bluuebunny/crossref_metadata_2025 huggingface dataset:
Size-resolved chemical composition of Australian dust aerosol during winter
Authors: Radhi M. , Box M. A. , Box G. P. , Keywood M. D. , Cohen D. D. , Stelcer E. , Mitchell R. M.
Published: June 2011

Environmental contextMineral dust aerosol is both an efficient scatterer of solar radiation, potentially cooling the planet, and a moderate absorber, potentially warming it: the exact balance is both uncertain, and geographically variable. Australian desert soils are noticeably more reddish than most Northern Hemisphere deserts, most probably a result of enhanced iron mineralogy. This paper contains results from a field campaign designed to increase our understanding of the chemistry of Australian mineral dust aerosol, especially in relation to iron and salt.
AbstractAustralia is the dominant source of mineral dust aerosol in the Southern Hemisphere, yet the physical, chemical and optical properties of this aerosol remain poorly understood. Four sets of size-resolved aerosol samples were collected at a site on the edge of the Lake Eyre Basin (LEB), in the south-east dust transport pathway. Back trajectory analysis shows that three samples were sourced from the LEB (one during a rare winter dust storm), and one from coastal regions to the south. All samples were subjected to both ion beam analysis and ion chromatography. A Fe/Al ratio of 0.9 was found, consistent with results from our other campaigns to sites in the LEB, significantly higher than typical Northern Hemisphere values (~0.45–0.6). This confirms the iron-rich character of central Australian soils. Clear evidence of marine advection in the fourth sample was also found, and evidence of chloride depletion by nitric acid in two samples.
Integration of complementary and alternative medicine information and advice in chronic disease management guidelines
Authors: Team Victoria , Canaway Rachel , Manderson Lenore
Published: June 2011

The growing evidence on the benefits and risks of complementary and alternative medicine (CAM) and its high rate of use (69% of Australians) – particularly for chronic or recurrent conditions – means increasing attention on CAM. However, few people disclose CAM use to their GP, and health professionals tend to inadequately discuss CAM-related issues with their patients, partly due to insufficient knowledge. As clinical and non-clinical chronic condition management guidelines are a means to educate primary health care practitioners, we undertook a content analysis of guidelines relevant to two common chronic conditions – cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) – to assess their provision of CAM-related information. Ten current Australian guidelines were reviewed, revealing scant CAM content. When available, the CAM-relevant information was brief, in some cases unclear, inconclusive and lacking in direction to the GP or health care provider. Although we focus on CVD and T2DM, we argue the value of all chronic condition management guidelines integrating relevant evidence-informed information and advice on CAM risks, benefits and referrals, to increase GP awareness and knowledge of appropriate CAM therapies, and potentially to facilitate doctor–client discussion about CAM.
Barriers to recruitment of professionals into a general practice childhood obesity program
Authors: Jones Kay M. , Dixon Maureen E. , Falkingham Leah , Piteman Leon , Dixon John B.
Published: June 2011

Recruiting general practitioners to take part in research in primary care is important and challenging. This paper describes the process, barriers and achievements experienced by a research team whilst recruiting Divisions and general practitioners (GPs)/practices into a project related to management of obesity in children, which used Breakthrough Series methodology in the intervention arm. The research team chose to recruit GPs through Divisions of General Practice, because of the existing positive relationship between the research team and the Divisions, and the Divisions’ positive relationships with the GPs/practices in their area. The project aimed to recruit four Divisions of General Practice, who in turn would recruit a total of 24 GPs/practices. Four Divisions (two rural, two metropolitan) were recruited initially, but the two rural Divisions withdrew before the project commenced and were replaced by two metropolitan Divisions. As Divisions were unable to recruit sufficient GPs/practices, two additional strategies were used, but despite all efforts, only 17 practices were recruited. Reflection on recruitment failure focussed on reasons from the perspective of Divisions, GPs, other projects using the Breakthrough Series methodology with a chronic disease focus and other projects conducted in Australia where the focus was childhood obesity. The results showed that even Divisions who were enthusiastic about joining a project may be unable to recruit sufficient GPs and practices, for reasons including staff changeover and GP reluctance. Caution is suggested when setting recruitment targets where the condition is sensitive, is not the presenting problem, is not routinely tackled in general practice, involves minors, where treatment is perceived to be of doubtful effectiveness, or where major government policies may need to be considered.
Importance of effective collaboration between health professionals for the facilitation of optimal community diabetes care
Authors: Melville-Smith Jo , Kendall Garth E.
Published: June 2011

