bluuebunny/crossref_metadata_2025 huggingface dataset:
White Matter Hyperintensities and the Progression of Frailty—The Tasmanian Study of Cognition and Gait
Authors: Siejka Timothy P , Srikanth Velandai K , Hubbard Ruth E , Moran Chris , Beare Richard , Wood Amanda , Phan Thanh , Balogun Saliu , Callisaya Michele L
Published: January 2020

Background

The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people.

Methods

People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume.

Results

At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (β = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty.

Conclusions

We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty.
DMD carrier model with mosaic dystrophin expression in the heart reveals complex vulnerability to myocardial injury
Authors: Meyers Tatyana A , Heitzman Jackie A , Townsend DeWayne
Published: January 2020

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease that causes progressive muscle wasting and cardiomyopathy. This X-linked disease results from mutations of the DMD allele on the X-chromosome resulting in the loss of expression of the protein dystrophin. Dystrophin loss causes cellular dysfunction that drives the loss of healthy skeletal muscle and cardiomyocytes. As gene therapy strategies strive toward dystrophin restoration through micro-dystrophin delivery or exon skipping, preclinical models have shown that incomplete restoration in the heart results in heterogeneous dystrophin expression throughout the myocardium. This outcome prompts the question of how much dystrophin restoration is sufficient to rescue the heart from DMD-related pathology. Female DMD carrier hearts can shed light on this question, due to their mosaic cardiac dystrophin expression resulting from random X-inactivation. In this work, a dystrophinopathy carrier mouse model was derived by breeding male or female dystrophin-null mdx mice with a wild type mate. We report that these carrier hearts are significantly susceptible to injury induced by one or multiple high doses of isoproterenol, despite expressing ~57% dystrophin. Importantly, only carrier mice with dystrophic mothers showed mortality after isoproterenol. These findings indicate that dystrophin restoration in approximately half of the heart still allows for marked vulnerability to injury. Additionally, the discovery of divergent stress-induced mortality based on parental origin in mice with equivalent dystrophin expression underscores the need for better understanding of the epigenetic, developmental, and even environmental factors that may modulate vulnerability in the dystrophic heart.
Clinical study of an outbreak of postoperative mediastinitis caused by Serratia marcescens in adult cardiac surgery
Authors: Fernández Angel L , Adrio Belén , Martínez Cereijo José M , Martínez Monzonis Maria Amparo , El-Diasty Mohammad M , Alvarez Escudero Julian
Published: January 2020

OBJECTIVES

Nosocomial infection caused by Serratia marcescens after cardiac surgery is rare but causes high rates of morbidity and mortality. Knowledge about postoperative mediastinitis due to S. marcescens is limited. The purpose of this work was to study the clinical presentation, management and outcome of an outbreak of postoperative sternal infection due to S. marcescens.

METHODS

During a 7-week period, a total of 54 patients underwent open heart procedures in our hospital. A postoperative wound infection caused by S. marcescens was diagnosed in 10 patients. We performed a clinical study to investigate patient characteristics and outcomes as well as the possible source of the infection.

RESULTS

The mean age of the infected patients was 74.5 ± 10 years. Mediastinitis was present in 6 cases, superficial wound infection in 3 and isolated bacteraemia in 1. Purulent exudate through the sternal incision was observed in all infected cases except in 1 patient, who presented only with bacteraemia. Serratia marcescens was isolated from the samples taken from all infected wounds. The mean time elapsed between the operation and the isolation S. marcescens was 5.9 ± 2.4 days. Response to treatment was favourable in all cases except 1, who died. Contamination of the aqueous chlorhexidine solution used to prepare the patients’ skin with S. marcescens was reported. Microbiological studies demonstrated that S. marcescens strains isolated from patients and from the aqueous chlorhexidine solution belonged to the same clone.

CONCLUSIONS

The use of an aqueous chlorhexidine solution contaminated with S. marcescens caused an outbreak of postoperative sternal wound infections. The time elapsed between wound contamination and signs of infection was brief, but the systemic inflammatory response and tissue necrosis were limited. Alcohol-based solutions are recommended for the prevention of surgical site infections.
A direct correlation between commissural orientation and annular shape in bicuspid aortic valves: a new anatomical and computed tomography classification
Authors: Chirichilli Ilaria , Irace Francesco Giosuè , Weltert Luca Paolo , Salica Andrea , Guerrieri Wolf Lorenzo , Fusca Samuel , Ricci Alessandro , De Paulis Ruggero
Published: January 2020

OBJECTIVES

The shape of the aortic annulus is still under debate. Recent findings suggest a possible gradual spectrum of circularity from tricuspid aortic valves (TAVs), to type 1 bicuspid aortic valves (BAVs) to type 0 BAVs. BAVs have been recently classified in a symmetrical (type A), asymmetrical (type B) or very asymmetrical (type C) phenotype according to the commissural orientation (CO) (160°–180°, 140°–159° and 120°–139°, respectively). The aim of this study is to verify in BAVs the correlation between the aortic annular shape and the CO of valve cusps and to suggest a new anatomical and geometric classification of BAVs based on CO and annular shape.

