bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergent effects of contact tracing robustly stabilize outbreaks
Authors: Kotil Seyfullah Enes
Published: March 2021

Covid-19 neither dissolved nor got out of control over a year. In many instances, the new daily cases exhibit an equilibrium at a meagre percentage of the population. Seemingly impossible due to the precise cancellation of positive and negative effects. Here, I propose models on real-world networks that capture the mysterious dynamics. I investigate the contact-tracing and related effects as possible causes. I differentiate the impact of contact-tracing into three—one direct and two emergent—effects: isolation of the documented patient’s direct infectees (descendants), isolation of non-descendant infectees, and temporary isolation of susceptible contacts. Contrary to expectation, isolation of descendants cannot stabilize an equilibrium; based on current data, the effect of the latter two are necessary and greater in effect overall. The reliance on emergent effects shows that even if contact-tracing is 100% efficient, its effect on the epidemic dynamics would be dependent. Moreover, This newly characterized dynamic claims that all outbreaks will eventually show such stable dynamics.
Burden of Post-COVID-19 Syndrome and Implications for Healthcare Service Planning: A Population-based Cohort Study
Authors: Menges Dominik , Ballouz Tala , Anagnostopoulos Alexia , Aschmann Hélène E , Domenghino Anja , Fehr Jan S , Puhan Milo A
Published: March 2021

Background

Longer-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization.

Methods

This population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes.

Results

Symptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care.

Conclusions

In this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.

Registration

ISRCTN14990068
Towards 3D-Bioprinting of an Endocrine Pancreas: A Building-Block Concept for Bioartificial Insulin-Secreting Tissue
Authors: Salg Gabriel Alexander , Poisel Eric , Munoz Matthias Neulinger , Cebulla Daniel , Vieira Vitor , Bludszuweit-Philipp Catrin , Nickel Felix , Herr Ingrid , Giese Nathalia A. , Hackert Thilo , Goetz Kenngott Hannes
Published: March 2021

Background & Aims

3D-Bioprinting of an endocrine pancreas is a promising future curative treatment for selected patients with insulin secretion deficiency. In this study we present an end-to-end integrative, scalable concept extending from the molecular to the macroscopic level.

Methods

A hybrid scaffold device was manufactured by 3D-(bio)printing. INS-1 cells with/without endothelial cells were bioprinted in gelatin methacrylate blend hydrogel. Polycaprolactone was 3D-printed and heparin-functionalized as structural scaffold component. In vitro evaluation was performed by viability and growth assays, total mRNA sequencing, and glucose-stimulated insulin secretion. In vivo, xenotransplantation to fertilized chicken eggs was used to investigate vascularization and function, and finite element analysis modeling served to detect boundary conditions and applicability for human islets of Langerhans.

Results

Insulin-secreting pseudoislets were formed and resulted in a viable and proliferative experimental model. Transcriptomics revealed upregulation of proliferative and β-cell-specific signaling cascades, downregulation of apoptotic pathways, and overexpression of extracellular matrix proteins and VEGF induced by pseudoislet formation and 3D culture. Co-culture with human endothelial cells created a natural cellular niche resulting in enhanced insulin response after glucose stimulation. Survival and function of the pseudoislets after explantation and extensive scaffold vascularization of both the hydrogel and heparinized polycaprolactone components were demonstratedin ovo.Computer simulations of oxygen, glucose, and insulin flows were used to evaluate scaffold architectures and Langerhans islets at a future transplantation site along neurovascular structures.

Conclusion

A defined end-to-end process for multidisciplinary bioconvergence research on a bioartificial endocrine pancreas was developed. A modular, patient-specific device architecture is proposed for future research studies.
Small Directional Treadmill Perturbations Induce Differential Gait Stability Adaptation
Authors: Li Jinfeng , Huang Helen J.
Published: March 2021

Introducing unexpected perturbations to challenge gait stability is an effective approach to investigate balance control strategies. Little is known about the extent to which people can respond to small perturbations during walking. This study aimed to determine how subjects adapted gait stability to multidirectional perturbations with small magnitudes applied on a stride-by-stride basis. Ten healthy young subjects walked on a treadmill that either briefly decelerated belt speed (“stick”), accelerated belt speed (“slip”), or shifted the platform medial-laterally at right leg mid-stance. We quantified gait stability adaptation in both anterior-posterior and medial-lateral directions using margin of stability and its components, base of support and extrapolated center of mass. Gait stability was disrupted upon initially experiencing the small perturbations as margin of stability decreased in the stick, slip, and medial shift perturbations and increased in the lateral shift perturbation. Gait stability metrics were generally disrupted more for perturbations in the coincident direction. Subjects employed both feedback and feedforward strategies in response to the small perturbations, but mostly use feedback strategies during adaptation. Subjects primarily used base of support (foot placement) control in the lateral shift perturbation and extrapolated center of mass control in the slip and medial shift perturbations. These findings provide new knowledge about the extent of gait stability adaptation to small magnitude perturbations applied on a stride-by-stride basis and reveal potential new approaches for balance training interventions to target foot placement and center of mass control.

