bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey of Turkish Nurses' Knowledge of Incontinence-Associated Dermatitis
Authors: Şahin Firdevs , Karadağ Ayişe , Avşar Pınar
Published: September 2019

PURPOSE:

The purpose of this study was to determine the knowledge of incontinence-associated dermatitis (IAD) among nurses working in intensive care units.

DESIGN:

Descriptive study.

SUBJECTS AND SETTING:

The study was conducted in 6 intensive care units of a 550-bed academic research hospital in Turkey. Licensed practical and registered nurses with a minimum of a Bachelor of Science in Nursing degree employed full-time on these units were invited to participate.

METHODS:

The survey consisted of statements that examined the demographic characteristics (14 questions) and knowledge levels (59 statements) of the nurses. For each statement, nurses were required to mark only one of the following options: “correct,” “incorrect,” or “no knowledge.” Data were collected from July to September 2016. The Shapiro-Wilk test, Mann-Whitney U test, Kruskal-Wallis H test, post hoc multiple comparison test, and Spearman's correlation coefficient were used to analyze the data.

RESULTS:

Of the 126 RNs who participated in the study, 46.83% (n = 59) had an undergraduate degree in nursing. The majority (29.37%) practiced in gastroenterology surgery and urology intensive care units. The mean knowledge score was 33.05 ± 10.16 (min = 0, max = 59). The most correctly answered statement (94.44%; n = 119) was “The pH of the skin plays a role in skin barrier function.” The statement with the most incorrect or “no knowledge” answers (96.03%; n = 120) was “The natural moisturizing factor found in the structure of corneocytes helps the skin to maintain its oil levels.” Based on correctly answered statements, we found knowledge levels of the prevention and treatment of IAD were higher among nurses with a master of science degree in nursing (40.67 ± 4.32) and lower among licensed practical nursing (29.12 ± 10.08) (P < .05).

CONCLUSION:

In this study, knowledge of the nurses on identification, prevention, and treatment of IAD was low. Comprehensive basic nursing education and in-service training programs on IAD are recommended.
Functional implications of dentition-based morphotypes in piscivorous fishes
Authors: Mihalitsis Michalis , Bellwood David
Published: September 2019

Teeth are crucial in elucidating the life history of vertebrates. However, most studies of teeth have focused on mammals. In heterodont mammals, tooth function is based on tooth shape and position along the jaw. However, the vast majority of vertebrates are homodont, and tooth function might not be based on the same principles (in homodonts, tooth shape is broadly similar along the jaw). We provide a quantitative framework and establish dentition-based morphotypes for piscivorous fishes. We then assess how these morphotypes relate to key functional feeding traits. We identified three broad morphotypes: edentulate, villiform and macrodont, with edentulate and villiform species displaying considerable functional overlap; macrodont species are more distinct. When analysing macrodonts exclusively, we found a major axis of variation between ‘front-fanged’ and ‘back-fanged’ species. The functional interpretations of this axis suggest that tooth-based functional decoupling could exist, even in homodont vertebrates, where teeth have similar shapes. This diversity is based not only on tooth shape but also solely on the position along the jaw.
Experimental and numerical studies on combustion characteristics of N
2
-diluted CH
4
and O
2
diffusion combustion in a packed bed
Authors: Li Houping , Shi Junrui , Mao Mingming , Liu Yongqi
Published: September 2019

Experimental and numerical studies were conducted to determine the combustion characteristics of gas diffusion combustion in a porous combustor packed with 2.5 mm or 3.5 mm alumina pellets, special attention being focused on the effect of packed bed height (
h
) on combustion, NO and CO emissions. The pollutant emission of diffusion filtration combustion is studied with different packed bed lengths in the range of 40 mm ≤
h
≤ 240 mm, fixed excess air ratio of 1.88 and fixed gas inlet velocity of 0.06 m s
−1
. Results show that both immersed and surface flames coexist in the combustor. Although porous media enhance the mixing and diffusion processes, the diffusion flame shape is still observed from the side and top views of the combustor, and the diffusion filtration retains properties of diffusion combustion. The immersed flame is always observed with increase in
h
, whereas the height of surface flame decreases. The NO emission decreases sharply when
h
is increased from 40 mm to 120 mm. However, the NO emission decreases slightly when
h
> 120 mm. In the investigated range of
h
, it is shown that
h
has a significant influence on the CO emission, an increase in
h
leading to a constant increase in CO for the combustors packed with 2.5 mm or 3.5 mm pellets. The maximum CO emission is 662 ppm and the minimum value is 67 ppm. In the scope of this study, the temperature on the external wall of the combustor reaches 434–513°C.
Stable isotope analyses reveal unique trophic role of reef manta rays (Mobula alfredi) at a remote coral reef
Authors: Peel Lauren R. , Daly Ryan , Keating Daly Clare A. , Stevens Guy M. W. , Collin Shaun P. , Meekan Mark G.
Published: September 2019

