bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aβ promotes amyloidogenic processing of APP through a Go/Gβγ signaling
Authors: Antonino Magdalena , Marmo Paula , Freites Carlos Leandro , Quassollo Gonzalo , Sanchez Maria Florencia , Lorenzo Alfredo , Anahí Bignante Elena 
Published: March 2021

ABSTRACTAlzheimer’s disease (AD) is characterized by a cognitive impairment associated to amyloid beta (Aβ) aggregation and deposition in the brain. Aβ is generated by sequential cleavage of the amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) and γ-secretase complex. The mechanisms that underlie exacerbated production of Aβ, favoring its deposition in the brain, is largely unknown. In vitro studies have shown that Aβ aggregates trigger enhanced production of Aβ by a yet non described mechanism. Here, we show that in different cell types, including human neurons derived from induced pluripotent stem cells (iPSC), oligomers and fibrils of Aβ enhance the convergence and interaction of APP and BACE1 in endosomal compartments. We demonstrated a key role of Aβ-APP/Go/Gβγ signaling on the amyloidogenic processing of APP. We show that APP mutants with impaired capacity to bind Aβ or to activate Go protein, are unable to exacerbate APP and BACE1 colocalization in the presence of Aβ. Moreover, pharmacological inhibition of Gβγ subunits signaling with gallein, abrogate Aβ-dependent interaction of APP and BACE1 in endosomes preventing β-processing of APP. Collectively, these findings uncover a feed-forward mechanism of amyloidogenesis that might contribute to Aβ pathology in early stages of AD and suggest that gallein might have clinical relevance.
TCR signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1
Authors: He Yujiao , Yang Zhiguo , Zhao Chen-Si , Gong Yu , Xiao Zhihui , Li Yun-Yi , Chen Yiqi , Feng Dianying , Altman Amnon , Li Yingqiu 
Published: March 2021

AbstractThe nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport and its dysfunction has been associated with many diseases. The NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1 and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in NPC assembly remain poorly understood. Here, we show that, following TCR stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504and Ser506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.
The Intervening Domain Is Required For DNA-binding and Functional Identity of Plant MADS Transcription Factors
Authors: Lai Xuelei , Vega-Leon Rosario , Hugouvieux Veronique , Blanc-Mathieu Romain , van der Wal Froukje , Lucas Jérémy , Silva Catarina S. , Jourdain Agnès , Muino Jose , Nanao Max H. , Immink Richard , Kaufmann Kerstin , Parcy François , Smaczniak Cezary , Zubieta Chloe 
Published: March 2021

AbstractThe MADS transcription factors (TF) are an ancient protein family with a high degree of sequence identity that bind almost identical DNA sequences across all eukaryotic kingdoms of life, yet fulfill dramatically different physiological roles. In plants, the family is divided into two main lineages, type I and II, based on sequence conservation of the DNA-binding MADS-box domain (M domain) with yeast and animal M domains. Here, we demonstrate that DNA binding in both lineages absolutely requires a short amino acid sequence C-terminal to the M domain called the Intervening domain (I domain) in type II MADS. Structural elucidation of the MI domains from the floral regulator, SEPALLATA3 (SEP3), shows a highly conserved MADS-box fold with the I domain forming an alpha helix and acting to stabilize the M domain. Based on secondary structure prediction, sequences fulfilling the same function as the SEP3 I domain can be found in both lineages of plant MADS TFs, suggesting the I domain is a conserved and required part of the DNA-binding domain. Using the floral organ identity MADS TFs, SEP3, APETALA1 (AP1) and AGAMOUS (AG), domain swapping demonstrate that the I domain alters DNA-binding specificity based on seq-DAP-seq experiments. Yeast 2-hybrid experiments further revealed the role of the I domain in dimerization specificity. Surprisingly, introducing AG carrying the I domain of AP1 in the Arabidopsisap1mutant, resulted in a high degree of complementation and restoration of first and second whorl organs. Taken together, these data demonstrate that the I domain acts both as an integral part of the DNA-binding domain and strongly contributes to the functional identity of the MADS TF.
A precise and adaptive neural mechanism for predictive temporal processing in the frontal cortex
Authors: Meirhaeghe Nicolas , Sohn Hansem , Jazayeri Mehrdad 
Published: March 2021

