bluuebunny/crossref_metadata_2025 huggingface dataset:
Professional faultlines and interprofessional differentiation in multidisciplinary team innovation: The moderating role of inclusive leadership
Authors: Mitchell Rebecca , Boyle Brendan
Published: February 2020

Background

Interprofessional health care teams are increasingly employed to solve complex problems through innovative solutions. However, there is evidence that such teams are not always successful. The impact of profession and professional divides is likely to be particularly important in health care teams as team membership and contribution typically derive from member’s unique professional expertise. Yet, there remains a dearth of research exploring the role of professional faultlines in multidisciplinary teams. In an effort to address this research gap, we explore the role of professional faultlines in interprofessional team innovation.

Purpose

Drawing on faultline theory and learning from the sociology of the professions, this study develops and investigates a model of team innovation predicted by professional faultlines. More specifically, we propose that professional faultlines increase interprofessional differentiation within teams and, through this mediator, increase innovation, contingent on interprofessional inclusive leadership.

Methodology

We investigate our model and hypothesis using a cross-sectional correlational design. Survey data of 70 interprofessional health care teams is used to investigate our model.

Results

Support is found for our moderated mediation model. We find evidence that professional faultlines increase interprofessional differentiation, which, in turn, increases team innovation contingent on inclusive leadership.

Conclusion

Our study finding allows us to contribute to the evolving discussion on health care teams and team faultlines, particularly professional faultlines, and their role in team innovation.

Practice Implications

A number of strategies to increase innovation in interprofessional teams are indicated by our findings. In particular, the role of inclusive leadership is highlighted as a useful approach, particularly when profession aligns with biodemographic attributes, such as gender.
Concussive Symptoms Following Pediatric Mild Traumatic Brain Injury
Authors: Yumul Joy Noelle , McKinlay Audrey , Than Martin , Anderson Vicki , Catroppa Cathy
Published: February 2020

Objectives:

To determine the proportion of children with postconcussive symptoms (PCSs) and to explore the influence of noninjury and injury factors on parents' PCS report at 3 months postinjury.

Design:

A cross-sectional analysis of the 3-month postinjury data from a larger, prospective, longitudinal study.

Methods:

Parents and their child aged 2 to 12 years who presented at the emergency department with either a mild traumatic brain injury (mTBI) or a superficial injury to the head (SIH) were recruited. Parents reported their child's symptoms at the time of injury and at 3 months postinjury. Child, family/parent, and injury characteristics were considered as potential predictors. Logistic regression was conducted to determine which factors increase the likelihood of parents' PCS report.

Results:

At 3 months postinjury, 30% and 13% of children in the mTBI and SIH groups exhibited 1 or more symptoms, respectively. On the other hand, 18% (mTBI) and 8% (SIH) continued to have ongoing problems when 2 or more symptoms were considered at follow-up. The final model, which included child's sex, injury group, number of symptoms at the time of injury, and parental stress, had a significant predictive utility in determining parents' report of 1 or more symptoms at follow-up. Only parental stress continued to be a significant predictor when considering 2 or more symptoms at 3 months postinjury.

Conclusions:

Children with mTBI have worse outcomes than children with SIH at follow-up, with parents more likely to report 1 or more ongoing symptoms if their children had an mTBI. Postinjury assessment of parental stress and ongoing symptom monitoring in young children with mTBI will allow for timely provision of support for the family.
Behavior Problems Following Childhood TBI: The Role of Sex, Age, and Time Since Injury
Authors: Wade Shari L. , Kaizar Eloise E. , Narad Megan E. , Zang Huaiyu , Kurowski Brad G. , Miley Aimee E. , Moscato Emily L. , Aguilar Jessica M. , Yeates Keith Owen , Taylor H. Gerry , Zhang Nanhua
Published: February 2020

Objective:

To examine the frequency of behavioral problems after childhood traumatic brain injury (TBI) and their associations with injury severity, sex, and social environmental factors.

Setting:

Children's hospitals in the Midwestern/Western United States.

Participants:

381 boys and 210 girls with moderate (n = 359) and severe (n = 227) TBI, with an average age at injury of 11.7 years (range 0.3-18) who were injured ≤3 years ago.

Design:

Secondary data analysis of a multistudy cohort.

Main Measures:

Child Behavior Checklist (CBCL) administered pretreatment.

Results:

Thirty-seven percent had borderline/clinical elevations on the CBCL Total Problem Scale, with comparable rates of Internalizing and Externalizing problems (33% and 31%, respectively). Less parental education was associated with higher rates of internalizing, externalizing, and total problems. Time since injury had a linear association with internalizing symptoms, with greater symptoms at longer postinjury intervals. Younger boys had significantly higher levels of oppositional defiant symptoms than girls, whereas older girls had significantly greater attention-deficit hyperactivity disorder symptoms than boys.

