bluuebunny/crossref_metadata_2025 huggingface dataset:
Origins of narcissism in children
Authors: Brummelman Eddie , Thomaes Sander , Nelemans Stefanie A. , Orobio de Castro Bram , Overbeek Geertjan , Bushman Brad J.
Published: March 2015

Significance

Narcissistic individuals feel superior to others, fantasize about personal successes, and believe they deserve special treatment. When they feel humiliated, they often lash out aggressively or even violently. Unfortunately, little is known about the origins of narcissism. Such knowledge is important for designing interventions to curtail narcissistic development. We demonstrate that narcissism in children is cultivated by parental overvaluation: parents believing their child to be more special and more entitled than others. In contrast, high self-esteem in children is cultivated by parental warmth: parents expressing affection and appreciation toward their child. These findings show that narcissism is partly rooted in early socialization experiences, and suggest that parent-training interventions can help curtail narcissistic development and reduce its costs for society.
Equality bias impairs collective decision-making across cultures
Authors: Mahmoodi Ali , Bang Dan , Olsen Karsten , Zhao Yuanyuan Aimee , Shi Zhenhao , Broberg Kristina , Safavi Shervin , Han Shihui , Nili Ahmadabadi Majid , Frith Chris D. , Roepstorff Andreas , Rees Geraint , Bahrami Bahador
Published: March 2015

Significance

When making decisions together, we tend to give everyone an equal chance to voice their opinion. To make the best decisions, however, each opinion must be scaled according to its reliability. Using behavioral experiments and computational modelling, we tested (in Denmark, Iran, and China) the extent to which people follow this latter, normative strategy. We found that people show a strong equality bias: they weight each other’s opinion equally regardless of differences in their reliability, even when this strategy was at odds with explicit feedback or monetary incentives.
Allelic polymorphism of
GIGANTEA
is responsible for naturally occurring variation in circadian period in
Brassica rapa
Authors: Xie Qiguang , Lou Ping , Hermand Victor , Aman Rashid , Park Hee Jin , Yun Dae-Jin , Kim Woe Yeon , Salmela Matti Juhani , Ewers Brent E. , Weinig Cynthia , Khan Sarah L. , Schaible D. Loring P. , McClung C. Robertson
Published: March 2015

Significance

The plant circadian clock affects many aspects of growth and development and influences both fitness in natural settings and performance in cultivated conditions. We show that
GIGANTEA
(
GI
) underlies a major quantitative trait locus for circadian period in
Brassica rapa
by fine-mapping, analysis of heterogeneous inbred lines, and transgenic rescue of an
Arabidopsis gi-201
loss-of-function mutant. Analysis of chimeric and mutated
B. rapa GI
alleles identified the causal nucleotide polymorphism responsible for the allelic variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Allelic variation of
GI
and of clock genes in general offers targets for marker-assisted (molecular) breeding for enhanced stress tolerance and potentially for improved crop yield.
Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish
Authors: Ma Yunyong , Juntti Scott A. , Hu Caroline K. , Huguenard John R. , Fernald Russell D.
Published: March 2015

Significance

The hypothalamus controls reproductive development and function via a small peptide, gonadotropin releasing hormone (GnRH1), delivered to the pituitary. To be effective, GnRH1 must be released in a pulsatile manner, but it is not known how this is achieved. We recorded from pairs of genetically labeled GnRH1 neurons in the brains of reproductively active fish and show that these cells are strongly and uniformly interconnected by electrical synapses that can be reversibly blocked. These electrical synapses likely contribute to the pulsatile firing of GnRH1 neurons, producing the coordinated output needed for reproduction, the most important act of any organism.
Environmental stress induces trinucleotide repeat mutagenesis in human cells
Authors: Chatterjee Nimrat , Lin Yunfu , Santillan Beatriz A. , Yotnda Patricia , Wilson John H.
Published: March 2015

Significance

Environmental stress induces complex cellular responses that improve the odds of survival. One effect of the cellular stress response is to relax the fidelity of DNA repair, with the counterintuitive strategy of increasing mutagenesis to improve fitness. Because microsatellite repeats, which are intrinsically highly mutable, serve as tuning knobs for evolutionary change, we asked whether environmental stress increased their mutagenesis. We found that cold, heat, hypoxic, and oxidative stresses induce trinucleotide repeat (TNR) mutagenesis, in a way that depends on stress response factors and apparently involves DNA rereplication. Because TNRs are overrepresented in gene-regulatory proteins, stress-induced TNR mutagenesis may provide a path for the environment to subtly alter gene regulatory networks—with attendant changes in cell behavior—during development, disease, and evolution.
Latent structure in random sequences drives neural learning toward a rational bias
Authors: Sun Yanlong , O’Reilly Randall C. , Bhattacharyya Rajan , Smith Jack W. , Liu Xun , Wang Hongbin
Published: March 2015