AbstractThe theory of predictive processing posits that the nervous system uses expectations to process information predictively. Direct empirical evidence in support of this theory however has been scarce and largely limited to sensory areas. Here, we report a precise and adaptive neural mechanism in the frontal cortex of non-human primates consistent with predictive processing of temporal events. We found that the speed at which neural states evolve over time is inversely proportional to the statistical mean of the temporal distribution of an expected stimulus. This lawful relationship was evident across multiple experiments and held true during learning: when temporal statistics underwent covert changes, neural responses underwent predictable changes that reflected the new mean. Together, these results highlight a precise mathematical relationship between temporal statistics in the environment and neural activity in the frontal cortex that could serve as a mechanistic foundation for predictive temporal processing.
Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation
Authors: Deganutti Giuseppe , Liang Yi-Lynn , Zhang Xin , Khoshouei Maryam , Clydesdale Lachlan , Belousoff Matthew J. , Venugopal Hari , Truong Tin T. , Glukhova Alisa , Keller Andrew N. , Gregory Karen J. , Leach Katie , Christopoulos Arthur , Danev Radostin , Reynolds Christopher A. , Zhao Peishen , Sexton Patrick M. , Wootten Denise 
Published: March 2021

ABSTRACTThe glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mechanistic understanding of how different peptides generate profound differences in G protein-mediated signalling is still lacking. Here we have combined cryo-electron microscopy, molecular dynamics simulations, receptor mutagenesis and pharmacological assays, to interrogate the mechanism and consequences of GLP-1R binding by four peptide agonists; glucagon-like peptide-1, oxyntomodulin, exendin-4 and exendin-P5. These data revealed that distinctions in peptide N-terminal interactions and dynamics with the GLP-1R transmembrane domain are reciprocally associated with differences in the allosteric coupling to G proteins. In particular, transient interactions with residues at the base of the binding cavity correlate with enhanced kinetics for G protein activation, providing a rationale for differences in G protein-mediated signalling efficacy from distinct agonists.
Distinct profiles of spatio-temporal brain dynamics along symptoms dimensions in autism
Authors: Mullier Emeline , Kojovic Nada , Denervaud Solange , Vohryzek Jakub , Hagmann Patric , Schaer Marie 
Published: March 2021

ABSTRACTAutism Spectrum Disorders are accompanied by atypical brain activity and impairments in brain connectivity. In particular, dynamic functional connectivity approaches highlighted aberrant brain fluctuations at rest in individuals with autism compared to a group composed of typically developed individuals, matched in age and gender. However, the characterization of these variations remains unclear. Here, we quantified the spatio-temporal network dynamics using two novel dynamic group-based measures, namely system diversity and spatio-temporal diversity. Using the public database ABIDE 1, we explored the differences between individuals with autism and typically developed individuals. Our results show evidence that individuals with autism have atypical connectivity patterns over time characterized by a lower integration of heterogeneous cognitive processes and unstable functional activity, except for the default mode network presenting its own specific dynamic pattern. Within the autism group, we find this pattern of results to be stronger in more severely affected patients with a predominance of symptoms in the social affect domain. However, patients with prominently restricted and repetitive behaviours demonstrate a more conservative profile of brain dynamics characterized by a lower spatio-temporal diversity of the default mode network.
Transfer Entropy Based Causality From Head Motion To Eye Movement
Authors: Lv Zezhong , Xu Qing , Schoeffmann Klaus , Parkinson Simon 
Published: March 2021

AbstractEye movement behavior, which provides the visual information acquisition and processing, plays an important role in performing sensorimotor tasks, such as driving, by human beings in everyday life. In the procedure of performing sensorimotor tasks, eye movement is contributed through a specific coordination of head and eye in gaze changes, with head motions preceding eye movements. Notably we believe that this coordination in essence indicates a kind of causality. In this paper, we investigate transfer entropy to set up a quantity for measuring an unidirectional causality from head motion to eye movement. A normalized version of the proposed measure, demonstrated by virtual reality based psychophysical studies, behaves very well as a proxy of driving performance, suggesting that quantitative exploitation of coordination of head and eye may be an effective behaviometric of sensorimotor activity.
Structured illumination microscopy with noise-controlled image reconstructions
Authors: Smith Carlas S. , Slotman Johan A. , Schermelleh Lothar , Chakrova Nadya , Hari Sangeetha , Vos Yoram , Hagen Cornelis W. , Müller Marcel , van Cappellen Wiggert , Houtsmuller Adriaan B. , Hoogenboom Jacob P. , Stallinga Sjoerd 
Published: March 2021