METHODS

We retrospectively selected 191 consecutive patients who underwent both electrocardiography-gated computed tomography scan of the aortic root and transthoracic echocardiography between January 2016 and June 2019. The population was divided into 2 groups: 54 BAVs and 137 TAVs. We analysed the subgroup of BAV patients and divided them into group A, group B and group C depending on the CO. The shape of the aortic annulus was considered ‘circular’ or ‘elliptic’ according to the ellipticity index (EI).We studied the possible correlation between CO and annular shape in BAVs. We also analysed the subgroup of TAV patients studying their annular shape and EI.

RESULTS

After univariate linear regression, BAV patients showed a significant correlation between the CO and the EI (R = −0, 445, R2 = 0, 198, P = 0.001). As the CO decreases, the EI increases and approaches an elliptical shape. After grouping BAVs according to the CO, a mean EI of 1.10 ± 0.07 was found in group A, 1.13 ± 0.08 in group B, 1.18 ± 0.07 in group C, P = 0.0097 indicating a gradual spectrum of ellipticity with the decrease of CO. TAVs subgroup showed a mean EI of 1.27 ± 0.09, suggesting that the more the CO is reduced in BAVs, the more the annulus probably tends towards the very elliptical shape of TAVs.

CONCLUSIONS

This study shows a linear correlation between CO and annular shape in BAVs. In particular, the aortic annulus follows a continuous spectrum of ellipticity depending on the CO. These findings lay the groundwork for a new anatomical classification of BAVs based on CO and annular shape.
Adult obesity and mid-life physical functioning in two British birth cohorts: investigating the mediating role of physical inactivity
Authors: Pinto Pereira Snehal M , De Stavola Bianca L , Rogers Nina T , Hardy Rebecca , Cooper Rachel , Power Chris
Published: January 2020

Background

Associations between obesity and physical inactivity are bi-directional. Both are associated with physical functioning (PF, ability to perform physical tasks of daily living) but whether obesity influences PF via inactivity is unknown. We investigated whether mid-adult obesity trajectories were associated with subsequent PF and mediated by inactivity.

Methods

Body mass index (BMI; kg/m²) and inactivity were recorded at: 36, 43, 53 and 60–64 years in the 1946 Medical Research Council (MRC) National Survey of Health and Development (1946-NSHD; n = 2427), and at 33, 42 and 50 years in the 1958 National Child Development Study (1958-NCDS; n = 8674). Poor PF was defined as the lowest (gender and cohort-specific) 10% on the Short-form 36 Physical Component Summary subscale at 60–64 years (1946-NSHD) and 50 years (1958-NCDS). Estimated randomized-interventional-analogue natural direct (rNDE) and indirect (rNIE) effects of obesity trajectories on PF via inactivity are expressed as risk ratios [overall total effect (rTE) is rNDE multiplied by rNIE].

Results

In both cohorts, most individuals (∼68%) were never obese in adulthood, 16–30% became obese and ≤11% were always obese. In 1946-NSHD, rTE of incident obesity at 43 years (vs never) on poor PF was 2.32 (1.13, 3.51); at 53 years it was 1.53 (0.91, 2.15). rNIEs via inactivity were 1.02 (0.97, 1.07) and 1.02 (0.99, 1.04), respectively. Estimated rTE of persistent obesity from 36 years was 2.91 (1.14, 4.69), with rNIE of 1.03 (0.96, 1.10). In 1958-NCDS, patterns of association were similar, albeit weaker.

Conclusions

Longer duration of obesity was associated with increased risk of poor PF. Inactivity played a small mediating role. Findings reinforce the importance of preventing and delaying obesity onset to protect against poor PF.
Asymptotic Estimates for the Willmore Flow With Small Energy
Authors: Kuwert Ernst , Scheuer Julian
Published: January 2020

Kuwert and Schätzle showed in 2001 that the Willmore flow converges to a standard round sphere, if the initial energy is small. In this situation, we prove stability estimates for the barycenter and the quadratic moment of the surface. Moreover, in codimension one, we obtain stability bounds for the enclosed volume and averaged mean curvature. As direct applications, we recover a quasi-rigidity estimate due to De Lellis and Müller (2006) and an estimate for the isoperimetric deficit by Röger and Schätzle (2012), whose original proofs used different methods.
Effects of vitamin B6 on the growth performance, intestinal morphology, and gene expression in weaned piglets that are fed a low-protein diet1
Authors: Yin Lanmei , Li Jun , Wang Huiru , Yi Zhenfeng , Wang Lei , Zhang Shuo , Li Xiaozhen , Wang Qiye , Li Jianzhong , Yang Huansheng , Yin Yulong
Published: January 2020

