bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic control and readout of qubits based on single impurity states in semiconductors
Authors: Petukhov A. G. , Osipov V. V. , Smelyanskiy V. N.
Published: October 2006

The authors demonstrate that a semiconductor n+∕i∕n+ junction is the most suitable candidate for electronic control and readout of semiconductor qubits based on shallow impurities. Tuning of the doping levels in n+ regions and self-induced interface barriers ensure that an impurity atom placed in i region is populated with one electron in equilibrium. They analyze Li donors in Si and show that a large signal qubit readout can be realized via polarization selective photoexcitation of resonant cotunneling current through an excited impurity state.
Hole-transport barrier and band bending at the indium tin oxide/polymer/p-AlGaN interface
Authors: Lin Yow-Jon
Published: October 2006

Nonalloyed Ohmic contacts on p-AlGaN were achieved using a thin polymer film [i.e., poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(4-styrenesulfonate)] as an interlayer for the electronic modification of indium tin oxide/p-AlGaN contacts. The electronic properties were investigated by current-voltage measurements and x-ray photoelectron spectroscopy (XPS). According to XPS measurements, the authors found a slight reduction in the surface band bending of p-AlGaN following PEDOT coating and the disappearance of the barrier for hole transport at indium tin oxide/PEDOT/p-AlGaN interfaces.
Logic gates with a single Hall bar heterostructure
Authors: Sordan R. , Miranda A. , Osmond J. , Chrastina D. , Isella G. , von Känel H.
Published: October 2006

A four-terminal Hall bar configuration is commonly used in the investigation of transport properties of modulation doped heterostructures. Here it is found that a single Hall bar can act as a multifunction logic gate if a gate electrode is patterned between the voltage probes. Four different logic functions can be obtained depending on the input voltage levels. Operation of all logic gates is demonstrated and merits of such gates with respect to conventional logic gates are discussed.
Effect of InAs dots on noise of quantum dot resonant tunneling single-photon detectors
Authors: Hees S. S. , Kardynal B. E. , See P. , Shields A. J. , Farrer I. , Ritchie D. A.
Published: October 2006

The authors present a systematic study of the effect of InAs deposition time on single photon detectors based on quantum dot resonant tunneling diodes. A dramatic improvement in the dark counts due to the electron generation-recombination events in the dots is found by reducing the size of the dots. The dark count rate can be improved to less than 6.6×10−10ns−1 while maintaining a single photon detection efficiency of 2%.
A new Neolitsea and a new Cryptocarya (Lauraceae) from Australia.
Authors: Kostermans AJGH
Published: October 2006

Neolitsea australiensis and Cryprocarya joydii are
described. The distribution and affinities are discussed for each species.
A revision of Wurmbea (Liliaceae) in Australia.
Authors: Macfarlane TD
Published: October 2006

After examining the morphology, anatomy, pollen and cytology of the Australian
species of Wurmbea and A nguillaria and comparing them with African species of Wurmbea
I concluded that all are congeneric, despite carpel differences between African and Aus-
tralian species, and should be called Wurmbea Thunberg. Descriptions, illustrations, distri-
bution maps and a key are given for the 18 Australian species. New taxa are: W. dioica
subsp. alba, W. dilatata, W. latifolia, W. humilis, W. odorata, W. inframediana, W. deser-
ticola, W. centralis, W. sinora and W. cernua. New combinations are: W. monantha (Endl.)
comb, nov., W. biglandulosa (R.Br.) comb, nov., W. uniflora (R.Br.) comb. nov. and W.
densiflora (Benth.) comb. nov.
A review of the genus Calytrix Labill. (Myrtaceae) in Northern Australia.
Authors: Craven LA
Published: October 2006

The genus Calytrix is reviewed for northern Australia and
12 species are recognized as occurring in the area. Six of these species are described
as new: C. decussata, C. faucicola, C. micrairoides, C. mimiana, C. surdiviperana and C.
verticillata. All names applicable to the northern Australian species are taken into account
and a key to the identification of these species is provided. All species are illustrated.
A revision of South American Myriophyllum (Haloragaceae) and its repercussions on some Australian and North American species.
Authors: Orchard AE
Published: October 2006

The three species of Myriophyllum occurring naturally in South America (M. aquaticum,
M. quitense and M. mattogrossensis) are keyed and described. M. quitense is an earlier
legitimate name for the plant generally known as M. elatinoides, a species until now
thought to extend from South America into North America, New Zealand and Australia.
Plants of 'M. elatinoides' in North America and Australia have been critically re-examined,
and the status of closely related taxa has been reconsidered. It has been found that, in
North America, M. quitense exists as two isolated populations in Arizona and Oregon.
The status of M. spicatum, M. exalbescens and M. magdalenense, the three previously
described species of the 'elatinoides' complex is discussed, and it is suggested that two
varieties should be recognized, M. spicatum var. spicatum and M. spicatum var. exalbescens.
M. magdalenense is considered to be a minor variant of M. spicatum var. spicatum. Aus-
tralian plants known until now as M. elatinoides are shown to be distinct from M. quitense,
and to constitute three new species, M. salsugineum, M. caput-medusae and M. porcatum,
which are here described.
Lectotypification of Neuburgia corynocarpa var. sarcantha (Loganiaceae).
Authors: Conn BJ
Published: October 2006

