightarrow M

on a compact connected symplectic manifold

M
M

and its associated momentum map

Φ
\Phi

. For certain Lagrangian submanifolds

Q
⊆
M

Q\subseteq M

we show that

Φ
(
Q
)

\Phi (Q)

is convex. The submanifolds

Q
Q

arise as the fixed point set of an involutive diffeomorphism

τ
:
M
→
M

\tau :M\rightarrow M

which satisfies several compatibility conditions with the torus action, but which is in general not anti-symplectic. As an application we complete a symplectic proof of Kostant’s non-linear convexity theorem.
On the Andrews-Stanley refinement of Ramanujan’s partition congruence modulo 5 and generalizations
Authors: Berkovich Alexander , Garvan Frank
Published: October 2005

In a recent study of sign-balanced, labelled posets, Stanley introduced a new integral partition statistic

s
r
a
n
k

(
π
)
=

O

(
π
)
−

O

(

π
′

)
,

\begin{equation*} \mathrm {srank}(\pi ) = {\mathcal O}(\pi ) - {\mathcal O}(\pi ’), \end{equation*}

where

O

(
π
)

{\mathcal O}(\pi )

denotes the number of odd parts of the partition

π
\pi

and

π
′

\pi ’

is the conjugate of

π
\pi

. In a forthcoming paper, Andrews proved the following refinement of Ramanujan’s partition congruence mod

5
5

:
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartLayout 1st Row 1st Column p 0 left-parenthesis 5 n plus 4 right-parenthesis 2nd Column a m p semicolon identical-to p 2 left-parenthesis 5 n plus 4 right-parenthesis identical-to 0 left-parenthesis mod 5 right-parenthesis comma p left-parenthesis n right-parenthesis 3rd Column a m p semicolon equals p 0 left-parenthesis n right-parenthesis plus p 2 left-parenthesis n right-parenthesis comma EndLayout">

p
0

(
5
n
+
4
)

a
m
p
;
≡

p
2

(
5
n
+
4
)
≡
0

(
mod

5
)
,
p
(
n
)

a
m
p
;
=

p
0

(
n
)
+

p
2

(
n
)
,

\begin{align*} p_0(5n+4) &\equiv p_2(5n+4) \equiv 0 \pmod {5}, p(n) &= p_0(n) + p_2(n), \end{align*}

where

p
i

(
n
)

p_i(n)

(

i
=
0
,
2

i=0,2

) denotes the number of partitions of

n
n

with

s
r
a
n
k

≡
i

(
mod

4
)

\mathrm {srank}\equiv i\pmod {4}

and

p
(
n
)

p(n)

is the number of unrestricted partitions of

n
n

. Andrews asked for a partition statistic that would divide the partitions enumerated by

p
i

(
5
n
+
4
)

p_i(5n+4)

(

i
=
0
,
2

i=0,2

) into five equinumerous classes. In this paper we discuss three such statistics: the ST-crank, the

2
2

-quotient-rank and the

5
5

-core-crank. The first one, while new, is intimately related to the Andrews-Garvan (1988) crank. The second one is in terms of the

2
2

-quotient of a partition. The third one was introduced by Garvan, Kim and Stanton in 1990. We use it in our combinatorial proof of the Andrews refinement. Remarkably, the Andrews result is a simple consequence of a stronger refinement of Ramanujan’s congruence mod

5
5

. This more general refinement uses a new partition statistic which we term the BG-rank. We employ the BG-rank to prove new partition congruences modulo

5
5

. Finally, we discuss some new formulas for partitions that are

5
5

-cores and discuss an intriguing relation between

3
3

-cores and the Andrews-Garvan crank.
Nondegenerate 𝑞-biresolving textile systems and expansive automorphisms of onesided full shifts
Authors: Nasu Masakazu
Published: October 2005

We study nondegenerate,

q
q

-biresolving textile systems and using properties of them, we prove a conjecture of Boyle and Maass on arithmetic constraints for expansive automorphisms of onesided full shifts and positively expansive endomorphisms of mixing topological Markov shifts. A similar result is also obtained for expansive leftmost-permutive endomorphisms of onesided full shifts.
Uniform bounds under increment conditions
Authors: Weber Michel
Published: October 2005

We apply a majorizing measure theorem of Talagrand to obtain uniform bounds for sums of random variables satisfying increment conditions of the type considered in Gál-Koksma Theorems. We give some applications.
MacNeille completions and canonical extensions
Authors: Gehrke Mai , Harding John , Venema Yde
Published: October 2005

Let

V
V

be a variety of monotone bounded lattice expansions, that is, bounded lattices endowed with additional operations, each of which is order preserving or reversing in each coordinate. We prove that if

