bluuebunny/crossref_metadata_2025 huggingface dataset:
The art and science of priority-setting: assessing the value of Public Health England’s Prioritization Framework
Authors: Maniatopoulos G , Hunter D J , Gray J
Published: January 2020

Background

Findings are presented from the evaluation of Public Health England’s (PHE) Prioritization Framework (PF) aimed to assist local authority commissioners with their public health investment and disinvestment decisions. The study explored the take up of the PF in three early adopter local authority settings.

Methods

Semi-structured interviews (n = 30) across three local authorities supplemented by participant observation of workshops.

Results

Participants acknowledged that the PF provided a systematic means of guiding priority-setting and one that encouraged transparency over investment and disinvestment decisions. The role performed by PHE and its regional teams in facilitating the process was especially welcomed and considered critical to the adoption process. However, uptake of the PF required a significant investment of time and commitment from public health teams at a time when resources were stretched. The impact of the political environment in the local government was a major factor determining the likely uptake of the PF. Ensuring committed leadership and engagement from senior politicians and officers was regarded as critical to success.

Conclusions

The study assessed the value and impact of PHE’s PF tool in three early adopter local authorities. Further research could explore the value of the tool in aiding investment and disinvestment decisions and its impact on spending.
After the social crisis: the transformation of employment relations at France Télécom
Authors: Doellgast Virginia , Bellego Maxime , Pannini Elisa
Published: January 2020

This article contributes to debates on the conditions for strengthening collective worker voice in financialized organizations. It examines change in employment relations at France Télécom/Orange (FT) following a social crisis associated with employee suicides in 2007–2009. FT’s labor unions developed creative approaches to study and publicize the negative effects of employment restructuring on workers’ psychosocial health. The common framing they developed became a source of ‘communicative power’, used to influence how the suicides were interpreted both within the firm and in the media. This power was deployed to encourage substantive social dialogue that institutionalized worker participation in management decision-making. Findings demonstrate the potentially transformative role of discursive strategies that assert the legitimacy of worker well-being as both a measure of and input to organizational performance.
Cephalic Tetanus: A Rare Case Report
Authors: Bağcı Zafer
Published: January 2020

Introduction

Tetanus is a preventable infectious disease with vaccination. Cephalic tetanus is the rarest form in which local tetanus can involve the cranial nerves.

Case

Herein, we report a case of cephalic tetanus in a 16-month-old girl who had never been vaccinated. The patient, who had a complaint of a wound on the cheek mucosa for 2 weeks, was seen playing with the soil in the garden 1 week ago and was found to have abundant soil removed by her mother. The patient was diagnosed as cephalic tetanus according to her complaints and clinical findings.

Discussion

We believe that, this is the first case reported in the literature of cephalic tetanus in such a young child wherein the disease focus of infection from a wound on the cheek mucosa. The symptom we defined as ‘a child who cries when she smiles’ presented in this case could only be associated with this disease.

Conclusion

In addition to detailed anamnesis and meticulous physical examination, the clinical symptoms that we have described for the first time in a child with cephalic tetanus should also be considered for early and accurate diagnosis.
Parents' Experiences About Support Following Stillbirth and Neonatal Death
Authors: Camacho Ávila Marcos , Fernández Medina Isabel María , Jiménez-López Francisca Rosa , Granero-Molina José , Hernández-Padilla José Manuel , Hernández Sánchez Encarnación , Fernández-Sola Cayetano
Published: January 2020

Background:

Stillbirth and neonatal death are one of the most stressful life events, with negative outcomes for parents. Society does not recognize this type of loss, and parental grieving is particularly complicated and intense.

Purpose:

The aim of this study was to describe and understand the experiences of parents in relation to professional and social support following stillbirth and neonatal death.

Methods:

This was a qualitative study based on Gadamer's hermeneutic phenomenology. Twenty-one semistructured interviews were carried out. Inductive analysis was used to find themes based on the data.

Results:

Twenty-one parents (13 mothers and 8 fathers) from 6 families participated in the study. The analysis identified 2 main themes: (1) “professional care in dealing with parents' grief,” with the subthemes “important aspects of professional care,” “continuing of pathways of care”; and (2) “effects of social support in parental grief,” including the subthemes “the silence that surrounds grieving parents,” “family and other children: a key element,” and “perinatal loss support groups: a reciprocal help.”

Implications for Practice:

Counseling and support according to parents' requirements by an interdisciplinary team of professionals educated in perinatal loss and ethical family-centered care is needed. A social support system for families is necessary to avoid negative emotional consequences.

Implications for Research:

Further research is needed to analyze midwives' and nurses' experience as facilitators to improve parental grief and the difficulties experienced by the family, other children, and friends of parents with perinatal loss in providing support.
Variables Associated With Lag Screw Sliding After Single-Screw Cephalomedullary Nail Fixation of Intertrochanteric Fractures
Authors: Parry Joshua A. , Sapp Travis , Langford Joshua R. , Koval Kenneth J. , Haidukewych George J.
Published: January 2020

Objectives:

To evaluate variables associated with lag screw sliding after single-screw cephalomedullary nail (CMN) fixation of intertrochanteric femur fractures.

Design:

Retrospective cohort study.

Setting:

Level-one trauma center.