Ledermann 13005 (B) is here chosen as the lectotype of
Couthovia sarcantha Gilg & Bened., which is automatically the lectotype of Neuburgia
corynocarpa (A. Gray) Leenh. var. sarcantha (Gilg & Bened.) Conn. A description of the
lectotype is also given.
The Australian species of Freycinetia (Pandanaceae).
Authors: Stone BC
Published: October 2006

Four species of Freydnetia Gaudich. (Pandanaceae) are reported from
Australia, one of which is an addition to the Australian flora. A key to the species,
descriptions, synonyms, and voucher specimen citations are provided. Each species
represents a different section of the genus; all four species occur also outside Australia in
New Guinea and sometimes elsewhere. The Freycinetias of Australia are an East Malesian
biogeographic element in the flora, and none has undergone any local evolutionary
specialization.
A name change in the genus Flindersia (Rutaceae)
Authors: Hartley TG , Jessup LW
Published: October 2006

The new combination Flindersia oppositifolia (F. Muell.) Hartley
& Jessup, based on Hypsophila oppositifolia F. Muell., is made for the name of the plant
more recently described as Flindersia unifoliolata Hartley.
The Tasmanian species of Persoonia Smith (Proteaceae)
Authors: Orchard AE
Published: October 2006

The number of species recognized for Tasmania is raised from two to
four, and three of the species are subdivided into varieties. Variation in P. juniperina
in the state is discussed, and four varieties (var. juniperina, var. ulicina Meissner, var.
brevifolia Meissner and var. mollis Orch.) are keyed and described. Only the last of these
is new. Two new species [P. muelleri (P. Parm.) Orch. and P. moscalii Orch.] are
segregated from P. gunnii. P. muelleri is divided into three varieties: var. muelleri, var.
densifolia Orch. and var. angustifolia (Benth.) Orch., while P. gunnii is divided into
two varieties: var. gunnii and var. oblanceolata Orch. All of these varieties are new taxa
or new combinations.
Two new Eastern Australian species of Glycine Willd. (Fabaceae)
Authors: Tindale MD
Published: October 2006

Two species of Glycine (Phaseoleae) are described as new: G. argyrea
(Queensland), and G. cyrtoloba (Queensland, New South Wales). Both species are
illustrated in detail.
The genus Codium (Codiales, Chlorophyta) at Lord Howe Island (NSW).
Authors: Jones R , Kraft GT
Published: October 2006

Five species of Codium have been
found on the world's southernmost coral reef at Lord Howe Island, New South Wales
(31�33'S.,159�03'E.). The genus forms, along with the brown algal order Dictyotales, a
dominant marine algal group on the island. One species, the South African C. extricatum
Silva, is a new record for the Australian region. Codium platydados is newly described
based on Lord Howe, Great Barrier Reef and Philippine collections. Codium bulbopilum
Setchell and C spongiosum Harvey have previously been recorded from the island and
are major cover species in shallow lagoon waters. Codium arabicum is reported from
the island and adjacent Australian mainland for the first time at what appear to be the
species' southernmost limits of distribution. Anatomical variability and taxonomic
relationships of the species are considered, and the geographical and local distributions
discussed.
New speceis of Tasmanian Monocotyledones in the families Juncaceae, Centrolepidaceae and Cyperaceae.
Authors: Curtis WM
Published: October 2006

Eight species are
described: Luzula poimena (Juncaceae); Centrolepis paludicola, Centrolepis pedderensis,
Gaimardia amblyphylla (Centrolepidaceae); Isolepis limbata, Oreobolus oligocephalus,
Carpha rodwayi, Carpha curvata (Cyperaceae).
The Australasian generic element in Malesia.
Authors: van  Steenis CGGJ
Published: October 2006

A checklist of Australasian genera in Malesia is presented. It is arranged
alphabetically by families. Each genus entry is provided with concise geographic data on
occurrence in Malesian islands. In the discussion various aspects of the generic list are
analysed for the 209 genera, their abundance by families, how many of these genera are
confined to New Guinea, the number of genera not represented in New Guinea, the
decrease of Australian genera from New Guinea westwards, and the numbers of genera
belonging to the various vegetation types, from the mangrove upwards to the alpine zone.
Taxonomic and Nomenclatural notes on Lechenaultia R.Br. (Goodeniaceae)
Authors: Morrison DA
Published: October 2006

There have been a large number of
nomenclatural and taxonomic problems within Lechenaultia, and these are resolved here.
A total of 24 names are lectotypified, two neotypes are chosen, a series of misapplied
names is elucidated, and L. agrostophylla is synonymised under L. filiformis for the first
time. As well, L. brevifolia, L. lutescens and L. papillata are described as new species, and
the considerable morphological variation within several of the species is reported in detail.
The phylogenetic relationships within the genus are also re-appraised, the sectional delimi-
tations are re-defined and section Patentes is described as new.
Some marine diatoms from the Australian region, especiallly from Port Phillip Bay and Tropical North-eastern Australia. 2. Survey of the genus Palmeria and of the family Lithodesmiaceae including the new genus Lithodesmioides.
Authors: Von Stosch HA
Published: October 2006

