bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Coalescent Model of a Sweep from a Uniquely Derived Standing Variant
Authors: Berg Jeremy J. , Coop Graham 
Published: May 2015

AbstractThe use of genetic polymorphism data to understand the dynamics of adaptation and identify the loci that are involved has become a major pursuit of modern evolutionary genetics. In addition to the classical “hard sweep” hitchhiking model, recent research has drawn attention to the fact that the dynamics of adaptation can play out in a variety of different ways, and that the specific signatures left behind in population genetic data may depend somewhat strongly on these dynamics. One particular model for which a large number of empirical examples are already known is that in which a single derived mutation arises and drifts to some low frequency before an environmental change causes the allele to become beneficial and sweeps to fixation. Here, we pursue an analytical investigation of this model, bolstered and extended via simulation study. We use coalescent theory to develop an analytical approximation for the effect of a sweep from standing variation on the genealogy at the locus of the selected allele and sites tightly linked to it. We show that the distribution of haplotypes that the selected allele is present on at the time of the environmental change can be approximated by considering recombinant haplotypes as alleles in the infinite alleles model. We show that this approximation can be leveraged to make accurate predictions regarding patterns of genetic polymorphism following such a sweep. We then use simulations to highlight which sources of haplotypic information are likely to be most useful in distinguishing this model from neutrality, as well as from other sweep models, such as the classic hard sweep, and multiple mutation soft sweeps. We find that in general, adaptation from a uniquely derived standing variant will be difficult to detect on the basis of genetic polymorphism data alone, and when it can be detected, it will be difficult to distinguish from other varieties of selective sweeps.
Dynamic effects of extrinsic noise in a simple oscillatory gene network with delayed negative-feedback regulation: an electronic modeling approach
Authors: Santillán Moisés 
Published: May 2015

AbstractGene expression is intrinsically stochastic due to the small number of molecules involved in some of the underlying biochemical reactions. The resulting molecule-count random fluctuations are known as biochemical noise. The dynamic effects of intrinsic noise (that originated within the system) have been widely studied. However, the effects of the noise coming from other sources the system is in contact with, or extrinsic noise, is not so well understood. In this work we introduce an electronic model for a simple gene oscillatory network, with delayed negative-feedback regulation. Notably, this model accounts for the intrinsic biochemical noise due to the slow promoter switching between the active and inactive states; but dismisses biochemical noise due to mRNA and protein production and degradation. We characterize the oscillatory behavior of this gene network by varying all the relevant parameter values within biologically meaningful ranges. Finally, we investigate how different sources of extrinsic noise affect the system dynamic behavior. To simulate extrinsic noise we consider stochastic time series coming from another circuit simulating a gene network. Our results indicate that, depending on the parameter affected by extrinsic noise and the power spectra of the stochastic time series, the system quasi-periodic behavior is affected in different ways.
Consistent inter-protocol differences in resting-state functional connectomes between normal aging and mild cognitive impairment
Authors: Tam Angela , Dansereau Christian , Badhwar AmanPreet , Orban Pierre , Belleville Sylvie , Chertkow Howard , Dagher Alain , Hanganu Alexandru , Monchi Oury , Rosa-Neto Pedro , Shmuel Amir , Wang Seqian , Breitner John , Bellec Pierre ,   Alzheimer’s Disease Neuroimaging Initiative
Published: May 2015

AbstractResting-state functional connectivity is a promising biomarker for Alzheimer’s disease. However, previous resting-state functional magnetic resonance imaging studies in Alzheimer’s disease and mild cognitive impairment (MCI) have shown limited reproducibility as they have had small sample sizes and substantial variation in study protocol. We sought to identify functional brain networks and connections that could consistently discriminate normal aging from MCI despite variations in scanner manufacturer, imaging protocol, and diagnostic procedure. We therefore pooled four independent datasets, including 112 healthy controls and 143 patients with MCI, systematically testing multiple brain connections for consistent differences. The largest effects associated with MCI involved the ventromedial and dorsomedial prefrontal cortex, striatum, and middle temporal lobe. Compared with controls, patients with MCI exhibited significantly decreased connectivity within the frontal lobe, between frontal and temporal areas, and between regions of the cortico-striatal-thalamic loop. Despite the heterogeneity of methods among the four datasets, we identified robust MCI-related connectivity changes with small to medium effect sizes and sample size estimates recommending a minimum of 150 to 400 total subjects to achieve adequate statistical power. If our findings can be replicated and associated with other established biomarkers of Alzheimer’s disease (e.g. amyloid and tau quantification), then these functional connections may be promising candidate biomarkers for Alzheimer’s disease.
Endless Forms Most Beau-toe-ful: Evolution of the Human Hallux
Authors: Throckmorton Zachary 
Published: May 2015

