bluuebunny/crossref_metadata_2025 huggingface dataset:
Dark current suppression in type II InAs∕GaSb superlattice long wavelength infrared photodiodes with M-structure barrier
Authors: Nguyen Binh-Minh , Hoffman Darin , Delaunay Pierre-Yves , Razeghi Manijeh
Published: October 2007

We presented an alternative design of type II superlattice photodiodes with the insertion of a mid-wavelength infrared M-structure AlSb∕GaSb∕InAs∕GaSb∕AlSb superlattice for the reduction of dark current. The M-structure superlattice has a larger carrier effective mass and a greater band discontinuity as compared to the standard type II superlattices at the valence band. It acts as an effective medium that weakens the diffusion and tunneling transport at the depletion region. As a result, a 10.5μm cutoff type II superlattice with 500nm M-superlattice barrier exhibited a R0A of 200Ωcm2 at 77K, approximately one order of magnitude higher than the design without the barrier. The quantum efficiency of such structures does not show dependence on either barrier thickness or applied bias.
Synthesis and superconducting properties of niobium nitride nanowires and nanoribbons
Authors: Patel U. , Avci S. , Xiao Z. L. , Hua J. , Yu S. H. , Ito Y. , Divan R. , Ocola L. E. , Zheng C. , Claus H. , Hiller J. , Welp U. , Miller D. J. , Kwok W. K.
Published: October 2007

Superconducting niobium nitride wires and ribbons with transverse dimensions down to tens of nanometers were synthesized by annealing NbSe3 nanostructure precursors in flowing ammonia gas at temperatures up to 1000°C. Their critical temperatures increase with increasing annealing temperatures and reach 9–11.2K when sintered at 950°C or above. X-ray diffraction analyses identified Nb4N5 and Nb5N6 phases, dominating at annealing temperatures below and above 950°C, respectively. Transport measurements show magnetoresistance oscillations at temperatures near the superconducting transition due to vortex-row confinement effects and voltage jumps in current-voltage characteristics at low temperatures attributed to hot-spot behavior.
Lasing in electrodeposited ZnO inverse opal
Authors: Teh L. K. , Wong C. C. , Yang H. Y. , Lau S. P. , Yu S. F.
Published: October 2007

We report room-temperature ultraviolet lasing in ZnO inverse opals fabricated via colloidal templating with electrochemical infiltration. Lasing occurs above an excitation threshold of 0.38MW∕cm2. Lasing modes associated with radiative recombinations of exciton-exciton (ex-ex) and electron-hole plasma (EHP) were discerned. Compared to ZnO polycrystalline film, lasing wavelength blueshifts and ex-ex lasing with a narrower bandwidth have been realized. Tuning the primary photonic pseudogap of inverse opals to gain maximum reduces the threshold for EHP lasing. We infer that periodic structures facilitate strain-induced change in lasing energy and provide modulation in refractive index for enhanced light confinement as well as optical feedback.
Characterizing the effects of disorder in metamaterial structures
Authors: Gollub Jonah , Hand Thomas , Sajuyigbe Soji , Mendonca Shawn , Cummer Steve , Smith David R.
Published: October 2007

We investigate the effects of disorder on metamaterial samples composed of split ring resonators with randomly introduced variation in their geometrical dimensions. We demonstrate that disorder broadens the negative permeability band and introduces effective losses into the system. Transmission measurements on samples with varying degrees of disorder are found to be in excellent agreement with predictions based on standard homogenization theories.
A Wave-Line Colour Illusion
Authors: Sohmiya Seiyu
Published: October 2007

A new colour-spreading illusion is reported. Illusory colours appear on a white background when three unconnected sinusoidal curves are aligned in parallel when the central line is of a different colour than the other two lines. For some combinations of colours, illusory colours appear not only around the central line but also around the other lines.
Reduced protein intake during the weaner period has variable effects on subsequent growth and carcass composition of pigs
Authors: Collins C. L. , Henman D. J. , Dunshea F. R.
Published: October 2007