Based on plankton samples collected in 1970 and on a survey of the
literature, the Australian members of the genus Palmeria and of the family
Lithodesmiaceae are critically listed or described. Both species of Palmeria are new for
the Australian region, as are one species each of Lithodesmium and of Ditylum, two
species of the genus Lithodesmioides, one species plus one variety of Bellerochea, as well
as one species and one form of Neostreptotheca. Lithodesmium duckerae,
Lithodesmioides polymorphum and L. minutum, Ditylum buchananii, Bellerochea
horologicalis var. recta and Neostreptotheca torta and its fo. triangularis are described for
the first time. Palmeria ostenfeldii, a species associated with an epiphytic ciliate, is sep-
arated from P. hardmaniana.
In Ditylum brightwellii, the proportion of thecae with the slotted versus the fimbriate
form of the marginal ridge is shown to be probably influenced by the ambient water
conditions. In the same species, the ontogenies of the resting spores (including germi-
nation) as well as of the gametes are described. Lithodesmioides presents new instances
of fissipariety (split wall character) in both of its species. 'Simple pores', which have
recently been demonstrated by Li and Volcani to be distinct in origin from areolae, are
common in all described species of Lithodesmium, Lithodesmioides and Ditylum in two
forms as either 'branching point pores' or 'intracostal pores'.
New species of Praparmelia (Lichenised Ascomycotina) from Australia and New Zealand.
Authors: Elix J.A. , Johnston J
Published: October 2006

Eleven new species of
Paraparmelia lichens are described from Australia: Paraparmelia arida, P. atrocapnodes,
P. colensoica, P. gregaria, P. hypoconstictica, P. pinguiacida, P. rugulosa, P. saginata,
P. subalpina, P. subspodochroa and P. subtropica. One of these species, P. atrocapnodes,
has also been found in New Guinea.
Pyxine rugulosa Stirton (Pyxinaceae, Lichenised Ascomycetes) in Queensland.
Authors: Rogers RW
Published: October 2006

The collection of material chemically identical to the fragmen-
tary type of Pyxine rugulosa Stirton has allowed clarification of the application of that
name. P. rugulosa can be distinguished from other species of Pyxine in Australia by its
combination of a broad-lobed, heavily pruinose thallus without vegetative propagules,
yellow medulla, and presence of atranorin but not lichexanthone in the cortex. It is appar-
ently restricted to regions west of the Great Dividing Range in Queensland.
Two new Ironbarks and a new Bloodwood (Eucalyptus, Myrtaceae) from Queensland.
Authors: Brooker MIH , Bean AR
Published: October 2006

Two new
ironbarks of the informal Eucalyptus series Crebrae Brooker, E. exilipes and E.
xanthoclada, and a new bloodwood of the informal E. section Rufaria Pryor & Johnson,
E. lamprophylla, are described. The three species occur in north Queensland, centred on
the Pentland area south-west of Townsville.
Two brown-spored species of the Lichen Genus Polyblastiopsis.
Authors: Upreti DK , Singh A
Published: October 2006

Two taxa of pyrenocarpous lichens with
brown, muriform spores, previously included in the genus Anthracothecium, are trans-
ferred to the genus Polyblastiopsis. An emended description of Polyblastiopsis is given.
A new species, Polyblastiopsis muelleri, is described and a new combination,
Polyblastiopsis monosporum, is made.
Time scales of membrane fusion revealed by direct imaging of vesicle fusion with high temporal resolution
Authors: Haluska Christopher K. , Riske Karin A. , Marchi-Artzner Valérie , Lehn Jean-Marie , Lipowsky Reinhard , Dimova Rumiana
Published: October 2006

Membrane fusion is a vital process of life involved, for example, in cellular secretion via exocytosis, signaling between nerve cells, and virus infection. In both the life sciences and bioengineering, controlled membrane fusion has many possible applications, such as drug delivery, gene transfer, chemical microreactors, or synthesis of nanomaterials. Until now, the fusion dynamics has been elusive because direct observations have been limited to time scales that exceed several milliseconds. Here, the fusion of giant lipid vesicles is induced in a controlled manner and monitored with a temporal resolution of 50 μs. Two different fusion protocols are used that are based on synthetic fusogenic molecules and electroporation. For both protocols, the opening of the fusion necks is very fast, with an average expansion velocity of centimeters per second. This velocity indicates that the initial formation of a single fusion neck can be completed in a few hundred nanoseconds.
Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1
Authors: Chen Shaoyong , Xu Youyuan , Yuan Xin , Bubley Glenn J. , Balk Steven P.
Published: October 2006

