bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotional Development
Authors: Gill Christopher
Published: December 2022

Chapter 5 is devoted to emotional development—a third strand in Stoic thinking on this subject, which is seen as dependent on success or failure in the two strands of appropriation. Bad or defective emotions reflect failure in ethical development whereas good emotions express successful development towards virtue, virtue-based happiness, and virtuous social relationships. Scholars sometimes regard the Stoics as advocating a kind of self-sufficiency that involves detachment from other people. This chapter argues against this view, maintaining that, in Stoic ethics, emotional development (or the ‘therapy’ of emotions) depends on engagement in virtuous relationships. In particular, a passage in Epictetus often taken as advocating detachment is interpreted as urging the combination of virtuous involvement with recognition of the fact of the future death of both partners in the relationship.
Sex differences in perceptions of sleep inertia following nighttime awakenings
Authors: Hilditch Cassie J , Pradhan Sean , Costedoat Gregory , Bathurst Nicholas G , Glaros Zachary , Gregory Kevin B , Shattuck Nita L , Flynn-Evans Erin E
Published: December 2022

Study Objectives

The influence of biological sex on sleep inertia symptoms is currently unknown. We investigated the role of sex differences in the subjective experience and objective cognitive manifestation of sleep inertia following nighttime awakenings.

Methods

Thirty-two healthy adults (16 female, 25.91 ± 5.63 years) completed a 1-week at-home study with one experimental night during which sleep was measured by polysomnography and participants were awakened during their habitual sleep time. Participants completed a psychomotor vigilance task, Karolinska Sleepiness Scale (KSS), visual analog mood scales, and a descending subtraction task (DST) prior to sleep (baseline) and at 2, 12, 22, and 32 min after awakening. A series of mixed-effects models with Bonferroni-corrected post hoc tests were used to examine the main effects of test bout and sex, and their interaction, with a random effect of participant, and order of wake-up and sleep history as covariates.

Results

All outcomes except for percent correct on the DST showed a significant main effect of test bout, with worse performance after waking compared to baseline (all ps < .003). Significant effects of sex (p = .002) and sex × test bout (p = .01; R2M = 0.49, R2C = 0.69) were observed for KSS, with females reporting a greater increase in sleepiness from baseline to after waking compared to males.

Conclusions

These results suggest that while females reported feeling sleepier than males following nighttime awakenings, their cognitive performance was comparable. Future research is needed to determine whether perceptions of sleepiness influence decision-making during the transition from sleep to wakefulness.
Everglades virus evolution: Genome sequence analysis of the envelope 1 protein reveals recent mutation and divergence in South Florida wetlands
Authors: Valente Monica C , Prakoso Dhani , Vittor Amy Y , Blosser Erik M , Abid Nabil , Pu Ruiyu , Beachboard Sarah E , Long Maureen T , Burkett-Cadena Nathan D , Mavian Carla N
Published: December 2022

Everglades virus (EVEV) is a subtype (II) of Venezuelan equine encephalitis virus (VEEV), endemic in southern Florida, USA. EVEV has caused clinical encephalitis in humans, and antibodies have been found in a variety of wild and domesticated mammals. Over 29,000 Culex cedecei females, the main vector of EVEV, were collected in 2017 from Big Cypress and Fakahatchee Strand Preserves in Florida and pool-screened for the presence of EVEV using reverse transcription real-time polymerase chain reaction. The entire 1 E1 protein gene was successfully sequenced from fifteen positive pools. Phylogenetic analysis showed that isolates clustered, based on the location of sampling, into two monophyletic clades that diverged in 2009. Structural analyses revealed two mutations of interest, A116V and H441R, which were shared among all isolates obtained after its first isolation of EVEV in 1963, possibly reflecting adaptation to a new host. Alterations of the Everglades ecosystem may have contributed to the evolution of EVEV and its geographic compartmentalization. This is the first report that shows in detail the evolution of EVEV in South Florida. This zoonotic pathogen warrants inclusion into routine surveillance given the high natural infection rate in the vectors. Invasive species, increasing urbanization, the Everglades restoration, and modifications to the ecosystem due to climate change and habitat fragmentation in South Florida may increase rates of EVEV spillover to the human population.
Novel Diagnostic and Treatment Techniques for Neurogenic Thoracic Outlet Syndrome
Authors: Wagner Eric R. , Gottschalk Michael B. , Ahmed Adil Shahzad , Graf Alexander R. , Karzon Anthony L.
Published: December 2022

