bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised characterization of dynamic functional connectivity reveals age-associated differences in temporal stability and connectivity states during rest and task
Authors: Sastry Nisha Chetana , Roy Dipanjan , Banerjee Arpan 
Published: July 2021

AbstractUnderstanding brain functions as an outcome of underlying neuro-cognitive network mechanisms in rest and task requires accurate spatiotemporal characterization of the relevant functional brain networks. Recent endeavours of the Neuroimaging community to develop the notion of dynamic functional connectivity is a step in this direction. A key goal is to detect what are the important events in time that delimits how one functional brain network defined by known patterns of correlated brain activity transitions into a “new” network. Such characterization can also lead to more accurate conceptual realization of brain states, thereby, defined in terms of time-resolved correlations. Nonetheless, identifying the canonical temporal window over which dynamic functional connectivity is operational is currently based on an ad-hoc selection of sliding windows that can certainly lead to spurious results. Here, we introduce a data-driven unsupervised approach to characterize the high dimensional dynamic functional connectivity into dynamics of lower dimensional patterns. The whole-brain dynamic functional connectivity states bearing functional significance for task or rest can be explored through the temporal correlations, both short and long range. The present study investigates the stability of such short- and long-range temporal correlations to explore the dynamic network mechanisms across resting state, movie viewing and sensorimotor action tasks requiring varied degrees of attention. As an outcome of applying our methods to the fMRI data of a healthy ageing cohort we could quantify whole-brain temporal dynamics which indicates naturalistic movie watching task is closer to resting state than the sensorimotor task. Our analysis also revealed an overall trend of highest short range temporal network stability in the sensorimotor task, followed by naturalistic movie watching task and resting state that remains similar in both young and old adults. However, the stability of neurocognitive networks in the resting state in young adults is higher than their older counterparts. Thus, healthy ageing related differences in quantification of network stability along task and rest provides a blueprint of how our approach can be used for cohort studies of mental health and neurological disorders.
A Mouse Model of Brittle Cornea Syndrome caused by mutation in Zfp469
Authors: Stanton Chloe M. , Findlay Amy S. , Drake Camilla , Mustafa Mohammad Z. , Gautier Philippe , McKie Lisa , Jackson Ian J. , Vitart Veronique 
Published: July 2021

AbstractBrittle Cornea Syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ZNF469 or PRDM5. In order to determine the function of ZNF469 and to elucidate pathogenic mechanisms, we used genome editing to recapitulate a human ZNF469 BCS mutation in the orthologous mouse gene, Zfp469. Ophthalmic phenotyping showed that homozygous Zfp469 mutation causes significant central and peripheral corneal thinning arising from reduced stromal thickness. Expression of key components of the corneal stroma in primary keratocytes from Zfp469BCS/BCS mice is affected, including decreased Col1a1 and Col1a2 expression. This alters the type I:type V collagen ratio and results in collagen fibrils with smaller diameter and increased fibril density in homozygous mutant corneas, correlating with decreased biomechanical strength in the cornea. Cell-derived matrices generated by primary keratocytes show reduced deposition of type I collagen offering an in vitro model for stromal dysfunction. Work remains to determine whether modulating ZNF469 activity will have therapeutic benefit in BCS or in conditions such as keratoconus where the cornea thins progressively.Summary statementA mouse model of Brittle Cornea Syndrome was created to elucidate molecular mechanisms underlying pathology of this rare connective tissue disorder in which extremely thin corneas rupture, causing irreversible blindness.
Transcranial photoacoustic characterization of neurovascular physiology during early-stage photothrombotic stroke in neonatal piglets in vivo
Authors: Kang Jeeun , Liu Xiuyun , Cao Suyi , Zeiler Steven R. , Graham Ernest M. , Boctor Emad M. , Koehler Raymond C. 
Published: July 2021