NEW & NOTEWORTHY

Little is known about if and how humans can adapt to small magnitude perturbations experienced on a stride-by-stride basis during walking. Here, we show that even small perturbations disrupted gait stability and that subjects could still adapt their reactive balance control. Depending on the perturbation direction, subjects might prefer adjusting their foot placement over their center of mass and vice versa. These findings could help potentially tune balance training to target specific aspects of balance.
Identification of Kinases Activated by Multiple Pro-Angiogenic Growth Factors
Authors: Gruver Scott , Rata Scott , Peshkin Leonid , Kirschner Marc W
Published: March 2021

Antiangiogenic therapy began as an effort to inhibit VEGF signaling, which was thought to be the sole factor driving tumor angiogenesis. It has become clear that there are more pro-angiogenic growth factors that can substitute for VEGF during tumor vascularization. This has led to the development of multi-kinase inhibitors which simultaneously target multiple growth factor receptors. These inhibitors perform better than monotherapies yet to date no multi-kinase inhibitor targets all receptors known to be involved in pro-angiogenic signaling and resistance inevitably occurs. Given the large number of pro-angiogenic growth factors identified, it may be impossible to simultaneously target all pro-angiogenic growth factor receptors. Here we search for kinase targets, some which may be intracellularly localized, that are critical in endothelial cell proliferation irrespective of the growth factor used. We develop a quantitative endothelial cell proliferation assay and combine it with “kinome regression” or KIR, a recently developed method capable of identifying kinases that influence a quantitative phenotype. We report the kinases implicated by KIR and provide orthogonal evidence of their importance in endothelial cell proliferation. Our approach may point to a new strategy to develop a more complete anti-angiogenic blockade.
The global carrier frequency and genetic prevalence of Upshaw-Schulman syndrome
Authors: Zhao Ting , Fan Shanghua , Sun Liu
Published: March 2021

Purpose

Upshaw–Schulman syndrome (USS) is an autosomal recessive disease of thrombotic microangiopathy, caused by pathogenic variants in ADAMTS13. We aimed to (1) perform data mining pathogenicity of ADAMTS13 variants, (2) estimate carrier frequency and genetic prevalence of USS from gnomAD data, and (3) curated ADAMTS13 gene pathogenic variants dataset.

Methods

PubMed and Scopus were comprehensive retrieved. All previously reported pathogenic ADAMTS13 variants were compiled and annotated with gnomAD allele frequencies. Pooled global and population-specific carrier frequency and genetic prevalence for USS were calculated using Hardy-Weinberg equation.

Results

we mined reported disease-causing variants, of these were present in gnomAD exomes v2.1.1, filtering by allele frequency, pathogenicity of variants were classified by American College of Medical Genetics and Genomics criteria. The genetic prevalence and carrier frequency of USS was 0.43 per 1 million (95% CI: [0.36, 0.55]) and 1.31 per thousand, respectively. Combining known with novel pathogenic/likely pathogenic variants, the genetic prevalence and carrier frequency are 1.1 per 1 million (95% CI: [0.89, 1.37]) and 2.1 per thousand, respectively.

Conclusion

the genetic prevalence and carrier frequency of Upshaw-Schulman syndrome are within range of previously rough estimated.
Social information used to elicit cache protection differs between pinyon jays and Clark’s nutcrackers
Authors: Vernouillet Alizée , Clary Dawson , Kelly Debbie M.
Published: March 2021