In total, 960 pigs (480 castrated males and 480 gilts), selected at ~28 days of age, were used to investigate the effect of restricting protein intake for a short period between 4 and 14 weeks of age. Pigs were selected over an 8-week period in groups of 120 pigs (three pens of 20 castrated males and three pens of 20 gilts per week). Pigs were given ad libitum access to commercial diets from weaning to slaughter. Pens of 20 pigs of each sex were allocated to one of six treatments: control (no restriction), restriction from 4 to 7 weeks of age, restriction from 7 to 10 weeks of age, restriction from 10 to 14 weeks of age, restriction from 4 to 10 weeks of age or a restriction from 4 to 14 weeks of age. During the period of restriction, pigs were offered ad libitum commercial diets that had been reduced in dietary lysine to digestible energy ratio by ~15%. Restricting protein intake between 7 and 10, 4 and 10 and 4 and 14 weeks of age reduced daily gain during the period of restriction. Pigs restricted from 7 to 10 weeks of age had reduced average daily feed intake (5.6%) from 7 to 10 weeks, followed by a reduction in average daily feed intake (5.5%) and improved feed efficiency (6.1%) in the subsequent period from 10 to 17 weeks of age. Daily gain for the entire experimental period was similar for all treatment groups, except those restricted from 7 to 10 weeks of age (3.9% lower than the controls), although there was no treatment effect on carcass weight. Interestingly, backfat was reduced by 10% in these animals compared with the controls, which may be economically beneficial in markets where producers are paid on backfat and carcass weight, such as those selling domestically in the Australian market. Economic benefits of reduced feed costs during both the restriction and realimentation periods were also observed when pigs were restricted from 10 to 14 weeks of age. Any economic benefits from short periods of protein restriction will vary depending on the specific market conditions and the local cost of feed protein sources.
Effects of genotype, sex and stocking rate on postweaning efficiency and value-adding potential at turnoff of weaners grazing improved pasture in the Douglas Daly region of the Northern Territory
Authors: Schatz T. J. , Ridley P. E. R. , Fontaine D. J. M. La , Hearnden M. N.
Published: October 2007

An experiment was undertaken to establish the effects of genotype, sex and stocking rate on postweaning growth and value-adding potential at turnoff of weaners grazing improved pasture in the Douglas Daly region of the Northern Territory, Australia. The growth of 27 steer and 27 heifer weaners of four genotypes was studied each year for 4 years (i.e. n = 216 animals per year). Animals from each group were run at one of three stocking rates. The cattle were weighed monthly and fat depth was measured ultrasonically at the end of the postweaning year. Genotype had no significant effect on weight gain but one-quarter Charolais × three-quarters Brahman and Droughtmaster animals were significantly (P < 0.0001) leaner than Brahman (purebred and commercial) cattle at the end of the postweaning year. Steers grew more (12%; P < 0.0001) and were leaner (2.6 mm less P8 fat depth; P < 0.0001) than heifers. Animals that grazed at lower stocking rates gained more weight (P < 0.0001) but were not significantly fatter than those at higher stocking rates. The way these factors can be used to produce leaner animals with more value-adding potential for South-East Asian feedlots is discussed.
Effects of cutting and grazing on newly sown plants of Phalaris aquatica cv. Sirosa at Tamworth, New South Wales
Authors: Lodge G. M.
Published: October 2007

A field study was conducted (1994–97) to investigate defoliation time and frequency effects on a newly sown stand of phalaris (Phalaris aquatica cv. Sirosa). Defoliation treatments were applied from spring 1994 to autumn 1995 and effects on plant frequency and basal cover monitored until June 1997. The experimental design was a randomised split-plot in three replicates, with 45 main plots and 90 subplots. Main plots included three types of defoliation (two cutting heights or grazing with Merino sheep) applied at four different times (early stem elongation, anthesis, end of summer and end of autumn) and an undefoliated control. The main plots were divided into two subplots for frequency of defoliation (once only or cut every 8 weeks). In September 1995, none of the treatments had a significant effect on plant frequency, basal cover, green tiller weight and weight of individual tillers. However, there were significant (P < 0.05) effects of defoliation type on green tiller number, defoliation time on basal bud weight and water soluble carbohydrates and defoliation type and frequency on basal bud water soluble carbohydrates. In February and April 1996, there were significant effects of defoliation time on green tiller number and weight, basal bud weight and water soluble carbohydrates. In 1996, Sirosa phalaris plant frequency and basal cover values were generally higher (P < 0.05) in the undefoliated control compared with those defoliated at early stem elongation. However, despite fertiliser application and moderate grazing, Sirosa phalaris plant frequency had declined to a mean of 23.6% by February 1997 and to <10% by June 1997.
Productivity of crops grown on raised beds on duplex soils prone to waterlogging in Western Australia
Authors: Bakker D. M. , Hamilton G. J. , Houlbrooke D. J. , Spann C. , Burgel A. Van
Published: October 2007