AbstractPerinatal ischemic stroke is estimated to occur in 1/2300–1/5000 live births, but early differential diagnosis from global hypoxia-ischemia is often difficult. In this study, we tested the ability of a hand-held transcranial photoacoustic (PA) imaging to non-invasively detect a focal photothrombotic stroke (PTS) within 2 hours of stroke onset in a gyrencephalic piglet brain. 17 stroke lesions of approximately 1-cm2 area were introduced randomly in anterior or posterior cortex via the light/dye PTS technique in anesthetized neonatal piglets (n = 11). The contralateral non-ischemic region served as control tissue for discrimination contrast for the PA hemoglobin metrics: HbO2 saturation, total hemoglobin (tHb), and individual quantities of oxygenated and deoxygenated hemoglobin (HbO2 and HbR). The PA-derived tissue HbO2 saturation at 2 hours yielded a significant separation between control and affected regions-of-interest (p < 0.0001), which were well matched with 24-hr post-stroke cerebral infarction confirmed in the triphenyltetrazolium chloride (TTC)-stained image. The quantity of HbO2 also displayed a significant contrast (p = 0.021), whereas tHb and HbR did not. The analysis on receiver operating characteristic curves and multivariate data analysis also agreed with the results above. This study shows that a hand-held transcranial PA neuroimaging can detect a regional thrombotic stroke in cerebral cortex of a neonatal piglet. In particular, we conclude that the HbO2 saturation metric can be used alone to identify regional stroke lesions. The lack of change in tHb may be related to arbitrary hand-held imaging configuration and/or entrapment of red blood cells within the thrombotic stroke.
Non-invasive imaging of gene expression and protein secretion dynamics in living mice: identification of ectopic prothrombin expression as driver of thrombosis in cancer
Authors: Nourse Jamie , Tokalov Sergey , Khokhar Shazad , Khan Essak , Schott Lina K. , Hinz Lisa , Eder Ludwig , Arnold-Schild Danielle , Satrapa Johanna , Lackner Karl J. , Cate Hugo Ten , Probst Hans Christian , Danckwardt Sven 
Published: July 2021

AbstractThe topology of gene expression and protein localization is a crucial characteristic of life, where the spatiotemporal dynamic of secretory proteins instruct higher order organization, including the orchestration of developmental and adaptive programs. However tools to non-invasively interrogate the fate of secretory proteins in vivo are scarce. Here we introduce a genetic tagging strategy for in vivo imaging of the secretion and expression dynamics of secretory proteins in living animals. Applying this to a prototypical liver-derived secretory protein, we demonstrate that this approach, combined with optical in-vivo imaging, uncovers extrahepatic prothrombin expression in multiple novel anatomical sites (including testes, placenta, brain, kidney, heart and lymphatic system) and in emerging tumors, resulting in significant amounts of tumor-derived prothrombin in the blood with procoagulant properties. Syngeneic cell lines from this mouse model enable unravelling regulatory mechanisms in high resolution, and in a scalable format ex vivo. Beyond discovering new functions of proteins in a targeted manner, this model allows identifying rheostats in the cross-talk between gene expression and availability of a secretory protein. It is also a valuable resource for uncovering novel (tissue-specific) therapeutic vulnerabilities.
Pyroptosis-dependent and -independent cross-priming of CD8+ T cells by intestinal epithelial cell-derived antigen
Authors: Deets Katherine A. , Nichols Randilea D. , Rauch Isabella , Vance Russell E. 
Published: July 2021

AbstractThe innate immune system detects pathogens and initiates adaptive immune responses. Inflammasomes are central components of the innate immune system, but whether inflammasomes provide sufficient signals to activate adaptive immunity is unclear. In intestinal epithelial cells (IECs), inflammasomes activate a lytic form of cell death called pyroptosis, leading to epithelial cell expulsion and the release of cytokines. Here we employed a genetic system to show that simultaneous antigen expression and inflammasome activation specifically in IECs is sufficient to activate CD8+ T cells. By genetic elimination of direct T cell priming by IECs, we found that IEC-derived antigens are cross-presented to CD8+ T cells. However, activation of CD8+ T cells by IEC-derived antigen only partially depended on IEC pyroptosis. In the absence of inflammasome activation, cross-priming of CD8+ T cells required Batf3+ dendritic cells (cDC1), whereas cross-priming in the presence of pyroptosis did not. These data suggest the existence of parallel pyroptosis-dependent and pyroptosis-independent but cDC1-dependent pathways for cross-presentation of IEC-derived antigens.
MLKL D144K mutation activates the necroptotic activity of the N-terminal MLKL domain
Authors: Hrovat-Schaale Katja , Kalič-Prolinšek Maruša , Hadži San , Lah Jurij , Gunčar Gregor 
Published: July 2021

AbstractMixed-lineage kinase domain-like protein (MLKL) is an essential effector protein of necroptotic cell death. The four-helix bundle domain (4HB) presented by the first 125 amino acids of the N-terminal domain is sufficient for its necroptotic activity. However, it has been proposed that the subsequent helix H6 of the brace region has a regulatory effect on its necroptotic activity. How the brace region restrains the necroptotic activity of the N-terminal domain of MLKL is currently unknown. Here, we demonstrate the importance of helix H6 to constrain the necroptotic activity. A single amino acid mutation D144K was able to activate the necroptotic activity of the N-terminal domain of MLKL by removing helix H6 away from 4HB domain. This enabled protein’s oligomerization and membrane translocation. Moreover, a biophysical comparison revealed that helix H6 becomes partially unstructured due to D144K mutation, leading to a lower overall thermodynamic stability of the mutant protein compared to the wild type.
Legionella pneumophila targets autophagosomes and promotes host autophagy during late infection
Authors: Noll Rebecca R. , Pike Colleen M. , Lehman Stephanie S. , Williamson Chad D. , Neunuebel M. Ramona 
Published: July 2021

