bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritability estimates in behavior genetics: Wasn't that station passed long ago?
Authors: Crusio Wim E.
Published: October 2012

Charney describes several mechanisms that will bias estimates of heritability in unpredictable directions. In addition, the mechanisms described by Charney explain the puzzling fact that research in human-behavior genetics routinely reports higher heritabilities than animal studies do. However, I argue that the concept of heritability has no real place in human research anyway.
Postgenomics and genetic essentialism
Authors: Dar-Nimrod Ilan
Published: October 2012

Traditional lay perceptions of genetics are plagued with essentialist biases leading to some unfortunate consequences. Changes in the scientific understanding of heredity in general, and in genotype–phenotype relationships more specifically, provide a vital basis for shifting public understanding of genetics. Facilitating postgenomic literacy among the public has the potential to have translational implications in diminishing deleterious attitudes, beliefs, and behaviors.
Preventing a paradigm shift: A plea for the computational genome
Authors: Garzillo Carmine , Trautteur Giuseppe
Published: October 2012

Against the opinion that DNA as program is not sufficiently explanatory, we maintain that the cellular machinery is entirely computational, and we identify the crucial notion of the interpreter that expresses the gene with the minimal gene set. Epigenetics research does not so much need paradigm shifts as the unraveling of an exceedingly complex computational machine.
Non-Mendelian etiologic factors in neuropsychiatric illness: Pleiotropy, epigenetics, and convergence
Authors: Deutsch Curtis K. , McIlvane William J.
Published: October 2012

The target article by Charney on behavior genetics/genomics discusses how numerous molecular factors can inform heritability estimations and genetic association studies. These factors find application in the search for genes for behavioral phenotypes, including neuropsychiatric disorders. We elaborate upon how single causal factors can generate multiple phenotypes, and discuss how multiple causal factors may converge on common neurodevelopmental mechanisms.
Humans, fruit flies, and automatons
Authors: Charney Evan
Published: October 2012

My response is divided into four sections: (1) is devoted to a potpourri of commentaries that are essentially in agreement with the substance of my target article (with one exception); in (2) I address, in response to one of the commentaries, several issues relating to the use of candidate gene association studies in behavior genetics (in particular those proposing a specific G×E interaction); in (3) I provide a detailed response to several defenses of the twin study methodology; and in (4) I conclude with several reflections on that methodology and the conception of human nature it has fostered.
A systematic review of behavioural weight-loss interventions involving primary-care physicians in overweight and obese primary-care patients (1999–2011)
Authors: Yoong Sze Lin , Carey Mariko , Sanson-Fisher Rob , Grady Alice
Published: October 2012

Objective

The present review aimed to examine the effectiveness of behavioural weight-loss interventions involving primary-care physicians in producing weight loss in overweight and obese primary-care patients.

Design

A systematic review was conducted by searching online databases (MEDLINE, EMBASE, Cochrane, PsycINFO and SCOPUS) from January 1999 to December 2011. All abstracts were screened and coded for eligibility. The Cochrane Effective Practice and Organisation of Care Group quality criteria were used to assess the methodological adequacy of included studies. Information related to study design, population characteristics and intervention details was extracted.

Setting

Primary care.

Subjects

Overweight or obese (defined as having a BMI ≥ 25·0 kg/m2) primary-care patients.

Results

Sixteen different studies were included. Of these, six assessed primary-care physicians’ delivery of weight-loss counselling; nine assessed weight-loss counselling delivered by non-physician personnel with monitoring by primary-care physicians; and one assessed a multi-component intervention. Overall, high-intensity weight-loss counselling by primary-care physicians resulted in moderate but not clinically significant weight loss. High-intensity weight-loss counselling delivered by non-physicians, meal replacements delivered in conjunction with dietitian counselling and referral to commercial weight-loss centre programmes accompanied by regular monitoring by a primary-care physician were effective in producing clinically significant weight loss. Dietitian-delivered care appeared effective in producing weight loss regardless of level of intervention intensity.

Conclusions

Overall, there were few studies on this topic and the methodological rigour of some included studies was poor. Additional studies assessing the effectiveness and acceptability of potential interventions are needed to confirm these findings.
The impact of megasplay faulting and permeability contrasts on Nankai Trough subduction zone pore pressures
Authors: Screaton Elizabeth J. , Ge Shemin
Published: October 2012

Results of a coupled fluid flow and deformation model indicate that megasplay fault slip may impact excess pore pressures within an accretionary prism. In a simulation with homogeneous low permeability representative of clay‐rich sediment, excess pore pressures build where compression occurs in the hanging wall and directly beneath the splay fault. In another simulation with heterogeneous permeability, the impact of high permeability fault zones and turbidite horizons lessens the effect of the megasplay fault slip. Overall, excess pore pressures are lower for the heterogeneous simulation than for the simulation with uniform low permeability. Within the footwall of the megasplay fault zone, simulated pore pressures increase across a transition from more permeable uplifted turbidites to less permeable clay‐rich sediments. Strong permeability contrasts might provide an alternate explanation for a previously observed decrease in seismic velocity beneath the megasplay fault of the Nankai Trough subduction zone.
Energetic particle injection, acceleration, and loss during the geomagnetic disturbances which upset Galaxy 15
Authors: Clilverd Mark A. , Rodger Craig J. , Danskin Donald , Usanova Maria E. , Raita Tero , Ulich Thomas , Spanswick Emma L.
Published: October 2012