V
V

is closed under MacNeille completions, then it is also closed under canonical extensions. As a corollary we show that in the case of Boolean algebras with operators, any such variety

V
V

is generated by an elementary class of relational structures. Our main technical construction reveals that the canonical extension of a monotone bounded lattice expansion can be embedded in the MacNeille completion of any sufficiently saturated elementary extension of the original structure.
An explicit characterization of Calogero–Moser systems
Authors: Gesztesy Fritz , Unterkofler Karl , Weikard Rudi
Published: October 2005

Combining theorems of Halphen, Floquet, and Picard and a Frobenius type analysis, we characterize rational, meromorphic simply periodic, and elliptic KdV potentials. In particular, we explicitly describe the proper extension of the Airault–McKean–Moser locus associated with these three classes of algebro-geometric solutions of the KdV hierarchy with special emphasis on the case of multiple collisions between the poles of solutions. This solves a problem left open since the mid-1970s.
Visualization of Vacuolar Acidification-induced Transcription of Genes of Pathogens inside Macrophages
Authors: Martin-Orozco Natalia , Touret Nicolas , Zaharik Michael L. , Park Edwin , Kopelman Raoul , Miller Samuel , Finlay B. Brett , Gros Philippe , Grinstein Sergio
Published: October 2005

The objective of these studies was to analyze the role of the ionic environment of phagosomal vacuoles in the control of pathogens by macrophages. Digital imaging and flow cytometry were used to follow the induction of the phoP promoter of Salmonella enterica Typhimurium within live macrophages. Manipulating the Mg2+concentration within the Salmonella-containing vacuole (SCV) was without effect on the early induction of PhoPQ. Moreover, direct measurement of [Mg2+] within the SCV using nanosensor particles showed that, during this initial period of phoP activation, the concentration of the divalent cation is rapidly regulated and stabilizes around 1 mm. Extrusion of other divalent cations via the Nramp1 efflux pump was similarly ruled out as an important contributor to the activation of the regulon. By contrast, induction of PhoP was greatly attenuated when the pH gradient across the SCV membrane was dissipated. A second, more modest pH-independent component of PhoP induction was unmasked by inhibition of the vacuolar proton pump. This second component was eliminated by pretreatment of cells with IFNγ, even though the cytokine augmented the overall PhoP response. These findings demonstrate the existence of at least three separate activators of phoP transcription: resting and IFNγ-stimulated pH-sensitive components, plus a pH-independent component.
Proteolytic Cleavage and Phosphorylation of a Tumor-associated ErbB4 Isoform Promote Ligand-independent Survival and Cancer Cell Growth
Authors: Määttä Jorma A. , Sundvall Maria , Junttila Teemu T. , Peri Liisa , Laine V. Jukka O. , Isola Jorma , Egeblad Mikala , Elenius Klaus
Published: October 2005

The ErbB1 and ErbB2 receptors are oncogenes with therapeutic significance in human cancer, whereas the transforming potential of the related ErbB4 receptor has remained controversial. Here, we have addressed whether four alternatively spliced ErbB4 isoforms differ in regulating cellular responses relevant for tumor growth. We show that the two tumor necrosis factor-α converting enzyme (TACE)-cleavable ErbB4 isoforms (the juxtamembrane [JM]-a isoforms) were overexpressed in a subset of primary human breast cancers together with TACE. The overexpression of the JM-a cytoplasmic (CYT)-2 ErbB4 isoform promoted ErbB4 phosphorylation, survival of interleukin-3-dependent cells, and proliferation of breast cancer cells even in the absence of ligand stimulation, whereas activation of the other three ErbB4 isoforms required ligand stimulation. Ligand-independent cellular responses to ErbB4 JM-a CYT-2 overexpression were regulated by both tyrosine kinase activity and a two-step proteolytic generation of an intracellular receptor fragment involving first a TACE-like proteinase, followed by γ-secretase activity. These data suggest a novel transforming mechanism for the ErbB4 receptor in human breast cancer that is 1) specific for a single receptor isoform and 2) depends on proteinase cleavage and kinase activity but not ligand activation of the receptor.
Actin Is Required for Endocytosis at the Apical Surface of Madin-Darby Canine Kidney Cells where ARF6 and Clathrin Regulate the Actin Cytoskeleton
Authors: Hyman Tehila , Shmuel Miri , Altschuler Yoram
Published: October 2005