Androgen receptors (ARs) are phosphorylated at multiple sites in response to ligand binding, but the kinases mediating AR phosphorylation and the importance of these kinases in AR function have not been established. Here we show that cyclin-dependent kinase 1 (Cdk1) mediates AR phosphorylation at Ser-81 and increases AR protein expression, and that Cdk1 inhibitors decrease AR Ser-81 phosphorylation, protein expression, and transcriptional activity in prostate cancer (PCa) cells. The decline in AR protein expression mediated by the Cdk inhibitor roscovitine was prevented by proteosome inhibitors, indicating that Cdk1 stabilizes AR protein, although roscovitine also decreased AR message levels. Analysis of an S81A AR mutant demonstrated that this site is not required for transcriptional activity or Cdk1-mediated AR stabilization in transfected cells. The AR is active and seems to be stabilized by low levels of androgen in “androgen-independent” PCas that relapse subsequent to androgen-deprivation therapy. Significantly, the expression of cyclin B and Cdk1 was increased in these tumors, and treatment with roscovitine abrogated responses to low levels of androgen in the androgen-independent C4-2 PCa cell line. Taken together, these findings identify Cdk1 as a Ser-81 kinase and indicate that Cdk1 stabilizes AR protein by phosphorylation at a site(s) distinct from Ser-81. Moreover, these results indicate that increased Cdk1 activity is a mechanism for increasing AR expression and stability in response to low androgen levels in androgen-independent PCas, and that Cdk1 antagonists may enhance responses to androgen-deprivation therapy.
An inherent role of microtubule network in the action of nuclear receptor
Authors: Manavathi Bramanandam , Acconcia Filippo , Rayala Suresh K. , Kumar Rakesh
Published: October 2006

Estrogen receptor α (ERα) functions as both a transcription factor and a mediator of rapid estrogen signaling. Recent studies have shown a role for ERα-interacting membranous and cytosolic proteins in ERα action, but our understanding of the role of the microtubule network in the modulation of ERα signaling remains unclear. Here we found that endogenous ERα associates with microtubules through the microtubule-binding protein hematopoietic PBX-interaction protein (HPIP). Biochemical and RNA-interference studies demonstrated that HPIP influences ERα-dependent rapid estrogen signaling by acting as a scaffold protein and recruits Src kinase and the p85 subunit of phosphatidylinositol 3-kinase to a complex with ERα, which in turn stimulates AKT and MAPK. We also found that ERα interacts with β-tubulin through HPIP. Destabilization of microtubules activated ERα signaling, whereas stabilization of microtubules repressed ERα transcriptional activity in a HPIP-dependent manner. These findings revealed a role for HPIP–microtubule complex in regulating 17β-estradiol–ERα responses in mammalian cells and discovered an inherent role of microtubules in the action of nuclear receptor.
The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II
Authors: Elmlund Hans , Baraznenok Vera , Lindahl Martin , Samuelsen Camilla O. , Koeck Philip J. B. , Holmberg Steen , Hebert Hans , Gustafsson Claes M.
Published: October 2006

CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II.
erbB2 is required for G protein-coupled receptor signaling in the heart
Authors: Negro Alejandra , Brar Bhawanjit K. , Gu Yusu , Peterson Kirk L. , Vale Wylie , Lee Kuo-Fen
Published: October 2006

erbB2/Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian development and human disease. The absence of erbB2 signaling in cardiac myocytes results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects observed in a subset of breast cancer patients treated with the anti-Her2 antibody herceptin. Emerging evidence suggests that erbB2 is pivotal for integrating signaling networks involving multiple classes of extracellular signals. However, its role in G protein-coupled receptor (GPCR) signaling remains undefined. Because the activation of the MAPK pathway through GPCR signaling is important for cardiac homeostasis, we investigated whether erbB2 is required for GPCR-mediated MAPK signaling in wild-type and heart-specific erbB2 mutant mice. Here we demonstrate that erbB2, but not EGF receptor, is essential for MAPK activation induced by multiple GPCR agonists in cardiac myocytes. erbB2 is immunocomplexed with a GPCR
in vivo
and is transactivated after ligand treatment
in vitro
. Coexpression of erbB2 with GPCRs in heterologous cells results in ligand-dependent complex formation and MAPK activation. Furthermore, MAPK activation and cardiac contractility are markedly impaired in heart-specific erbB2 mutants infused with a GPCR agonist. These results reveal an essential mechanism requiring erbB2 as a coreceptor for GPCR signaling in the heart. The obligatory role of erbB2 in GPCR-dependent signaling may also be important in other cellular systems.
Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A
2
Authors: Sitkiewicz Izabela , Nagiec Michal J. , Sumby Paul , Butler Stephanie D. , Cywes-Bentley Colette , Musser James M.
Published: October 2006

The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A
2
(designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A
Streptococcus
. Although several lines of circumstantial evidence suggest that SlaA is a virulence factor, this issue has not been addressed experimentally. We found that an isogenic Δ
slaA
mutant strain was significantly impaired in ability to adhere to and kill human epithelial cells compared with the wild-type parental strain. The mutant strain was less virulent for mice than the wild-type strain, and immunization with purified SlaA significantly protected mice from invasive disease. Importantly, the mutant strain was significantly attenuated for colonization in a monkey model of pharyngitis. We conclude that transductional acquisition of the ability of a GAS strain to produce SlaA enhanced the spread and virulence of the serotype M3 precursor strain. Hence, these studies identified a crucial molecular event underlying the evolution, rapid emergence, and widespread dissemination of unusually severe human infections caused by a distinct bacterial clone.
Dynamic subcompartmentalization of the mitochondrial inner membrane
Authors: Vogel Frank , Bornhövd Carsten , Neupert Walter , Reichert Andreas S.
Published: October 2006

