bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic relationships reveal significant dominance effects for growth in hybridEucalyptus
Authors: Tan Biyue , Grattapaglia Dario , Wu Harry X. , Ingvarsson Pär K. 
Published: August 2017

AbstractNon-additive genetic effects can be effectively exploited in control-pollinated families with the availability of genome-wide markers. We used 41,304 SNP markers and compared pedigreevs.marker-based genetic models by analysing height, diameter, basic density and pulp yield for 338Eucalyptus urophyllaxE.grandiscontrol-pollinated families represented by 949 informative individuals. We evaluated models accounting for additive, dominance, and first-order epistatic interactions (additive by additive, dominance by dominance, and additive by dominance). We showed that the models can capture a large proportion of the genetic variance from dominance and epistasis for growth traits as those components are typically not independent. We also show that we could partition genetic variances more precisely when using relationship matrices derived from markers compared to using only pedigree information. In addition, phenotypic prediction accuracies were only slightly increased by including dominance effects for growth traits since estimates of non-additive variances yielded rather high standard errors. This novel result improves our current understanding of the architecture of quantitative traits and recommends accounting for dominance variance when developing genomic selection strategies in hybridEucalyptus.
Oxytocin Signaling in the Medial Amygdala is required for Sex Discrimination of Social Cues
Authors: Yao Shenqin , Bergan Joseph , Lanjuin Anne , Dulac Catherine 
Published: August 2017

AbstractThe neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single unit recording in the MeA uncovered significant changes in the sensory representation of conspecific cues in the absence of oxytocin signaling. Finally, acute manipulation of oxytocin signaling in adults is sufficient to alter social interaction preferences in males as well as responses of MeA neurons to chemosensory cues. These results uncover the critical role of oxytocin signaling in a molecularly defined neuronal population in order to modulate the behavioral and physiological responses of male mice to females on a moment-to-moment basis.
Biofilm formation and toxin production provide a fitness advantage in mixed colonies of natural yeast isolates
Authors: Deschaine Bernadette M. , Heysel Angela R. , Lenhart Adam , Murphy Helen A. 
Published: August 2017

AbstractMicrobes exist in complex communities and can engage in social interactions ranging from cooperation to warfare. Biofilms are structured, cooperative microbial communities; they are pervasive and ancient, representing the first fossilized life. Like all cooperative communities, biofilms are susceptible to invasion by selfish individuals who benefit from cooperation, but do not contribute. The ubiquity of biofilms therefore poses a challenge to evolutionary theory. One hypothesis for biofilm stability is spatial structure: patches of related cooperative cells are able to outcompete unrelated cells. These dynamics have been explored computationally and in bacterial systems; however, their relevance to eukaryotic microbes remains an open question. Here, we investigate the interactions of environmental yeast isolates with different social phenotypes. Our results show that biofilm strains spatially exclude non-biofilm strains, and that biofilm spatial structure confers a consistent and robust fitness advantage in direct competition. We also find that biofilms protect against killer toxin, a warfare phenotype. During biofilm formation, cells are susceptible to toxin from nearby competitors; however, increased spatial use by biofilms provides an escape from toxin-producers. Our results suggest that yeast biofilms represent a competitive strategy, and that principles elucidated for the evolution and stability of bacterial biofilms may apply to eukaryotes.
Systemic HIV-1 Infection Produces a Unique Glial Footprint in Humanized Mouse Brains
Authors: Li Weizhe , Gorantla Santhi , Gendelman Howard E. , Poluektova Larisa Y. 
Published: August 2017

