bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional genomics of inflamm-aging and immunosenescence
Authors: Lu Ryan J , Wang Emily K , Benayoun Bérénice A
Published: February 2021

The aging population is at a higher risk for age-related diseases and infections. This observation could be due to immunosenescence: the decline in immune efficacy of both the innate and the adaptive immune systems. Age-related immune decline also links to the concept of ‘inflamm-aging,’ whereby aging is accompanied by sterile chronic inflammation. Along with a decline in immune function, aging is accompanied by a widespread of ‘omics’ remodeling. Transcriptional landscape changes linked to key pathways of immune function have been identified across studies, such as macrophages having decreased expression of genes associated to phagocytosis, a major function of macrophages. Therefore, a key mechanism underlying innate immune cell dysfunction during aging may stem from dysregulation of youthful genomic networks. In this review, we discuss both molecular and cellular phenotypes of innate immune cells that contribute to age-related inflammation.
RNAxplorer: harnessing the power of guiding potentials to sample RNA landscapes
Authors: Entzian Gregor , Hofacker Ivo L , Ponty Yann , Lorenz Ronny , Tanzer Andrea
Published: February 2021

Motivation

Predicting the folding dynamics of RNAs is a computationally difficult problem, first and foremost due to the combinatorial explosion of alternative structures in the folding space. Abstractions are therefore needed to simplify downstream analyses, and thus make them computationally tractable. This can be achieved by various structure sampling algorithms. However, current sampling methods are still time consuming and frequently fail to represent key elements of the folding space.

Method

We introduce RNAxplorer, a novel adaptive sampling method to efficiently explore the structure space of RNAs. RNAxplorer uses dynamic programming to perform an efficient Boltzmann sampling in the presence of guiding potentials, which are accumulated into pseudo-energy terms and reflect similarity to already well-sampled structures. This way, we effectively steer sampling toward underrepresented or unexplored regions of the structure space.

Results

We developed and applied different measures to benchmark our sampling methods against its competitors. Most of the measures show that RNAxplorer produces more diverse structure samples, yields rare conformations that may be inaccessible to other sampling methods and is better at finding the most relevant kinetic traps in the landscape. Thus, it produces a more representative coarse graining of the landscape, which is well suited to subsequently compute better approximations of RNA folding kinetics.

Availabilityand implementation

https://github.com/ViennaRNA/RNAxplorer/.

Supplementary information

Supplementary data are available at Bioinformatics online.
multiclassPairs: an R package to train multiclass pair-based classifier
Authors: Marzouka Nour-Al-Dain , Eriksson Pontus
Published: February 2021

Motivation

k–Top Scoring Pairs (kTSP) algorithms utilize in-sample gene expression feature pair rules for class prediction, and have demonstrated excellent performance and robustness. The available packages and tools primarily focus on binary prediction (i.e. two classes). However, many real-world classification problems e.g. tumor subtype prediction, are multiclass tasks.

Results

Here, we present multiclassPairs, an R package to train pair-based single sample classifiers for multiclass problems. multiclassPairs offers two main methods to build multiclass prediction models, either using a one-versus-rest kTSP scheme or through a novel pair-based Random Forest approach. The package also provides options for dealing with class imbalances, multiplatform training, missing features in test data and visualization of training and test results.

Availability and implementation

‘multiclassPairs’ package is available on CRAN servers and GitHub: https://github.com/NourMarzouka/multiclassPairs.

Supplementary information

Supplementary data are available at Bioinformatics online.
Sea Change: Using Citizen Science to Inform Fisheries Management
Authors: Bonney Rick , Byrd Julia , Carmichael John T , Cunningham Leda , Oremland Laura , Shirk Jennifer , Von Harten Amber
Published: January 2021

Increasing costs are challenging the capacity for resource management agencies to keep up with mounting needs for robust data about fish populations and their habitats. Furthermore, trust among scientists, government agencies, and the public is fundamental to effective fisheries management, and relations among these three groups are increasingly strained when decisions about fishing limits are made (or are perceived to be made) on the basis of limited information or analysis. In the South Atlantic region of the United States, the South Atlantic Fishery Management Council has begun building a citizen science program to increase the quantity and quality of data used for fisheries management decisions throughout the region and to build trust and foster mutual understanding among those involved in the process. The goal is to build on existing management infrastructure to address key challenges to managing fisheries for long-term sustainability. In the present article, we examine the collaborative process used to establish the program.
Exosomes of adult human fibroblasts cultured on 3D silk fibroin nonwovens intensely stimulate neoangiogenesis
Authors: Hu Peng , Chiarini Anna , Wu Jun , Freddi Giuliano , Nie Kaiyu , Armato Ubaldo , Prà Ilaria Dal
Published: February 2021

Background

Bombyx mori silk fibroin is a biomacromolecule that allows the assembly of scaffolds for tissue engineering and regeneration purposes due to its cellular adhesiveness, high biocompatibility and low immunogenicity. Earlier work showed that two types of 3D silk fibroin nonwovens (3D-SFnws) implanted into mouse subcutaneous tissue were promptly vascularized via undefined molecular mechanisms. The present study used nontumorigenic adult human dermal fibroblasts (HDFs) adhering to a third type of 3D-SFnws to assess whether HDFs release exosomes whose contents promote neoangiogenesis.