Neurogenic thoracic outlet syndrome is a challenging condition to diagnose and treat, often precipitated by the triad of repetitive overhead activity, pectoralis minor contracture, and scapular dyskinesia. The resultant protracted scapular posture creates gradual repetitive traction injury of the suprascapular nerve via tethering at the suprascapular notch and decreases the volume of the brachial plexus cords and axillary vessels in the retropectoralis minor space. A stepwise and exhaustive diagnostic protocol is essential to exclude alternate pathologies and confirm the diagnosis of this dynamic pathologic process. Ultrasound-guided injections of local anesthetic or botulinum toxin are a key factor in confirming the diagnosis and prognosticating potential response from surgical release. In patients who fail over 6 months of supervised physical therapy aimed at correcting scapular posture and stretching of the pectoralis minor, arthroscopic surgical release is indicated. We present our diagnostic algorithm and technique for arthroscopic suprascapular neurolysis, pectoralis minor release, brachial plexus neurolysis, and infraclavicular thoracic outlet decompression.
Is a strict restricted-iodine diet necessary for preparation of radioactive iodine therapy?
Authors: Genc Mustafa , Yildirim Aslihan , Yildirim Nilufer
Published: December 2022

Objective

A restricted-iodine diet (RID) increases the effectiveness of radioiodine therapy (RAIT) by decreasing the body’s iodine pool, especially in iodine-rich regions. However, there is no consensus on the RID that should be applied in iodine-deficient areas. This study aims to assess the effect of strict and flexible RID before RAIT.

Methods

For the study, 144 patients were randomized into the strict or flexible RID group. All patients stopped levothyroxine before RAIT and followed a RID. After 2 weeks of RID, 24-h urine samples were taken. The urinary iodine excretion was compared. In 52 of 144 patients, the spot urine samples were taken before and after RID. The reduction in urinary iodine excretion was compared according to the iodine/creatinine ratio.

Results

Our study included 47 males and 97 females with a mean age of 45 years. After RID in the 24-h urine samples, the mean iodine level was 47.9 µg/day, and both protocols were sufficient to reduce the body iodine pool. There was no significant difference between the strict and the flexible group, 43.06 and 52.89 µg/day (P:0.147). The reduction in urinary iodine excretion was not statistically different in both groups according to spot urine samples (68.20 vs. 60.53%; P:0.377).

Conclusion

The flexible RID protocol that less disrupts the patient’s quality of life can be preferred for RAIT preparation in iodine-deficient countries.
Structural Equation Modeling of Stigma and HIV Prevention Clinical Services Among Transgender and Gender Diverse Adults: The Mediating Role of Substance Use and HIV Sexual Risk
Authors: Wolfe Hill L. , Drainoni Mari-Lynn , Klasko-Foster Lynne , Fix Gemmae M. , Siegel Jennifer , Mimiaga Matthew J. , Reisner Sari L. , Hughto Jaclyn M.W.
Published: December 2022

Background:

Transgender and gender diverse (TGD) adults experience high levels of stigma that contributes to elevated substance use and HIV sexual risk behaviors. Despite higher burdens of substance use and HIV compared to cisgender adults, TGD individuals may be less likely to engage in health care to avoid further discrimination.

Setting:

This analysis included 529 TGD adults in Massachusetts and Rhode Island who were HIV negative or had an unknown HIV serostatus and were purposively sampled between March and August 2019.

Methods:

We used structural equation modeling to test whether substance use, HIV sexual risk behaviors (ie, condom use, sex work, and multiple partners), and receiving gender-affirming hormone therapy mediate any observed association between TGD-related stigma and utilization of HIV prevention clinical services (ie, HIV prevention programs, PrEP use, and HIV testing).

Results:

Substance use and HIV sexual risk mediated the relationship between TGD-related stigma and utilization of HIV prevention clinical services (β = 0.08; 95% CI = 0.05, 0.17; P = 0.03 and β = 0.26; 95% CI = 0.14 to 0.37; P < 0.001). Having a hormone therapy prescription was not a mediator between TGD-related stigma and HIV prevention clinical services.

Conclusions:

Future interventions that aim to improve HIV prevention clinical services among TGD adults should consider the impact of TGD-related stigma on participants' substance use and sexual risk behaviors. These efforts require that health care organizations and community organizations make a deliberate investment in the reach and success of interventions and programs.
EXTRACELLULAR VESICLES AS REGULATORS OF IMMUNE FUNCTION IN TRAUMATIC INJURIES AND SEPSIS
Authors: Seim Roland F. , Willis Micah L. , Wallet Shannon M. , Maile Robert , Coleman Leon G.
Published: December 2022

Despite advancements in critical care and resuscitation, traumatic injuries are one of the leading causes of death around the world and can bring about long-term disabilities in survivors. One of the primary causes of death for trauma patients are secondary phase complications that can develop weeks or months after the initial insult. These secondary complications typically occur because of systemic immune dysfunction that develops in response to injury, which can lead to immunosuppression, coagulopathy, multiple organ failure, unregulated inflammation, and potentially sepsis in patients. Recently, extracellular vesicles (EVs) have been identified as mediators of these processes because their levels are increased in circulation after traumatic injury and they encapsulate cargo that can aggravate these secondary complications. In this review, we will discuss the role of EVs in the posttrauma pathologies that arise after burn injuries, trauma to the central nervous system, and infection. In addition, we will examine the use of EVs as biomarkers for predicting late-stage trauma outcomes and as therapeutics for reversing the pathological processes that develop after trauma. Overall, EVs have emerged as critical mediators of trauma-associated pathology and their use as a therapeutic agent represents an exciting new field of biomedicine.
Mechanisms driving spatial distribution of residents in colony biofilms: an interdisciplinary perspective
Authors: Eigentler Lukas , Davidson Fordyce A. , Stanley-Wall Nicola R.
Published: December 2022

