bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAbnormal 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 StatementPatients 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

AbstractContemporary 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

AbstractThe 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

AbstractColorectal 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

ABSTRACTTheE. 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

AbstractThe 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 StatementThe 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

AbstractIn 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.
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

PurposeThe 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/approachThis paper is predominantly conceptual but it also draws on available secondary data, such as mortality statistics, media reports and developing research.FindingsThe 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/implicationsThe 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 implicationsIf 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/valueResearch 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

PurposeIntegration, 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/approachThe 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.FindingsOf 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/valueThis 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

PurposeThe 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/approachData 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.FindingsThe 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/implicationsThis 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/valueThe 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.