Diabetes places a significant burden on the individuals concerned, their families and society as a whole. The debilitating sequelae of diabetes can be limited or prevented altogether through strict glycaemic control. Despite the seemingly uncomplicated nature of the disorder, effective management can be elusive, as the impact of having to deal with diabetes on a daily basis can be profound and appropriate professional support is not always readily available. As the roles of general practitioners (GPs) and allied health professionals have evolved, a major issue now facing all is that of developing and maintaining effective collaborative relationships for the facilitation of optimal community diabetes care. Using a simple survey methodology, the present exploratory study investigated the referral patterns of GPs to diabetic educators (DEs) working for a community health service in an Australian town, and reasons for referral and non-referral in order to identify factors that contribute to a sound and sustainable collaborative relationship. The results provide some evidence that GPs and DEs in this town do work collaboratively towards achieving client-centred goals and highlight the need to inform GPs who are new to communities, such as this one, of the available DE services. Most importantly, the study identified that there are many opportunities to strengthen collaboration so as to facilitate optimal community diabetes care. This information is valuable, because there is limited empirical evidence either nationally or internationally about the process of collaboration between health professionals in the management of chronic diseases, such as diabetes.
A local study of costs for private allied health in Australian primary health care: variability and policy implications
Authors: Pearce-Brown Carmen L. , Grealish Laurie , McRae Ian S. , Douglas Kirsty A. , Yen Laurann E. , Wells Robert W. , Wareham Susan
Published: June 2011

Multidisciplinary approaches to primary health care improve outcomes for individuals living with chronic conditions. However, emerging evidence suggests access to allied health professionals in Australia is problematic. This paper reports findings of a telephone survey of allied health professionals’ billing practices in one urban area. The survey was undertaken as a quality improvement project in response to the affordability queries raised by patients and carers in the clinical setting. The aim was to determine financial cost of access to allied health professionals in one urban primary health care setting. Participant practices included: physiotherapy (n = 21), podiatry (n = 8) and dietitians (n = 3). Fees were variable, with cost of the initial (assessment) appointment higher than subsequent (follow-up) appointments in 92% of practices. The average out of pocket expenses for assessment and three follow-up appointments ranged from $258 to $302. When available, the Medicare rebate reduced this to $58–106. Bulk billing was not offered. Variable costs, minimal concessions and absence of bulk billing in this confined geographical area creates a cost barrier to access for patients from lower socioeconomic groups and has implications for access to multidisciplinary care in Australian primary health care.
Parents's plans to supply their adolescents with alcohol
Authors: Ward Bernadette M. , Snow Pamela C.
Published: June 2011

The aim was to determine the extent to which parent and adolescent characteristics and patterns of alcohol use influence parents’ plans to supply their adolescent aged 14–16 years with full serves of alcohol (i.e. not necessarily initiation) in the next 6 months. A cross-sectional sample of parents from Victoria, Australia, completed an online survey. Parents’ plans to supply alcohol in the next 6 months was significantly associated with their reports of supplying alcohol in the previous 3 months (β = 0.51, P < 0.01), perceptions that their adolescent drinks (β = 0.34, P < 0.01), reports of not practising religion (β = 0.13, P < 0.01), and Alcohol Use Disorders Identification Test scores (β = 0.09, P = 0.04). The total variance explained by the model was 57.4% F (9, 242) = 36.2, P < 0.01. Parents’ plans to supply their adolescent with alcohol might be a reflection of the normalisation of alcohol use in Australia. There is a need to support Australian parents to review their own alcohol use, clarify their views on alcohol use by their adolescent and confidently restrict their child’s access to alcohol, irrespective of their own drinking patterns.
A novel primary care clinical prediction rule for early detection of osteoporosis
Authors: Kimber Cheryl , Grimmer-Somers Karen
Published: June 2011

The effects of osteoporosis (OP) can be significantly slowed if disease is detected early. We report on a clinical risk prediction rule developed from patient histories taken in an orthopaedic outpatient clinic, before confirmatory testing for OP. Data were extracted from routine audits of consecutive records of patients with recent wrist fracture, comprising demographic details, medications, past and current disease, and fracture details. Clinical prediction rule elements were tested against clinical suspicion of OP. The clinical prediction elements comprised sex and age risk, medications that predispose patients to OP and/or falls, previous fractures and disease/medical conditions that are known OP risks. The best cut point (6.5) demonstrated 100% sensitivity with clinical suspicion of OP. Patient history information is often available before OP is clinically suspected or a definitive diagnosis is made. Our clinical prediction rule will be useful in primary care settings where objective measures of bone health are not readily available. It will raise OP awareness amongst health care providers and patients, particularly those not previously suspected of having OP. It will assist in identifying at-risk patients early and commencing them on appropriate management, without waiting for definitive bone health tests.
Responding to rural health needs through community participation: addressing the concerns of children and young adults
Authors: Jeffery Vivienne , Ervin Kaye
Published: June 2011

A small rural health service undertook a major needs analysis in 2008 to identify gaps in service delivery and duplication of services. This exercise was intended to inform strategic direction but the result was consumer and community consultation and outcomes that far exceeded everyone’s expectations. Organisations often pay lip service to the concept of community participation and consultation and the importance of consumer involvement. Turning this rhetoric into action is challenging and requires dedicated staff, organisational support and momentum for it to occur. The project described resulted in targeted, purposeful action regarding community engagement, and the findings and outcomes are reflective of this. The unexpected findings required an organisational shift, which was embraced by the health service and resulted in collaborative partnerships with consumers and organisations that are proving beneficial to the entire community and outlying areas. Few organisations would demonstrate the willingness to accommodate such change, or undertake a needs analysis that is chiefly community driven.
Nutrition advice in general practice: the role of general practitioners and practice nurses
Authors: Mitchell Lana J. , MacDonald-Wicks Lesley , Capra Sandra
Published: June 2011

General practice is an ideal setting to be providing nutrition advice; however, it is important that the role of general practitioners (GPs) and practice nurses in providing nutrition advice is acknowledged and defined. This article aims to discuss the role of GPs and practice nurses in the delivery of nutrition advice. Ten general practitioners and 12 practice nurses from a NSW urban Division of General Practice participated in questionnaires and a Lifescripts© implementation study, as well as their consenting patients receiving Lifescripts© (n = 13). An online survey was conducted with 90 Australian private practice dietitians. Semi-structured telephone interviews were conducted with 52 Australian private practice dietitians. The provision of basic nutrition advice is acknowledged to be part of the role of GPs and practice nurses, as they are the first point of contact for patients, allowing them to raise nutrition awareness. However, it is important that this advice is evidence based and able to be delivered in a time-efficient manner. Increased nutrition education and the availability of appropriate resources and nutrition-related best practice guidelines will assist in this process.
Glass–liquid transition of water at high pressure
Authors: Andersson Ove
Published: June 2011

The knowledge of the existence of liquid water under extreme conditions and its concomitant properties are important in many fields of science. Glassy water has previously been prepared by hyperquenching micron-sized droplets of liquid water and vapor deposition on a cold substrate (ASW), and its transformation to an ultraviscous liquid form has been reported on heating. A densified amorphous solid form of water, high-density amorphous ice (HDA), has also been made by collapsing the structure of ice at pressures above 1 GPa and temperatures below approximately 140 K, but a corresponding liquid phase has not been detected. Here we report results of heat capacity
C

p

and thermal conductivity, in situ, measurements, which are consistent with a reversible transition from annealed HDA to ultraviscous high-density liquid water at 1 GPa and 140 K. On heating of HDA, the
C

p

increases abruptly by (3.4 ± 0.2) J mol
-1
 K
-1
before crystallization starts at (153 ± 1) K. This is larger than the
C

p

rise at the glass to liquid transition of annealed ASW at 1 atm, which suggests the existence of liquid water under these extreme conditions.
The cultural niche: Why social learning is essential for human adaptation
Authors: Boyd Robert , Richerson Peter J. , Henrich Joseph
Published: June 2011

In the last 60,000 y humans have expanded across the globe and now occupy a wider range than any other terrestrial species. Our ability to successfully adapt to such a diverse range of habitats is often explained in terms of our cognitive ability. Humans have relatively bigger brains and more computing power than other animals, and this allows us to figure out how to live in a wide range of environments. Here we argue that humans may be smarter than other creatures, but none of us is nearly smart enough to acquire all of the information necessary to survive in any single habitat. In even the simplest foraging societies, people depend on a vast array of tools, detailed bodies of local knowledge, and complex social arrangements and often do not understand why these tools, beliefs, and behaviors are adaptive. We owe our success to our uniquely developed ability to learn from others. This capacity enables humans to gradually accumulate information across generations and develop well-adapted tools, beliefs, and practices that are too complex for any single individual to invent during their lifetime.
Kinship, greenbeards, and runaway social selection in the evolution of social insect cooperation
Authors: Nonacs Peter
Published: June 2011

Social Hymenoptera have played a leading role in development and testing of kin selection theory. Inclusive fitness models, following from Hamilton's rule, successfully predict major life history characteristics, such as biased sex investment ratios and conflict over parentage of male offspring. However, kin selection models poorly predict patterns of caste-biasing nepotism and reproductive skew within groups unless kin recognition constraints or group-level selection is also invoked. These successes and failures mirror the underlying kin recognition mechanisms. With reliable environmental cues, such as the sex of offspring or the origin of male eggs, predictions are supported. When only genetic recognition cues are potentially available, predictions are not supported. Mathematical simulations demonstrate that these differing mechanisms for determining kinship produce very different patterns of behavior. Decisions based on environmental cues for relatedness result in a robust mixture of cooperation and noncooperation depending on whether or not Hamilton's rule is met. In contrast, cooperation evolves under a wider range of conditions and to higher frequencies with genetic kin recognition as shared greenbeard traits. This “excess of niceness” matches the existing patterns in caste bias and reproductive skew; individuals often help others at an apparent cost to their inclusive fitness. The results further imply a potential for greenbeard-type kin recognition to create arbitrary runaway social selection for shared genetic traits. Suggestive examples in social evolution may be alloparental care and unicoloniality in ants. Differences in kin recognition mechanisms also can have consequences for maintenance of advantageous genetic diversity within populations.
Endemic social diversity within natural kin groups of a cooperative bacterium
Authors: Kraemer Susanne A. , Velicer Gregory J.
Published: June 2011

The spatial structure of genetic diversity underlying social variation is a critical determinant of how cooperation and conflict evolve. Here we investigated whether natural social groups of the cooperative soil bacterium
Myxococcus xanthus
harbor internal genetic and phenotypic variation and thus the potential for social conflict between interacting cells. Ten
M. xanthus
fruiting bodies isolated from soil were surveyed for variation in multiple social phenotypes and genetic loci, and patterns of diversity within and across fruiting body groups were examined. Eight of the 10 fruiting bodies were found to be internally diverse, with four exhibiting significant variation in social swarming phenotypes and five harboring large variation in the number of spores produced by member clones in pure culture. However, genetic variation within fruiting bodies was much lower than across fruiting bodies, suggesting that migration across even spatially proximate groups is limited relative to mutational generation of persisting endemic diversity. Our results simultaneously highlight the potential for social conflict within
Myxococcus
social groups and the possibility of social coevolution among diverse related lineages that are clustered in space and cotransmitted across generations.
Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration
Authors: Ding Jin-Dong , Johnson Lincoln V. , Herrmann Rolf , Farsiu Sina , Smith Stephanie G. , Groelle Marybeth , Mace Brian E. , Sullivan Patrick , Jamison Jeffrey A. , Kelly Una , Harrabi Ons , Bollini Sangeetha Subbarao , Dilley Jeanette , Kobayashi Dione , Kuang Bing , Li Wenlin , Pons Jaume , Lin John C. , Rickman Catherine Bowes
Published: June 2011

Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid β (Aβ) peptides, Aβ1–40 (Aβ40) and Aβ1–42 (Aβ42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for Aβ, we show here that a mouse model of AMD that invokes multiple factors that are known to modify AMD risk (aged human
apolipoprotein E 4
targeted replacement mice on a high-fat, cholesterol-enriched diet) presents with Aβ-containing deposits basal to the retinal pigmented epithelium (RPE), histopathologic changes in the RPE, and a deficit in scotopic electroretinographic response, which is reflective of impaired visual function. Strikingly, these electroretinographic deficits are abrogated in a dose-dependent manner by systemic administration of an antibody targeting the C termini of Aβ40 and Aβ42. Concomitant reduction in the levels of Aβ and activated complement components in sub-RPE deposits and structural preservation of the RPE are associated with anti-Aβ40/42 antibody immunotherapy and visual protection. These observations are consistent with the reduction in amyloid plaques and improvement of cognitive function in mouse models of Alzheimer's disease treated with anti-Aβ antibodies. They also implicate Aβ in the pathogenesis of AMD and identify Aβ as a viable therapeutic target for its treatment.
Pathology from evolutionary conflict, with a theory of X chromosome versus autosome conflict over sexually antagonistic traits
Authors: Frank Steven A. , Crespi Bernard J.
Published: June 2011

Evolutionary conflicts cause opponents to push increasingly hard and in opposite directions on the regulation of traits. One can see only the intermediate outcome from the balance of the exaggerated and opposed forces. Intermediate expression hides the underlying conflict, potentially misleading one to conclude that trait regulation is designed to achieve efficient and robust expression, rather than arising by the precarious resolution of conflict. Perturbation often reveals the underlying nature of evolutionary conflict. Upon mutation or knockout of one side in the conflict, the other previously hidden and exaggerated push on the trait may cause extreme, pathological expression. In this regard, pathology reveals hidden evolutionary design. We first review several evolutionary conflicts between males and females, including conflicts over mating, fertilization, and the growth rate of offspring. Perturbations of these conflicts lead to infertility, misregulated growth, cancer, behavioral abnormalities, and psychiatric diseases. We then turn to antagonism between the sexes over traits present in both males and females. For many traits, the different sexes favor different phenotypic values, and constraints prevent completely distinct expression in the sexes. In this case of sexual antagonism, we present a theory of conflict between X-linked genes and autosomal genes. We suggest that dysregulation of the exaggerated conflicting forces between the X chromosome and the autosomes may be associated with various pathologies caused by extreme expression along the male–female axis. Rapid evolution of conflicting X-linked and autosomal genes may cause divergence between populations and speciation.
Multiscale approach to link red blood cell dynamics, shear viscosity, and ATP release
Authors: Forsyth Alison M. , Wan Jiandi , Owrutsky Philip D. , Abkarian Manouk , Stone Howard A.
Published: June 2011

RBCs are known to release ATP, which acts as a signaling molecule to cause dilation of blood vessels. A reduction in the release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. Furthermore, reduced deformation of RBCs has been correlated with myocardial infarction and coronary heart disease. Because ATP release has been linked to cell deformation, we undertook a multiscale approach to understand the links between single RBC dynamics, ATP release, and macroscopic viscosity all at physiological shear rates. Our experimental approach included microfluidics, ATP measurements using a bioluminescent reaction, and rheology. Using microfluidics technology with high-speed imaging, we visualize the deformation and dynamics of single cells, which are known to undergo motions such as tumbling, swinging, tanktreading, and deformation. We report that shear thinning is not due to cellular deformation as previously believed, but rather it is due to the tumbling-to-tanktreading transition. In addition, our results indicate that ATP release is constant at shear stresses below a threshold (3 Pa), whereas above the threshold ATP release is increased and accompanied by large cellular deformations. Finally, performing experiments with well-known inhibitors, we show that the Pannexin 1 hemichannel is the main avenue for ATP release both above and below the threshold, whereas, the cystic fibrosis transmembrane conductance regulator only contributes to deformation-dependent ATP release above the stress threshold.
Uncertainties in climate assessment for the case of aviation NO
Authors: Holmes Christopher D. , Tang Qi , Prather Michael J.
Published: June 2011

Nitrogen oxides emitted from aircraft engines alter the chemistry of the atmosphere, perturbing the greenhouse gases methane (CH
4
) and ozone (O
3
). We quantify uncertainties in radiative forcing (RF) due to short-lived increases in O
3
, long-lived decreases in CH
4
and O
3
, and their net effect, using the ensemble of published models and a factor decomposition of each forcing. The decomposition captures major features of the ensemble, and also shows which processes drive the total uncertainty in several climate metrics. Aviation-specific factors drive most of the uncertainty for the short-lived O
3
and long-lived CH
4
RFs, but a nonaviation factor dominates for long-lived O
3
. The model ensemble shows strong anticorrelation between the short-lived and long-lived RF perturbations (
R
2
 = 0.87). Uncertainty in the net RF is highly sensitive to this correlation. We reproduce the correlation and ensemble spread in one model, showing that processes controlling the background tropospheric abundance of nitrogen oxides are likely responsible for the modeling uncertainty in climate impacts from aviation.
Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in
Plasmodium yoelii
Authors: Li Jian , Pattaradilokrat Sittiporn , Zhu Feng , Jiang Hongying , Liu Shengfa , Hong Lingxian , Fu Yong , Koo Lily , Xu Wenyue , Pan Weiqing , Carlton Jane M. , Kaneko Osamu , Carter Richard , Wootton John C. , Su Xin-zhuan
Published: June 2011

Plasmodium yoelii
is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. Here, we performed 14 genetic crosses between three pairs of
P. yoelii
clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. Microsatellite genotypes from the progeny formed 14 linkage groups belonging to the 14 parasite chromosomes, allowing assignment of sequence contigs to chromosomes. Growth-related virulent phenotypes from 25 progeny of one of the crosses were significantly associated with a major locus on chromosome 13 and with two secondary loci on chromosomes 7 and 10. The chromosome 10 and 13 loci are both linked to day 5 parasitemia, and their effects on parasite growth rate are independent but additive. The locus on chromosome 7 is associated with day 10 parasitemia. The chromosome 13 locus spans ∼220 kb of DNA containing 51 predicted genes, including the
P. yoelii
erythrocyte binding ligand, in which a C741Y substitution in the R6 domain is implicated in the change of growth rate. Similarly, the chromosome 10 locus spans ∼234 kb with 71 candidate genes, containing a member of the 235-kDa rhoptry proteins (Py235) that can bind to the erythrocyte surface membrane. Atypical virulent phenotypes among the progeny were also observed. This study provides critical tools and information for genetic investigations of virulence and biology of
P. yoelii
.
Endogenous GABA
A
and GABA
B
receptor-mediated electrical suppression is critical to neuronal anoxia tolerance
Authors: Pamenter Matthew E. , Hogg David W. , Ormond Jake , Shin Damian S. , Woodin Melanie A. , Buck Leslie T.
Published: June 2011

Anoxic insults cause hyperexcitability and cell death in mammalian neurons. Conversely, in anoxia-tolerant turtle brain, spontaneous electrical activity is suppressed by anoxia (i.e., spike arrest; SA) and cell death does not occur. The mechanism(s) of SA is unknown but likely involves GABAergic synaptic transmission, because GABA concentration increases dramatically in anoxic turtle brain. We investigated this possibility in turtle cortical neurons exposed to anoxia and/or GABA
A/B
receptor (GABAR) modulators. Anoxia increased endogenous slow phasic GABAergic activity, and both anoxia and GABA reversibly induced SA by increasing GABA
A
R-mediated postsynaptic activity and Cl
−
conductance, which eliminated the Cl
−
driving force by depolarizing membrane potential (∼8 mV) to GABA receptor reversal potential (∼−81 mV), and dampened excitatory potentials via shunting inhibition. In addition, both anoxia and GABA decreased excitatory postsynaptic activity, likely via GABA
B
R-mediated inhibition of presynaptic glutamate release. In combination, these mechanisms increased the stimulation required to elicit an action potential >20-fold, and excitatory activity decreased >70% despite membrane potential depolarization. In contrast, anoxic neurons cotreated with GABA
A+B
R antagonists underwent seizure-like events, deleterious Ca
2+
influx, and cell death, a phenotype consistent with excitotoxic cell death in anoxic mammalian brain. We conclude that increased endogenous GABA release during anoxia mediates SA by activating an inhibitory postsynaptic shunt and inhibiting presynaptic glutamate release. This represents a natural adaptive mechanism in which to explore strategies to protect mammalian brain from low-oxygen insults.
Tungsten tetraboride, an inexpensive superhard material
Authors: Mohammadi Reza , Lech Andrew T. , Xie Miao , Weaver Beth E. , Yeung Michael T. , Tolbert Sarah H. , Kaner Richard B.
Published: June 2011

Tungsten tetraboride (WB
4
) is an interesting candidate as a less expensive member of the growing group of superhard transition metal borides. WB
4
was successfully synthesized by arc melting from the elements. Characterization using powder X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) indicates that the as-synthesized material is phase pure. The zero-pressure bulk modulus, as measured by high-pressure X-ray diffraction for WB
4
, is 339 GPa. Mechanical testing using microindentation gives a Vickers hardness of 43.3 ± 2.9 GPa under an applied load of 0.49 N. Various ratios of rhenium were added to WB
4
in an attempt to increase hardness. With the addition of 1 at.% Re, the Vickers hardness increased to approximately 50 GPa at 0.49 N. Powders of tungsten tetraboride with and without 1 at.% Re addition are thermally stable up to approximately 400 °C in air as measured by thermal gravimetric analysis.
Kinetic design of the respiratory oxidases
Authors: von Ballmoos Christoph , Gennis Robert B. , Ädelroth Pia , Brzezinski Peter
Published: June 2011

Energy conservation in all kingdoms of life involves electron transfer, through a number of membrane-bound proteins, associated with proton transfer across the membrane. In aerobic organisms, the last component of this electron-transfer chain is a respiratory heme-copper oxidase that catalyzes reduction of O
2
to H
2
O, linking this process to transmembrane proton pumping. So far, the molecular mechanism of proton pumping is not known for any system that is driven by electron transfer. Here, we show that this problem can be addressed and elucidated in a unique cytochrome
c
oxidase (cytochrome
ba
3
) from a thermophilic bacterium,
Thermus thermophilus
. The results show that in this oxidase the electron- and proton-transfer reactions are orchestrated in time such that previously unresolved proton-transfer reactions could be directly observed. On the basis of these data we propose that loading of the proton pump occurs upon electron transfer, but before substrate proton transfer, to the catalytic site. Furthermore, the results suggest that the pump site alternates between a protonated and deprotonated state for every second electron transferred to the catalytic site, which would explain the noninteger pumping stoichiometry (0.5 H
+
/e
-
) of the
ba
3
oxidase. Our studies of this variant of Nature’s palette of mechanistic solutions to a basic problem offer a route toward understanding energy conservation in biological systems.
Simulations of nuclear pore transport yield mechanistic insights and quantitative predictions
Authors: Mincer Joshua S. , Simon Sanford M.
Published: June 2011

To study transport through the nuclear pore complex, we developed a computational simulation that is based on known structural elements rather than a particular transport model. Results agree with a variety of experimental data including size cutoff for cargo transport with (30-nm diameter) and without (< 10 nm) nuclear localization signals (NLS), macroscopic transport rates (hundreds per second), and single cargo transit times (milliseconds). The recently observed bimodal cargo distribution is predicted, as is the relative invariance of single cargo transit times out to large size (even as macroscopic transport rate decreases). Additional predictions concern the effects of the number of NLS tags, the RanGTP gradient, and phenylalanine-glycine nucleopore protein (FG-Nup) structure, flexibility, and cross-linking. Results are consistent with and elucidate the molecular mechanisms of some existing hypotheses (selective phase, virtual gate, and selective gate models). A model emerges that is a hybrid of a number of preexisting models as well as a Brownian ratchet model, in which a cargo-karyopherin complex remains bound to the same FG-Nups for its entire trajectory through the nuclear pore complex until RanGTP severs the cargo-Nup bonds to effect release into the nucleus.
Female gamete competition in an ancient angiosperm lineage
Authors: Bachelier Julien B. , Friedman William E.
Published: June 2011

InTrimenia moorei, an extant member of the ancient angiosperm clade Austrobaileyales, we found a remarkable pattern of female gametophyte (egg-producing structure) development that strikingly resembles that of pollen tubes and their intrasexual competition within the maternal pollen tube transmitting tissues of most flowers. In contrast with most other flowering plants, inTrimenia, multiple female gametophytes are initiated at the base (chalazal end) of each ovule. Female gametophytes grow from their tips and compete over hundreds of micrometers to reach the apex of the nucellus and the site of fertilization. Here, the successful female gametophyte will mate with a pollen tube to produce an embryo and an endosperm. Moreover, the central tissue within the ovules ofTrimenia, through which the embryo sacs grow, contains starch and other carbohydrates similar to the pollen tube transmitting tissues in the styles of most flowers. The pattern of female gametophyte development found inTrimeniais rare but by no means unique in angiosperms. Importantly, it seems that multiple female gametophytes are occasionally or frequently initiated in members of other ancient angiosperm lineages. The intensification of pollen tube (male gametophyte) competition and enhanced maternal selection among competing pollen tubes are considered to have been major contributors to the rise of angiosperms. Based on insights fromTrimenia, we posit that prefertilization female gametophyte (egg) competition within individual ovules in addition to male gametophyte (sperm) competition and maternal mate choice may have been key features of the earliest angiosperms.
Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2
Authors: Gregory Sonia M. , Harada Erisa , Liang Binyong , Delos Sue E. , White Judith M. , Tamm Lukas K.
Published: June 2011

Ebolavirus (Ebov), an enveloped virus of the familyFiloviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus–host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the α-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH ≤5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an ∼90° bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus–host cell membrane contact and, hence, initiate Ebov fusion.
Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR
Authors: Bachas Sharrol , Eginton Christopher , Gunio Drew , Wade Herschel
Published: June 2011

Current views of multidrug (MD) recognition focus on large drug-binding cavities with flexible elements. However, MD recognition in BmrR is supported by a small, rigid drug-binding pocket. Here, a detailed description of MD binding by the noncanonical BmrR protein is offered through the combined use of X-ray and solution studies. Low shape complementarity, suboptimal packing, and efficient burial of a diverse set of ligands is facilitated by an aromatic docking platform formed by a set of conformationally fixed aromatic residues, hydrophobic pincer pair that locks the different drug structures on the adaptable platform surface, and a trio of acidic residues that enables cation selectivity without much regard to ligand structure. Within the binding pocket is a set of BmrR-derived H-bonding donor and acceptors that solvate a wide range of ligand polar substituent arrangements in a manner analogous to aqueous solvent. Energetic analyses of MD binding by BmrR are consistent with structural data. A common binding orientation for the different BmrR ligands is in line with promiscuous allosteric regulation.
Membrane fusion by the GTPase atlastin requires a conserved C-terminal cytoplasmic tail and dimerization through the middle domain
Authors: Moss Tyler J. , Andreazza Camilla , Verma Avani , Daga Andrea , McNew James A.
Published: June 2011

The biogenesis and maintenance of the endoplasmic reticulum (ER) requires membrane fusion. ER homotypic fusion is driven by the large GTPase atlastin. Domain analysis of atlastin shows that a conserved region of the C-terminal cytoplasmic tail is absolutely required for fusion activity. Atlastin in adjacent membranes must associate to bring the ER membranes into molecular contact.
Drosophila
atlastin dimerizes in the presence of GTPγS but is monomeric with GDP or without nucleotide. Oligomerization requires the juxtamembrane middle domain three-helix bundle, as does efficient GTPase activity. A soluble version of the N-terminal cytoplasmic domain that contains the GTPase domain and the middle domain three-helix bundle serves as a potent, concentration-dependent inhibitor of membrane fusion both in vitro and in vivo. However, atlastin domains lacking the middle domain are without effect. GTP-dependent dimerization of atlastin generates an enzymatically active protein that drives membrane fusion after nucleotide hydrolysis and conformational reorganization.
New family of tilings of three-dimensional Euclidean space by tetrahedra and octahedra
Authors: Conway John H. , Jiao Yang , Torquato Salvatore
Published: June 2011

It is well known that two regular tetrahedra can be combined with a single regular octahedron to tile (complete fill) three-dimensional Euclidean space

. This structure was called the “octet truss” by Buckminster Fuller. It was believed that such a tiling, which is the Delaunay tessellation of the face-centered cubic (fcc) lattice, and its closely related stacking variants, are the only tessellations of

that involve two different regular polyhedra. Here we identify and analyze a unique family comprised of a noncountably infinite number of periodic tilings of

whose smallest repeat tiling unit consists of one regular octahedron and six smaller regular tetrahedra. We first derive an extreme member of this unique tiling family by showing that the “holes” in the optimal lattice packing of octahedra, obtained by Minkowski over a century ago, are congruent tetrahedra. This tiling has 694 distinct concave (i.e., nonconvex) repeat units, 24 of which possess central symmetry, and hence is distinctly different and combinatorically richer than the fcc tetrahedra-octahedra tiling, which only has two distinct tiling units. Then we construct a one-parameter family of octahedron packings that continuously spans from the fcc to the optimal lattice packing of octahedra. We show that the “holes” in these packings, except for the two extreme cases, are tetrahedra of two sizes, leading to a family of periodic tilings with units composed four small tetrahedra and two large tetrahedra that contact an octahedron. These tilings generally possess 2,068 distinct concave tiling units, 62 of which are centrally symmetric.
Expanding the role of Drosha to the regulation of viral gene expression
Authors: Lin Yao-Tang , Sullivan Christopher S.
Published: June 2011

It is well-appreciated that viruses use host effectors for macromolecular synthesis and as regulators of viral gene expression. Viruses can encode their own regulators, but often use host-encoded factors to optimize replication. Here, we show that Drosha, an endoribonuclease best known for its role in the biogenesis of microRNAs (miRNAs), can also function to directly regulate viral gene expression. Kaposi's Sarcoma-associated Herpesvirus (KSHV) is associated with various tumors, and like all herpesviruses, has two modes of infection, latent and lytic, which are characterized by differential expression of viral gene products. Kaposin B (KapB) is a KSHV-encoded protein associated with cytokine production and cytotoxicity. We demonstrate that in addition to previously known transcriptional mechanisms, differences in Drosha levels contribute to low levels of KapB expression in latency and robust increases in expression during lytic replication. Thus, surprisingly, KSHV modulates Drosha activity differentially depending on the mode of replication. This regulation is dependent on Drosha-mediated cleavage, and KapB transcripts lacking the Drosha cleavage sites express higher levels of KapB, resulting in increased cell death. This work increases the known functions of Drosha and implies that tying viral gene expression to Drosha activity is advantageous for viruses.
Majority of CD4
+
T cells from peripheral blood of HIV-1–infected individuals contain only one HIV DNA molecule
Authors: Josefsson Lina , King Martin S. , Makitalo Barbro , Brännström Johan , Shao Wei , Maldarelli Frank , Kearney Mary F. , Hu Wei-Shau , Chen Jianbo , Gaines Hans , Mellors John W. , Albert Jan , Coffin John M. , Palmer Sarah E.
Published: June 2011

Neither the number of HIV-1 proviruses within individual infected cells in HIV-1–infected patients nor their genetic relatedness within individual infected cells and between cells and plasma virus are well defined. To address these issues we developed a technique to quantify and genetically characterize HIV-1 DNA from single infected cells in vivo. Analysis of peripheral blood CD4
+
T cells from nine patients revealed that the majority of infected cells contain only one copy of HIV-1 DNA, implying a limited potential for recombination in virus produced by these cells. The genetic similarity between HIV populations in CD4
+
T cells and plasma implies ongoing exchange between these compartments both early and late after infection.
Evolution of cyclic peptide protease inhibitors
Authors: Young Travis S. , Young Douglas D. , Ahmad Insha , Louis John M. , Benkovic Stephen J. , Schultz Peter G.
Published: June 2011

We report a bacterial system for the evolution of cyclic peptides that makes use of an expanded set of amino acid building blocks. Orthogonal aminoacyl-tRNA synthetase/tRNACUApairs, together with a split intein system were used to biosynthesize a library of ribosomal peptides containing amino acids with unique structures and reactivities. This peptide library was subsequently used to evolve an inhibitor of HIV protease using a selection based on cellular viability. Two of three cyclic peptides isolated after two rounds of selection contained the keto amino acidp-benzoylphenylalanine (pBzF). The most potent peptide (G12: GIXVSL;X = pBzF) inhibited HIV protease through the formation of a covalent Schiff base adduct of thepBzF residue with the ϵ-amino group of Lys 14 on the protease. This result suggests that an expanded genetic code can confer an evolutionary advantage in response to selective pressure. Moreover, the combination of natural evolutionary processes with chemically biased building blocks provides another strategy for the generation of biologically active peptides using microbial systems.
Regulation of apoptosis by the circadian clock through NF-κB signaling
Authors: Lee Jin Hyup , Sancar Aziz
Published: June 2011

In mice and humans the circadian rhythm of many biochemical reactions, physiology, and behavior is generated by a transcriptional-translation feedback loop (TTFL) made up of the so-called core clock genes/proteins. The circadian system interfaces with most signaling pathways including those involved in cell proliferation and inflammation. Cryptochrome (CRY) is a core clock protein that plays an essential role in the repressive arm of the TTFL. It was recently reported that mutation of CRY in p53-null mice delayed the onset of cancer. It was therefore suggested that CRY mutation may activate p53-independent apoptosis pathways, which eliminate premalignant and malignant cells and thus delay overt tumor formation. Here we show that CRY mutation sensitizes p53 mutant and oncogenically transformed cells to tumor necrosis factor α (TNFα)-initiated apoptosis by interfacing with the NF-κB signaling pathway through the GSK3β kinase and alleviating prosurvival NF-κB signaling. These findings provide a mechanistic foundation for the delayed onset of tumorigenesis in clock-disrupted p53 mutant mice and suggest unique therapeutic strategies for treating cancers associated with p53 mutation.