Behavioral plasticity can be described as the ability to adjust behavior depending on environmental information. We used a food-storing (caching) paradigm, during which individuals either ate or cached food under different conditions, to investigate whether they could adjust their caching behavior when observed by conspecifics and heterospecifics, and which cues they used to elicit these behavioral changes. We examined the location and number of caches made by two corvid species differing in sociality, highly social pinyon jays (Gymnorhinus cyanocephalus) and less social Clark’s nutcrackers (Nucifraga columbiana). Although pinyon jays cached a similar amount of food across conditions, they allocated more caches to areas less accessible to the observer. Nutcrackers, however, reduced the number of seeds cached when another nutcracker was present in comparison to when they cached alone. Both species relied on different social cues to elicit re-caching: pinyon jays responded to the amount of time the observer spent close to the caching locations, whereas nutcrackers responded to the amount of time the observer spent pilfering their caches. The differences in cache protection behaviors and the social cues eliciting them may be explained by the species’ social organization. Pinyon jays may only adjust their caching behavior when necessary, as they are often surrounded by other individuals. Clark’s nutcrackers reduce their caching when observed, as they have more opportunities to cache alone, and may resort to additional cache protection when experiencing pilferage. Overall, our results provide insight into understanding how pressures associated with the social environment may influence foraging behaviors.
Delivering on Biden’s 2030 conservation commitment
Authors: Simmons B. Alexander , Nolte Christoph , McGowan Jennifer
Published: March 2021

On January 27, 2021, President Biden signed an executive order,Tackling the Climate Crisis at Home and Abroad, committing the United States to various goals within his campaign’s major climate policy, theBiden Plan for a Clean Energy Revolution and Environmental Justice. Included in this executive order is a commitment to “conserving at least 30 percent of [the United States’] lands and oceans by 2030.” This ambitious conservation target signals a promising direction for biodiversity in the United States. However, while the executive order outlines several goals for climate mitigation, the ‘30×30’ target remains vague in its objectives, actions, and implementation strategies for protecting biodiversity. Biodiversity urgently needs effective conservation action, but it remains unclearwhereandwhatthis 30% target will be applied to. Achieving different climate and biodiversity objectives will require different strategies and, in combination with the associated costs of implementation, will lead to different priority areas for conservation actions. Here, we illustrate what the 30% target could look like across four objectives reflective of the ambitious goals outlined in the executive order. We compile several variations of terrestrial protected area networks guided by these different objectives and examine the trade-offs in costs, ecosystem representation, and climate mitigation potential between each. We find little congruence in priority areas across objectives, emphasizing just how crucial it will be for the Biden administration to develop clear objectives and establish appropriate performance metrics from the outset to maximize both conservation and climate outcomes in support of the 30×30 target. We discuss important considerations that must guide the administration’s conservation strategies in order to ensure meaningful conservation outcomes can be achieved over the next decade.
Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain
Authors: Samanta Jayshree , Silva Hernandez Moura , Lafaille Juan J. , Salzer James L.
Published: March 2021

In the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they generate new oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet which induces widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.
Assessing heterogeneity in spatial data using the HTA index with applications to spatial transcriptomics and imaging
Authors: Levy-Jurgenson Alona , Tekpli Xavier , Yakhini Zohar
Published: March 2021

Motivation

Tumour heterogeneity is being increasingly recognised as an important characteristic of cancer and as a determinant of prognosis and treatment outcome. Emerging spatial transcriptomics data hold the potential to further our understanding of tumour heterogeneity and its implications. However, existing statistical tools are not sufficiently powerful to capture heterogeneity in the complex setting of spatial molecular biology.

Results

We provide a statistical solution, the HeTerogeneity Average index (HTA), specifically designed to handle the multivariate nature of spatial transcriptomics. We prove that HTA has an approximately normal distribution, therefore lending itself to efficient statistical assessment and inference. We first demonstrate that HTA accurately reflects the level of heterogeneity in simulated data. We then use HTA to analyse heterogeneity in two cancer spatial transcriptomics datasets: spatial RNA sequencing by 10x Genomics and spatial transcriptomics inferred from H&E. Finally, we demonstrate that HTA also applies to 3D spatial data using brain MRI. In spatial RNA sequencing we use a known combination of molecular traits to assert that HTA aligns with the expected outcome for this combination. We also show that HTA captures immune-cell infiltration at multiple resolutions. In digital pathology we show how HTA can be used in survival analysis and demonstrate that high levels of heterogeneity may be linked to poor survival. In brain MRI we show that HTA differentiates between normal ageing, Alzheimer’s disease and two tumours. HTA also extends beyond molecular biology and medical imaging, and can be applied to many domains, including GIS.

Availability

.