Methods

Electron microscopy imaging and physical tests defined the features of the novel carded/hydroentangled 3D-SFnws. HDFs were cultured on 3D-SFnws and polystyrene plates in an exosome-depleted medium. DNA amounts and D-glucose consumption revealed the growth and metabolic activities of HDFs on 3D-SFnws. CD9-expressing total exosome fractions were from conditioned media of 3D-SFnws and 2D polystyrene plates HDF cultures. Angiogenic growth factors (AGFs) in equal amounts of the two groups of exosomal proteins were analysed via double-antibody arrays. A tube formation assay using human dermal microvascular endothelial cells (HDMVECs) was used to evaluate the exosomes’ angiogenic power.

Results

The novel features of the 3D-SFnws met the biomechanical requirements typical of human soft tissues. By experimental day 15, 3D-SFnws-adhering HDFs had increased 4.5-fold in numbers and metabolized 5.4-fold more D-glucose than at day 3 in vitro. Compared to polystyrene-stuck HDFs, exosomes from 3D-SFnws-adhering HDFs carried significantly higher amounts of AGFs, such as interleukin (IL)-1α, IL-4 and IL-8; angiopoietin-1 and angiopoietin-2; angiopoietin-1 receptor (or Tie-2); growth-regulated oncogene (GRO)-α, GRO-β and GRO-γ; matrix metalloproteinase-1; tissue inhibitor metalloproteinase-1; and urokinase-type plasminogen activator surface receptor, but lesser amounts of anti-angiogenic tissue inhibitor metalloproteinase-2 and pro-inflammatory monocyte chemoattractant protein-1. At concentrations from 0.62 to 10 μg/ml, the exosomes from 3D-SFnws-cultured HDFs proved their angiogenic power by inducing HDMVECs to form significant amounts of tubes in vitro.

Conclusions

The structural and mechanical properties of carded/hydroentangled 3D-SFnws proved their suitability for tissue engineering and regeneration applications. Consistent with our hypothesis, 3D-SFnws-adhering HDFs released exosomes carrying several AGFs that induced HDMVECs to promptly assemble vascular tubes in vitro. Hence, we posit that once implanted in vivo, the 3D-SFnws/HDFs interactions could promote the vascularization and repair of extended skin wounds due to burns or other noxious agents in human and veterinary clinical settings.
Innovative Thin-Layer Chromatography/Fluorescence Detection Approach for Sensitive and Specific Determination of Ledipasvir in Rats’ Feces and Pharmaceutical Dosage Form
Authors: Abdel-Lateef Mohamed A , Omar Mahmoud A , Ali Ramadan , Almahri Albandary , Derayea Sayed M
Published: February 2021

An innovative thin-layer chromatography method coupled with the fluorescence detection was developed for a specific estimation of ledipasvir. The separation was achieved on plates of silica gel 60 F254 using ethylacetate: hexane: acetonitrile: triethylamine; (6: 3.5: 1.5: 0.5, $\mathrm{v}/\mathrm{v}/\mathrm{v}/\mathrm{v}$) as a mobile phase system. The method involved the exposure of the developed thin-layer chromatography plate of ledipasvir to strong ultraviolet irradiation, resulting in a great enhancement in the fluorescence properties of ledipasvir. The irradiated plates were scanned after the excitation at 315 $\mathrm{nm}$. The method provided a sufficient separation of ledipasvir from sofosbuvir with ${R}_F$values of 0.28 and 0.36 for ledipasvir and sofosbuvir, respectively. The developed procedures were validated based on guidelines from the International Conference on Harmonization and Food and Drug Administration guidelines. The calibration curve was linear over the range of 5–50 $\mathrm{ng}/\mathrm{band}$. The excellent analytical features of the proposed method allow to the specific determination of ledipasvir in pharmaceutical tablets without interference from sofosbuvir or excipients. As the main elimination route for ledipasvir is via the fecal excretion (86%), the method was applied for the estimation of ledipasvir in fecal specimens with adequate recovery. In addition, the proposed method was applied for testing the content uniformity of ledipasvir in the pharmaceutical tablets.
Development and Validation of an LC–MS/MS Method for AC1LPSZG and Pharmacokinetics Application in Rats
Authors: Chen Yuan , Gao Xiuqing , Gupta Ritu , Ma Jing , Dere Ruhee , Liang Dong , Xie Huan
Published: February 2021

Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC–MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3 min per sample. A linear dose–response for quantification was observed over the range of 10–5000 ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87–102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6 h after collection and stored at −80 °C until analysis within 30 days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.
Emerging views of statin pleiotropy and cholesterol lowering
Authors: Yu Dongbo , Liao James K
Published: February 2021