Significance

The human mind has a unique capacity to find order in chaos. The way the neocortex integrates information over time enables the mind to capture rich statistical structures embedded in random sequences. We show that a biologically motivated neural network model reacts to not only how often a pattern occurs (mean time) but also when a pattern is first encountered (waiting time). This behavior naturally produces the alternation bias in the gambler’s fallacy and provides a neural grounding for the Bayesian models of human behavior in randomness judgments. Our findings support a rational account for human probabilistic reasoning and a unifying perspective that connects the implicit learning without instruction with the generalization under structured and expressive rules.
ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading–induced autophagy
Authors: Wang Shuhui , Robinet Peggy , Smith Jonathan D. , Gulshan Kailash
Published: March 2015

Significance

Accumulation of toxic lipids in macrophages or human plaques leads to endoplasmic reticulum (ER) stress and induction of autophagy. However, the mechanism by which ER stress and autophagy help in fine tuning cellular lipid homeostasis to counter free-cholesterol toxicity is not clear. Our studies demonstrate that cholesterol induces the translocation of ORMDL orosomucoid-like proteins out of the ER and targets them to autophagosomes, thereby relieving their negative regulation on cellular de novo sphingolipid synthesis. In addition, ORMDL3 has been recently implicated in childhood asthma and in eosinophil trafficking and activation. Thus, our finding of increased turnover of ORMDL proteins by free cholesterol is relevant not only in context to atherosclerotic disease progression but may also shed new insights on lipid homeostasis in other human diseases.
Visual Turing test for computer vision systems
Authors: Geman Donald , Geman Stuart , Hallonquist Neil , Younes Laurent
Published: March 2015

Significance

In computer vision, as in other fields of artificial intelligence, the methods of evaluation largely define the scientific effort. Most current evaluations measure detection accuracy, emphasizing the classification of regions according to objects from a predefined library. But detection is not the same as understanding. We present here a different evaluation system, in which a query engine prepares a written test (“visual Turing test”) that uses binary questions to probe a system’s ability to identify attributes and relationships in addition to recognizing objects.
Environments and trypanosomiasis risks for early herders in the later Holocene of the Lake Victoria basin, Kenya
Authors: Chritz Kendra L. , Marshall Fiona B. , Zagal M. Esperanza , Kirera Francis , Cerling Thure E.
Published: March 2015

Significance

Herding was the earliest form of African food production and transformed local populations of people and animals. Herders migrated from eastern to southern Africa around 2,000 years ago, but only in small numbers. Zoonotic disease vectors, specifically the tsetse fly, which carries sleeping sickness, are thought to have impeded these movements. Archaeologists have argued that the presence of tsetse flies around Lake Victoria, Kenya, created a barrier that prevented migration and forced subsistence diversification. This study, using stable isotope analysis of animal teeth, reveals the existence of ancient grassy environments east of Lake Victoria, rather than tsetse-rich bushy environments. This overturns previous assumptions about environmental constraints on livestock management in a key area for southward movement of early herders.
Propensity of undulatory swimmers, such as worms, to go against the flow
Authors: Yuan Jinzhou , Raizen David M. , Bau Haim H.
Published: March 2015

Significance

Undulating swimmers, such as worms, are ubiquitous and play important roles in the ecosystem; agriculture; human, animal, and plant health; and medical research. The ability of undulatory swimmers to align against the flow (rheotax) is important in the animals’ life cycles, enabling them to navigate their environment and to maintain their positions in the presence of adverse flows such as in the hosts’ guts and blood vessels. We elucidate, for the first time to our knowledge, the mechanism responsible for rheotaxis in low-Reynolds-number, undulatory swimmers. This knowledge will provide a better understanding of the animals’ life cycles, will enable the development of strategies to disturb their life cycles, and will improve the design of microfluidic devices for biological research.
Synchronous down-modulation of miR-17 family members is an early causative event in the retinal angiogenic switch
Authors: Nunes Diana N. , Dias-Neto Emmanuel , Cardó-Vila Marina , Edwards Julianna K. , Dobroff Andrey S. , Giordano Ricardo J. , Mandelin Jami , Brentani Helena P. , Hasselgren Catrin , Yao Virginia J. , Marchiò Serena , Pereira Carlos A. B. , Passetti Fabio , Calin George A. , Sidman Richard L. , Arap Wadih , Pasqualini Renata
Published: March 2015