On 5 April 2010 a series of energetic electron injections, acceleration, and loss events appeared to induce an operational anomaly in the Galaxy 15 geosynchronous communications satellite. We describe the energetic electron precipitation conditions leading to the anomaly. A few hours prior to the anomaly electron acceleration at >0.6 MeV, and loss at >30 keV, were observed simultaneously. The acceleration took place in the region of the Galaxy 15 satellite on the nightside and the precipitation of electrons primarily on the dayside. The precipitation was confined to L‐shells outside of the plasmapause and appeared to be driven by chorus waves via a weak diffusion process. An hour prior to the anomaly, a solar wind shock event generated a few minutes of 30–150 keV electron precipitation but only on the dayside, over a largeL‐shell range (4.8 <L < 13). The timing of the precipitation burst was consistent with electromagnetic ion cyclotron (EMIC) waves seen on the dayside, but the high geomagnetic latitude of the precipitation suggests that EMIC wave growth associated with high cold density regions in the plasmasphere is unlikely to have played a role. A substorm injection event shortly after the shock appears to have ultimately triggered the upset on Galaxy 15. However, the peak >30 keV electron precipitation fluxes of 1.35 × 107 el cm−2 s−1 sr−1 were roughly the same level as other large substorm events previously analyzed, indicating either a sensitivity to the energetic electron environment prior to the event or that the satellite was in a vulnerable situation.
Low seismic velocities below mid‐ocean ridges: Attenuation versus melt retention
Authors: Goes Saskia , Armitage John , Harmon Nick , Smith Hannah , Huismans Ritske
Published: October 2012

The first comprehensive seismic experiment sampling subridge mantle revealed a pronounced low‐velocity zone between 40 and 100 km depth below the East Pacific Rise (EPR) that has been attributed to substantial retained melt fractions of 0.3–2%. Such high melt fractions are at odds with low melt productivity and high melt mobility inferred from petrology and geochemistry. Here, we evaluate whether seismic attenuation can reconcile subridge seismic structure with low melt fractions. We start from a dynamic spreading model which includes melt generation and migration and is converted into seismic structure, accounting for temperature‐, pressure‐, composition‐, phase‐, and melt‐dependent anharmonicity, and temperature‐, pressure‐, frequency‐ and hydration‐dependent anelasticity. Our models predict a double low‐velocity zone: a shallow—approximately triangular—region due to dry melting, and a low‐velocity channel between 60 and 150 km depth dominantly controlled by solid state high‐temperature seismic attenuation in a damp mantle, with only a minor contribution of (<0.1%) melt. We test how tomographic inversion influences the imaging of our modeled shear velocity features. The EPR experiment revealed a double low‐velocity zone, but most tomographic studies would only resolve the deeper velocity minimum. Experimentally constrained anelasticity formulations produce VSas low as observed and can explain lateral variations in near‐ridge asthenospheric VS with ±100 K temperature variations and/or zero to high water content. Furthermore, such QS formulations also reproduce low asthenospheric VS below older oceans and continents from basic lithospheric cooling models. Although these structures are compatible with global QS images, they are more attenuating than permitted by EPR data.
Endogenous Ovarian Hormones Affect Mitochondrial Efficiency in Cerebral Endothelium via Distinct Regulation of PGC-1 Isoforms
Authors: Kemper Martin F , Zhao Yuanzi , Duckles Sue P , Krause Diana N
Published: October 2012

Mitochondria support the energy-intensive functions of brain endothelium but also produce damaging-free radicals that lead to disease. Previously, we found that estrogen treatment protects cerebrovascular mitochondria, increasing capacity for ATP production while decreasing reactive oxygen species (ROS). To determine whether these effects occur specifically in endothelium in vivo and also explore underlying transcriptional mechanisms, we studied freshly isolated brain endothelial preparations from intact and ovariectomized female mice. This preparation reflects physiologic influences of circulating hormones, hemodynamic forces, and cell–cell interactions of the neurovascular unit. Loss of ovarian hormones affected endothelial expression of the key mitochondrial regulator family, peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), but in a unique way. Ovariectomy increased endothelial PGC-1α mRNA but decreased PGC-1β mRNA. The change in PGC-1β correlated with decreased mRNA for crucial downstream mitochondrial regulators, nuclear respiratory factor 1 and mitochondrial transcription factor A, as well as for ATP synthase and ROS protection enzymes, glutamate-cysteine ligase and manganese superoxide dismutase. Ovariectomy also decreased mitochondrial biogenesis (mitochondrial/nuclear DNA ratio). These results indicate ovarian hormones normally act through a distinctive regulatory pathway involving PGC-1β to support cerebral endothelial mitochondrial content and guide mitochondrial function to favor ATP coupling and ROS protection.
RAB-5 and RAB-10 cooperate to regulate neuropeptide release in
Caenorhabditis elegans
Authors: Sasidharan Nikhil , Sumakovic Marija , Hannemann Mandy , Hegermann Jan , Liewald Jana F. , Olendrowitz Christian , Koenig Sabine , Grant Barth D. , Rizzoli Silvio O. , Gottschalk Alexander , Eimer Stefan
Published: October 2012

Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all
Caenorhabditis elegans
Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from
C. elegans
motoneurons.
rab
-5
and
rab
-10
mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other’s GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi–endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.
Mechanism of oxygen detoxification by the surprisingly oxygen-tolerant hyperthermophilic archaeon,
Pyrococcus furiosus
Authors: Thorgersen Michael P. , Stirrett Karen , Scott Robert A. , Adams Michael W. W.
Published: October 2012

The anaerobic archaeon
Pyrococcus furiosus
grows by fermenting carbohydrates producing H
2
, CO
2
, and acetate. We show here that it is surprisingly tolerant to oxygen, growing well in the presence of 8% (vol/vol) O
2
. Although cell growth and acetate production were not significantly affected by O
2
, H
2
production was reduced by 50% (using 8% O
2
). The amount of H
2
produced decreased in a linear manner with increasing concentrations of O
2
over the range 2–12% (vol/vol), and for each mole of O
2
consumed, the amount of H
2
produced decreased by approximately 2 mol. The recycling of H
2
by the two cytoplasmic hydrogenases appeared not to play a role in O
2
resistance because a mutant strain lacking both enzymes was not more sensitive to O
2
than the parent strain. Decreased H
2
production was also not due to inactivation of the H
2
-producing, ferredoxin-dependent membrane-bound hydrogenase because its activity was unaffected by O
2
exposure. Electrons from carbohydrate oxidation must therefore be diverted to relieve O
2
stress at the level of reduced ferredoxin before H
2
production. Deletion strains lacking superoxide reductase (SOR) and putative flavodiiron protein A showed increased sensitivity to O
2
, indicating that these enzymes play primary roles in resisting O
2
. However, a mutant strain lacking the proposed electron donor to SOR, rubredoxin, was unaffected in response to O
2
. Hence, electrons from sugar oxidation normally used to produce H
2
are diverted to O
2
detoxification by SOR and putative flavodiiron protein A, but the electron flow pathway from ferredoxin does not necessarily involve rubredoxin.|
The Sedimentary Record of the Eutrophication of Lake Washington
Authors: Edmondson W. T.
Published: October 2012

Lake Washington changed in productivity, abundance of organisms, and chemical character as a result of enrichment with sewage effluent and subsequent diversion of the effluent. A record of many of the changes is left in the sediments in the form of concentrations of specific elements or compounds and recognizable remains of organisms, especially diatoms. The vertical distribution of diatoms in dried cores of sediment can be determined with considerable precision with scanning electron microscopy. Such data provide information about the character of the lake before limnological studies were made.
Intensive versus extensive management systems in commercial egg production.
Authors: Golden J. B. , Arbona D. V.
Published: October 2012

Despite the degree of environmental protection and economic feasibility offered by traditional poultry production systems, the practice of housing laying hens in cages has been widely criticized worldwide because of the public perception that caged housing systems provide poor welfare for laying hens. As a result of increasing public interest in laying hen welfare, alternative management systems such as free-range environments have been resurrected and new legislation such as the California Proposition Two is expediting a shift back towards extensive practices. The transition from intensive back to extensive practices coupled with the advent and increasing popularity of novel alternative layer housing management methods in recent years necessitates an examination of the influence of environmental stressors associated with different housing methods on layer egg production, immunological response and reproductive well-being. In this review, the evolution of intensive and extensive management practices is comparatively examined based on how these different management practices impact layer hen well-being and productivity. Different welfare assessment techniques are also examined in an effort to provide insight into the progression of research concerning layer hen welfare in different management systems.
The ethical dimensions of life and analytic work through a Levinasian lens
Authors: Brooks Robin McCoy
Published: October 2012

This paper contextualizes Jung's method of amplification within the larger history of philosophical hermeneutics and most particularly within the relational ethics of the post-modern, post-phenomenological and post-Heideggarian philosopher Emmanuel Levinas. While finding the epistemological assumptions (foundationalism) of subject formation guiding Jung's interpretative method incompatible with the extra-ontology perspective of Levinas, this paper underscores the necessity for revitalizing our theory and practice by bringing back the unthought in Jung's corpus so that the truly ethical dimensions of life and analytic work are in alignment with our present epoch. Finally, one enigmatic analytic moment demonstrates how the radical Levinasian primacy of ethical experience in subject formation can emerge in a contemporary clinical encounter. The Levinasian sensibility will be shown to open up new perspectives that contrast with the formulaic ways in which we tend to understand the effects of counter-transference, transcendence, time and ethics.
The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking
Authors: Li Shupeng , Li ZhaoXia , Pei Lin , Le Anh D. , Liu Fang
Published: October 2012

Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmful consequences, it is difficult to quit smoking because of its positive effects on mood and cognition that are strong reinforcers contributing to addiction. Furthermore, a formidable challenge for the treatment of nicotine addiction is the high vulnerability to relapse after abstinence. There is no currently available smoking cessation product able to achieve a >20% smoking cessation rate after 52 wk, and there are no medications that directly target the relapse process. We report here that the α7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein–protein interaction. Chronic nicotine exposure promotes α7nAChR–NMDAR complex formation. Interestingly, administration of an interfering peptide that disrupts the α7nAChR–NMDAR complex decreased extracellular signal-regulated kinase (ERK) activity and blocked cue-induced reinstatement of nicotine seeking in rat models of relapse, without affecting nicotine self-administration or locomotor activity. Our results may provide a novel therapeutic target for the development of medications for preventing nicotine relapse.
Grothendieck ordered Banach spaces with an interpolation property
Authors: Polyrakis Ioannis , Xanthos Foivos
Published: October 2012

In this paper we prove that if

E
E

is an ordered Banach space with the countable interpolation property,

E
E

has an order unit and

E
+

E_+

is closed and normal, then

E
E

is a Grothendieck space; i.e. any weak-star convergent sequence of

E
∗

E^*

is weakly convergent. By the countable interpolation property we mean that for any

A
,
B
⊆
E

A,B\subseteq E

countable, with

A
≤
B

A\leq B

, we have

A
≤
{
x
}
≤
B

A\leq \{x\}\leq B

for some

x
∈
E

x\in E

.
Incidence and trends of heart failure admissions after coronary artery bypass grafting surgery
Authors: Moreyra Abel E. , Deng Yingzi , Wilson Alan C. , Cosgrove Nora M. , Kostis William J. , Kostis John B. ,   for the MIDAS 18 study group
Published: October 2012

Aims

Factors related to hospitalization for heart failure (HF) following coronary artery bypass grafting (CABG) surgery were studied.

Methods and results

Patients (n = 65 377) undergoing CABG surgery in New Jersey from 1998 to 2007 were identified from the state cardiac surgery database; subsequent hospitalizations for HF were assessed using the Myocardial Infarction Data Acquisition System database. Patients were classified based on pre‐operative ejection fraction (EF). Multivariate models were used to identify factors related to HF admission and mortality. Post‐CABG HF admission rates among patients with pre‐operative EF <35% increased over the 10‐year period (P = 0.02), but no significant trend was seen among patients with EF ≥35%. Independent factors associated with post‐CABG HF admission within 2 years were: EF, age, female gender, Black race, smoking, diabetes, renal disease, hypertension, and cerebrovascular disease. Pre‐operative use of beta‐blockers increased over the years (P < 0.0001) and reduced the risk of admission for HF by 13%, with greater benefit in patients with lower EF. Mortality remained unchanged from 1998 to 2007, averaging 1.8% in‐hospital and 5.1% and 7.2% at 1‐year and 2‐year follow‐up, respectively.

Conclusions

Pre‐operative EF is a strong predictor of HF admission within 2 years after CABG surgery. The use of beta‐blockers decreased HF admission after CABG, especially in patients with EF <35%. Despite the more pronounced benefit and increasing use of beta‐blockers in patients with a low EF, HF admission rates in this group of patients are rising. This suggests that more comprehensive management of factors associated with HF is necessary.
A mouse model reveals an important role for catecholamine‐induced lipotoxicity in the pathogenesis of stress‐induced cardiomyopathy
Authors: Shao Yangzhen , Redfors Björn , Ståhlman Marcus , Täng Margareta Scharin , Miljanovic Azra , Möllmann Helge , Troidl Christian , Szardien Sebastian , Hamm Christian , Nef Holger , Borén Jan , Omerovic Elmir
Published: October 2012

Aim

Stress‐induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy, is an acute cardiac syndrome with substantial morbidity and mortality. The unique hallmark of SIC is extensive ventricular dysfunction (akinesia) involving apical segments with preserved function in basal segments. Adrenergic overstimulation plays an important role in initiating SIC, but the pathomechanisms involved are unknown. We tested the hypothesis that excessive catecholamines cause perturbation of myocardial lipid metabolism and that cardiac lipotoxicity is responsible for the pathogenesis of SIC.

Methods and results

A single dose injection of isoprenaline (ISO; 400 mg/kg) induced SIC‐like regional akinesia in mice. Oil red O staining revealed severe lipid accumulation in the heart 2 h post‐ISO. Both intramyocardial lipid accumulation and cardiac function were normalized within 1 week post‐ISO and no significant amount of fibrosis was detected. We found that gene expression of lipid importers and exporters (ApoB lipoprotein) was depressed 2 h post‐ISO. These results were confirmed by similar findings in SIC patients and in ISO/patient serum‐stressed HL‐1 cardiomyocytes. Moreover, overexpression of ApoB in the heart was found to protect against the development of ISO‐induced cardiac toxicity and cardiac dysfunction. We also found that ISO‐induced intramyocardial lipid accumulation caused electrophysiological disturbance and stunning in ISO/patient serum‐stressed HL‐1 cardiomyocytes.