Stable isotope analyses provide the means to examine the trophic role of animals in complex food webs. Here, we used stable isotope analyses to characterize the feeding ecology of reef manta rays (Mobula alfredi) at a remote coral reef in the Western Indian Ocean. Muscle samples ofM. alfrediwere collected from D'Arros Island and St. Joseph Atoll, Republic of Seychelles, in November 2016 and 2017. Prior to analysis, lipid and urea extraction procedures were tested on freeze-dried muscle tissue in order to standardize sample treatment protocols forM. alfredi. The lipid extraction procedure was effective at removing both lipids and urea from samples and should be used in future studies of the trophic ecology of this species. The isotopic signatures of nitrogen (δ15N) and carbon (δ13C) forM. alfredidiffered by year, but did not vary by sex or life stage, suggesting that all individuals occupy the same trophic niche at this coral reef. Furthermore, the isotopic signatures forM. alfredidiffered to those for co-occurring planktivorous fish species also sampled at D'Arros Island and St. Joseph Atoll, suggesting that the ecological niche ofM. alfrediis unique. Pelagic zooplankton were the main contributor (45%) to the diet ofM. alfredi, combined with emergent zooplankton (38%) and mesopelagic prey items (17%). Given the extent of movement that would be required to undertake this foraging strategy, individualM. alfrediare implicated as important vectors of nutrient supply around and to the coral reefs surrounding D'Arros Island and St. Joseph Atoll, particularly where substantial site fidelity is displayed by these large elasmobranchs.
A nonlinear hyperelasticity model for single layer blue phosphorus based on
ab initio
calculations
Authors: Ghaffari Reza , Shirazian Farzad , Hu Ming , Sauer Roger A.
Published: September 2019

A new hyperelastic membrane material model is proposed for single layer blue phosphorus (
β
-P), also known as blue phosphorene. The model is fully nonlinear and captures the anisotropy of
β
-P at large strains. The material model is calibrated from density functional theory (DFT) calculations considering a set of elementary deformation states. Those are pure dilatation and uniaxial stretching along the armchair and zigzag directions. The DFT calculations are performed with the Quantum ESPRESSO package. The material model is compared and validated with additional DFT results and existing DFT results from the literature, and the comparison shows good agreement. The new material model can be directly used within computational shell formulations that are, for example, based on rotation-free isogeometric finite elements. This is demonstrated by simulations of the indentation and vibration of single layer blue phosphorus sheets at micrometer scales. The elasticity constants at small deformations are also reported.
Crack formation during solid pyrolysis: evolution, pattern formation and statistical behaviour
Authors: Nguyen Yen T. , Pence Thomas J. , Wichman Indrek S.
Published: September 2019

As solids pyrolyse during combustion, they lose chemical and structural integrity by gradually degrading into residual char and forming defects such as voids, fissures and cracks. The material degradation process, which is coupled to the crack formation process, is described using a theoretical model and is numerically simulated using the finite-element method for a generic, charring, rubber-like material. In this model, a slab of material is subjected to an external, localized heat flux and, as the material degrades, cracks form when the local principal stress exceeds a defined cracking threshold. The magnitude of the cracking threshold
σ

c

is systematically varied in order to examine its influences on crack initiation, evolution, distribution and behaviour over time. When
σ

c

exceeds the maximum principal stress for the entire process,
σ

m

, then no cracks are generated. We quantify how the average crack spacing, total crack length and crack initiation time depend upon the ratio
σ

c

/
σ

m

. Two characteristic domains of crack formation behaviour are identified from the crack initiation behaviour. Correlations are produced for the crack length evolution and final crack length values as functions of
σ

c

/
σ

m

. Crack intersection patterns and behaviour are described and characterized.
Some similarity solutions for three-dimensional boundary layers
Authors: Vaz R. H. , Mestel A. J.
Published: September 2019

A similarity solution of a three-dimensional boundary layer is investigated. The outer flow is given by
U
 = ( − 
xz
, − 
yz
,
z
2
), corresponding to an axisymmetric poloidal circulation with constant potential vorticity. This flow is an exact solution of the Navier–Stokes. A wall is introduced at
y
 = 0 along which a boundary layer develops towards
x
 = 0. We show that a similarity reduction to a system of ODEs is possible. Two distinct solutions are found, one of them through numerical path-continuation, and their stability is investigated. A second three-dimensional solution is also identified for two-dimensional outer flow. The solutions are generalized for outer flows scaling with different powers of
z
and similar results are found. This behaviour is related to the non-uniqueness of the Falkner–Skan flows in a three-dimensional sense, with a transverse wall-jet.
Geometric localization in supported elastic struts
Authors: Michaels T. C. T. , Kusters R. , Dear A. J. , Storm C. , Weaver J. C. , Mahadevan L.
Published: September 2019

Localized deformation patterns are a common motif in morphogenesis and are increasingly finding applications in materials science and engineering, in such instances as mechanical memories. Here, we describe the emergence of spatially localized deformations in a minimal mechanical system by exploring the impact of growth and shear on the conformation of a semi-flexible filament connected to a pliable shearable substrate. We combine numerical simulations of a discrete rod model with theoretical analysis of the differential equations recovered in the continuum limit to quantify (in the form of scaling laws) how geometry, mechanics and growth act together to give rise to such localized structures in this system. We find that spatially localized deformations along the filament emerge for intermediate shear modulus and increasing growth. Finally, we use experiments on a 3D-printed multi-material model system to demonstrate that external control of the amount of shear and growth may be used to regulate the spatial extent of the localized strain texture.
Kin but less than kind: within-group male relatedness does not increase female fitness in seed beetles
Authors: Berg Elena C. , Lind Martin I. , Monahan Shannon , Bricout Sophie , Maklakov Alexei A.
Published: September 2019