Over the past four decades, no class of drugs has had more impact on cardiovascular health than the 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins. Developed as potent lipid-lowering agents, statins were later shown to reduce morbidity and mortality of patients who are at risk for cardiovascular disease. However, retrospective analyses of some of these clinical trials have uncovered some aspects of their clinical benefits that may be additional to their lipid-lowering effects. Such ‘pleiotropic’ effects of statins garnered intense interest and debate over its contribution to cardiovascular risk reduction. This review will provide a brief background of statin pleiotropy, assess the available clinical evidence for and against their non-lipid-lowering benefits, and propose future research directions in this field.
The structural heart disease interventional imager rationale, skills and training: a position paper of the European Association of Cardiovascular Imaging
Authors: Agricola Eustachio , Ancona Francesco , Brochet Eric , Donal Erwan , Dweck Marc , Faletra Francesco , Lancellotti Patrizio , Mahmoud-Elsayed Hani , Marsan Nina Ajmone , Maurovich-Hovart Pal , Monaghan Mark , Ribeiro José , Sade Leyla Elif , Swaans Martin , Von Bardeleben Ralph Stephan , Wunderlich Nina , Zamorano Jose-Luis , Popescu Bogdan A , Cosyns Bernard , Edvardsen Thor ,   Reviewers: This document was reviewed by members of the 2018-2020 EACVI Scientific Documents Committee, Bertrand Philippe , Delgado Victoria , Gerber Bernard , Stankovic Ivan
Published: February 2021

Percutaneous therapeutic options for an increasing variety of structural heart diseases (SHD) have grown dramatically. Within this context of continuous expansion of devices and procedures, there has been increased demand for physicians with specific knowledge, skills, and advanced training in multimodality cardiac imaging. As a consequence, a new subspecialty of ‘Interventional Imaging’ for SHD interventions and a new dedicated professional figure, the ‘Interventional Imager’ with specific competencies has emerged. The interventional imager is an integral part of the heart team and plays a central role in decision-making throughout the patient pathway, including the appropriateness and feasibility of a procedure, pre-procedural planning, intra-procedural guidance, and post-procedural follow-up. However, inherent challenges exist to develop a training programme for SHD imaging that differs from traditional cardiovascular imaging pathways. The purpose of this document is to provide the standard requirements for the training in SHD imaging, as well as a starting point for an official certification process for SHD interventional imager.
Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases
Authors: Garcia-Pavia Pablo , Rapezzi Claudio , Adler Yehuda , Arad Michael , Basso Cristina , Brucato Antonio , Burazor Ivana , Caforio Alida L P , Damy Thibaud , Eriksson Urs , Fontana Marianna , Gillmore Julian D , Gonzalez-Lopez Esther , Grogan Martha , Heymans Stephane , Imazio Massimo , Kindermann Ingrid , Kristen Arnt V , Maurer Mathew S , Merlini Giampaolo , Pantazis Antonis , Pankuweit Sabine , Rigopoulos Angelos G , Linhart Ales
Published: February 2021

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.
Single-cell visualization of mir-9a and Senseless co-expression during Drosophila melanogaster embryonic and larval peripheral nervous system development
Authors: Gallicchio Lorenzo , Griffiths-Jones Sam , Ronshaugen Matthew
Published: January 2021

The Drosophila melanogaster peripheral nervous system (PNS) comprises the sensory organs that allow the fly to detect environmental factors such as temperature and pressure. PNS development is a highly specified process where each sensilla originates from a single sensory organ precursor (SOP) cell. One of the major genetic orchestrators of PNS development is Senseless, which encodes a zinc finger transcription factor (Sens). Sens is both necessary and sufficient for SOP differentiation. Senseless expression and SOP number are regulated by the microRNA miR-9a. However, the reciprocal dynamics of Senseless and miR-9a are still obscure. By coupling single-molecule FISH with immunofluorescence, we are able to visualize transcription of the mir-9a locus and expression of Sens simultaneously. During embryogenesis, we show that the expression of mir-9a in SOP cells is rapidly lost as Senseless expression increases. However, this mutually exclusive expression pattern is not observed in the third instar imaginal wing disc, where some Senseless-expressing cells show active sites of mir-9a transcription. These data challenge and extend previous models of Senseless regulation and show complex co-expression dynamics between mir-9a and Senseless. The differences in this dynamic relationship between embryonic and larval PNS development suggest a possible switch in miR-9a function. Our work brings single-cell resolution to the understanding of dynamic regulation of PNS development by Senseless and miR-9a.
In vivo transcriptome analysis provides insights into host-dependent expression of virulence factors by Yersinia entomophaga MH96, during infection of Galleria mellonella
Authors: Paulson Amber R , O’Callaghan Maureen , Zhang Xue-Xian , Rainey Paul B , Hurst Mark R H
Published: January 2021