Vitamin B6 (VB6), which is an essential functional substance for biosome, plays an irreplaceable role in animal health. However, there are few studies that focus on the correlation between VB6 and intestinal health in weaned piglets. This study was conducted to investigate the effects of VB6 on the growth performance, intestinal morphology, and inflammatory cytokines and amino acid (AA) transporters mRNA expression in weaned piglets that are fed a low crude-protein (CP, 18%) diet. Eighteen crossbred piglets with initial body weights of 7.03 ± 0.17 kg (means ± SEM), weaned at 21-d age, were randomly assigned three diets with 0, 4, and 7 mg/kg VB6 supplementation, respectively. The experimental period lasted 14 days. Our results showed that there were no significant differences in growth performance, diarrhea rate, and biochemical parameters among the three treatments. In the jejunum, dietary VB6 supplementation did not affect the morphology and positive Ki67 counts. Dietary supplementation with 4 mg/kg VB6 decreased the mRNA expression of COX-2, IL-10, and TGF-β (P < 0.05). Dietary supplementation with 7 mg/kg VB6 increased the mRNA expression of SLC7A1, SLC7A6, SLC16A14, and SLC38A5 (P < 0.05) and 4 or 7 mg/kg VB6 decreased SLC36A1 mRNA expression (P < 0.05). In the ileum, VB6 supplementation did not affect positive Ki67 counts but significantly decreased villus area (P < 0.05) and tended to decrease villus height (P = 0.093). Dietary supplementation with 4 mg/kg VB6 had significantly increased the mRNA expression of IL-1β, TNF-α, COX-2, IL-10, and TGF-β (P < 0.05). Dietary supplementation with 4 or 7 mg/kg VB6 had significantly decreased SLC6A20, SLC7A1, SLC7A6, SLC16A14, and SLC38A5 mRNA expression (P < 0.05). These findings suggest that dietary supplementation of VB6 mainly down-regulated inflammatory cytokines and up-regulated AA transporters mRNA expression in jejunum, while up-regulated (4 mg/kg) inflammatory cytokines and down-regulated AA transporters mRNA expression in ileum, which may provide a reference for the intestinal development of weaned piglets that are fed a low-CP diet.
Application of variational mode decomposition to seismic random noise reduction
Authors: Liu Wei , Cao Siyuan , Wang Zhiming
Published: January 2020

We have proposed a new denoising method for the simultaneous noise reduction and preservation of seismic signals based on variational mode decomposition (VMD). VMD is a recently developed adaptive signal decomposition method and an advance in non-stationary signal analysis. It solves the mode-mixing and non-optimal reconstruction performance problems of empirical mode decomposition that have existed for a long time. By using VMD, a multi-component signal can be non-recursively decomposed into a series of quasi-orthogonal intrinsic mode functions (IMFs), each of which has a relatively local frequency range. Meanwhile, the signal will focus on a smaller number of obtained IMFs after decomposition, and thus the denoised result is able to be obtained by reconstructing these signal-dominant IMFs. Synthetic examples are given to demonstrate the effectiveness of the proposed approach and comparison is made with the complete ensemble empirical mode decomposition, which demonstrates that the VMD algorithm has lower computational cost and better random noise elimination performance. The application of on field seismic data further illustrates the superior performance of our method in both random noise attenuation and the recovery of seismic events.
Changes in vegetation and soil properties following 6 years of enclosure in riparian corridors
Authors: Wang Di , Zhang Yi-Ran , Feng Yu-Long , Liu Zhi , Qu Bo
Published: January 2020

Aims

Riparian corridors play vital roles in the maintenance of biodiversity. Nonetheless, plant species diversity and vegetation coverage in riparian corridors are seriously threatened by increasing pressure owing to livestock consumption and anthropogenic disturbance; even the stability of river courses has been threatened. The establishment of enclosures is a widely used strategy to restore degraded grassland ecosystems, but its impact on degraded herbaceous riparian vegetation and soil properties remains unclear. The aim of this study was to evaluate whether species composition, richness, diversity, and soil properties can be recovered by the enclosure.

Methods

Twenty long-term monitoring sample plots were set in the Liaohe main stream river, Liaohe main stream river was enclosed for grazing and farmland exclusion in 2012. The height, coverage and individual numbers of plant were recorded for species richness and diversity evaluation from 2012 to 2017; soil nutrients were measured for comparative analysis in 2012 and 2017. We examined the effects of the establishment of enclosures on plant species diversity and soil properties from 2012 to 2017 in the riparian corridors of the Liaohe River system in China.

Important Findings

Plant species richness and diversity significantly increased from 2012 to 2017. The dominance of Asteraceae plants increased, while the abundance of Gramineae plants decreased over time. The difference in abundance increased each year since enclosure was implemented in 2012. The concentrations of phosphorus and potassium in the soil significantly decreased as a result of the combined effects of vegetation restoration and prohibition of farming practices following the establishment of enclosures. There was also a lag time related to the response of soil organic matter to the establishment of enclosures. In conclusion, our study provides new evidence regarding the response of species diversity, species composition and soil properties following riparian vegetation restoration efforts through enclosure development.
On the secondary’s rotation in a synchronous binary asteroid
Authors: Wang H S , Hou X Y
Published: January 2020