The inner membrane of mitochondria is organized in two morphologically distinct domains, the inner boundary membrane (IBM) and the cristae membrane (CM), which are connected by narrow, tubular cristae junctions. The protein composition of these domains, their dynamics, and their biogenesis and maintenance are poorly understood at the molecular level. We have used quantitative immunoelectron microscopy to determine the distribution of a collection of representative proteins in yeast mitochondria belonging to seven major processes: oxidative phosphorylation, protein translocation, metabolite exchange, mitochondrial morphology, protein translation, iron–sulfur biogenesis, and protein degradation. We show that proteins are distributed in an uneven, yet not exclusive, manner between IBM and CM. The individual distributions reflect the physiological functions of proteins. Moreover, proteins can redistribute between the domains upon changes of the physiological state of the cell. Impairing assembly of complex III affects the distribution of partially assembled subunits. We propose a model for the generation of this dynamic subcompartmentalization of the mitochondrial inner membrane.
Membranes of the world unite!
Authors: Chernomordik Leonid V. , Zimmerberg Joshua , Kozlov Michael M.
Published: October 2006

Despite diverse origins, cellular fusion mechanisms converge at a pathway of phospholipid bilayer fusion. In this mini-review, we discuss how proteins can mediate each of the three major stages in the fusion pathway: contact, hemifusion, and the opening of an expanding fusion pore.
Triggering CD40 on endothelial cells contributes to tumor growth
Authors: Chiodoni Claudia , Iezzi Manuela , Guiducci Cristiana , Sangaletti Sabina , Alessandrini Isabella , Ratti Chiara , Tiboni Francesca , Musiani Piero , Granger D. Neil , Colombo Mario P.
Published: October 2006

Inflammatory cells can either promote or inhibit tumor growth. Here we studied whether CD40, a key molecule for adaptive immune response, has any role in mammary carcinogenesis of BALB/NeuT transgenic tumor-prone mice. We transferred the HER2/neu oncogene into CD40-null background to obtain the CD40-KO/NeuT strain. CD40-KO/NeuT mice showed delayed tumor onset and reduced tumor multiplicity. BM (BM) transplantation experiments excluded a role of BM-derived cells in the reduced tumorigenicity associated with CD40 deficiency. Rather, CD40 expressed by endothelial cells (ECs) takes part to the angiogenic process. Accordingly, large vessels, well organized around the tumor lobular structures, characterize BALB/NeuT tumors, whereas tiny numerous vessels with scarce extracellular matrix are dispersed in the parenchyma of poorly organized CD40-KO/NeuT tumors.

Activated platelets, which may interact with and activate ECs, are a possible source of CD40L. Their localization within tumor vessels prompted the idea of treating BALB/NeuT and CD40-KO/NeuT mice chronically with the anti-platelet drug clopidogrel, known to inhibit platelet CD40L expression. Treatment of BALB/NeuT mice reduced tumor growth to a level similar to CD40-deficient mice, whereas CD40-KO/NeuT mice treated or not showed the same attenuated tumor outgrowth, indicating that activated platelets are the likely source of CD40L in this model. Collectively, these data point to a participation of CD40/CD40L in the angiogenic processes associated with mammary carcinogenesis of BALB/NeuT mice.
Follicular lymphoma-like B cells in healthy individuals: a novel intermediate step in early lymphomagenesis
Authors: Roulland Sandrine , Navarro Jean-Marc , Grenot Pierre , Milili Michèle , Agopian Julie , Montpellier Bertrand , Gauduchon Pascal , Lebailly Pierre , Schiff Claudine , Nadel Bertrand
Published: October 2006

Follicular lymphoma is one of the most common adult lymphoma, and remains virtually incurable despite its relatively indolent nature. t(14;18)(q32;q21) translocation, the genetic hallmark and early initiating event of follicular lymphoma (FL) pathogenesis, is also present at low frequency in the peripheral blood of healthy individuals. It has long been assumed that in healthy individuals t(14;18) is carried by circulating quiescent naive B cells, where its oncogenic potential would be restrained. Here, we question this current view and demonstrate that in healthy individuals, t(14;18) is actually carried by an expanding population of atypical B cells issued from germinal centers, displaying genotypic and phenotypic features of FL, and prone to constitute potent premalignant FL niches. These findings strongly impact both on the current understanding of disease progression and on the proper handling of t(14;18) frequency in blood as a potential early biomarker for lymphoma.
Thermodynamics of CFTR Channel Gating: A Spreading Conformational Change Initiates an Irreversible Gating Cycle
Authors: Csanády László , Nairn Angus C. , Gadsby David C.
Published: October 2006