The function of microbes can be inferred from knowledge of genes specifically expressed in natural environments. Here, we report the in vivo transcriptome of the entomopathogenic bacterium Yersinia entomophaga MH96, captured during initial, septicemic, and pre-cadaveric stages of intrahemocoelic infection in Galleria mellonella. A total of 1285 genes were significantly upregulated by MH96 during infection; 829 genes responded to in vivo conditions during at least one stage of infection, 289 responded during two stages of infection, and 167 transcripts responded throughout all three stages of infection compared to in vitro conditions at equivalent cell densities. Genes upregulated during the earliest infection stage included components of the insecticidal toxin complex Yen-TC (chi1, chi2, and yenC1), genes for rearrangement hotspot element containing protein yenC3, cytolethal distending toxin cdtAB, and vegetative insecticidal toxin vip2. Genes more highly expressed throughout the infection cycle included the putative heat-stable enterotoxin yenT and three adhesins (usher-chaperone fimbria, filamentous hemagglutinin, and an AidA-like secreted adhesin). Clustering and functional enrichment of gene expression data also revealed expression of genes encoding type III and VI secretion system-associated effectors. Together these data provide insight into the pathobiology of MH96 and serve as an important resource supporting efforts to identify novel insecticidal agents.
Global translational landscape of the Candida albicans morphological transition
Authors: Mundodi Vasanthakrishna , Choudhary Saket , Smith Andrew D , Kadosh David
Published: January 2021

Candida albicans, a major human fungal pathogen associated with high mortality and/or morbidity rates in a wide variety of immunocompromised individuals, undergoes a reversible morphological transition from yeast to filamentous cells that is required for virulence. While previous studies have identified and characterized global transcriptional mechanisms important for driving this transition, as well as other virulence properties, in C. albicans and other pathogens, considerably little is known about the role of genome-wide translational mechanisms. Using ribosome profiling, we report the first global translational profile associated with C. albicans morphogenesis. Strikingly, many genes involved in pathogenesis, filamentation, and the response to stress show reduced translational efficiency (TE). Several of these genes are known to be strongly induced at the transcriptional level, suggesting that a translational fine-tuning mechanism is in place. We also identify potential upstream open reading frames (uORFs), associated with genes involved in pathogenesis, and novel ORFs, several of which show altered TE during filamentation. Using a novel bioinformatics method for global analysis of ribosome pausing that will be applicable to a wide variety of genetic systems, we demonstrate an enrichment of ribosome pausing sites in C. albicans genes associated with protein synthesis and cell wall functions. Altogether, our results suggest that the C. albicans morphological transition, and most likely additional virulence processes in fungal pathogens, is associated with widespread global alterations in TE that do not simply reflect changes in transcript levels. These alterations affect the expression of many genes associated with processes essential for virulence and pathogenesis.
Genetic variation in aneuploidy prevalence and tolerance across Saccharomyces cerevisiae lineages
Authors: Scopel Eduardo F C , Hose James , Bensasson Douda , Gasch Audrey P
Published: February 2021

Individuals carrying an aberrant number of chromosomes can vary widely in their expression of aneuploidy phenotypes. A major unanswered question is the degree to which an individual’s genetic makeup influences its tolerance of karyotypic imbalance. Here we investigated within-species variation in aneuploidy prevalence and tolerance, using Saccharomyces cerevisiae as a model for eukaryotic biology. We analyzed genotypic and phenotypic variation recently published for over 1,000 S. cerevisiae strains spanning dozens of genetically defined clades and ecological associations. Our results show that the prevalence of chromosome gain and loss varies by clade and can be better explained by differences in genetic background than ecology. The relationships between lineages with high aneuploidy frequencies suggest that increased aneuploidy prevalence emerged multiple times in S. cerevisiae evolution. Separate from aneuploidy prevalence, analyzing growth phenotypes revealed that some genetic backgrounds—such as the European Wine lineage—show fitness costs in aneuploids compared to euploids, whereas other clades with high aneuploidy frequencies show little evidence of major deleterious effects. Our analysis confirms that chromosome gain can produce phenotypic benefits, which could influence evolutionary trajectories. These results have important implications for understanding genetic variation in aneuploidy prevalence in health, disease, and evolution.
Gender Disparities in Life Satisfaction After Retirement: The Roles of Leisure, Family, and Finances
Authors: Calasanti Toni , Carr Dawn , Homan Patricia , Coan Victoria
Published: February 2021

Background and Objectives

Recent research on life satisfaction in retirement explores gender differences but yields inconsistent patterns and does not consider gendered sources of satisfaction. We use a gender relations framework to examine whether women and men experience different changes in life satisfaction with retirement, and whether observed differences are a consequence of different assessments of the leisure, family, and financial situations that characterize their post-retirement lives.