AbstractAutophagy is a fundamental eukaryotic process that mediates clearance of unwanted molecules and facilitates nutrient release. The bacterial pathogen Legionella pneumophila establishes an intracellular niche within phagocytes by manipulating host cellular processes, such as autophagy. Effector proteins translocated by L. pneumophila’s Dot/Icm type IV secretion system have been shown to suppress autophagy. However evidence suggests that overall inhibition of autophagy may be detrimental to the bacterium. As autophagy contributes to cellular homeostasis and nutrient acquisition, L. pneumophila may translocate effectors that promote autophagy for these benefits. Here, we show that effector protein Lpg2411 binds phosphatidylinositol-3-phosphate lipids and preferentially binds autophagosomes. Translocated Lpg2411 accumulates late during infection and co-localizes with the autophagy receptor p62 and ubiquitin. Furthermore, autophagy is inhibited to a greater extent in host cells infected with a mutant strain lacking Lpg2411 compared to those infected with wild-type L. pneumophila, indicating that Lpg2411 stimulates autophagy to support the bacterium’s intracellular lifestyle.SummaryLegionella pneumophila translocates several effector proteins that inhibit autophagic processes. In this study, we find that the effector protein Lpg2411 targets autophagosomes during late stages of infection and promotes autophagy.
The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics
Authors: Kollewe Astrid , Chubanov Vladimir , Tseung Fong Tsuen , Haupt Alexander , Müller Catrin Swantje , Bildl Wolfgang , Schulte Uwe , Nicke Annette , Fakler Bernd , Gudermann Thomas 
Published: July 2021

AbstractThe transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of ion channel and protein kinase domains. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn2+, Mg2+ and Ca2+, and thus shapes cellular excitability, plasticity and metabolic activity. The molecular appearance and operation of TRPM7 channel complexes in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative MS analysis. We found that native TRPM7 channels are high molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ARL15. Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that ARL15 effectively and specifically impacts TRPM7 channel activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels.Impact StatementHigh-resolution proteomics in conjunction with biochemical and electrophysiological experiments revealed that the channel-kinase TRPM7 in the rodent brain forms macromolecular complexes containing the metal transporters CNNM1-4 and a small G protein ARL15.
Functional diversity increases the efficacy of phage combinations
Authors: Wright Rosanna C. T. , Friman Ville-Petri , Smith Margaret C. M. , Brockhurst Michael A. 
Published: July 2021

AbstractPhage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from 1 to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximised at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.
Whistleblowing and accounting for the public interest: a call for new directions
Authors: Quayle Annette 
Published: July 2021

PurposeThis paper aims to generate new research directions at the intersection of accounting, whistleblowing and publicness: defined as the attainment of public goals, interests and values.Design/methodology/approachA problematising review is used to challenge and rethink the existing accounting and whistleblowing literature by incorporating readings from the public interest and public value literature. The paper draws on the work of Dewey (1927), Bozeman (2007) and Benington (2009) to open up new ways of theorising relations between accounting, whistleblowing and publicness.FindingsFirstly, the paper develops a public interest theoretical framework which shows whistleblowing is a public value activity that moves organisational wrongdoing into the public sphere where it is subject to democratic debate and dialogue required to reconcile the public's interests with what the public values. Secondly, this framework provides one answer to continuing questions in the literature of how to define accountings relationship to the public interest. Finally, the paper suggests this conceptual framework be used to stimulate debate on whether and how one should expand existing accounting and accountability knowledge boundaries to incorporate the broader social, political and moral concerns highlighted by whistleblowers acting in the public interest.Originality/valueAccounting and whistleblowing research has ignored the theoretical implications of whistleblowing in the public interest. The paper shows how accounting and accountability can respond to the challenges of a shifting and intangible public interest by providing a conceptual framework to guide current and future theoretical questions of how accounting is connected to the public interest.
Unveiling the veiled: Wikipedia collaborating with academic libraries in Africa in creating visibility for African women through Art+Feminism Wikipedia edit-a-thon
Authors: Ukwoma Scholastica Chizoma , Osadebe Ngozi Eunice , Okafor Victoria Nwamaka , Ezeani Chinwe Nwogo 
Published: July 2021

Purpose
This study aims to show that digital literacy can serve as a tool for effecting social change and highlights the achievements of an academic library in digital content creation using the Wikipedia platform.