AbstractSuper-resolution structured illumination microscopy (SIM) has become a widely used method for biological imaging. Standard reconstruction algorithms, however, are prone to generate noise-specific artefacts that limit their applicability for lower signal-to-noise data. Here, we present a physically realistic noise model that explains the structured noise artefact and that is used to motivate new complementary reconstruction approaches. True Wiener-filtered SIM optimizes contrast given the available signal-to-noise ratio, flat-noise SIM fully overcomes the structured noise artefact while maintaining resolving power. Both methods eliminate ad-hoc user adjustable reconstruction parameters in favour of physical parameters, enhancing objectivity. The new reconstructions point to a trade-off between contrast and a natural noise appearance. This trade-off can be partly overcome by additional notch filtering, but at the expense of a decrease in signal-to-noise ratio. The benefits of the proposed approaches are demonstrated on focal adhesion and tubulin samples in 2D and 3D, and on nano-fabricated fluorescent test patterns.
Happy Self Publishing
Authors: Ramachandran Sathyanarayanan 
Published: March 2021

Study level/applicability
The case could be effectively used in courses on entrepreneurship, strategy and brand management in MBA programs and executive-level training programs.

Subject area
Entrepreneurship, strategy, marketing, women leadership and women in business.

Case overview
This case deals with the business decision-making situation of Ms Jyotsna Ramachandran, a first-generation woman entrepreneur from Southern India, who has created a Global collaborative business network in self-publishing of books from India. After gaining industry experience for five years in some of the leading retail brands of India, she decided to take a plunge in entrepreneurship. She tried several businesses ranging from retail staffing to custom-made chocolates. Though it was profitable, the volumes and margins were smaller, and Jyotsna aspired big. As, at that time she was on her family way, she decided to identify a profitable business with better value creation and premium for the consumers and at the same time free from minute-by-minute concentration to take care of her child. In other words, a less-hassle home-based business with better revenue streams and margins. The case gives a thorough background of her rise in the industry and talks about some of her new ideas and plans.

Expected learning outcomes
Students will be in a position to: 1. Understand gender issues and bias affecting women in work. 2. Illustrate the initial phases of entrepreneurship. 3. Understand and apply the evaluation tools like PESTLE, SWOT and then business model canvas. 4. Understand the value chain and the intensive and integrative growth strategies. 5. Illustrate blue oceans in an industry setup – irrespective of the industry growth rate. 6. Apply perspectives on brand management.

Supplementary materials
Detailed teaching notes attached. Teaching notes are available for educators only.

Social implications
The case addresses the important gender issues affecting women’s work–life balance. It will also inspire many women through the success of the woman protagonist and her project head well documented in this case study.

Subject code
CSS 3: Entrepreneurship
Leading change and Plato
Authors: Georgiadis Vasileios , Sarigiannidis Lazaros , Theriou Georgios 
Published: March 2021

PurposeThis paper aims at identifying critical components of leading change through relations of relevance with platonic philosophy. During this process, well-known aspects of change leadership are detected, but interpreted differently. Based on this relevance, a seven-stage tripartite model is proposed, in order to facilitate change implementation in the business world.Design/methodology/approachContemporary trends in leading change are reviewed and enriched with platonic insights. A synthetic analysis is attempted, in which philosopher stochasticity and discernment validates modern synergetic and anthropocentric approaches to the field of change leadership, featuring key behavioral and perceptual characteristics, emerging during change process.FindingsAs the process of change is highly dependent on human behavior, Plato grants an enriched approach of its origins and causal causes. Therefore, key change factors are not only discussed in the light of his worldview, but also upgraded through the distillation of applicable ideas, summarized in the proposed three phase model.Practical implicationsThe proposed tripartite model of leading change can function as a powerful guide of designing and successfully implement organizational change.Originality/valueThe screening of specific insights from platonic works in leading change conveys an alternative, more “poetic”, yet effectively flexible attitude endorsed and incorporated into a potentially applicable model.
“A little bit of everything?” Conceptualising performance measurement in hybrid public sector organisations through a literature review
Authors: De Waele Lode , Polzer Tobias , van Witteloostuijn Arjen , Berghman Liselore 
Published: March 2021

PurposeNumerous of today's public sector organisations (PSOs) can be characterised as hybrids. Hybridity is caused by different (at times conflicting) demands that stem from the institutional environment, which is likely to affect performance measurement in these organisations. This paper focuses on the relationship between hybridity and organisational performance, which has so far not been studied in detail.Design/methodology/approachBased on a literature review (final sample of 56 articles), the authors systematise performance dimensions alongside the pillars “economy”, “efficiency”, “effectiveness” and “(social) equity”. The article summarises results in a framework for measuring performance in hybrid PSOs. The authors outline strategies as to how public managers can tailor frameworks to the requirements and idiosyncrasies of organisations.FindingsSince hybrid PSOs combine logics from different administrative models (Weberian bureaucracy, market-capitalism and democracy), so need their organisational performance measurement systems. Potential synergies from and frictions between the different performance dimensions related to the four pillars are discussed.Originality/valueThis is the first literature review on performance dimensions and their application in hybrid PSOs. The distilled “hybrid performance measurement framework” can be scrutinised and further refined in future research.
Validating eDNA measurements of the richness and abundance of anurans at a large scale
Authors: Li Wenhao , Hou Xianglei , Xu Chunxia , Qin Mingshuo , Wang Supen , Wei Li , Wang Yanping , Liu Xuan , Li Yiming 
Published: March 2021

Abstract

In some situations, environmental DNA (eDNA) metabarcoding is a more accurate tool for measuring species richness of a taxon than conventional methods. Whether this tool can reliably estimate the abundance of a taxon remains unresolved.