This article studies the secondary’s rotation in a synchronous binary asteroid system in which the secondary enters the 1:1 spin-orbit resonance. The model used is the planar full two-body problem, composed of a spherical primary plus a triaxial ellipsoid secondary. Compared with classical spin-orbit work, there are two differences: (1) influence of the secondary’s rotation on the mutual orbit is considered and (2) instead of the Hamiltonian approach, the approach of periodic orbits is adopted. Our studies find the following. (1) The genealogy of the two families of periodic orbits is the same as that of the families around triangular libration points in the restricted three-body problem. That is, the long-period family terminates on to a short-period orbit travelling N times. (2) In the limiting case where the secondary’s mass is negligible, our results can be reduced to classical spin-orbit theory, by equating the long-period orbit with free libration and the short-period orbit with the forced libration caused by orbit eccentricity. However, the two models show obvious differences when the secondary’s mass is non-negligible. (3) By studying the stability of periodic orbits for a specific binary asteroid system, we are able to obtain the maximum libration amplitude of the secondary (which is usually less than 90°) and the maximum mutual orbit eccentricity that does not break the secondary’s synchronous state. We also find an anti-correlation between the secondary’s libration amplitude and the orbit eccentricity. The (65803) Didymos system is taken as an example to show the results.
A survey for variable young stars with small telescopes: II – mapping a protoplanetary disc with stable structures at 0.15 au
Authors: Evitts Jack J , Froebrich Dirk , Scholz Aleks , Eislöffel Jochen , Campbell-White Justyn , Furnell Will , Stecklum Bringfried , Urtly Thomas , Pickard Roger , Wiersema Klaas , Dubovský Pavol A , Kudzej Igor , Naves Ramon , Morales Aimar Mario , Castillo García Rafael , Vanmunster Tonny , Schwendeman Erik , Soldán Alfaro Francisco C , Johnstone Stephen , Gonzalez Farfán Rafael , Killestein Thomas , DelgadoCasal Jesús , García de la Cuesta Faustino , Roberts Dean , Kolb Ulrich , Montoro Luís , Licchelli Domenico , Escartin Perez Alex , Perelló Perez Carlos , Deldem Marc , Futcher Stephen R L , Nelson Tim , Dvorak Shawn , Moździerski Dawid , Quinn Nick , Kotysz Krzysztof , Kowalska Katarzyna , Mikołajczyk Przemysław , Fleming George , Phillips Mark , Vale Tony , Dubois Franky , Logie Ludwig , Rau Steve , Vanaverbeke Siegfried , Merrikin Barry , Fernández Mañanes Esteban , Erdelyi Emery , Gonzalez Carballo Juan-Luis , Limon Martinez Fernando , Long Timothy P , San Segundo Delgado Adolfo , Salto González Josép Luis , Tremosa Espasa Luis , Piehler Georg , Crumpton James , Billington Samuel J , D’Arcy Emma , Makin Sally V , Dover Lord
Published: January 2020

The HOYS citizen science project conducts long-term, multifilter, high-cadence monitoring of large YSO samples with a wide variety of professional and amateur telescopes. We present the analysis of the light curve of V1490 Cyg in the Pelican Nebula. We show that colour terms in the diverse photometric data can be calibrated out to achieve a median photometric accuracy of 0.02 mag in broad-band filters, allowing detailed investigations into a variety of variability amplitudes over time-scales from hours to several years. Using Gaia DR2, we estimate the distance to the Pelican Nebula to be 870 $^{+70}_{-55}$ pc. V1490 Cyg is a quasi-periodic dipper with a period of 31.447 ± 0.011 d. The obscuring dust has homogeneous properties, and grains larger than those typical in the ISM. Larger variability on short time-scales is observed in U and Rc−H α, with U amplitudes reaching 3 mag on time-scales of hours, indicating that the source is accreting. The H α equivalent width and NIR/MIR colours place V1490 Cyg between CTTS/WTTS and transition disc objects. The material responsible for the dipping is located in a warped inner disc, about 0.15 au from the star. This mass reservoir can be filled and emptied on time-scales shorter than the period at a rate of up to 10−10 M⊙ yr−1, consistent with low levels of accretion in other T Tauri stars. Most likely, the warp at this separation from the star is induced by a protoplanet in the inner accretion disc. However, we cannot fully rule out the possibility of an AA Tau-like warp, or occultations by the Hill sphere around a forming planet.
Limits on the electromagnetic counterpart to S190814bv
Authors: Watson A M , Butler N R , Lee W H , Becerra R L , Pereyra M , Angeles F , Farah A , Figueroa L , Gónzalez-Buitrago D , Quirós F , Ruíz-Díaz-Soto J , Tejada de Vargas C , Tinoco S J , Wolfram T
Published: January 2020

We derive limits on any electromagnetic counterpart to the compact binary merger S190814bv, whose parameters are consistent with the merger of a black hole and a neutron star. We present observations with the new wide-field optical imager DDOTI and also consider Swift/BAT observations reported by Palmer et al. We show that Swift/BAT would have detected a counterpart with similar properties to a typical on-axis short GRB at the 98 per cent confidence level, whereas our DDOTI observations only rule out such a counterpart at the 27 per cent confidence level. Neither has sufficient sensitivity to rule out an off-axis counterpart like GW 170817. We compare the efficiency of Swift/BAT and DDOTI for future observations, and show that DDOTI is likely to be about twice as efficient as Swift/BAT for off-axis events up to about 100 Mpc.
Simulating star clusters across cosmic time – II. Escape fraction of ionizing photons from molecular clouds
Authors: He Chong-Chong , Ricotti Massimo , Geen Sam
Published: January 2020