In epithelial cell lines, apical but not basolateral clathrin-mediated endocytosis has been shown to be affected by actin-disrupting drugs. Using electron and fluorescence microscopy, as well as biochemical assays, we show that the amount of actin dedicated to endocytosis is limiting at the apical surface of epithelia. In part, this contributes to the low basal rate of clathrin-dependent endocytosis observed at this epithelial surface. ARF6 in its GTP-bound state triggers the recruitment of actin from the cell cortex to the clathrin-coated pit to enable dynamin-dependent endocytosis. In addition, we show that perturbation of the apical endocytic system by expression of a clathrin heavy-chain mutant results in the collapse of microvilli. This phenotype was completely reversed by the expression of an ARF6-GTP-locked mutant. These observations indicate that concomitant to actin recruitment, the apical clathrin endocytic system is deeply involved in the morphology of the apical plasma membrane.
Cis-Golgi Matrix Proteins Move Directly to Endoplasmic Reticulum Exit Sites by Association with Tubules
Authors: Mardones Gonzalo A. , Snyder Christopher M. , Howell Kathryn E.
Published: October 2005

The role of cis-medial Golgi matrix proteins in retrograde traffic is poorly understood. We have used imaging techniques to understand the relationship between the cis-medial Golgi matrix and transmembrane proteins during retrograde traffic in control and brefeldin A (BFA)-treated cells. All five of the cis-medial matrix proteins tested were associated with retrograde tubules within 2-3 min of initiation of tubule formation. Then, at later time points (3-10 min), transmembrane proteins are apparent in the same tubules. Strikingly, both the matrix proteins and the transmembrane proteins moved directly to endoplasmic reticulum (ER) exit sites labeled with p58 and Sec13, and there seemed to be a specific interaction between the ER exit sites and the tips or branch points of the tubules enriched for the matrix proteins. After the initial interaction, Golgi matrix proteins accumulated rapidly (5-10 min) at ER exit sites, and Golgi transmembrane proteins accumulated at the same sites ∼2 h later. Our data suggest that Golgi cis-medial matrix proteins participate in Golgi-to-ER traffic and play a novel role in tubule formation and targeting.
Interactions between EHD Proteins and Rab11-FIP2: A Role for EHD3 in Early Endosomal Transport
Authors: Naslavsky Naava , Rahajeng Juliati , Sharma Mahak , Jović Marko , Caplan Steve
Published: October 2005

Eps15 homology domain (EHD) 1 enables membrane recycling by controlling the exit of internalized molecules from the endocytic recycling compartment (ERC) en route to the plasma membrane, similar to the role described for Rab11. However, no physical or functional connection between Rab11 and EHD-family proteins has been demonstrated yet, and the mode by which they coordinate their regulatory activity remains unknown. Here, we demonstrate that EHD1 and EHD3 (the closest EHD1 paralog), bind to the Rab11-effector Rab11-FIP2 via EH–NPF interactions. The EHD/Rab11-FIP2 associations are affected by the ability of the EHD proteins to bind nucleotides, and Rab11-FIP2 is recruited to EHD-containing membranes. These results are consistent with a coordinated role for EHD1 and Rab11-FIP2 in regulating exit from the ERC. However, because no function has been attributed to EHD3, the significance of its interaction with Rab11-FIP2 remained unclear. Surprisingly, loss of EHD3 expression prevented the delivery of internalized transferrin and early endosomal proteins to the ERC, an effect differing from that described upon EHD1 knockdown. Moreover, the subcellular localization of Rab11-FIP2 and endogenous Rab11 were altered upon EHD3 knockdown, with both proteins absent from the ERC and retained in the cell periphery. The results presented herein promote a coordinated role for EHD proteins and Rab11-FIP2 in mediating endocytic recycling and provide evidence for the function of EHD3 in early endosome to ERC transport.
Essential Roles in Development and Pigmentation for theDrosophilaCopper Transporter DmATP7
Authors: Norgate Melanie , Lee Esther , Southon Adam , Farlow Ashley , Batterham Philip , Camakaris James , Burke Richard
Published: October 2005

Defects in the mammalian Menkes and Wilson copper transporting P-type ATPases cause severe copper homeostasis disease phenotypes in humans. Here, we find that DmATP7, the sole Drosophila orthologue of the Menkes and Wilson genes, is vital for uptake of copper in vivo. Analysis of a DmATP7 loss-of-function allele shows that DmATP7 is essential in embryogenesis, early larval development, and adult pigmentation and is probably required for copper uptake from the diet. These phenotypes are analogous to those caused by mutation in the mouse and human Menkes genes, suggesting that like Menkes, DmATP7 plays at least two roles at the cellular level: delivering copper to cuproenzymes required for pigmentation and neuronal function and removing excess cellular copper via facilitated efflux. DmATP7 displays a dynamic and unexpected expression pattern in the developing embryo, implying novel functions for this copper pump and the lethality observed in DmATP7 mutant flies is the earliest seen for any copper homeostasis gene.
A Genomewide Screen Reveals a Role of Mitochondria in Anaerobic Uptake of Sterols in Yeast
Authors: Reiner Sonja , Micolod Delphine , Zellnig Günther , Schneiter Roger
Published: October 2005