Significance

Retinal angiogenesis is a finely tuned biological phenomenon and a major cause of blindness. We studied the regulation of this phenomenon and identified cross-talk involving microRNAs (miRs) that share the same seed sequence, transcription factors, and angiogenesis effectors. In a mouse model of retinopathy of prematurity, we show the down-regulation of all miR-17 family members as an early event in the angiogenic switch, which resulted in increased levels of hypoxia-inducible factor-1α and Vegfa in vitro. Notably, this coordinated regulation did not require the marked quantitative alterations of an individual miR but instead, relied on synchronous changes in members that share the same seed sequence. These results identify potential therapeutic targets in eye diseases with abnormal retinal angiogenesis.
Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors
Authors: Bye Chris R. , Jönsson Marie E. , Björklund Anders , Parish Clare L. , Thompson Lachlan H.
Published: March 2015

Significance

An important challenge for improving cell-based approaches for Parkinson’s disease is the development of techniques that facilitate greater standardization of the donor material. This report describes the enrichment of transplantable progenitors for dopamine neurons from the ventral mesencephalon based on targeting of transmembrane proteins. It is an important step toward the development of clinically relevant techniques that allow for greater standardization of cell preparations used in transplantation and potentially, more predictable clinical outcomes. The findings are highly relevant for current efforts to develop stem cell-based therapies for Parkinson’s disease, where current techniques yield mixed cell populations that may contain unwanted cell types and thus, would benefit from a cell selection step prior to grafting.
Orbital forcing of climate 1.4 billion years ago
Authors: Zhang Shuichang , Wang Xiaomei , Hammarlund Emma U. , Wang Huajian , Costa M. Mafalda , Bjerrum Christian J. , Connelly James N. , Zhang Baomin , Bian Lizeng , Canfield Donald E.
Published: March 2015

Significance

There is a wealth of evidence pointing to dramatic short-term climate change on Earth over the last few million years. Much of this climate change is driven by variations of Earth’s orbit around the Sun with characteristic frequencies known as Milankovitch cycles. Robust evidence for orbitally driven climate change, however, becomes rare as one descends deep into Earth time. We studied an exceptional record of climate change as recorded in 1.4-billion-year-old marine sediments from North China. This record documents regular changes in subtropical/tropical Hadley Cell dynamics. These changes in dynamics controlled wind strength, rainfall, and ocean circulation, translated into cyclic variations in sediment geochemistry, much like the orbital control on climate today and in the recent past.
Dysfunctional conformational dynamics of protein kinase A induced by a lethal mutant of phospholamban hinder phosphorylation
Authors: Kim Jonggul , Masterson Larry R. , Cembran Alessandro , Verardi Raffaello , Shi Lei , Gao Jiali , Taylor Susan S. , Veglia Gianluigi
Published: March 2015

Significance

In the heart, phospholamban regulates Ca
2+
-ATPase function, controlling cardiac output. A single deletion (R14del) in the phospholamban recognition sequence kinase A is linked to the progression of familial dilated cardiomyopathy, a leading cause of death worldwide. Here, we provide the molecular mechanism for the sluggish phosphorylation of R14del by protein kinase A. We found that the R14 deletion affects the organization of the active site, which remains partially open and quite dynamic, preventing the formation of catalytically committed complex. We conclude that well-tuned structural and dynamic interplay between kinase and substrate is crucial for efficient phosphorylation. These results provide new structural basis to understand for the reduced phosphorylation levels of the R14del phospholamban and impaired Ca
2+
transport in heart muscle.
Arabidopsis
DET1 degrades HFR1 but stabilizes PIF1 to precisely regulate seed germination
Authors: Shi Hui , Wang Xin , Mo Xiaorong , Tang Chao , Zhong Shangwei , Deng Xing Wang
Published: March 2015

Significance

How organisms respond to environment changes is a fundamental and intriguing question in biology. Light is the energy resource and a crucial environmental cue for plant major developmental switches, such as seed germination. Studying the underlying mechanism is important for us to understand the basic principles of plant development and improve crop productions. Here we identify DET1 as a novel central repressor of seed germination. We further reveal that seeds use a multilevel regulatory circuit of triple feed-forward loops to sensitively and precisely mediate light-regulated germination. This study provides a comprehensive framework of how light regulates seed germination.
Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin: Epitope-specific neutralizing antibodies correlate with protection
Authors: Roy Chad J. , Brey Robert N. , Mantis Nicholas J. , Mapes Kelly , Pop Iliodora V. , Pop Laurentiu M. , Ruback Stephen , Killeen Stephanie Z. , Doyle-Meyers Lara , Vinet-Oliphant Heather S. , Didier Peter J. , Vitetta Ellen S.
Published: March 2015

Significance

Ricin toxin (RT) is a CDC-designated select agent that can be dispersed as an aerosol. In mammals, aerosolized RT causes rapid and irreversible necrosis of the lung epithelium, multifocal hemorrhagic edema, and death within 24–36 h. A safe and effective recombinant subunit vaccine (RiVax) has been developed and formulated as a thermostable, lyophilized, adjuvant-containing “powder.” This formulation of RiVax elicited neutralizing antibodies against RT, which protected macaques from the lethality of aerosolized RT. The epitope-specific antibody responses in macaques revealed a distinctive profile that was also observed in vaccinated humans. This profile might represent a signature of protection in both species.
Microbial community transcriptional networks are conserved in three domains at ocean basin scales
Authors: Aylward Frank O. , Eppley John M. , Smith Jason M. , Chavez Francisco P. , Scholin Christopher A. , DeLong Edward F.
Published: March 2015