Biofilms are consortia of microorganisms that form collectives through the excretion of extracellular matrix compounds. The importance of biofilms in biological, industrial and medical settings has long been recognized due to their emergent properties and impact on surrounding environments. In laboratory situations, one commonly used approach to study biofilm formation mechanisms is the colony biofilm assay, in which cell communities grow on solid–gas interfaces on agar plates after the deposition of a population of founder cells. The residents of a colony biofilm can self-organize to form intricate spatial distributions. The assay is ideally suited to coupling with mathematical modelling due to the ability to extract a wide range of metrics. In this review, we highlight how interdisciplinary approaches have provided deep insights into mechanisms causing the emergence of these spatial distributions from well-mixed inocula.
How environment affects active particle swarms: a case study
Authors: Degond Pierre , Manhart Angelika , Merino-Aceituno Sara , Peurichard Diane , Sala Lorenzo
Published: December 2022

We investigate the collective motion of self-propelled agents in an environment filled with obstacles that are tethered to fixed positions via springs. The active particles are able to modify the environment by moving the obstacles through repulsion forces. This creates feedback interactions between the particles and the obstacles from which a breadth of patterns emerges (trails, band, clusters, honey-comb structures, etc.). We will focus on a discrete model first introduced in Aceves-Sanchez P
et al.
(2020,
Bull. Math. Biol.
82,
125 (
doi:10.1007/s11538-020-00805-z
)), and derived into a continuum PDE model. As a first major novelty, we perform an in-depth investigation of pattern formation of the discrete and continuum models in two dimensions: we provide phase-diagrams and determine the key mechanisms for bifurcations to happen using linear stability analysis. As a result, we discover that the agent-agent repulsion, the agent-obstacle repulsion and the obstacle’s spring stiffness are the key forces in the appearance of patterns, while alignment forces between the particles play a secondary role. The second major novelty lies in the development of an innovative methodology to compare discrete and continuum models that we apply here to perform an in-depth analysis of the agreement between the discrete and continuum models.
Painlevé-type asymptotics for the defocusing Hirota equation in transition region
Authors: Xun Weikang , Ju Luman , Fan Engui
Published: December 2022

We consider the long-time asymptotics for the defocusing Hirota equation with Schwartz Cauchy data in the transition region. On the basis of direct and inverse scattering transform of the Lax pair of Hirota equations, we first express the solution of the Cauchy problem in terms of the solution of a Riemann–Hilbert problem. Further, we apply nonlinear steepest descent analysis to obtain the long-time asymptotics of the solution in the critical transition region

|

x

/

t

−
(

α
2

/

3
β

)

|

t

2

/

3

≤
M

, where

M

is a positive constant. Our result shows that the long-time asymptotics of the Hirota equation can be expressed in terms of the solution of the Painlevé

II

equation.
Pathogen transmission modes determine contact network structure, altering other pathogen characteristics
Authors: Collier Melissa , Albery Gregory F. , McDonald Grant C. , Bansal Shweta
Published: December 2022

Pathogen traits can vary greatly and heavily impact the ability of a pathogen to persist in a population. Although this variation is fundamental to disease ecology, little is known about the evolutionary pressures that drive these differences, particularly where they interact with host behaviour. We hypothesized that host behaviours relevant to different transmission routes give rise to differences in contact network structure, constraining the space over which pathogen traits can evolve to maximize fitness. Our analysis of 232 contact networks across mammals, birds, reptiles, amphibians, arthropods, fish and molluscs found that contact network topology varies by contact type, most notably in networks that are representative of fluid-exchange transmission. Using infectious disease model simulations, we showed that these differences in network structure suggest pathogens transmitted through fluid-exchange contact types will need traits associated with high transmissibility to successfully proliferate, compared to pathogens that transmit through other types of contact. These findings were supported through a review of known traits of pathogens that transmit in humans. Our work demonstrates that contact network structure may drive the evolution of compensatory pathogen traits according to transmission strategy, providing essential context for understanding pathogen evolution and ecology.
Warming signals in temperate reef communities following more than a decade of ecological stability
Authors: Soler G. A. , Edgar G. J. , Barrett N. S. , Stuart-Smith R. D. , Oh E. , Cooper A. , Ridgway K. R. , Ling S. D.
Published: December 2022