Research Design and Methods

We use longitudinal data drawn from men and women in the Health and Retirement Study who transitioned into retirement between ages 62 and 72 for the first time between 2008 and 2016 (N = 593). We employ ordinary least squares regression and mediation tests to assess gender differences in overall and domain-specific life satisfaction (i.e., leisure, family, finances).

Results

Men reported increased life satisfaction following retirement, but women did not. No gender differences related to leisure or family life post-retirement emerged. Gender was associated with post-retirement satisfaction with finances (p < .001), with men reporting higher financial satisfaction. Mediation models confirmed a gender disparity in overall life satisfaction mediated by satisfaction with finances post-retirement (p < .01), explaining approximately one-third of the disparity.

Discussion and Implications

This study shows men derive greater improvements in life satisfaction in association with retirement than do women, and some of this disparity relates to women’s lower satisfaction with their finances. These findings should caution policy-makers from assuming how women’s increased labor force participation influences financial security in retirement, and encourage scholars to consider how gender influences subjective assessments of later life.
A self-similar dynamic rupture model based on the simplified wave-rupture analogy
Authors: Dahm T , Heimann S , Metz M , Isken M P
Published: February 2021

The investigation of stresses, faults, structure and seismic hazards requires a good understanding and mapping of earthquake rupture and slip. Constraining the finite source of earthquakes from seismic and geodetic waveforms is challenging because the directional effects of the rupture itself are small and dynamic numerical solutions often include a large number of free parameters. The computational effort is large and therefore difficult to use in an exploratory forward modelling or inversion approach. Here, we use a simplified self-similar fracture model with only a few parameters, where the propagation of the fracture front is decoupled from the calculation of the slip. The approximative method is flexible and computationally efficient. We discuss the strengths and limitations of the model with real-case examples of well-studied earthquakes. These include the Mw 8.3 2015 Illapel, Chile, megathrust earthquake at the plate interface of a subduction zone and examples of continental intraplate strike-slip earthquakes like the Mw 7.1 2016 Kumamoto, Japan, multisegment variable slip event or the Mw 7.5 2018 Palu, Indonesia, supershear earthquake. Despite the simplicity of the model, a large number of observational features ranging from different rupture-front isochrones and slip distributions to directional waveform effects or high slip patches are easy to model. The temporal evolution of slip rate and rise time are derived from the incremental growth of the rupture and the stress drop without imposing other constraints. The new model is fast and implemented in the open-source Python seismology toolbox Pyrocko, ready to study the physics of rupture and to be used in finite source inversions.
Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis
Authors: Friligou Irene , Gassner Jana , Knoblauch Dominic , Kagerer Gabriele , Popp Franziska , Voit Susanne , Engel Alfred M , Leinenbach Andreas , Steffen Wojtek , Haberger Markus , Tabarés Glòria
Published: February 2021

Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years. Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling. In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region. However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts. Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage. In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression. Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures. The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs. O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs. Substitution of this threonine allowed an almost complete Fab fragment cleavage. Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance.
IP Licensing Contracts in Italy ‒ Royalty Rate Determination and Dispute Resolution Clauses
Authors: Gelato Paola , Vergano Stefano
Published: February 2021

The present work is aimed at exploring IP license agreements under Italian law, with a focus on trademark licensing in the fashion, cosmetics and perfumery sectors, as well as on patent and know-how licensing in the pharmaceuticals industry. In particular, we will address the issue of royalty rate determination and dispute resolution clauses, which constitute key elements of a license agreement. These clauses will be analyzed in light of the above-mentioned fields of interest, in order to show how IP contractual tools may vary, in consideration of a particular sector. Moreover, the article tries to combine the legal analysis with the economic implications for business and entrepreneurs. The fact is that license agreements are business-oriented contracts, the study of which is particularly useful for understanding how and to what extent an IP agreement may influence and even shape, in some cases, a whole sector, as we will see with, for example, the perfumery sector.
Educating outdoor workers using tailored and financial messages to encourage safe-sun behaviors
Authors: Entringer Aaron C , Brannon Laura A , Whitaker Whitney K
Published: February 2021

Excessive and unsafe sun exposure represents a concerning hazard to the health of individuals. Of particular interest are those who are most susceptible to sun exposure, such as outdoor workers. The current study used a 3 × 2 between-subjects design to investigate the effectiveness of messages that varied the extent of personalization (i.e. generic message; occupation targeted message; individual tailored message) and the inclusion of content regarding financial consequences of skin cancer. Participants (N = 304) were recruited from the USA through Amazon’s Mechanical Turk and randomly assigned to view a generic message, occupation targeted message, or individual tailored message. Additionally, participants were randomly assigned to view messages in which financial information was either present or not. Participants responded to questions assessing pre- and post-test sun protection behaviors. Individual tailored messaging was as effective as occupation targeted messaging, with both being more effective than generic messaging. This finding indicates that some degree of personalization is necessary when promoting safe-sun practices to outdoor workers, but that tailoring to individuals may not always be necessary. Inclusion of financial content in messaging resulted in greater intentions to practice sun protection behaviors. Results provide insight into effective methods for promoting sun protection.
Trends and Outcomes of Acute Diverticulitis in Inflammatory Bowel Disease: A Propensity-matched National Study
Authors: Garg Rajat , Mohammed Abdul , Singh Amandeep , Regueiro Miguel , Click Benjamin
Published: February 2021

Background

Patients with inflammatory bowel disease (IBD) may be at increased risk for acute diverticulitis (AD) complications due to luminal inflammation and immune modifying medications. We aimed to assess outcomes of acute diverticulitis in patients with IBD.

