bluuebunny/crossref_metadata_2025 huggingface dataset:
Independent Emergence of Resistance to Seven Chemical Classes of Fungicides in Botrytis cinerea
Authors: Fernández-Ortuño Dolores , Grabke Anja , Li Xingpeng , Schnabel Guido
Published: October 2014

Gray mold, caused by the fungal pathogen Botrytis cinerea, is one of the most destructive diseases of small fruit crops and control is largely dependent on the application of fungicides. As part of a region-wide resistance-monitoring program that investigated 1,890 B. cinerea isolates from 189 fields in 10 states of the United States, we identified seven isolates (0.4%) from five locations in four different states with unprecedented resistance to all seven Fungicide Resistance Action Committee (FRAC) codes with single-site modes of action including FRAC 1, 2, 7, 9, 11, 12, and 17 registered in the United States for gray mold control. Resistance to thiophanate-methyl, iprodione, boscalid, pyraclostrobin, and fenhexamid was based on target gene mutations that conferred E198A and F200Y in β-tubulin, I365N/S in Bos1, H272R/Y in SdhB, G143A in Cytb, and T63I and F412S in Erg27. Isolates were grouped into MDR1 and MDR1h phenotypes based on sensitivity to fludioxonil and variations in transcription factor mrr1. MDR1h isolates had a previously described 3-bp deletion at position 497 in mrr1. Expression of ABC transporter atrB was increased in MDR1 isolates but highest in MDR1h isolates. None of the isolates with seven single resistances (SR) had identical nucleotide variations in target genes, indicating that they emerged independently. Multifungicide resistance phenotypes did not exhibit significant fitness penalties for the parameters used in this study, but MDR1h isolates produced more sclerotia at low temperatures and exhibited increased sensitivity to salt stress. In this study we show that current resistance management strategies have not been able to prevent the geographically independent development of resistance to all seven site-specific fungicides currently registered for gray mold control in the United States and document the presence of MDR1h in North America.
Geckos significantly alter foot orientation to facilitate adhesion during downhill locomotion
Authors: Birn-Jeffery Aleksandra V. , Higham Timothy E.
Published: October 2014

Geckos employ their adhesive system when moving up an incline, but the directionality of the system may limit function on downhill surfaces. Here, we use a generalist gecko to test whether limb modulation occurs on downhill slopes to allow geckos to take advantage of their adhesive system. We examined three-dimensional limb kinematics for geckos moving up and down a 45° slope. Remarkably, the hind limbs were rotated posteriorly on declines, resulting in digit III of the pes facing a more posterior direction (opposite to the direction of travel). No significant changes in limb orientation were found in any other condition. This pes rotation leads to a dramatic shift in foot function that facilitates the use of the adhesive system as a brake/stabilizer during downhill locomotion and, although this rotation is not unique to geckos, it is significant for the deployment of adhesion. Adhesion is not just advantageous for uphill locomotion but can be employed to help deal with the effects of gravity during downhill locomotion, highlighting the incredible multi-functionality of this key innovation.
Extreme nomadism in desert waterbirds: flights of the banded stilt
Authors: Pedler R. D. , Ribot R. F. H. , Bennett A. T. D.
Published: October 2014

In contrast to well-studied Northern Hemisphere birds with spatially and temporally predictable seasonal migrations, waterbirds in desert biomes face major challenges in exploiting stochastic, rich, yet short-lived resource pulses in vast arid landscapes, leading to the evolution of nomadic behaviour. An extreme example is the banded stilt (
Cladorhynchus leucocephalus
), an opportunistic colonial breeder at remote inland salt lakes after infrequent rain events. Using satellite telemetry on 21 birds (tracked for a mean of 196.2 days), we reveal extensive, rapid and synchronized movement among individuals to and from salt lakes. Two birds left coastal refugia for the inland following rain, flying 1000–2000 km, while 12 others rapidly moved a mean of 684 km (range 357–1298 km) away from drying inland sites to the coast. Two individuals moved longitudinally across the continent, departing and arriving at the same points, yet travelling very different routes; one bird moving more than 2200 km in less than 2.5 days, the other more than 1500 km in 6 days. Our findings reveal movements nearly twice as long and rapid as recorded in other desert waterbirds. We reveal capability to rapidly detect and exploit ephemeral wetland resource pulses across the stochastic Australian desert.
Contrast influences female attraction to performance-based sexual signals in a songbird
Authors: Lyons Susan M. , Beaulieu Michaël , Sockman Keith W.
Published: October 2014

Animals do not make decisions in a bubble but often refer to previous experience when discriminating between options. Contrast effects occur when the value of a stimulus affects the response to another value of the stimulus, and the changes in value and response are in the same direction. Although contrast effects appear irrational, they could benefit decision makers when there is spatial or temporal variation and autocorrelation in the value of stimuli that elicit decisions. Here, we examined whether contrasts influence female evaluation of male performance-based sexual signals. We exposed female Lincoln's sparrows (
Melospiza lincolnii
) to one week of songs that we had experimentally reduced or elevated in performance, followed by a novel song of intermediate performance. We found that high-performance songs were more attractive to females than low-performance songs. Moreover, the intermediate songs were more attractive following exposure to low- than to high-performance songs. These results indicate that contrast can influence evaluation of performance-based sexual stimuli. By examining contrast effects in the ecologically relevant context of mate choice for performance, we can better understand both the adaptive value of comparative evaluation as well as the mechanisms that underlie variation in mate choice and sexual selection.
Reproductive niche conservatism in the isolated New Zealand flora over 23 million years
Authors: Conran John G. , Lee William G. , Lee Daphne E. , Bannister Jennifer M. , Kaulfuss Uwe
Published: October 2014