Significance

Microbes drive biogeochemical cycles across the globe, collectively playing a central role in shaping the biosphere. Despite their immense importance, the in situ activities of communities of microbes, in particular uncultivated lineages of “microbial dark matter,” remain poorly elucidated. In this study, we report that common temporal and ecological dynamics underpin disparate marine microbial communities, providing the first evidence that trans-Pacific diurnal transcriptional patterns in these communities may regulate ecological and biogeochemical processes across the ocean. In total, our findings indicate a remarkable regularity in the timing of community-wide activity in the ocean, and suggest that global patterns of a variety of biogeochemical transformations may be temporally predictable and governed by structured ecological determinants.
Thermal stability of cytochrome c′ from mesophilic Shewanella amazonensis
Authors: Kato Yuki , Fujii Sotaro , Kuribayashi Taka-aki , Masanari Misa , Sambongi Yoshihiro
Published: March 2015

Cytochrome c′ (SACP) from mesophilic Shewanella amazonensis, growing optimally at 37 °C, was thermally more stable than cytochrome c′ (AVCP) from mesophilic Allochromatium vinosum, growing optimally at 25 °C. In contrast, SACP was less stable than cytochrome c′ (PHCP) from thermophilic Hydrogenophilus thermoluteolus, growing optimally at 52 °C. Although only 28% of the SACP amino acid sequence was identical to those of AVCP and PHCP, the latter two being 55% identical, the overall main chain structures of the three cytochromes c′ were similar, and SACP exhibited thermal stability intermediate between those of AVCP and PHCP. For these three proteins, the higher the stability is, the lesser the number of Gly residues in the putative α-helical regions is. Cytochromes c′ including the present three are suitable for examining the protein stabilization mechanisms, because they are structurally similar and available from environments with a wide range of temperatures.
Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos
Authors: Tavernier Nicolas , Noatynska Anna , Panbianco Costanza , Martino Lisa , Van Hove Lucie , Schwager Françoise , Léger Thibaut , Gotta Monica , Pintard Lionel
Published: March 2015

The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho–SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing.
GGCX and VKORC1 inhibit osteocalcin endocrine functions
Authors: Ferron Mathieu , Lacombe Julie , Germain Amélie , Oury Franck , Karsenty Gérard
Published: March 2015

Osteocalcin (OCN) is an osteoblast-derived hormone favoring glucose homeostasis, energy expenditure, male fertility, brain development, and cognition. Before being secreted by osteoblasts in the bone extracellular matrix, OCN is γ-carboxylated by the γ-carboxylase (GGCX) on three glutamic acid residues, a cellular process requiring reduction of vitamin K (VK) by a second enzyme, a reductase called VKORC1. Although circumstantial evidence suggests that γ-carboxylation may inhibit OCN endocrine functions, genetic evidence that it is the case is still lacking. Here we show using cell-specific gene inactivation models that γ-carboxylation of OCN by GGCX inhibits its endocrine function. We further show that VKORC1 is required for OCN γ-carboxylation in osteoblasts, whereas its paralogue, VKORC1L1, is dispensable for this function and cannot compensate for the absence of VKORC1 in osteoblasts. This study genetically and biochemically delineates the functions of the enzymes required for OCN modification and demonstrates that it is the uncarboxylated form of OCN that acts as a hormone.
LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation
Authors: Sohet Fabien , Lin Christina , Munji Roeben N. , Lee Seo Yeon , Ruderisch Nadine , Soung Allison , Arnold Thomas D. , Derugin Nikita , Vexler Zinaida S. , Yen Frances T. , Daneman Richard
Published: March 2015

The blood–brain barrier (BBB) is a term used to describe the unique properties of central nervous system (CNS) blood vessels. One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs). Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues. We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis. We further demonstrate that the BBB does not seal during embryogenesis in Lsr knockout mice with a leakage to small molecules. Finally, in mouse models in which BBB was disrupted, including an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and a middle cerebral artery occlusion (MCAO) model of stroke, LSR was down-regulated, linking loss of LSR and pathological BBB leakage.
The time lag between a carbon dioxide emission and maximum warming increases with the size of the emission
Authors: Zickfeld Kirsten , Herrington Tyler
Published: March 2015

In a recent letter, Ricke and Caldeira (2014 Environ. Res. Lett.