Waterlogging of duplex soils in Western Australia has long been recognised as a major constraint to the production of agricultural crops and pastures. The work described in this paper examines the application of raised beds to arable land that is frequently waterlogged for the production of crops such as wheat, barley, field peas, lupins and canola. Raised beds are 138 cm wide, seed beds separated by 45 cm wide furrows 183 cm apart. These beds were made with a commercial bed former. Seven sites were selected across the south-eastern wheat belt of Western Australia with the experimental areas varying in size from 10 to 57 ha. These large sites were used to accommodate commercial farm machinery. Each site had raised beds formed with a commercial bedformer. The production from the bedded areas was compared with crops grown conventionally on flat ground under minimum tillage as the control. The experiments were established in 1997 and 1998 and the sites were monitored for a maximum of 5 years. In 11 of the 28 site-years of the experiments, grain yields on the raised beds were statistically significantly higher than the yield from crops grown on the control, with an average yield increase of 0.48 t/ha. Across the whole dataset, growing crops on raised beds did not produce significantly lower yields. Below average rainfall was received for much of the experimental period at several sites. Growing season rainfall had a large effect on grain yield and high rainfall over a period of 40 days after seeding significantly increased the grain yield difference between the raised bed and the control. These data indicate that the use of raised beds lead to higher grain yields when seasonal conditions are appropriate.
Pasture management in semiarid tropical woodlands: improving the herbage quality of stylos and grasses
Authors: McIvor John G.
Published: October 2007

The impacts of season and pasture management (tree killing, superphosphate application, stocking rate) on the herbage quality of stylos and grasses were measured at Hillgrove and Cardigan, north-east Queensland. Plucked samples of Verano, Seca and buffel grass (both sites) and a native grass (spear grass at Cardigan and desert blue grass at Hillgrove) were collected over a 4-year period and concentrations of nitrogen, phosphorus and sulfur and in vitro digestibility were measured. There were large seasonal variations in herbage quality of all species with high quality in the early growing season and low quality in dry periods. The stylos had higher nitrogen concentrations and in vitro digestibilities than the grasses, buffel grass had a higher phosphorus concentration than the other species and there were no consistent differences in sulfur concentration between species. Buffel grass generally had higher nitrogen and phosphorus concentrations and in vitro digestibility than the native grasses. Management had relatively minor impacts but where differences did occur, herbage quality was higher in plots with live trees than where trees were killed, on plots where superphosphate was applied compared with plots without fertiliser and was greater at high stocking rate. Oversowing native pastures with stylos had no effect on the herbage quality of desert blue grass which had similar quality in oversown pasture and native pasture.
Reading the public mind: a novel approach to improving the adoption of new science and technology
Authors: Fisher N. I. , Cribb J. H. J. , Peacock A. J.
Published: October 2007

This paper describes a new approach to measuring and monitoring the quality of dialogue between research groups and the wider community about specific scientific matters. It is an adaptation of a proven marketing process for monitoring customer satisfaction: key drivers of community perception are elicited and measured, so that managers can respond to the issues that are most important to the community, rather than relying on their own perceptions. One important benefit of the approach is that the method provides a means of linking an overall score for the community’s perceived value of a research project to an important business driver such as ‘percentage of people very willing to support deployment of the research results’. The method is illustrated by a case study exploring the views of the Australian public about research into genetic manipulation for pest mouse control. For the population surveyed (the community in New South Wales, Australia), some 40% were very willing to support the use of genetic manipulation to manage pest mice. If an increase of 1.5 in the score for the perceived value of a research project (measured on a scale from 1 to 10) were achieved, the prediction is that overall community support for eventual deployment would rise to about 80%. The approach would appear to have a useful role to play in assisting eventual technology adoption.
Relationship between real-time ultrasound and carcass measures and composition in heavy sheep
Authors: Hopkins D. L. , Stanley D. F. , Ponnampalam E. N.
Published: October 2007

Fat depth over the M. longissimus thoracis et lumborum (LL) at the 12th rib (USFat C) and the depth of the LL (USEMD) were measured before slaughter using a real-time ultrasound machine in 147 mixed sex, 22-month-old sheep of five genotypes. Equivalent measures were obtained on the carcasses (Fat C and EMD) and each carcass side was scanned by dual energy X-ray absorptiometry to provide an estimate of composition (percentage lean and fat). There was a significant (P < 0.001) correlation between USFat C and Fat C (fat depth over the LL at the 12th rib measured on the carcass) at r = 0.67. This was also the case for USEMD and EMD (muscle depth of the LL at the 12th rib measured on the carcass) with a significant (P < 0.001) correlation of r = 0.55. Liveweight per se was a poor predictor of Fat C and was of minimal value when used in combination with ultrasonic fat depth measurements. The prediction of Fat C was significantly underestimated by USFat C and this increased as the animals became fatter. The relationship between carcass and ultrasonic measurements of EMD was poor, but better when liveweight was used in combination with USEMD. The prediction of EMD was significantly overestimated by USEMD and this increased as the animals became heavier. Combining USFat C measurement with liveweight significantly (P < 0.001) improved the accuracy (R2) and precision (r.s.d.) with which either the percentage of fat or lean could be estimated. Measurement of USEMD was of no value for the estimation of the percentage of fat or lean. There was no significant (P > 0.05) sex effect on any of the relationships. Ultrasonic measurement of subcutaneous fat depth and muscle depth in heavy fat animals is subject to undefined error, but still provides a means to predict in vivo fat levels and muscle depth. However, the bias associated with the predictions suggest caution should be exercised when measuring heavy fat sheep and the need for further work to confirm the findings of the present study.
Spatial determinants of poverty in rural Kenya
Authors: Okwi Paul O. , Ndeng'e Godfrey , Kristjanson Patti , Arunga Mike , Notenbaert An , Omolo Abisalom , Henninger Norbert , Benson Todd , Kariuki Patrick , Owuor John
Published: October 2007