Theory maintains within-group male relatedness can mediate sexual conflict by reducing male–male competition and collateral harm to females. We tested whether male relatedness can lessen female harm in the seed beetle
Callosobruchus maculatus
. Male relatedness did not influence female lifetime reproductive success or individual fitness across two different ecologically relevant scenarios of mating competition. However, male relatedness marginally improved female survival. Because male relatedness improved female survival in late life when
C. maculatus
females are no longer producing offspring, our results do not provide support for the role of within-group male relatedness in mediating sexual conflict. The fact that male relatedness improves the post-reproductive part of the female life cycle strongly suggests that the effect is non-adaptive. We discuss adaptive and non-adaptive mechanisms that could result in reduced female harm in this and previous studies, and suggest that cognitive error is a likely explanation.
Exposure to perfluoroalkyl substances in a cohort of women firefighters and office workers in San Francisco
Authors: Trowbridge Jessica , Gerona Roy , Lin Thomas , Rudel Ruthann A. , Bessonneau Vincent , Buren Heather , Morello-Frosch Rachel
Published: September 2019

Background

Studies in male firefighters have demonstrated increased exposures to carcinogenic compounds and increased rates of certain cancers compared to the general population. Many chemicals related to these occupational exposures have been associated with breast tumor development in animal and human studies, yet, there have been no studies on women firefighters due to their low numbers in most fire departments. To address this data gap, the Women Firefighters Biomonitoring Collaborative (WFBC) created a biological sample archive and analyzed levels of perfluoroalkyl substances (PFAS) among women firefighters and office workers in San Francisco.

Methods

Active duty women firefighters (n=86) and office workers (n=84) were recruited from the San Francisco Fire Department and the City and County of San Francisco, respectively. Serum samples were collected and analyzed using liquid chromatography tandem mass spectrometry (LC MS/MS) to measure and compare PFAS levels between firefighters and office workers. For PFAS congeners detected in at least 70% of our study population, we examined differences in serum PFAS levels controlling for dietary, demographic and other confounders. Among firefighters, we assessed associations between occupational activities and PFAS levels.

Results

Eight of 12 PFAS congeners were detected at levels above the limit of detection and seven were detected in at least 70% of the study population. Four PFAS were detected in all study participants (PFNA, PFOA, PFOS, PFHxS). In regression models comparing PFAS levels by occupation and adjusting for potential confounders, firefighters had higher geometric mean (GM) concentrations of PFAS compared to office workers: 2.39 (95%CI = 1.64,3.48), 2.32 (95% CI = 1.17,4.62) and 1.26 (95% CI = 0.99, 1.59) times higher for PFHxS, PFUnDA and PFNA, respectively. In analyses limited to firefighters, PFAS levels varied by assigned position in the fire department—firefighters and officers had higher PFNA, PFOA, PFDA, and PFUnDA compared to drivers. Additionally, firefighters who reported having used firefighting foam had higher concentrations of PFOA compared firefighters who reported never having used foam.

Conclusion

Our study found ubiquitous exposures to PFAS among WFBC participants, with women firefighters exposed to higher levels of some PFAS compared to office workers, suggesting that some of these exposures may be occupationally related.
Sex-related differences in the clinical diagnosis of frontotemporal dementia
Authors: Llorca-Bofí Vicent , Illán-Gala Ignacio , Blesa Rafael
Published: September 2019

Disclaimer text: The authors have withdrawn this manuscript because some authors did not consent with its publication and the data are too preliminary to be disseminated. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Absence of Testicular Adrenal Rest Tumors in Newborns, Infants, and Toddlers with Classical Congenital Adrenal Hyperplasia
Authors: Kim Mimi S. , Koppin Christina M. , Mohan Pankhuri , Goodarzian Fariba , Ross Heather M. , Geffner Mitchell E. , De Filippo Roger , Kokorowski Paul
Published: September 2019

INTRODUCTION

Testicular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH.

OBJECTIVE

We assessed the prevalence of TART in newborn, infant, and toddler males with classical CAH via scrotal ultrasound.

METHODS

Males with CAH had scrotal ultrasounds during the first 4 years of life, evaluating testes for morphology, blood flow, and presence of TART. Newborn screen 17-hydroxyprogesterone (17-OHP) and serum 17-OHP at the time of ultrasound were recorded. Bone ages were considered very advanced if ≥ 2SD above chronological age.

