bluuebunny/crossref_metadata_2025 huggingface dataset:
Widely tunable distributed-feedback lasers with chirped gratings
Authors: Xue Liang , Brueck S. R. J. , Kaspi R.
Published: April 2009

A quasicontinuous tuning range of 65 nm at 3.2 μm was obtained for continuous wave, single-longitudinal-mode operation at 77 K of an optically pumped distributed-feedback laser with a chirped grating. Interferometric lithography with spherical wavefronts was used to fabricate a large-area chirped grating whose period varied continuously in the direction of the grating lines. Tuning was achieved by translating the optical pump stripe relative to the device to activate regions with different grating periods. Methane absorption spectra, obtained using this tunable distributed-feedback laser, closely match the high-resolution transmission molecular absorption database simulations.
How accurate are the marker orders in crop linkage maps generated from large marker datasets?
Authors: Collard Bertrand , Mace Emma , McPhail Mark , Wenzl Peter , Cakir Mehmet , Fox Glen , Poulsen David , Jordan David
Published: April 2009

Marker ordering during linkage map construction is a critical component of QTL mapping research. In recent years, high-throughput genotyping methods have become widely used, and these methods may generate hundreds of markers for a single mapping population. This poses problems for linkage analysis software because the number of possible marker orders increases exponentially as the number of markers increases. In this paper, we tested the accuracy of linkage analyses on simulated recombinant inbred line data using the commonly used Map Manager QTX (Manly et al. 2001: Mammalian Genome 12, 930–932) software and RECORD (Van Os et al. 2005: Theoretical and Applied Genetics 112, 30–40). Accuracy was measured by calculating two scores: % correct marker positions, and a novel, weighted rank-based score derived from the sum of absolute values of true minus observed marker ranks divided by the total number of markers. The accuracy of maps generated using Map Manager QTX was considerably lower than those generated using RECORD. Differences in linkage maps were often observed when marker ordering was performed several times using the identical dataset. In order to test the effect of reducing marker numbers on the stability of marker order, we pruned marker datasets focusing on regions consisting of tightly linked clusters of markers, which included redundant markers. Marker pruning improved the accuracy and stability of linkage maps because a single unambiguous marker order was produced that was consistent across replications of analysis. Marker pruning was also applied to a real barley mapping population and QTL analysis was performed using different map versions produced by the different programs. While some QTLs were identified with both map versions, there were large differences in QTL mapping results. Differences included maximum LOD and R2 values at QTL peaks and map positions, thus highlighting the importance of marker order for QTL mapping.
Response of peanut genotypes to mid-season moisture stress: phenological, morpho-physiological, and yield traits
Authors: Lal Chuni , Hariprasanna K. , Rathnakumar A. L. , Misra J. B. , Samdur M. Y. , Gor H. K. , Chikani B. M. , Jain V. K.
Published: April 2009

Nine peanut genotypes were evaluated in two seasons under irrigated and simulated mid-season drought conditions to investigate the influence of water stress on some phenological, morpho-physiological, and yield traits. Analysis of variance revealed significant genotypic differences for all the traits studied. Water saturation deficit and epicuticular wax load increased in response to water stress and age of the crop, while specific leaf area decreased with water stress and age of the crop. In general, correlations of water saturation deficit (WSD), epicuticular wax load (EWL), and specific leaf area (SLA) with yield traits were fairly weak. WSD in the early stage under irrigated conditions was found to be positively associated with pod yield under water stress; EWL in the early stage was negatively associated with harvest index (HI) under stress. Although significant and negative correlations of SLA were found only when it was recorded in the early stage under stress and the later stage under irrigated conditions with HI and pod yield (PY), both under irrigated conditions, the trends of its associations showed that SLA had rather weak and negative correlations with PY and HI both under irrigated and stress conditions. Genotypes that accumulated flowers sooner after initiation showed less yield reduction. The negative association between HI under stress and its reduction deems HI under moisture stress an important criterion of selection for drought tolerance in peanut.
Prevalence of ToxA-sensitive alleles of the wheat gene Tsn1 in Australian and Chinese wheat cultivars
Authors: Oliver Richard P. , Rybak Kasia , Solomon Peter S. , Ferguson-Hunt Margo
Published: April 2009

A recent survey of worldwide isolates of Stagonospora nodorum showed that all Australian isolates expressed the host-specific toxin ToxA (Stukenbrock and McDonald 2007). In contrast, very few Chinese isolates did. All the Australian Pyrenophora tritici-repentis isolates that were tested expressed ToxA. We therefore postulated that the wheat gene that confers sensitivity to ToxA, Tsn1, would vary in prevalence in wheat cultivars in use in the two countries. Contrary to expectation, 10 out of 21 Chinese cultivars responded to ToxA as did 26 out of 46 Australian cultivars. The result suggests that ToxA has not had a determining effect on the survival of wheat cultivars in either country. They also suggest that despite the widespread use of Tsn1 markers in Australia, sensitive alleles are still commonplace. The removal of sensitive alleles from breeders’ lines could be readily achieved and could significantly affect the resistance of wheat to both diseases.
Genetic diversity analysis among pre-green revolution, post-green revolution era cultivars, and wheat landraces as revealed by microsatellite markers
Authors: Jain Neelu , Yadav Rajbir
Published: April 2009