Patients/Participants:

One hundred fifty-eight intertrochanteric fractures in patients older than 65 years with an average follow-up of 22 months.

Intervention:

Single-screw CMN fixation.

Main Outcome Measurements:

Lag screw sliding and revision surgeries.

Results:

The average amount of lag screw sliding was 5 ± 5 mm (range, 0–21 mm). Lag screw sliding was greater with unstable fracture patterns (mean difference 2 mm, 95% confidence interval 0.4–3.5 mm, P = 0.01) and calcar gapping >4 mm (mean difference 3.7 mm, 95% confidence interval 2–5 mm, P < 0.01). No association was found between lag screw sliding and age, female gender, implants, long versus short nails, distal interlock screw use, postoperative neck-shaft angle, or tip-apex distance (P > 0.05). Revision surgeries were performed in 6 (4%) patients. Indications included symptomatic lag screw removal (n = 2), avascular necrosis (n = 1), cutout (n = 1), loss of reduction (n = 1), and perimplant fracture (n = 1).

Conclusions:

Unstable fracture patterns are unavoidable; however, careful attention to calcar reduction and selection of dual-screw CMN implants may minimize lag screw sliding and its detrimental effects on outcomes.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
En-Bloc Resection Versus Resection After Evacuation and Suction of the Content for Orbital Optic Nerve Glioma Causing Visual Loss and Disfiguring Proptosis
Authors: Mohammad Abd El-Nasser A.
Published: January 2020

Purpose:

To evaluate the surgical outcomes of two different techniques of resection for optic nerve gliomas confined to the intra-orbital segment.

Methods:

This prospective, comparable, clinical interventional case series was conducted at the orbital clinic of Assiut University Hospital, the referral centre of Upper Egypt in the period between 2006 and 2018. The study included 10 children with optic nerve gliomas confined to the intra-orbital part without intracanalicular or intracranial extension and causing severe visual loss and disfiguring proptosis. In all cases, lateral orbitotomy was performed to expose the mass. In 5 cases (group A), the glioma was resected en-bloc. In 5 cases (group B), a new technique of resection was introduced. The wall of the glioma was incised, the content was evacuated and suctioned and followed by resection under good visualization of the markedly reduced mass in size.

Results:

In the 2 groups, no tumour regrowth was reported during the follow-up period of 3–12 years. In group A, the 5 cases developed postoperative third nerve damage with paralytic ptosis and one case had severe neurotrophic keratitis ended by dense corneal opacity. In group B, a healthy ipsilateral eye was preserved in all cases and no one case developed postoperative paralytic ptosis.

Conclusions:

Reduction of size of an intra-orbital optic nerve glioma by evacuation and suction of the content before resection is highly recommended. This makes the surgical field during resection more visible and minimizes the possibility of third or other nerves damage.
Hearing in Noise With Unilateral Versus Bilateral Bone Conduction Hearing Aids in Adults With Pseudo-conductive Hearing Loss
Authors: Hilly Ohad , Sokolov Meirav , Finkel Reut Beck , Zavdy Ofir , Shemesh Rafael , Attias Joseph
Published: January 2020

Objective:

The role of bilateral bone conduction amplification in patients with bilateral conductive hearing loss is unclear because cranial attenuation is usually considered negligible, and both cochleae can be stimulated with similar efficacy by each device. The aim of the study was to determine if bilateral bone-conduction hearing aids can improve hearing in noise in a homogeneous group of normal-hearing subjects with bilateral pseudo-conductive hearing loss.

Study Design:

Prospective, comparative.

Setting:

Department of Communication Sciences and Disorders in University of Haifa, Israel.

Subjects:

Department of Communication Sciences and Disorders in University of Haifa, Israel.

Interventions:

Induction of bilateral pseudo-conductive hearing loss of more than 35 dB using earplugs and earmuffs.

Main Outcome Measures:

Hearing quality on blinded comparison of unilateral versus bilateral amplification with bone-conduction hearing aids under different locations of noise.

Results:

Unilateral and bilateral amplification had similar efficacy when both signal and noise were presented from the front. However, bilateral amplification was significantly better when signals were presented from the front and noise was presented from both sides (SNR −10: 92% vs. 84%,p = 0.001; SNR −15: 84% vs. 78%,p = 0.005). Analysis of subject responses on blinded questionnaires revealed that 81% found hearing easier with bilateral amplification. Noise was reported to be more disturbing with unilateral amplification by 55% of the subjects and with bilateral amplification, by 9%.

Conclusions:

Bilateral amplification with bone conduction devices can improve understanding in noise in the binaural squelch setting. Subjective improvements with bilateral bone-conduction aids included better sound quality and reduced noise disturbance. These findings are consistent with the binaural mechanism of spectral release from masking.
Intrinsic Measures and Shape Analysis of the Intratemporal Facial Nerve
Authors: Hudson Thomas J. , Gare Bradley , Allen Daniel G. , Ladak Hanif M. , Agrawal Sumit K.
Published: January 2020

Hypothesis:

To characterize anatomical measurements and shape variation of the facial nerve within the temporal bone, and to create statistical shape models (SSMs) to enhance knowledge of temporal bone anatomy and aid in automated segmentation.