The temporal stability of plant reproductive features on islands has rarely been tested. Using flowers, fruits/cones and seeds from a well-dated (23 Ma) Miocene
Lagerstätte
in New Zealand, we show that across 23 families and 30 genera of forest angiosperms and conifers, reproductive features have remained constant for more than 20 Myr. Insect-, wind- and bird-pollinated flowers and wind- and bird-dispersed diaspores all indicate remarkable reproductive niche conservatism, despite widespread environmental and biotic change. In the past 10 Myr, declining temperatures and the absence of low-latitude refugia caused regional extinction of thermophiles, while orogenic processes steepened temperature, precipitation and nutrient gradients, limiting forest niches. Despite these changes, the palaeontological record provides empirical support for evidence from phylogeographical studies of strong niche conservatism within lineages and biomes.
Calcifying tissue regeneration via biomimetic materials chemistry
Authors: Green David W. , Goto Tazuko K. , Kim Kye-Seong , Jung Han-Sung
Published: October 2014

Materials chemistry is making a fundamental impact in regenerative sciences providing many platforms for tissue development. However, there is a surprising paucity of replacements that accurately mimic the structure and function of the structural fabric of tissues or promote faithful tissue reconstruction. Methodologies in biomimetic materials chemistry have shown promise in replicating morphologies, architectures and functional building blocks of acellular mineralized tissues dentine, enamel and bone or that can be used to fully regenerate them with integrated cell populations. Biomimetic materials chemistry encompasses the two processes of crystal formation and mineralization of crystals into inorganic formations on organic templates. This review will revisit the successes of biomimetics materials chemistry in regenerative medicine, including coccolithophore simulants able to promotein vivobone formation. In-depth knowledge of biomineralization throughout evolution informs the biomimetic materials chemist of the most effective techniques for regenerative framework construction exemplified via exploitation of liquid crystals (LCs) and complex self-organizing media. Therefore, a new innovative direction would be to create chemical environments that perform reaction–diffusion exchanges as the basis for building complex biomimetic inorganic structures. This has evolved widely in biology, as have LCs, serving as self-organizing templates in pattern formation of structural biomaterials. For instance, a study is highlighted in which artificially fabricated chiral LCs, made from bacteriophages are transformed into a faithful copy of enamel. While chemical-based strategies are highly promising at creating new biomimetic structures there are limits to the degree of complexity that can be generated. Thus, there may be good reason to implement living or artificial cells in ‘morphosynthesis’ of complex inorganic constructs. In the future, cellular construction is probably key to instruct building of ultimate biomimetic hierarchies with a totality of functions.
Wing tucks are a response to atmospheric turbulence in the soaring flight of the steppe eagle
Aquila nipalensis
Authors: Reynolds Kate V. , Thomas Adrian L. R. , Taylor Graham K.
Published: October 2014

Turbulent atmospheric conditions represent a challenge to stable flight in soaring birds, which are often seen to drop their wings in a transient motion that we call a tuck. Here, we investigate the mechanics, occurrence and causation of wing tucking in a captive steppe eagle
Aquila nipalensis
, using ground-based video and onboard inertial instrumentation. Statistical analysis of 2594 tucks, identified automatically from 45 flights, reveals that wing tucks occur more frequently under conditions of higher atmospheric turbulence. Furthermore, wing tucks are usually preceded by transient increases in airspeed, load factor and pitch rate, consistent with the bird encountering a headwind gust. The tuck itself immediately follows a rapid drop in angle of attack, caused by a downdraft or nose-down pitch motion, which produces a rapid drop in load factor. Positive aerodynamic loading acts to elevate the wings, and the resulting aerodynamic moment must therefore be balanced in soaring by an opposing musculoskeletal moment. Wing tucking presumably occurs when the reduction in the aerodynamic moment caused by a drop in load factor is not met by an equivalent reduction in the applied musculoskeletal moment. We conclude that wing tucks represent a gust response precipitated by a transient drop in aerodynamic loading.
The effects of relative food item size on optimal tooth cusp sharpness during brittle food item processing
Authors: Berthaume Michael A. , Dumont Elizabeth R. , Godfrey Laurie R. , Grosse Ian R.
Published: October 2014