Bread wheat (Triticum aestivum L.) is the most widely grown crop in the world, and India is the second largest wheat producer after China. Introduction of input-responsive, semi-dwarf varieties set the foundation for the green revolution in the mid-1960s. To meet the future challenge of increasing food production with a shrinking land base, new varieties with higher yield potential and increased yield stability have to be developed by using the diverse genetic resource. The objective of this study was to evaluate genetic diversity in 74 wheat genotypes including released varieties in India occupying the pre-green revolution period (before 1965) and post-green revolution period (after 1965) and land races with microsatellite markers. SSRs represent a powerful tool to quantify genetic diversity in wheat. In total, 170 alleles were detected with an average of 3.3 alleles per locus. Overall, 24 rare alleles were present and 11 unique alleles were found in the studied landraces only. A positive correlation was found between the number of alleles and genetic diversity. Genetic relationships as determined by UPGMA (NTSYS-pc) and structure analyses grouped all modern wheat cultivars under one node. The traditional tall varieties released during the pre-green revolution era were clustered along with some of the landraces, indicating that they had possibly been developed through selection among the landraces. Diversity among the released varieties in the post-green revolution era has widened rather than narrowing down. Molecular variance analysis showed that variance was mainly distributed within (91.9%) rather than among (8.01%) the bread wheat varieties and landraces. The diversity obtained within the landraces proves them to be an important reservoir of biodiversity and source of novel alleles for use in breeding programs. Landraces such as MPG 62 and MPG 82 can be used for introgressing rare and unique alleles in the genetic background of high-yielding varieties.
Cold tolerance in rice varieties at different growth stages
Authors: Ye C. , Fukai S. , Godwin I. , Reinke R. , Snell P. , Schiller J. , Basnayake J.
Published: April 2009

Low temperature is a common production constraint in rice cultivation in temperate zones and high-elevation environments, with the potential to affect growth and development from germination to grain filling. There is a wide range of genotype-based differences in cold tolerance among rice varieties, these differences often reflecting growth conditions in the place of origin, as well as breeding history. However, improving low temperature tolerance of varieties has been difficult, due to a lack of clarity of the genetic basis to low temperature tolerance for different growth stages of the rice plant. Seeds or plants of 17 rice varieties of different origins were exposed to low temperature during germination (15°C), seedling, booting, and flowering stages (18.5°C), to assess their cold tolerance at different growth stages. Low temperature at the germination stage reduced both the percentage and speed of germination. Varieties from China (B55, Banjiemang, and Lijianghegu) and Hungary (HSC55) were more tolerant of low temperature than other varieties. Most of the varieties showed moderate levels of low temperature tolerance during the seedling stage, the exceptions being some varieties from Australia (Pelde, YRL39, and YRM64) and Africa (WAB160 and WAB38), which were susceptible to low temperature at the seedling stage. Low temperature at booting and flowering stages reduced plant growth and caused a significant decline in spikelet fertility. Some varieties from China (B55, Bangjiemang, Lijiangheigu), Japan (Jyoudeki), the USA (M103, M104), and Australia (Quest) were tolerant or moderately tolerant, while the remaining varieties were susceptible or moderately susceptible to low temperature at booting and flowering stages. Three varieties from China (B55, Lijianghegu, Banjiemang) and one from Hungary (HSC55) showed consistent tolerance to low temperature at all growth stages. These varieties are potentially important gene donors for breeding and genetic studies. The cold tolerance of the 17 rice varieties assessed at different growth stages was correlated. Screening for cold tolerance during early growth stages can therefore potentially be an effective way for assessing cold tolerance in breeding programs.
Flexible neural mechanisms of cognitive control within human prefrontal cortex
Authors: Braver Todd S. , Paxton Jessica L. , Locke Hannah S. , Barch Deanna M.
Published: April 2009

A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) were examined that, in a prior study, exhibited contrasting temporal dynamics between older and younger adults during performance of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit a proactive control pattern (primarily cue-based activation), whereas in older adults a reactive control pattern was found (primarily probe-based activation). In the current study, we found that following a period of task-strategy training, these older adults exhibited a proactive shift within a subset of the PFC regions, normalizing their activity dynamics toward young adult patterns. Conversely, under conditions of penalty-based monetary incentives, the younger adults exhibited a reactive shift some of the same regions, altering their temporal dynamics toward the older adult baseline pattern. These experimentally induced crossover patterns of temporal dynamics provide strong support for dual modes of cognitive control that can be flexibly shifted within PFC regions, via modulation of neural responses to changing task conditions or behavioral goals.
A continuum of genetic divergence from sympatric host races to species in the pea aphid complex
Authors: Peccoud Jean , Ollivier Anthony , Plantegenest Manuel , Simon Jean-Christophe
Published: April 2009