AbstractBackgroundThe adduction of the first pedal ray in humans, such that the hallux is incapable of functional opposability, is a major feature of the evolution of the hominin foot (e.g. Darwin 1872, Haeckel 1879, Latimer and Lovejoy 1990). While hallucal adduction facilitates obligate bipedalism, it inhibits but does not eliminate arboreal grasping ability. The angle of the hallux (as determined by the longitudinal axis of the first metatarsal) relative to the rest of the foot (as determined by the longitudinal axis of the second metatarsal) is a product of both hard-and soft-tissues. Given the failure of soft tissue to fossilize, direct evidence for hallucal angle evolution is scanty, and consensus has not emerged as to when and how the modern human condition of hallucal non-opposability evolved.Methodology/Principal FindingsAnalysis of a large sample (n = 331) of radiographs taken from the dorsal aspect of living human feet elucidates the relationship between osteological measures and the magnitude of hallucal adduction, which is resultant of both hard-and soft-tissue anatomy (Lovejoyet al.2009). I describe the correlation of hallucal convergence with first metatarsal posterior articular facet morphology, which allows inference of hallucal convergence in the absence of the medial cuneiform. I report parameters of modern human hallucal convergence variation and offer insight into the hominin fossil record. I infer that the hallucal convergence of the recently reported specimen from Burtele (BRT-VP-2/73) falls within the range of living human variation, inconsistent with the interpretation that this hominin retained the ability to oppose its great toe for the purpose of arboreal locomotion (Haile-Selassieet al. 2012). Of the fossil hominin first metatarsals surveyed, all fall within the range of living human variation, consistent with previous research on medial cuneiform (McHenry and Jones 2006) and first metatarsal (Berillon 1999) morphology.Conclusions/SignificanceThis study finds that the modern human condition of hallucal non-opposability was present in the genusAustralopithecus. However, while the Burtele specimen (BRT-VP-2/73) falls within the range of living human variation, it displays a markedly divergent hallux compared to most living humans. This study suggests that, as in humans today, there was variation in hallucal divergence in Plio-Pleistocene hominins. Rather than using the terms ‘opposability’ and the ambiguously synonymous ‘grasping,’ I suggest here the term ‘clamping’ (as in the motion performed by a clamp) be used to describe the less powerful and less dexterous ability of modern humans to place and hold a thin, narrow object between the great toe and second toe ray in a limited, albeit functional, manner.
A Perspective on Interaction Tests in Genetic Association Studies
Authors: Aschard Hugues 
Published: May 2015

AbstractThe identification of gene-gene and gene-environment interaction in human traits and diseases is an active area of research that generates high expectation, and most often lead to high disappointment. This is partly explained by a misunderstanding of some of the inherent characteristics of interaction effects. Here, I untangle several theoretical aspects of standard regression-based interaction tests in genetic association studies. In particular, I discuss variables coding scheme, interpretation of effect estimate, power, and estimation of variance explained in regard of various hypothetical interaction patterns. I show first that the simplest biological interaction models—in which the magnitude of a genetic effect depends on a common exposure—are among the most difficult to identify. Then, I demonstrate the demerits of the current strategy to evaluate the contribution of interaction effects to the variance of quantitative outcomes and argue for the use of new approaches to overcome these issues. Finally I explore the advantages and limitations of multivariate models when testing for interaction between multiple SNPs and/or multiple exposures, using either a joint test, or a test of interaction based on risk score. Theoretical and simulated examples presented along the manuscript demonstrate that the application of these methods can provide a new perspective on the role of interaction in multifactorial traits.
The effects of time-varying temperature on delays in genetic networks
Authors: Gomez Marcella M. , Murray Richard M. , Bennett Matthew R. 
Published: May 2015

AbstractDelays in gene networks result from the sequential nature of protein assembly. However, it is unclear how models of gene networks that use delays should be modified when considering time-dependent changes in temperature. This is important, as delay is often used in models of genetic oscillators that can be entrained by periodic fluctuations in temperature. Here, we analytically derive the time dependence of delay distributions in response to time-varying temperature changes. We find that the resulting time-varying delay is nonlinearly dependent on parameters of the time-varying temperature such as amplitude and frequency, therefore, applying an Arrhenius scaling may result in erroneous conclusions. We use these results to examine a model of a synthetic gene oscillator with temperature compensation. We show that temperature entrainment follows from the same mechanism that results in temperature compensation. Under a common Arrhenius scaling alone, the frequency of the oscillator is sensitive to changes in the mean temperature but robust to changes in the frequency of a periodically time-varying temperature. When a mechanism for temperature compensation is included in the model, however, we show that the oscillator is entrained by periodically varying temperature even when maintaining insensitivity to the mean temperature.
Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes
Authors: Henn Brenna M. , Botigué Laura R. , Peischl Stephan , Dupanloup Isabelle , Lipatov Mikhail , Maples Brian K. , Martin Alicia R. , Musharoff Shaila , Cann Howard , Snyder Michael , Excoffier Laurent , Kidd Jeffrey M. , Bustamante Carlos D. 
Published: May 2015

AbstractThe Out-of-Africa (OOA) dispersal ~50,000 years ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from 7 geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.
Genomic epidemiology of the current wave of artemisinin resistant malaria
Authors: Amato Roberto , Miotto Olivo , Woodrow Charles , Almagro-Garcia Jacob , Sinha Ipsita , Campino Susana , Mead Daniel , Drury Eleanor , Kekre Mihir , Sanders Mandy , Amambua-Ngwa Alfred , Amaratunga Chanaki , Amenga-Etego Lucas , Anderson Tim J C , Andrianaranjaka Voahangy , Apinjoh Tobias , Ashley Elizabeth , Auburn Sarah , Awandare Gordon A , Baraka Vito , Barry Alyssa , Boni Maciej F , Borrmann Steffen , Bousema Teun , Branch Oralee , Bull Peter C , Chotivanich Kesinee , Conway David J , Craig Alister , Day Nicholas P , Djimdé Abdoulaye , Dolecek Christiane , Dondorp Arjen M , Drakeley Chris , Duffy Patrick , Echeverri-Garcia Diego F , Egwang Thomas G , Fairhurst Rick M , Faiz Abul , Fanello Caterina I , Hien Tran Tinh , Hodgson Abraham , Imwong Mallika , Ishengoma Deus , Lim Pharath , Lon Chanthap , Marfurt Jutta , Marsh Kevin , Mayxay Mayfong , Mobegi Victor , Mokuolu Olugbenga , Montgomery Jacqui , Mueller Ivo , Kyaw Myat Phone , Newton Paul N , Nosten Francois , Noviyanti Rintis , Nzila Alexis , Ocholla Harold , Oduro Abraham , Onyamboko Marie , Ouedraogo Jean-Bosco , Phyo Aung Pyae , Plowe Christopher V , Price Ric N , Pukrittayakamee Sasithon , Randrianarivelojosia Milijaona , Ringwald Pascal , Ruiz Lastenia , Saunders David , Shayo Alex , Siba Peter , Takala-Harrison Shannon , Thanh Thuy-Nhien Nguyen , Thathy Vandana , Verra Federica , White Nicholas J , Htut Ye , Cornelius Victoria J , Giacomantonio Rachel , Muddyman Dawn , Henrichs Christa , Malangone Cinzia , Jyothi Dushyanth , Pearson Richard D , Rayner Julian C , McVean Gilean , Rockett Kirk , Miles Alistair , Vauterin Paul , Jeffery Ben , Manske Magnus , Stalker Jim , MacInnis Bronwyn , Kwiatkowski Dominic P ,   MalariaGEN Plasmodium falciparum Community Project
Published: May 2015

AbstractArtemisinin resistantPlasmodium falciparumis advancing across Southeast Asia in a soft selective sweep involving at least 20 independentkelch13mutations. In a large global survey, we find thatkelch13mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that Africankelch13mutations have originated locally, and thatkelch13shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus,kelch13is not currently undergoing strong selection in Africa, despite a deep reservoir of standing variation that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely onkelch13data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.
Determining Exon Connectivity in Complex mRNAs by Nanopore Sequencing
Authors: Bolisetty Mohan T. , Rajadinakaran Gopinath , Graveley Brenton R. 
Published: May 2015

AbstractThough powerful, short-read high throughput RNA sequencing is limited in its ability to directly measure exon connectivity in mRNAs containing multiple alternative exons located farther apart than the maximum read lengths. Here, we use the Oxford Nanopore MinION™sequencer to identify 7,899 ‘full-length’ isoforms expressed from fourDrosophilagenes,Dscam1,MRP,Mhc, andRdl. These results demonstrate that nanopore sequencing can be used to deconvolute individual isoforms and that it has the potential to be an important method for comprehensive transcriptome characterization.
Regulation of Jasmonate-Mediated Stamen Development and Seed Production by a bHLH-MYB Complex in Arabidopsis
Authors: Qi Tiancong , Huang Huang , Song Susheng , Xie Daoxin 
Published: May 2015

Abstract
Stamens are the plant male reproductive organs essential for plant fertility. Proper development of stamens is modulated by environmental cues and endogenous hormone signals. Deficiencies in biosynthesis or perception of the phytohormone jasmonate (JA) attenuate stamen development, disrupt male fertility, and abolish seed production in Arabidopsis thaliana. This study revealed that JA-mediated stamen development and seed production are regulated by a bHLH-MYB complex. The IIIe basic helix-loop-helix (bHLH) transcription factor MYC5 acts as a target of JAZ repressors to function redundantly with other IIIe bHLH factors such as MYC2, MYC3, and MYC4 in the regulation of stamen development and seed production. The myc2 myc3 myc4 myc5 quadruple mutant exhibits obvious defects in stamen development and significant reduction in seed production. Moreover, these IIIe bHLH factors interact with the MYB transcription factors MYB21 and MYB24 to form a bHLH-MYB transcription complex and cooperatively regulate stamen development. We speculate that the JAZ proteins repress the bHLH-MYB complex to suppress stamen development and seed production, while JA induces JAZ degradation and releases the bHLH-MYB complex to subsequently activate the expression of downstream genes essential for stamen development and seed production.
The Arabidopsis R-SNARE VAMP721 Interacts with KAT1 and KC1 K+ Channels to Moderate K+ Current at the Plasma Membrane
Authors: Zhang Ben , Karnik Rucha , Wang Yizhou , Wallmeroth Niklas , Blatt Michael R. , Grefen Christopher 
Published: May 2015

Abstract
SNARE (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptor) proteins drive vesicle traffic, delivering membrane and cargo to target sites within the cell and at its surface. They contribute to cell homeostasis, morphogenesis, and pathogen defense. A subset of SNAREs, including the Arabidopsis thaliana SNARE SYP121, are known also to coordinate solute uptake via physical interactions with K+ channels and to moderate their gating at the plasma membrane. Here, we identify a second subset of SNAREs that interact to control these K+ channels, but with opposing actions on gating. We show that VAMPs (vesicle-associated membrane proteins), which target vesicles to the plasma membrane, also interact with and suppress the activities of the inward-rectifying K+ channels KAT1 and KC1. Interactions were evident in yeast split-ubiquitin assays, they were recovered in vivo by ratiometric bimolecular fluorescence complementation, and they were sensitive to mutation of a single residue, Tyr-57, within the longin domain of VAMP721. Interaction was also recovered on exchange of the residue at this site in the homolog VAMP723, which normally localizes to the endoplasmic reticulum and otherwise did not interact. Functional analysis showed reduced channel activity and alterations in voltage sensitivity that are best explained by a physical interaction with the channel gates. These actions complement those of SYP121, a cognate SNARE partner of VAMP721, and lead us to propose that the channel interactions reflect a “hand-off” in channel control between the two SNARE proteins that is woven together with vesicle fusion.
Pathogenesis and association of Mycoplasma pneumoniae infection with cardiac and hepatic damage
Authors: Fan Qing , Meng Jun , Li Peijie , Liu Zhigang , Sun Ying , Yan Ping 
Published: May 2015

ABSTRACTThe aim of this study was to investigate the pathogenesis of Mycoplasma pneumoniae (MP) infection and its association with cardiac and hepatic damage. Between March 2013 and March 2014, 59 children with MP pneumonia (MPP) and 30 healthy children were enrolled. Serum titers of TLR4, T cell immunoglobulin and mucin‐domain (TIM) 3, IL‐10, TNF‐α, and IFN‐γ were measured both in children with MPP and healthy children. Additionally, MP‐specific antibody titer and creatine kinase‐MB (CK‐MB), and alanine transaminase (ALT) titers were measured in patients with MPP. There were significant differences between the MPP patients and healthy controls in titers of TIM1 (P < 0.01), TLR2 (P = 0.028), TLR4 (P = 0.019), IL‐10 (P < 0.01), TNF‐α (P < 0.01) and IFN‐γ (P < 0.01); however, no significant difference was found in TIM3 titers (P = 0.8181). TIM1 was correlated with CK‐MB (P = 0.025), whereas both TIM1 and TLR2 titers were correlated with MP‐specific antibody titers (P < 0.001; P = 0.003, respectively). Additionally, there were correlations between ALT, TIM3, and TLR2 titers (P = 0.025; P = 0.037, respectively). The titers of TIM1 were significantly higher in patients with cardiac damage (P = 0.007) than in those without it, whereas the titers of TLR2 were significantly higher in patients with hepatic damage (P = 0.026) than in those without it. TLR2, TLR4 and TIM1 may be involved in the process of MP infection. Additionally, TLR2, TLR4, TIM1 and TIM3 may play particular roles in the pathogenesis of MPP‐associated cardiac and hepatic damage.
Capturing Key NANDA‐I Nursing Diagnoses From Actual Clinical Data for Patients With Heart Failure
Authors: Park Hyejin , Tucker Denise A. 
Published: May 2015

PurposeThe purpose of the study was to identify key nursing diagnoses with related factors and signs/symptoms using NANDA‐I for patients with heart failure (HF).MethodsA retrospective descriptive design was used to address the research questions. Data were obtained from the records of patients discharged for 1 year with the medical diagnoses of HF from a Midwestern community hospital. A total of 272 inpatient records were analyzed to describe the frequency and percentage of NANDA‐I diagnosis with related factors and signs/symptoms.ResultsThe top 10 NANDA‐I diagnoses associated with related factors and signs/symptoms were identified.ConclusionFurther research related to standardized nursing terminologies such as NANDA‐I using large clinical databases from health information systems is needed to support evidence‐based nursing diagnosis decision making.
Respiratory Nursing Diagnoses: Presenting Evidence for Identification of the Defining Characteristics in Neonatal and Pediatric Populations
Authors: Avena Marta J. , da Luz Gonçalves Pedreira Mavilde , Herdman T. Heather , Gutiérrez Maria G. R. 
Published: May 2015

PurposeTo identify and summarize clinical data supporting selection of nursing diagnoses related to the respiratory system for pediatric and neonatal populations.MethodA literature review conducted in indexed publications was used.FindingsThe final sample consisted of 13 studies conducted in children with cardiac disease, respiratory infection, and asthma with nursing diagnoses such as ineffective breathing pattern, impaired gas exchange, and ineffective airway clearance.ConclusionThe higher frequency defining characteristics were dyspnea, abnormal breathing pattern, use of accessory muscle to breathe, change in frequency and respiratory rate, decreased SaO2, and agitation.Implication for Nursing KnowledgeThis literature review may provide a basis for consideration of important diagnostic criteria in the pediatric population; however, clinical validation in different stages of development is critical for ensuring diagnostic accuracy.