This article investigates the link between poverty incidence and geographical conditions within rural locations in Kenya. Evidence from poverty maps for Kenya and other developing countries suggests that poverty and income distribution are not homogenous. We use spatial regression techniques to explore the effects of geographic factors on poverty. Slope, soil type, distance/travel time to public resources, elevation, type of land use, and demographic variables prove to be significant in explaining spatial patterns of poverty. However, differential influence of these and other factors at the location level shows that provinces in Kenya are highly heterogeneous; hence different spatial factors are important in explaining welfare levels in different areas within provinces, suggesting that targeted propoor policies are needed. Policy simulations are conducted to explore the impact of various interventions on location-level poverty levels. Investments in roads and improvements in soil fertility are shown to potentially reduce poverty rates, with differential impacts in different regions.
Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals
Authors: Bodyak Natalya , Ayus Juan Carlos , Achinger Steven , Shivalingappa Venkatesha , Ke Qingen , Chen Yee-Shiuan , Rigor Debra L. , Stillman Isaac , Tamez Hector , Kroeger Paul E. , Wu-Wong Ruth R. , Karumanchi S. Ananth , Thadhani Ravi , Kang Peter M.
Published: October 2007

Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 19-nor-1,25(OH)
2
D
2
), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet (6% NaCl for 6 weeks), HS+PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS+PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.
Optimally wired subnetwork determines neuroanatomy of
Caenorhabditis elegans
Authors: Pérez-Escudero Alfonso , de Polavieja Gonzalo G.
Published: October 2007

Wiring cost minimization has successfully explained many structures of nervous systems. However, in the nematode
Caenorhabditis elegans
, for which anatomical data are most detailed, wiring economy is thought to play only a partial role and alone has failed to account for the grouping of neurons into ganglia [Chen BL, Hall DH, Chklovskii DB (2006)
Proc Natl Acad Sci USA
103:4723–4728; Kaiser M, Hilgetag CC (2006)
PLoS Comput Biol
2:e95; Ahn Y-Y, Jeong H, Kim BJ (2006)
Physica A
367:531–537]. Here, we test the hypothesis that optimally wired subnetworks can exist within nonoptimal networks, thus allowing wiring economy to give an improved prediction of spatial structure. We show in
C. elegans
that the small subnetwork of wires connecting sensory and motor neurons with sensors and muscles, comprising only 15% of connections, is close to optimal and alone predicts the main features of the spatial segregation of neurons into ganglia and encephalization. Moreover, a method to dissect networks into optimal and nonoptimal components is shown to find a large near-optimal subnetwork of 84% of neurons with a very low position error of 5.4%, and that explains clustering of neurons into ganglia and encephalization to fine detail. In general, we expect realistic networks not to be globally optimal in wire cost. We thus propose the strategy of using near-optimal subnetworks to understand neuroanatomical structure.
Arp2/3-independent assembly of actin by
Vibrio
type III effector VopL
Authors: Liverman Amy D. B. , Cheng Hui-Chun , Trosky Jennifer E. , Leung Daisy W. , Yarbrough Melanie L. , Burdette Dara L. , Rosen Michael K. , Orth Kim
Published: October 2007

Microbial pathogens use a variety of mechanisms to disrupt the actin cytoskeleton during infection.
Vibrio parahaemolyticus
(
V. para
) is a Gram-negative bacterium that causes gastroenteritis, and new pandemic strains are emerging throughout the world. Analysis of the
V. para
genome revealed a type III secretion system effector, VopL, encoding three Wiskott–Aldrich homology 2 domains that are interspersed with three proline-rich motifs. Infection of HeLa cells with
V. para
induces the formation of long actin fibers in a VopL-dependent manner. Transfection of VopL promotes the assembly of actin stress fibers.
In vitro
, recombinant VopL potently induces assembly of actin filaments that grow at their barbed ends, independent of eukaryotic factors.
Vibrio
VopL is predicted to be a bacterial virulence factor that disrupts actin homeostasis during an enteric infection of the host.
Single phage T4 DNA packaging motors exhibit large force generation, high velocity, and dynamic variability
Authors: Fuller Derek N. , Raymer Dorian M. , Kottadiel Vishal I. , Rao Venigalla B. , Smith Douglas E.
Published: October 2007