We calculate the hydrogen- and helium-ionizing radiation escaping star-forming molecular clouds, as a function of the star cluster mass and compactness, using a set of high-resolution radiation-magnetohydrodynamic simulations of star formation in self-gravitating, turbulent molecular clouds. In these simulations, presented in He et al., the formation of individual massive stars is well resolved, and their UV radiation feedback and lifetime on the main sequence are modelled self-consistently. We find that the escape fraction of ionizing radiation from molecular clouds, $\langle f_{\rm esc}^{\scriptscriptstyle \rm MC}\rangle$ , decreases with increasing mass of the star cluster and with decreasing compactness. Molecular clouds with densities typically found in the local Universe have negligible $\langle f_{\rm esc}^{\scriptscriptstyle \rm MC}\rangle$ , ranging between $0.5{{\ \rm per\ cent}}$ and $5{{\ \rm per\ cent}}$. 10 times denser molecular clouds have $\langle f_{\rm esc}^{\scriptscriptstyle \rm MC}\rangle$ $\approx 10{{\ \rm per\ cent}}{-}20{{\ \rm per\ cent}}$, while 100× denser clouds, which produce globular cluster progenitors, have $\langle f_{\rm esc}^{\scriptscriptstyle \rm MC}\rangle$ $\approx 20{{\ \rm per\ cent}}{-}60{{\ \rm per\ cent}}$. We find that $\langle f_{\rm esc}^{\scriptscriptstyle \rm MC}\rangle$ increases with decreasing gas metallicity, even when ignoring dust extinction, due to stronger radiation feedback. However, the total number of escaping ionizing photons decreases with decreasing metallicity because the star formation efficiency is reduced. We conclude that the sources of reionization at z > 6 must have been very compact star clusters forming in molecular clouds about 100× denser than in today’s Universe, which lead to a significant production of old globular clusters progenitors.
Dynamic changes in cis-regulatory occupancy by Six1 and its cooperative interactions with distinct cofactors drive lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium
Authors: Li Jun , Zhang Ting , Ramakrishnan Aarthi , Fritzsch Bernd , Xu Jinshu , Wong Elaine Y M , Loh Yong-Hwee Eddie , Ding Jianqiang , Shen Li , Xu Pin-Xian
Published: January 2020

The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1’s downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one of the most significantly enriched motifs in Six1-bound sites, and we demonstrate that Six1-RFX proteins cooperatively regulate gene expression through binding to SIX:RFX-motifs. Six1 targets a wide range of hair-bundle regulators and late Six1 deletion disrupts hair-bundle polarity. This study provides a mechanistic understanding of how Six1 cooperates with distinct cofactors in feedforward loops to control lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.
Exo1 phosphorylation inhibits exonuclease activity and prevents fork collapse in rad53 mutants independently of the 14-3-3 proteins
Authors: Morafraile Esther C , Bugallo Alberto , Carreira Raquel , Fernández María , Martín-Castellanos Cristina , Blanco Miguel G , Segurado Mónica
Published: January 2020

The S phase checkpoint is crucial to maintain genome stability under conditions that threaten DNA replication. One of its critical functions is to prevent Exo1-dependent fork degradation, and Exo1 is phosphorylated in response to different genotoxic agents. Exo1 seemed to be regulated by several post-translational modifications in the presence of replicative stress, but the specific contribution of checkpoint-dependent phosphorylation to Exo1 control and fork stability is not clear. We show here that Exo1 phosphorylation is Dun1-independent and Rad53-dependent in response to DNA damage or dNTP depletion, and in both situations Exo1 is similarly phosphorylated at multiple sites. To investigate the correlation between Exo1 phosphorylation and fork stability, we have generated phospho-mimic exo1 alleles that rescue fork collapse in rad53 mutants as efficiently as exo1-nuclease dead mutants or the absence of Exo1, arguing that Rad53-dependent phosphorylation is the mayor requirement to preserve fork stability. We have also shown that this rescue is Bmh1–2 independent, arguing that the 14-3-3 proteins are dispensable for fork stabilization, at least when Exo1 is downregulated. Importantly, our results indicated that phosphorylation specifically inhibits the 5' to 3'exo-nuclease activity, suggesting that this activity of Exo1 and not the flap-endonuclease, is the enzymatic activity responsible of the collapse of stalled replication forks in checkpoint mutants.
Quantitative global studies reveal differential translational control by start codon context across the fungal kingdom
Authors: Wallace Edward W J , Maufrais Corinne , Sales-Lee Jade , Tuck Laura R , de Oliveira Luciana , Feuerbach Frank , Moyrand Frédérique , Natarajan Prashanthi , Madhani Hiten D , Janbon Guilhem
Published: January 2020