AbstractStudies of innate glial cell responses for progressive human immunodeficiency virus type one (HIV-1) infection are hindered by the availability of relevant small-animal models. To overcome this hindrance, a mouse model reconstituted with humanized brain and immune systems was created. Newborn NOD/SCID/IL2Rγc-/-mice of both sexes were transplanted with human neuroglial progenitors (NPC) and hematopoietic stem cells. Intraventricular injection of NPC yielded an anatomical symmetrical glia (human astrocyte and oligodendrocyte) repopulation of the mouse brain. The human glia were observed in periventricular areas, white matter tracts, the olfactory bulb and brain stem. HIV-1 infection of these dual humanized mice led to meningeal and perivascular human leukocyte infiltration into brain. The species-specific viral-neuroimmune interactions in the infected animals were identified by deep RNA sequencing. In the corpus callosum and hippocampus overlapping human-specific transcriptional alterations were seen for interferon type 1 and 2 signaling pathways (STAT1, 2, IRF9, ISG15, IFI6) and a range of host antiviral responses (MX1, OAS1, RSAD2, BST2, SAMHD1)in infected animals. Glial cytoskeleton reorganization, oligodendrocyte differentiation and myelin ensheathment (MBP, MOBP, PLP1, MAGandZNF488) were downregulated. The data sets were confirmed by real-time PCR. The viral defense signaling patterns observed in these mice parallels the neuroimmune communication networks present in the HIV-1 infected human brain. In this manner, the new mouse model can facilitate discovery of therapeutics, viral eradication targets for virus induced nervous system diseases, and simplify HIVCure research approaches.Summary StatementWe created mice with both a humanized brain and an immune system. The animals were used to investigate glial responses to HIV-1 infection. At a transcriptional level we defined the interactions between human glia and immune cells in the presence of the systemic HIV-1 infection. Noticeably, altered transcriptional changes were human specific. At five weeks after viral infection humanized mouse brain displayed potent interferon-mediated antiviral innate immune responses and alteration of neuronal progenitors differentiation and myelination. This model can be used to tests both diagnostic and therapeutic interventions for cure HIV-associated brain impairment.
Pathogen-Host Analysis Tool (PHAT): an Integrative Platform to Analyze Pathogen-Host Relationships in Next-Generation Sequencing Data
Authors: Gibb Christopher M. , Jackson Robert , Mohammed Sabah , Fiaidhi Jinan , Zehbe Ingeborg 
Published: August 2017

AbstractSummaryThe Pathogen-Host Analysis Tool (PHAT) is an application for processing and analyzing next-generation sequencing (NGS) data as it relates to relationships between pathogen and host organisms. Unlike custom scripts and tedious pipeline programming, PHAT provides an integrative platform encompassing raw and aligned sequence and reference file input, quality control (QC) reporting, alignment and variant calling, linear and circular alignment viewing, and graphical and tabular output. This novel tool aims to be user-friendly for life scientists studying diverse pathogen-host relationships.Availability and ImplementationThe project is publicly available on GitHub (https://github.com/chgibb/PHAT) and includes convenient installers, as well as portable and source versions, for both Windows and Linux (Debian and RedHat). Up-to-date documentation for PHAT, including user guides and development notes, can be found athttps://chgibb.github.io/PHATDocs/. We encourage users and developers to provide feedback (error reporting, suggestions, and comments) using GitHub Issues.ContactLead software developer:chris.gibb@outlook.com
Extraordinary Self-Sacrifice
Authors: Krupp D.B. 
Published: August 2017

AbstractTheories of self-sacrifice ordinarily assume that actors will have larger fitness effects on recipients than on themselves. There are, however, conditions in which actors can pay costs that exceed the altruistic benefits they provide or the spiteful costs they impose. In a spatially structured population, I show that such “extraordinary” self-sacrifice evolves when actors use information about kinship and dispersal to maximize inclusive fitness. The result can be described by a simple rule: extraordinary self-sacrifice evolves when the actor’s neighbors are kin and the recipient’s neighbors are not.
Recurring infection with ecologically distinct human papillomavirus (HPV) types explains high prevalence and diversity
Authors: Ranjeva Sylvia , Baskerville Edward B. , Dukic Vanja , Villa Luisa , Lazcano-Ponce Eduardo , Giuliano Anna , Dwyer Greg , Cobey Sarah 
Published: August 2017