Contact

levyalona@gmail.comzohar.yakhini@gmail.com

Supplementary information

Supplementary data are available atBioinformaticsonline.
Poly(rC)-binding protein 1 limits hepatitis C virus virion assembly and secretion
Authors: Cousineau Sophie E. , Rheault Marylin , Sagan Selena M.
Published: March 2021

The hepatitis C virus (HCV) co-opts numerous cellular elements – including proteins, lipids, and microRNAs – to complete its viral life cycle. The cellular RNA-binding protein, poly(rC)-binding protein 1 (PCBP1), was previously reported to bind to the 5’ untranslated region (UTR) of the HCV genome; however, its importance in the viral life cycle has remained unclear. Herein, we sought to clarify the role of PCBP1 in the HCV life cycle. Using the HCV cell culture (HCVcc) system, we found that knockdown of endogenous PCBP1 resulted in an overall decrease in viral RNA accumulation, yet resulted in an increase in extracellular viral titers. To dissect PCBP1’s specific role in the HCV life cycle, we carried out assays for viral entry, translation, genome stability, RNA replication, as well as virion assembly and secretion. We found that PCBP1 knockdown did not directly affect viral entry, translation, RNA stability, or RNA replication, but resulted in an overall increase in infectious particle secretion. This increase in virion secretion was evident even when viral RNA synthesis was inhibited, and blocking virus secretion could partially restore the viral RNA accumulation decreased by PCBP1 knockdown. We therefore propose a model where endogenous PCBP1 normally limits virion assembly and secretion, which increases viral RNA accumulation in infected cells by preventing the departure of viral genomes packaged into virions. Overall, our findings improve our understanding of how cellular RNA-binding proteins influence viral genomic RNA utilization during the HCV life cycle.
Somatosensory processing deficits and altered cortico-hippocampal connectivity inShank3b−/−mice
Authors: Balasco Luigi , Pagani Marco , Pangrazzi Luca , Schlosman Evgenia , Mattioni Lorenzo , Galbusera Alberto , Provenzano Giovanni , Gozzi Alessandro , Bozzi Yuri
Published: March 2021

Abnormal tactile response is considered an integral feature of Autism Spectrum Disorders (ASDs), and hypo-responsiveness to tactile stimuli is often associated with the severity of ASDs core symptoms. Patients with Phelan-McDermid syndrome (PMS), caused by mutations in the SHANK3 gene, show ASD-like symptoms associated with aberrant tactile responses. However, the neural underpinnings of these somatosensory abnormalities are still poorly understood. Here we investigated, inShank3b−/−adult mice, the neural substrates of whisker-guided behaviors, a key component of rodents’ interaction with the surrounding environment. To this aim, we assessed whisker-dependent behaviors inShank3b−/−adult mice and age-matched controls, using the textured novel object recognition (tNORT) and whisker nuisance (WN) test.Shank3b−/−mice showed deficits in whisker-dependent texture discrimination in tNORT and behavioral hypo-responsiveness to repetitive whisker stimulation in WN. Notably, sensory hypo-responsiveness was accompanied by a significantly reduced activation of the primary somatosensory cortex (S1) and hippocampus, as measured by c-fosmRNAin situhybridization, a proxy of neuronal activity following whisker stimulation. Moreover, resting-state fMRI showed a significantly reduced S1-hippocampal connectivity inShank3bmutant mice. Together, these findings suggest that impaired crosstalk between hippocampus and S1 might underlieShank3b−/−hypo-reactivity to whisker-dependent cues, highlighting a potentially generalizable form of dysfunctional somatosensory processing in ASD.

Significance Statement

Patients with Phelan-McDermid syndrome, a syndromic form of ASD caused by mutation of the SHANK3 gene, often show aberrant responses to touch. However, the neural basis of atypical sensory responses in ASD remains undetermined. Here we usedShank3deficient mice to investigate the neural substrates of behavioral responses to repetitive stimulation of the whiskers, a highly developed sensory organ in mice. We found that mice lacking theShank3gene are hypo-responsive to repetitive whisker stimulation. This trait was associated with reduced engagement and connectivity between the primary somatosensory cortex and hippocampus. These results suggest that dysfunctional cortico-hippocampal coupling may underlie somatosensory processing deficits in SHANK3 mutation carriers and related syndromic forms of ASD.
The LOTUS Initiative for Open Natural Products Research: Knowledge Management through Wikidata
Authors: Rutz Adriano , Sorokina Maria , Galgonek Jakub , Mietchen Daniel , Willighagen Egon , Gaudry Arnaud , Graham James G. , Stephan Ralf , Page Roderic , Vondrášek Jiří , Steinbeck Christoph , Pauli Guido F. , Wolfender Jean-Luc , Bisson Jonathan , Allard Pierre-Marie
Published: March 2021

Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges for data access, both within the discipline and for integration and interoperability between related fields. The fundamental elements of exchange are referenced structure-organism pairs that establish relationships between distinct molecular structures and the living organisms from which they were identified. Consolidating and sharing such informationviaan open platform has strong transformative potential for natural products research and beyond. This is the ultimate goal of the newly established LOTUS initiative, which has now completed the first steps toward the harmonization, curation, validation and open dissemination of 750,000+ referenced structure-organism pairs. LOTUS data is hosted on Wikidata and regularly mirrored onhttps://lotus.naturalproducts.net. Data sharing within the Wikidata framework broadens data access and interoperability, opening new possibilities for community curation and evolving publication models. Furthermore, embedding LOTUS data into the vast Wikidata knowledge graph will facilitate new biological and chemical insights. The LOTUS initiative represents an important advancement in the design and deployment of a comprehensive and collaborative natural products knowledge base.
The status of current and tentative marine natural World Heritage areas
Authors: Kuempel Caitlin D. , Simmons B. Alexander , Davey Madeline
Published: March 2021

The 1972 World Heritage Convention (WHC), along with the 1994 Global Strategy, aim to preserve the outstanding universal value of internationally important cultural and natural sites within a “representative, balanced and credible” network of highly-protected areas. Increasing human pressures and shortfalls in representation have been documented across the World Heritage network, particularly in terrestrial and cultural sites, threatening the integrity and primary goals of the WHC. However, the conservation status of current and tentative (i.e., proposed) marine natural World Heritage areas remains relatively unknown. We assessed the extent of recent (2013) and historical (2008-2013) cumulative human impacts and several metrics of representation (country, continent, ecoregion, wilderness, and threatened species) within existing and tentative marine natural World Heritage areas. We found moderate yet increasing cumulative human impacts across most existing sites, and high or very high impacts across the majority of tentative sites. Climate change impacts comprised nearly 75% of impact scores, on average, and differences in land and marine impacts across sites could help prioritise management decisions. Over 75% of marine ecoregions and 85% of threatened species considered in this study have no representation within the existing marine natural World Heritage network. We outline examples of how prioritizing representation across tentative sites for future World Heritage listing could greatly increase these measures. We urge the WHC to adopt quantitative, systematic and transparent evaluations of how current and tentative sites contribute to the overarching goals of maintaining a representative World Heritage network and preserving their outstanding universal values for future generations.
Dual Drug Targeting to Kill Colon Cancer Cells
Authors: Corona Silvia Paola , Walker Francesca , Weinstock Janet , Lessene Guillaume , Faux Maree , Burgess Antony W
Published: March 2021

Colorectal cancer (CRC) is driven by a small set of oncogenic and tumor suppressor mutations. However, different combinations of mutations often lead to poor tumor responses to individual anti-cancer drugs. We have investigated the anti-proliferative andin vitrocytotoxic activity of pair-wise combinations of inhibitors which target specific signalling pathways. Colon cancer cells in non-adherent cultures were killed more effectively by combinations of pyrvinium pamoate (a Wnt pathway inhibitor) and ABT263 (a pro-apoptotic Bcl-2 family inhibitor) or Ly29004 (a PI3kinase inhibitor). However, in a mouse xenograft model, the formulation and toxicity of the ABT737/PP combination prevent the use of these drugs for treatment of tumors. Fortunately, oral analogues of PP (pyrvinium phosphate, PPh) and ABT737(ABT263) have equivalent activity and can be used for treatment of mice carrying SW620 colorectal cancer xenografts. The PPh/ABT263 induced SW620 tumor cell apoptosis and reduced the rate of SW620 tumor growth. Combinations of Wnt signaling inhibitors and specific inhibitor of pro-survival proteins should be considered for the treatment of precancerous colon adenomas and advanced colorectal cancers with APC mutations.
Dynamic Consequences of Specificity within the Cytidine Repressor DNA-Binding Domain
Authors: Moody Colleen L. , Soto Jenaro , Tretyachenko-Ladokhina Vira , Senear Donald F. , Cocco Melanie J.
Published: March 2021