Ecosystem structure and function are increasingly threatened by changing climate, with profound effects observed globally in recent decades. Based on standardized visual censuses of reef biodiversity, we describe 27 years of community-level change for fishes, mobile macroinvertebrates and macroalgae in the Tasmanian ocean-warming hotspot. Significant ecological change was observed across 94 reef sites (5–10 m depth range) spanning four coastal regions between three periods (1992–95, 2006–07, 2017–19), which occurred against a background of pronounced sea temperature rise (+0.80°C on average). Overall, fish biomass increased, macroinvertebrate species richness and abundance decreased and macroalgal cover decreased, particularly during the most recent decade. While reef communities were relatively stable and warming was slight between the 1990s and mid-2000s (+0.12°C mean temperature rise), increased abundances of warm affinity fishes and invertebrates accompanied warming during the most recent decade (+0.68°C rise). However, significant rises in the community temperature index (CTI) were only found for fishes, invertebrates and macroalgae in some regions. Coastal warming was associated with increased fish biomass of non-targeted species in fished zones but had little effect on reef communities within marine reserves. Higher abundances of larger fishes and lobsters inside reserves appeared to negate impacts of ‘thermophilization’.
Diving into a dead-end: asymmetric evolution of diving drives diversity and disparity shifts in waterbirds
Authors: Tyler Joshua , Younger Jane L.
Published: December 2022

Diving is a relatively uncommon and highly specialized foraging strategy in birds, mostly observed within the Aequorlitornithes (waterbirds) by groups such as penguins, cormorants and alcids. Three key diving techniques are employed within waterbirds: wing-propelled pursuit diving (e.g. penguins), foot-propelled pursuit diving (e.g. cormorants) and plunge diving (e.g. gannets). How many times diving evolved within waterbirds, whether plunge diving is an intermediate state between aerial foraging and submarine diving, and whether the transition to a diving niche is reversible are not known. Here, we elucidate the evolutionary history of diving in waterbirds. We show that diving has been acquired independently at least 14 times within waterbirds, and this acquisition is apparently irreversible, in a striking example of asymmetric evolution. All three modes of diving have evolved independently, with no evidence for plunge diving as an intermediate evolutionary state. Net diversification rates differ significantly between diving versus non-diving lineages, with some diving clades apparently prone to extinction. We find that body mass is evolving under multiple macroevolutionary regimes, with unique optima for each diving type with varying degrees of constraint. Our findings highlight the vulnerability of highly specialized lineages during the ongoing sixth mass extinction.
Evaluation of three Staphylococcus aureus proteins involved in the adhesion process as antigens for the detection of bovine intramammary infections
Authors: Torres Giovanny , Sánchez-Jiménez Miryan , Reyes-Vélez Julián , Bach Horacio , Olivera-Angel Martha
Published: December 2022

Introduction. Fast and accurate diagnosis is one of the key strategies in the successful control of intramammary infections caused by

Staphylococcus aureus

. Immunoassays are one of the diagnostic tools that have been proposed for the detection of

S. aureus

infection because they offer an advantage in terms of cost and are fast and easy to use compared to other diagnostic tests.

Gap statement. The main challenge of the immunoassays is to identify antigens or serological markers that allow accurate discrimination between infected and uninfected cows with

S. aureus

, since this bacterium can naturally colonize different areas of the animal body.

Aim. To evaluate three

S. aureus

proteins (IsdA, ClfA, SdrD) involved in the adhesion process as antigens to detect indicator antibodies of bovine intramammary infections.

Methodology. Ninety-six cows in lactation and not vaccinated against

S. aureus

were included. Forty-eight of these cows were infected with

S. aureus

, while the rest (n=48 cows) were uninfected. Blood and milk samples were collected from each animal to recover serum and whey. IgG titres against the three proteins individually and combined (Mix) were measured in each sample using an enzyme-linked immunosorbent assay (ELISA) test.

Results. Significant differences in the IgG response against the proteins evaluated were observed, highlighting the antigenic potential of IsdA and demonstrating that some antigens can detect specific antibodies of infection better than others. According to receiver operating characteristic (ROC) curve analysis, the combined proteins showed the most remarkable capacity (sensitivity of 79 % and specificity of 77 %) to differentiate between infected and uninfected cows when blood samples were used. In addition, the combined proteins also showed the highest specificity (94 %) when using milk samples.

Conclusion. Our findings provide information on the usefulness of three adhesion-associated

S. aureus

proteins in detecting serological markers of intramammary infections in bovines.
At the threshold of symbiosis: the genome of obligately endosymbiotic ‘Candidatus Nebulobacter yamunensis’ is almost indistinguishable from that of a cultivable strain
Authors: Giannotti Daniele , Boscaro Vittorio , Husnik Filip , Vannini Claudia , Keeling Patrick J.
Published: December 2022

Comparing obligate endosymbionts with their free-living relatives is a powerful approach to investigate the evolution of symbioses, and it has led to the identification of several genomic traits consistently associated with the establishment of symbiosis. ‘Candidatus Nebulobacter yamunensis’ is an obligate bacterial endosymbiont of the ciliate Euplotes that seemingly depends on its host for survival. A subsequently characterized bacterial strain with an identical 16S rRNA gene sequence, named