RESULTS

Thirty-one ultrasounds in 16 males were performed. An initial ultrasound was obtained in four newborns at diagnosis (6.8 ±2.1 days), six infants (2.2 ±0.9 months), and six toddlers (2.4 ±0.9 years). Eleven males had at least one repeat ultrasound. A large proportion (11/16) were in poor hormonal control with an elevated 17-OHP (325 ±298 nmol/L). One infant was in very poor hormonal control (17-OHP 447 nmol/L) at initial ultrasound, and two toddlers had advanced bone ages (+3.2 and +4.5 SD) representing exposure to postnatal androgens. However, no TART were detected in any subjects.

CONCLUSIONS

TART were not found in males up to 4 years of age with classical CAH despite settings with expected high ACTH drive. Further research into the occurrence of TART in CAH may elucidate factors which contribute to the detection and individual predisposition to TART.
Dissociative experiences in fibromyalgia are mediated by symptoms of autonomic dysfunction
Authors: Aslanyan Daron , Iodice Valeria , Davies Kevin A , Critchley Hugo D , Eccles Jessica A
Published: September 2019

Background

Fibromyalgia is characterised by chronic widespread pain. Quality of life is further reduced by autonomic and cognitive symptoms, including subjective ‘brain-fog’ and dissociative experiences. Although an association with joint hypermobility suggests variant connective tissue is a factor in both fibromyalgia and dysautonomia, the mechanisms underlying the neuropsychiatric symptoms are poorly understood.

Methods

21 fibromyalgia patients and 21 healthy controls were assessed for joint hypermobility dissociative experiences, autonomic symptoms and interoceptive sensibility. Mediation analyses were conducted according to the method of Baron and Kenny.

Results

Patients with fibromyalgia reported greater dissociative experiences and autonomic symptoms. The relationship between fibromyalgia and dissociative experiences was fully mediated by symptoms of orthostatic intolerance. Fibromyalgia, dissociative experiences and orthostatic intolerance all were associated with joint hypermobility and interoceptive sensibility.

Conclusions

This exploratory investigation highlights the relationship between dissociative experiences in the context of fibromyalgia and subjective experience of aberrant physiological responses. These findings can enhance the recognition and management of neuropsychiatric symptoms in patients with fibromyalgia, wherein dissociative experiences reflect disturbance of self-representation that can arise through abnormalities in internal agency, autonomic (dys)control and interoceptive prediction errors.
AsCRISPR: a web server for allele-specific sgRNA design in precision medicine
Authors: Zhao Guihu , Li Jinchen , Tang Yu
Published: September 2019

Allele-specific genomic targeting by CRISPR provides a point of entry for personalized gene therapy of dominantly inherited diseases, by selectively disrupting the mutant alleles or disease-causing single nucleotide polymorphisms (SNPs), ideally while leaving normal alleles intact. Moreover, the allele-specific engineering has been increasingly exploited not only in treating inherited diseases and mutation-driven cancers, but also in other important fields such as genome imprinting, haploinsufficiency, genome loci imaging and immunocompatible manipulations. Despite the tremendous utilities of allele-specific targeting by CRISPR, very few bioinformatic tools have been implemented for the allele-specific purpose. We thus developed AsCRISPR (Allele-specific CRISPR), a web tool to aid the design of guide RNA (gRNA) sequences that can discriminate between alleles. It provides users with limited bioinformatics skills to analyze both their own identified variants and heterozygous SNPs deposited in the dbSNP database. Multiple CRISPR nucleases and their engineered variants including newly-developed Cas12b and CasX are included for users’ choice. Meanwhile, AsCRISPR evaluates the on-target efficiencies, specificities and potential off-targets of gRNA candidates, and also displays the allele-specific restriction enzyme sites that might be disrupted upon successful genome edits. In addition, AsCRISPR analyzed with dominant single nucleotide variants (SNVs) retrieved from ClinVar and OMIM databases, and generated a Dominant Database of candidate discriminating gRNAs that may specifically target the alternative allele for each dominant SNV site. A Validated Database was also established, which manually curated the discriminating gRNAs that were experimentally validated in the mounting literatures. AsCRISPR is freely available at http://www.genemed.tech/ascrispr.
Multi-hit autism genomic architecture evidenced from consanguineous families with involvement of FEZF2 and mutations in high-risk genes
Authors: Bensaid Mounia , Loe-Mie Yann , Lepagnol-Bestel Aude-Marie , Han Wenqi , Santpere Gabriel , Klarić Thomas , Plançon Christine , Roudies Rim , Benhima Imane , Tarik Nisrine , Nitschke Patrick , Plaza Jean-Marc , Kisra Hassan , Deleuze Jean-François , Sestan Nenad , Moalic Jean-Marie , Simonneau Michel
Published: September 2019