AbstractThe high prevalence of human papillomavirus (HPV), the most common sexually transmitted infection, arises from the coexistence of over 200 genetically distinct types. Accurately predicting the impact of vaccines that target multiple types requires understanding the factors that determine HPV diversity. The diversity of many pathogens is driven by type-specific or “homologous” immunity, which promotes the spread of variants to which hosts have little immunity. To test for homologous immunity and to identify mechanisms determining HPV transmission, we fitted nonlinear mechanistic models to longitudinal data on genital infections in unvaccinated men. Our results provide no evidence for homologous immunity, instead showing that infection with one HPV type strongly increases the risk of infection with that type for years afterwards. For HPV16, the type responsible for most HPV-related cancers, an initial infection increases the one-year probability of reinfection by 20-fold, and the probability of reinfection remains 14-fold higher two years later. This increased risk occurs in both sexually active and celibate men, suggesting that it arises from auto-inoculation, episodic reactivation of latent virus, or both. Overall our results show that high HPV prevalence and diversity can be explained by a combination of a lack of homologous immunity, frequent reinfections, weak competition between types, and variation in type fitness between host subpopulations. Due to the high risk of reinfection, vaccinating boys that have not yet been exposed may be crucial to reduce prevalence, but our results suggest that there may also be large benefits from vaccinating previously infected individuals.
Gymnastics between school desks
Authors: Brunelli Marta , Meda Juri 
Published: August 2017

Purpose
The purpose of this paper is to explore the evolution and use of the school desk in unified Italy as a multifunctional and highly efficient tool, which was required not only to efficiently support in-class activities, to facilitate the classroom management and finally to maintain a correct body posture in order to preserve pupils’ health, but also to accomplish the additional task of working as real “gymnastic equipment”, i.e. suitable for performing various gymnastic exercises inside the classroom.

Design/methodology/approach
The assumption upon which this paper rests is that school desks have always been signifiers charged with multiple meanings related to the evolution of curriculum, pedagogic ideas and daily school practices, which have often been forgotten, abandoned or, for some reasons, underrepresented in the official history of education as well as in the collective memory of school. In order to rebuild this forgotten history, and retrace the possible theoretical-pedagogical basis underlying such practice, the authors have systematically reviewed the Italian manuals on gymnastics between desks from the 1870s to the 1970s, retraced sources documenting this practice in the daily school life (government rules, school programmes, school hygiene prescriptions, iconographic sources, teachers and school managers’ testimonies) and finally, compared with other foreign practices (such as “calisthenics”).

Findings
The convergence between many differentiated sources has demonstrated the longevity of this school practice, which was not only the fruit of educational theories of gymnastic teachers but was also determined by the backwardness and logistic inadequacies of many Italian schools. The paper reveals how this gymnastic practice, after establishing itself in the post-Unification Italian schools, continued almost uninterrupted until the Second World War and even until the 1970s, evidencing how gymnastic teachers, hygienists, educationalists and lawmakers continued, over almost a century, to scientifically legitimise (from the top downwards) an educational practice that was actually driven from the bottom upwards, i.e. determined by an endemic lack of adequate spaces and tools for physical education in Italian schools.

Originality/value
For the very first time, the special source of Italian manuals and booklets on gymnastics between desks has been located, analysed and systematically reviewed for the period 1870s-1970s, and then cross-checked against differentiated sources. This study actually represents the first step of a research which must be still further developed. Undoubtedly, the “new” source represented by the manuals of “gymnastics between school desks” offered a first original perspective from which to explore the use of this furniture in the school of the past, thereby enabling historians of education to shed the first light on a school practice that has been overlooked or forgotten, and still hidden within the “black box of schooling”.
The Economic Consequences of Perk Disclosure
Authors: Grinstein Yaniv , Weinbaum David , Yehuda Nir 
Published: August 2017