CFTR is the only ABC (ATP-binding cassette) ATPase known to be an ion channel. Studies of CFTR channel function, feasible with single-molecule resolution, therefore provide a unique glimpse of ABC transporter mechanism. CFTR channel opening and closing (after regulatory-domain phosphorylation) follows an irreversible cycle, driven by ATP binding/hydrolysis at the nucleotide-binding domains (NBD1, NBD2). Recent work suggests that formation of an NBD1/NBD2 dimer drives channel opening, and disruption of the dimer after ATP hydrolysis drives closure, but how NBD events are translated into gate movements is unclear. To elucidate conformational properties of channels on their way to opening or closing, we performed non-equilibrium thermodynamic analysis. Human CFTR channel currents were recorded at temperatures from 15 to 35°C in inside-out patches excised from Xenopus oocytes. Activation enthalpies(ΔH‡) were determined from Eyring plots. ΔH‡ was 117 ± 6 and 69 ± 4 kJ/mol, respectively, for opening and closure of partially phosphorylated, and 96 ± 6 and 73 ± 5 kJ/mol for opening and closure of highly phosphorylated wild-type (WT) channels. ΔH‡ for reversal of the channel opening step, estimated from closure of ATP hydrolysis–deficient NBD2 mutant K1250R and K1250A channels, and from unlocking of WT channels locked open with ATP+AMPPNP, was 43 ± 2, 39 ± 4, and 37 ± 6 kJ/mol, respectively. Calculated upper estimates of activation free energies yielded minimum estimates of activation entropies (ΔS‡), allowing reconstruction of the thermodynamic profile of gating, which was qualitatively similar for partially and highly phosphorylated CFTR. ΔS‡ appears large for opening but small for normal closure. The large ΔH‡ and ΔS‡ (TΔS‡ ≥ 41 kJ/mol) for opening suggest that the transition state is a strained channel molecule in which the NBDs have already dimerized, while the pore is still closed. The small ΔS‡ for normal closure is appropriate for cleavage of a single bond (ATP's beta-gamma phosphate bond), and suggests that this transition state does not require large-scale protein motion and hence precedes rehydration (disruption) of the dimer interface.
Cooperative Gating between Single HCN Pacemaker Channels
Authors: Dekker John P. , Yellen Gary
Published: October 2006

HCN pacemaker channels (If, Iq, or Ih) play a fundamental role in the physiology of many excitable cell types, including cardiac myocytes and central neurons. While cloned HCN channels have been studied extensively in macroscopic patch clamp experiments, their extremely small conductance has precluded single channel analysis to date. Nevertheless, there remain fundamental questions about HCN gating that can be resolved only at the single channel level. Here we present the first detailed single channel study of cloned mammalian HCN2. Excised patch clamp recordings revealed discrete hyperpolarization-activated, cAMP-sensitive channel openings with amplitudes of 150–230 fA in the activation voltage range. The average conductance of these openings was ∼1.5 pS at −120 mV in symmetrical 160 mM K+. Some traces with multiple channels showed unusual gating behavior, characterized by a variable long delay after a voltage step followed by runs of openings. Noise analysis on macroscopic currents revealed fluctuations whose magnitudes were systematically larger than predicted from the actual single channel current size, consistent with cooperativity between single HCN channels.
Detection of the Opening of the Bundle Crossing in KcsA with Fluorescence Lifetime Spectroscopy Reveals the Existence of Two Gates for Ion Conduction
Authors: Blunck Rikard , Cordero-Morales Julio F. , Cuello Luis G. , Perozo Eduardo , Bezanilla Francisco
Published: October 2006

The closed KcsA channel structure revealed a crossing of the cytosolic ends of the transmembrane helices blocking the permeation pathway. It is generally agreed that during channel opening this helical bundle crossing has to widen in order to enable access to the inner cavity. Here, we address the question of whether the opening of the inner gate is sufficient for ion conduction, or if a second gate, located elsewhere, may interrupt the ion flow. We used fluorescence lifetime measurements on KcsA channels labeled with tetramethylrhodamine at residues in the C-terminal end of TM2 to report on the opening of the lower pore region.

We found two populations of channels with different fluorescence lifetimes, whose relative distribution agrees with the open probability of the channel. The absolute fraction of channels found with an open bundle crossing is too high to explain the low open probability of the KcsA-WT channel. We found the same distribution as in the WT channel between open and closed bundle crossing for two KcsA mutants, A73E and E71A, which significantly increase open probability at low pH. These two results strongly suggest that a second gate in the ion permeation pathway exists. The location of the mutations A73E and E71A suggests that the second gate may be the selectivity filter, which resides in an inactivated state under steady-state conditions. Since the long closed times observed in KcsA-WT are not present in KcsA-A73E or -E71A, we propose that KcsA-WT remains predominantly in a state with an open bundle crossing but closed (inactivated) second gate, while the mutations A73E and E71A sharply decrease the tendency to enter in the inactivated state, and as a consequence, the second gate is predominantly open at steady state. The ability to monitor the opening of the bundle crossing optically enables the direct recording of the movement of the pore helices while the channel is functioning.
Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program
Authors: Navarro Pablo , Page Damian R. , Avner Philip , Rougeulle Claire
Published: October 2006

Initiation of X inactivation depends on the coordinated expression of the sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like state in undifferentiated embryonic stem (ES) cells and shifts to a pseudoeuchromatic structure upon Tsix truncation. We further demonstrate that the epigenetic state of the Xist 5′ region prior to differentiation predicts the efficiency of transcriptional machinery recruitment to the Xist promoter during differentiation. Our results provide mechanistic insights into the Tsix-mediated epigenetic regulation of Xist resulting in Xist promoter activation and initiation of X inactivation in differentiating ES cells.
Meta‐analysis: alvimopan vs. placebo in the treatment of post‐operative ileus
Authors: TAN E. K. , CORNISH J. , DARZI A. W. , TEKKIS P. P.
Published: October 2006

Background

Alvimopan is a selective, competitive μ‐opioid receptor antagonist with limited oral bioavailability which may be used to reduce length of post‐operative ileus.

Aim

The study compared alvimopan with placebo following bowel resection or total abdominal hysterectomy.