Terminase enzyme complexes, which facilitate ATP-driven DNA packaging in phages and in many eukaryotic viruses, constitute a wide and potentially diverse family of molecular motors about which little dynamic or mechanistic information is available. Here we report optical tweezers measurements of single DNA molecule packaging dynamics in phage T4, a large, tailed
Escherichia coli
virus that is an important model system in molecular biology. We show that a complex is formed between the empty prohead and the large terminase protein (gp17) that can capture and begin packaging a target DNA molecule within a few seconds, thus demonstrating a distinct viral assembly pathway. The motor generates forces >60 pN, similar to those measured with phage φ29, suggesting that high force generation is a common property of viral DNA packaging motors. However, the DNA translocation rate for T4 was strikingly higher than that for φ29, averaging ≈700 bp/s and ranging up to ≈2,000 bp/s, consistent with packaging by phage T4 of an enormous, 171-kb genome in <10 min during viral infection and implying high ATP turnover rates of >300 s
−1
. The motor velocity decreased with applied load but averaged 320 bp/s at 45 pN, indicating very high power generation. Interestingly, the motor also exhibited large dynamic changes in velocity, suggesting that it can assume multiple active conformational states gearing different translocation rates. This capability, in addition to the reversible pausing and slipping capabilities that were observed, may allow phage T4 to coordinate DNA packaging with other ongoing processes, including viral DNA transcription, recombination, and repair.
Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus
Authors: Temel Yasin , Boothman Laura J. , Blokland Arjan , Magill Peter J. , Steinbusch Harry W. M. , Visser-Vandewalle Veerle , Sharp Trevor
Published: October 2007

Bilateral, high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the surgical therapy of choice for movement disability in advanced Parkinson's disease (PD), but this procedure evokes debilitating psychiatric effects, including depressed mood, of unknown neural origin. Here, we report the unexpected finding that HFS of the STN inhibits midbrain 5-hydroxytryptamine (5-HT) neurons to evoke depression-related behavioral changes. We found that bilateral HFS of the STN consistently inhibited (40–50%) the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat, but not neighboring non-5-HT neurons. This effect was apparent at clinically relevant stimulation parameters (≥100 Hz, ≥30 μA), was not elicited by HFS of either neighboring or remote structures to the STN, and was still present in rat models of PD. We also found that bilateral HFS of the STN evoked clear-cut, depressive-like behavior in a widely used experimental paradigm of depression (forced swim test), and this effect was also observed in a PD model. Importantly, the depressive-like behavior elicited by HFS of the STN was reversed by a selective 5-HT-enhancing antidepressant, thereby linking the behavioral change to decreased 5-HT neuronal activity. Overall, these findings link reduced 5-HT function to the psychiatric effects of HFS of the STN observed in PD patients and provide a rational basis for their clinical management. More generally, the powerful interaction between the STN and 5-HT system uncovered here offers insights into the high level of comorbidity of basal ganglia disease and mood disorder.
Quantification of dynamic protein complexes using
Renilla
luciferase fragment complementation applied to protein kinase A activities
in vivo
Authors: Stefan E. , Aquin S. , Berger N. , Landry C. R. , Nyfeler B. , Bouvier M. , Michnick S. W.
Published: October 2007

The G protein-coupled receptor (GPCR) superfamily represents the most important class of pharmaceutical targets. Therefore, the characterization of receptor cascades and their ligands is a prerequisite to discovering novel drugs. Quantification of agonist-induced second messengers and downstream-coupled kinase activities is central to characterization of GPCRs or other pathways that converge on GPCR-mediated signaling. Furthermore, there is a need for simple, cell-based assays that would report on direct or indirect actions on GPCR-mediated effectors of signaling. More generally, there is a demand for sensitive assays to quantify alterations of protein complexes
in vivo
. We describe the development of a
Renilla
luciferase (
R
luc)-based protein fragment complementation assay (PCA) that was designed specifically to investigate dynamic protein complexes. We demonstrate these features for GPCR-induced disassembly of protein kinase A (PKA) regulatory and catalytic subunits, a key effector of GPCR signaling. Taken together, our observations show that the PCA allows for direct and accurate measurements of live changes of absolute values of protein complex assembly and disassembly as well as cellular imaging and dynamic localization of protein complexes. Moreover, the
R
luc-PCA has a sufficiently high signal-to-background ratio to identify endogenously expressed Gα
s
protein-coupled receptors. We provide pharmacological evidence that the phosphodiesterase-4 family selectively down-regulates constitutive β-2 adrenergic- but not vasopressin-2 receptor-mediated PKA activities. Our results show that the sensitivity of the
R
luc-PCA simplifies the recording of pharmacological profiles of GPCR-based candidate drugs and could be extended to high-throughput screens to identify novel direct modulators of PKA or upstream components of GPCR signaling cascades.
ARF1-mediated actin polymerization produces movement of artificial vesicles
Authors: Heuvingh Julien , Franco Michel , Chavrier Philippe , Sykes Cécile
Published: October 2007