9 124002) estimated that the timing between an emission and the maximum temperature response is a decade on average. In their analysis, they took into account uncertainties about the carbon cycle, the rate of ocean heat uptake and the climate sensitivity but did not consider one important uncertainty: the size of the emission. Using simulations with an Earth System Model we show that the time lag between a carbon dioxide (CO2) emission pulse and the maximum warming increases for larger pulses. Our results suggest that as CO2 accumulates in the atmosphere, the full warming effect of an emission may not be felt for several decades, if not centuries. Most of the warming, however, will emerge relatively quickly, implying that CO2 emission cuts will not only benefit subsequent generations but also the generation implementing those cuts.
Prevalence and risk factors for carriage of antimicrobial-resistant Escherichia coli on household and small-scale chicken farms in the Mekong Delta of Vietnam
Authors: Nguyen Vinh Trung , Carrique-Mas Juan J. , Ngo Thi Hoa , Ho Huynh Mai , Ha Thanh Tuyen , Campbell James I. , Nguyen Thi Nhung , Hoang Ngoc Nhung , Pham Van Minh , Wagenaar Jaap A. , Hardon Anita , Thai Quoc Hieu , Schultsz Constance
Published: March 2015

Objectives

To describe the prevalence of antimicrobial resistance among commensal Escherichia coli isolates on household and small-scale chicken farms, common in southern Vietnam, and to investigate the association of antimicrobial resistance with farming practices and antimicrobial usage.

Methods

We collected data on farming and antimicrobial usage from 208 chicken farms. E. coli was isolated from boot swab samples using MacConkey agar (MA) and MA with ceftazidime, nalidixic acid or gentamicin. Isolates were tested for their susceptibility to 11 antimicrobials and for ESBL production. Risk factor analyses were carried out, using logistic regression, at both the bacterial population and farm levels.

Results

E. coli resistant to gentamicin, ciprofloxacin and third-generation cephalosporins was detected on 201 (96.6%), 191 (91.8%) and 77 (37.0%) of the farms, respectively. Of the 895 E. coli isolates, resistance to gentamicin, ciprofloxacin and third-generation cephalosporins was detected in 178 (19.9%), 291 (32.5%) and 29 (3.2%) of the isolates, respectively. Ciprofloxacin resistance was significantly associated with quinolone usage (OR = 2.26) and tetracycline usage (OR = 1.70). ESBL-producing E. coli were associated with farms containing fish ponds (OR = 4.82).

Conclusions

Household and small farms showed frequent antimicrobial usage associated with a high prevalence of resistance to the most commonly used antimicrobials. Given the weak biocontainment, the high prevalence of resistant E. coli could represent a risk to the environment and to humans.
Bactericidal mode of action of bedaquiline
Authors: Hards Kiel , Robson Jennifer R. , Berney Michael , Shaw Lisa , Bald Dirk , Koul Anil , Andries Koen , Cook Gregory M.
Published: March 2015

Objectives

It is not fully understood why inhibiting ATP synthesis in Mycobacterium species leads to death in non-replicating cells. We investigated the bactericidal mode of action of the anti-tubercular F1Fo-ATP synthase inhibitor bedaquiline (Sirturo™) in order to further understand the lethality of ATP synthase inhibition.

Methods

Mycobacterium smegmatis strains were used for all the experiments. Growth and survival during a bedaquiline challenge were performed in multiple media types. A time-course microarray was performed during initial bedaquiline challenge in minimal medium. Oxygen consumption and proton-motive force measurements were performed on whole cells and inverted membrane vesicles, respectively.

Results

A killing of 3 log10 cfu/mL was achieved 4-fold more quickly in minimal medium (a glycerol carbon source) versus rich medium (LB with Tween 80) during bedaquiline challenge. Assessing the accelerated killing condition, we identified a transcriptional remodelling of metabolism that was consistent with respiratory dysfunction but inconsistent with ATP depletion. In glycerol-energized cell suspensions, bedaquiline caused an immediate 2.3-fold increase in oxygen consumption. Bedaquiline collapsed the transmembrane pH gradient, but not the membrane potential, in a dose-dependent manner. Both these effects were dependent on binding to the F1Fo-ATP synthase.

Conclusions

Challenge with bedaquiline results in an electroneutral uncoupling of respiration-driven ATP synthesis. This may be a determinant of the bactericidal effects of bedaquiline, while ATP depletion may be a determinant of its delayed onset of killing. We propose that bedaquiline binds to and perturbs the a-c subunit interface of the Fo, leading to futile proton cycling, which is known to be lethal to mycobacteria.
Impact of the meaningful use incentive program on electronic health record adoption by US children's hospitals
Authors: Nakamura Mari M. , Harper Marvin B. , Castro Allan V. , Yu Feliciano B. , Jha Ashish K.
Published: March 2015

Objective We determined adoption rates of pediatric-oriented electronic health record (EHR) features by US children's hospitals and assessed perceptions regarding the suitability of commercial EHRs for pediatric care and the influence of the meaningful use incentive program on implementation of pediatric-oriented features.