Methods

A meta‐analysis of randomized–controlled trials published between 2001 and 2006 of alvimopan vs. placebo was performed. The primary efficacy end‐points were composite measures of passage of flatus, stool, and tolerance of solid food (GI‐3) and passage of stool and tolerance of solid food (GI‐2). The incidence of treatment emergent adverse events was assessed.

Results

Five trials matched the selection criteria, reporting on 2195 patients. A total of 1521 (69.3%) had alvimopan and 674 (30.7%) placebo. GI‐3 significantly improved (hazard ratio 1.30; 95% confidence intervals 1.16, 1.45, P < 0.001), as did GI‐2 (hazard ratio 1.61; 95% confidence intervals 1.26, 2.05, P < 0.001) on alvimopan 12 mg. Time to discharge (hazard ratio 1.26; 95% confidence intervals 1.13, 1.40, P < 0.001), time to bowel motion (hazard ratio 1.74; 95% confidence intervals 1.29, 2.35, P < 0.001), and time to solid food (hazard ratio 1.14; 95% confidence intervals 1.01, 1.30, P < 0.04) also improved significantly. No difference was noted in the incidence of treatment emergent adverse events.

Conclusions

Alvimopan showed significant advantages over placebo in restoring gastro‐intestinal function, and reduced time to discharge following major abdominal surgery, with acceptable side effects.
The ability of climate envelope models to predict the effect of climate change on species distributions
Authors: HIJMANS ROBERT J. , GRAHAM CATHERINE H.
Published: October 2006

Climate envelope models (CEMs) have been used to predict the distribution of species under current, past, and future climatic conditions by inferring a species' environmental requirements from localities where it is currently known to occur. CEMs can be evaluated for their ability to predict current species distributions but it is unclear whether models that are successful in predicting current distributions are equally successful in predicting distributions under different climates (i.e. different regions or time periods). We evaluated the ability of CEMs to predict species distributions under different climates by comparing their predictions with those obtained with a mechanistic model (MM). In an MM the distribution of a species is modeled based on knowledge of a species' physiology. The potential distributions of 100 plant species were modeled with an MM for current conditions, a past climate reconstruction (21 000 years before present) and a future climate projection (double preindustrial CO2 conditions). Point localities extracted from the currently suitable area according to the MM were used to predict current, future, and past distributions with four CEMs covering a broad range of statistical approaches: Bioclim (percentile distributions), Domain (distance metric), GAM (general additive modeling), and Maxent (maximum entropy). Domain performed very poorly, strongly underestimating range sizes for past or future conditions. Maxent and GAM performed as well under current climates as under past and future climates. Bioclim slightly underestimated range sizes but the predicted ranges overlapped more with the ranges predicted with the MM than those predicted with GAM did. Ranges predicted with Maxent overlapped most with those produced with the MMs, but compared with the ranges predicted with GAM they were more variable and sometimes much too large. Our results suggest that some CEMs can indeed be used to predict species distributions under climate change, but individual modeling approaches should be validated for this purpose, and model choice could be made dependent on the purpose of a particular study.
Clinical significance of pre‐S mutations in patients with genotype C hepatitis B virus infection
Authors: Choi M. S. , Kim D. Y. , Lee D. H. , Lee J. H. , Koh K. C. , Paik S. W. , Rhee J. C. , Yoo B. C.
Published: October 2006

Summary.  We investigated the overall and site‐specific prevalence of pre‐S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre‐S mutations were determined by nucleotide sequence analysis. Possible correlations between pre‐S mutations and clinical/virological parameters were examined. Pre‐S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre‐S2 deletion was the most commonly found mutation (10.7%), followed by pre‐S2 start codon mutation (9.7%), pre‐S1–S2 deletion (3.0%) and both pre‐S2 deletion and start codon mutation (2.7%). Pre‐S2 deletion and pre‐S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre‐S mutations were associated with older age and higher rates of positive HBV DNA (≥0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre‐S mutations by logistic regression analysis. These findings suggest that pre‐S mutations, especially pre‐S2 deletions and pre‐S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.
Colonic luminal proteases activate colonocyte proteinase‐activated receptor‐2 and regulate paracellular permeability in mice
Authors: Róka R. , Demaude J. , Cenac N. , Ferrier L. , Salvador‐cartier C. , Garcia‐villar R. , Fioramonti J. , Bueno L.
Published: October 2006

Abstract  Luminal activation of protease‐activated receptors‐2 (PAR2) on colonocytes by trypsin or PAR2‐activating peptide increases colonic paracellular permeability (CPP). The aim of this study was to evaluate the role of proteases from endogenous and bacterial origin in the modulation of CPP and colonocyte PAR2 expression in mice. CPP was assessed with 51Cr‐EDTA after intracolonic administration of different protease inhibitors. After 12 days of oral antibiotic treatment, measurements of colonic luminal serine protease activity (CLSPA), CPP, mucosal mouse mast cell proteinase‐1 (MMCP‐1) content, immunochemistry of PAR2 and assessment of effects of PAR2 agonist (SLIGRL) and mast cell degranulator (C48/80) on CPP in Ussing chambers were performed. Immunochemistry was repeated after intracolonic trypsin administration. Colonic infusion of protease inhibitors significantly reduced CPP. In antibiotic‐treated mice, CLSPA was reduced coupled with a decrease in PAR2 expression, but with no change in CPP and MMCP‐1 content. Trypsin administration restored PAR2 expression. The increase in CPP induced by SLIGRL and C48/80 was reduced after antibiotic treatment. Protease activity of colonic content plays an important role in the regulation of mucosal barrier through activation of PAR2.
A monograph of Nephilengys, the pantropical ‘hermit spiders’ (Araneae, Nephilidae, Nephilinae)
Authors: KUNTNER MATJAŽ
Published: October 2006