Fastidiosibacter lacustris

, can instead be maintained in pure culture. We analysed the genomes of ‘Candidatus Nebulobacter’ and

Fastidiosibacter

seeking to identify key differences between their functional traits and genomic structure that might shed light on a recent transition to obligate endosymbiosis. Surprisingly, we found almost no such differences: the two genomes share a high level of sequence identity, the same overall structure, and largely overlapping sets of genes. The similarities between the genomes of the two strains are at odds with their different ecological niches, confirmed here with a parallel growth experiment. Although other pairs of closely related symbiotic/free-living bacteria have been compared in the past, ‘Candidatus Nebulobacter’ and

Fastidiosibacter

represent an extreme example proving that a small number of (unknown) factors might play a pivotal role in the earliest stages of obligate endosymbiosis establishment.
Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell
Authors: Foong Tian Yong , Hua Yi , Amini Rouzbeh , Sigal Ian A.
Published: December 2022

Collagen is the main load-bearing component of cornea and sclera. When stretched, both of these tissues exhibit a behavior known as collagen fiber recruitment. In recruitment, as the tissues stretch the constitutive collagen fibers lose their natural waviness, progressively straightening. Recruited, straight, fibers bear substantially more mechanical load than non-recruited, wavy, fibers. As such, the process of recruitment underlies the well-established nonlinear macroscopic behavior of the corneoscleral shell. Recruitment has an interesting implication: when recruitment is incomplete, only a fraction of the collagen fibers is actually contributing to bear the loads, with the rest remaining “in reserve”. In other words, at a given intraocular pressure (IOP), it is possible that not all the collagen fibers of the cornea and sclera are actually contributing to bear the loads.

To the best of our knowledge, the fraction of corneoscleral shell fibers recruited and contributing to bear the load of IOP has not been reported. Our goal was to obtain regionally-resolved estimates of the fraction of corneoscleral collagen fibers recruited and in reserve. We developed a fiber-based microstructural constitutive model that could account for collagen fiber undulations or crimp via their tortuosity. We used experimentally-measured collagen fiber crimp tortuosity distributions in human eyes to derive region-specific nonlinear hyperelastic mechanical properties. We then built a three-dimensional axisymmetric model of the globe, assigning region-specific mechanical properties and regional anisotropy. The model was used to simulate the IOP-induced shell deformation. The model-predicted tissue stretch was then used to quantify collagen recruitment within each shell region. The calculations showed that, at low IOPs, collagen fibers in the posterior equator were recruited the fastest, such that at a physiologic IOP of 15 mmHg, over 90% of fibers were recruited, compared with only a third in the cornea and the peripapillary sclera. The differences in recruitment between regions, in turn, mean that at a physiologic IOP the posterior equator had a fiber reserve of only 10%, whereas the cornea and peripapillary sclera had two thirds. At an elevated IOP of 50 mmHg, collagen fibers in the limbus and the anterior/posterior equator were almost fully recruited, compared with 90% in the cornea and the posterior sclera, and 70% in the peripapillary sclera and the equator. That even at such an elevated IOP not all the fibers were recruited suggests that there are likely other conditions that challenge the corneoscleral tissues even more than IOP. The fraction of fibers recruited may have other potential implications. For example, fibers that are not bearing loads may be more susceptible to enzymatic digestion or remodeling. Similarly, it may be possible to control tissue stiffness through the fraction of recruited fibers without the need to add or remove collagen.
Chromosome 8 gain drives cancer progression by hijacking the translation factor 4E-BP1 sensitizing for targeted CDK4/6 inhibition
Authors: Funk Cornelius M. , Ehlers Anna C. , Orth Martin F. , Aljakouch Karim , Li Jing , Hölting Tilman L. B. , Will Rainer , Ceranski A. Katharina , Willis Franziska , Vinca Endrit , Ohmura Shunya , Imle Roland , Siebenlist Jana , Yershova Angelina , Knott Maximilian M. L. , Zahnow Felina , Sastre Ana , Alonso Javier , Sahm Felix , Peterziel Heike , Loboda Anna , Schneider Martin , Banito Ana , Leprivier Gabriel , Hartmann Wolfgang , Dirksen Uta , Witt Olaf , Oehme Ina , Pfister Stefan M. , Romero-Pérez Laura , Krijgsveld Jeroen , Cidre-Aranaz Florencia , Grünewald Thomas G. P. , Musa Julian
Published: December 2022

Chromosome 8 (chr8) gains are common in cancer. However, their potential contribution to tumor heterogeneity is largely unexplored. Ewing sarcoma (EwS) is characterized by pathognomonicFET::ETSfusions but a general paucity of other recurrent somatic mutations that could explain the observed clinical diversity. In EwS, chr8 gains are the second most common genetic alteration rendering EwS an ideal model to investigate the relevance of chr8 gains in an otherwise silent genomic context.