We examined the reliability of metabarcoding for measuring anuran diversity compared to a commonly used traditional line transect method (TLTM) through the replicate sampling of three visits across 71 waterbodies (ponds or reservoirs) in Liuheng, China. We also investigated the relative contributions of species‐specific characteristics and the physiochemical properties of a waterbody on the relative read count across species and waterbodies.

We found that eDNA metabarcoding had a higher detection probability for each of seven anuran species found in the sampling region than TLTM. Furthermore, the relative read count estimated by metabarcoding was positively correlated with the density or relative density of individuals identified with the TLTM across waterbodies for every species. Species‐specific characteristics of anurans, such as density, relative density, body mass, biomass and relative biomass, accounted for substantial variations in the read count across species and waterbodies, while physiochemical factors, including pH, temperature, water volume, vegetation and elevation, had little effect on the read count.

Our results based on robust sampling suggest that metabarcoding enables more reliable and efficient measurements of anuran occurrence at a large scale during a short‐term survey (within 15 days) than that obtained by the TLTM, and offers an alternative tool for quantifications of anuran abundance. Density or biomass is better and more reliable indicator of anuran abundance associated with read count than relative density or relative biomass.
Ontogenetic diversity buffers communities against consequences of species loss
Authors: Rudolf Volker H. W. , Eveland Lauren 
Published: March 2021

AbstractBiodiversity can be measured at multiple organizational scales. While traditional studies have focused at taxonomic diversity, recent studies have emphasized the ecological importance of diversity within populations. However, it is unclear how these different scales of diversity interact to determine the consequence of species loss.Here we asked how predator diversity and presence of ontogenetic diversity within predator populations influences community structure. Ontogenetic diversity arises from shifts in the traits and ecology of individuals during ontogeny and it is one of the biggest sources of intraspecific diversity. However, whether it dampens or strengthens the negative consequences of with species loss is poorly understood.To study the interaction of species diversity and ontogenetic diversity, we experimentally manipulated predator species diversity and diversity of developmental stages within focal predator species and analysed their joint effect on predator and prey survival, biomass and prey community structure in experimental pond systems.While individual effects of ontogenetic diversity were often species specific, losing predator species from the community often had a much smaller or no effect on prey survival, biomass or community structure when all predator populations had high ontogenetic diversity. Thus, ontogenetic diversity within populations buffered against some of the consequences of biodiversity loss at higher organizational levels. Because the experiment controlled mean per capita size and biomass across structured versus unstructured populations, this pattern was not driven by differences in biomass of predators. Instead, results suggest that effects were driven by changes in the functional roles and indirect interactions across and within species. This indicates that even if all environmental conditions are similar, differences in the intrinsic structure of populations can modify the consequences of biodiversity loss.Together, these results revealed the importance of ontogenetic diversity within species for strengthening the resilience of natural communities to consequences of biodiversity loss and emphasize the need to integrate biodiversity patterns across organizational scales.
Imagining the newcomer–supervisor relationship: Future relational self in the workplace
Authors: Morandin Gabriele , Russo Marcello , Bergami Massimo 
Published: March 2021

AbstractPeople develop images of themselves in the future reflecting hopes in relation to their work, namely the future work self. In this study, we introduce the concept of Future Relational Self (FRS), conceived as a relevant dimension of the future work self that illustrates the representation of the relationship that an employee aspires to build with significant stakeholders in the workplace (i.e., the supervisor). In addition, we investigate its motivational power shaping role and relational outcomes at work. Using data collected among 215 newcomers in three different waves with a one‐month time lag, we examine the indirect effect of two characteristics of the FRS––namely salience and attribution of control––on newcomers' adjustment (i.e., role clarity and social adjustment) via leader–member exchange (LMX) quality. Results reveal that only the FRS attribution of control is positively associated with LMX quality. Moreover, the results indicate that LMX quality mediates the effects of attribution of control on both newcomers' social adjustment and role clarity. Contributions for theory and implications for practice are highlighted.