Autism Spectrum Disorders (ASDs) are a heterogeneous collection of neurodevelopmental disorders with a strong genetic basis. Recent studies identified that a single hit of either a de novo or transmitted gene-disrupting, or likely gene-disrupting, mutation in a subset of 65 strongly associated genes can be sufficient to generate an ASD phenotype. We took advantage of consanguineous families with an ASD proband to evaluate this model. By a genome-wide homozygosity mapping of ten families with eleven children displaying ASD, we identified a linkage region of 133 kb in five families at the 3p14.2 locus that includes FEZF2 with a LOD score of 5.8 suggesting a founder effect. Sequencing FEZF2 revealed a common deletion of four codons. However, the damaging FEZF2 mutation did not appear to be sufficient to induce the disease as non-affected parents also carry the mutation and, similarly, Fezf2 knockout mouse embryos electroporated with the mutant human FEZF2 construct did not display any obvious defects in the corticospinal tract, a pathway whose development depends on FEZF2. We extended the genetic analysis of these five FEZF2-linked families versus five FEZF2 non-linked families by studying de novo and transmitted copy number variation (CNV) and performing Whole Exome Sequencing (WES). We identified damaging mutations in the subset of 65 genes strongly associated with ASD whose co-expression analysis suggests an impact on the prefrontal cortex during the mid-fetal periods. From these results, we propose that both FEZF2 deletion and multiple hits in the repertoire of these 65 genes are necessary to generate an ASD phenotype.

Significance Statement

The human neocortex is a highly organized laminar structure with neuron positioning and identity of deep-layer cortical neurons that depend on key transcription factors, such as FEZF2, SATB2, TSHZ3 and TBR1. These genes have a specific spatio-temporal pattern of expression in human midfetal deep cortical projection neurons and display mutations in patients with Autism Spectrum Disorder (ASD). Here, we identified a linkage region involving FEZF2 gene in five consanguineous families with an ASD proband. For these FEZF2-allele linked probands, we identified a four-codon deletion in FEZF2 and damaging mutations in other high-risk ASD genes, that exhibit regional and cell type–specific convergence in neocortical deep-layer excitatory neurons, suggesting a multi-hit genomic architecture of ASD in these consanguineous families.
Host nutrition mediates interactions between plant viruses, altering transmission and predicted disease spread
Authors: Kendig Amy E. , Borer Elizabeth T. , Boak Emily N. , Picard Tashina C. , Seabloom Eric W.
Published: September 2019

Interactions among co-infecting pathogens are common across host taxa and can affect infectious disease dynamics. Host nutrition can mediate these among-pathogen interactions, altering the establishment and growth of pathogens within hosts. It is unclear, however, how nutrition-mediated among-pathogen interactions affect transmission and the spread of disease through populations. We manipulated the nitrogen (N) and phosphorus (P) supplies to oat plants in growth chambers and evaluated interactions between two aphid-vectored Barley and Cereal Yellow Dwarf Viruses: PAV and RPV. We quantified the effect of each virus on the other’s establishment, within-plant density, and transmission. Co-inoculation significantly increased PAV density when N and P supplies were low and tended to increase RPV density when N supply was high. Co-infection increased PAV transmission when N and P supplies were low and tended to increase RPV transmission when N supply was high. Despite the parallels between the effects of among-pathogen interactions on density and transmission, changes in virus density only partially explained changes in transmission, suggesting that virus density–independent processes contribute to transmission. A mathematical model describing the spread of two viruses through a plant population, parameterized with empirically derived transmission values, demonstrated that nutrition-mediated among-pathogen interactions could affect disease spread. Interactions that altered transmission through virus density–independent processes determined overall disease dynamics. Our work suggests that host nutrition alters disease spread through among-pathogen interactions that modify transmission.
ECM-body: A cell-free 3D biomimetic scaffold derived from intact planarian body
Authors: Sonpho Ekasit , Wootthichairangsan Chanida , Ishida Miyuki , Inoue Takeshi , Agata Kiyokazu , Maleehuan Anchuleerat , Charngkaew Komgrid , Chomanee Nusara , Moonsom Saengduen , Wongtrakoongate Patompon , Chairoungdua Arthit , Ounjai Puey
Published: September 2019

Extracellular matrix (ECM) plays key roles in shaping fates of stem cells, not only by providing suitable niche but also by mediating physical and biochemical cues. Despite intensive investigations on regeneration, the roles of ECM on fate determination of stem cells in animal with great regenerative potency, such as planarian, remained unclear. Here, we developed a method to decellularizing and isolating extracellular matrix from planarians. Although the isolated scaffold appears translucent, it contains all the internal features, resembling the structure of intact planarian, and which we thus called “ECM-body”. Nuclear staining demonstrated that ECM-body contains very little or no cell remained. Histological sections displayed a well-preserved morphological integrity of the specimen. Scanning electron microscope showed porous surface on ECM-body, potentially suitable for housing cells. Furthermore, our preliminary experiment suggested that ECM-body can be utilized as biomimetic scaffold for cell culture as it may support survival of injected neoblasts.
Exploiting a Mechanical Perturbation of Titin Domain to Identify How Force Field Parameterization Affects Protein Refolding Pathways
Authors: Wang David , Marszalek Piotr E.
Published: September 2019