Methods

A propensity-matched analysis of the National Inpatient Sample database was performed to assess outcomes of AD in adult patients (older than 18 years) from 2004 to 2013 with and without IBD. Outcomes included in-hospital mortality, need for percutaneous drainage, surgery, venous thromboembolism (VTE), total cost, and length of stay (LOS). A subgroup analysis comparing patients with Crohn’s disease (CD) and ulcerative colitis (UC) was performed.

Results

After propensity matching, compared with non-IBD patients (n = 15,015); Patients with IBD (n = 15,106) did not have significantly higher rate of mortality and surgical intervention but had significantly higher rates of percutaneous drainage (4% vs 3.4%; P = 0.002), VTE (1.1% vs 0.7%; P < 0.001), longer LOS (P < 0.001), and total cost (P < 0.001). Compared with CD, UC was associated with significantly higher rates of surgical intervention (20.3% vs 19%; P = 0.04), in-hospital mortality (1.4% vs 0.4%; P < 0.001), VTE (1.6% vs 0.7%; P < 0.001), total cost ($41,672 ± $61,358 vs $33,951 ± $54,376; P < 0.001), and LOS (6.4 ± 6.4 vs 5.7 ± 5.3; P < 0.001). From 2004 to 2013, there was a significant increase of IBD (range 0.5% to 0.8%; P = < 0.001) in AD patients with overall stable mortality (0.5% to 1.0%; P = 0.47) of AD in patients with IBD.

Conclusions

Patients with IBD are at increased risk of complicated diverticulitis and worse outcomes compared with matched controls. Optimal AD management strategies in IBD are needed.
Sidney Holt, a giant in the history of fisheries science who focused on the future: his legacy and challenges for present-day marine scientists
Authors: Raicevich Saša , Caswell Bryony A , Bartolino Valerio , Cardinale Massimiliano , Eddy Tyler D , Giovos Ioannis , Lescrauwaet Ann-Katrien , Thurstan Ruth H , Engelhard Georg H , Klein Emily S
Published: January 2021

Sidney J. Holt (1926–2019) was more than a founding father of quantitative fisheries science, and the man who “helped save the great whales.” His accomplishments, over a career spanning seven decades, run deeper: he was a champion of reductionism (i.e. able to identify the factors essential for management) and a systemic thinker who inspired scientists to think critically about marine conservation and management. This article draws on first-hand experiences with Sidney over the last 15 years, when he regularly collaborated with scholars of the ICES Working Group on the History of Fish and Fisheries and the Oceans Past Initiative. Four main themes emerged from our reflections on Sidney’s life and legacy, which constitute ongoing scientific challenges: (1) the suitability of maximum sustainable yield as a target reference point for fisheries management; (2) the future of marine mammal conservation; (3) successful implementation of ecosystem-based marine management; and (4) the value of historical perspectives for conservation and management. We consider Sidney’s work across these themes, in which he readily collaborated, focused on evidence-based solutions, and, where evidence was lacking, he advocated for the “precautionary principle.” We posit there is much that we, and future generations of scientists, can learn from his example.
Casting a wide net and making the most of the catch
Authors: Varanasi Usha
Published: February 2021

I describe lessons learned and the people and principles that influenced six decades of professional endeavours from graduate schools to ascending, often unexpectedly, the science and management ladder in National Oceanic and Atmospheric Administration (NOAA) fisheries, which manages US living marine resources. For this woman chemist from India, the twists of fate and love of adventure presented amazing opportunities as well as challenges. My research on cetacean biosonar as well as on the impact of fossil fuel pollution on seafood safety and the health of marine organisms taught me the value of multidisciplinary approaches and unusual alliances. Transitioning into management, and eventually as the director of Northwest Fisheries Science Center, I learned the value of transparency and empathy while communicating our results to impacted communities, and the resolve to support the science regardless of the consequences. My advice to young professionals is that the journey should be as fulfilling as reaching the goalpost. At the twilight of my own journey, I networked with NOAA Fisheries and India’s marine science community to encourage scientist exchanges and training. My participation in University of Washington’s nature and human health programme confirms my conviction that conserving healthy ecosystems is a powerful and practical approach for people and our planet.
Multiple Identities and Scholarship: Black Scholars’ Struggles for Acceptance and Recognition in the United States of America
Authors: Kuradusenge-McLeod Claudine
Published: February 2021