Sympatric populations of insects adapted to different host plants, i.e., host races, are good models to investigate how natural selection can promote speciation in the face of ongoing gene flow. However, host races are documented in very few model systems and their gradual evolution into good species, as assumed under a Darwinian view of species formation, lacks strong empirical support. We aim at resolving this uncertainty by investigating host specialization and gene flow among populations of the pea aphid complex,Acyrthosiphon pisum. Genetic markers and tests of host plant specificity indicate the existence of at least 11 well-distinguished sympatric populations associated with different host plants in Western Europe. Population assignment tests show variable migration and hybridization rates among sympatric populations, delineating 8 host races and 3 possible species. Notably, hybridization correlates negatively with genetic differentiation, forming a continuum of population divergence toward virtually complete speciation. The pea aphid complex thus illustrates how ecological divergence can be sustained among many hybridizing populations and how insect host races blend into species by gradual reduction of gene flow.
A gain in GABA
A
receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures
Authors: Schofield Claude M. , Kleiman-Weiner Max , Rudolph Uwe , Huguenard John R.
Published: April 2009

Neural inhibition within the thalamus is integral in shaping thalamocortical oscillatory activity. Fast, synaptic inhibition is primarily mediated by activation of heteropentameric GABA
A
receptor complexes. Here, we examined the synaptic physiology and network properties of mice lacking GABA
A
receptor α3, a subunit that in thalamus is uniquely expressed by inhibitory neurons of the reticular nucleus (nRT). Deletion of this subunit produced a powerful compensatory gain in inhibitory postsynaptic response in nRT neurons. Although, other forms of inhibitory and excitatory synaptic transmission in the circuit were unchanged, evoked thalamic oscillations were strongly dampened in α3 knockout mice. Furthermore, pharmacologically induced thalamocortical absence seizures displayed a reduction in length and power in α3 knockout mice. These studies highlight the role of GABAergic inhibitory strength within nRT in the maintenance of thalamic oscillations, and demonstrate that inhibitory intra-nRT synapses are a critical control point for regulating higher order thalamocortical network activity.
PIF3 is a repressor of chloroplast development
Authors: Stephenson Patrick G. , Fankhauser Christian , Terry Matthew J.
Published: April 2009

The phytochrome-interacting factor PIF3 has been proposed to act as a positive regulator of chloroplast development. Here, we show that the
pif3
mutant has a phenotype that is similar to the
pif1
mutant, lacking the repressor of chloroplast development PIF1, and that a
pif1pif3
double mutant has an additive phenotype in all respects. The
pif
mutants showed elevated protochlorophyllide levels in the dark, and etioplasts of
pif
mutants contained smaller prolamellar bodies and more prothylakoid membranes than corresponding wild-type seedlings, similar to previous reports of constitutive photomorphogenic mutants. Consistent with this observation,
pif1
,
pif3
, and
pif1pif3
showed reduced hypocotyl elongation and increased cotyledon opening in the dark. Transfer of 4-d-old dark-grown seedlings to white light resulted in more chlorophyll synthesis in
pif
mutants over the first 2 h, and analysis of gene expression in dark-grown
pif
mutants indicated that key tetrapyrrole regulatory genes such as
HEMA1
encoding the rate-limiting step in tetrapyrrole synthesis were already elevated 2 d after germination. Circadian regulation of
HEMA1
in the dark also showed reduced amplitude and a shorter, variable period in the
pif
mutants, whereas expression of the core clock components
TOC1
,
CCA1
, and
LHY
was largely unaffected. Expression of both
PIF1
and
PIF3
was circadian regulated in dark-grown seedlings. PIF1 and PIF3 are proposed to be negative regulators that function to integrate light and circadian control in the regulation of chloroplast development.
Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic β-cells
Authors: Zhang Sharon S. , Hao Ergeng , Yu Jianxiu , Liu Wen , Wang Jing , Levine Fred , Feng Gen-Sheng
Published: April 2009

Intracellular signaling by which pancreatic β-cells synthesize and secrete insulin in control of glucose homeostasis is not fully understood. Here we show that Shp2, a cytoplasmic tyrosine phosphatase possessing 2 SH2 domains, coordinates signaling events required for insulin biosynthesis in β-cells. Mice with conditional ablation of the
Shp2
/
Ptpn11
gene in the pancreas exhibited defective glucose-stimulated insulin secretion and impaired glucose tolerance. Consistently, siRNA-mediated Shp2-knockdown in rat insulinoma INS-1 832/13 cells resulted in decreased insulin production and secretion despite an increase in cellular ATP. Shp2 modulates the strength of signals flowing through Akt/FoxO1 and Erk pathways, culminating in control of Pdx1 expression and activity on
Ins1
and
Ins2
promoters, and forced
Pdx1
expression rescued insulin production in Shp2-knockdown β-cells. Therefore, Shp2 acts as a signal coordinator in β-cells, orchestrating multiple pathways controlling insulin biosynthesis to maintain glucose homeostasis.
Phonon softening and crystallographic orientation of strained graphene studied by Raman spectroscopy
Authors: Huang Mingyuan , Yan Hugen , Chen Changyao , Song Daohua , Heinz Tony F. , Hone James
Published: April 2009