Teeth are often assumed to be optimal for their function, which allows researchers to derive dietary signatures from tooth shape. Most tooth shape analyses normalize for tooth size, potentially masking the relationship between relative food item size and tooth shape. Here, we model how relative food item size may affect optimal tooth cusp radius of curvature (RoC) during the fracture of brittle food items using a parametric finite-element (FE) model of a four-cusped molar. Morphospaces were created for four different food item sizes by altering cusp RoCs to determine whether optimal tooth shape changed as food item size changed. The morphospaces were also used to investigate whether variation in efficiency metrics (i.e. stresses, energy and optimality) changed as food item size changed. We found that optimal tooth shape changed as food item size changed, but that all optimal morphologies were similar, with one dull cusp that promoted high stresses in the food item and three cusps that acted to stabilize the food item. There were also positive relationships between food item size and the coefficients of variation for stresses in food item and optimality, and negative relationships between food item size and the coefficients of variation for stresses in the enamel and strain energy absorbed by the food item. These results suggest that relative food item size may play a role in selecting for optimal tooth shape, and the magnitude of these selective forces may change depending on food item size and which efficiency metric is being selected.
Integrable and superintegrable systems associated with multi-sums of products
Authors: van der Kamp Peter H. , Kouloukas Theodoros E. , Quispel G. R. W. , Tran Dinh T. , Vanhaecke Pol
Published: October 2014

We construct and study certain Liouville integrable, superintegrable and non-commutative integrable systems, which are associated with multi-sums of products.
Light's twist
Authors: Padgett Miles
Published: October 2014

That light travels in straight lines is a statement of the obvious. However, the energy and momentum flow within light beams can twist to form vortices such as eddies in a stream. These twists carry angular momentum, which can make microscopic objects spin, be used to encode extra information in communication systems, enable the design of novel imaging systems and allow new tests of quantum mechanics.
Preference for outbred host plants and positive effects of inbreeding on egg survival in a specialist herbivore
Authors: Kalske Aino , Muola Anne , Mutikainen Pia , Leimu Roosa
Published: October 2014

Inbreeding can profoundly affect the interactions of plants with herbivores as well as with the natural enemies of the herbivores. We studied how plant inbreeding affects herbivore oviposition preference, and whether inbreeding of both plants and herbivores alters the probability of predation or parasitism of herbivore eggs. In a laboratory preference test with the specialist herbivore moth
Abrostola asclepiadis
and inbred and outbred
Vincetoxicum hirundinaria
plants, we discovered that herbivores preferred to oviposit on outbred plants. A field experiment with inbred and outbred plants that bore inbred or outbred herbivore eggs revealed that the eggs of the outbred herbivores were more likely to be lost by predation, parasitism or plant hypersensitive responses than inbred eggs. This difference did not lead to differences in the realized fecundity as the number of hatched larvae did not differ between inbred and outbred herbivores. Thus, the strength of inbreeding depression in herbivores decreases when their natural enemies are involved. Plant inbreeding did not alter the attraction of natural enemies of the eggs. We conclude that inbreeding can significantly alter the interactions of plants and herbivores at different life-history stages, and that some of these alterations are mediated by the natural enemies of the herbivores.
Personality composition is more important than group size in determining collective foraging behaviour in the wild
Authors: Keiser Carl N. , Pruitt Jonathan N.
Published: October 2014

Describing the factors that shape collective behaviour is central to our understanding of animal societies. Countless studies have demonstrated an effect of group size in the emergence of collective behaviours, but comparatively few have accounted for the composition/diversity of behavioural phenotypes, which is often conflated with group size. Here, we simultaneously examine the effect of personality composition and group size on nest architecture and collective foraging aggressiveness in the social spiderStegodyphus dumicola. We created colonies of two different sizes (10 or 30 individuals) and four compositions of boldness (all bold, all shy, mixed bold and shy, or average individuals) in the field and then measured their collective behaviour. Larger colonies produced bigger capture webs, while colonies containing a higher proportion of bold individuals responded to and attacked prey more rapidly. The number of attackers during collective foraging was determined jointly by composition and size, although composition had an effect size more than twice that of colony size: our results suggest that colonies of just 10 bold spiders would attack prey with as many attackers as colonies of 110 ‘average’ spiders. Thus, personality composition is a more potent (albeit more cryptic) determinant of collective foraging in these societies.
Fighting experience alters brain androgen receptor expression dependent on testosterone status
Authors: Li Cheng-Yu , Earley Ryan L. , Huang Shu-Ping , Hsu Yuying
Published: October 2014

Contest decisions are influenced by the outcomes of recent fights (winner–loser effects). Steroid hormones and serotonin are closely associated with aggression and therefore probably also play important roles in mediating winner–loser effects. In mangrove rivulus fish,
Kryptolebias marmoratus
, individuals with higher testosterone (T), 11-ketotestosterone and cortisol levels are more capable of winning, but titres of these hormones do not directly mediate winner–loser effects. In this study, we investigated the effects of winning/losing experiences on brain expression levels of the receptor genes for androgen (AR), oestrogen α/β (ER
α/β
), glucocorticoid (GR) and serotonin (5-HT
1A
R). The effect of contest experience on AR gene expression depended on T levels: repeated losses decreased, whereas repeated wins increased AR gene expression in individuals with low T but not in individuals with medium or high T levels. These results lend strong support for AR being involved in mediating winner–loser effects, which, in previous studies, were more detectable in individuals with lower T. Furthermore, the expression levels of ER
α/β
, 5-HT
1A
R and GR genes were higher in individuals that initiated contests against larger opponents than in those that did not. Overall, contest experience, underlying endocrine state and hormone and serotonin receptor expression patterns interacted to modulate contest decisions jointly.
C, N and P fertilization in an Amazonian rainforest supports stoichiometric dissimilarity as a driver of litter diversity effects on decomposition
Authors: Barantal Sandra , Schimann Heidy , Fromin Nathalie , Hättenschwiler Stephan
Published: October 2014