Materials and Methods We surveyed members of the Children's Hospital Association. We measured adoption of 19 pediatric-oriented features and asked whether commercial EHRs include key pediatric-focused capabilities. We inquired about the meaningful use program's relevance to pediatrics and its influence on EHR implementation priorities.

Results Of 164 general acute care children's hospitals, 100 (61%) responded to the survey. Rates of comprehensive (across all pediatric units) adoption ranged from 37% (age-, gender-, and weight-adjusted blood pressure percentiles and immunization contraindication warnings) to 87% (age in appropriate units). Implementation rates for several features varied significantly by children's hospital type. Nearly 60% of hospitals reported having EHRs that do not contain all features essential for high-quality care. A majority of hospitals indicated that the meaningful use program has had no effect on their adoption of pediatric features, while 26% said they have delayed or forgone incorporation of such features because of the program.

Conclusions Children's hospitals are implementing pediatric-focused features, but a sizable proportion still finds their systems suboptimal for pediatric care. The meaningful use incentive program is failing to promote and in some cases delaying uptake of pediatric-oriented features.
The subsurface of Pluto from submillimetre observations
Authors: Greaves J. S. , Whitelaw A. C. M. , Bendo G. J.
Published: March 2015

Surface areas on Pluto change in brightness and colour, at optical to infrared wavelengths, over time-scales as short as years. The subsurface contains a reservoir of frozen volatiles, but little is known about it because Pluto is out of reach for cm-radar. Here we present a 0.85 mm wavelength light curve of the Pluto system, from archival data taken in 1997 August with the SCUBA (Submillimetre Common-User Bolometer Array) camera on the James Clerk Maxwell Telescope (JCMT). This wavelength probes for the first time to just below the skin depth of thermal changes over Pluto's day. The light curve differs significantly from counterparts in the mid- to far-infrared, in a longitude range that is optically dark on Pluto's surface. An estimate from Herschel of the 0.5 mm flux in 2012 is comparable to the mean 0.45 mm flux from SCUBA in 1997, suggesting that layers centimetres below the surface have not undergone any gross temperature change. The longitudes that are relatively submillimetre-faint could have a different emissivity, perhaps with a subsurface layer richer in nitrogen or methane ices than at the surface. The Radio Science Experiment (REX) instrument on New Horizons may be able to constrain physical properties deeper down, as it looks back on Pluto's nightside after the 2015 July flyby.
Refined critical balance in strong Alfvénic turbulence
Authors: Mallet A. , Schekochihin A. A. , Chandran B. D. G.
Published: March 2015

We present numerical evidence that in strong Alfvénic turbulence, the critical balance principle – equality of the non-linear decorrelation and linear propagation times – is scale invariant, in the sense that the probability distribution of the ratio of these times is independent of scale. This result only holds if the local alignment of the Elsasser fields is taken into account in calculating the non-linear time. At any given scale, the degree of alignment is found to increase with fluctuation amplitude, supporting the idea that the cause of alignment is mutual dynamical shearing of Elsasser fields. The scale-invariance of critical balance (while all other quantities of interest are strongly intermittent, i.e. have scale-dependent distributions) suggests that it is the most robust of the scaling principles used to describe Alfvénic turbulence. The quality afforded by situ fluctuation measurements in the solar wind allows for direct verification of this fundamental principle.
The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer
Authors: Kozak Margaret M. , von Eyben Rie , Pai Jonathan S. , Anderson Eric M. , Welton Mark L. , Shelton Andrew A. , Kin Cindy , Koong Albert C. , Chang Daniel T.
Published: March 2015

Objectives:

The prognostic value of several hematologic parameters, including platelet, lymphocyte, and neutrophil counts, has been studied in a variety of solid tumors. In this study, we examined the significance of inflammatory markers and their prognostic implications in patients with colorectal cancer (CRC).

Materials and Methods:

Patients with stage I-III CRC who underwent surgical resection at the Stanford Cancer Institute between 2005 and 2009 were included. Patients were excluded if they did not have preoperative complete blood counts performed within 1 month of surgical resection, underwent preoperative chemotherapy or radiation, had metastatic disease at diagnosis, or had another previous malignancy. We included 129 eligible patients with available preoperative complete blood counts in the final analysis.

Results:

A preoperative neutrophil-to-lymphocyte ratio of>3.3 was significantly associated with worse disease-free (DFS) and overall survival (OS) (P=0.009, 0.003), as was a preoperative lymphocyte-to-monocyte ratio of ≤2.6 (P=0.01, 0.002). Preoperative lymphopenia (P=0.002) was associated with worse OS but not DFS (P=0.09). In addition, preoperative thrombocytosis was associated with worse DFS (P=0.006) and OS (P=0.010). Preoperative leukocytosis was associated with worse OS (P=0.048) but not DFS (P=0.49). Preoperative hemoglobin was neither associated with OS (P=0.24) or DFS (P=0.15).