Background:

The facial nerve is a fundamental structure in otologic surgery, and detailed anatomic knowledge with surgical experience are needed to avoid its iatrogenic injury. Trainees can use simulators to practice surgical techniques, however manual segmentation required to develop simulations can be time consuming. Consequently, automated segmentation algorithms have been developed that use atlas registration, SSMs, and deep learning.

Methods:

Forty cadaveric temporal bones were evaluated using three dimensional microCT (μCT) scans. The image sets were aligned using rigid fiducial registration, and the facial nerve canals were segmented and analyzed. Detailed measurements were performed along the various sections of the nerve. Shape variability was then studied using two SSMs: one involving principal component analysis (PCA) and a second using the Statismo framework.

Results:

Measurements of the nerve canal revealed mean diameters and lengths of the labyrinthine, tympanic, and mastoid segments. The landmark PCA analysis demonstrated significant shape variation along one mode at the distal tympanic segment, and along three modes at the distal mastoid segment. The Statismo shape model was consistent with this analysis, emphasizing the variability at the mastoid segment. The models were made publicly available to aid in future research and foster collaborative work.

Conclusion:

The facial nerve exhibited statistical variation within the temporal bone. The models used form a framework for automated facial nerve segmentation and simulation for trainees.
Oxidative Stress in Pregnant Women Between 12 and 20 Weeks of Gestation and Preterm Birth
Authors: Moore Tiffany A. , Samson Kaeli , Ahmad Iman M. , Case Adam J. , Zimmerman Matthew C.
Published: January 2020

Background

A known relationship exists between oxidative stress and preterm birth (PTB). However, few studies have measured oxidative stress prospectively in early or midpregnancy, and no studies have used electron paramagnetic resonance (EPR) spectroscopy prospectively to predict PTB.

Objective

The purpose of this study was to identify predictive relationships between antioxidants and reactive oxygen species (ROS), specifically, superoxide (O2
•−), peroxynitrite (OONO−), and hydroxyl radical (●OH), using EPR spectroscopy, measured between 12 and 20 weeks of gestation and compare with the incidence of PTB.

Methods

Blood was obtained from pregnant women (n = 140) recruited from a tertiary perinatal center. Whole blood was analyzed directly for ROS, O2
•−, OONO−, and ●OH using EPR spectroscopy. Red blood cell lysate was used to measure antioxidants. PTB was defined as parturition at <37 weeks of gestation.

Results

No differences were found between ROS, O2
•−, OONO−, or ●OH with the incidence of PTB. Catalase activity, glutathione, and reduced/oxidized glutathione ratio were significantly lower with PTB. Logistic regression suggests decreased catalase activity in pregnant women is associated with increased odds of delivering prematurely.

Discussion

We prospectively compared antioxidants and specific ROS using EPR spectroscopy in pregnant women between 12 and 20 weeks of gestation with the incidence of PTB. Results are minimal but do suggest that antioxidants—specifically decreased catalase activity—in early pregnancy may be associated with PTB; however, these findings should be cautiously interpreted and may not have clinical significance.
Optimizing Quality of Life for Patients with Breast Cancer–Related Lymphedema: A Prospective Study Combining DIEP Flap Breast Reconstruction and Lymphedema Surgery
Authors: Chang Edward I. , Ibrahim Amir , Liu Jun , Robe Charee , Suami Hiroo , Hanasono Matthew M. , Nguyen Alexander T.
Published: January 2020

Background:

Patients with breast cancer–related lymphedema can be treated with a simultaneous deep inferior epigastric perforator (DIEP) flap, vascularized inguinal lymph node transfer, and lymphovenous anastomosis for aesthetic breast reconstruction and lymphedema in one operation.

Methods:

The authors performed a comparison of prospectively followed patients who underwent free flap breast reconstruction with vascularized inguinal lymph node transfer and anastomosis to a retrospective cohort of patients who underwent free flap breast reconstruction with vascularized inguinal lymph node transfer alone.

Results:

Thirty-three patients underwent DIEP flap reconstruction with vascularized inguinal lymph node transfer and lymphovenous anastomosis, and 21 received a free flap with lymph node transfer alone. There were no significant differences in demographics, adjuvant chemotherapy, or radiation therapy. The average number of nodes removed was also equivalent (21.2 versus 21.4 nodes). Two anastomoses per patient, on average, were performed (range, one to four) in the combined cohort, and all patients (100 percent) reported a subjective improvement in symptoms, compared with 81.0 percent of patients undergoing only lymph node transfer (p = 0.019). Perometer measurements demonstrated a significant reduction between the groups at early time points [3 months, 40.7 percent versus 20.0 percent (p = 0.037); 6 months, 57.0 percent versus 44.5 percent (p = 0.043)]; however, the difference was not statistically significant at 12 months (60.4 percent versus 57.8 percent; p = 0.43).

Conclusion:

This is the first prospective study demonstrating the safety and efficacy of a combined DIEP flap with vascularized inguinal lymph node transfer and lymphovenous anastomosis, which may be superior to lymph node transfer alone.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Simultaneous Multislice Diffusion-Weighted Imaging of the Kidneys at 3 T
Authors: Tavakoli Andrej , Krammer Julia , Attenberger UIrike I. , Budjan Johannes , Stemmer Alto , Nickel Dominik , Kannengiesser Stephan , Morelli John N. , Schoenberg Stefan O. , Riffel Philipp
Published: January 2020

Purpose

The aim of this study was to compare respiratory-triggered diffusion-weighted imaging with simultaneous-multislice acceleration (SMS-RT-DWI) to a standard free-breathing echoplanar DWI (s-DWI) for 3 T renal imaging with respect to image quality and artifacts.

Materials and Methods

A total of 40 patients who had undergone renal magnetic resonance imaging were included in this retrospective analysis of a prospectively planned cohort study. All examinations were performed on a 3 T whole-body magnetic resonance system. Both s-DWI and SMS-RT-DWI were obtained and images were independently reviewed by 2 radiologists on a 5-point Likert scale with respect to overall preference and image quality, renal edge and parenchymal sharpness, cortico-medullary differentiation, and sequence-related artifacts. Furthermore, discernibility of renal lesions was assessed. The signal-to-noise ratio (SNR) was measured from SNR maps. The derived mean apparent diffusion coefficients were also compared. Qualitative parameters were assessed with the Wilcoxon rank-sum test, and quantitative parameters, with the Student t test.

Results

Overall image quality, renal edge, and parenchymal sharpness of SMS-RT-DWI were rated as superior to s-DWI by the readers, with fewer sequence-related artifacts (P < 0.01 for all). Lesion discernibility was significantly improved for SMS-RT-DWI (P < 0.01). Both readers preferred SMS-RT-DWI to s-DWI in all cases (40/40). The acquisition time for SMS-RT-DWI was 30% shorter than for s-DWI. Mean SNR heterogeneity of SMS-RT-DWI at b = 800 s/mm2 was statistically significantly lower than s-DWI, whereas mean SNR was significantly higher for SMS-RT-DWI. Mean apparent diffusion coefficient values from both sequences were comparably homogeneous throughout the kidneys.

Conclusion

Simultaneous multislice DWI of the kidney at 3 T with respiratory triggering yields substantially improved image quality and lesion discernibility compared with standard single-shot echoplanar DWI with a 30% reduction in scan acquisition time.
Constructing plasticity phenotypes to classify experience-dependent development of the visual cortex
Authors: Balsor Justin L. , Jones David G. , Murphy Kathryn M.
Published: January 2020

Many neural mechanisms regulate experience-dependent plasticity in the visual cortex (V1) and new techniques for quantifying large numbers of proteins or genes are transforming how plasticity is studied into the era of big data. With those large data sets comes the challenge of extracting biologically meaningful results about visual plasticity from data-driven analytical methods designed for high-dimensional data. In other areas of neuroscience, high-information content methodologies are revealing more subtle aspects of neural development and individual variations that give rise to a richer picture of brain disorders. We have developed an approach for studying V1 plasticity that takes advantage of the known functions of many synaptic proteins for regulating visual plasticity and using that to rebrand the results of high-dimensional analyses into a plasticity phenotype. Here we provide a primer for analyzing experience-dependent plasticity in V1 using example R code to identify high-dimensional changes in a group of proteins. We describe using PCA to classify high-dimensional plasticity features and use them to construct a plasticity phenotype. In the examples, we show how the plasticity phenotype can be visualized and used to identify neurobiological features in V1 that change during development or after different visual rearing conditions. We include an R package “v1hdexplorer” that aggregates the various coding packages and custom visualization scripts written in R Studio.
Spatiotemporal Genetic Diversity of Lions
Authors: Curry Caitlin J. , Davis Brian W. , Bertola Laura D. , White Paula A. , Murphy William J. , Derr James N.
Published: January 2020

The Scramble for Africa in the late 1800s marked the beginning of increased human population growth in Africa. Here, we determined the genetic architecture of both historical and modern lions to identify changes in genetic diversity that occurred during this period of landscape and anthropogenic change. We surveyed microsatellite and mitochondrial genetic variation from 143 high-quality museum specimens of known provenance and combined them with data from recently published nuclear and mitochondrial studies. Analysis of variation at 9 microsatellites and 280 polymorphic mitogenome SNPs indicate the presence of male-mediated gene flow and recent isolation of local subpopulations, likely due to habitat fragmentation. Nuclear markers showed a significant decrease in genetic diversity from the historical (HE=0.833) to the modern (HE=0.796) populations, while mitochondrial genetic diversity was maintained (Hd=0.98 for both). While the historical population appears to have been panmictic based on nDNA data, hierarchical structure analysis identified four tiers of fine structure in modern populations, able to detect most sampling locations. Mitochondrial analyses identified 4 clusters: Southern, Mixed, Eastern, and Western; and were consistent between modern and historically sampled haplotypes. Within the last century, habitat fragmentation caused lion subpopulations to become more isolated as human expansion changed the African landscape. This resulted in an increase in fine-scale nuclear genetic structure and loss of genetic diversity as subpopulations became more differentiated, while mitochondrial structure and diversity was maintained over time.
Unequal contribution of two paralogous centromeric histones to function the cowpea centromere
Authors: Ishii Takayoshi , Juranić Martina , Maheshwari Shamoni , de Oliveira Bustamante Fernanda , Vogt Maximilian Moritz , Salinas-Gamboa Rigel , Dreissig Steven , Gursanscky Nial , How Tracy , Fuchs Joerg , Schubert Veit , Spriggs Andrew , Vielle-Calzada Jean-Philippe , Comai Luca , Koltunow Anna M. G. , Houben Andreas
Published: January 2020

The legume cowpea (Vigna unguiculata, 2n=2x=22) has significant tolerance to drought and heat stress. Here we analysed and manipulated cowpea centromere-specific histone H3 (CENH3) genes, aiming to establish a centromere-based doubled-haploid method for use in genetic improvement of this dryland crop in future. Cowpea encodes two functional CENH3 variants (CENH3.1 and CENH3.2) and two CENH3 pseudogenes. Phylogenetic analysis suggests that gene duplication of CENH3 occurred independently during the speciation ofV. unguiculataand the relatedV. mungowithout a genome duplication event. Both functional cowpeaCENH3variants are transcribed, and the corresponding proteins are intermingled in subdomains of different types of centromere sequences in a tissue-specific manner together with the outer kinetochore protein CENPC. CENH3.2 is removed from the generative cell of mature pollen, while CENH3.1 persists. Differences between both CENH3 paralogs are restricted to the N-terminus. The complete CRISPR/Cas9-based inactivation ofCENH3.1resulted in delayed vegetative growth and sterility, indicating that this variant is needed for plant development and reproduction. By contrast,CENH3.2knockout individuals did not show obvious defects during vegetative and reproductive development, suggesting that the gene is an early stage of subfunctionalization or pseudogenization.

One-sentence summary

The two paralogous centromeric histones (CENH3) of cowpea contribute unequal to the function of the centromere.
Metacognition and memory of emotional information: Judgments of learning predict the affectivity congruence effect in free recall
Authors: Siedlecka Marta , Blaut Agata , Paulewicz Borys , Kłosowska Joanna
Published: January 2020

Memory of emotional information often depends on the current mood and the dominant affective state. For example, studies show that people tend to recall emotional information of valence that is congruent with their affective traits. However, not much is known about whether this tendency is captured by metacognitive judgments of learning (JOLs). The aim of this study was to find out how people who score low or high on affectivity scales assess their memory of emotional material. We used a free-recall task with self-referential neutral, positive, and negative adjectives. The results show the affectivity congruence effect: the number of negative words recalled is related to affectivity; it increases with Negative Affectivity (NA) and decreases with Positive Affectivity (PA). Metacognitive assessment of future recall is also related to affectivity. Higher PA is related to higher JOLs for positive words and lower JOLs for negative words. Higher NA is related to higher JOLs for negative words and lower JOLs for positive words. The results suggest that metacognitive processes are sensitive to affective trait-specific memory bias.
Work horse strainClostridioides difficile630Δermis oblivious to its anaerobic lifestyle
Authors: Troitzsch Daniel , Zhang Hao , Dittmann Silvia , Düsterhöft Dorothee , Michel Annika-Marisa , Jänsch Lothar , Riedel Katharina , Borrero-de Acuña José Manuel , Jahn Dieter , Sievers Susanne
Published: January 2020

The laboratory reference strain 630Δermof the anaerobic human pathogenClostridioides difficileis characterized by a remarkable high oxygen tolerance. We show that an amino acid exchange in the DNA binding domain of the hydrogen peroxide sensor PerR results in a constitutive derepression of PerR-controlled genes and thus in an oxidative stress response even under anaerobic conditions. This questions the model status, strain 630Δermclaims inC. difficileresearch.
ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration
Authors: Aharonov Alla , Shakked Avraham , Umansky Kfir Baruch , Savidor Alon , Kain David , Lendengolts Daria , Revach Or-Yam , Morikawa Yuka , Dong Jixin , Levin Yishai , Geiger Benjamin , Martin James F. , Tzahor Eldad
Published: January 2020

Cardiomyocyte (CM) loss after injury results in adverse remodelling and fibrosis, which inevitably lead to heart failure. ERBB2-Neuregulin and Hippo-YAP signaling pathways are key mediators of CM proliferation and regeneration, yet the crosstalk between these pathways is unclear. Here, we demonstrate in adult mice that transient over-expression (OE) of activated ERBB2 in CMs promotes cardiac regeneration in a heart failure model. OE CMs present an EMT-like regenerative response manifested by cytoskeletal remodelling, junction dissolution, migration, and ECM turnover. Molecularly, we identified YAP as a critical mediator of ERBB2 signaling. In OE CMs, YAP interacts with nuclear envelope and cytoskeletal components, reflecting the altered mechanic state elicited by ERBB2. Hippo-independent activating phosphorylation on YAP at S352 and S274 were enriched in OE CMs, peaking during metaphase, and viral overexpression of YAP phospho-mutants dampened the proliferative competence of OE CMs. Taken together, we demonstrate a potent ERBB2-mediated YAP mechanosensory signaling, involving EMT-like characteristics, resulting in heart regeneration.

Highlights

ERBB2-driven regeneration of scarred hearts recapitulates core-EMT processes

YAP is activated and required downstream to ERBB2 signaling in CMs

YAP activity is mechanically driven by cytoskeleton and nuclear envelope remodeling

YAP S274 and S352 phosphorylation is essential for CM mitosis
The Latent Genetic Structure of Impulsivity and its Relation to Internalizing Psychopathology
Authors: Gustavson Daniel E. , Friedman Naomi P. , Fontanillas Pierre , Elson Sarah L. ,   the 23andMe Research Team, Palmer Abraham A. , Sanchez-Roige Sandra
Published: January 2020

Factor analyses suggest that impulsivity traits that capture tendencies to act prematurely or take risks tap partially distinct constructs. We applied genomic structure equation modeling to evaluate the genetic factor structure of two well-established impulsivity questionnaires, using published genome-wide association study statistics from up to 22,861 participants. We also tested the hypotheses that delay discounting would be genetically separable from other impulsivity factors, and that emotionally-triggered facets of impulsivity (urgency) would be those most strongly genetically correlated with an internalizing latent factor. A five-factor model best fit the impulsivity data. Delay discounting was genetically distinct from these five factors. As expected, the two urgency subscales were most strongly related to an Internalizing Psychopathology latent factor. These findings provide empirical genetic evidence that impulsivity can be disarticulated into distinct categories of differential relevance for internalizing psychopathology. They also demonstrate how measured genetic markers can be used to inform theories of psychology/personality.
Atomistic basis of microtubule dynamic instability assessed via multiscale modeling
Authors: Hemmat Mahya , Odde David J.
Published: January 2020

Microtubule “dynamic instability,” the abrupt switching from assembly to disassembly caused by the hydrolysis of GTP to GDP within the β subunit of the αβ-tubulin heterodimer, is necessary for vital cellular processes such as mitosis and migration. Despite existing high-resolution structural data, the key mechanochemical differences between the GTP and GDP states that mediate dynamic instability behavior remain unclear. Starting with a published atomic-level structure as an input, we used multiscale modeling to find that GTP hydrolysis results in both longitudinal bond weakening (~4 kBT) and an outward bending preference (~1.5 kBT) to both drive dynamic instability and give rise to the microtubule tip structures previously observed by light and electron microscopy. More generally, our study provides an example where atomic level structural information is used as the sole input to predict cellular level dynamics without parameter adjustment.
siRNA-mediatedde novosilencing ofAc/Dstransposons is initiated by alternative transposition in maize
Authors: Wang Dafang , Zhang Jianbo , Zuo Tao , Lisch Damon , Zhao Meixia , Peterson Thomas
Published: January 2020

Although Transposable Elements (TEs) comprise a major fraction of many higher eukaryotic genomes, most TEs are silenced by host defense mechanisms. The means by which otherwise active TEs are recognized and silenced remains poorly understood. Here we analyzed two independent cases of spontaneous silencing of the active maizeAc/Dstransposon system. This silencing was initiated by Alternative Transposition (AT), a type of aberrant transposition event that engages the termini of two nearby separate TEs. AT during DNA replication can generate Composite Insertions (CIs) that contain inverted duplications of the transposon sequences. We show that the inverted duplications of two CIs are transcribed to produce dsRNAs that trigger the production of two distinct classes of siRNAs: a 24-nt class complementary to the TE terminal inverted repeats (TIRs) and non-coding sub-terminal regions, and a 21-22 nt class corresponding to the TE transcribed regions. Plants containing these siRNA-generating CIs exhibit decreased levels ofActranscript and heritable repression ofAc/Dstransposition. This study documents the first case of TE silencing attributable to transposon self-initiated AT and may represent a general initiating mechanism for silencing of DNA transposons.

Article summary

Transposable Elements (TEs) are often silenced by their hosts, but how TEs are initially recognized for silencing remains unclear. Here we describe two independent loci that inducede novoheritable silencing of maizeAc/Dstransposons. Plants containing these loci produce dsRNA andAc-homologous small interfering RNAs, and exhibit decreased levels ofActranscript and heritable repression ofAc/Dstransposition. We show that these loci comprise inverted duplications of TE sequences generated by Alternative Transposition coupled with DNA re-replication. This study documents the first case of transposon silencing induced by AT and may represent a general initiating mechanism for TE silencing.
Genomic surveillance enables suitability assessment ofSalmonellagene targets used for culture-independent diagnostic testing
Authors: Rockett Rebecca J. , Arnott Alicia , Wang Qinning , Howard Peter , Sintchenko Vitali
Published: January 2020

Salmonellais a highly diverse genus consisting of over 2600 serovars responsible for high-burden food- and water-borne gastroenteritis worldwide. Sensitivity and specificity of PCR-based culture-independent diagnostic testing (CIDT) systems forSalmonella, which depend on a highly conserved gene target, can be affected by single nucleotide polymorphisms (SNPs), indels and genomic rearrangements within primer and probe sequences. This report demonstrates the value of prospectively collected genomic data for verifying CIDT targets.

We utilised the genomes of 3165Salmonellaisolates prospectively collected and sequenced in Australia. The sequence ofSalmonellaCIDT PCR gene targets (ttrA, spaOandinvA) were systematically interrogated to measure nucleotide dissimilarity. Analysis of 52 different serovars and 79 MLST types demonstrated dissimilarity within and between PCR gene targets ranging between 0 – 81.3 SNP/Kbp (0 and 141 SNPs). Lowest average dissimilarity was observed in thettrAtarget gene used by the Roche LightMix at 2.0 SNP/Kbp [range 0 – 46.7]), however entropy across the gene demonstrates it may not be the most stable CIDT target.

While debate continues over the benefits and pitfalls of replacing bacterial culture with molecular assays, the growing volumes of genomic surveillance data enable periodic regional reassessment and validation of CIDT targets against both prevalent and emerging serovars. If PCR systems are to become the primary screening and diagnostic tool for laboratory diagnosis of salmonellosis, ongoing monitoring of the genomic diversity in PCR target regions is warranted as is the potential inclusion of twoSalmonellaPCR targets into frontline diagnostic systems.
ALPPL2 is a highly specific and targetable tumor cell surface antigen
Authors: Su Yang , Zhang Xin , Bidlingmaier Scott , Behrens Christopher R. , Lee Nam-Kyung , Liu Bin
Published: January 2020

It has been challenging to identify tumor-specific cell surface antigens as the vast majority of tumor-associated antigens are also expressed by some normal tissues. In the course of our study on mesothelioma, we identified a highly specific tumor cell surface antigen that can be targeted for therapy development. Mesothelioma is caused by malignant transformation of the mesothelium, incurable and categorized into three histological subtypes, epithelioid, biphasic and sarcomatoid. To identity novel mesothelioma cell surface antigens with broad subtype coverage and high tissue specificity, we have previously selected phage antibody display libraries on live mesothelioma cells and tissues following counter-selection on normal cells, and identified a panel of human antibodies that bind all subtypes of mesothelioma but not normal mesothelium. One of the antibodies, M25, showed high specificity, and we hereby report the identification of the M25 antigen as ALPPL2. We performed immunohistochemistry on normal human tissues and found that ALPPL2 is expressed only on placental trophoblasts but not any other normal tissues. This exquisite tissue specificity and broad tumor type coverage suggests that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, we developed an ALPPL2-targeted antibody-drug conjugate and demonstrated potent and specific tumor killingin vitroandin vivoagainst both epithelioid and sarcomatoid mesothelioma. Thus ALPPL2 belongs to a rare class of cell surface antigens that can be said as being truly tumor specific and is well suited for therapy development against ALPPL2 expressing tumors.
Homogeneous multifocal excitation for high-throughput super-resolution imaging
Authors: Mahecic Dora , Gambarotto Davide , Douglass Kyle M. , Fortun Denis , Banterle Niccoló , Le Guennec Maeva , Ibrahim Khalid , Gönczy Pierre , Hamel Virginie , Guichard Paul , Manley Suliana
Published: January 2020

Super-resolution microscopies, which allow features below the diffraction limit to be resolved, have become an established tool in biological research. However, imaging throughput remains a major bottleneck in using them for quantitative biology, which requires large datasets to overcome the noise of the imaging itself and to capture the variability inherent to biological processes. Here, we develop a multi-focal flat illumination for field independent imaging (mfFIFI) module, and integrate it into an instant structured illumination microscope (iSIM). Our instrument extends the field of view (FOV) to >100×100 µm2without compromising image quality, and maintains high-speed (100 Hz), multi-color, volumetric imaging at double the diffraction-limited resolution. We further extend the effective FOV by stitching multiple adjacent images together to perform fast live-cell super-resolution imaging of dozens of cells. Finally, we combine our flat-fielded iSIM setup with ultrastructure expansion microscopy (U-ExM) to collect 3D images of hundreds of centrioles in human cells, as well as of thousands of purifiedChlamydomonas reinhardtiicentrioles per hour at an effective resolution of ∼35 nm. We apply classification and particle averaging to these large datasets, allowing us to map the 3D organization of post-translational modifications of centriolar microtubules, revealing differences in their coverage and positioning.
Sucrose promotes etiolated stem branching through activation of cytokinin accumulation followed by vacuolar invertase activity
Authors: Salam Bolaji Babajide , Barbier Francois , Danieli Raz , Ziv Carmit , Spíchal Lukáš , Teper-Bamnolker Paula , Jiang Jiming , Ori Naomi , Beveridge Christine , Eshel Dani
Published: January 2020

The potato (Solanum tuberosumL.) tuber is a swollen stem. Sprouts growing from the tuber nodes represent dormancy release and loss of apical dominance. We recently identified sucrose as a key player in triggering potato stem branching. To decipher the mechanisms by which sucrose induces stem branching, we investigated the nature of the inducing molecule and the involvement of vacuolar invertase (VInv) and the plant hormone cytokinin (CK) in this process. Sucrose was more efficient at enhancing lateral bud burst and elongation than either of its hexose moieties (glucose and fructose), or a slowly metabolizable analog of sucrose (palatinose). Sucrose feeding induced expression of the sucrose transporter geneSUT2, followed by enhanced expression and activity of VInv in the lateral bud prior to its burst. We observed a reduction in the number of branches on stems ofVInv-RNA interference lines during sucrose feeding, suggesting that sucrose breakdown is needed for lateral bud burst. Sucrose feeding led to increased CK content in the lateral bud base prior to bud burst. Inhibition of CK synthesis or perception inhibited the sucrose-induced bud burst, suggesting that sucrose induces stem branching through CK. Together, our results indicate that sucrose is transported to the bud, where it promotes bud burst by inducing CK accumulation and VInv activity.
A Bayesian Multi-Task Approach for Detecting Global Microbiome Associations
Authors: Hatami Farhad , Beamish Emma , Rigby Rachael , Dondelinger Frank
Published: January 2020

Motivation

The human gut microbiome has been shown to be associated with a variety of human diseases, including cancer, metabolic conditions and inflammatory bowel disease. Current statistical techniques for microbiome association studies are limited by relying on measures of ecological distance, or only allowing for the detection of associations with individual bacterial species, rather than the whole microbiome.

Results

In this work, we develop a novel Bayesian multi-task approach for detecting global microbiome associations. Our method is not dependent on a choice of distance measure, and is able to incorporate phylogenetic information about microbial species. We apply our method to simulated data and show that it allows for consistent estimation of global microbiome effects. Additionally, we investigate the performance of the model on two real-world microbiome studies: a study of microbiome-metabolome associations in inflammatory bowel disease (Beamish, 2017), and a study of associations between diet and the gut microbiome in mice (Turnbaughet al., 2009). We show that we can use the method to reliably detect associations in real-world datasets with varying numbers of samples and covariates.

Availability

Our method is implemented using the R interface to the Stan Hamiltonian Monte Carlo sampler. Software for running our methods is available athttps://github.com/FrankD/MicrobiomeGlobalAssociations.

Contact

f.dondelinger@lancaster.ac.uk
Proteomics Dissection of Cardiac Protein Profiles of Humans and Model Organisms
Authors: Linscheid Nora , Santos Alberto , Poulsen Pi Camilla , Mills Robert W. , Stolte Christian , Leurs Ulrike , Ye Johan Z. , Calloe Kirstine , Thomsen Morten B. , Bentzen Bo H. , Lundegaard Pia R. , Olesen Morten S. , Jensen Lars J. , Olsen Jesper V. , Lundby Alicia
Published: January 2020

The study of human cardiac pathologies often relies on research conducted in model organisms to gain molecular insight into disease and to develop novel treatment strategies; however, translating findings from model organisms back to human can present a significant challenge, in part due to a lack of knowledge about the differences across species in cardiac protein abundances and their interactions. Here we set out to bridge this knowledge gap by presenting a global analysis of cardiac protein expression profiles in humans and commonly used model organisms. Using quantitative mass spectrometry-based proteomics, we measured the abundance of ~7,000 proteins in samples from the separate chambers of human, pig, horse, rat, mouse and zebrafish hearts. This knowledgebase of cardiac protein signatures is accessible through an online database at: atlas.cardiacproteomics.com. Quantitative comparison of the protein profiles support the pig as model organism of choice for arrhythmogenic right ventricular cardiomyopathy whereas comparison of profiles from the two-chambered zebrafish heart suggests a better resemblance to the right side of mammalian hearts. This proteomics resource facilitates translational prospect of cardiac studies from model organisms to humans by enabling direct comparison of disease-linked protein networks across species.
Sound context modulates perceived vocal emotion
Authors: Liuni Marco , Ponsot Emmanuel , Bryant Gregory A. , Aucouturier JJ
Published: January 2020

Many animal vocalizations contain nonlinear acoustic phenomena as a consequence of physiological arousal. In humans, nonlinear features are processed early in the auditory system, and are used to efficiently detect alarm calls and other urgent signals. Yet, high-level emotional and semantic contextual factors likely guide the perception and evaluation of roughness features in vocal sounds. Here we examined the relationship between perceived vocal arousal and auditory context. We presented listeners with nonverbal vocalizations (yells of a single vowel) at varying levels of portrayed vocal arousal, in two musical contexts (clean guitar, distorted guitar) and one non-musical context (modulated noise). As predicted, vocalizations with higher levels of portrayed vocal arousal were judged as more negative and more emotionally aroused than the same voices produced with low vocal arousal. Moreover, both the perceived valence and emotional arousal of vocalizations were significantly affected by both musical and non-musical contexts. These results show the importance of auditory context in judging emotional arousal and valence in voices and music, and suggest that nonlinear features in music are processed similarly to communicative vocal signals.
Individual differences among deep neural network models
Authors: Mehrer Johannes , Spoerer Courtney J. , Kriegeskorte Nikolaus , Kietzmann Tim C.
Published: January 2020

Deep neural networks (DNNs) excel at visual recognition tasks and are increasingly used as a modelling framework for neural computations in the primate brain. However, each DNN instance, just like each individual brain, has a unique connectivity and representational profile. Here, we investigate individual differences among DNN instances that arise from varying only the random initialization of the network weights. Using representational similarity analysis, we demonstrate that this minimal change in initial conditions prior to training leads to substantial differences in intermediate and higher-level network representations, despite achieving indistinguishable network-level classification performance. We locate the origins of the effects in an under-constrained alignment of category exemplars, rather than a misalignment of category centroids. Furthermore, while network regularization can increase the consistency of learned representations, considerable differences remain. These results suggest that computational neuroscientists working with DNNs should base their inferences on multiple networks instances instead of single off-the-shelf networks.