Conclusions

The present study demonstrates that lipotoxicity is closely associated with catecholamine‐induced myocardial dysfunction, including neurogenic stunning, metabolic stunning, and electrophysiological stunning. Cardiac lipotoxicity may originate from direct inhibition of myocardial ApoB lipoprotein and subsequent decreased lipid export, caused by supraphysiological levels of catecholamines.
Extragalactic number counts at 100 μm, free from cosmic variance
Authors: Sibthorpe B. , Ivison R. J. , Massey R. J. , Roseboom I. G. , van der Werf P. P. , Matthews B. C. , Greaves J. S.
Published: October 2012

We use data from the Disc Emission via a Bias-free Reconnaissance in the Infrared/Submillimetre (DEBRIS) survey, taken at 100 μm with the Photoconductor Array Camera and Spectrometer instrument on board the Herschel Space Observatory, to make a cosmic variance independent measurement of the extragalactic number counts. These data consist of 323 small-area mapping observations performed uniformly across the sky, and thus represent a sparse sampling of the astronomical sky with an effective coverage of ∼2.5 deg2.

We find our cosmic variance independent analysis to be consistent with previous count measurements made using relatively small area surveys. Furthermore, we find no statistically significant cosmic variance on any scale within the errors of our data. Finally, we interpret these results to estimate the probability of galaxy source confusion in the study of debris discs.
Relating the Progeny Production Curve to the Speed of an Epidemic
Authors: Ferrandino Francis J.
Published: October 2012

The dependence of the initial infection rate, r, on the basic reproductive number, R0, and the temporal moments of the progeny production curve are examined. A solution to the linearized Kermack-McKendrick equation is presented and used to analyze a variety of theoretical models of pathogen reproduction. The solution yields a relation between r and the basic reproductive number, R0; the mean time between pathogen generations, μ; and the standard deviation about this mean, σ. A transformation using the dimensionless variables rμ and rσ is introduced, which maps the solution onto a one-dimensional curve. An approximation for the value of r in terms of R0and the first four temporal moments of the reproductive curve is derived. This allows direct comparison of epidemics resulting from theoretical models with those generated using experimentally obtained reproduction curves. For epidemics characterized by a value of rμ < 5, the value of r is well determined (<2%) by this fourth-order expansion regardless of the functional form of the reproduction curve.
Female happy wrens select songs to cooperate with their mates rather than confront intruders
Authors: Templeton Christopher N. , Ríos-Chelén Alejandro A. , Quirós-Guerrero Esmeralda , Mann Nigel I. , Slater Peter J. B.
Published: October 2012

Vocal duetting occurs in many taxa, but its function remains much-debated. Like species in which only one sex sings, duetting birds can use their song repertoires to signal aggression by singing song types that match those of territorial intruders. However, when pairs do not share specific combinations of songs (duet codes), individuals must choose to signal aggression by matching the same-sex rival, or commitment by replying appropriately to their mate. Here, we examined the song types used by female happy wrens (
Pheugopedius felix
) forced to make this decision in a playback experiment. We temporarily removed the male from the territory and then played songs from two loudspeakers to simulate an intruding female and the removed mate's response, using song types that the pair possessed but did not naturally combine into duets. Females were aggressive towards the female playback speaker, approaching it and overlapping the female playback songs, but nevertheless replied appropriately to their mate's songs instead of type matching the intruding female. This study indicates that females use song overlapping to signal aggression but use their vocal repertoires to create pair-specific duet codes with their mates, suggesting that duetting functions primarily to demonstrate pair commitment.
The modulatory effect of cell–cell contact on the tumourigenic potential of pre-malignant epithelial cells: a computational exploration
Authors: Walker D. C. , Southgate J.
Published: October 2012

Malignant development cannot be attributed alone to genetic changes in a single cell, but occurs as a result of the complex interplay between the failure of cellular regulation mechanisms and the presence of a permissive microenvironment. Although E-cadherin is classified as a ‘metastasis suppressor’ owing to its role in intercellular adhesion, the observation that it may be downregulated at a premalignant stage is indicative of additional roles in neoplastic development. We have used an agent-based computational model to explore the emergent behaviour resulting from the interaction of single and subpopulations of E-cadherin-compromised cells with unaffected normal epithelial cells within a monolayer environment. We have extended this to investigate the importance of local tissue perturbations in the form of scratch-wounding, or ablation of randomly-dispersed normal cells, on the growth of a single cell exhibiting E-cadherin loss. Our results suggest that the microenvironment with respect to localized cell density and normal/E-cadherin-compromised neighbours is crucial in determining whether an abnormal individual cell proliferates or remains dormant within the monolayer. These predictions raise important questions relating to the propensity for individual mutations to give rise to disease, and future experimental exploration of these will enhance our understanding of a complex, multifactorial pathological process.
Surface waves guided by topography in an anisotropic elastic half-space
Authors: Fu Y. B. , Rogerson G. A. , Wang W. F.
Published: October 2012