Eukaryotic protein synthesis generally initiates at a start codon defined by an AUG and its surrounding Kozak sequence context, but the quantitative importance of this context in different species is unclear. We tested this concept in two pathogenic Cryptococcus yeast species by genome-wide mapping of translation and of mRNA 5′ and 3′ ends. We observed thousands of AUG-initiated upstream open reading frames (uORFs) that are a major contributor to translation repression. uORF use depends on the Kozak sequence context of its start codon, and uORFs with strong contexts promote nonsense-mediated mRNA decay. Transcript leaders in Cryptococcus and other fungi are substantially longer and more AUG-dense than in Saccharomyces. Numerous Cryptococcus mRNAs encode predicted dual-localized proteins, including many aminoacyl-tRNA synthetases, in which a leaky AUG start codon is followed by a strong Kozak context in-frame AUG, separated by mitochondrial-targeting sequence. Analysis of other fungal species shows that such dual-localization is also predicted to be common in the ascomycete mould, Neurospora crassa. Kozak-controlled regulation is correlated with insertions in translational initiation factors in fidelity-determining regions that contact the initiator tRNA. Thus, start codon context is a signal that quantitatively programs both the expression and the structures of proteins in diverse fungi.
The landscape of chimeric RNAs in non-diseased tissues and cells
Authors: Singh Sandeep , Qin Fujun , Kumar Shailesh , Elfman Justin , Lin Emily , Pham Lam-Phong , Yang Amy , Li Hui
Published: January 2020

Chimeric RNAs and their encoded proteins have been traditionally viewed as unique features of neoplasia, and have been used as biomarkers and therapeutic targets for multiple cancers. Recent studies have demonstrated that chimeric RNAs also exist in non-cancerous cells and tissues, although large-scale, genome-wide studies of chimeric RNAs in non-diseased tissues have been scarce. Here, we explored the landscape of chimeric RNAs in 9495 non-diseased human tissue samples of 53 different tissues from the GTEx project. Further, we established means for classifying chimeric RNAs, and observed enrichment for particular classifications as more stringent filters are applied. We experimentally validated a subset of chimeric RNAs from each classification and demonstrated functional relevance of two chimeric RNAs in non-cancerous cells. Importantly, our list of chimeric RNAs in non-diseased tissues overlaps with some entries in several cancer fusion databases, raising concerns for some annotations. The data from this study provides a large repository of chimeric RNAs present in non-diseased tissues, which can be used as a control dataset to facilitate the identification of true cancer-specific chimeras.
Double negative T cells, a potential biomarker for systemic lupus erythematosus
Authors: Alexander Jessy J , Jacob Alexander , Chang Anthony , Quigg Richard J , Jarvis James N
Published: January 2020

Systemic lupus erythematosus (SLE) is an autoimmune disease that is a challenge to diagnose and treat. There is an urgent need for biomarkers to help define organ involvement, and more effective therapies. A unique population of T cells, the CD3+CD4−CD8− (DNeg) cells, is significantly increased in lupus patients. Twenty-seven cases (53%) of pediatric SLE patients had elevated DNeg cells in their peripheral blood, which correlated with kidney function (R2 = 0.54). Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by immunofluorescence. For the first time, this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus mice. In lupus mice, the increase in DNeg cells tracked with worsening disease and correlated with kidney function (R2 = 0.85). Our results show that DNeg cells per se can cause kidney dysfunction, increase in number with increase in disease pathology, and could serve as a potential biomarker.
Countercyclical Bank Equity Issuance
Authors: Baron Matthew
Published: January 2020

Over the period 1980–2012, large U.S. commercial banks raise and retain less equity during credit expansions, which amplifies their leverage. The decrease in equity issuance is large relative to subsequent banking losses. I consider a variety of explanations for why banks resist raising equity and find evidence consistent with the diminishment of creditor market discipline due to government guarantees. I test this explanation by analyzing the removal of government guarantees to German Landesbank creditors and find that creditor market discipline and equity issuance increase. These findings help explain why banks resist raising equity, making financial distress more likely.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Multidimensional tracking of phenotypes and organ involvement in a complete nationwide systemic sclerosis cohort
Authors: Fretheim Håvard , Halse Anne-Kristine , Seip Marit , Bitter Helle , Wallenius Marianne , Garen Torhild , Salberg Anne , Brunborg Cathrine , Midtvedt Øyvind , Molberg Øyvind , Hoffmann-Vold Anna-Maria
Published: January 2020

Objective

SSc is a severe, heterogeneous multi-organ disease where population-based estimates on phenotypic spectrum, overall disease burden and societal impact are largely missing. Here the objective was to provide the first-ever complete national-level data on phenotype and major organ afflictions in SSc.

Methods

A stepwise strategy was applied to find and characterize every SSc patient resident in Norway from 2000 to 2012. First we identified every case in the country registered with an International Classification of Diseases, Tenth Revision code for SSc (M34). Next we manually reviewed all cases coded as M34 to determine whether they met the 1980 ACR and/or 2013 ACR/EULAR classification criteria for SSc and could be included in the Norwegian SSc cohort (Nor-SSc). Finally, all disease features from SSc onset to study end were reviewed.