We present a systematic study of the Raman spectra of optical phonons in graphene monolayers under tunable uniaxial tensile stress. Both the G and 2D bands exhibit significant red shifts. The G band splits into 2 distinct subbands (G
+
, G
−
) because of the strain-induced symmetry breaking. Raman scattering from the G
+
and G
−
bands shows a distinctive polarization dependence that reflects the angle between the axis of the stress and the underlying graphene crystal axes. Polarized Raman spectroscopy therefore constitutes a purely optical method for the determination of the crystallographic orientation of graphene.
Sustainable water deliveries from the Colorado River in a changing climate
Authors: Barnett Tim P. , Pierce David W.
Published: April 2009

The Colorado River supplies water to 27 million users in 7 states and 2 countries and irrigates over 3 million acres of farmland. Global climate models almost unanimously project that human-induced climate change will reduce runoff in this region by 10–30%. This work explores whether currently scheduled future water deliveries from the Colorado River system are sustainable under different climate-change scenarios. If climate change reduces runoff by 10%, scheduled deliveries will be missed ≈58% of the time by 2050. If runoff reduces 20%, they will be missed ≈88% of the time. The mean shortfall when full deliveries cannot be met increases from ≈0.5–0.7 billion cubic meters per year (bcm/yr) in 2025 to ≈1.2–1.9 bcm/yr by 2050 out of a request of ≈17.3 bcm/yr. Such values are small enough to be manageable. The chance of a year with deliveries <14.5 bcm/yr increases to 21% by midcentury if runoff reduces 20%, but such low deliveries could be largely avoided by reducing scheduled deliveries. These results are computed by using estimates of Colorado River flow from the 20th century, which was unusually wet; if the river reverts to its long-term mean, shortfalls increase another 1–1.5 bcm/yr. With either climate-change or long-term mean flows, currently scheduled future water deliveries from the Colorado River are not sustainable. However, the ability of the system to mitigate droughts can be maintained if the various users of the river find a way to reduce average deliveries.
Charting the molecular network of the drug target Bcr-Abl
Authors: Brehme Marc , Hantschel Oliver , Colinge Jacques , Kaupe Ines , Planyavsky Melanie , Köcher Thomas , Mechtler Karl , Bennett Keiryn L. , Superti-Furga Giulio
Published: April 2009

The tyrosine kinase Bcr-Abl causes chronic myeloid leukemia and is the cognate target of tyrosine kinase inhibitors like imatinib. We have charted the protein–protein interaction network of Bcr-Abl by a 2-pronged approach. Using a monoclonal antibody we have first purified endogenous Bcr-Abl protein complexes from the CML K562 cell line and characterized the set of most tightly-associated interactors by MS. Nine interactors were subsequently subjected to tandem affinity purifications/MS analysis to obtain a molecular interaction network of some hundred cellular proteins. The resulting network revealed a high degree of interconnection of 7 “core” components around Bcr-Abl (Grb2, Shc1, Crk-I, c-Cbl, p85, Sts-1, and SHIP-2), and their links to different signaling pathways. Quantitative proteomics analysis showed that tyrosine kinase inhibitors lead to a disruption of this network. Certain components still appear to interact with Bcr-Abl in a phosphotyrosine-independent manner. We propose that Bcr-Abl and other drug targets, rather than being considered as single polypeptides, can be considered as complex protein assemblies that remodel upon drug action.
Rapid sensitive analysis of cysteine rich peptide venom components
Authors: Ueberheide Beatrix M. , Fenyö David , Alewood Paul F. , Chait Brian T.
Published: April 2009

Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions, and certain marine snails represent one of nature's great diversity libraries of bioactive molecules. The various species of marine cone shells have alone been estimated to produce >50,000 distinct peptide venoms. These peptides have stimulated considerable interest because of their ability to potently alter the function of specific ion channels. To date, only a small fraction of this immense resource has been characterized because of the difficulty in elucidating their primary structures, which range in size between 10 and 80 aa, include up to 5 disulfide bonds, and can contain extensive posttranslational modifications. The extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest present major analytical challenges. Here, we describe a strategy that uses mass spectrometry for the elucidation of the mature peptide toxin components of crude venom samples. Key to this strategy is our use of electron transfer dissociation (ETD), a mass spectrometric fragmentation technique that can produce sequence information across the entire peptide backbone. However, because ETD only yields comprehensive sequence coverage when the charge state of the precursor peptide ion is sufficiently high and the
m
/
z
ratio is low, we combined ETD with a targeted chemical derivatization strategy to increase the charge state of cysteine-containing peptide toxins. Using this strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the crude venom from the venom gland of a single cone snail (
Conus textile
).
Role of a distal pocket in the catalytic O
2
reduction by cytochrome
c
oxidase models immobilized on interdigitated array electrodes
Authors: Collman James P. , Decréau Richard A. , Lin Hengwei , Hosseini Ali , Yang Ying , Dey Abhishek , Eberspacher Todd A.
Published: April 2009