Plant leaf litter generally decomposes faster as a group of different species than when individual species decompose alone, but underlying mechanisms of these diversity effects remain poorly understood. Because resource C : N : P stoichiometry (i.e. the ratios of these key elements) exhibits strong control on consumers, we supposed that stoichiometric dissimilarity of litter mixtures (i.e. the divergence in C : N : P ratios among species) improves resource complementarity to decomposers leading to faster mixture decomposition. We tested this hypothesis with: (i) a wide range of leaf litter mixtures of neotropical tree species varying in C : N : P dissimilarity, and (ii) a nutrient addition experiment (C, N and P) to create stoichiometric similarity. Litter mixtures decomposed in the field using two different types of litterbags allowing or preventing access to soil fauna. Litter mixture mass loss was higher than expected from species decomposing singly, especially in presence of soil fauna. With fauna, synergistic litter mixture effects increased with increasing stoichiometric dissimilarity of litter mixtures and this positive relationship disappeared with fertilizer addition. Our results indicate that litter stoichiometric dissimilarity drives mixture effects via the nutritional requirements of soil fauna. Incorporating ecological stoichiometry in biodiversity research allows refinement of the underlying mechanisms of how changing biodiversity affects ecosystem functioning.
Aposematism increases acoustic diversification and speciation in poison frogs
Authors: Santos Juan C. , Baquero Margarita , Barrio-Amorós César , Coloma Luis A. , Erdtmann Luciana K. , Lima Albertina P. , Cannatella David C.
Published: October 2014

Multimodal signals facilitate communication with conspecifics during courtship, but they can also alert eavesdropper predators. Hence, signallers face two pressures: enticing partners to mate and avoiding detection by enemies. Undefended organisms with limited escape abilities are expected to minimize predator recognition over mate attraction by limiting or modifying their signalling. Alternatively, organisms with anti-predator mechanisms such as aposematism (i.e. unprofitability signalled by warning cues) might elaborate mating signals as a consequence of reduced predation. We hypothesize that calls diversified in association with aposematism. To test this, we assembled a large acoustic signal database for a diurnal lineage of aposematic and cryptic/non-defended taxa, the poison frogs. First, we showed that aposematic and non-aposematic species share similar extinction rates, and aposematic lineages diversify more and rarely revert to the non-aposematic phenotype. We then characterized mating calls based on morphological (spectral), behavioural/physiological (temporal) and environmental traits. Of these, only spectral and temporal features were associated with aposematism. We propose that with the evolution of anti-predator defences, reduced predation facilitated the diversification of vocal signals, which then became elaborated or showy via sexual selection.
Coordination strategies of chimpanzees and human children in a Stag Hunt game
Authors: Duguid Shona , Wyman Emily , Bullinger Anke F. , Herfurth-Majstorovic Katharina , Tomasello Michael
Published: October 2014

Much of human cooperation takes place in mutualistic contexts in which the main challenge for individuals is how to coordinate decisions. In the current studies, we compared the abilities of chimpanzees and young children to coordinate with a partner in two versions of a Stag Hunt game. When risks were low (the hare was of low value) and information was cheap (the partner's behaviour was readily observable), partners of both species were able to successfully coordinate on the higher value stag more than 90% of the time. By contrast, when the risks were raised and observing the partner was more difficult, the chimpanzees became less successful, whereas the children compensated, and so remained highly successful, by communicating more often and more specifically. This pattern of results is consistent with the hypothesis that humans evolved unique skills of coordination and communication in the context of especially risky coordination problems.
FinisherSC : A repeat-aware tool for upgrading de-novo assembly using long reads
Authors: Lam Ka-Kit , LaButti Kurt , Khalak Asif , Tse David
Published: October 2014

We introduce FinisherSC, a repeat-aware and scalable tool for upgrading de-novo assembly using long reads. Experiments with real data suggest that FinisherSC can provide longer and higher quality contigs than existing tools while maintaining high concordance.

Availability

The tool and data are available and will be maintained athttp://kakitone.github.io/finishingTool/

Contact

dntse@stanford.edu
Recent evolution of the mutation rate and spectrum in Europeans
Authors: Harris Kelley
Published: October 2014