TheE. colicytidine repressor (CytR) is a member of the LacR family of bacterial repressors that regulates nine operons with distinct spacing and orientations of recognition sites. Understanding the structural features of the CytR DNA-binding domain (DBD) when bound to DNA is critical to understanding differential mechanisms of gene regulation. We previously reported the structure of the CytR DBD monomer bound specifically to half-site DNA and found that the DBD exists as a three-helix bundle containing a canonical helix-turn-helix motif, similar to other proteins that interact with DNA [Moody, et al (2011), Biochemistry50:6622-32]. We also studied the free state of the monomer and found that since NMR spectra show it populates up to four distinct conformations, the free state exists as an intrinsically disordered protein (IDP). Here, we present further analysis of the DBD structure and dynamics in the context of full-site operator or nonspecific DNA. DBDs bound to full-site DNA show one set of NMR signals, consistent with fast exchange between the two binding sites. When bound to full-length DNA, we observed only slight changes in structure compared to the monomer structure and no folding of the hinge helix. Notably, the CytR DBD behaves quite differently when bound to nonspecific DNA compared to LacR. A dearth of NOEs and complete lack of protection from hydrogen exchange are consistent with the protein populating a flexible, molten state when associated with DNA nonspecifically, similar to fuzzy complexes. The CytR DBD structure is significantly more stable when bound specifically to theudphalf-site substrate. For CytR, the transition from nonspecific association to specific recognition results in substantial changes in protein mobility that are coupled to structural rearrangements. These effects are more pronounced in the CytR DBD compared to other LacR family members.
Direct cochlear recordings in humans show a theta rhythmic modulation of the auditory nerve by selective attention
Authors: Gehmacher Quirin , Reisinger Patrick , Hartmann Thomas , Keintzel Thomas , Rösch Sebastian , Schwarz Konrad , Weisz Nathan
Published: March 2021

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow-up analysis showed that the effect was not driven by a narrow frequency in particular. Using direct cochlear recordings from deaf individuals, our findings suggest that cochlear spiral ganglion cells are sensitive to top-down attentional modulations. Given the putatively broad hair-cell degeneration of these individuals, the effects are likely mediated by alternative efferent pathways as compared to previous studies using otoacoustic emissions. Successful classification of single-trial data could additionally have a significant impact on future closed-loop CI developments that incorporate real-time optimization of CI parameters based on the current mental state of the user.

Significance Statement

The efferent auditory system in principle allows top-down modulation of auditory nerve activity, however evidence for this is lacking in humans. Using cochlear recordings in participants performing an audiovisual attention task, we show that ongoing auditory nerve activity in the silent cue-target period is directly modulated by selective attention. Specifically, ongoing auditory nerve activity is enhanced within the theta range when attending upcoming auditory input. Furthermore, over a broader frequency range, the attended modality can be decoded from single-trial data. Demonstrating this direct top-down influence on auditory nerve activity substantially extends previous works that focus on outer hair cell activity. Generally, our work could promote the use of standard cochlear implant electrodes to study cognitive neuroscientific questions.
Avalanches During Epithelial Tissue Growth; Uniform Growth and a Drosophila Eye Disc Model
Authors: Courcoubetis George , Xu Chi , Nuzhdin Sergey , Haas Stephan
Published: March 2021

In the physicists’ perspective, epithelial tissues constitute an exotic type of active matter with non-linear properties reminiscent of amorphous materials. In the context of a circular proliferating epithelium, modeled by the quasistatic vertex model, we identify novel discrete tissue scale rearrangements, i.e. cellular flow avalanches, which are a form of collective cell movement. During the avalanches, the cellular trajectories are radial in the periphery and form a vortex in the core. After the onset of these avalanches, the epithelial area grows discontinuously. The avalanches are found to be stochastic, and their strength is determined by the density of cells in the tissue. Overall, avalanches regularize the spatial tension distribution along tissue. Furthermore, the avalanche distribution is found to obey a power law, with an exponent consistent with sheer induced avalanches in amorphous materials. To decipher the role of avalanches in organ development, we simulate epithelial growth of theDrosophilaeye disc during the third instar using a computational model, which includes both signaling and mechanistic signalling. During the third instar, the morphogenetic furrow (MF), a ∼10 cell wide wave of apical area constriction propagates through the epithelium, making it a system with interesting mechanical properties. These simulations are used to understand the details of the growth process, the effect of the MF on the growth dynamics on the tissue scale, and to make predictions. The avalanches are found to depend on the strength of the apical constriction of cells in the MF, with stronger apical constriction leading to less frequent and more pronounced avalanches. The results herein highlight the dependence of simulated tissue growth dynamics on relaxation timescales, and serve as a guide forin vitroexperiments.
Etmopteruslantern sharks use coelenterazine as the substrate for their luciferin-luciferase bioluminescence system
Authors: Mizuno Gaku , Yano Daichi , Paitio José , Endo Hiromitsu , Oba Yuichi
Published: March 2021

The lantern shark genusEtmopterusis a group of deep-sea bioluminescent fishes. They emit blue light mainly from the ventral body surface, and the primary biological function is considered to be for camouflage by counterillumination. In this study, we detected both coelenterazine and coelenterazine-specific luciferase activity in the ventral photophore tissues. The results suggested that bioluminescence in lantern sharks is produced using coelenterazine as the substrate for the luciferin-luciferase reaction.
Biotronik: bypassing the commodity trap of medical devices in South African healthcare
Authors: Barden Stephanie , Bick Geoff
Published: March 2021

Learning outcomes

The learning outcomes of this paper is as follows: to analyse the drivers, mediators and threats of commoditisation. To critically evaluate the merits of different marketing options that may be employed to avoid commoditisation. To critically assess the branding-focussed or customer-focussed strategies that could be used. To develop appropriate strategies for Biotronik SA to counter commoditisation in the future.