Results

The Nor-SSc cohort included 815 SSc patients. The mean age at diagnosis was 53 years, with 84% females and 77% limited cutaneous SSc. The estimated incidence increased from 4 per million in 2000 to 13 per million in 2012. We identified high cumulative frequencies of internal organ involvement, coexistence of multiple organ afflictions across disease subsets and autoantibody status and stable frequencies of pulmonary arterial hypertension across haemodynamic definitions, but indications of referral-related differences in pulmonary hypertension detection rates across the study area.

Conclusion

This nationwide cohort study provides new, unbiased evidence for a high disease burden in SSc patients of Caucasian descent and indicates the existence of hurdles preventing equality of assessment across the SSc population.
Neural activity in human ventromedial prefrontal cortex reflecting the intention to save reward
Authors: Zangemeister Leopold , Grabenhorst Fabian , Schultz Wolfram
Published: January 2020

Saving behavior usually requires individuals to perform several consecutive choices before collecting the final reward. The overt behavior is preceded by an intention to perform an appropriate choice sequence. We studied saving sequences for which each participant rated the intention numerically as willingness to save. Each sequence resulted in a specific reward amount and thus had a particular value for the participant, which we assessed with a Becker-DeGroot-Marschak auction-like mechanism. Using functional MRI, we found that blood-oxygen-level-dependent signals in human ventromedial prefrontal cortex (vmPFC) correlated with the participant’s stated intention before each choice sequence. An adjacent vmPFC region showed graded activation that reflected the value of the sequence. These results demonstrate an involvement of vmPFC in intentional processes preceding sequential economic choices.
Trust arbitration: 99 problems and 99 solutions
Authors: Clover Alcolea Lucas
Published: January 2020

Although in recent years there has been considerable interest in arbitrating internal trust disputes with a large body of literature produced on the subject, as well as statutory reform to permit it in several jurisdictions, it remains the fact that trust arbitration is still relatively uncommon. This is likely due to the complex problems of cross-border testamentary, trust, arbitration and human rights law. However, the aim of this article is to demonstrate that these difficulties are often exaggerated and can be solved with proper drafting and a little creativity.
The effect of varicocele on semen quality in boars exposed to heat stress1
Authors: Gruhot Tasha R , Rempel Lea A , White Brett R , Mote Benny E
Published: January 2020

Semen quality has a dramatic impact on reproductive efficiency in the swine industry, influencing both conception rate and litter size. The objective of this study was to assess whether the presence of varicocele hinders semen quality in both thermoneutral and heat stress (HS) conditions. At approximately 6 mo of age, ultrasonography was used to measure left and right pampiniform plexus area in order to detect varicocele in maternal line boars at the University of Nebraska–Lincoln. Between 10 and 12 mo of age, semen was collected from each boar (n = 28) twice weekly. Boars were collected under thermoneutral conditions, were then heat stressed for 7 d to exacerbate any semen quality issues, and semen was collected post-HS for 6 wk. Sperm characteristics were determined by computer-assisted semen analysis. The presence of varicocele had a significant effect on sperm concentration (P = 0.04) and trended toward significance for mean sperm head area (P = 0.06) throughout the duration of the study. An interaction existed between varicocele and collection time point at weeks 2–5 post-HS for distal droplet percentage, suggesting that boars with varicocele were possibly more susceptible to heat-stress-induced semen quality issues than boars without varicocele. Moreover, semen quality was reduced in boars with versus without varicocele under both thermoneutral and HS conditions. Therefore, detection of varicocele by ultrasound could represent a potential marker of fertility in young boars or as a component trait in selection indices for fertility.
Evaluation of dietary trace mineral supplementation in young horses challenged with intra-articular lipopolysaccharide1
Authors: Millican Allison A , Leatherwood Jessica L , Coverdale Josie A , Arnold Carolyn E , Bradbery Amanda N , Larson Connie K , Lamprecht Emily D , White Sarah H , Paulk Chad B , Welsh Thomas H , Wickersham Tryon A
Published: January 2020

Sixteen weanling Quarter Horses (255 ± 22 kg) were utilized in a 56-d trial to evaluate the effects of trace mineral (TM) source on intra-articular inflammation following a single acute inflammatory insult. Horses were stratified by age, sex, and BW and then randomly assigned to dietary treatment: concentrate formulated with Zn, Mn, Cu, and Co as inorganic sources (CON; n = 8) or complexed TMs (CTM; n = 8). Added TM were formulated at iso-levels across treatments and intakes met or exceeded NRC requirements. Horses were offered 1.75% BW (as-fed) of treatment concentrate and 0.75% BW (as-fed) coastal Bermudagrass hay. Growth measurements were collected on days 0, 28, and 56, and plasma was collected biweekly for determination of Mn, Cu, Zn, and Co concentrations. On day 42, carpal joints were randomly assigned to receive injections of 0.5 ng lipopolysaccharide (LPS) or sterile lactated Ringer’s solution (LRS; contralateral control). Synovial fluid was collected at preinjection hours (PIH) 0, and 6, 12, 24, 168, and 336 h post-injection and analyzed for TM concentration, prostaglandin E2 (PGE2), carboxypeptide of type II collagen (CPII), collagenase cleavage neopeptide (C2C), and aggrecan chondroitin sulfate 846 epitope (CS846). Data were analyzed using the MIXED procedure of SAS. Results showed a TM source × LPS × h effect for synovial fluid Co, Cu, and Se (P < 0.05); concentrations of TM peaked at hour 6 and decreased to preinjection values by hour 168 in both CON and CTM–LPS knees. A delayed peak was observed at hour 12 for CTM–LRS. Peak synovial fluid Cu and Se concentrations were higher in LPS knees, and Co was highest in CTM–LPS. A TM source × h interaction was observed for Zn (P < 0.05); concentrations peaked at hour 6 in CON vs. hour 12 for CTM. An LPS × h interaction was observed for Mn (P < 0.01); synovial concentration peaked at hour 6 in LPS knees compared with hour 24 in LRS. Synovial PGE2, C2C, CPII, and CS846 concentrations were greater with LPS (P ≤ 0.01), and C2C was greater (P < 0.01) in CTM compared with CON. Concentrations of CPII and PGE2 were unaffected by diet. A TM source × h × LPS interaction was observed for CS846 (P = 0.02). Concentrations of CS846 in CTM peaked at 12 h, whereas CON peaked at a lower concentration at 24 h (P < 0.05). Data indicate sufficient intake of a complexed TM source may support cartilage metabolism through increased aggrecan synthesis and type II collagen breakdown following an intra-articular LPS challenge in growing horses.
Technical note: validation of an automated feeding system for measuring individual animal feed intake in sheep housed in groups
Authors: Muir Stephanie K , Linden Nick P , Kennedy Andrew , Calder Grace , Kearney Gavin , Roberts Richard , Knight Matthew I , Behrendt Ralph
Published: January 2020

The development of feeding systems that can individually measure and control feed intake in a group-housed environment would allow a greater understanding of sheep intake without compromising animal welfare and behavior through the removal of social interactions between sheep. This study validated an automated feeding system for measuring feed intake of individual sheep when housed in groups. Validation of the feeding system was conducted during three separate experiments. The validation sampling involved the activation of four individual “feed events,” whereby four separate samples weighing approximately 50, 100, 200, and 400 g were removed from each feeder, with each feed event being linked to a specific radio frequency identification (RFID) tag. The feeder validation experiments evaluated the ability of the feeding system to 1) create a unique feed event every time a sample of pellets was collected from the feeder, 2) link the feed event to the correct RFID, and 3) accurately record the weight of feed that was manually removed. All feed events were initiated and logged in the feeding system with 100% of the events being linked to the correct test RFID. Concordance correlation coefficients between the feeding system-recorded feed weight and the manually removed weight were 0.99 within all three experiments. There was also no overall and little level-dependent bias between the weights measured by the feeding system and weights measured on the external scales. These results indicate the stability of the feeding system over time and consistency between the feeders within and across the three experiments. In conclusion, the automated feeding system developed for measuring individual animal feed intake was able to detect and record the unique electronic RFID associated with unique feed events and accurately capture the weight of feed removed. Furthermore, there was no change in the accuracy of the system from the start to the end of experimental periods, and the amount of feed removed in the feed event (or meal size) did not impact the accuracy of the results.
An Exemplar Interprofessional Academic Emergency Nurse Practitioner Program
Authors: Evans Dian Dowling , Ashooh Meredith Pollock , Kimble Laura P. , Heilpern Katherine L.
Published: January 2020

Emergency department census rates and manpower gaps have continued to rise over the past decade, creating a demand for well-prepared emergency nurse practitioners (ENPs). The implementation of the consensus model for advanced practice nurses has brought acknowledgment by leading health care, physician, and nursing organizations of the ENP specialty as critical to building a high-quality emergency care workforce. Recognition of the ENP's unique skill set, and therefore need of specialty certification, has led to a growing interest in the expansion of nurse practitioner curricula in emergency care. This article describes a novel approach for ENP education based on an interprofessional training model, with an in-depth discussion of curriculum development and clinical placement, as well as program outcomes and implications.
Emergency Nurses as Second Victims of Error
Authors: Ajri-Khameslou Mehdi , Abbaszadeh Abbas , Borhani Fariba
Published: January 2020

There are many nurses who are victims of errors in the hospital environment. It is quite essential to perceive the outcome of mistakes in nurses' profession. The aim of this scientific study was to interpret the causes that place nurses in danger of errors in emergency departments and also the consequences resulting from confronting the errors in the job environment. This research was designed to pursue a qualitative approach following S. Elo and H. Kyngäs's (2008) content analysis. Through the purposeful sampling, 18 emergency nurses were selected to participate in this study. In-depth semi-structured interviews were used for data collection. Participants were selected by purposive sampling. Data collection continued until saturation was reached. The results of data analysis were presented in three different categories: the psychological reactions to error, learning from errors, and avoiding reactions. The current study revealed that errors could create positive and negative impacts on the emergency nurses' attitude. Confronting the errors through learning from the mistakes can result in the improvement of patients' safety whereas the negative outcomes can provoke destructive effects on nurses' career. Nurses are considered as victims of errors; therefore, they need support and protection to enhance their career.