As humans dispersed out of Africa, they adapted to new environmental challenges including changes in exposure to mutagenic solar radiation. Humans in temperate latitudes have acquired light skin that is relatively transparent to ultraviolet light, and some evidence suggests that their DNA damage response pathways have also experienced local adaptation. This raises the possibility that different populations have experienced different selective pressures affecting genome integrity. Here, I present evidence that the rate of a particular mutation type has recently increased in the European population, rising in frequency by 50% during the 40,000–80,000 years since Europeans began diverging from Asians. A comparison of single nucleotide polymorphisms (SNPs) private to Africa, Asia, and Europe in the 1000 Genomes data reveals that private European variation is enriched for the transition 5’-TCC-3’→5’-TTC-3’. Although it is not clear whether UV played a causal role in the changing the European mutational spectrum, 5’-TCC-3’→5’-TTC-3’ is known to be the most common somatic mutation present in melanoma skin cancers, as well as the mutation most frequently inducedin vitroby UV. Regardless of its causality, this change indicates that DNA replication fidelity has not remained stable even since the origin of modern humans and might have changed numerous times during our recent evolutionary history.
NeuroVault.org: A web-based repository for collecting and sharing unthresholded statistical maps of the human brain
Authors: Gorgolewski Krzysztof Jacek , Varoquaux Gael , Rivera Gabriel , Schwartz Yannick , Ghosh Satrajit S. , Maumet Camille , Sochat Vanessa , Nichols Thomas E. , Poldrack Russell A. , Poline Jean-Baptiste , Yarkoni Tal , Margulies Daniel S.
Published: October 2014

Here we present NeuroVault - a web based repository that allows researchers to store, share, visualize, and decode statistical maps of the human brain. NeuroVault is easy to use and employs modern web technologies to provide informative visualization of data without the need to install additional software. In addition, it leverages the power of the Neurosynth database to provide cognitive decoding of deposited maps. The data are exposed through a public REST API enabling other services and tools to take advantage of it. NeuroVault is a new resource for researchers interested in conducting meta- and coactivation analyses.
Similar efficacies of selection shape mitochondrial and nuclear genes inDrosophila melanogasterandHomo sapiens
Authors: Cooper Brandon S. , Burrus Chad R. , Ji Chao , Hahn Matthew W. , Montooth Kristi L.
Published: October 2014

Deleterious mutations contribute to polymorphism even when selection effectively prevents their fixation. The efficacy of selection in removing deleterious mitochondrial mutations from populations depends on the effective population size (Ne) of the mtDNA, and the degree to which a lack of recombination magnifies the effects of linked selection. Using complete mitochondrial genomes fromDrosophila melanogasterand nuclear data available from the same samples, we re-examine the hypothesis that non-recombining animal mtDNA harbor an excess of deleterious polymorphisms relative to the nuclear genome. We find no evidence of recombination in the mitochondrial genome, and the much-reduced level of mitochondrial synonymous polymorphism relative to nuclear genes is consistent with a reduction inNe. Nevertheless, we find that the neutrality index (NI), a measure of the excess of nonsynonymous polymorphism relative to the neutral expectation, is not significantly different between mitochondrial and nuclear loci. Reanalysis of published data fromHomo sapiensreveals the same lack of a difference between the two genomes, though small samples in previous studies had suggested a strong difference in both species. Thus, despite a smallerNe, mitochondrial loci of both flies and humans appear to experience similar efficacies of selection as do loci in the recombining nuclear genome.
Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants
Authors: Belkadi Aziz , Bolze Alexandre , Itan Yuval , Cobat Aurélie , Vincent Quentin B. , Antipenko Alexander , Shang Lei , Boisson Bertrand , Casanova Jean-Laurent , Abel Laurent
Published: October 2014

We compared whole-exome sequencing (WES) and whole-genome sequencing (WGS) in six unrelated individuals. In the regions targeted by WES capture (81.5% of the consensus coding genome), the mean numbers of single-nucleotide variants (SNVs) and small insertions/deletions (indels) detected per sample were 84,192 and 13,325, respectively, for WES, and 84,968 and 12,702, respectively, for WGS. For both SNVs and indels, the distributions of coverage depth, genotype quality, and minor read ratio were more uniform for WGS than for WES. After filtering, a mean of 74,398 (95.3%) high-quality (HQ) SNVs and 9,033 (70.6%) HQ indels were called by both platforms. A mean of 105 coding HQ SNVs and 32 indels were identified exclusively by WES, whereas 692 HQ SNVs and 105 indels were identified exclusively by WGS. We Sanger sequenced a random selection of these exclusive variants. For SNVs, the proportion of false-positive variants was higher for WES (78%) than for WGS (17%). The estimated mean number of real coding SNVs (656, ∼3% of all coding HQ SNVs) identified by WGS and missed by WES was greater than the number of SNVs identified by WES and missed by WGS (26). For indels, the proportions of false-positive variants were similar for WES (44%) and WGS (46%). Finally, WES was not reliable for the detection of copy number variations, almost all of which extended beyond the targeted regions. Although currently more expensive, WGS is more powerful than WES for detecting potential disease-causing mutations within WES regions, particularly those due to SNVs.