We consider the propagation of free surface waves on an elastic half-space that has a localized geometric inhomogeneity perpendicular to the direction of wave propagation (such waves are known as topography-guided surface waves). Our aim is to investigate how such a weak inhomogeneity modifies the surface-wave speed slightly. We first recover previously known results for isotropic materials and then present additional results for a generally anisotropic elastic half-space assuming only one plane of material symmetry. It is shown that a topography-guided surface wave in the present context may or may not propagate depending on a number of factors. In particular, they cannot propagate if the original two-dimensional surface wave on a flat half-space is supersonic with respect to the speed of anti-plane shear waves. For the case when a topography-guided surface wave may exist, the existence and computation of wave speed correction is reduced to the solution of a simple eigenvalue problem whose properties are previously well understood. As a by-product of our analysis, we deduce that there exists at least one topography-guided surface wave on an isotropic elastic half-space, and that it is unique when the geometric inhomogeneity has sufficiently small amplitude.
Are large perimeter- minimizing two-dimensional clusters of equal-area bubbles hexagonal or circular?
Authors: Cox S. J. , Morgan F. , Graner F.
Published: October 2012

A computer study of clusters of up to
N
=200 000 equal-area bubbles shows for the first time that partially rounding conjectured optimal hexagonal planar soap bubble clusters reduces perimeter. Different methods of creating optimal clusters are compared, and new candidate minimizers for several
N
are given.
Grey matter volume in early human visual cortex predicts proneness to the sound-induced flash illusion
Authors: de Haas Benjamin , Kanai Ryota , Jalkanen Lauri , Rees Geraint
Published: October 2012

Visual perception can be modulated by sounds. A drastic example of this is the sound-induced flash illusion: when a single flash is accompanied by two bleeps, it is sometimes perceived in an illusory fashion as two consecutive flashes. However, there are strong individual differences in proneness to this illusion. Some participants experience the illusion on almost every trial, whereas others almost never do. We investigated whether such individual differences in proneness to the sound-induced flash illusion were reflected in structural differences in brain regions whose activity is modulated by the illusion. We found that individual differences in proneness to the illusion were strongly and significantly correlated with local grey matter volume in early retinotopic visual cortex. Participants with smaller early visual cortices were more prone to the illusion. We propose that strength of auditory influences on visual perception is determined by individual differences in recurrent connections, cross-modal attention and/or optimal weighting of sensory channels.
Three novel benzothiazine-fused triazoles as potential centrally acting muscle relaxants
Authors: Ravikumar Krishnan , Sridhar Balasubramanian , Hariharakrishnan Venkatasubramanian , Singh Awadesh Narain
Published: October 2012

The structures of the novel triazolobenzothiazines 2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one (IDPH-791), C9H7N3OS, (I), a potential muscle relaxant, its benzoyl derivative, 2-(2-oxo-2-phenylethyl)-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one, C20H17N3O4S, (II), and the β-keto ester derivative, ethyl 3-oxo-2-(1-oxo-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-2-yl)-3-phenylpropanoate, C17H13N3O2S, (III), are the first examples of benzothiazine-fused triazoles in the crystallographic literature. The heterocyclic thiazine rings in all three structures adopt a distorted half-chair conformation. Compound (III) exists in thetrans-β-diketo form. Other than N—H...O hydrogen bonds in (I) forming dimers, no formal intermolecular hydrogen bonds are involved in the crystal packing of any of the three structures, which is dominated by C—H...O/N and π–π stacking interactions.
Influence of intermolecular contacts on the structure of recombinant prolidase fromThermococcus sibiricus
Authors: Trofimov A. A. , Slutskaya E. A. , Polyakov K. M. , Dorovatovskii P. V. , Gumerov V. M. , Popov V. O.
Published: October 2012

Prolidases are peptidases that are specific for dipeptides with proline as the second residue. The structure of recombinant prolidase from the hyperthermophilic archaeonThermococcus sibiricus(Tsprol) was determined at 2.6 Å resolution. The homodimer ofTsprol is characterized by a complete lack of interactions between the N- and C-terminal domains of the two subunits and hence can be considered to be the most open structure when compared with previously structurally studied prolidases. This structure exists owing to intermolecular coordination bonds between cadmium ions derived from the crystallization solution and histidine residues of a His tag and aspartate and glutamate residues, which link the dimers to each other. This linking leads to the formation of a crystal with a loose packing of protein molecules and low resistance to mechanical influence and temperature increase.
Structure of the recombinant BPTI/Kunitz-type inhibitorrShPI-1A from the marine invertebrateStichodactyla helianthus
Authors: García-Fernández Rossana , Pons Tirso , Meyer Arne , Perbandt Markus , González-González Yamile , Gil Dayrom , de los Angeles Chávez María , Betzel Christian , Redecke Lars
Published: October 2012