Vesicular trafficking and actin dynamics on Golgi membranes are both regulated by ADP-ribosylation factor 1 (ARF1) through the recruitment of various effectors, including vesicular coats. Actin assembly on Golgi membranes contributes to the architecture of the Golgi complex, vesicle formation, and trafficking and is mediated by ARF1 through a cascade that leads to Arp2/3 complex activation. Here we addressed the role of Golgi actin downstream of ARF1 by using a biomimetic assay consisting of liposomes of defined lipid composition, carrying an activated form of ARF1 incubated in cytosolic cell extracts. We observed actin polymerization around the liposomes resulting in thick actin shells and actin comet tails that pushed the ARF1 liposomes forward. The assay was used to characterize the ARF1-dependent pathway, leading to actin polymerization, and confirmed a dependency on CDC42 and its downstream effector N-WASP. Overall, this study demonstrates that actin polymerization driven by the complex multicomponent signaling cascade of the Golgi apparatus can be reproduced with a biomimetic system. Moreover, our results are consistent with the view that actin-based force generation at the site of vesicle formation contributes to the mechanism of fission. In addition to its well established function in coat recruitment, the ARF1 machinery also might produce movement- and fission-promoting forces through actin polymerization.
Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing
Authors: Wang Hong-Wei , Wang Jianjun , Ding Fang , Callahan Kevin , Bratkowski Matthew A. , Butler J. Scott , Nogales Eva , Ke Ailong
Published: October 2007

The eukaryotic core exosome (CE) is a conserved nine-subunit protein complex important for 3′ end trimming and degradation of RNA. In yeast, the Rrp44 protein constitutively associates with the CE and provides the sole source of processive 3′-to-5′ exoribonuclease activity. Here we present EM reconstructions of the core and Rrp44-bound exosome complexes. The two-lobed Rrp44 protein binds to the RNase PH domain side of the exosome and buttresses the bottom of the exosome-processing chamber. The Rrp44 C-terminal body part containing an RNase II-type active site is anchored to the exosome through a conserved set of interactions mainly to the Rrp45 and Rrp43 subunit, whereas the Rrp44 N-terminal head part is anchored to the Rrp41 subunit and may function as a roadblock to restrict access of RNA to the active site in the body region. The Rrp44–exosome (RE) architecture suggests an active site sequestration mechanism for strict control of 3′ exoribonuclease activity in the RE complex.
Chimpanzees modify recruitment screams as a function of audience composition
Authors: Slocombe Katie E. , Zuberbühler Klaus
Published: October 2007

Wild chimpanzees produce acoustically distinct scream vocalizations depending on their social role during agonistic interactions with other group members. Here, we show that victims during such agonistic interactions alter the acoustic structure of their screams depending on the severity of aggression experienced, providing nearby listeners with important cues about the nature of the attack. However, we also found that victims of severe attacks produced screams that significantly exaggerated the true level of aggression experienced, but they did so only if there was at least one listener in the audience who matched or surpassed the aggressor in rank. Our results are consistent with the more general hypothesis that chimpanzees possess sophisticated understanding of third-party relationships, so-called triadic awareness, and that this knowledge influences their vocal production.
Ohno's dilemma: Evolution of new genes under continuous selection
Authors: Bergthorsson Ulfar , Andersson Dan I. , Roth John R.
Published: October 2007

New genes with novel functions arise by duplication and divergence, but the process poses a problem. After duplication, an extra gene copy must rise to sufficiently high frequency in the population and remain free of common inactivating lesions long enough to acquire the rare mutations that provide a new selectable function. Maintaining a duplicated gene by selection for the original function would restrict the freedom to diverge. (We refer to this problem as Ohno's dilemma). A model is described by which selection continuously favors both maintenance of the duplicate copy and divergence of that copy from the parent gene. Before duplication, the original gene has a trace side activity (the innovation) in addition to its original function. When an altered ecological niche makes the minor innovation valuable, selection favors increases in its level (the amplification), which is most frequently conferred by increased dosage of the parent gene. Selection for the amplified minor function maintains the extra copies and raises the frequency of the amplification in the population. The same selection favors mutational improvement of any of the extra copies, which are not constrained to maintain their original function (the divergence). The rate of mutations (per genome) that improve the new function is increased by the multiplicity of target copies within a genome. Improvement of some copies relaxes selection on others and allows their loss by mutation (becoming pseudogenes). Ultimately one of the extra copies is able to provide all of the new activity.
The relationship between evolutionary and physiological variation in hemoglobin
Authors: Milo Ron , Hou Jennifer H. , Springer Michael , Brenner Michael P. , Kirschner Marc W.
Published: October 2007