Significance

Whole-exome sequencing (WES) is gradually being optimized to identify mutations in increasing proportions of the protein-coding exome, but whole-genome sequencing (WGS) is becoming an attractive alternative. WGS is currently more expensive than WES, but its cost should decrease more rapidly than that of WES. We compared WES and WGS on six unrelated individuals. The distribution of quality parameters for single-nucleotide variants (SNVs) and insertions/deletions (indels) was more uniform for WGS than for WES. The vast majority of SNVs and indels were identified by both techniques, but an estimated 650 high-quality coding SNVs (∼3% of coding variants) were detected by WGS and missed by WES. WGS is therefore slightly more efficient than WES for detecting mutations in the targeted exome.
Human high-altitude adaptation: forward genetics meets the HIF pathway
Authors: Bigham Abigail W. , Lee Frank S.
Published: October 2014

Humans have adapted to the chronic hypoxia of high altitude in several locations, and recent genome-wide studies have indicated a genetic basis. In some populations, genetic signatures have been identified in the hypoxia-inducible factor (HIF) pathway, which orchestrates the transcriptional response to hypoxia. In Tibetans, they have been found in the HIF2A (EPAS1) gene, which encodes for HIF-2α, and the prolyl hydroxylase domain protein 2 (PHD2, also known as EGLN1) gene, which encodes for one of its key regulators, PHD2. High-altitude adaptation may be due to multiple genes that act in concert with one another. Unraveling their mechanism of action can offer new therapeutic approaches toward treating common human diseases characterized by chronic hypoxia.
A gene-specific role for the Ssu72 RNAPII CTD phosphatase in HIV-1 Tat transactivation
Authors: Chen Yupeng , Zhang Lirong , Estarás Conchi , Choi Seung H. , Moreno Luis , Karn Jonathan , Moresco James J. , Yates John R. , Jones Katherine A.
Published: October 2014

HIV-1 Tat stimulates transcription elongation by recruiting the P-TEFb (positive transcription elongation factor-b) (CycT1:CDK9) C-terminal domain (CTD) kinase to the HIV-1 promoter. Here we show that Tat transactivation also requires the Ssu72 CTD Ser5P (S5P)-specific phosphatase, which mediates transcription termination and intragenic looping at eukaryotic genes. Importantly, HIV-1 Tat interacts directly with Ssu72 and strongly stimulates its CTD phosphatase activity. We found that Ssu72 is essential for Tat:P-TEFb-mediated phosphorylation of the S5P-CTD in vitro. Interestingly, Ssu72 also stimulates nascent HIV-1 transcription in a phosphatase-dependent manner in vivo. Chromatin immunoprecipitation (ChIP) experiments reveal that Ssu72, like P-TEFb and AFF4, is recruited by Tat to the integrated HIV-1 proviral promoter in TNF-α signaling 2D10 T cells and leaves the elongation complex prior to the termination site. ChIP-seq (ChIP combined with deep sequencing) and GRO-seq (genome-wide nuclear run-on [GRO] combined with deep sequencing) analysis further reveals that Ssu72 predominantly colocalizes with S5P–RNAPII (RNA polymerase II) at promoters in human embryonic stem cells, with a minor peak in the terminator region. A few genes, like NANOG, also have high Ssu72 at the terminator. Ssu72 is not required for transcription at most cellular genes but has a modest effect on cotranscriptional termination. We conclude that Tat alters the cellular function of Ssu72 to stimulate viral gene expression and facilitate the early S5P–S2P transition at the integrated HIV-1 promoter.
Mutation of the Inducible ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE2 Alters Lignin Composition and Improves Saccharification
Authors: Sundin Lisa , Vanholme Ruben , Geerinck Jan , Goeminne Geert , Höfer René , Kim Hoon , Ralph John , Boerjan Wout
Published: October 2014

ARABIDOPSIS THALIANA CYTOCHROME P450 REDUCTASE1 (ATR1) and ATR2 provide electrons from NADPH to a large number of CYTOCHROME P450 (CYP450) enzymes in Arabidopsis (Arabidopsis thaliana). Whereas ATR1 is constitutively expressed, the expression of ATR2 appears to be induced during lignin biosynthesis and upon stresses. Therefore, ATR2 was hypothesized to be preferentially involved in providing electrons to the three CYP450s involved in lignin biosynthesis: CINNAMATE 4-HYDROXYLASE (C4H), p-COUMARATE 3-HYDROXYLASE1 (C3H1), and FERULATE 5-HYDROXYLASE1 (F5H1). Here, we show that the atr2 mutation resulted in a 6% reduction in total lignin amount in the main inflorescence stem and a compositional shift of the remaining lignin to a 10-fold higher fraction of p-hydroxyphenyl units at the expense of syringyl units. Phenolic profiling revealed shifts in lignin-related phenolic metabolites, in particular with the substrates of C4H, C3H1 and F5H1 accumulating in atr2 mutants. Glucosinolate and flavonol glycoside biosynthesis, both of which also rely on CYP450 activities, appeared less affected. The cellulose in the atr2 inflorescence stems was more susceptible to enzymatic hydrolysis after alkaline pretreatment, making ATR2 a potential target for engineering plant cell walls for biofuel production.
Insights into the relationship between the haem-binding pocket and the redox potential ofc6cytochromes: four atomic resolution structures ofc6andc6-like proteins fromSynechococcussp. PCC 7002
Authors: Bialek Wojciech , Krzywda Szymon , Zatwarnicki Pawel , Jaskolski Mariusz , Kolesinski Piotr , Szczepaniak Andrzej
Published: October 2014