Conclusions:

Pediatric TBI is associated with high rates of behavior problems, with lower socioeconomic status predicting substantially elevated risk. Associations of higher levels of internalizing symptoms with greater time since injury highlight the importance of tracking children over time.
Insulin-like growth factor 2 binding protein 3 expression on endoscopic ultrasound guided fine needle aspiration specimens in pancreatic ductal adenocarcinoma
Authors: Tadic Mario , Stoos-Veic Tajana , Kujundzic Milan , Turcic Petra , Aralica Gorana , Boskoski Ivo
Published: February 2020

Background:

Despite numerous investigations, we still do not have a specific marker for pancreatic ductal adenocarcinoma. Only guideline-recommended biomarker for pancreatic ductal adenocarcinoma is the CA19-9, but it is also present in other gastrointestinal diseases. IMP3 is a new potential biomarker that is over-expressed in some cancers. The aims of our study were (1) to assess IMP3 in benign pancreatic lesions and pancreatic cancer, and (2) to estimate its concentrations in localized and advanced pancreatic cancer.

Patients and methods:

Seventy-five patients with solid pancreatic lesions who underwent EUS-FNA were included. Patients were divided into three groups: benign lesions, cancer localized only on the pancreas, and patients with advanced pancreatic cancer (locally advanced or with distal metastases). Immunoreactivity of IMP3 was assessed on cytological smears sampled by endoscopic ultrasound.

Results:

IMP3 was expressed in 89% of the patients with pancreatic cancer and not in benign lesions. Stronger expression of IMP3 protein and stage of the pancreatic cancer was statistically significant. IMP3 was expressed in all localized cancers and in 85% of patients with advanced pancreatic cancer. In the subgroup with locally advanced cancer, IMP3 was expressed in 88%, and in 83% of patients in the subgroup with distal metastasis (P = 0.007). In the present study, sensitivity was 89%, specificity 100%, with positive predictive value of 100% and negative predictive value of 63%.

Conclusion:

There is a positive correlation between IMP3 expression and TNM stages of the pancreatic cancer. Higher expression of IMP3 on EUS-FNA specimens can suggest poorer prognosis.
Assessment of Lesion Detectability in Dynamic Whole-Body PET Imaging Using Compartmental and Patlak Parametric Mapping
Authors: Zaker Neda , Kotasidis Fotis , Garibotto Valentina , Zaidi Habib
Published: February 2020

Purpose

Hybrid dynamic imaging allows not only the estimation of whole-body (WB) macroparametric maps but also the estimation of microparameters in the initial bed position targeting the blood pool region containing the pathology owing to the limited axial field of view of PET scanners. In this work, we assessed the capability of multipass WB 18F-FDG PET parametric imaging in terms of lesion detectability through qualitative and quantitative evaluation of simulation and clinical studies.

Methods

Simulation studies were conducted by generating data incorporating 3 liver and 3 lung lesions produced by 3 noise levels and 20 noise realizations for each noise level to estimate bias and lesion detection features. The total scan time for the clinical studies of 8 patients addressed for lung and liver lesions staging, including dynamic and static WB imaging, lasted 80 minutes. An in-house–developed MATLAB code was utilized to derive the microparametric and macroparametric maps. We compared lesion detectability and different image-derived PET metrics including the SUVs, Patlak-derived influx rate constant (K
i) and distribution volume (V) and K1, k2, k3, blood volume (bv) microparameters, and K
i estimated using the generalized linear least square approach.

Results

In total, 104 lesions were detected, among which 47 were located in the targeted blood pool bed position where all quantitative parameters were calculated, thus enabling comparative analysis across all parameters. The evaluation encompassed visual interpretation performed by an expert nuclear medicine specialist and quantitative analysis. High correlation coefficients were observed between SUVmax and K
imax derived from the generalized linear least square approach, as well as K
i generated by Patlak graphical analysis. Moreover, 3 contrast-enhanced CT-proven malignant lesions located in the liver and a biopsy-proven malignant liver lesion not visible on static SUV images and Patlak maps were clearly pinpointed on K1 and k2 maps.

Conclusions

Our results demonstrate that full compartmental modeling for the region containing the pathology has the potential of providing complementary information and, in some cases, more accurate diagnosis than conventional static SUV imaging, favorably comparing to Patlak graphical analysis.
18F-FDG PET/CT in Tuberculosis
Authors: Sood Apurva , Mittal Bhagwant Rai , Modi Manish , Chhabra Rajesh , Verma Roshan , Rana Nivedita , Parihar Ashwin Singh , Satapathy Swayamjeet , Kumar Rajender
Published: February 2020

Purpose of the Report

Tuberculosis (TB) is a major health problem. Activated macrophages in TB lesions show high metabolic activity and can be assessed using 18F-FDG PET/CT. This retroprospective study was done to evaluate the utility of 18F-FDG PET/CT in initial assessment and therapeutic response in patients with TB.

Materials and Methods

Eighty-seven patients (male-to-female ratio, 46:41) diagnosed with pulmonary TB and extrapulmonary TB underwent whole-body 18F-FDG PET/CT for initial assessment and a follow-up scan 3 to 4 months after initiation of antitubercular therapy (ATT). Visual and semiquantitative (SUVmax) analyses were used for scan assessment. Treatment responses on interim scans were categorized as complete metabolic response (CMR), favorable response to therapy (FRT), stable disease (SD), and disease progression (DP). CMR, FRT, and SD cases were considered as responders and DP cases as nonresponders. Treatment response was correlated with clinical outcome (mortality) and ATT duration.

Results

Baseline 18F-FDG PET/CT scans were positive in all the patients and detected additional disease sites than suspected clinically in 72% patients. On interim PET/CT, 13 patients showed CMR, 43 showed FRT, 8 showed SD, and 23 showed DP. A longer duration of ATT was seen in nonresponders (P ≤ 0.001) than responders. During follow-up, 9/87 patients died, out of which 8 patients were of DP group and 1 patient belonged to SD. Nonresponders showed 35% mortality compared with 1.6% in the responder group (P ≤ 0.001).

Conclusions

18F-FDG PET/CT is a valuable imaging modality for disease mapping and assessing therapeutic response. Treatment response in the interim PET/CT done at 3 to 4 months predicted the duration of ATT and clinical outcome of the patients.
Nlrp3 Inflammasome Inhibitor MCC950 Ameliorates Obliterative Bronchiolitis by Inhibiting Th1/Th17 Response and Promoting Treg Response After Orthotopic Tracheal Transplantation in Mice
Authors: Xu Kai-Ying , Tong Song , Wu Chuang-Yan , Ding Xiang-Chao , Chen Jiu-Ling , Ming Yu , Wang Si-Hua
Published: February 2020

Background.

Obliterative bronchiolitis (OB) remains the major complication limiting long-term survival of patients after lung transplantation. We aimed to explore the effects of the selective NACHT, LRR, and PYD domains-containing protein 3 (Nlrp3) inflammasome inhibitor MCC950 on the pathogenesis of OB.

Methods.

Mouse orthotopic tracheal transplants were performed to mimic OB. MCC950 (50 mg/kg) or saline was intraperitoneally injected daily. The luminal occlusion rate and collagen deposition were evaluated by hematoxylin and eosin and Masson’s trichrome staining, respectively. Infiltration of CD4+, CD8+ T cells, and neutrophils was detected with immunohistochemical staining. The frequencies of T helper 1 cell (Th1), T helper 17 cell (Th17), and regulatory T cells (Treg) were measured by flow cytometry. Cytokine levels were measured by ELISA kits.

Results.

MCC950 treatment significantly inhibited Nlrp3 inflammasome activation after allogeneic tracheal transplant and markedly decreased the luminal occlusion rate and collagen deposition in the allograft. The numbers of infiltrating CD4+, CD8+ T cells, and neutrophils in the allograft were also significantly reduced by MCC950 treatment. MCC950 dramatically decreased the frequencies of Th1/Th17 cells and the levels of interferon gamma/interleukin (IL)-17A and increased the Treg cell frequencies and IL-10 level; however, these effects were abolished by the addition of IL-1β and IL-18 both in vitro and in vivo. OB was also rescued by the addition of IL-1β and/or IL-18.

Conclusions.

Blocking Nlrp3 inflammasome activation with MCC950 ameliorates OB lesions. The mechanistic analysis showed that MCC950 regulated the balance of Th1/Th17 and Treg cells and that this process is partially mediated by inhibition of IL-1β and IL-18. Therefore, targeting the Nlrp3 inflammasome is a promising strategy for controlling OB after lung transplantation.
External Validation of the DynPG for Kidney Transplant Recipients
Authors: Lenain Rémi , Dantan Etienne , Giral Magali , Foucher Yohann , Asar Özgür , Naesens Maarten , Hazzan Marc , Fournier Marie-Cécile
Published: February 2020

Background.

In kidney transplantation, dynamic prediction of patient and kidney graft survival (DynPG) may help to promote therapeutic alliance by delivering personalized evidence-based information about long-term graft survival for kidney transplant recipients. The objective of the current study is to externally validate the DynPG.

Methods.

Based on 6 baseline variables, the DynPG can be updated with any new serum creatinine measure available during the follow-up. From an external validation sample of 1637 kidney recipients with a functioning graft at 1-year posttransplantation from 2 European transplantation centers, we assessed the prognostic performance of the DynPG.

Results.

As one can expect from an external validation sample, differences in several recipient, donor, and transplantation characteristics compared with the learning sample were observed. Patients were mainly transplanted from deceased donors (91.6% versus 84.8%; P < 0.01), were less immunized against HLA class I (18.4% versus 32.7%; P < 0.01) and presented less comorbidities (62.2% for hypertension versus 82.7%, P < 0.01; 25.1% for cardiovascular disease versus 33.9%, P < 0.01). Despite these noteworthy differences, the area under the ROC curve varied from 0.70 (95% confidence interval [CI], 0.64-0.76) to 0.76 (95% CI, 0.64-0.88) for prediction times at 1 and 6 years posttransplantation respectively, and calibration plots revealed reasonably accurate predictions.

Conclusions.

We validated the prognostic capacities of the DynPG in terms of both discrimination and calibration. Our study showed the robustness of the DynPG for informing both the patient and the physician, and its transportability for a cohort presenting different features than the one used for the DynPG development.
Whole-body integration of gene expression and single-cell morphology
Authors: Vergara Hernando M. , Pape Constantin , Meechan Kimberly I. , Zinchenko Valentyna , Genoud Christel , Wanner Adrian A. , Titze Benjamin , Templin Rachel M. , Bertucci Paola Y. , Simakov Oleg , Machado Pedro , Savage Emily L. , Schwab Yannick , Friedrich Rainer W. , Kreshuk Anna , Tischer Christian , Arendt Detlev
Published: February 2020

Animal bodies are composed of hundreds of cell types that differ in location, morphology, cytoarchitecture, and physiology. This is reflected by cell type-specific transcription factors and downstream effector genes implementing functional specialisation. Here, we establish and explore the link between cell type-specific gene expression and subcellular morphology for the entire body of the marine annelidPlatynereis dumerilii. For this, we registered a whole-body cellular expression atlas to a high-resolution electron microscopy dataset, automatically segmented all cell somata and nuclei, and clustered the cells according to gene expression or morphological parameters. We show that collective gene expression most efficiently identifies spatially coherent groups of cells that match anatomical boundaries, which indicates that combinations of regionally expressed transcription factors specify tissue identity. We provide an integrated browser as a Fiji plugin to readily explore, analyse and visualise multimodal datasets with remote on-demand access to all available datasets.
KDM3A regulates alternative splicing of cell-cycle genes following DNA damage
Authors: Baker Mai , Petasny Mayra , Bentata Mercedes , Kay Gillian , Engal Eden , Nevo Yuval , Siam Ahmad , Dahan Sara , Salton Maayan
Published: February 2020

Changes in the cellular environment result in chromatin structure alteration, which in turn regulates gene expression. To learn about the effect of the cellular environment on the transcriptome, we studied the H3K9 de-methylase KDM3A. Using RNA-seq, we found that KDM3A regulates the transcription and alternative splicing of genes associated with cell cycle and DNA damage. We showed that KDM3A undergoes phosphorylation by PKA at serine 265 following DNA damage, and that the phosphorylation is important for a proper cell cycle regulation. We demonstrated that SAT1 alternative splicing, regulated by KDM3A, plays a role in cell cycle regulation. Furthermore we found that KDM3A’s demethylase activity is not needed for SAT1 alternative splicing regulation. In addition, we identified KDM3A’s protein partner ARID1A, the SWI/SNF subunit, and SRSF3 as regulators of SAT1 alternative splicing and showed that KDM3A is essential for SRSF3 binding to SAT1 pre-mRNA. These results suggest that KDM3A serves as a sensor of the environment and an adaptor for splicing factor binding. Our work reveals chromatin sensing of the environment in the regulation of alternative splicing.
Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue
Authors: Aquilano Katia , Sciarretta Francesca , Turchi Riccardo , Li Bo-Han , Rosina Marco , Ceci Veronica , Guidobaldi Giulio , Arena Simona , D’Ambrosio Chiara , Audano Matteo , Salvatori Illari , Colella Barbara , Faraonio Raffaella , Panebianco Concita , Pazienza Valerio , Caruso Donatella , Mitro Nico , Bartolomeo Sabrina Di , Scaloni Andrea , Li Jing-Ya , Lettieri-Barbato Daniele
Published: February 2020

Low-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.
TIRAP drives myelosuppression through an Ifnγ-Hmgb1 axis that disrupts the marrow microenvironment
Authors: Ibrahim Rawa , Gopal Aparna , Fuller Megan , Umlandt Patricia , Chang Linda , Wegrzyn-Woltosz Joanna , Lam Jeffrey , Li Jenny , Lu Melody , Parker Jeremy , Karsan Aly
Published: February 2020

Activation of inflammatory pathways is associated with bone marrow failure syndromes, but how specific molecules impact on the marrow microenvironment is not well elucidated. We report a novel role for the miR-145 target, Toll/Interleukin-1 receptor domain containing adaptor protein (TIRAP), in driving bone marrow failure. We show that TIRAP is overexpressed in various types of myelodysplastic syndromes (MDS), and suppresses all three major hematopoietic lineages.. Constitutive expression of TIRAP in hematopoietic stem/progenitor cells (HSPC) promotes upregulation ofIfnγ, leading to bone marrow failure. Myelopoiesis is suppressed through Ifnγ-Ifnγr-mediated release of the alarmin, Hmgb1, which disrupts the marrow endothelial niche. Deletion ofIfnγor Ifnγr blocks Hmgb1 release and is sufficient to reverse the endothelial defect and prevent myelosuppression. In contrast, megakaryocyte and erythroid production is repressed independently of the Ifnγ receptor. Contrary to current dogma, TIRAP-activated Ifnγ-driven marrow suppression is independent of T cell function or pyroptosis. In the absence of Ifnγ, TIRAP drives myeloproliferation, implicating Ifnγ in suppressing the transformation of bone marrow failure syndromes to myeloid malignancy. These findings reveal novel, non-canonical roles of TIRAP, Hmgb1 and Ifnγ function in the marrow microenvironment,and provide insight into the pathophysiology of preleukemic syndromes.