Molecular mechanics force fields have been shown to differ in their predictions of processes such as protein folding. To test how force field differences affect predicted protein behavior, we created a mechanically perturbed model of the beta-stranded I91 titin domain based on atomic force spectroscopy data and examined its refolding behavior using six different force fields. To examine the transferability of the force field discrepancies identified by this model, we compared the results to equilibrium simulations of the weakly helical peptide Ac-(AAQAA)3-NH2. The total simulation time was 80 µs. From these simulations we found significant differences in I91 perturbation refolding ability between force fields. Concurrently, Ac-(AAQAA)3-NH2 equilibration experiments indicated that although force fields have similar overall helical frequencies, they can differ in helical lifetimes. The combination of these results suggests that differences in force field parameterization may allow a more direct transition between the beta and alpha regions of the Ramachandran plot thereby affecting both beta-strand refolding ability and helical lifetimes. Furthermore, the combination of results suggests that using mechanically perturbed models can provide a controlled method to gain more insight into how force fields affect protein behavior.
Mapping the Global Network of Extracellular Protease Regulation inStaphylococcus aureus
Authors: Gimza Brittney D. , Larias Maria I. , Budny Bridget G. , Shaw Lindsey N.
Published: September 2019

A primary function of the extracellular proteases ofStaphylococcus aureusis to control the progression of infection by selectively modulating the stability of virulence factors. Consequently, a regulatory network exists to titrate protease abundance/activity, to influence accumulation, or lack thereof, of individual virulence factors. Herein, we comprehensively map this system, exploring regulation of the four protease loci by known and novel factors. In so doing, we determine that seven major elements (SarS, SarR, Rot, MgrA, CodY, SaeR, and SarA) form the primary network of control, with the latter three being the most powerful. We note that expression of aureolysin is largely repressed by these factors, whilst thesploperon is subject to the strongest upregulation of any protease loci, particularly by SarR and SaeR. Furthermore, when exploringscpAexpression, we find it to be profoundly influenced in opposing fashions by SarA (repressor) and SarR (activator). We also present the screening of >100 regulator mutants ofS. aureus, identifying 7 additional factors (ArgR2, AtlR, MntR, Rex, XdrA, Rbf, and SarU) that form a secondary circuit of protease control. Primarily these elements serve as activators, although we reveal XdrA as a new repressor of protease expression. With the exception or ArgR2, each of the new effectors appear to work through the primary network of regulation to influence protease production. Collectively, we present a comprehensive regulatory circuit that emphasizes the complexity of protease regulation and suggest that its existence speaks to the importance of these enzymes toS. aureusphysiology and pathogenic potential.

Importance

The complex regulatory role of the proteases necessitates very tight coordination and control of their expression. Whilst this process has been well studied, a major oversight has been the consideration of proteases as a single entity, rather than 10 enzymes produced from four different promoters. As such, in this study we comprehensively characterized the regulation of each protease promoter, discovering vast differences in the way each protease operon is controlled. Additionally, we broaden the picture of protease regulation using a global screen to identify novel loci controlling protease activity, uncovering a cadre of new effectors of protease expression. The impact of these elements on the activity of proteases and known regulators was characterized producing a comprehensive regulatory circuit that emphasizes the complexity of protease regulation inStaphylococcus aureus.
Attention to rhythms: sensory-specific constrained sampling of temporal regularities
Authors: Zalta Arnaud , Petkoski Spase , Morillon Benjamin
Published: September 2019

That attention is a fundamentally rhythmic process has recently received abundant empirical evidence. The essence of temporal attention, however, is to flexibly focus in time. Whether this function is hampered by an underlying rhythmic mechanism is unknown. In six interrelated experiments, we behaviourally quantify the sampling capacities of periodic temporal attention during auditory or visual perception. We reveal the presence of limited attentional capacities, with an optimal sampling rate of ~1.4 Hz in audition and ~0.7 Hz in vision. Investigating the motor contribution to temporal attention, we show that it scales with motor rhythmic precision, maximal at ~1.7 Hz. Critically, the motor modulation is beneficial to auditory but detrimental to visual temporal attention. These results are captured by a computational model of coupled oscillators, that reveals the underlying structural constraints governing the temporal alignment between motor and attention fluctuations.
A Ponceau Staining based Dot-Blot Assay for reliable and cost-effective Protein Quantification
Authors: Helbing Dario-Lucas , Böhm Leopold , Cui Yan , Stabenow Leonie Karoline , Morrison Helen
Published: September 2019

Reliable quantification of protein extracts from tissues can be a challenge e.g. due to interference of the high fat content in tissues of the nervous system. Further problems like under- or overerstimation of protein concentrations in protein quantification kits like the bicinchoninic acid (BCA) assay can occur. In addition, common lysis buffers such as RIPA buffer are known to be unable to solubilize a large amount of proteins (~10-30%) leading to unsatisfactory and unreliable experimental results with techniques such as immunoblotting. In this work, we have developed a Ponceau S staining based protein quantification assay. This assay is compatible with tissues or cells directly lysed in 2x SDS gel loading buffer, containing bromophenolblue, leading to more complete protein extraction. Protein concentrations of several samples can be determined in a fast and cost-effective manner and subsequent experiments (e.g. Western blot) can be performed without loss of proteins. The presented protein quantification method is highly reliable, fast and economical. Using this method, it is possible to save between 2300 to 3200€ per 1000 lysates as compared to the costs of a commercial BCA kit.
Effect of Feedback Valence on Family Resemblance Category Learning
Authors: Che Jing-Shang , Xing Qiang , Li Ai-mei
Published: September 2019