Physiological and evolutionary adaptations operate at very different time scales. Nevertheless, there are reasons to believe there should be a strong relationship between the two, as together they modify the phenotype. Physiological adaptations change phenotype by altering certain microscopic parameters; evolutionary adaptation can either alter genetically these same parameters or others to achieve distinct or similar ends. Although qualitative discussions of this relationship abound, there has been very little quantitative analysis. Here, we use the hemoglobin molecule as a model system to quantify the relationship between physiological and evolutionary adaptations. We compare measurements of oxygen saturation curves of 25 mammals with those of human hemoglobin under a wide range of physiological conditions. We fit the data sets to the Monod–Wyman–Changeux model to extract microscopic parameters. Our analysis demonstrates that physiological and evolutionary change act on different parameters. The main parameter that changes in the physiology of hemoglobin is relatively constant in evolution, whereas the main parameter that changes in the evolution of hemoglobin is relatively constant in physiology. This orthogonality suggests continued selection for physiological adaptability and hints at a role for this adaptability in evolutionary change.
Impaired face and body perception in developmental prosopagnosia
Authors: Righart Ruthger , de Gelder Beatrice
Published: October 2007

Prosopagnosia is a deficit in face recognition in the presence of relatively normal object recognition. Together with older lesion studies, recent brain-imaging results provide evidence for the closely related representations of faces and objects and, more recently, for brain areas sensitive to faces and bodies. This evidence raises the issue of whether developmental prosopagnosics may also have an impairment in encoding bodies. We investigated the first stages of face, body, and object perception in four developmental prosopagnosics by comparing event-related potentials to canonically and upside-down presented stimuli. Normal configural encoding was absent in three of four developmental prosopagnosics for faces at the P1 and for both faces and bodies at the N170 component. Our results demonstrate that prosopagnosics do not have this normal processing routine readily available for faces or bodies. A profound face recognition deficit characteristic of developmental prosopagnosia may not necessarily originate in a category-specific face recognition deficit in the initial stages of development. It may also have its roots in anomalous processing of the configuration, a visual routine that is important for other stimuli besides faces. Faces and bodies trigger configuration-based visual strategies that are crucial in initial stages of stimulus encoding but also serve to bootstrap the acquisition of more feature-based visual skills that progressively build up in the course of development.
Imaging cortical dynamics of language processing with the event-related optical signal
Authors: Tse Chun-Yu , Lee Chia-Lin , Sullivan Jason , Garnsey Susan M. , Dell Gary S. , Fabiani Monica , Gratton Gabriele
Published: October 2007

Language processing involves the rapid interaction of multiple brain regions. The study of its neurophysiological bases would therefore benefit from neuroimaging techniques combining both good spatial and good temporal resolution. Here we use the event-related optical signal (EROS), a recently developed imaging method, to reveal rapid interactions between left superior/middle temporal cortices (S/MTC) and inferior frontal cortices (IFC) during the processing of semantically or syntactically anomalous sentences. Participants were presented with sentences of these types intermixed with nonanomalous control sentences and were required to judge their acceptability. ERPs were recorded simultaneously with EROS and showed the typical activities that are elicited when processing anomalous stimuli: the N400 and the P600 for semantic and syntactic anomalies, respectively. The EROS response to semantically anomalous words showed increased activity in the S/MTC (corresponding in time with the N400), followed by IFC activity. Syntactically anomalous words evoked a similar sequence, with a temporal-lobe EROS response (corresponding in time with the P600), followed by frontal activity. However, the S/MTC activity corresponding to a semantic anomaly was more ventral than that corresponding to a syntactic anomaly. These data suggest that activation related to anomaly processing in sentences proceeds from temporal to frontal brain regions for both semantic and syntactic anomalies. This first EROS study investigating language processing shows that EROS can be used to image rapid interactions across cortical areas.
HOXB13 promotes ovarian cancer progression
Authors: Miao Jiangyong , Wang Zuncai , Provencher Heather , Muir Beth , Dahiya Sonika , Carney Erin , Leong Chee-Onn , Sgroi Dennis C. , Orsulic Sandra
Published: October 2007

Deregulated expression of HOXB13 in a subset of estrogen receptor-positive breast cancer patients treated with tamoxifen monotherapy is associated with an aggressive clinical course and poor outcome. Because the ovary is another hormone-responsive organ, we investigated whether HOXB13 plays a role in ovarian cancer progression. We show that HOXB13 is expressed in multiple human ovarian cancer cell lines and tumors and that knockdown of endogenous HOXB13 by RNA interference in human ovarian cancer cell lines is associated with reduced cell proliferation. Ectopic expression of HOXB13 is capable of transforming
p53
−/−
mouse embryonic fibroblasts and promotes cell proliferation and anchorage-independent growth in mouse ovarian cancer cell lines that contain genetic alterations in
p53
,
myc
, and
ras
. In this genetically defined cell line model of ovarian cancer, we demonstrate that HOXB13 collaborates with activated
ras
to markedly promote tumor growth
in vivo
and that HOXB13 confers resistance to tamoxifen-mediated apoptosis. Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer.
Potent D-peptide inhibitors of HIV-1 entry
Authors: Welch Brett D. , VanDemark Andrew P. , Heroux Annie , Hill Christopher P. , Kay Michael S.
Published: October 2007

During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC50= 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS.
A DNA methylation ratchet governs progression through a bacterial cell cycle
Authors: Collier Justine , McAdams Harley H. , Shapiro Lucy
Published: October 2007

The
Caulobacter
cell cycle is driven by a cascade of transient regulators, starting with the expression of DnaA in G
1
and ending with the expression of the essential CcrM DNA methyltransferase at the completion of DNA replication. The timing of DnaA accumulation was found to be regulated by the methylation state of the
dnaA
promoter, which in turn depends on the chromosomal position of
dnaA
near the origin of replication and restriction of CcrM synthesis to the end of the cell cycle. The
dnaA
gene is preferentially transcribed from a fully methylated promoter. DnaA initiates DNA replication and activates the transcription of the next cell-cycle regulator, GcrA. With the passage of the replication fork, the
dnaA
promoter becomes hemimethylated, and DnaA accumulation drops. GcrA then activates the transcription of the next cell-cycle regulator, CtrA, once the replication fork passes through the
ctrA
P1 promoter, generating two hemimethylated copies of
ctrA
. The
ctrA
gene is preferentially transcribed from a hemimethylated promoter. CtrA then activates the transcription of
ccrM
, to bring the newly replicated chromosome to the fully methylated state, promoting
dnaA
transcription and the start of a new cell cycle. We show that the cell-cycle timing of CcrM is critical for
Caulobacter
fitness. The sequential changes in the chromosomal methylation state serve to couple the progression of DNA replication to cell-cycle events regulated by the master transcriptional regulatory cascade, thus providing a ratchet mechanism for robust cell-cycle control.
Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy
Authors: Ebos John M. L. , Lee Christina R. , Christensen James G. , Mutsaers Anthony J. , Kerbel Robert S.
Published: October 2007

Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes. However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered protein expression was found in a broad variety of tissues, and dose-dependent elevations were observed of several plasma proteins previously unassociated with this class of inhibitor, including G-CSF, SDF-1α, SCF, and osteopontin. Our results suggest that observed sunitinib-induced molecular plasma changes, including those both directly and indirectly targeted by drug, represent a systemic tumor-independent response to therapy and may correlate with the most efficacious antitumor doses, potentially having utility for defining the optimal biologic dose range for this drug class but not as predictive markers of tumor response or clinical benefit. They may also be relevant to drug-associated toxicities, drug resistance, and observed rapid tumor (re)growth seen after cessation of therapy.
The structures of cyclic dihydronium cations
Authors: Wallace Sonjae , Huang Lulu , Massa Lou , Mukhopadhyay Uday , Bernal Ivan , Karle Jerome
Published: October 2007

Recent experimental discoveries have revealed the existence of hitherto unexpected cyclic hydronium di-cations trapped within crystal structures. The molecular formulas are (H
14
O
6
)
2+
, present as two isomers, four- and six-member cyclic structures, and (H
18
O
8
)
2+
, an eight-member cyclic structure. As these unprecedented hydronium species are stabilized by the crystal structures in which they are captured, the question arises whether they could be stable as independent species as, for example, in solution or gas phase. Quantum mechanical density functional theory calculations are used to investigate this question. We find these doubly charged cyclic hydronium structures to be energetically stable and, as between the four- and six-member structures, the former has more binding energy than the latter. We also determine the theoretically optimized structures for all three ions and give their calculated atomic charges for both their crystal and optimized geometries.
Chemical evolution: The mechanism of the formation of adenine under prebiotic conditions
Authors: Roy Debjani , Najafian Katayoun , von Ragué Schleyer Paul
Published: October 2007

Fundamental building blocks of life have been detected extraterrestrially, even in interstellar space, and are known to form nonenzymatically. Thus, the HCN pentamer, adenine (a base present in DNA and RNA), was first isolated in abiogenic experiments from an aqueous solution of ammonia and HCN in 1960. Although many variations of the reaction conditions giving adenine have been reported since then, the mechanistic details remain unexplored. Our predictions are based on extensive computations of sequences of reaction steps along several possible mechanistic routes. H
2
O- or NH
3
-catalyzed pathways are more favorable than uncatalyzed neutral or anionic alternatives, and they may well have been the major source of adenine on primitive earth. Our report provides a more detailed understanding of some of the chemical processes involved in chemical evolution, and a partial answer to the fundamental question of molecular biogenesis. Our investigation should trigger similar explorations of the detailed mechanisms of the abiotic formation of the remaining nucleic acid bases and other biologically relevant molecules.