The mechanisms that govern intracellular transport of sterols in eukaryotic cells are not well understood. Saccharomyces cerevisiae is a facultative anaerobic organism that becomes auxotroph for sterols and unsaturated fatty acids in the absence of oxygen. To identify pathways that are required for uptake and transport of sterols, we performed a systematic screen of the yeast deletion mutant collection for genes that are required for growth under anaerobic conditions. Of the ∼4800 nonessential genes represented in the deletion collection, 37 were essential for growth under anaerobic conditions. These affect a wide range of cellular functions, including biosynthetic pathways for certain amino acids and cofactors, reprogramming of transcription and translation, mitochondrial function and biogenesis, and membrane trafficking. Thirty-three of these mutants failed to grow on lipid-supplemented media when combined with a mutation in HEM1, which mimics anaerobic conditions in the presence of oxygen. Uptake assays with radio- and fluorescently labeled cholesterol revealed that 17 of the 33 mutants strongly affect uptake and/or esterification of exogenously supplied cholesterol. Examination of the subcellular distribution of sterols in these uptake mutants by cell fractionation and fluorescence microscopy indicates that some of the mutants block incorporation of cholesterol into the plasma membrane, a presumably early step in sterol uptake. Unexpectedly, the largest class of uptake mutants is affected in mitochondrial functions, and many of the uptake mutants show electron-dense mitochondrial inclusions. These results indicate that a hitherto uncharacterized mitochondrial function is required for sterol uptake and/or transport under anaerobic conditions and are discussed in light of the fact that mitochondrial import of cholesterol is required for steroidogenesis in vertebrate cells.
Rac1 Leads to Phosphorylation-dependent Increase in Stability of the p66shc Adaptor Protein: Role in Rac1-induced Oxidative Stress
Authors: Khanday Firdous A. , Yamamori Tohru , Mattagajasingh Ilwola , Zhang Zhe , Bugayenko Artem , Naqvi Asma , Santhanam Lakshmi , Nabi Nusrat , Kasuno Kenji , Day Billy W. , Irani Kaikobad
Published: October 2005

The rac1 GTPase and the p66shc adaptor protein regulate intracellular levels of reactive oxygen species (ROS). We examined the relationship between rac1 and p66shc. Expression of constitutively active rac1 (rac1V12) increased phosphorylation, reduced ubiquitination, and increased stability of p66shc protein. Rac1V12-induced phosphorylation and up-regulation of p66shc was suppressed by inhibiting p38MAPK and was dependent on serine 54 and threonine 386 in p66shc. Phosphorylation of recombinant p66shc by p38MAPK in vitro was also partly dependent on serine 54 and threonine 386. Reconstitution of p66shc in p66shc-null fibroblasts increased intracellular ROS generated by rac1V12, which was significantly dependent on the integrity of residues 54 and 386. Overexpression of p66shc increased rac1V12-inducd apoptosis, an effect that was also partly dependent on serine 54 and threonine 386. Finally, RNA interference-mediated down-regulation of endogenous p66shc suppressed rac1V12-induced cell death. These findings identify p66shc as a mediator of rac1-induced oxidative stress. In addition, they suggest that serine 54 and threonine 386 are novel phosphorylatable residues in p66shc that govern rac1-induced increase in its expression, through a decrease in its ubiquitination and degradation, and thereby mediate rac1-stimulated cellular oxidative stress and death.
DNA Replication Origins Fire Stochastically in Fission Yeast
Authors: Patel Prasanta K. , Arcangioli Benoit , Baker Stephen P. , Bensimon Aaron , Rhind Nicholas
Published: October 2005

DNA replication initiates at discrete origins along eukaryotic chromosomes. However, in most organisms, origin firing is not efficient; a specific origin will fire in some but not all cell cycles. This observation raises the question of how individual origins are selected to fire and whether origin firing is globally coordinated to ensure an even distribution of replication initiation across the genome. We have addressed these questions by determining the location of firing origins on individual fission yeast DNA molecules using DNA combing. We show that the firing of replication origins is stochastic, leading to a random distribution of replication initiation. Furthermore, origin firing is independent between cell cycles; there is no epigenetic mechanism causing an origin that fires in one cell cycle to preferentially fire in the next. Thus, the fission yeast strategy for the initiation of replication is different from models of eukaryotic replication that propose coordinated origin firing.