This research uses ERPs method to study how different valence of feedback influence family resemblance category learning. The results showed that at the behavioral level, participants in the negative feedback condition received higher test scores than those in the positive feedback condition; at the physiological level, the four kinds of ERPs evoked by both negative and positive feedback are P200, P300, and FRN. Compared with the non-feedback condition, P300 is more sensitive to negative feedback, and negative feedback induces larger amplitude, while P300 is not sensitive to positive feedback. For both negative and positive feedback, when feedback was presented after 200-300ms, the reaction to errors induced FRN production, and FRN produced under negative feedback condition led to more activation. This research has deepened our understanding of the influence of feedback valence on category learning from the brain mechanisms as well.
Dynactin p150 promotes processive motility of DDB complexes by minimizing diffusional behavior of dynein
Authors: Feng Qingzhou , Gicking Allison M. , Hancock William O.
Published: September 2019

Cytoplasmic dynein is activated by forming a complex with dynactin and the adaptor protein BicD2. We used Interferometric Scattering (iSCAT) microscopy to track dynein-dynactin-BicD2 (DDB) complexes in vitro and developed a regression-based algorithm to classify switching between processive, diffusive and stuck motility states. We find that DDB spends 65% of its time undergoing processive stepping, 4% undergoing 1D diffusion, and the remaining time transiently stuck to the microtubule. Although the p150 subunit was previously shown to enable dynactin diffusion along microtubules, blocking p150 enhanced the proportion of time DDB diffused and reduced the time DDB processively walked. Thus, DDB diffusive behavior most likely results from dynein switching into an inactive (diffusive) state, rather than p150 tethering the complex to the microtubule. DDB - kinesin-1 complexes, formed using a DNA adapter, moved slowly and persistently, and blocking p150 led to a 70 nm/s plus-end shift in the average velocity, in quantitative agreement with the increase in diffusivity seen in isolated DDB. The data suggest a DDB activation model in which engagement of dynactin p150 with the microtubule promotes dynein processivity, serves as an allosteric activator of dynein, and enhances processive minus-end motility during intracellular bidirectional transport.

TOC Highlight

Dynein-dynactin-BicD2 (DDB) is highly processive, but also shows transient pausing and diffusion, which we analyzed using iSCAT microscopy. Blocking dynactin p150 results in more diffusion of isolated DDB and a plus-end shift of kinesin-1 – DDB complexes. Thus, we conclude that p150 is an allosteric activator of dynein in the DDB complex.
MADloy: Robust detection of mosaic loss of chromosome Y from genotype-array-intensity data
Authors: González Juan R , López-Sánchez Marcos , Cáceres Alejandro , Puig Pere , Esko Tonu , Pérez-Jurado Luis A
Published: September 2019

Accurate protocols and methods to robustly detect the mosaic loss of chromosome Y (mLOY) are needed given its reported role in cancer, several age-related disorders and overall male mortality. Intensity SNP-array data have been used to infer mLOY status and to determine its prominent role in male disease. However, discrepancies of reported findings can be due to the uncertainty and variability of the methods used for mLOY detection and to the differences in the tissue-matrix used. We proposed MADloy, the first publicly available software tool that incorporates previous methods and includes a new robust approach, allowing efficient calling in large studies and comparisons between methods. The new method implemented in MADloy optimizes mLOY calling by correctly modeling the underlying reference population with no-mLOY status and incorporating B-deviation information. We observed improvements in the calling accuracy with respect to previous methods, using experimentally validated samples, and an increment in the statistical power to detect associations with disease and mortality, using simulation studies and real dataset analyses. We applied MADloy to detect the increment of mLOY cellularity in blood on 18 individuals after 3 years, and to confirm that its detection in saliva was sub-optimal (41%). We illustrate the use of MADloy to detect the down-regulation genes in the chromosome Y in kidney and bladder tumors with mLOY, and to perform pathway analyses for the detection of mLOY in blood. MADloy is a new software tool implemented in R for easy and robust calling of mLOY status in men aimed to facilitate its study in large epidemiological studies.
Integrated transcriptomic correlation network analysis identifies COPD molecular determinants
Authors: Paci Paola , Fiscon Giulia , Conte Federica , Licursi Valerio , Morrow Jarrett , Hersh Craig , Cho Michael , Castaldi Peter , Glass Kimberly , Silverman Edwin K. , Farina Lorenzo
Published: September 2019

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex syndrome. Network-based analysis implemented by SWIM software can be exploited to identify key molecular switches - called “switch genes” - for disease. Genes contributing to common biological processes or define given cell types are frequently co-regulated and co-expressed, giving rise to expression network modules. Consistently, we found that the COPD correlation network built by SWIM consists of three well-characterized modules: one populated by switch genes, all up-regulated in COPD cases and related to the regulation of immune response, inflammatory response, and hypoxia (like TIMP1, HIF1A, SYK, LY96, BLNK and PRDX4); one populated by well-recognized immune signature genes, all up-regulated in COPD cases; one where the GWAS genes AGER and CAVIN1 are the most representative module genes, both down-regulated in COPD cases. Interestingly, 70% of AGER negative interactors are switch genes including PRDX4, whose activation strongly correlates with the activation of known COPD GWAS interactors SERPINE2, CD79A, and POUF2AF1. These results suggest that SWIM analysis can identify key network modules related to complex diseases like COPD.
Neurocognitive patterns dissociating semantic processing from executive control are linked to more detailed off-task mental time travel
Authors: Wang Hao-Ting , Ping Ho Nerissa Siu , Bzdok Danilo , Bernhardt Boris C. , Margulies Daniel S. , Jefferies Elizabeth , Smallwood Jonathan
Published: September 2019