The BPTI/Kunitz-type inhibitor family includes several extremely potent serine protease inhibitors. To date, the inhibitory mechanisms have only been studied for mammalian inhibitors. Here, the first crystal structure of a BPTI/Kunitz-type inhibitor from a marine invertebrate (rShPI-1A) is reported to 2.5 Å resolution. Crystallization of recombinantrShPI-1A required the salt-induced dissociation of a trypsin complex that was previously formed to avoid intrinsic inhibitor aggregates in solution. TherShPI-1A structure is similar to the NMR structure of the molecule purified from the natural source, but allowed the assignment of disulfide-bridge chiralities and the detection of an internal stabilizing water network. A structural comparison with other BPTI/Kunitz-type canonical inhibitors revealed unusual φ angles at positions 17 and 30 to be a particular characteristic of the family. A significant clustering of φ and ψ angle values in the glycine-rich remote fragment near the secondary binding loop was additionally identified, but its impact on the specificity ofrShPI-1A and similar molecules requires further study.
Structure ofEscherichia coliRutC, a member of the YjgF family and putative aminoacrylate peracid reductase of therutoperon
Authors: Knapik Aleksandra Alicja , Petkowski Janusz Jurand , Otwinowski Zbyszek , Cymborowski Marcin Tadeusz , Cooper David Robert , Chruszcz Maksymilian , Krajewska Wanda Małgorzata , Minor Wladek
Published: October 2012

RutC is the third enzyme in theEscherichia coli rutpathway of uracil degradation. RutC belongs to the highly conserved YjgF family of proteins. The structure of the RutC protein was determined and refined to 1.95 Å resolution. The crystal belonged to space groupP21212 and contained six molecules in the asymmetric unit. The structure was solved by SAD phasing and was refined to anRworkof 19.3% (Rfree= 21.7%). The final model revealed that this protein has aBacilluschorismate mutase-like fold and forms a homotrimer with a hydrophobic cavity in the center of the structure and ligand-binding clefts between two subunits. A likely function for RutC is the reduction of peroxy-aminoacrylate to aminoacrylate as a part of a detoxification process.
Diagnosis of Skull Fractures According to Postmortem Interval: An Experimental Approach in a Porcine Model
Authors: Jordana Fabienne , Colat‐Parros Jacques , Bénézech Michel
Published: October 2012

Most studies on fracture morphology of fresh or dry bones, specifically skull bones, have a limited focus, and they are often based on observations rather than experimental tests. This study characterized pig cranial fractures sustained under known impact conditions. An impact machine (mobile carriage guided by columns) was used to perform a fracture on each skull. Impacts were performed at the same energy level on fresh and dry bones, with two types of impactor: a sharp striker (n = 50) and a blunt striker (n = 50). We found distinct features under different conditions, including osseous flakes on fresh bones, 90° fracture angles on dry bones, and more fractures with greater fragmentation on dry bones. These features highlighted the effects of time on perimortem fracture characteristics and the importance of bone storage conditions in the study of fracture genesis.
Hepatoprotective effect of DT56a is associated with changes in natural killer T cells and regulatory T cells
Authors: Shabat Yehudit , Lichtenstein Yoav , Zolotarov Lydya , Ben Ya'acov Ami , Ilan Yaron
Published: October 2012

Objective

To determine the metabolic and immunological effects of the oral administration of DT56a, an enzymatic isolate of soybeans.

Methods

DT56a was orally administered to mice in three animal models: leptin deficiency, high‐fat diet (HFD) supplementation and immune‐mediated hepatitis. Liver damage and immunological status were assessed.

Results

Oral administration of DT56a to leptin‐deficient (ob/ob) and HFD mice led to a significant reduction in serum triglyceride (TG) and total cholesterol (TC) levels. DT56a‐treated mice in both models exhibited a significant reduction in hepatic levels of TG and marked alleviation of glycemic control as indicated by significant decreases in fasting blood glucose levels and glucose tolerance tests. The levels of liver enzymes were reduced. These metabolic effects were associated with altered distributions of regulatory T (Tregs) and natural killer T (NKT) cells. DT56a suppressed the immune‐mediated liver damage induced by concanavalin A indicated by decreased liver enzymes and serum interferon‐γ levels and by improved histology and decreased hepatic apoptosis. Oral administration of DT56a also alleviated immune‐mediated hepatitis and affected Tregs and NKT cells.

Conclusions

Oral administration of DT56a promotes a hepatoprotective effect associated with an alteration in the distribution of Tregs and NKT cells.
DNA barcoding in a biodiversity hot spot: potential value for the identification of Malagasy Euphorbia L. listed in CITES Appendices I and II
Authors: Aubriot Xavier , Lowry Porter P. , Cruaud Corinne , Couloux Arnaud , Haevermans Thomas
Published: October 2012