Conclusions:

Pretreatment lymphopenia, thrombocytosis, a decreased lymphocyte-to-monocyte ratio, and an elevated neutrophil-to-lymphocyte ratio independently predict for worse OS in patients with CRC.
Complexity of dendritic SER increases at enlarging synapses during LTP
Authors: Chirillo Michael A. , Bourne Jennifer N. , Lindsey Laurence F. , Harris Kristen M.
Published: March 2015

Smooth endoplasmic reticulum (SER) forms a membranous network that extends throughout neurons. SER regulates intracellular calcium and the posttranslational modification and trafficking of membrane and proteins. As the structure of dendritic SER shifts from a tubular to a more complex, branched form, the movement of membrane cargo slows and delivery to nearby spines increases. Here we discovered changes in the structural complexity of SER that have important functional implications during long-term potentiation (LTP) in adult rat hippocampus. By 2 hours after the induction of LTP with theta-burst stimulation, synapse enlargement was greatest on spines that contained SER. More spines had an elaborate spine apparatus than a simple tubule of SER. The SER in dendritic shafts became more complex beneath spines with both polyribosomes and SER, and less complex along aspiny dendritic regions. The findings suggest that local changes in dendritic SER support enhanced growth of specific synapses during LTP.
Tissue dynamics of the forebrain neural plate
Authors: Young Stephen , Jennings Joel N. , Blanchard Guy B. , Kabla Alexandre J. , Adams Richard J.
Published: March 2015

The forebrain has the most complex shape and structure of the vertebrate brain regions and the mechanisms of its formation remain obscure. Convergence and extension movements are characteristic of the posterior (spinal cord and hindbrain) neural plate (pNP) while tissue deformations and underlying cellular dynamics during the early shaping of the forebrain neural plate (fNP) are undefined. Here, we apply live imaging, automated cell tracking and computational analysis to quantitatively map cell behaviour in the zebrafish fNP. We demonstrate a novel mechanism in which planar cell rearrangements, with a passive signature, are orthogonal to those in the pNP, and cell divisions lacking planar-polarity facilitate thickening from two to three layers. We develop a mechanical model of the fNP in which polarised cell behaviour arises from interactions with dissimilar bordering tissues rather than from intrinsically polarised cells. The model unifiesin vivoobservations and provides a mechanistic understanding of fNP morphogenesis.
Phylogeography by Diffusion on a Sphere
Authors: Bouckaert Remco R.
Published: March 2015

Techniques for reconstructing geographical history along a phylogeny can answer many interesting question about the geographical origins of species. Bayesian models based on the assumption that taxa move through a diffusion process have found many applications. However, these methods rely on diffusion processes on a plane, and do not take the spherical nature of our planet in account. This makes it hard to perform analysis that cover the whole world, or do not take in account the distortions caused by projections like the Mercator projection.

In this paper, we introduce a Bayesian phylogeographical method based on diffusion on a sphere. When the area where taxa are sampled from is small, a sphere can be approximated by a plane and the model results in the same inferences as with models using diffusion on a plane. For taxa samples from the whole world, we obtain substantial differences. We present an efficient algorithm for performing inference in an Markov Chain Monte Carlo (MCMC) algorithm, and show applications to small and large samples areas.

Availability: The method is implemented in the GEO_SPHERE package in BEAST 2, which is open source licensed under LGPL.
The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
Authors: Schoenfelder Stefan , Furlan-Magaril Mayra , Mifsud Borbala , Tavares-Cadete Filipe , Sugar Robert , Javierre Biola-Maria , Nagano Takashi , Katsman Yulia , Sakthidevi Moorthy , Wingett Steven W. , Dimitrova Emilia , Dimond Andrew , Edelman Lucas B. , Elderkin Sarah , Tabbada Kristina , Darbo Elodie , Andrews Simon , Herman Bram , Higgs Andy , LeProust Emily , Osborne Cameron S. , Mitchell Jennifer A. , Luscombe Nicholas M. , Fraser Peter
Published: March 2015

The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression.
Crystal structure of [2,6-difluoro-3-(pyridin-2-yl-κN)pyridin-4-yl-κC4](pentane-2,4-dionato-κ2O,O′)platinum(II)
Authors: Park Ki-Min , Lee Jieun , Kang Youngjin
Published: March 2015

The asymmetric unit of the title compound, [Pt(C10H5F2N2)(C5H7O2)], comprises one PtIIatom, one 2,6-difluoro-2,3-bipyridine ligand and one acetylacetonate anion. The PtIIatom adopts a distorted square-planar coordination geometry, beingC,N-chelated by the 2,6-difluoro-3-(pyridin-2-yl)pyridin-4-yl ligand andO,O′-chelated by the pentane-2,4-dionate ligand. The two pyridine rings of the bipyridine ligand are approximately coplanar, making a dihedral angle of 1.2 (2)°. A variety of intra- and intermolecular C—H...O and C—H...F hydrogen bonds, as well as π–π interactions [centroid–centroid distances = 4.337 (3) and 3.774 (3) Å] contribute to the stabilization of the molecular and crystal structures, and result in the formation of a three-dimensional supramolecular framework.
Crystal structure of bis(4-acetylpyridine-κN)bis(ethanol-κO)bis(thiocyanato-κN)manganese(II)
Authors: Werner Julia , Jess Inke , Näther Christian
Published: March 2015

In the crystal structure of the title compound, [Mn(NCS)2(C7H7NO)2(C2H5OH)2], the MnIIatom is coordinated by twoN-bonded thiocyanate anions, two 4-acetylpyridine ligands, and two ethanol molecules within a slightly distorted octahedron. The asymmetric unit consits of one manganese cation, located on a centre of inversion, one thiocyanate anion, one 4-acetylpyridine ligand and one ethanol molecule in general positions. The discrete complexes are connected by intermolecular O—H...O hydrogen bonds between the alcohol OH group and the carbonyl O atom into chains parallel to [011].
Predictors of the integration of Sri Lankan Tamil refugees in Canada: pre-migration adversity, mental health, personal attributes, and post-migration experience
Authors: Beiser Morton , Goodwill Alasdair M. , Albanese Patrizia , McShane Kelly , Kanthasamy Parvathy
Published: March 2015

Purpose

– Refugees integrate less successfully than other immigrants. Pre-migration stress, mental disorder and lack of human capital are the most popular explanations, but these propositions have received little empirical testing. The current study of Sri Lankan Tamils in Toronto, Canada, examines the respective contributions of pre-migration adversity, human capital, mental health and social resources in predicting integration. The paper aims to discuss these issues.

Design/methodology/approach

– Participants are a probability sample of 1,603 Sri Lankan Tamils living in Toronto, Canada. The team, with a community advisory council, developed structured interviews containing information about pre- and post-migration stressors, coping strategies, and family, community, and institutional support. The questionnaire included the World Health Organization Composite International Diagnostic Interview module for post-traumatic stress disorder (PTSD). Interviews were translated, back-translated and administered by bilingual interviewers.

Findings

– Two dimensions of integration emerged from a factor analysis of integration-related items: economic and psychosocial. Hierarchical multiple regression analyses revealed that PTSD militated against refugee economic integration, whereas pre-migration adversity (but not PTSD) compromised psychosocial integration. On both measures, increasing length of residence in Canada, and gender (male) were predictors of good integration, whereas age at arrival had an inverse relationship with integration. Religiosity had a positive effect on psychosocial integration but a negative effect on economic. Favourable perceptions of the health care system predicted economic integration and non-family support predicted psychosocial integration.

Originality/value

– Results underline the importance of studying integration as a multifaceted phenomenon, help explain why refugees integrate less successfully than other immigrants, and highlight the importance of including mental health and mental health-related issues in integration discourse.
The refugee experience of acquiring a family doctor
Authors: Grant Karen J. , Mayhew Maureen , Mota Lorena , Klein Michael C. , Kazanjian Arminée
Published: March 2015

Purpose

– The purpose of this paper is to explore refugees’ experiences of the barriers and facilitators involved in finding a regular family doctor.

Design/methodology/approach

– Hermeneutic phenomenology was used to produce an integrated description sensitive to the lifeworlds of refugees who came from multiple cultural perspectives. Participants consisted of refugees from Iran, Afghanistan, Myanmar, Vietnam, and Latin America who arrived in Canada between 2005 and 2007. Texts for analysis came from first language focus group discussions and interviews with the interpreters for those groups.

Findings

– The principal themes that emerged from the experience of barriers were “futility,” “dependence,” and “relevance.” Themes related to the experience of facilitators were “inclusion,” “congruence,” and “benefit to family.” These themes provide key messages about sources of patient decisions to seek or not seek care, not comply, attend irregularly, and not disclose symptoms, which can be used by doctors and other health providers to enhance care planning.

Practical implications

– The factors that facilitate refugees’ access to a regular family doctor have implications for the development of culturally appropriate healthcare information, policies that support adequate interpreter services, and cultural sensitivity training for physicians.

Originality/value

– Previous research documents barriers such as lack of language access, differences in health beliefs, and lack of knowledge about western healthcare systems. However, little is known about how refugees experience these barriers, nor how they overcome them. This study contributes a rich and deeper understanding of how refugees experience these barriers and elucidates factors that facilitate their process of obtaining a regular family doctor.