Graphical Abstract: Model of proposed mechanism of TIRAP-induced BMF

Constitutive TIRAP expression in marrow cells releases Ifnγ, which directly impacts on megakaryocyte and erythroid production, but indirectly suppresses myelopoiesis through the release of the alarmin, Hmgb1, which disrupts the marrow endothelial compartment.
Automated detection of glaucoma with interpretable machine learning using clinical data and multi-modal retinal images
Authors: Mehta Parmita , Petersen Christine , Wen Joanne C. , Banitt Michael R. , Chen Philip P. , Bojikian Karine D. , Egan Catherine , Lee Su-In , Balazinska Magdalena , Lee Aaron Y. , Rokem Ariel ,   The UK Biobank Eye and Vision Consortium
Published: February 2020

Glaucoma, the leading cause of irreversible blindness worldwide, is a disease that damages the optic nerve. Current machine learning (ML) approaches for glaucoma detection rely on features such as retinal thickness maps; however, the high rate of segmentation errors when creating these maps increase the likelihood of faulty diagnoses. This paper proposes a new, comprehensive, and more accurate ML-based approach for population-level glaucoma screening. Our contributions include: (1) a multi-modal model built upon a large data set that includes demographic, systemic and ocular data as well as raw image data taken from color fundus photos (CFPs) and macular Optical Coherence Tomography (OCT) scans, (2) model interpretation to identify and explain data features that lead to accurate model performance, and (3) model validation via comparison of model output with clinician interpretation of CFPs. We also validated the model on a cohort that was not diagnosed with glaucoma at the time of imaging but eventually received a glaucoma diagnosis. Results show that our model is highly accurate (AUC 0.97) and interpretable. It validated biological features known to be related to the disease, such as age, intraocular pressure and optic disc morphology. Our model also points to previously unknown or disputed features, such as pulmonary capacity and retinal outer layers.
In silico design of Phl p 6 variants with altered folding stability significantly impacts antigen processing, immunogenicity and immune polarization
Authors: Winter Petra , Stubenvoll Stefan , Scheiblhofer Sandra , Joubert Isabella A , Strasser Lisa , Briganser Carolin , Tuck Soh Wai , Hofer Florian , Kamenik Anna Sophia , Dietrich Valentin , Michelini Sara , Laimer Josef , Lackner Peter , Horejs-Hoeck Jutta , Tollinger Martin , Liedl Klaus R. , Brandstetter Johann , Huber Christian G. , Richard Weiss
Published: February 2020

Abstact

Introduction

Protein fold stability has been proposed to represent an intrinsic feature contributing to immunogenicity and immune polarization by influencing the amount of peptide-MHC II complexes (pMHCII). Usingin silicoprediction, we introduced point mutations in proteins that either increase or decrease their fold-stability without altering immunodominant epitopes or changing the overall structure of the protein. Here, we investigated how modulation of the fold-stability of the grass pollen allergen Phl p 6 affects its ability to stimulate immune responses and T cell polarization.

Methods

Using the MAESTRO software tool, stabilizing or destabilizing mutations were selected and verified by molecular dynamics simulations. The mutants were expressed in E. coli, purified tag-free, and analyzed for thermal stability and resistance to endolysosomal proteases. The resulting peptides were analysed by degradome assay and mass spectrometry. The structure of the most stable mutant protein was obtained by X-ray crystallography. We evaluated the capacity of the mutants to stimulate T cell proliferationin vitro, as well as antibody responses and T cell polarizationin vivoin an adjuvant-free BALB/c mouse model.

Results

Four stabilizing and two destabilizing mutations were identified by MAESTRO. Experimentally determined changes in thermal stability compared to the wild type protein ranged from -5 to +14 °C. Destabilization led to faster proteolytic processingin vitro, whereas highly stabilized mutants were degraded very slowly. However, the overall pattern of identified peptides remained very similar. This was confirmed in bone marrow derived dendritic cells that processed and presented the immune dominant epitope from a destabilized mutant more efficiently.In vivo, stabilization resulted in a shift in immune polarization as indicated by higher levels of IgG2a and increased secretion of TH1/TH17 cytokines.

Conclusion

MAESTRO was very efficient in detecting single point mutations that increase or reduce fold-stability. Thermal stability correlated well with susceptibility to protease resistance and presentation of pMHCII on the surface of dendritic cellsin vitro. This change in processing kinetics significantly influenced the polarization of T cell responsesin vivo. Modulating the fold-stability of proteins thus has the potential to optimize and polarize immune responses, which opens the door to more efficient design of molecular vaccines.
Forelimb unloading impairs glenohumeral muscle development in growing rats
Authors: Tushak Sophia K. , Tamburro Margaret K. , Fawcett Emily B. , Merritt LE Lauren E. , Saul Katherine R. , Cole Jacqueline H.
Published: February 2020

Proper joint loading is essential for healthy musculoskeletal development. Many pediatric neuromuscular disorders cause irreversible muscle impairments resulting from both physiological changes and mechanical unloading of the joint. While previous studies have examined the effects of hindlimb unloading on musculoskeletal development in the lower limb, none have examined solely forelimb unloading. Thus, a large deficit in knowledge of the effect of upper limb unloading exists and must be addressed in order to better understand how the glenohumeral joint adapts during development. Two forelimb unloading models were developed to study the effects of varying degrees of unloading on the glenohumeral joint in growing rats: forelimb suspension (n=6, intervention 21 days post-natal) with complete unloading of both limbs via a novel suspension system and forearm amputation (n=8, intervention 3-6 days post-natal) with decreased loading and limb use in one limb after below-elbow amputation. After 8 weeks of unloading, changes in muscle architecture and composition were examined in ten muscles surrounding the shoulder. Results were compared to control rats from a previous study (n=8). Both methods of altered loading significantly affected muscle mass, sarcomere length, and optimal muscle length compared to control rats, with the biceps long head and triceps long head observing the most marked differences. Forearm amputation also significantly affected muscle mass, sarcomere length, and optimal muscle length in the affected limb relative to the contralateral limb. Muscle composition, assessed by collagen content, remained unchanged in all groups. This study demonstrated that forearm amputation, which was administered closer to birth, had greater effects on muscle than forelimb suspension, which was administered a few weeks later than amputation.
Motor cortical plasticity in response to skill acquisition in adult monkeys
Authors: Gupta Ankur , Nashef Abdulraheem , Israely Sharon , Segal Michal , Harel Ran , Prut Yifat
Published: February 2020

Cortical maps often undergo plastic changes during learning or in response to injury. In sensory areas, these changes are thought to be triggered by alterations in the pattern of converging inputs and a functional reassignment of the deprived cortical region. In the motor cortex, training on a task that engages distal effectors was shown to increase their cortical representation (as measured by response to intracortical microstimulation). However, this expansion could be a specific outcome of using a demanding dexterous task. We addressed this question by measuring the long-term changes in cortical maps of monkeys that were sequentially trained on two different tasks involving either proximal or distal joints. We found that motor cortical remodeling in adult monkeys was symmetric such that both distal and proximal movements can comparably alter motor maps in a fully reversible manner according to task demands. Further, we found that the change in mapping often included a switch between remote joints (e.g., a finger site switched to a shoulder site) and reflected a usage-consistent reorganization of the map rather than the local expansion of one representation into nearby sites. Finally, although cortical maps were considerably affected by the performed task, motor cortical neurons throughout the motor cortex were equally likely to fire in a task-related manner independent of the task and/or the recording site. These results may imply that in the motor system, enhanced motor efficiency is achieved through a dynamical allocation of larger cortical areas and not by specific recruitment of task-relevant cells.
Latent learning drives sleep-dependent plasticity in distinct CA1 subpopulations
Authors: Guo Wei , Zhang Jie J. , Newman Jonathan P. , Wilson Matthew A.
Published: February 2020

Latent learning allows the brain the transform experiences into cognitive maps, a form of implicit memory, without reinforced training. Its mechanism is unclear. We tracked the internal states of the hippocampal neural ensembles and discovered that during latent learning of a spatial map, the state space evolved into a low-dimensional manifold that topologically resembled the physical environment. This process requires repeated experiences and sleep in-between. Further investigations revealed that a subset of hippocampal neurons, instead of rapidly forming place fields in a novel environment, remained weakly tuned but gradually developed correlated activity with other neurons. These ‘weakly spatial’ neurons bond activity of neurons with stronger spatial tuning, linking discrete place fields into a map that supports flexible navigation.
Prmt5 promotes vascular morphogenesis independently of its methyltransferase activity
Authors: Quillien Aurélie , Boulet Manon , Ethuin Séverine , Vandel Laurence
Published: February 2020

During development, the vertebrate vasculature undergoes major growth and remodeling. While the transcriptional cascade underlying blood vessel formation starts to be better characterized, little is known concerning the role and mode of action of epigenetic enzymes during this process. Here, we explored the role of the Protein Arginine Methyl Transferase Prmt5 during blood vessel formation and hematopoiesis in zebrafish. Through the generation of aprmt5mutant, we highlighted a key role of Prmt5 in both hematopoiesis and blood vessel formation. Notably, we showed that Prmt5 promotes vascular morphogenesis through the transcriptional control of ETS transcription factors and adhesion proteins in endothelial cells. Interestingly, we found that Prmt5 methyltransferase activity is not required to regulate gene expression, and the comparison of chromatin architecture impact on reporter genes expression leads us to propose that Prmt5 rather regulates transcription by acting as a scaffold protein that facilitates chromatin looping in these cells.
Biosonar spatial resolution along the distance axis: revisiting the clutter interference zone
Authors: Wagenhäuser Peter A. , Wiegrebe Lutz , Baier A. Leonie
Published: February 2020

Unlike all other remote senses like vision or hearing, echolocation allows estimating the distance of an object. Not only have echolocating bats and toothed whales been shown to measure distance by echolocation extremely precisely, distance information is even topographically represented by a neuro-computational map in bats’ auditory cortex. This topographic representation and the corresponding tuning of cortical cells to object distance suggests the bats may be able to perceptually resolve multiple, simultaneously present objects along the distance axis. Here we use a novel psychophysical paradigm with complex phantom targets to quantity spatial resolution along the distance axis in the echolocating batPhyllostomus discolor. We show that our bats can indeed perceptually resolve objects along the distance axis when they are separated by about 40 cm (around a reference distance of 108 cm) along the distance axis. These results are well comparable to earlier work on bats’ clutter interference zone (Simmons et al., 1988) and confirm those results with a more robust psychophysical paradigm.

Summary statement

Echolocating bats perceive absolute distance to objects by measuring the time delay between call and echo. In addition, they possess spatial resolution along the distance axis.
ICOS enhances follicular T helper responses and deteriorates the pathogenic process of liver in mice infected withSchistosoma japonicum
Authors: Wang Bo , Liang Song , Wang Yan-Yan , Wang Yu , Xia Chao-Ming
Published: February 2020

Background

Humoral immune responses play an important role in mediating liver granulomatous inflammation and fibrosis in schistosomiasis. Follicular helper T (Tfh) cells have a central role in mediating humoral immune responses. Generation of Tfh cells depends on inducible T cell costimulator (ICOS) signaling, but the underlying molecular mechanisms are incompletely understood in pathogenesis of schistosomiasis.

Methodology/Principal Findings

We used a strain of ICOS-transgenic (Tg) mice to test the degrees of liver granulomatous inflammation and fibrosis, the frequency of splenic Tfh cells and soluble egg antigen-specific cytokine responses longitudinally in mice followingSchistosoma japonicum(S. japonicum)infection. In comparison with that in wide-type (WT) mice, significantly severer liver granulomatous inflammation and fibrosis and higher mortality were observed in ICOS-Tg mice. Significantly higher frequency of splenic Tfh cells was accompanied by significantly higher levels of Bcl-6 and CXCR5 expression in the livers of ICOS-Tg mice. Furthermore, significantly higher levels of SEA-specific IL-4, IL-6, IL-10, IL-13, IL-17A, IL-21 and TGF-β1 responses, but lower levels of IFN-γ responses were detected in ICOS-Tg mice, which were abrogated by treatment with ICOS blockers in vitro. In addition, significantly higher levels of serum anti-SEA IgG were detected in ICOS-Tg mice.

Conclusions/Significance

The ICOS-related signaling may promote the pathogenesis of murine schistosomiasis by polarizing Tfh cells, which may be immune check points for the prevention and intervention of schistosomiasis.

Author summary

Granulomatous inflammation and fibrosis in the liver are the major pathogenic characteristics of schistosomiasis. ICOS is crucial for the development of Tfh cells, which are the key modulators of B cell activation and humoral immunity. However, the underlying molecular mechanisms are incompletely understood in pathogenesis of schistosomiasis. Here, our results showed that the ICOS over-expression would significantly induce severer liver inflammation and fibrosis, higher frequency of splenic Tfh, higher levels of anti-SEA IgG as well as imbalanced SEA-specific cytokine responses in ICOS-Tg mice. The findings suggested that ICOS signaling may promote the pathogenesis of murine schistosoma-related liver inflammation and fibrosis by polarizing Tfh cells. Potentially, ICOS signaling and Tfh cells may be immune check points for the prevention and intervention of schistosomiasis.
Representing Organic Matter Thermodynamics in Biogeochemical Reactions via Substrate-Explicit Modeling
Authors: Song Hyun-Seob , Stegen James C. , Graham Emily B. , Lee Joon-Yong , Garayburu-Caruso Vanessa A. , Nelson William C. , Chen Xingyuan , Moulton J. David , Scheibe Timothy D.
Published: February 2020

Predictive biogeochemical modeling requires data-model integration that enables explicit representation of the sophisticated roles of microbial processes that transform substrates. Data from high-resolution organic matter (OM) characterization are increasingly available and can serve as a critical resource for this purpose, but their incorporation into biogeochemical models is often prohibited due to an over-simplified description of reaction networks. To fill this gap, we proposed a new concept of biogeochemical modeling—termedsubstrate-explicit modeling—that enables parameterizing OM-specific oxidative degradation pathways and reaction rates based on the thermodynamic properties of OM pools. The resulting kinetic models are characterized by only two parameters regardless of the complexity of OM profiles, which can greatly facilitate the integration with reactive transport models for ecosystem simulations by alleviating the difficulty in parameter identification. For every detected organic molecule in a given sample, our approach provides a systematic way to formulate reaction kinetics from chemical formula, which enables the evaluation of the impact of OM character on biogeochemical processes across conditions. In a case study of two sites with distinct OM thermodynamics, our method not only predicted oxidative degradation to be primarily driven by thermodynamic efficiency of OM consistent with experimental rate measurements, but also revealed previously unknown critically important aspects of biogeochemical reactions, including their condition-specific response to carbon and/or oxygen limitations. Lastly, we showed that the proposed substrate-explicit modeling approach can be synergistically combined with enzyme-explicit approach to provide improved predictions. This result led us to presentintegrative biogeochemical modelingas a unifying framework that can ideally describe the dynamic interplay among microbes, enzymes, and substrates to address advanced questions and hypotheses in future studies. Altogether, the new modeling concept we propose in this work provides a foundational platform for unprecedented predictions of biogeochemical and ecosystem dynamics through enhanced integration with diverse experimental data and extant modeling approaches.
SAFE Acoustics: an open-source, real-time eco-acoustic monitoring network in the tropical rainforests of Borneo
Authors: Sethi Sarab S. , Ewers Robert M. , Jones Nick S. , Signorelli Aaron , Picinali Lorenzo , Orme C. David L.
Published: February 2020

Automated monitoring approaches offer an avenue to deep, large-scale insight into how ecosystems respond to human pressures. Since sensor technology and data analyses are often treated independantly, there are no open-source examples of end-to-end, real-time ecological monitoring networks.