Five iron porphyrins with different superstructures were immobilized on self-assembled-monolayer (SAM)-coated interdigitated-array (IDAs) gold–platinum electrodes. The selectivity of the catalysts i.e., limited formation of partially reduced oxygen species (PROS) in the electrocatalytic reduction of dioxygen, is a function of 2 rates: (
i
) the rate of electron transfer from the electrode to the catalyst, which is controlled by the length, and conjugation of the linker from the catalyst to the electrode and (
ii
) the rate of bound oxygen (superoxide) hydrolysis, which correlates with the presence of a water cluster in the gas-binding pocket influencing the rate of oxygen binding; these factors are controlled by the nature of the porphyrin superstructure. The structurally biomimetic Tris-imidazole model is the most selective.
Specific glycosphingolipids mediate epithelial-to-mesenchymal transition of human and mouse epithelial cell lines
Authors: Guan Feng , Handa Kazuko , Hakomori Sen-itiroh
Published: April 2009

Epithelial-to-mesenchymal cell transition (EMT) is a basic process in embryonic development and cancer progression. The present study demonstrates involvement of glycosphingolipids (GSLs) in the EMT process by using normal murine mammary gland NMuMG, human normal bladder HCV29, and human mammary carcinoma MCF7 cells. Treatment of these cells with
d
-
threo
-1-(3′,4′-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4), the glucosylceramide (GlcCer) synthase inhibitor, which depletes all GSLs derived from GlcCer, (
i
) down-regulated expression of a major epithelial cell marker, E-cadherin; (
ii
) up-regulated expression of mesenchymal cell markers vimentin, fibronectin, and N-cadherin; (
iii
) enhanced haptotactic cell motility; and (
iv
) converted epithelial to fibroblastic morphology. These changes also were induced in these cell lines with TGF-β, which is a well-documented EMT inducer. A close association between specific GSL changes and EMT processes induced by EtDO-P4 or TGF-β is indicated by the following findings: (
i
) The enhanced cell motility of EtDO-P4-treated cells was abrogated by exogenous addition of GM2 or Gg4, but not GM1 or GM3, in all 3 cell lines. (
ii
) TGF-β treatment caused changes in the GSL composition of cells. Notably, Gg4 or GM2 was depleted or reduced in NMuMG, and GM2 was reduced in HCV29. (
iii
) Exogenous addition of Gg4 inhibited TGF-β-induced changes of morphology, motility, and levels of epithelial and mesenchymal markers. These observations indicate that specific GSLs play key roles in defining phenotypes associated with EMT and its reverse process (i.e., mesenchymal-to-epithelial transition).
Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity
Authors: Zhang Pei , Zhong Lilin , Struble Evi Budo , Watanabe Hisayoshi , Kachko Alla , Mihalik Kathleen , Virata Maria Luisa , Alter Harvey J. , Feinstone Stephen , Major Marian
Published: April 2009

Using human immune globulins made from antihepatitis C virus (HCV)-positive plasma, we recently identified two antibody epitopes in the E2 protein at residues 412–426 (epitope I) and 434–446 (epitope II). Whereas epitope I is highly conserved among genotypes, epitope II varies. We discovered that epitope I was implicated in HCV neutralization whereas the binding of non-neutralizing antibody to epitope II disrupted virus neutralization mediated by antibody binding at epitope I. These findings suggested that, if this interfering mechanism operates in vivo during HCV infection, a neutralizing antibody against epitope I can be restrained by an interfering antibody, which may account for the persistence of HCV even in the presence of an abundance of neutralizing antibodies. We tested this hypothesis by affinity depletion and peptide-blocking of epitope-II-specific antibodies in plasma of a chronically HCV-infected patient and recombinant E1E2 vaccinated chimpanzees. We demonstrate that, by removing the restraints imposed by the interfering antibodies to epitope-II, neutralizing activity can be revealed in plasma that previously failed to neutralize viral stock in cell culture. Further, cross-genotype neutralization could be generated from monospecific plasma. Our studies contribute to understanding the mechanisms of antibody-mediated neutralization and interference and provide a practical approach to the development of more potent and broadly reactive hepatitis C immune globulins.
Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development
Authors: Montgomery Rusty L. , Hsieh Jenny , Barbosa Ana C. , Richardson James A. , Olson Eric N.
Published: April 2009

The molecular mechanism by which neural progenitor cells commit to a specified lineage of the central nervous system remains unknown. We show that HDAC1 and HDAC2 redundantly control neuronal development and are required for neuronal specification. Mice lacking HDAC1 or HDAC2 in neuronal precursors show no overt histoarchitectural phenotypes, whereas deletion of both HDAC1 and HDAC2 in developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7. These abnormalities in brain formation can be attributed to a failure of neuronal precursors to differentiate into mature neurons and to excessive cell death. These results reveal redundant and essential roles for HDAC1 and HDAC2 in the progression of neuronal precursors to mature neurons in vivo.
Insights into pilus assembly and secretion from the structure and functional characterization of usher PapC
Authors: Huang Yihua , Smith Barbara S. , Chen Lucy X. , Baxter Richard H. G. , Deisenhofer Johann
Published: April 2009

