bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarization anisotropy of individual core/shell GaAs/AlGaAs nanowires by photocurrent spectroscopy
Authors: Persano Anna , Nabet Bahram , Taurino Antonietta , Prete Paola , Lovergine Nico , Cola Adriano
Published: April 2011

We investigate the photodetection properties of individual core/shell GaAs/AlGaAs nanowires (NWs) and, in particular, their behavior under linearly polarized light. The NWs are grown by Au-assisted metalorganic vapor phase epitaxy and electrical contacts are defined on NWs by electron beam induced deposition. The spectral photocurrent of the single NW is measured and the dependence of the polarization anisotropy ρ (varying from ∼0.1 to ∼0.55) on the absorption wavelength is found to be clearly affected by the core/shell structure. High quantum efficiency values (10% at 600 nm) are obtained which are attractive for a wide range of optoelectronic devices.
Charge transport by modulating spin-orbit gauge fields for quasi-one-dimensional holes
Authors: Kernreiter T. , Governale M. , Hamilton A. R. , Zülicke U.
Published: April 2011

We present a theoretical study of ac charge transport arising from adiabatic temporal variation of zero-field spin splitting in a quasi-one-dimensional hole system (realized, e.g., in a quantum wire or point contact). As in conduction-electron systems, part of the current results from spin-dependent electromotive forces. We find that the magnitude of this current contribution is two orders of magnitude larger for holes and exhibits parametric dependences that make it more easily accessible experimentally. Our results suggest hole structures to be good candidates for realizing devices where spin currents are pumped by time-varying electric fields.
Silicon-based tunneling field-effect transistor with elevated germanium source formed on (110) silicon substrate
Authors: Han Genquan , Guo Pengfei , Yang Yue , Zhan Chunlei , Zhou Qian , Yeo Yee-Chia
Published: April 2011

Si-based tunneling field-effect transistors (TFETs) with elevated Ge source were fabricated on Si(110) substrate. The in situ B-doped Ge (Ge:B) source grown on Si(110) has a substitutional B concentration up to 7.8×1020 cm−3, that is more than one order of magnitude higher than that in Ge grown on Si(100) under the same growth conditions. Ge:B epitaxy on (110) and (100) Si is discussed. The TFET with elevated Ge source formed on Si(110) has a subthreshold swing of 85 mV/decade, which is a substantial improvement over that of the control TFET formed on Si(100). This is attributed to the high B doping concentration in the Ge:B(110) source as well as the band gap narrowing effect.
Note: Resonant microwave compressor with two output ports for synchronous energy extraction
Authors: Avgustinovich V. A. , Artemenko S. N. , Kaminsky V. L. , Novikov S. A. , Yushkov Yu. G.
Published: April 2011

The brief theoretical analysis shows the resonant microwave compressor provides the output pulse power higher than the traveling wave power in the storage cavity. The experimental study was made with the model of the S-band microwave compressor. The power of pulses generated by the device reached the value three times as much as the value of the traveling wave power in the storage cavity at the maximum amplification 23 dB, peak power 400 MW, and pulse width 4–5 ns.
Bare Life: Border-Crossing Deaths and Spaces of Moral Alibi
Authors: Doty Roxanne Lynn
Published: April 2011

This paper examines the US border control strategy of ‘prevention through deterrence’ as an instance of biopolitics that has resulted in an alarming increase in migrant deaths over the past sixteen years. I argue that this policy renders unauthorized migrants as ‘bare life’, individuals whose deaths are deemed of little consequence. Geographic space has been an essential aspect of this policy, both for its presumed (though not realized) deterrent power and in the fact that it provides a moral alibi that enables policy makers to deny responsibility for the deaths. This study contributes to recent conversations on biopower and bare life by (1) highlighting the fact that biopower as it pertains to the constitution of ‘the population’ is far from being solely a local or national phenomenon, but rather is inherently connected to drawing distinctions between the national and the international and by (2) arguing for the significance of race in this process.
Variability of acidity in agricultural soils—the impact of timber burning at land clearing
Authors: Fraser Mark A. , Scott Brendan J.
Published: April 2011

Patchiness in the growth of barrel medic, Medicago truncatula, in the central west of New South Wales, near Condobolin, has been associated with variability of soil acidity. There is evidence of the effect of timber burning on soil properties and it is possible that such burning of timber stacks and windrows on land recently cleared for agriculture may add alkali and contribute to such pasture growth. Of the three sites used, two were already in a 20-year farming system and one was constructed in a recently cleared paddock. Soil sampled at the 0–0.10, 0.10–0.20, and 0.20–0.30 m soil depths indicated significant increases in soil pHCa and extractable Ca to a soil depth of at least 0.20 m for up to 20 years after timber had been burnt. The effect of the timber burn on soil chemistry was due to the conversion of alkali oxides to either hydroxides or carbonates. This addition of alkali moved relatively rapidly through the soil profile in a low-rainfall farming system. Additional alkali was found in the soil, mainly at the 0–0.10 m depth, in the form of free lime. Using assumed rates of soil acidification, the burn effect could persist for up to 1227 years before reverting to the pre-burn soil pH. It was also found that timber burning at the sites contributed to the spatial variability of soil acidity.
Phosphorus budget and organic phosphorus fractions in response to long-term applications of chemical fertilisers and pig manure in a Mollisol
Authors: Song Chun , Han Xiaozeng , Wang Enli
Published: April 2011

This paper describes the effects of chemical fertiliser and pig manure application on the phosphorus (P) balance and changes of soil organic P (Po) fractions in a Mollisol following 14 years of maize–soybean–wheat rotation in Northeast China. The experiment was designed according to the local crop rotation and management system, consisting of a control treatment with no fertiliser application, a treatment with chemical nitrogen (N) and P fertilisers, and a treatment with chemical N and P fertilisers plus pig manure. The results suggest that the levels of local chemical fertiliser applications seem to balance the P removal by the crops, while the additional P in the pig manure resulted in substantial accumulation of P in the soil despite greater crop production. Analysis of Po fractions showed that long-term cultivation without fertilisation reduced the soil labile Po. Additions of P through application of chemical fertilisers only preserved the labile Po content, whereas addition of chemical P fertiliser plus pig manure increased the labile Po content. Comparison between 1993 and 2007 soil samples indicates that the moderately labile Po content declined in all treatments, whereas the non-labile Po content increased. These results suggest that the moderately labile Po may be transformed into labile Po and Pi, and that some active P fractions were immobilised during long-term cultivation. Adding fertiliser increased P availability and alleviated soil P immobilisation.
Heading for greener pastures? Defining the foraging preferences of urban long-nosed bandicoots
Authors: Hughes Nelika K. , Banks Peter B.
Published: April 2011

The impact of urbanisation is delayed for many species, as populations that manage to survive the initial loss of habitat gradually decline throughout the urban–bushland mosaic. Yet many species’ chances of persistence within urban areas can be increased through relatively simple management techniques, and an understanding of how remnant populations use the interface between urban and natural landscapes is therefore crucial to their long-term management. Here we examine the habitat preferences of a semi-urban population of long-nosed bandicoots (Perameles nasuta) that inhabits a matrix of urban open lawn and dense native heath macrohabitats. We radio-tracked animals in these two distinct macrohabitats and compared the microhabitat features between core and peripheral areas of home ranges. Core and peripheral areas did not differ in their characteristics for either macrohabitat; however, individuals showed a high level of fidelity to distinct foraging patches. We then related microhabitat features to an index of foraging activity using generalised linear modelling and found that diggings were more abundant in areas with moist, soft soils close to cover. Soil softness and moisture were experimentally increased via artificial watering on selected sites. After only 10 days there were significantly more diggings on watered than non-watered sites. Thus, bandicoots appear to be a matrix-sensitive species, using some open grass areas of the matrix but requiring the vegetation cover of remnant bush. We suggest, however, that artificial watering and additional cover may be one way to increase foraging opportunities to make this, and other semi-urban, populations matrix-occupying, and thus facilitate bandicoot persistence in the urban mosaic.
Microclimate preferences of the grey-headed flying fox (Pteropus poliocephalus) in the Sydney region
Authors: Snoyman Stephanie , Brown Culum
Published: April 2011

The population size of the grey-headed flying fox (Pteropus poliocephalus) has decreased dramatically as a result of a variety of threatening processes. This species spends a great proportion of time in roosting large social aggregations in urban areas, causing conflict between wildlife and humans. Little is known about why these bats choose to roost in some locations in preference to others. Roost selection by cave-dwelling bats can be greatly influenced by microclimatic variables; however, far less is known about microclimate selection in tree-roosting species despite the direct management implications. This study aimed to determine the microclimate characteristics of P. poliocephalus camps. Temperature and humidity data were collected via data-loggers located both in six camps and the bushland immediately adjacent to the camps in the greater Sydney region. We found significant differences between the microclimate within the camps and the surrounding bushland. In general, areas within the camps had a greater variance in temperature and humidity than the alternative locations. We hypothesise that camps may be specifically located in areas with high microclimate variance to accommodate a range of individual preferences that vary depending on demography.
Distribution and population genetic structure of the critically endangered skink Nangura spinosa, and the implications for management
Authors: Borsboom Adrian C. , Couper Patrick J. , Amey Andrew , Hoskin Conrad J.
Published: April 2011

Many threatened species occur as small, isolated populations. Understanding the extent and genetic distinctiveness of these populations is essential for management. Nangura spinosa is a critically endangered skink known from two small populations in dry rainforest in south-east Queensland. We conducted targeted surveys between 2001 and 2010 at the two known N. spinosa sites (Nangur National Park, Oakview National Park area) and in 22 nearby forest blocks with potentially suitable habitat. N. spinosa was found only at the two previously known sites, which are ~36 km apart. The skink appears to be declining at Nangur NP, to an estimated extent of occurrence of 7.4 ha and potentially no more than 35 adults. In contrast, we increase the extent of occurrence at Oakview to 360 ha, where the population is at least in the hundreds. Sequencing of two mtDNA genes revealed considerable genetic divergence between the two populations (3.8% for ND4; 1.2% for 16S), suggesting an extended period of separation. Population fragmentation is therefore not the result of recent land clearing, but of long-term isolation by unsuitable habitat. Each population should be considered a distinct management unit. More data are required on population size and trends, recruitment and threats, particularly for the Nangur population.
Transkingdom signaling based on bacterial cyclodipeptides with auxin activity in plants
Authors: Ortiz-Castro Randy , Díaz-Pérez César , Martínez-Trujillo Miguel , del Río Rosa E. , Campos-García Jesús , López-Bucio José
Published: April 2011

Microorganisms and their hosts communicate with each other through an array of signals. The plant hormone auxin (indole-3-acetic acid; IAA) is central in many aspects of plant development. Cyclodipeptides and their derivative diketopiperazines (DKPs) constitute a large class of small molecules synthesized by microorganisms with diverse and noteworthy activities. Here, we present genetic, chemical, and plant-growth data showing that in
Pseudomonas aeruginosa
, the LasI quorum-sensing (QS) system controls the production of three DKPs—namely, cyclo(
l
-Pro-
l
-Val), cyclo(
l
-Pro-
l
-Phe), and cyclo(
l
-Pro-
l
-Tyr)—that are involved in plant growth promotion by this bacterium. Analysis of all three bacterial DKPs in
Arabidopsis thaliana
seedlings provided detailed information indicative of an auxin-like activity, based on their efficacy at modulating root architecture, activation of auxin-regulated gene expression, and response of auxin-signaling mutants
tir1
,
tir1 afb2 afb3
,
arf7
,
arf19
, and
arf7arf19
. The observation that QS-regulated bacterial production of DKPs modulates auxin signaling and plant growth promotion establishes an important function for DKPs mediating prokaryote/eukaryote transkingdom signaling.
Cisplatin binds human copper chaperone Atox1 and promotes unfolding in vitro
Authors: Palm Maria E. , Weise Christoph F. , Lundin Christina , Wingsle Gunnar , Nygren Yvonne , Björn Erik , Naredi Peter , Wolf-Watz Magnus , Wittung-Stafshede Pernilla
Published: April 2011

Cisplatin (cisPt), Pt(NH
3
)
2
Cl
2
, is a cancer drug believed to kill cells via DNA binding and damage. Recent work has implied that the cellular copper (Cu) transport machinery may be involved in cisPt cell export and drug resistance. Normally, the Cu chaperone Atox1 binds Cu(I) via two cysteines and delivers the metal to metal-binding domains of ATP7B; the ATP7B domains then transfer the metal to the Golgi lumen for loading on cuproenzymes. Here, we use spectroscopic methods to test if cisPt interacts with purified Atox1 in solution in vitro. We find that cisPt binds to Atox1’s metal-binding site regardless of the presence of Cu or not: When Cu is bound to Atox1, the near-UV circular dichroism signals indicate Cu-Pt interactions. From NMR data, it is evident that cisPt binds to the folded protein. CisPt-bound Atox1 is however not stable over time and the protein begins to unfold and aggregate. The reaction rates are limited by slow cisPt dechlorination. CisPt-induced unfolding of Atox1 is specific because this effect was not observed for two unrelated proteins that also bind cisPt. Our study demonstrates that Atox1 is a candidate for cisPt drug resistance: By binding to Atox1 in the cytoplasm, cisPt transport to DNA may be blocked. In agreement with this model, cell line studies demonstrate a correlation between Atox1 expression levels, and cisplatin resistance.
Identification and characterization of an oocyte factor required for development of porcine nuclear transfer embryos
Authors: Miyamoto Kei , Nagai Kouhei , Kitamura Naoya , Nishikawa Tomoaki , Ikegami Haruka , Binh Nguyen T. , Tsukamoto Satoshi , Matsumoto Mai , Tsukiyama Tomoyuki , Minami Naojiro , Yamada Masayasu , Ariga Hiroyoshi , Miyake Masashi , Kawarasaki Tatsuo , Matsumoto Kazuya , Imai Hiroshi
Published: April 2011

Nuclear reprogramming of differentiated cells can be induced by oocyte factors. Despite numerous attempts, these factors and mechanisms responsible for successful reprogramming remain elusive. Here, we identify one such factor, necessary for the development of nuclear transfer embryos, using porcine oocyte extracts in which some reprogramming events are recapitulated. After incubating somatic nuclei in oocyte extracts from the metaphase II stage, the oocyte proteins that were specifically and abundantly incorporated into the nuclei were identified by mass spectrometry. Among 25 identified proteins, we especially focused on a multifunctional protein, DJ-1. DJ-1 is present at a high concentration in oocytes from the germinal vesicle stage until embryos at the four-cell stage. Inhibition ofDJ-1function compromises the development of nuclear transfer embryos but not that of fertilized embryos. Microarray analysis of nuclear transfer embryos in whichDJ-1function is inhibited shows perturbed expression ofP53pathway components. In addition, embryonic arrest of nuclear transfer embryos injected with anti–DJ-1antibody is rescued byP53inhibition. We conclude thatDJ-1is an oocyte factor that is required for development of nuclear transfer embryos. This study presents a means for identifying natural reprogramming factors in mammalian oocytes and a unique insight into the mechanisms underlying reprogramming by nuclear transfer.
Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones
Authors: Zhuravleva Anastasia , Gierasch Lila M.
Published: April 2011

The 70-kDa heat shock protein (Hsp70) chaperones perform a wide array of cellular functions that all derive from the ability of their N-terminal nucleotide-binding domains (NBDs) to allosterically regulate the substrate affinity of their C-terminal substrate-binding domains in a nucleotide-dependent mechanism. To explore the structural origins of Hsp70 allostery, we performed NMR analysis on the NBD of DnaK, the
Escherichia coli
Hsp70, in six different states (ligand-bound or apo) and in two constructs, one that retains the conserved and functionally crucial portion of the interdomain linker (residues

) and another that lacks the linker. Chemical-shift perturbation patterns identify residues at subdomain interfaces that constitute allosteric networks and enable the NBD to act as a nucleotide-modulated switch. Nucleotide binding results in changes in subdomain orientations and long-range perturbations along subdomain interfaces. In particular, our findings provide structural details for a key mechanism of Hsp70 allostery, by which information is conveyed from the nucleotide-binding site to the interdomain linker. In the presence of ATP, the linker binds to the edge of the IIA β-sheet, which structurally connects the linker and the nucleotide-binding site. Thus, a pathway of allosteric communication leads from the NBD nucleotide-binding site to the substrate-binding domain via the interdomain linker.
Symmetry-breaking orbital anisotropy observed for detwinned Ba(Fe

1-
x

Co

x

)
2
As
2
above the spin density wave transition
Authors: Yi Ming , Lu Donghui , Chu Jiun-Haw , Analytis James G. , Sorini Adam P. , Kemper Alexander F. , Moritz Brian , Mo Sung-Kwan , Moore Rob G. , Hashimoto Makoto , Lee Wei-Sheng , Hussain Zahid , Devereaux Thomas P. , Fisher Ian R. , Shen Zhi-Xun
Published: April 2011

Nematicity, defined as broken rotational symmetry, has recently been observed in competing phases proximate to the superconducting phase in the cuprate high-temperature superconductors. Similarly, the new iron-based high-temperature superconductors exhibit a tetragonal-to-orthorhombic structural transition (i.e., a broken C
4
symmetry) that either precedes or is coincident with a collinear spin density wave (SDW) transition in undoped parent compounds, and superconductivity arises when both transitions are suppressed via doping. Evidence for strong in-plane anisotropy in the SDW state in this family of compounds has been reported by neutron scattering, scanning tunneling microscopy, and transport measurements. Here, we present an angle-resolved photoemission spectroscopy study of detwinned single crystals of a representative family of electron-doped iron-arsenide superconductors, Ba(Fe

1-
x

Co

x

)
2
As
2
in the underdoped region. The crystals were detwinned via application of in-plane uniaxial stress, enabling measurements of single domain electronic structure in the orthorhombic state. At low temperatures, our results clearly demonstrate an in-plane electronic anisotropy characterized by a large energy splitting of two orthogonal bands with dominant
d

xz

and
d

yz

character, which is consistent with anisotropy observed by other probes. For compositions
x
 > 0, for which the structural transition (
T

S

) precedes the magnetic transition (
T
SDW
), an anisotropic splitting is observed to develop above
T
SDW
, indicating that it is specifically associated with
T

S

. For unstressed crystals, the band splitting is observed close to
T

S

, whereas for stressed crystals, the splitting is observed to considerably higher temperatures, revealing the presence of a surprisingly large in-plane nematic susceptibility in the electronic structure.
Rescue of expression and signaling of human luteinizing hormone G protein-coupled receptor mutants with an allosterically binding small-molecule agonist
Authors: Newton Claire L. , Whay Adele M. , McArdle Craig A. , Zhang Meilin , van Koppen Chris J. , van de Lagemaat Ruud , Segaloff Deborah L. , Millar Robert P.
Published: April 2011

Naturally occurring mutations of G protein-coupled receptors (GPCRs) causing misfolding and failure to traffic to the cell surface can result in disease states. Some small-molecule orthosteric ligands can rescue such misfolded receptors, presumably by facilitating their correct folding and shuttling to the plasma membrane. Here we show that a cell-permeant, allosterically binding small-molecule agonist (Org 42599) rescues the folding and cell surface expression, and therefore target cell signaling, of mutant human luteinizing hormone (LH) receptors (A593P and S616Y) that cause Leydig cell hypoplasia in man. Both mutant receptors were retained in the cytoplasm whereas WT receptor localized at the cell membrane, and binding of LH to cells expressing the mutant receptors was markedly lower than to those expressing the WT receptor. Incubation with Org 42599 increased mutant receptor expression, cell surface localization, and the proportion of mutant receptor in the mature glycosylated form. Importantly, although LH stimulated little (S616Y) or no (A593P) activation of cells expressing mutant receptors, incubation of cells with Org 42599 facilitated rescue of expression and stimulation by the native ligand, LH. Although Org 42599 could activate these receptors, it could not displace
125
I-labeled human LH binding to the WT receptor, indicating that it acts in an allosteric manner. Here we demonstrate a small-molecule GPCR allosteric agonist that functionally rescues intracellularly retained mutant LH receptors by facilitating their cell surface expression. This approach may have application for treatment of infertile patients bearing such mutations and, more broadly, for other misfolded GPCR mutants resulting in human pathologic processes.
Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3′ termini
Authors: Martin Arnold , Hoefs Nadja , Tadewaldt Josefine , Staeheli Peter , Schneider Urs
Published: April 2011

The terminal structures of the Borna disease virus (BDV) genome (vRNA) and antigenome (cRNA) differ from those of other negative strand RNA viruses, as both molecules possess four nucleotides at the 3′ terminus without an apparent template at the 5′ end of the opposite strand. Consequently, the v- and cRNA molecules are not perfect mirror images, a situation that is not compatible with conventional strategies to maintain genetic information. We show here that recombinant viruses recovered from cDNA lacking the nontemplated nucleotides efficiently reconstitute the 3′ overhangs. Analyses of recombinant viruses encoding genetic markers in potential alternative template sequences demonstrated that the BDV v- and cRNA molecules are extended by a realign-and-elongation process on internal template motifs located in close proximity to the 3′ ends of v- and cRNA, respectively. The data further suggest that cRNA elongation is restricted to a single template motif of the nascent strand, whereas elongation of vRNA might use multiple template motifs. We propose that the elongation of the 3′ termini supports the terminal integrity of the genomic RNA molecules during BDV persistence, and furthermore provides an elegant strategy to eliminate the triphosphate groups from the 5′ termini of the BDV v- and cRNA without compromising the genetic information of the virus.
Comparative analysis of constraints and caste differences in brain investment among social paper wasps
Authors: O'Donnell Sean , Clifford Marie , Molina Yamile
Published: April 2011

We compared species mean data on the size of functionally distinct brain regions to test the relative rates at which investment in higher-order cognitive processing (mushroom body calyces) versus peripheral sensory processing (optic and antennal lobes) increased with increasing brain size. Subjects were eusocial paper wasps from queen and worker castes of 10 species from different genera. Relative investment in central processing tissue increased with brain size at a higher rate than peripheral structure investment, demonstrating that tissue devoted to higher-order cognitive processing is more constrained by brain size. This pattern held for raw data and for phylogenetically independent contrasts. These findings suggest that there is a minimum necessary investment in peripheral sensory processing brain tissue, with little to gain from additional investment. In contrast, increased brain size provides opportunities to invest in additional higher-order cognitive processing tissue. Reproductive castes differed within species in brain tissue investment, with higher central-to-peripheral brain tissue ratios in queens than in workers. Coupled with previous findings that paper wasp queen, but not worker, brain architecture corresponds to ecological and social variation, queen brain evolution appears to be most strongly shaped by cognitive demands, such as social interactions. These evolutionary patterns of neural investment echo findings in other animal lineages and have important implications, given that a greater investment in higher-order processing has been shown to increase the prevalence of complex and flexible behaviors across the animal kingdom.
Minimum energy compact structures in force-quench polyubiquitin folding are domain swapped
Authors: Xia Fei , Thirumalai D. , Gräter Frauke
Published: April 2011

Single molecule experiments that initiate folding using mechanical force are uniquely suited to reveal the nature of populated states in the folding process. Using a strategy proposed on theoretical grounds, which calls for repeated cycling of force from high to low values using force pulses, it was demonstrated in atomic force spectroscopy (AFM) experiments that an ensemble of minimum energy compact structures (MECS) are sampled during the folding of polyubiquitin. The structures in the ensemble are mechanically resistant to a lesser extent than the native state. Remarkably, forced unfolding of the populated intermediates reveals a broad distribution of extensions including steps up to 30 nm and beyond. We show using molecular simulations that favorable interdomain interactions leading to domain swapping between adjacent ubiquitin modules results in the formation of the ensemble of MECS, whose unfolding leads to an unusually broad distribution of steps. We obtained the domain-swapped structures using coarse-grained ubiquitin dimer models by exchanging native interactions between two monomeric ubiquitin molecules. Brownian dynamics force unfolding of the proposed domain-swapped structures, with mechanical stability that is approximately 100-fold lower than the native state, gives rise to a distribution of extensions from 2 to 30 nm. Our results, which are in quantitative agreement with AFM experiments, suggest that domain swapping may be a general mechanism in the assembly of multi-sub-unit proteins.
Revealing protein oligomerization and densities in situ using spatial intensity distribution analysis
Authors: Godin Antoine G. , Costantino Santiago , Lorenzo Louis-Etienne , Swift Jody L. , Sergeev Mikhail , Ribeiro-da-Silva Alfredo , De Koninck Yves , Wiseman Paul W.
Published: April 2011

Measuring protein interactions is key to understanding cell signaling mechanisms, but quantitative analysis of these interactions in situ has remained a major challenge. Here, we present spatial intensity distribution analysis (SpIDA), an analysis technique for image data obtained using standard fluorescence microscopy. SpIDA directly measures fluorescent macromolecule densities and oligomerization states sampled within single images. The method is based on fitting intensity histograms calculated from images to obtain density maps of fluorescent molecules and their quantal brightness. Because spatial distributions are acquired by imaging, SpIDA can be applied to the analysis of images of chemically fixed tissue as well as live cells. However, the technique does not rely on spatial correlations, freeing it from biases caused by subcellular compartmentalization and heterogeneity within tissue samples. Analysis of computer-based simulations and immunocytochemically stained GABA
B
receptors in spinal cord samples shows that the approach yields accurate measurements over a broader range of densities than established procedures. SpIDA is applicable to sampling within small areas (6 μm
2
) and reveals the presence of monomers and dimers with single-dye labeling. Finally, using GFP-tagged receptor subunits, we show that SpIDA can resolve dynamic changes in receptor oligomerization in live cells. The advantages and greater versatility of SpIDA over current techniques open the door to quantificative studies of protein interactions in native tissue using standard fluorescence microscopy.
Vaccination strategies for epidemic cholera in Haiti with implications for the developing world
Authors: Chao Dennis L. , Halloran M. Elizabeth , Longini Ira M.
Published: April 2011

In October 2010, a virulent South Asian strain of El Tor cholera began to spread in Haiti. Interventions have included treatment of cases and improved sanitation. Use of cholera vaccines would likely have further reduced morbidity and mortality, but such vaccines are in short supply and little is known about effective vaccination strategies for epidemic cholera. We use a mathematical cholera transmission model to assess different vaccination strategies. With limited vaccine quantities, concentrating vaccine in high-risk areas is always most efficient. We show that targeting one million doses of vaccine to areas with high exposure to
Vibrio cholerae
, enough for two doses for 5% of the population, would reduce the number of cases by 11%. The same strategy with enough vaccine for 30% of the population with modest hygienic improvement could reduce cases by 55% and save 3,320 lives. For epidemic cholera, we recommend a large mobile stockpile of enough vaccine to cover 30% of a country's population to be reactively targeted to populations at high risk of exposure.
Severity of innate immune-mediated colitis is controlled by the cytokine deficiency-induced colitis susceptibility-1 (
Cdcs1
) locus
Authors: Ermann Joerg , Garrett Wendy S. , Kuchroo Juhi , Rourida Khadija , Glickman Jonathan N. , Bleich Andre , Glimcher Laurie H.
Published: April 2011

Genetic modifier loci influence the phenotypic expression of many Mendelian traits; insight into disease pathogenesis gained from their identification in animal disease models may impact the treatment of human multigenic disorders. We previously described an innate immune-driven model of spontaneous ulcerative colitis in T-bet
−/−
.Rag2
−/−
double-deficient mice that resembles human ulcerative colitis. On a BALB/c background, this disease is highly penetrant and results in the development of colorectal cancer. However, we observed that colitis in T-bet
−/−
.Rag2
−/−
mice on a C57BL/6 background was significantly less severe. Quantitative trait locus analysis using an N2 backcross strategy revealed a single major quantitative trait locus on chromosome 3 that mapped to the
Cdcs1
(cytokine deficiency-induced colitis susceptibility-1) locus previously identified in the

Il10
−/−

and

Gnai2
−/−

colitis models. Congenic introduction of the susceptible
Cdcs1
interval from C3H/He into the C57BL/6 background restored colitis severity. Bone marrow reconstitution experiments further mapped the effect of host genetics on disease severity to the hematopoietic compartment. There were distinct differences in the expression of several
Cdcs1
genes in bone marrow-derived dendritic cells from
Cdcs1
congenic mice. We conclude that the
Cdcs1
locus controls colitis severity in T-bet
−/−
.Rag2
−/−
mice through innate immune cells.
Identities of dis/ability and music
Authors: Watts Michael , Ridley Barbara
Published: April 2011

Centring on a small‐scale capability‐based case study of music provision for adults with profound dis/abilities, this paper considers the significance of music and music education in people's lives. It offers a philosophical defence of music's importance in enjoying a truly human life and then, drawing on an overview of the work of dis/abled artists and the findings of the case study, it addresses two issues that may inhibit those with dis/abilities from achieving the good life through musical endeavour: the provision of specialised musical equipment to enable people of different physical abilities to achieve the same end of making music; and the element of shame that may cause those with dis/abilities to accept a reduced standard of living. Although our immediate concern is with musical provision for those with profound dis/abilities, our argument is pertinent to other marginalised groups and curricula.
MDC1 collaborates with TopBP1 in DNA replication checkpoint control
Authors: Wang Jiadong , Gong Zihua , Chen Junjie
Published: April 2011

Human TopBP1 is a major player in the control of the DNA replication checkpoint. In this study, we identified MDC1, a key checkpoint protein involved in the cellular response to DNA double-strand breaks, as a TopBP1-associated protein. The specific TopBP1–MDC1 interaction is mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr (SDT) repeats of MDC1. In addition, we demonstrated that TopBP1 accumulation at stalled replication forks is promoted by the H2AX/MDC1 signaling cascade. Moreover, MDC1 is important for ATR-dependent Chk1 activation in response to replication stress. Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint.
Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins
Authors: Dantas Tiago J. , Wang Yifan , Lalor Pierce , Dockery Peter , Morrison Ciaran G.
Published: April 2011

The principal microtubule-organizing center in animal cells, the centrosome, contains centrin, a small, conserved calcium-binding protein unique to eukaryotes. Several centrin isoforms exist and have been implicated in various cellular processes including nuclear export and deoxyribonucleic acid (DNA) repair. Although centrins are required for centriole/basal body duplication in lower eukaryotes, centrin functions in vertebrate centrosome duplication are less clear. To define these roles, we used gene targeting in the hyperrecombinogenic chicken DT40 cell line to delete all three centrin genes in individual clones. Unexpectedly, centrin-deficient cells underwent normal cellular division with no detectable cell cycle defects. Light and electron microscopy analyses revealed no significant difference in centrosome composition or ultrastructure. However, centrin deficiency made DT40 cells highly sensitive to ultraviolet (UV) irradiation, with Cetn3 deficiency exacerbating the sensitivity of Cetn4/Cetn2 double mutants. DNA damage checkpoints were intact, but repair of UV-induced DNA damage was delayed in centrin nulls. These data demonstrate a role for vertebrate centrin in nucleotide excision repair.
Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front–back polarity in migrating cells
Authors: Vicente-Manzanares Miguel , Newell-Litwa Karen , Bachir Alexia I. , Whitmore Leanna A. , Horwitz Alan Rick
Published: April 2011

Migratory front–back polarity emerges from the cooperative effect of myosin IIA (MIIA) and IIB (MIIB) on adhesive signaling. We demonstrate here that, during polarization, MIIA and MIIB coordinately promote localized actomyosin bundling, which generates large, stable adhesions that do not signal to Rac and thereby form the cell rear. MIIA formed dynamic actomyosin proto-bundles that mark the cell rear during spreading; it also bound to actin filament bundles associated with initial adhesion maturation in protrusions. Subsequent incorporation of MIIB stabilized the adhesions and actomyosin filaments with which it associated and formed a stable, extended rear. These adhesions did not turn over and no longer signal to Rac. Microtubules fine-tuned the polarity by positioning the front opposite the MIIA/MIIB-specified rear. Decreased Rac signaling in the vicinity of the MIIA/MIIB-stabilized proto-bundles and adhesions was accompanied by the loss of Rac guanine nucleotide exchange factor (GEFs), like βPIX and DOCK180, and by inhibited phosphorylation of key residues on adhesion proteins that recruit and activate Rac GEFs. These observations lead to a model for front–back polarity through local GEF depletion.
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells
Authors: Inami Yoshihiro , Waguri Satoshi , Sakamoto Ayako , Kouno Tsuguka , Nakada Kazuto , Hino Okio , Watanabe Sumio , Ando Jin , Iwadate Manabu , Yamamoto Masayuki , Lee Myung-Shik , Tanaka Keiji , Komatsu Masaaki
Published: April 2011

Suppression of autophagy is always accompanied by marked accumulation of p62, a selective autophagy substrate. Because p62 interacts with the Nrf2-binding site on Keap1, which is a Cullin 3–based ubiquitin ligase adapter protein, autophagy deficiency causes competitive inhibition of the Nrf2–Keap1 interaction, resulting in stabilization of Nrf2 followed by transcriptional activation of Nrf2 target genes. Herein, we show that liver-specific autophagy-deficient mice harbor adenomas linked to both the formation of p62- and Keap1-positive cellular aggregates and induction of Nrf2 targets. Importantly, similar aggregates were identified in more than 25% of human hepatocellular carcinomas (HCC), and induction of Nrf2 target genes was recognized in most of these tumors. Gene targeting of p62 in an HCC cell line markedly abrogates the anchorage-independent growth, whereas forced expression of p62, but not a Keap1 interaction-defective mutant, resulted in recovery of the growth defect. These results indicate the involvement of persistent activation of Nrf2 through the accumulation of p62 in hepatoma development.
KLF13 sustains thymic memory-like CD8+ T cells in BALB/c mice by regulating IL-4–generating invariant natural killer T cells
Authors: Lai Dazhi , Zhu Jinfang , Wang Tianhong , Hu-Li Jane , Terabe Masaki , Berzofsky Jay A. , Clayberger Carol , Krensky Alan M.
Published: April 2011

“Memory-like T cells” are a subset of thymic cells that acquire effector function through the maturation process rather than interaction with specific antigen. Disruption of genes encoding T cell signaling proteins or transcription factors have provided insights into the differentiation of such cells. In this study, we show that in BALB/c, but not C57BL/6, mice, a large portion of thymic CD4-CD8+ T cells exhibit a memory-like phenotype. In BALB/c mice, IL-4 secreted by invariant natural killer T (iNKT) cells is both essential and sufficient for the generation of memory-like T cells. In C57BL/6 mice, iNKT cells are less abundant, producing IL-4 that is insufficient to induce thymic memory-like CD8+ T cells. BALB/c mice deficient in the transcription factor Kruppel-like factor (KLF) 13 have comparable numbers of iNKT cells to C57BL/6 mice and extremely low levels of thymic memory-like CD8+ T cells. This work documents the impact of a small number of KLF13-dependent iNKT cells on the generation of memory-like CD8+ T cells.
Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain
Authors: Artegiani Benedetta , Lindemann Dirk , Calegari Federico
Published: April 2011

Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)–cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4–cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.
Evaluating management strategies for eastern Bering Sea walleye pollock (Theragra chalcogramma) in a changing environment
Authors: Ianelli James N. , Hollowed Anne B. , Haynie Alan C. , Mueter Franz J. , Bond Nicholas A.
Published: April 2011

Ianelli, J. N., Hollowed, A. B., Haynie, A. C., Mueter, F. J., and Bond, N. A. 2011. Evaluating management strategies for eastern Bering Sea walleye pollock (Theragra chalcogramma) in a changing environment. – ICES Journal of Marine Science, 68: 1297–1304. The impacts of climate change on fish and fisheries is expected to increase the demand for more accurate stock projections and harvest strategies that are robust to shifting production regimes. To address these concerns, we evaluate the performance of fishery management control rules for eastern Bering Sea walleye pollock stock under climate change. We compared the status quo policy with six alternative management strategies under two types of recruitment pattern simulations: one that follows temperature-induced trends and the other that follows a stationary recruitment pattern similar to historical observations. A subset of 82 Intergovernmental Panel on Climate Change climate models provided temperature inputs from which an additional 100 stochastic simulated recruitments were generated to obtain the same overall recruitment variability as observed for the stationary recruitment simulations. Results indicate that status quo management with static reference points and current ecosystem considerations will result in much lower average catches and an increased likelihood of fishery closures, should reduced recruitment because of warming conditions hold. Alternative reference point calculations and control rules have similar performance under stationary recruitment relative to status quo, but may offer significant gains under the changing environmental conditions.
Development of a stock–recruit model for simulating stock dynamics for uncertain situations: the example of Northeast Atlantic mackerel (Scomber scombrus)
Authors: Simmonds E. John , Campbell Andrew , Skagen Dankert , Roel Beatriz A. , Kelly Ciaran
Published: April 2011

Simmonds, E. J., Campbell, A., Skagen, D., Roel, B. A., and Kelly, C. 2011. Development of a stock–recruit model for simulating stock dynamics for uncertain situations: the example of Northeast Atlantic mackerel (Scomber scombrus). – ICES Journal of Marine Science, 68: 848–859. The assumption of a relationship between recruitment and a spawning stock is the cornerstone of the precautionary approach and may constrain the use of a maximum sustainable yield (MSY) target for fisheries management, because the failure to include such a relationship suggests that providing a measure of stock protection is unnecessary. The implications of fitting different functional forms and stochastic distributions to stock-and-recruit data are investigated. The importance of these considerations is shown by taking a practical example from management: the management plan for Northeast Atlantic mackerel (Scomber scombrus), a fish stock with an average annual catch of 600 000 t. The historical range of spawning-stock biomass is narrow, and historical data from a stock assessment explain only a small proportion of the recruitment variability. We investigate how best to reflect the uncertainty in the stock–recruit relationship. Selecting a single model based on simple statistical criteria can have major consequences for advice and is problematic. Selecting a distribution of models with derived probabilities gives a more complete perception of uncertainty in dynamics. Differences in functional form, distribution of deviations, and variability of coefficients are allowed. The approach appropriately incorporates uncertainty in the stock–recruit relationship for FMSY estimation.
Nine decades of North Sea sole and plaice distribution
Authors: Engelhard Georg H. , Pinnegar John K. , Kell Laurence T. , Rijnsdorp Adriaan D.
Published: April 2011

Engelhard, G. H., Pinnegar, J. K., Kell, L. T., and Rijnsdorp, A. D. 2011. Nine decades of North Sea sole and plaice distribution. – ICES Journal of Marine Science, 68: 1090–1104. Recent studies based mainly on research survey data suggest that within the North Sea, sole Solea solea and plaice Pleuronectes platessa have exhibited distribution shifts in recent decades—on average southward for sole and northward to deeper waters for plaice. Various hypotheses may account for such shifts, including climate change effects and more intensive fishing in southern and shallower waters; but the relatively short time-span of datasets analysed so far (∼3 decades) has complicated the separation of these two effects. We have made use of a unique dataset of catch and effort data for British North Sea trawlers; these cover nine decades (spanning the period 1913–2007) and are spatially detailed by ICES rectangle (0.5° latitude by 1° longitude). We quantify, for the first time, long-term distribution changes of North Sea sole and plaice over a period approaching a century, and demonstrate that the distribution shift in plaice was attributable to climate change rather than to fishing, but that both climate and fishing played a role in the distribution shift of sole. The discussion also highlights the potential impact of additional factors, including eutrophication, prey availability, and habitat modification.