The structure of cytochromec6Cfrom the mesophilic cyanobacteriumSynechococcussp. PCC 7002 has been determined at 1.03 Å resolution. This is the first structural report on the recently discovered cyanobacterial cytochromec6-like proteins found in marine and nitrogen-fixing cyanobacteria. Despite high similarity in the overall three-dimensional fold between cytochromesc6andc6C, the latter shows saliently different electrostatic properties in terms of surface charge distribution and dipole moments. Its midpoint redox potential is less than half of the value for typicalc6cytochromes and results mainly from the substitution of one residue in the haem pocket. Here, high-resolution crystal structures of mutants of both cytochromesc6andc6Care presented, and the impact of the mutation of specific residues in the haem-binding pocket on the redox potential is discussed. These findings contribute to the elucidation of the structure–function relationship ofc6-like cytochromes.
Anchoring protein crystals to mounting loops with hydrogel using inkjet technology
Authors: Shinoda Akira , Tanaka Yoshikazu , Yao Min , Tanaka Isao
Published: October 2014

X-ray crystallography is an important technique for structure-based drug discovery, mainly because it is the only technique that can reveal whether a ligand binds to the target protein as well as where and how it binds. However, ligand screening by X-ray crystallography involves a crystal-soaking experiment, which is usually performed manually. Thus, the throughput is not satisfactory for screening large numbers of candidate ligands. In this study, a technique to anchor protein crystals to mounting loops by using gel and inkjet technology has been developed; the method allows soaking of the mounted crystals in ligand-containing solution. This new technique may assist in the design of a fully automated drug-screening pipeline.
Anthrax toxin lethal factor domain 3 is highly mobile and responsive to ligand binding
Authors: Maize Kimberly M. , Kurbanov Elbek K. , De La Mora-Rey Teresa , Geders Todd W. , Hwang Dong-Jin , Walters Michael A. , Johnson Rodney L. , Amin Elizabeth A. , Finzel Barry C.
Published: October 2014

The secreted anthrax toxin consists of three components: the protective antigen (PA), edema factor (EF) and lethal factor (LF). LF, a zinc metalloproteinase, compromises the host immune system primarily by targeting mitogen-activated protein kinase kinases in macrophages. Peptide substrates and small-molecule inhibitors bind LF in the space between domains 3 and 4 of the hydrolase. Domain 3 is attached on a hinge to domain 2viaresidues Ile300 and Pro385, and can move through an angular arc of greater than 35° in response to the binding of different ligands. Here, multiple LF structures including five new complexes with co-crystallized inhibitors are compared and three frequently populated LF conformational states termed `bioactive', `open' and `tight' are identified. The bioactive position is observed with large substrate peptides and leaves all peptide-recognition subsites open and accessible. The tight state is seen in unliganded and small-molecule complex structures. In this state, domain 3 is clamped over certain substrate subsites, blocking access. The open position appears to be an intermediate state between these extremes and is observed owing to steric constraints imposed by specific bound ligands. The tight conformation may be the lowest-energy conformation among the reported structures, as it is the position observed with no bound ligand, while the open and bioactive conformations are likely to be ligand-induced.
Structure of mouse muskelin discoidin domain and biochemical characterization of its self-association
Authors: Kim Kook-Han , Hong Seung Kon , Hwang Kwang Yeon , Kim Eunice EunKyeong
Published: October 2014

Muskelin is an intracellular kelch-repeat protein comprised of discoidin, LisH, CTLH and kelch-repeat domains. It is involved in cell adhesion and the regulation of cytoskeleton dynamics as well as being a component of a putative E3 ligase complex. Here, the first crystal structure of mouse muskelin discoidin domain (MK-DD) is reported at 1.55 Å resolution, which reveals a distorted eight-stranded β-barrel with two short α-helices at one end of the barrel. Interestingly, the N- and C-termini are not linked by the disulfide bonds found in other eukaryotic discoidin structures. A highly conserved MIND motif appears to be the determinant for MK-DD specific interaction together with the spike loops. Analysis of interdomain interaction shows that MK-DD binds the kelch-repeat domain directly and that this interaction depends on the presence of the LisH domain.
The boundaryless career at 20: where do we stand, and where can we go?
Authors: B. Arthur Michael
Published: October 2014

Purpose

– The purpose of this paper is to reflect on a broad body of work that responds to the boundaryless career concept, first introduced in 1993, and to anticipate new theory-building and research.

Design/methodology/approach

– Covers the origination of the concept, its meaning and definition, the underlying influence of an earlier group of careers scholars from Massachusetts Institute of Technology (MIT), and the importance of an interdisciplinary perspective.

Findings

– Identifies three categories of activity – involving internal debates, fresh theoretical contributions, and new collaborative opportunities – that have occurred citing boundaryless career scholarship.

Research limitations/implications

– Suggests how scholars can build on the legacy of both organizational and boundaryless careers research in their future work.

Originality/value

– Links between foundational MIT work on careers, boundaryless careers and current debates to suggests future research directions.
Boundarylessness as a dynamic construct: the case of Chinese early career expatriates
Authors: Yao Christian , Thorn Kaye , Doherty Noeleen
Published: October 2014

Purpose

– The purpose of this paper is to explore the dynamic nature of boundaryless careers of Chinese early career corporate expatriates. It also investigates the demographic and contextual factors influencing individual perceived career mobility.

Design/methodology/approach

– Qualitative, semi-structured interviews with 31 Chinese corporate expatriates were conducted and a template analysis approach was used to analyze the data.

Findings

– Results suggest that Chinese early career corporate expatriates’ perceptions of boundaries as facilitating or limiting career mobility change over time. Changing boundary properties are found to be linked to the salience of Chinese cultural values, demographics and career/life stages. Based on expatriates’ narratives, this study highlights how these demographic and contextual factors shape domains of career boundarylessness.

Originality/value

– Using an under-researched sample of Chinese corporate expatriates, this paper contributes to the conceptualization of boundaryless careers identifying the changing nature of the boundaries that facilitate or restrict mobility over time. The study calls for the use of combined, multi-dimensional approaches incorporating individual agency, organizational and cultural factors to understand individual career development.
Organizational boundaries and beyond
Authors: Gubler Martin , Arnold John , Coombs Crispin
Published: October 2014

Purpose

– The purpose of this paper is to develop a new conceptualization of the boundaryless career – a widely acknowledged contemporary career concept – that reflects its original description more fully than previous literature has done, and to apply this conceptualization in an empirical investigation of career behavior and intentions of a large sample of European information technology (IT) professionals.

Design/methodology/approach

– As part of a large study of IT professionals in Europe (N=1,350), the paper had three research objectives. First, the paper developed and empirically tested a new operationalization of a person’s boundaryless career orientation (BCO) that reflects the originally proposed boundaryless career meanings more closely than existing approaches. Second, the paper used this to identify in a holistic manner different patterns of BCO. Third, the paper examined the nature and extent of links between BCO and self-reported career behavior and intentions.

Findings

– The paper identified five BCO factors that differentiate individuals into three distinct clusters. Although organizational boundaries appeared to be salient for most individuals, they did not differentiate the clusters. Instead, geographical mobility preference and rejection of career opportunities emerged as highly differentiating but hitherto rarely examined types of career boundaries.

Practical implications

– The findings can help HR managers to gain a better understanding of different mobility preferences among different groups of employees, which could lead to the development and implementation of more refined reward schemes and career development practices in organizations.

Originality/value

– This study provides a new operationalization of the BCO that is grounded in its original definition and offers a new empirically tested 15-item BCO measure. It contributes to career research with scarce empirical findings regarding the components of the BCO, their salience for individuals, and the connections between BCO and behavior.
Management communication, unionization, FDI and company performance in a developing country
Authors: Croucher Richard , Rizov Marian , Goolaup Ram
Published: October 2014

Purpose

– The purpose of this paper is to examine the associations between management direct communication to employees, unionization, foreign direct investment (FDI) and company performance in Mauritius, Africa's most successful economy.

Design/methodology/approach

– The authors use firm data from a survey conducted in Mauritius in late 2011. The authors conduct regression analysis to study the relationship between direct communication, unionization and performance conditional on ownership type.

Findings

– Mauritian labour unions, in common with their counterparts from mainland Africa, are strongest in the public sector. They have been characterized as weak and lacking in influence on management. Yet the authors find a strong association between unionization and management communication in the private sector. The authors also find a positive association between direct communication and company performance which the authors argue is likely to be an indirect consequence of unionization. FDI shows no particular effects.

Research limitations/implications

– It appears that the consequences of union presence transcend pay and conditions. The effects are unexpectedly marked, particularly when the stress by some authors on union weakness in the private sector is taken into account.

Originality/value

– It may be that local unions’ strong focus on the enterprise – a form of representation favoured by US-based multinational companies, constitutes a strength in stimulating management communication to employees by focusing union activities at that level. Whilst the authors have suggested that this is unlikely to be primarily a result of conscious union strategy, the enterprise focus may serve to buttress existing employee attitudes. In any event, unionization is certainly closely associated in this African country with a practice that is linked to positive economic effects at the enterprise level.
The recovery-orientation of three mental health units
Authors: Bass Hollie , Tickle Anna , Lewis Nicholas
Published: October 2014

Purpose

– The purpose of this paper is to measure service user and staff views of the recovery orientation of three mental health rehabilitation units; two “open” and one “locked”. It identified elements of recovery that were important to service users. It measured the units’ performance on domains of recovery, attending to differences between staff members’ and service users’ perceptions and between the locked and open units.

Design/methodology/approach

– A cross-sectional design was used. Staff and service users completed the “Developing Recovery Enhancing Environment Measure (DREEM)”.

Findings

– Findings revealed some differences between staff and service user views. Service users in the locked unit reported the organisational climate to be more recovery oriented on some domains than those in the open units. Service users’ responses highlighted potential areas for service improvement.

Research limitations/implications

– The sample was small but reflected the applied setting. Some service users were not invited to participate because of significant communication or cognitive difficulties and it is recognised that they may have had alternative views that remain unrepresented.

Practical implications

– The DREEM provided valuable information about current practice and potential for service development. Both locked and open units can provide recovery-oriented environments. Services should be aware of discrepant views between staff and service users.

Originality/value

– To the knowledge, this is the first study to use the DREEM to evaluate the recovery orientation of a locked recovery unit and to compare locked and unlocked units.