Case overview/synopsis

The case begins with the protagonist and managing director of Biotronik SA, Robbie Nel, brewing over a new industry development. One of the leading private hospital groups has sent an open invitation to medical device suppliers to tender, where the lowest-priced products will win shelf space in their cathlabs. Robbie has to decide whether to sacrifice Biotronik SA’s profit margins to win the tender or risk not being stocked in their cathlabs. Or, he must find an alternative non-price-based strategy to pursue. The medical device industry is facing increasing price pressures from various stakeholders in the device-purchasing process. The decision to purchase is no longer the responsibility of specialist physicians alone. International and local market trends indicate that the medical device industry is threatened by commoditisation. Robbie has to make a decision on changing the Biotronik SA business model and strategy in response to these macro trends.

Complexity academic level

This teaching case is aimed at postgraduate students, particularly those pursuing MBA, EMBA and Postgraduate Diploma programmes, as well as specialist masters and executive education. The students should have some work experience to comprehend and assess the case from a practical perspective.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 8: Marketing.
Structural discrimination and abuse: COVID-19 and people in care homes in England and Wales
Authors: Parker Jonathan
Published: March 2021

Purpose

The purpose of this paper is to explore the significant and high death toll of COVID-19 on care home residents and social care staff in England and Wales. These mortality figures, alongside differential treatment of residents and staff during the pandemic, are conceptualized as a form of structural abuse. Arguments are made for the inclusion of structural abuse as a separate category of elder abuse.

Design/methodology/approach

This paper is predominantly conceptual but it also draws on available secondary data, such as mortality statistics, media reports and developing research.

Findings

The lack of appropriate personal protective equipment, paucity of guidance and high mortality rate among care home staff and residents during the pandemic is indicative of social discourses that, when underpinned by ageism, reflect structural elder abuse.

Research limitations/implications

The research is limited by its focus on a specific time period and its recency. It is also limited in not being based on primary empirical research but it remains exploratory and conceptual and provides a base for ongoing research in this area.

Social implications

If structural elder abuse was to be included in classifications, it demands a rethink of social and health-care services and the policies and practices associated with them and reinforces the government message that safeguarding is everyone’s business.

Originality/value

Research concerning the effects and impact of COVID-19 are still in their early stages. However, the central element of originality in the paper concerns the linking of practices, policies and underlying social assumptions and structural, or societally ingrained, elder abuse.
Explaining integration and differentiation by identifying the rules and coordination mechanisms in a hospital's logistical system
Authors: van der Ham Annelies , van Raak Arno , Ruwaard Dirk , van Merode Frits
Published: March 2021

Purpose

Integration, that is, the coordination and alignment of tasks, is widely promoted as a means to improve hospital performance. A previous study examined integration and differentiation, that is, the extent to which tasks are segmented into subsystems, in a hospital's social network. The current study carries this research further, aiming to explain integration and differentiation by studying the rules and coordination mechanisms that agents in a hospital network use.

Design/methodology/approach

The current case study deepens the analysis of the social network in a hospital. All planning tasks and tasks for surgery performance were studied, using a naturalistic inquiry approach and a mixed method.

Findings

Of the 314 rules found, 85% predominantly exist in people's minds, 31% are in documents and 7% are in the information system. In the early planning stages for a surgery procedure, mutual adjustment based on hospital-wide rules is dominant. Closer to the day of surgery, local rules are used and open loops are closed through mutual adjustment, thus achieving integration. On the day of surgery, there is mainly standardization of work and output, based on hospital-wide rules. The authors propose topics for future research, focusing on increasing the hospital's robustness and stability.

Originality/value

This exploratory case study provides an overview of the rules and coordination mechanisms that are used for organizing hospital-wide logistics for surgery patients. The findings are important for future research on how integration and differentiation are effectively achieved in hospitals.
Factors influencing eco-friendly apparel purchase behavior of Bangladeshi young consumers: case study
Authors: Sobuj Md. , Khan Adnan Maroof , Habib Md. Ahashan , Islam Md. Mazedul
Published: March 2021

Purpose

The purpose of this study is to investigate the factors that influence eco-friendly apparel purchase behaviors concerning Bangladeshi young consumers in light of the theory of planned behavior.