Abstract The nephilid genus Nephilengys, known for its synanthropic habits, large webs with a retreat and the extreme sexual size dimorphism, is revised. Of the twenty‐three available names, only four species with a globally allopatric distribution are recognized, illustrated and described from both sexes: N. cruentata (Fabricius, 1775) inhabits tropical Africa and South America, where it has probably been introduced; N. borbonica (Vinson, 1863) is found on Madagascar, Comoros, Seychelles and the Mascarene Islands; N. malabarensis (Walckenaer, 1842) ranges from India and Sri Lanka to China, Japan and eastern Indonesia; N. papuana Thorell, 1881 stat.n. is known from New Guinea and tropical Australia. Nephila instigans Butler, 1876 is the proposed syn.n. of N. borbonica; N. borbonica livida Vinson, 1863 is syn.n. of N. borbonica; N. niahensis Deeleman‐Reinhold, 1989 is syn.n. of N. malabarensis; N. rainbowi Hogg, 1899 is syn.n. of N. papuana. N. kenmorei Barrion & Litsinger, 1995, here proposed as a nomen dubium, is an araneid. Nephilengys biology is reviewed and its anatomy summarized for use in a phylogenetic analysis of 197 characters scored for all Nephilengys, selected nephilid species and non‐nephilid outgroups. Two new clades are circumscribed, the ‘cruentata species group’ (with N. cruentata and N. borbonica) and the ‘malabarensis species group’ (with N. malabarensis and N. papuana).
Uncovering and responding to needs for sexual and reproductive health care among poor urban female adolescents in Nicaragua
Authors: Meuwissen Liesbeth E. , Gorter Anna C. , Segura Zoyla , Kester Arnold D. M. , Knottnerus J. A.
Published: October 2006

Background  To meet the needs of female adolescents from low‐income urban areas for sexual and reproductive health (SRH) care, vouchers providing free‐of‐charge access to SRH care at 19 primary care clinics were distributed in Managua, Nicaragua. These vouchers substantially increased the use of services, demonstrating that many adolescents are willing to use such services, if readily accessible. The voucher redemption made it possible to identify the nature of existing, but largely unmet, needs for SRH care.

Method  The medical files from 3301 consultations with female adolescents were analysed using descriptive statistical methods and multiple logistic regression.

Results  Female adolescents presented SRH problems that merited medical attention. The mean number of problems presented was 1.5 per consultation: 34% of the vouchers were used for contraceptives, 31% for complaints related to sexually transmitted infection (STI) or reproductive tract infection (RTI), 28% for advice/counselling, 28% for antenatal check‐up and 18% for pregnancy testing. A new category of health care users emerged: sexually active girls who were neither pregnant nor mothers and who sought contraceptives or STI/RTI treatment. Contraceptive use doubled among the sexually active non‐pregnant voucher redeemers. Consultation with a female doctor younger than 36 years was associated with a higher chance of having contraceptives prescribed.

Conclusion  Accessible and appropriate SRH care has the potential to make an important contribution to the increased contraceptive use, decreased risk of unwanted teenage pregnancies and decreased prevalence of STIs/RTIs among underserved adolescents. Once adolescents access the services, providers have a crucial role in ensuring current and continuing needs are met.
Leishmania and sand flies: proximity to woodland as a risk factor for infection in a rural focus of visceral leishmaniasis in west central Venezuela
Authors: Feliciangeli M. Dora , Delgado Olinda , Suarez Benny , Bravo Arturo
Published: October 2006

Objective  To relate entomological, epidemiological and geographical data to understand the transmission dynamics of visceral leishmaniasis (VL) in a closed focus in western Venezuela.

Methods  Spatial and temporal patterns of Lutzomyia pseudolongipalpis, the most prevalent phlebotomine sand fly species (99.7%), were studied in El Brasilar, Curarigua, Lara State, Venezuela, a small rural community of 20 dwellings and 118 inhabitants. The sand fly population was monitored using Centers for Disease Control light traps monthly throughout 1 year in the domestic and sylvatic habitats and for 3 months in all inhabited houses.

Results  Temporal variation followed the yearly bimodal pattern of precipitation with the highest population densities in April and December. Infection with flagellates suggestive of Leishmania spp. was detected in 0.01% of 10 026 dissected females of L. pseudolongipalpis, which proved to be highly endophilic. Prevalence of Leishmania infection in people, as measured by the leishmanin skin test, was correlated with distance of the houses from the woodland and with sand fly abundance. A logistic regression model showed that for people who live in the village, the proximity to the woodland (linear) should be considered a risk factor for Leishmania infection (binary) (z = −2.02, P = 0.04, OR = 0.98, 95% CI = 0.97–0.99). This was consistent with the association between the proportion of VL infection and the log of sand fly abundance, which was negatively correlated with distance from the woodland.

Conclusion  We discuss strategies that might be useful in controlling VL transmission in this endemic focus.