Here, we present the complete implementation of an autonomous acoustic monitoring network deployed in the tropical rainforests of Borneo. Real-time audio is uploaded remotely from the field, indexed by a central database, and delivered via an API to a public-facing website.

We provide the open-source code and design of our monitoring devices, the central web2py database and the ReactJS website. Furthermore, we demonstrate an extension of this infrastructure to deliver real-time analyses of the eco-acoustic data.

By detailing a fully functional, open-source, and extensively tested design, our work will accelerate the rate at which fully autonomous monitoring networks mature from technological curiosities, and towards genuinely impactful tools in ecology.
brt index: an integration of biological relevance andp-value for -omics data along with demonstration in microarray data using a developed R package
Authors: Zheng Le , Li Jin , Yu Peng
Published: February 2020

This manuscript has been withdrawn by bioRxiv as it was submitted without full consent of all of the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Synthesis and crystal structure of (1,4,7,10-tetraazacyclododecane-κ4
N)(tetrasulfido-κ2
S
1,S
4)manganese(II)
Authors: Danker Felix , Näther Christian , Bensch Wolfgang
Published: February 2020

The title compound, [Mn(S4)(C8H20N4)], was accidentally obtained by the hydrothermal reaction of Mn(ClO4)2·6H2O, cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) and Na3SbS4·9H2O in water at 413 K, indicating that polysulfide anions might represent intermediates in the synthesis of thiometallate compounds using Na3SbS4·9H2O as a reactant. X-ray powder diffraction proves that the sample is slightly contaminated with NaSb(OH)6 and an unknown crystalline phase. The crystal investigated was twinned with a twofold rotation axis as the twin element, and therefore a twin refinement using data in HKLF-5 format was performed. The asymmetric unit of the title compound consists of one MnII cation, one [S4]2− anion and one cyclen ligand in general positions. The MnII cation is sixfold coordinated by two cis-S atoms of the [S4]2− anions, as well as four N atoms of the cyclen ligand within an irregular coordination. The complexes are linked via pairs of N—H...S hydrogen bonds into chains, which are further linked into layers by additional N—H...S hydrogen bonding. These layers are connected into a three-dimensional network by intermolecular N—H...S and C—H...S hydrogen bonding. It is noted that only one similar complex with MnII is reported in the literature.
No more fairytales: a quest for alternative narratives of sustainable business
Authors: O’Dochartaigh Aideen
Published: February 2020

Purpose

The purpose of this paper is to explore storytelling in sustainability reporting. The author posits that large PLCs use their sustainability reports to support the construction of a fairytale of “sustainable business”, and asks if organisations with an alternative purpose (social enterprises, values-based SMEs) and/or ownership structure (co-operatives, partnerships) can offer a counter-narrative of the sustainability–business relationship.

Design/methodology/approach

The paper uses the literature on storytelling and organisational mythmaking to gain insight into the construction of narratives and their impact on the reader. A narrative analysis is conducted of the sustainability reports of 40 organisations across a range of entity classes, including large PLCs, values-based SMEs, co-owned businesses and social enterprises.

Findings

The analysis indicates that the narratives presented in sustainability reporting are of much the same form across entity classes. The author argues on this basis that sustainability reports represent stories targeted at specific stakeholders rather than accounts of the organisation’s relationship with ecological and societal sustainability, and urges scholars to challenge organisations across entity classes to engage with sustainability at a planetary level.

Originality/value

The paper seeks to contribute to the literature in two ways. First, the author illustrates how the literature on storytelling can be used to analyse organisational narratives of sustainability, and how narrative forms and genres can be mobilised to support potential counter-narratives. Second, the author explores and ultimately challenges the proposition that organisations less often examined in the literature, such as social enterprises and co-operatives, can offer alternative narratives of the sustainability–business relationship.
The influence of firm performance and (level of) assurance on the believability of management's environmental report
Authors: Sheldon Mark D. , Jenkins J. Gregory
Published: February 2020

Purpose

This study empirically examines perceptions of environmental report believability based on a firm's relative performance and level of assurance obtained on environmental activities under the recently clarified and recodified attestation standards in the United States.

Design/methodology/approach

The paper uses a 2 × 3 between-subjects experiment to identify differences in 153 non-expert environmental report users' perceptions of report believability based on positive or negative firm performance and (level of) assurance provided by an accounting firm.

Findings

Results show a main effect in that negative performance reports are perceived to be more believable than positive performance reports, as driven by negative performance reports being significantly more believable when no assurance is present. The firm performance effect is eliminated once limited or reasonable assurance is provided. Further, positive performance reports with limited, but not reasonable, assurance are perceived to be more believable than reports without assurance. No differences are identified within the negative performance condition.

Practical implications

Limited assurance might be used as an impression management tool to enhance the believability of positive performance environmental reports. Users, practitioners, and standard-setters should also be aware that users might believe environmental reports are assured, even when no such assurance has been provided.

Originality/value

This paper examines the impact of assured environmental reporting on users that review firms' environmental reports outside of a shareholder/investor role. The study also demonstrates conditions in which firm performance and assurance impact perceptions of report believability.