1

Features of ongoing experience are common across individuals and cultures. However, certain people express specific patterns to a greater extent than others. The current psychological theory assumes that individual differences in thought patterns occur because different types of experience depend on differences in associated neurocognitive mechanisms. Consequently, individual variation in the underlying neurocognitive architecture is hypothesised to determine the ease with which certain thought patterns are generated or maintained. Our study (N=178) tested this hypothesis using multivariate pattern analysis to infer shared variance among measures of cognitive function and neural organisation and examined whether these hidden structures explain reports of the patterns of on-going thoughts people experienced in the lab. We found that relatively better performance on tasks requiring primarily semantic knowledge, rather than executive control, was linked to a neural functional organisation that was associated, via meta-analysis, with task labels related to semantic associations (sentence processing, reading and verbal semantics). Variability of this functional mode predicted significant individual variation in the types of thoughts that individuals experienced in the laboratory: Neurocognitive patterns linked to better performance at tasks that required guidance from semantic representation, rather than those dependent on executive control, were associated with patterns of thought characterised by greater subjective detail and a focus on time periods other than the here and now. These relationships were consistent across different days and did not vary with task condition, indicating they are relatively stable features of an individual’s cognitive profile. Together these data confirm that individual variation in aspects of ongoing experience can be inferred from hidden neurocognitive architecture and demonstrate that performance trade-offs between executive control and long term semantic knowledge are linked to a person’s tendency to imagine situations that transcend the here and now.
Static growth alters PrrF- and 2-alkyl-4(1H)-quinolone regulation of virulence trait expression in Pseudomonas aeruginosa
Authors: Brewer Luke K. , Huang Weiliang , Hackert Brandy , Kane Maureen A. , Oglesby Amanda G.
Published: September 2019

Pseudomonas aeruginosa is an opportunistic pathogen that is frequently associated with both acute and chronic infections, the latter of which are often polymicrobial. P. aeruginosa possesses a complex regulatory network that modulates nutrient acquisition and virulence, but our knowledge of these networks is largely based on studies with shaking cultures, which are not likely representative of conditions during infection. Here, we provide proteomic, metabolic, and genetic evidence that regulation by iron, a critical metallo-nutrient, is altered in static P. aeruginosa cultures. We identified type VI secretion as a target of iron regulation in P. aeruginosa in static but not shaking conditions, and we present evidence that this regulation occurs via PrrF sRNA-dependent production of 2-alkyl-4(1H)-quinolone metabolites. We further discovered that iron-regulated interactions between P. aeruginosa and a Gram-positive opportunistic pathogen, Staphylococcus aureus, are mediated by distinct factors in shaking versus static bacterial cultures. These results yield new bacterial iron regulation paradigms and highlight the need to re-define iron homeostasis in static microbial communities.
Testosterone and cortisol are negatively associated with ritualized bonding behavior in male macaques
Authors: Rincon Alan V. , Heistermann Michael , Schülke Oliver , Ostner Julia
Published: September 2019

Neuroendocrine research on the formation of social bonds has primarily focused on the role of nonapeptides. However, steroid hormones often act simultaneously to either inhibit or facilitate bonding. Testosterone is proposed to mediate a trade-off between male mating effort and nurturing behavior; therefore, low levels are predicted during periods of nurturing infant care and social bonding. In species where social bonding and support regulates hypothalamic-pituitary-adrenal axis activity, we also expect glucocorticoid levels to be low during bonding periods. We investigated how immunoreactive urinary testosterone (iuT) and cortisol (iuC) were related to triadic male-infant-male interactions – a ritualized male bonding behavior – as well as infant care in male Barbary macaques (Macaca sylvanus). We collected >3000 hours of behavioral observation data during full-day focal animal follows from 14 adult males and quantified iuT and iuC from 650 urine samples. As predicted, both iuT and iuC were negatively correlated with rates of triadic interactions within-subjects in the hours preceding urination. We found no relationship between iuT and iuC with triadic interactions between-subjects. Infant care was weakly positively correlated to iuT and iuC within-subjects, but not between-subjects. The observed negative relationship between iuT and triadic interactions may be beneficial to lower competitive tendencies between adult males and to not inhibit bond formation. Lowered iuC could reflect increased bonding and perceived social support as triadic interactions predict future coalition formation in this species. Additionally, lowered iuC may be reflective of buffered tensions between males. The positive relationship of iuT and iuC with infant care suggests that the handling of infants in may be less nurturing but rather protective or competitive in this species. Measuring steroid hormones in relation to bonding and nurturing can help us interpret behaviors within the ecological contexts that they occur.