Design/methodology/approach

Data were collected by a survey among 198 respondents in Bangladesh in terms of consumer attitude, subjective norm (SN), perceived behavioral control (PBC), environmental concern (EC), environmental knowledge (EK) and purchase intention (PI). Structural equation modeling approach was used to find out the influencing factors.

Findings

The study reveals that purchase intention is significantly influenced by attitudes, SN, EC and EK of consumers. Consumers perceived behaviors variable is always not an accurate predictor to control actual purchase behavior. SN and EK were found to be highly influential to eco-friendly apparel purchase patterns among young consumers in Bangladesh.

Research limitations/implications

This study provides key marketing insights for retailers and practitioners on how strategically they can decide for fashion consumers, specifically the young group in Bangladesh. Eco-friendly apparel purchase behaviors will gradually influence the retail business contexts for retailers. The study reveals the need for eco-labeling and marketing strategies of eco-friendly apparel products among young consumers to communicate benefits and green values among wider consumers. Findings were restricted to specific young consumers group in Bangladesh and did not examine purchase behaviors of other consumer segment.

Originality/value

The study reveals that Bangladeshi young consumers are becoming concerned about purchasing apparel products. It provides valuable insights for entrepreneurs, practitioners and marketers to trace and perceive purchase behavior of the Bangladeshi young consumers while adopting a strategic marketing approach.
The efficacy of manual soft‐tissue mobilization in ankylosing spondylitis: A randomized controlled study
Authors: Gur Kabul Elif , Basakci Calik Bilge , Oztop Mucahit , Cobankara Veli
Published: March 2021

Aim

The aim of this randomized controlled study was to investigate the effect of soft‐tissue mobilization in patients with ankylosing spondylitis (AS).

Method

Twenty‐one patients (mean age 44.57 ± 10.40 years) were randomly divided into two groups. There were 13 patients (11 females, 2 males, age 43.69 ± 9.94 years) in the intervention group and 8 patients (5 females, 3 males, age 46.00 ± 11.67 years) in the control group. In the intervention group, soft‐tissue mobilization therapy and 20 spinal mobility exercises were applied. The control group received only 20 spinal mobility exercises. The Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI) were used for assessment of disease activity, functional level, and mobility, respectively. Nottingham Health Profile (NHP) for quality of life and Roland Morris Disability Questionnaire (RMDQ) were used to determine disability levels.

Results

We found significant differences between pretreatment and post‐treatment scores of BASDAI (P = 0.049); BASFI (P = 0.009; lateral lumbar flexion (P = 0.005), maximal intermalleolar distance (P = 0.001) and total score (P = 0.001) of BASMI; pain subtest (P = 0.036) and total score (P = 0.036) of NHP; and RMDQ score (P = 0.004) in the intervention group. However, in the control group the BASMI score (P = 0.049) was observed to worsen significantly. Delta values were compared and differences in BASFI (P = 0.039), and in lateral lumbar flexion (P = 0.027), maximal intermalleolar distance (P = 0.045) and total score (P = 0.001) of BASMI were significant in favor of intervention group. Only tragus‐to‐wall distance (P = 0.039) of BASMI was observed to worsen significantly in the control group.

Conclusion

We recommend the use of soft‐tissue mobilization in addition to the exercises to treat AS patients.
Low‐frequency ultrasound combined with microbubbles improves gene transfection in prostate cancer cells in vitro and in vivo
Authors: Zhang Wei , Nan Shu‐liang , Bai Wen‐kun , Hu Bing
Published: March 2021

Objectives

The aim of this study is to explore whether low‐frequency ultrasound combined with microbubbles improves pEGFP genes transfection into human prostate cancer cells.

Methods

Ultrasound with frequency of 80 kHz and duty cycle of 50% was adopted in the study; in in vitro experiments, cell lysis, and membrane damage were evaluated after ultrasound exposure; and the membrane continuity and transfection efficiency were observed by transmission electron microscope and laser scanner, respectively. Human prostate cancer xenograft models were exposed to ultrasound and transfection efficiency and histological examination were analyzed.

Results

Compared with the control group, ultrasound combined with microbubbles significantly improves gene transfection efficiency (P < .05). In in vitro study, ultrasound combined with microbubbles resulted in cell lysis and the interruption of cell membrane continuity, and its average transfection efficiency was 9.9%; the green fluorescence intensity was 15.2% in the ultrasound combined with microbubbles group in vivo; both values were higher than that in the control group (P < .05).

Conclusion

Low‐frequency ultrasound combined with microbubbles could be used as a method to promote gene transfection in prostate cancer cells.