The island of Madagascar is a key hot spot for the genus Euphorbia, with at least 170 native species, almost all endemic. Threatened by habitat loss and illegal collection of wild plants, nearly all Malagasy Euphorbia are listed in CITES Appendices I and II. The absence of a reliable taxonomic revision makes it particularly difficult to identify these plants, even when fertile, and thereby compromises the application of CITES regulations. DNA barcoding, which can facilitate species‐level identification irrespective of developmental stage and the presence of flowers or fruits, may be a promising tool for monitoring and controlling trade involving threatened species. In this study, we test the potential value of barcoding on 41 Euphorbia species representative of the genus in Madagascar, using the two widely adopted core barcode markers (matK and rbcL), along with two additional DNA regions, nuclear internal transcribed spacer (ITS) and the chloroplastic intergenic spacer psbA‐trnH. For each marker and for selected marker combinations, inter‐ and intraspecific distance estimates and species discrimination rates are calculated. Results using just the ‘official’ barcoding markers yield overlapping inter‐ and intraspecific ranges and species discrimination rates below 60%. When ITS is used, whether alone or in combination with the core markers, species discrimination increases to nearly 100%, whereas the addition of psbA‐trnH produces less satisfactory results. This study, the first ever to test barcoding on the large, commercially important genus Euphorbia shows that this method could be developed into a powerful identification tool and thereby contribute to more effective application of CITES regulations.
Quantitative vs qualitative vegetation sampling methods: a lesson from a grazing experiment in a Mediterranean grassland
Authors: Golodets Carly , Kigel Jaime , Sapir Yuval , Sternberg Marcelo
Published: October 2012

Question

How well does a time‐saving, qualitative sampling method compare with an intensive, quantitative sampling method in identifying the effects of reduction and cessation of cattle grazing on compositional change in a Mediterranean grassland?

Location

Upper Galilee, northern Israel.

Methods

Experimental treatments involved two levels of grazing intensity and protection from grazing for different time periods. Sampling methods included a quantitative method, involving harvesting of vegetative biomass from small (25 × 25 cm) quadrats within 10 × 10 m exclosures, and a qualitative method, involving recording presence only of plant species within the same exclosures.

Results

Both sampling methods revealed differences between protected vegetation and grazed vegetation; however they were not comparable in the way they described differences in species composition between grazed and ungrazed vegetation, and neither method could discriminate between the two levels of grazing intensity. The discrepancy between the two methods in the number and identity of species recorded ranged from 37% to 51% per plot for species recorded by both methods.

Conclusions

Qualitative sampling highlighted species that are indicative of protection from grazing; however it did not satisfactorily describe alteration in community composition, since the studied grassland is characterized by changing dominance of common species among treatments, instead of major species turnover. Suitable methods of data collection and monitoring will depend primarily on manpower and the specific characteristics of the studied community.
Abnormal serum free light chain ratio predicts poor overall survival in mantle cell lymphoma
Authors: Furtado Michelle , Shah Nimish , Levoguer Alison , Harding Stephen , Rule Simon
Published: October 2012

Serum free light Chain (sFLC) ratios have been correlated with survival outcomes in Hodgkin and non‐Hodgkin lymphoma subtypes. This study was undertaken to investigate the prognostic impact of abnormal sFLC ratios in mantle cell lymphoma (MCL). two patient cohorts were analysed for sFLC parameters: a preliminary retrospective cohort and a uniformly treated cohort of 20 relapsed/refractory MCL patients, enrolled in a phase II clinical trial of single agent lenalidomide treatment. 52% of patients had an abnormality of one or more sFLC parameter (71% of the first cohort and 40% of the second cohort). In cohort two, a high baseline SFLC ratio correlated with poorer overall survival (OS) compared to a low/normal ratio (median OS: 1·4 months vs. 19 months respectively; P = 0·001). For patients presenting with an elevated sFLC ratio at trial entry a rise of >35% in the sFLC ratio correlated with disease progression and a sFLC ratio of >2× normal at trial entry correlated with aggressive disease. These data are the first to show a clear clinical correlation between sFLC ratios and survival outcomes in a uniformly treated cohort of MCL patients. We suggest that these markers may be useful in managing patients with MCL in the future.
How we decide when a neonate needs a transfusion
Authors: Venkatesh Vidheya , Khan Rizwan , Curley Anna , New Helen , Stanworth Simon
Published: October 2012

The decision to transfuse a neonate can be approached by addressing a series of questions that cover the cause of anaemia, alternatives to transfusion, the need for transfusion and the risks. Recent clinical trials of red cell transfusions have started to inform evidence‐based transfusion practice, but have raised uncertainties about neurological outcomes when policies advocating use of fewer red cell transfusions at lower haemoglobin concentration (Hb) thresholds were tested. Red cell transfusions should be considered when the Hb <120 g/l for premature neonates requiring mechanical ventilation support, with lower thresholds applying for oxygen‐dependent neonates not requiring ventilation or for late anaemia (Hb <70–100 g/l, depending on gestational and post‐natal age). There is no recent high quality evidence to inform thresholds for prophylactic platelet transfusions in stable non‐bleeding premature neonates with platelet count levels of 50 × 109/l, although common practice has become more restrictive, using lower safe thresholds for platelet transfusion between 20 and 30 × 109/l. A more appropriate transfusion strategy for fresh frozen plasma (FFP) in neonates is one that emphasizes the therapeutic use of FFP in the face of bleeding, rather than prophylactic use in stable non‐bleeding neonates who often have mild to moderate apparent abnormalities of standard coagulation tests, after allowing for appropriate reference ranges.