Design/methodology/approach
The study adopted qualitative research method, Interview and document analysis were used for data gathering. Data gathered were analysed using content (conceptual) analysis.

Findings
Findings showed that the library has created or edited digital content for various categories of women, such as women in academia, industry and politics. These entries have received more than eight million views over a period of two years, which shows that the entries are being utilised. However, the editing exercise had been confronted with challenges such as accessing reliable citations in terms of the notability and verifiability policy of Wikipedia amongst others.

Practical implications
Currently, people rely more on online resources for their research, leaving physical library resources unused. Even, more students start their research online using Wikipedia. Thus, libraries could create visibility for their physical material using regularly visited sites like Wikipedia and its sister projects such as Wikidata; otherwise, these physical materials will remain invisible to the people that needed them.

Originality/value
Contributing to Wikipedia by creating a new entry or editing an existing one can help students to deepen their knowledge about a subject; Wikipedia editing may serve as an avenue for improving information literacy skills. Drawing from the theory of cyberfeminism as used in the study, information and communications technology has the potential to empower women and transform gender relations.
Jindal panther: the creation of a brand
Authors: Tapar Archit Vinod , Bhattacharjee Somraj , Kumar Jitender 
Published: July 2021

Learning outcomes
The case focuses on the importance of the brand-building process, which takes place in B2B companies. Commodity companies focus a lot on the sales and distribution aspect of their marketing strategies but do not emphasize the importance of developing their brands. At the end of the discussion, the participants would be able: to examine the steps involved in conceptualizing the brand identity for an existing product in a highly competitive B2B market, as per Kapferer’s Brand Identity Matrix. To understand the steps involved in the journey of internal and external brand-building processes in B2B. To analyze the various challenges and issues faced by large organizations dealing in the metals and commodity business.

Case overview/synopsis
The case discusses a marketing challenge faced by Jindal Steel and Power Limited (JSPL) in launching a new brand of thermomechanical treatment (TMT) products in the market. Traditionally, the company had focused on the sales and distribution aspect of their marketing strategies but did not emphasize the importance of developing their brands. This case is based upon the challenges faced in the creation of a new brand identity for JSPL’s TMT products by the protagonist, Mr Paras Sharma (who is the brand custodian and manager in this case).

Complexity academic level
Postgraduate/Masters in Business Administration (MBA), Masters in Management Studies, Executive MBA.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS 8: Marketing.
Netflix in India: expanding to success
Authors: Nafees Lubna , Mehdi Mokhalles , Gupta Rakesh , Kalia Shalini , Banerjee Sayan , Kapoor Shivani 
Published: July 2021

Learning outcomes
After completing the case, students should be able to understand: the importance and uniqueness of the individual market and developing a suitable marketing strategy. The concept of value creation and learn the importance of developing the right value proposition to compete and succeed in a market. The target audience and how to create the right marketing mix. Competition in a digital landscape and the importance of developing an appropriate strategy to counter its rivals and position the brand effectively.

Case overview/synopsis
During his visit to India in December 2019, Netflix’s founder and chief executive officer Reed Hastings talked about a series of steps the company had taken in the recent past to successfully face stiff competition and move towards achieving its stated target of 100 million viewers. These steps involved significant changes in their marketing mix such as reworking their pricing, developing a rich portfolio of Indian content and building various partnerships. Since Netflix’s launch in India (December 2016), it faced fierce competition from players such as Hotstar and Amazon Prime, both of whom had developed a rich portfolio of Indian content and adopted a very aggressive pricing strategy thus, making these changes essential. At the time of their launch, Netflix had set a very ambitious target of gaining 100 million viewers within five years (by 2021) while adopting a premium pricing strategy and positioning themselves uniquely based on their international content. They quickly learned that they would have to reevaluate their approach if they wanted to achieve their target on time. The changes announced by Hastings were an effort in that direction. The moot question was whether these steps would help Netflix India reach its goal. This challenge was further compounded by an almost 40% hike in data tariffs by three major wireless carriers considering most Indians watched over-the-top media content on their mobile phones.

Complexity academic level
The case is designed for undergraduates, as well as for fundamental marketing courses in the Master of Business Administration and other graduate level programmes. It can be taught in the Principles of Marketing, Marketing Strategy and International Marketing courses. It is ideal for topics such as understanding the operation of a digital business in a new market, customer value creation and value drivers, brand and brand positioning, product promotion, strategies for business growth and expansion, fighting competition in a digital landscape.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS 8: Marketing.