This article explores the stories of African and African American scholars in predominantly white institutions. It sheds light on the challenges of underrepresentation, sexism, and racial identity in an area of white fragility: academia. The lack of representation among International Studies scholars in the United States and Europe has not only had an impact on academia, but has also put heavy pressure on minority scholars, since they are often asked, by their institutions and students, to advise and mentor students who too often feel out of place or misunderstood by the faculty available to them. Therefore, it is imperative that we embrace minority faculty members, whether they are from the United States, Europe, or the Global South. Using narrative analysis, I examine conversations that I had with thirteen Black women who work at prestigious white universities and ten students who took classes with at least one Black, female professor. Although our field has expanded and accepted new members, many minority scholars still see it as a very selective, almost all Western, boys’ club.
A muramidase from Acremonium alcalophilum hydrolyse peptidoglycan found in the gastrointestinal tract of broiler chickens
Authors: Frederiksen Carsten Østergaard , Cohn Marianne Thorup , Skov Lars Kobberøe , Schmidt Esben Gjerløff Wedebye , Schnorr Kirk Matthew , Buskov Steen , Leppänen Miika , Maasilta Ilari , Perez-Calvo Estefania , Lopez-Ulibarri Rual , Klausen Mikkel
Published: February 2021

This study evaluates peptidoglycan hydrolysis by a microbial muramidase from the fungus Acremonium alcalophilum in vitro and in the gastrointestinal tract of broiler chickens. Peptidoglycan used for in vitro studies was derived from 5 gram-positive chicken gut isolate type strains. In vitro peptidoglycan hydrolysis was studied by three approaches: (a) helium ion microscopy to identify visual phenotypes of hydrolysis, (b) reducing end assay to quantify solubilization of peptidoglycan fragments, and (c) mass spectroscopy to estimate relative abundances of soluble substrates and reaction products. Visual effects of peptidoglycan hydrolysis could be observed by helium ion microscopy and the increase in abundance of soluble peptidoglycan due to hydrolysis was quantified by a reducing end assay. Mass spectroscopy confirmed the release of hydrolysis products and identified muropeptides from the five different peptidoglycan sources. Peptidoglycan hydrolysis in chicken crop, jejunum, and caecum samples was measured by quantifying the total and soluble muramic acid content. A significant increase in the proportion of the soluble muramic acid was observed in all three segments upon inclusion of the microbial muramidase in the diet.
Neurite Outgrowth Inhibitor (NogoA) Is Upregulated in White Matter Lesions of Complex Cortical Malformations
Authors: Scholl Theresa , Gruber Victoria-Elisabeth , Samueli Sharon , Lehner Reinhard , Kasprian Gregor , Czech Thomas , Reinten Roy J , Hoogendijk Lisette , Hainfellner Johannes A , Aronica Eleonora , Mühlebner Angelika , Feucht Martha
Published: January 2021

Complex cortical malformations (CCMs), such as hemimegalencephaly and polymicrogyria, are associated with drug-resistant epilepsy and developmental impairment. They share certain neuropathological characteristics including mammalian target of rapamycin (mTOR) activation and an atypical number of white matter neurons. To get a better understanding of the pathobiology of the lesion architecture, we investigated the role of neurite outgrowth inhibitor A (NogoA), a known regulator of neuronal migration. Epilepsy surgery specimens from 16 CCM patients were analyzed and compared with sections of focal cortical dysplasia IIB (FCD IIB, n = 22), tuberous sclerosis complex (TSC, n = 8) as well as healthy controls (n = 15). Immunohistochemistry was used to characterize NogoA, myelination, and mTOR signaling. Digital slides were evaluated automatically with ImageJ. NogoA staining showed a significantly higher expression within the white matter of CCM and FCD IIB, whereas cortical tubers presented levels similar to controls. Further analysis of possible associations of NogoA with other factors revealed a positive correlation with mTOR and seizure frequency. To identify the main expressing NogoA cell type, double staining revealed dysmorphic neuronal white matter cells. Increased NogoA expression is associated with profound inhibition of neuritic sprouting and therefore contributes to a decrease in neuronal network complexity in CCM patients.
A staged hybrid approach to an aberrant right subclavian artery with symptomatic Kommerell’s diverticulum
Authors: Dinh Krystal , Manuel Lucy , Perera Kalpa , Daly Thomas
Published: January 2021

Aberrant right subclavian is a rare anomaly presenting in 0.3–3.0% of the population. Kommerell’s diverticulum is an aneurysm associated with this phenomen; data relating to its incidence is sparse. Currently there are no well-established guidelines for the treatment of Kommerell’s diverticulum, limitation being the rare occurrence of disease and heterogenous population with disease presentation. This case report illustrates a novel approach to the repair of a symptomatic Kommerrel’s diverticulum with severe coronary disease. Management should be tailored on a case by case basis to the individual patient.
Spatial Genealogies: Mobility, Settlement, and Empire-Building in the Brazilian Backlands, 1650–1800
Authors: Barleta Leonardo
Published: February 2021

This study examines the territorial expansion of Portuguese colonization in South America by analyzing the spatial practices of Luso-Brazilian families in the captaincy of São Paulo, Brazil during the seventeenth and eighteenth centuries. After the 1690s, successive discoveries of mineral wealth lured thousands of colonists to scattered settlements in the interior of the continent, challenging the long-established maritime orientation of the Portuguese empire. Given obstacles posed by distance and lack of infrastructure as well as the near absence of formal institutions, this study asks how the Portuguese extended the occupation into the backlands and what mechanisms enabled the integration of these new pockets of settlement into the rest of the empire. It combines different computational methods, such as text mining, data modeling and analysis, and digital mapping to examine a large corpus of genealogical writings about prominent families of colonial São Paulo, reconstituting patterns of geographic mobility of more than 3,000 individuals. These patterns indicate that mobility was shaped by family ties, which allowed colonists to marshal resources, share geographic knowledge, and forge alliances for travel and exploration. Because kinship was an enduring form of social relationship, it provided lasting linkages that connected distant settlements to the consolidated areas of occupation and gave a sense of spatial cohesion that sustained the empire inland.
Price review arbitration in the Asian LNG markets—‘‘The times they are a-changin’’
Authors: Talus Kim
Published: February 2021

This article will focus on price review clauses in Asian LNG markets from the point of view of price review arbitration and the jurisdiction of the tribunal. The basic conclusion reach is that there is no simple answer but that various considerations speak in favour of establishing the jurisdiction of arbitral tribunals in respect of gas prices. The background to the article is a number of gas price arbitrations that have been initiated in Asian markets and the assumption that these early cases will be followed by many more. One of the questions raised in this context is jurisdiction of the tribunal.
Cross-Institutional Evaluation of the Abbott ARCHITECT SARS-CoV-2 IgG Immunoassay
Authors: Wiencek Joesph R , Bachmann Lorin M , Dinwiddie Kelly , Miller Greg W , Bazydlo Lindsay A L
Published: February 2021

Objective

To describe a cross-institutional approach to verify the Abbott ARCHITECT SARS-CoV-2 antibody assay and to document the kinetics of the serological response.

Methods

We conducted analytical performance evaluation studies using the Abbott ARCHITECT SARS-CoV-2 antibody assay on 5 Abbott ARCHITECT i2000 automated analyzers at 2 academic medical centers.

Results

Within-run and between-run coefficients of variance (CVs) for the antibody assay did not exceed 5.6% and 8.6%, respectively, for each institution. Quantitative and qualitative results agreed for lithium heparin plasma, EDTA-plasma and serum specimen types. Results for all SARS-CoV-2 IgG-positive and -negative specimens were concordant among analyzers except for 1 specimen at 1 institution. Qualitative and quantitative agreement was observed for specimens exchanged between institutions. All patients had detectable antibodies by day 10 from symptom onset and maintained seropositivity throughout specimen procurement.

Conclusions

The analytical performance characteristics of the Abbott ARCHITECT SARS-CoV-2 antibody assay within and between 2 academic medical center clinical laboratories were acceptable for widespread clinical-laboratory use.
The origin of X-ray coronae around simulated disc galaxies
Authors: Kelly Ashley J , Jenkins Adrian , Frenk Carlos S
Published: February 2021

The existence of hot, accreted gaseous coronae around massive galaxies is a long-standing central prediction of galaxy formation models in the ΛCDM cosmology. While observations now confirm that extraplanar hot gas is present around late-type galaxies, the origin of the gas is uncertain with suggestions that galactic feedback could be the dominant source of energy powering the emission. We investigate the origin and X-ray properties of the hot gas that surrounds galaxies of halo mass, $(10^{11}\!-\!10^{14}) \, \mathrm{M}_\odot$, in the cosmological hydrodynamical eagle simulations. We find that the central X-ray emission, ≤0.10Rvir, of haloes of mass $\le 10^{13} \, \mathrm{M}_\odot$ originates from gas heated by supernovae (SNe). However, beyond this region, a quasi-hydrostatic, accreted atmosphere dominates the X-ray emission in haloes of mass $\ge 10^{12} \, \mathrm{M}_\odot$. We predict that a dependence on halo mass of the hot gas to dark matter mass fraction can significantly change the slope of the LX–Mvir relation (which is typically assumed to be 4/3 for clusters) and we derive the scaling law appropriate to this case. As the gas fraction in haloes increases with halo mass, we find a steeper slope for the LX–Mvir in lower mass haloes, $\le 10^{14} \, \mathrm{M}_\odot$. This varying gas fraction is driven by active galactic nuclei feedback. We also identify the physical origin of the so-called ‘missing feedback’ problem, the apparently low X-ray luminosities observed from high star-forming, low-mass galaxies. This is explained by the ejection of SNe-heated gas from the central regions of the halo.