Here, we report that chr8 gain-driven gene expression patterns correlate with poor overall survival of EwS patients. This effect is predominantly mediated by increased expression of the translation initiation factor binding protein 4E-BP1 encoded byEIF4EBP1on chr8. HighEIF4EBP1expression showed the strongest association with poor patient survival among all chr8-encoded genes and correlated with chr8 gains in EwS tumors. Similar findings were made in numerous entities of The Cancer Genome Atlas (TCGA). Integrated multi-omics profiling uncovered that 4E-BP1 orchestrates a pro-proliferative proteomic network. Consistently, silencing of 4E-BP1 in the EwS model reduced cell proliferation, clonogenicity, spheroidal growthin vitro, and tumorigenesisin vivo. Drug screens and functional assays revealed that high 4E-BP1 expression sensitizes for pharmacological CDK4/6 inhibition in preclinical models.

Collectively, we establish chr8 gains and high 4E-BP1 expression as prognostic biomarkers in EwS and demonstrate that their association with patient outcome is primarily mediated by 4E-BP1 orchestrating a pro-proliferative proteomic network sensitizing EwS for CDK4/6 inhibitors. Our data suggest that testing for chr8 gains may improve risk-stratification and therapeutic management in EwS and other cancers.
Hearables: Feasibility of Recording Cardiac Rhythms from Single Ear Locations
Authors: Yarici Metin , Von Rosenberg Wilhelm , Hammour Ghena , Davies Harry , Amadori Pierluigi , Ling Nico , Demiris Yiannis , Mandic Danilo P.
Published: December 2022

Wearable technologies are envisaged to provide critical support to future healthcare systems. Hearables - devices worn in the ear - are of particular interest due to their ability to provide health monitoring in an efficient, reliable and unobtrusive way. Despite the considerable potential of these devices, the ECG signal that can be acquired through a hearable device worn on a single ear is still relatively unexplored. Biophysics modelling of ECG volume conduction was used to establish principles behind the single ear ECG signal, and measurements of cardiac rhythms from 10 subjects were found to be in good correspondence with simulated equivalents. Additionally, the viability of the single ear ECG in real-world environments was determined through one hour duration measurements during a simulated driving task on 5 subjects. Results demonstrated that the single ear ECG resembles the Lead I signal, the most widely used ECG signal in the identification of heart conditions such as myocardial infarction and atrial fibrillation, and was robust against real-world measurement noise, even after prolonged measurements. This study conclusively demonstrates that hearables can enable continuous monitoring of vital signs in an unobtrusive and seamless way, with the potential for reliable identification and management of heart conditions such as myocardial infarction and atrial fibrillation.
Dynamics of interaction networks and species’ contributions to community-scale flexibility
Authors: Toju Hirokazu , Suzuki Sayaka S. , Baba Yuki G.
Published: December 2022

Architecture of species interaction networks is a key factor determining stability of ecological communities. However, the fact that ecological network architecture can change through time is often overlooked in discussions on community-level processes despite its theoretical importance. By compiling a time-series community dataset involving 50 spider species and 974 Hexapoda prey species/strains, we quantified the extent to which architecture of predator–prey interaction networks can shift across time points. We then developed a framework for finding species that could promote flexibility of interaction network architecture. Those “network coordinator” species are expected to promote persistence of species-rich ecological communities by buffering perturbations to communities. Although spiders are often considered as generalist predators, contributions to network flexibility varied greatly among species. We also found that detritivorous prey species can be cores of interaction rewiring, dynamically interlinking below-ground and above-ground community dynamics. Analyses of network coordinators will add a new dimension to our understanding of species coexistence mechanisms and provide platforms for systematically prioritizing species in terms of their potential contributions in ecosystem conservation and restoration.

Significance Statement

Like networks of human relations, webs of interactions between species are dynamically restructured through time. By compiling time-series time-series dataset including > 1,000 species/strains, we quantified the magnitude of ecological network dynamics in the wild. The analytical framework developed in this study highlighted “network coordinator” species, which are keys to conserve and restore endangered ecosystems.
Macromolecular crowding is surprisingly unable to deform the structure of a model biomolecular condensate
Authors: Shillcock Julian C. , Thomas David B. , Ipsen John H. , Brown Andrew D.
Published: December 2022

The crowded interior of a living cell makes experiments on simplerin vitrosystems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically-disordered proteins into biomolecular condensates, which is proposed to underlie the membraneless compartmentalisation of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally-varying cytoplasm is an important question for understanding cellular homeostasis. Computer simulations are often used to study the phase behaviour of model biomolecular condensates, but the number of relevant parameters explodes as the number of protein components increases. It is unfeasible to exhaustively simulate such models for all parameter combinations, although interesting phenomena are almost certainly hidden in the jungle of their high-dimensional parameter space. Here we have studied the phase behaviour of a model biomolecular condensate in the presence of a polymeric crowding agent. We used a novel compute framework to execute dozens of simultaneous simulations spanning the protein/crowder concentration space. We then combined the results into a graphical representation for human interpretation, which provided an efficient way to search the model’s high-dimensional parameter space. We found that steric repulsion from the crowder drives a near-critical system across the phase boundary, but the molecular arrangement within the resulting biomolecular condensate is rather insensitive to the crowder concentration and molecular weight. We propose that a cell may use the local cytoplasmic concentration to assist formation of biomolecular condensates, while relying on the dense phase reliably providing a stable, structured, fluid milieu for cellular biochemistry despite being open to its changing environment.
Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine
Authors: Ou Ben S. , Saouaf Olivia M. , Yan Jerry , Bruun Theodora U.J. , Baillet Julie , Zhou Xueting , King Neil P. , Appel Eric A.
Published: December 2022

Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS-CoV-2 vaccines require an initial two-shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations-scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune-escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, we developed a single immunization SARS-CoV-2 subunit vaccine that could rapidly generate potent, broad, and durable humoral immunity. We leveraged injectable polymer-nanoparticle (PNP) hydrogels as a depot technology for the sustained delivery of a nanoparticle COVID antigen displaying multiple copies of the SARS-CoV-2 receptor-binding-domain (RBD-NP), and potent adjuvants including CpG and 3M-052. Compared to a clinically relevant prime-boost regimen with soluble vaccines formulated with CpG/Alum or 3M-052/Alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single-immunization hydrogel-based vaccines elicited potent and consistent neutralizing responses. Overall, we show that PNP hydrogels elicit improved anti-COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance our overall pandemic readiness.
The bacterial microbiome of the coral skeleton algal symbiontOstreobiumshows preferential associations and signatures of phylosymbiosis
Authors: Pushpakumara B.L.D. Uthpala , Tandon Kshitij , Willis Anusuya , Verbruggen Heroen
Published: December 2022

Ostreobium, the major algal symbiont of the coral skeleton, remains understudied despite extensive research on the coral holobiont. The enclosed nature of the coral skeleton might reduce the dispersal and exposure of residing bacteria to the outside environment, allowing stronger associations with the algae. Here, we describe the bacterial communities associated with cultured strains of 5Ostreobiumclades using 16S rRNA sequencing. We shed light on their likely physical associations by comparative analysis of three datasets generated to capture (1) all algae associated bacteria (2) enriched tightly attached and potential intracellular bacteria and (3) bacteria in spent media. Our data showed that while some bacteria may be loosely attached, some tend to be tightly attached or potentially intracellular. Although colonised with diverse bacteria,Ostreobiumpreferentially associated with 34 bacterial taxa revealing a core microbiome. These bacteria include taxa known as nitrogen cyclers, polysaccharide degraders, sulphate reducers, antimicrobial compound producers, methylotrophs and vitamin B12 producers. By analysing co-occurrence networks of 16S rRNA datasets fromPorites luteaandParagoniastrea australensisskeleton samples, we show that theOstreobium-bacterial associations present in the cultures are likely to also occur in their natural environment. Finally, our data show significant congruence between theOstreobiumphylogeny and the community composition of its tightly associated microbiome, largely due to the phylosymbiotic signal originating from the core bacterial taxa. This study offers insight into theOstreobiummicrobiome and reveals preferential associations that warrant further testing from functional and evolutionary perspectives.
Biophysical basis of phage liquid crystalline droplet-mediated antibiotic tolerance in pathogenic bacteria
Authors: Böhning Jan , Graham Miles , Letham Suzanne C. , Davis Luke K. , Schulze Ulrike , Stansfeld Phillip J. , Corey Robin A. , Pearce Philip , Tarafder Abul K. , Bharat Tanmay A. M.
Published: December 2022

Inoviruses are abundant filamentous phages infecting numerous prokaryotic phyla, where they can symbiotically promote host fitness and increase bacterial virulence. Due to their unique properties, inoviruses have also been utilised in biotechnology for phage display and as models for studying phase behaviour of colloidal rods. Inoviral phages secreted by bacteria can self-assemble into liquid crystalline droplets that protect bacterial cells in biofilms from antibiotics, however, factors governing the formation of such droplets and the mechanism of antibiotic protection are poorly understood. Here, we investigate the structural, biophysical, and protective properties of liquid crystalline droplets formed byPseudomonas aeruginosaandEscherichia coliinoviral phages. We report a cryo-EM structure of the capsid from the highly studiedE. colifd phage, revealing distinct biochemical properties of fd compared to Pf4 phage fromP. aeruginosa. We show that fd and Pf4 form liquid crystalline droplets with diverse morphologies governed by the underlying phage particle geometry and biophysics, rather than their surface biochemical properties. Finally, we show that these morphologically diverse droplets made of either phage can protect rod-shaped bacteria from antibiotic treatment, despite differing modes of association with cells. This study advances our understanding of phage assembly into liquid crystalline droplets, and provides insights into how filamentous molecules protect bacteria from extraneous molecules under crowding conditions, which are found in biofilms or on infected host tissues.
A universal workflow for creation, validation and generalization of detailed neuronal models
Authors: Reva Maria , Rössert Christian , Arnaudon Alexis , Damart Tanguy , Mandge Darshan , Tuncel Anıl , Ramaswamy Srikanth , Markram Henry , Van Geit Werner
Published: December 2022