Ushers constitute a family of bacterial outer membrane proteins responsible for the assembly and secretion of surface organelles such as the pilus. The structure at 3.15-Å resolution of the usher pyelonephritis-associated pili C (PapC) translocation domain reveals a 24-stranded kidney-shaped β-barrel, occluded by an internal plug domain. The dimension of the pore allows tandem passage of individual folded pilus subunits in an upright pilus growth orientation, but is insufficient for accommodating donor strand exchange. The molecular packing revealed by the crystal structure shows that 2 PapC molecules in head-to-head orientation interact via exposed β-strand edges, which could be the preferred dimer interaction in solution. In vitro reconstitution of fiber assemblies suggest that PapC monomers may be sufficient for fiber assembly and secretion; both the plug domain and the C-terminal domain of PapC are required for filament assembly, whereas the N-terminal domain is mainly responsible for recruiting the chaperone–subunit complexes to the usher. The plug domain has a dual function: gating the β-pore and participating in pilus assembly.
EphrinB2 coordinates the formation of a morphological boundary and cell epithelialization during somite segmentation
Authors: Watanabe Tadayoshi , Sato Yuki , Saito Daisuke , Tadokoro Ryosuke , Takahashi Yoshiko
Published: April 2009

During early morphogenesis, tissue segregation is often accompanied by changes in cell shape. To understand how such coordination is regulated, somitogenesis was used as a model. When a somite forms in the anterior end of the presomitic mesoderm, an intersomitic boundary (gap) emerges, and it is rapidly followed by cell epithelialization at this border. It has been known that the gap formation is regulated by intercellular signals. We here demonstrate that cMeso-1, the chicken homolog of mouse Mesp2, up-regulates EphA4 in the cells located posteriorly to a forming boundary. This in turn activates EphrinB2-reverse signals in the anteriorly juxtaposed cells, where the EphrinB2 signal is sufficient to cause a gap formation and cell epithelialization cell-autonomously. During these processes, Cdc42 needs to be repressed via tyrosine phosphorylation of EphrinB2. This is the first demonstration that Ephrin-reverse signal acts as a platform that couples distinct morphogenetic changes in cell polarity and tissue shape.
An integrated multi-generational model for language maintenance and shift
Authors: Villa Daniel J. , Rivera-Mills Susana
Published: April 2009

Many researchers investigating the maintenance and loss of non-English languages in the U.S. base their work on fairly homogeneous language groups, those who have immigrated here during a relatively restricted period of time. The European-origin migrations during the early decades of the twentieth century represent these types of language communities. However, Spanish is not strictly an immigrant language when compared to other non-English, non-indigenous languages. It shares in common with indigenous languages the fact that it was spoken in what is now the U.S. before the arrival of English speakers. However, it is unlike indigenous languages in that it continues to be reinforced by the arrival of Spanish-speaking immigrants. Given the complexities of this bilingual population, the purpose of the present article is to examine the variables that set apart the Spanish-speaking populations of the U.S., and particularly of the Southwest, in order to provide a revised model for language maintenance and shift that goes beyond the limitations of classic intergenerational models.
Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members
Authors: Gallenne Tristan , Gautier Fabien , Oliver Lisa , Hervouet Eric , Noël Belinda , Hickman John A. , Geneste Olivier , Cartron Pierre-François , Vallette François M. , Manon Stephen , Juin Philippe
Published: April 2009

It is still unclear whether the BH3-only protein Puma (p53 up-regulated modulator of apoptosis) can prime cells to death and render antiapoptotic BH3-binding Bcl-2 homologues necessary for survival through its ability to directly interact with proapoptotic Bax and activate it. In this study, we provide further evidence, using cell-free assays, that the BH3 domain of Puma binds Bax at an activation site that comprises the first helix of Bax. We also show that, in yeast, Puma interacts with Bax and triggers its killing activity when Bcl-2 homologues are absent but not when Bcl-xL is expressed. Finally, endogenous Puma is involved in the apoptotic response of human colorectal cancer cells to the Bcl-2/Bcl-xL inhibitor ABT-737, even in conditions where the expression of Mcl-1 is down-regulated. Thus, Puma is competent to trigger Bax activity by itself, thereby promoting cellular dependence on prosurvival Bcl-2 family members.
ESCRT ubiquitin-binding domains function cooperatively during MVB cargo sorting
Authors: Shields S. Brookhart , Oestreich Andrea J. , Winistorfer Stanley , Nguyen Doris , Payne Johanna A. , Katzmann David J. , Piper Robert
Published: April 2009

Ubiquitin (Ub) sorting receptors facilitate the targeting of ubiquitinated membrane proteins into multivesicular bodies (MVBs). Ub-binding domains (UBDs) have been described in several endosomal sorting complexes required for transport (ESCRT). Using available structural information, we have investigated the role of the multiple UBDs within ESCRTs during MVB cargo selection. We found a novel UBD within ESCRT-I and show that it contributes to MVB sorting in concert with the known UBDs within the ESCRT complexes. These experiments reveal an unexpected level of coordination among the ESCRT UBDs, suggesting that they collectively recognize a diverse set of cargo rather than act sequentially at discrete steps.
Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis
Authors: Paronetto Maria Paola , Messina Valeria , Bianchi Enrica , Barchi Marco , Vogel Gillian , Moretti Costanzo , Palombi Fioretta , Stefanini Mario , Geremia Raffaele , Richard Stéphane , Sette Claudio
Published: April 2009

Sam68 is a KH-type RNA-binding protein involved in several steps of RNA metabolism with potential implications in cell differentiation and cancer. However, its physiological roles are still poorly understood. Herein, we show that Sam68−/− male mice are infertile and display several defects in spermatogenesis, demonstrating an essential role for Sam68 in male fertility. Sam68−/− mice produce few spermatozoa, which display dramatic motility defects and are unable to fertilize eggs. Expression of a subset of messenger mRNAs (mRNAs) is affected in the testis of knockout mice. Interestingly, Sam68 is associated with polyadenylated mRNAs in the cytoplasm during the meiotic divisions and in round spermatids, when it interacts with the translational machinery. We show that Sam68 is required for polysomal recruitment of specific mRNAs and for accumulation of the corresponding proteins in germ cells and in a heterologous system. These observations demonstrate a novel role for Sam68 in mRNA translation and highlight its essential requirement for the development of a functional male gamete.
Puma strikes Bax
Authors: Letai Anthony
Published: April 2009

The commitment to programmed cell death via apoptosis is largely made upon activation of the proapoptotic mitochondrial proteins Bax or Bak. In this issue, Gallenne et al. (Gallenne, C., F. Gautier, L. Oliver, E. Hervouet, B. Noël, J.A. Hickman, O. Geneste, P.-F. Cartron, F.M. Vallette, S. Manon, and P. Juin. 2009. J. Cell Biol. 185:279–290) provide evidence that the p53 up-regulated modulator of apoptosis (Puma) protein can directly activate Bax.
Temperament and Character Profiles of Sasang Typology in an Adult Clinical Sample
Authors: Park Soo Hyun , Kim Myoung-geun , Lee Soo Jin , Kim Jong Yeol , Chae Han
Published: April 2009

The purpose of this study was to examine the biopsychological personality profiles of traditional Korean Sasang typology based on the Temperament and Character Inventory (TCI) in a Korean adult clinical sample. A total of 97 adults completed the Korean version of the TCI. The participants were classified as one of three traditional Korean Sasang types (31 So‐Yang, 41 Tae‐Eum, 25 So‐Eum) by three specialists in Sasang typology. The seven dimensions of TCI were compared between the different Sasang types using analysis of variance (ANOVA) and profile analysis. There were no significant differences in age, gender and education across the Sasang types. The TCI profile for each of the Sasang types was significantly different (profile analysis, df = 5.038, F = 3.546, P = .004). There were significant differences in the temperament dimensions of Novelty Seeking (F = 3.43, P = .036) and Harm Avoidance (F = 5.43, P = .006) among the Sasang types. The Novelty Seeking score of the So‐Yang type (31.90 ± 9.87) was higher than that of the So‐Eum type (25.24 ± 9.21; P = .019) while the So‐Eum type (44.64 ± 8.47) scored higher on the Harm Avoidance score compared to the So‐Yang type (35.16 ± 11.50; P = .003). There were no significant differences in the temperament dimension of Reward Dependence and Persistence, and the three character dimensions of Self‐Directedness, Cooperativeness and Self‐Transcendence. Results demonstrated distinct temperament traits associated with traditional Korean Sasang types using an objective biopsychological personality inventory. With further study, the Sasang typology may lead to enhanced clinical safety and efficacy as part of personalized medicine with traditional medicine.
Passive- and active-acoustic properties of a spawning Atlantic cod (Gadus morhua) aggregation
Authors: Fudge Susan B. , Rose George A.
Published: April 2009

Fudge, S. B., and Rose, G. A. 2009. Passive- and active-acoustic properties of a spawning Atlantic cod (Gadus morhua) aggregation. – ICES Journal of Marine Science, 66: 1259–1263. A spawning aggregation of Atlantic cod (Gadus morhua) was observed at depths of 40–50 m with passive- and active-acoustic sensors at the Bar Haven grounds in Placentia Bay, Newfoundland, in April 2003. A hydrophone was positioned on the seabed beneath the aggregation, while a 38-kHz split-beam echosounder was moored at the sea surface above it for 18.5 h. Ten grunts were recorded with peak frequencies ranging from 30 to 250 Hz and durations of nearly 300 ms. These grunts are similar to the sounds recorded in the presence of captive, spawning cod from the same substock. The echogram reveals that cod exhibit diel, vertical-migratory behaviour, densely aggregating near the seabed by day and forming columns that extend approximately halfway to the surface at night. This is the first study to demonstrate that cod produce sounds and form columns while migrating vertically during night-time spawning.
Insurance mechanisms to mediate economic risks in marine fisheries
Authors: Mumford J. D. , Leach A. W. , Levontin P. , Kell L. T.
Published: April 2009

Mumford, J. D., Leach, A. W., Levontin, P., and Kell, L. T. 2009. Insurance mechanisms to mediate economic risks in marine fisheries. – ICES Journal of Marine Science, 66: 950–959. Uncertainty affects the behaviour of fishers and fisheries regulators in a way that can adversely affect the sustainability of fish stocks, fisheries income, and productivity. In agriculture, there has been a long history of using levy funds and public and private insurance schemes to mediate economic risks to growers resulting from environmental variability and quarantine risks. In the United States, the federal government continues to underwrite funds (collected by contracted private agents) that are used to protect contributors from the effects of extreme weather and pest and disease losses. In Europe, there are examples of industry-based mutual funds to mediate risks from exotic agricultural diseases. In agriculture, insurance mechanisms have been successful in reducing risk-inducing behaviour by contractual compliance to risk-reducing codes of practice. For fisheries, insurance may provide a tool to address some elements of uncertainty in a way that would help both the fishing industry and the regulators achieve objectives of sustainability, income security, and productivity. This paper presents a brief review of insurance in agriculture and capture fisheries and uses a stochastic model to illustrate how insurance funds could protect revenue and encourage increased sustainability of fisheries and improve compliance with and enforcement of fisheries regulation. Although insurance may be a partial solution to unsatisfactory fisheries management and fishing performance, some potential challenges to this novel approach are also discussed.
A Review on Specialization in Pharmacy—Part I
Authors: Laven David L.
Published: April 2009

Many opportunities exist for pharmacists who desire to expand their role in providing comprehensive pharmaceutical care services to patients and other health care providers whom they serve and collaborate with on a daily basis. Consequently, there is a strong trend within pharmacy to specialize in areas of professional interest. In many respects, pharmacy has turned towards the medical model in addressing its needs and providing a framework for specialization in practice. With respect to generalist and specialized practitioners and varying initiatives relative to the medical model, the concept of specialization in pharmacy has recently developed some interesting tangents when issues of certification, credentialing, disease-state management, and added-qualifications enter the discussion. In this, the first of a 2-part series (Part II in the upcoming issue) focusing on specialization in pharmacy, a review of the current initiatives by which a pharmacist can achieve specialty status will be addressed.
Fluid Therapy in the Critically Ill Patient
Authors: Aber Tracy S. , Hosac Anita Marie , Veach Marianne Penrose , Pierre Yvette Whitney
Published: April 2009

The administration of intravenous fluids in the critically ill patient presents many challenges for clinicians. Intravenous fluids are usually categorized as either crystalloids or colloids, with each having distinct advantages and disadvantages in various patient populations. The appropriate selection of fluid type remains an issue of great debate in the critical care literature and has been the subject of numerous comparative studies. Despite the vast amount of data available, there is no clear consensus in the literature to direct the clinician in the choice of fluid type. This article will provide an overview of fluid distribution within the body and the factors that affect this distribution, a review of the various types of fluids administered in the critically ill patient, and the rationale for the selection of each type. A review of the literature surrounding the colloid-crystalloid controversy is provided.
Frontiers in Neuropharmacotherapy Part II: Multiple Sclerosis and Parkinson’s Disease
Authors: Chappell Jill C. , Cohen Henry
Published: April 2009

Disease-modifying agents such as β-interferons and glatiramer acetate have a significant impact on slowing the course of relapsing-remitting multiple sclerosis (MS). Therapeutic guidelines recommend initiating therapy with 1 of the 3 agents shortly after diagnosis of clinically definite MS, but there is insufficient data to specifically select one of the therapies. New research helps differentiate the therapies based on their induction of neutralizing antibodies, optimal dosing, and monitoring strategies. New treatments for secondary progressive MS are also emerging with evidence for the use of interferon β-1b and the approval of mitoxantrone. Future therapies for MS include oral glatiramer acetate and combination therapy.

Levodopa continues to be the standard of care for the treatment of Parkinson’s disease, but the approval of newer therapies that spare the use of levodopa and improve safety profiles are changing the management of the disease. Dopamine agonists such as bromocriptine and pergolide have been used to manage complications of levodopa therapy in patients with advanced disease, but new research supports the use of the more selective dopamine agonists, pramipexole and ropinirole, as monotherapy in early Parkinson’s disease. The combination of a catechol-O-methyltransferase (COMT) inhibitor with levodopa provides a new therapeutic option for treating patients with motor complications in advanced disease.
A Review of Stress Ulcer Prophylaxis
Authors: MacLaren Robert
Published: April 2009

Stress-related mucosal damage (SRMD) is an erosive process of the gastroduodenum that occurs frequently in critically ill patients. Symptomatic lesions may range from overt bleeding (by hematemesis, melena, bloody or coffee ground aspirates, or hematochezia) to clinically significant hemorrhage (hypotension, tachycardia, or acute anemia requiring transfusion). SRMD is caused by mucosal ischemia that produces an imbalance between injurious factors and the protective mechanisms. Common patient risk factors include mechanical ventilation, coagulopathy, shock, hepatic dysfunction, renal dysfunction, thermal injury, trauma, kidney or liver transplant, head injury or spinal cord injury, recent gastrointestinal hemorrhage, and pharmacologic interventions. Stress ulcer prophylaxis may be provided by administering one of the following pharmacologic agents: an antacid, a histamine2 receptor antagonist, sucralfate, or a proton pump inhibitor. All agents possess equal efficacies but differ in their mechanisms of action, adverse event profile, drug interactions, monitoring requirements, costs, and personnel requirements for preparation and administration. Implementation of institution-specific protocols for stress ulcer prophylaxis provides cost minimization by maximizing appropriate drug usage.