AbstractIn December 2006, the SEC issued new rules requiring enhanced disclosure by public U.S. firms of perquisites granted to their executives. The rules applied to perquisites granted in fiscal year 2006 and thereafter. Because the rules were implemented quickly, the perks disclosed for 2006 reflect the arrangements firms made under prior disclosure rules: firms could not revise perks to reflect the new rules until 2007. For firms that disclose for the first time in 2006, we predict and find that perks decrease in 2007, reflecting both the costs of increased disclosure and enhanced monitoring. This decrease in perks is offset by higher levels of non‐perk compensation, however. We also predict and find that the effect of perk disclosure by formerly non‐disclosing firms in 2006 leads to higher perks in 2007 for firms that were disclosing perks prior to the rule change.
Role of surface electrocardiogram precordial leads in localizing different anatomic sites of ectopic atrial tachycardia arising from lower right atrium in pediatric population
Authors: Allam Lamyaa Elsayed , Ahmed Rania Samir , Ghanem Mazen Tawfik 
Published: August 2017

BackgroundThe study was designed to examine P wave morphology (PWM) in precordial leads (V1–V6) during ectopic atrial tachycardia (EAT) originating from low right atrium (RA) to identify the anatomic sites of these foci in children.MethodsTwenty‐three consecutive pediatric patients (56% females, mean age 8.5 ± 2.5) with EAT originating from the low RA underwent detailed atrial endocardial activation mapping and radiofrequency ablation. PWM during EAT was analyzed using standard 12‐lead ECG in relation to successful ablation sites in RA.ResultsEctopic atrial tachycardia originated from coronary sinus ostium (CSo) in 12 patients, nonseptal tricuspid annulus (TA) in five, lower crista terminalis (CT) in three and lower free wall in three. In lead V1, PWM showed a positive pattern during EAT originating from CSo (8/12) [91.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), 100% negative predictive value (NPV)]. A negative pattern was observed in EAT originating from lower free wall (1/3) and nonseptal TA (5/5) [50% sensitivity, 100% specificity, 100% PPV, 75% NPV], while isoelectric pattern was in EAT originating from lower CT (3/3) [100% sensitivity, 100% specificity, 100% PPV, 100% NPV]. In leads V3–V6, PWM showed a negative pattern in at least two consecutive leads during EAT from CSo (12/12), nonseptal TA (5/5) and lower free wall (3/3) while it was positive in EAT originating from lower CT (3/3) [100% sensitivity, 95% specificity, 75% PPV and 100% NPV].ConclusionsP wave morphology in precordial leads can help differentiate the anatomic sites of EAT from lower RA with high PPVs and NPVs.
Autophagic dysfunction and autophagosome escape in the mdx mus musculus model of Duchenne muscular dystrophy
Authors: Spaulding H. R. , Kelly E. M. , Quindry J. C. , Sheffield J. B. , Hudson M. B. , Selsby J. T. 
Published: August 2017

AbstractAimDuchenne muscular dystrophy is caused by the absence of functional dystrophin protein and results in a host of secondary effects. Emerging evidence suggests that dystrophic pathology includes decreased pro‐autophagic signalling and suppressed autophagic flux in skeletal muscle, but the relationship between autophagy and disease progression is unknown. The purpose of this investigation was to determine the extent to which basal autophagy changes with disease progression. We hypothesized that autophagy impairment would increase with advanced disease.MethodsTo test this hypothesis, 7‐week‐old and 17‐month‐old dystrophic diaphragms were compared to each other and age‐matched controls.ResultsChanges in protein markers of autophagy indicate impaired autophagic stimulation through AMPK, however, robust pathway activation in dystrophic muscle, independent of disease severity. Relative protein abundance of p62, an inverse correlate of autophagic degradation, was dramatically elevated with disease regardless of age. Likewise, relative protein abundance of Lamp2, a lysosome marker, was decreased twofold at 17 months of age in dystrophic muscle and was confirmed, along with mislocalization, in histological samples, implicating lysosomal dysregulation in this process. In dystrophic muscle, autophagosome‐sized p62‐positive foci were observed in the extracellular space. Moreover, we found that autophagosomes were released from both healthy and dystrophic diaphragms into the extracellular environment, and the occurrence of autophagosome escape was more frequent in dystrophic muscle.ConclusionThese findings suggest autophagic dysfunction proceeds independent of disease progression and blunted degradation of autophagosomes is due in part to decreased lysosome abundance, and contributes to autophagosomal escape to the extracellular space.
Population pharmacokinetic meta‐analysis of ramucirumab in cancer patients
Authors: O'Brien Lisa , Westwood Paul , Gao Ling , Heathman Michael 
Published: August 2017

AimsRamucirumab is a human IgG1 monoclonal antibody that specifically binds vascular endothelial growth factor receptor‐2 (VEGFR‐2) and blocks binding of VEGF‐A, VEGF‐C and VEGF‐D. The objective of the analysis was to characterize the clinical pharmacology profile of ramucirumab using a population pharmacokinetic approach.MethodsA total of 1639 patients with 6427 serum concentrations from 11 Phase 1b, 2 and 3 clinical trials in patients with various cancer indications were included in the analysis. Ramucirumab was administered as an intravenous infusion over 1 h at 8 mg kg−1 every 2 weeks or 10 mg kg−1 every 3 weeks. A series of pharmacostatistical models were developed to describe the concentration data. The best model was used to evaluate patient factors for their effect on ramucirumab pharmacokinetics.ResultsThe pharmacokinetics of ramucirumab were well characterized by a two‐compartment model. Mean population estimates of clearance, volume of distribution and half‐life for a typical 68‐kg patient were 0.0148 l h−1, 5.30 l and 13.4 days, respectively. A modest relationship was observed between body weight and ramucirumab disposition; clearance and central compartment volume increased with body weight. No other patient characteristics were shown to influence the disposition of ramucirumab in this patient population.ConclusionsThe final model adequately described the concentration–time profile of ramucirumab in patients with a range of cancer indications. The model confirmed that a weight‐normalized dosing regimen is appropriate for ramucirumab therapy. Dose adjustment was not required for patients with mild to moderate renal impairment or mild hepatic impairment.
Hippocampal sclerosis, hippocampal neuron loss patterns and TDP‐43 in the aged population
Authors: Hokkanen Suvi R. K. , Hunter Sally , Polvikoski Tuomo M. , Keage Hannah A. D. , Minett Thais , Matthews Fiona E. , Brayne Carol ,   MRC CFAS and CC75C Study Group
Published: August 2017

AbstractHippocampal neuron loss is a common neuropathological feature in old age with various underlying etiologies. Hippocampal sclerosis of aging (HS‐Aging) is neuropathologically characterized by severe CA1 neuronal loss and frequent presence of transactive response DNA‐binding protein of 43 kDa (TDP‐43) aggregations. Its etiology is unclear and currently no standardized approaches to measure HS‐Aging exist. We developed a semi‐quantitative protocol, which captures various hippocampal neuron loss patterns, and compared their occurrence in the context of HS‐Aging, TDP‐43, vascular and tau pathology in 672 brains (TDP‐43 staining n = 642/672, 96%) donated for the population‐based Cambridge City over‐75s Cohort and the Cognitive Function and Ageing Study. HS‐Aging was first evaluated independently from the protocol using the most common criteria defined in literature, and then described in detail through examination of neuron loss patterns and associated pathologies. 34 (5%) cases were identified, with a maximum of five pyramidal neurons in each of over half CA1 fields‐of‐view (x200 magnification), no vascular damage, no neuron loss in CA2‐CA4, but consistent TDP‐43 neuronal solid inclusions and neurites. We also report focal CA1 neuron loss with vascular pathology to affect predominantly CA1 bordering CA2 (Fisher's exact, P = 0.009), whereas neuron loss in the subicular end of CA1 was associated with TDP‐43 inclusions (Fisher's exact, P < 0.001) and high Braak stage (Fisher's exact, P = 0.001). Hippocampal neuron loss in CA4‐CA2 was not associated with TDP‐43. We conclude that hippocampal neuron loss patterns are associated with different etiologies within CA1, and propose that these patterns can be used to form objective criteria for HS‐Aging diagnosis. Finally, based on our results we hypothesize that neuron loss leading to HS‐Aging starts from the subicular end of CA1 when it is associated with TDP‐43 pathology, and that this neurodegenerative process is likely to be significantly more common than “end‐stage” HS‐Aging only.