Detailed single neuron modeling is widely used to study neuronal functions. While cellular and functional diversity across the mammalian cortex is vast, most of the available computational tools are dedicated to the reproduction of a small set of specific features characteristic of a single neuron. Here, we present a generalized automated workflow for the creation of robust electrical models and illustrate its performance by building cell models for the rat somatosensory cortex (SSCx). Each model is based on a 3D morphological reconstruction and a set of ionic mechanisms specific to the cell type. We use an evolutionary algorithm to optimize passive and active ionic parameters to match the electrophysiological features extracted from whole-cell patch-clamp recordings. To shed light on which parameters are constrained by experimental data and which could be degenerate, we perform a parameter sensitivity analysis. We also validate the optimized models against additional experimental stimuli and assess their generalizability on a population of morphologies with the same morphological type. With this workflow, we generate SSCx neuronal models producing the variability of neuronal responses. Due to its versatility, our workflow can be used to build robust biophysical models of any neuronal type.
Accountability and accounting for fisheries – six decades of reporting by the Electricity Supply Board of Ireland, 1935–1993
Authors: Quinn Martin , Moreno Alonso , Bhatta Bibek
Published: December 2022

Purpose

This study aims to contribute to the relatively limited historic literature on social and environmental accounting/accountability. More specifically, the study explores accounting and accountability for fisheries over time and determines potential legitimacy relations as conveyed through reporting.

Design/methodology/approach

A content analysis method is used to analyse a fisheries-related section of an annual report of a state-owned electricity firm for 56 years (1935/36–1993). The time frame analysed is a period when environmental or social reporting was, in general, informal and not mandated. However, accountability was established for the company under study, through the legally mandated provision of (unspecific/discretional) information about fisheries activities. A lens evoking legitimacy relationships as a dyad is utilised.

Findings

The fisheries reporting within the case organisation is an early example of recognition of the important effects of business activities on the environment and biodiversity. The findings of the analyses suggest the content aligns with what may be anticipated in a contemporary setting. Drawing on trends noted from the content analysis, three potential legitimacy relationships are identified around the fisheries reporting. Only one is determined as a complete legitimacy relationship.

Research limitations/implications

The research is limited in that it is an analysis of one case in a single context. Also, the content analysis methods used were developed specifically for the study, which may limit their application. Finally, the data source used, and the historic nature of the study, to some extent limits the ability to determine some legitimacy relationships.

Originality/value

This study offers some insights on the historic nature of environmental reporting from a fisheries perspective in the Northern Hemisphere. The longitudinal nature of the analysis also offers insights into how the content of the reporting changed over time. Additionally, the use of a relatively new approach to operationalising legitimacy may prove useful for future researchers in the accounting discipline, especially given recent concerns on how the concept of legitimacy has been utilised in such research.
39 Bakers: roadmap to profitability through customer management
Authors: Jha Suchita , Gupta Sunakshi , Kumar Jitender , Rawat Sandeep
Published: December 2022

Learning outcomes

1. To analyze the various business models and choose the best model to contribute maximum profit to the company.2. To understand the importance of customer management with the help of the Net Promoter Score in the food retail context.3. To develop customer loyalty strategies and implement them to improve customer management?

Case overview/synopsis

39 Bakers, a multi-outlet bakery chain in Jammu, India, is run by its founder Gagan. 39 Bakers, through its retail outlets across the Jammu region, offers a variety of products, ranging from bakery items that include blends of Indian and Italian cuisines, offering more than 1000 stock keeping units (SKUs). Through its high-quality offerings at an affordable price range, the brand has carved a niche in the hyper-competitive bakery market of the Jammu region. Gagan, has closely seen the Jammu market and customer preferences and strongly perceived that the customers in the Jammu region are very price sensitive. Thus, he has always been very reluctant to increase the prices of his product offerings at 39 Bakers. He has always believed that any drastic price rise may lead to immediate dissatisfaction and customer churn and therefore has not increased the prices at 39 Bakers for two years in a row. While this decision of Gagan paid off in terms of its popularity and recognition as one of the highly recommended bakery chains among customers, it drastically impacted the bottom line (i.e. profitability) at 39 Bakers, especially in the year 2020–21. Getting popularity at the cost of dipping profitability made Gagan rethink his decision to be protective of price increases at 39 bakers. How can he measure customer satisfaction and loyalty? Which loyalty strategies will work for the huge customer base of Jammu? Should he change his business model from B2C to B2B? How can loyalty be established? How can he manage his existing and loyal customers through price increases?

Complexity academic level

The case study is suitable for undergraduate and postgraduate courses in Marketing Management and Retail Marketing. The case study’s focus can be on the importance of pricing, business model evaluation, customer management analysis, customer loyalty, Customer Loyalty analysis, and net promoters score. The case can also be useful to entrepreneurs and regulators.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship.