bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stoichiometric Analysis of Protein Complexes by Cell Fusion and Single Molecule Imaging
Authors: Singh Avtar , Van Slyke Alexander L. , Sirenko Maria , Song Alexander , Kammermeier Paul J. , Zipfel Warren R. 
Published: January 2020

ABSTRACTThe composition, stoichiometry and interactions of supramolecular protein complexes are a critical determinant of biological function. Several techniques have been developed to study molecular interactions and quantify subunit stoichiometry at the single molecule level; however, these typically require artificially low expression levels to achieve the low fluorophore concentration required for single molecule imaging, or use of detergent isolation of complexes that may perturb native subunit interactions. Here we present an alternative approach where protein complexes are assembled at physiological concentrations and subsequently dilutedin situfor single-molecule level observations while preserving them in a near-native cellular environment. We show that coupling thisin situdilution strategy with single molecule techniques such asin vivoFluorescence Correlation Spectroscopy (FCS), bleach step counting for quantifying protein complex stoichiometry, and two-color single molecule colocalization, improves the quality of data obtained using these single molecule fluorescence methods. Single Protein Recovery After Dilution (SPReAD) is a simple and versatile means of extending the concentration range of single molecule measurements into the cellular regime while minimizing potential artifacts and perturbations of protein complex stoichiometry.SIGNIFICANCE STATEMENTQuantifying the composition and stoichiometry of protein complexes in live cells is critical to understanding mechanisms involved in their function. Here we detail a method in which protein complexes are assembled intracellularly at physiological concentrations, but then diluted to levels suitable for single-molecule fluorescence observations while still within a cellular environment. The technique permits the use of common single molecule analysis techniques such as stepwise photobleaching quantification and fluorescence correlation spectroscopy to determine stoichiometry and functional interactions while avoiding artifacts that may occur from the use of detergent isolation methods or from the artificially low expression levels sometimes used to attain single molecule observation levels.
Non-invasive red-light optogenetic control ofDrosophilacardiac function
Authors: Men Jing , Li Airong , Jerwick Jason , Li Zilong , Tanzi Rudolph E. , Zhou Chao 
Published: January 2020

ABSTRACTDrosophila is a powerful genetic model system for cardiovascular studies. Recently, optogenetic pacing tools have been developed to controlDrosophilaheart rhythm noninvasively with blue light, which has a limited penetration depth. Here we developed both a red-light sensitive opsin expressingDrosophilasystem and an integrated red-light stimulation and optical coherence microscopy (OCM) imaging system. We demonstrated noninvasive control ofDrosophilacardiac rhythms, including simulated tachycardia in ReaChR-expressing flies and bradycardia and cardiac arrest in halorhodopsin (NpHR)-expressing flies at multiple developmental stages. By using red excitation light, we were able to pace flies at higher efficiency and with lower power than with equivalent blue light excitation systems. The recovery dynamics after red-light stimulation of NpHR flies were observed and quantified. The combination of red-light stimulation, OCM imaging, and transgenicDrosophilasystems provides a promising and easily manipulated research platform for noninvasive cardiac optogenetic studies.
Thm2interacts with paralog,Thm1, and sensitizes to Hedgehog signaling in postnatal skeletogenesis
Authors: Allard Bailey A , Wang Wei , Pottorf Tana S , Mumtaz Hammad , Silva Luciane M , Jacobs Damon T , Wang Jinxi , Bumann Erin E , Tran Pamela V 
Published: January 2020

AbstractCiliopathies are genetic syndromes that link osteochondrodysplasias to dysfunction of primary cilia. Primary cilia extend from the surface of bone and cartilage cells, to receive extracellular cues and mediate signaling pathways. Mutations in several genes that encode components of the intraflagellar transport-A ciliary protein complex have been identified in skeletal ciliopathies, includingTHM1. Here, we report a role for genetic interaction betweenThm1and its paralog,Thm2,in skeletogenesis. THM2 localizes to the ciliary axoneme, but unlike its paralog,Thm2deficiency does not affect ciliogenesis andThm2-null mice survive into adulthood. Since paralogs often have redundant functions, we crossed aThm1null (aln) allele into theThm2colony. After 5 generations of backcrossing the colony onto a C57BL6/J background, we observed that by postnatal day 14,Thm2-/-; Thm1aln/+mice are smaller than control littermates.Thm2-/-; Thm1aln/+mice exhibit shortened long bones, narrow ribcage, shortened cranium and mandibular defects. Mutant mice also show aberrant architecture of the tibial growth plate, with an expanded proliferation zone and diminished hypertrophic zone, indicating impaired chondrocyte differentiation. Using microcomputed tomography,Thm2-/-; Thm1aln/+tibia were revealed to have reduced cortical and trabecular bone mineral density. Deletion of one allele ofGli2, a major transcriptional activator of the Hedgehog (Hh) pathway, exacerbated the small phenotype ofThm2-/-; Thm1aln/+mice and caused small stature inThm2-null mice. Together, these data revealThm2as a novel locus that sensitizes to Hh signaling in skeletal development. Further,Thm2-/-; Thm1aln/+mice present a new postnatal ciliopathy model of osteochondrodysplasia.
A Multivariate View of Parallel Evolution
Authors: De Lisle Stephen P. , Bolnick Daniel I. 
Published: January 2020

AbstractA growing number of empirical studies have quantified the degree to which evolution is geometrically parallel, by estimating and interpreting pairwise angles between evolutionary change vectors in multiple replicate lineages. Similar comparisons, of distance in trait space, are used to assess the degree of convergence. These approaches amount to element-by-element interpretation of distance matrices, and can fail to capture the true extent of multivariate parallelism when evolution involves multiple traits sampled across multiple lineages. We suggest an alternative set of approaches, co-opted from evolutionary quantitative genetics, involving eigen analysis and comparison of among-lineage covariance matrices. Such approaches not only allow the full extent of multivariate parallelism to be revealed and interpreted, but also allow for the definition of biologically tenable null hypotheses against which empirical patterns can be tested. Reanalysis of a dataset of multivariate evolution across a replicated lake/stream gradient in threespine stickleback reveals that most of the variation in the direction of evolutionary change can be captured in just a few dimensions, indicating a greater extent of parallelism than previously appreciated. We suggest that applying such multivariate approaches may often be necessary to fully understand the extent and form of parallel and convergent evolution.
Mapping Functional Protein Neighborhoods in the Mouse Brain
Authors: Liebeskind Benjamin J. , Young Rebecca L. , Halling D. Brent , Aldrich Richard W. , Marcotte Edward M. 
Published: January 2020

ABSTRACTNew proteomics methods make it possible to determine protein interaction maps at the proteome scale without the need for genetically encoded tags, opening up new organisms and tissue types to investigation. Current molecular and computational methods are oriented towards protein complexes that are soluble, stable, and discrete. However, the mammalian brain, among the most complicated and most heavily studied tissue types, derives many of its unique functions from protein interactions that are neither discrete nor soluble. Proteomics investigations into the global protein interaction landscape of the brain have therefore leveraged non-proteomics datasets to supplement their experiments. Here, we develop a novel, integrative proteomics pipeline and apply it to infer a global map of functional protein neighborhoods in the mouse brain without the aid of external datasets. By leveraging synaptosome enrichment and interactomics methods that target both soluble and insoluble protein fractions, we resolved protein interactions for key neural pathways, including those from refractory subcellular fractions such as the membrane and cytoskeleton. In comparison to external datasets, our observed interactions perform similarly to hand-curated synaptic protein interactions while also suggesting thousands of novel connections. We additionally employed cleavable chemical cross-linkers to detect direct binding partners and provide structural context. Our combined map suggests new protein pathways and novel mechanisms for proteins that underlie neurological diseases, including autism and epilepsy. Our results show that proteomics methods alone are sufficient to determine global interaction maps for proteins that are of broad interest to neuroscience. We anticipate that our map will be used to prioritize new research avenues and will pave the way towards future proteomics techniques that resolve protein interactions at ever greater resolution.
Transient “rest” induces functional reinvigoration and epigenetic remodeling in exhausted CAR-T cells
Authors: Weber Evan W. , Lynn Rachel C. , Parker Kevin R. , Anbunathan Hima , Lattin John , Sotillo Elena , Good Zinaida , Malipatlolla Meena , Xu Peng , Vandris Panos , Majzner Robbie G. , Qi Yanyan , Chen Ling-Chun , Gentles Andrew J. , Wandless Thomas J. , Satpathy Ansuman T. , Chang Howard Y. , Mackall Crystal L. 
Published: January 2020

SUMMARYT cell exhaustion limits immune responses against cancer and is a major cause of resistance to CAR-T cell therapeutics. Using a model wherein tonic CAR signaling induces hallmark features of exhaustion, we employed a drug-regulatable CAR to test the impact of transient cessation of receptor signaling (i.e. “rest”) on the development and maintenance of exhaustion. Induction of rest in exhausting or already-exhausted CAR-T cells resulted in acquisition of a memory-like phenotype, improved anti-tumor functionality, and wholescale transcriptional and epigenetic reprogramming. Similar results were achieved with the Src kinase inhibitor dasatinib, which reversibly suppresses CAR signaling. The degree of functional reinvigoration was proportional to the duration of rest and was associated with expression of transcription factors TCF1 and LEF1. This work demonstrates that transient cessation of CAR-T cell signaling can enhance anti-tumor potency by preventing or reversing exhaustion and challenges the paradigm that exhaustion is an epigenetically fixed state.
Transcriptional regulator PAX4 links Receptor Tyrosine Kinases (RTKs) and cytoskeleton stability in Alzheimer’s disease and type 2 diabetes
Authors: Majumder Piyali , Chanda Kaushik , Das Debajyoti , Singh Brijesh Kumar , Chakrabarti Partha , Jana Nihar Ranjan , Mukhopadhyay Debashis 
Published: January 2020

AbstractAlzheimer’s Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Besides Insulin Receptor (IR), two non-canonical RTKs, ALK and RYK, exhibit significant and consistent functional downregulation inpost-mortemAD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor. Here we show that Grb2 and NOX4 play critical roles in reducing the severity of both the diseases. The study demonstrates that the abundance of Grb2 in degenerative conditions, in conjunction with NOX4, reverse cytoskeletal degradation by counterbalancing the network of small GTPases. PAX4, a transcription factor for both Grb2 and NOX4, emerges as the key link between the common pathways of AD and T2D. Both ALK and RYK downregulation elevate the PAX4 level by reducing its suppressor ARX via Wnt/β-Catenin signaling pathway. For the first time, this study brings together RTKs other than Insulin Receptor (IR), their common transcription factor PAX4 and both AD and T2D pathologies on a common regulatory platform.
The effect of service innovation on customer behavioral intention in the Taiwanese insurance sector: the role of word of mouth and corporate social responsibility
Authors: Chang Jui-I , Lee Chen-Ying 
Published: January 2020

Purpose
Service innovation has been one of the essential elements to meet the customers’ requirements, but few studies discuss service innovation regarding behavioral intention in the insurance industry. This paper aims to investigate the effects of service innovation on customer behavioral intention and examines the role of word-of-mouth (WOM) and corporate social responsibility (CSR).

Design/methodology/approach
This paper used a survey to assess consumer behavioral intention regarding service innovation activities from life insurance. Questionnaires were administered to consumers who have purchased life insurance in Taiwan and the survey questions were tested through factor analysis. An analysis of multiple and hierarchical regression was performed to test the hypotheses.

Findings
The empirical results demonstrate that life insurance service innovation has a significantly positive influence on WOM and behavioral intention. Additionally, WOM has a partially mediating effect between service innovation and behavioral intention. Furthermore, the study indicates that CSR has a moderating effect on the relationship between service innovation and behavioral intentions.

Originality/value
Considering the uniqueness of this study in the context of Taiwan, the research draws on signaling theory as the framework to explore service innovation and the impact of social responsibility on consumer behavioral intentions in the Taiwanese insurance industry. Additionally, the results can be considered a service marketing strategy and are applicable to the financial service industry in some developing Asian countries
The determinants of bank insolvency risk: evidence from Finland
Authors: Huhtilainen Matias 
Published: January 2020

Purpose
This paper aims to contribute to the literature on the determinants of bank-specific insolvency risk.

Design/methodology/approach
By applying a dynamic two-step System GMM estimator on a novel, representative panel of 339 Finnish unlisted cooperative and savings banks over the period 2002-2018.

Findings
This study contributes to the literature on the determinants of bank-specific insolvency risk by applying a dynamic two-step System GMM estimator on a novel, representative panel of 339 Finnish unlisted cooperative and savings banks over the period 2002-2018. The key findings suggest that Finnish banks have become less fragile under the renewed EU banking regulation. In particular, the CRD IV has affected banks’ equity levels. This study also captures the detrimental effect of cost inefficiency as well as a positive relationship between the income diversification and insolvency risk. A negative relationship between the GDP growth rate and the insolvency risk is also reported although results suggest that the effect is not immediate.

Originality/value
This result is discussed together with other macroeconomic factors. The consequent conclusion underlines the fundamental significance of overall macroeconomic dynamics. From the perspective of regulatory harmonization, more research is needed to address the level of homogeneity of macroeconomic dynamics between different geographical and cultural regions.
What’s done in the dark will be brought to the light: effects of influencer transparency on product efficacy and purchase intentions
Authors: Woodroof Parker J. , Howie Katharine M. , Syrdal Holly A. , VanMeter Rebecca 
Published: January 2020

Purpose
The purpose of this paper is to examine the impact of the type of disclosure used by social media influencers on consumer evaluations of influencer transparency, product performance expectations and how those factors ultimately influence purchase intentions.

Design/methodology/approach
An experiment was conducted with 321 participants recruited from MTurk to test a moderated serial-mediation model.

Findings
The results indicate that when consumers become cognizant that an influencer’s branded promotional post may have been motivated by an underlying financial relationship, they evaluate the influencer as significantly less transparent if a more ambiguous disclosure is used relative to a clearer disclosure. Transparency perceptions of the influencer impact consumers’ perceptions of product efficacy as well as purchase intentions.

Originality/value
Social media influencers are rapidly emerging as a popular marketing tool for brand managers, but consumer response to this form of promotion is not well understood. To the best of the authors’ knowledge, this is the first study to investigate how the type of endorsement disclosure used by a social media influencer impacts consumer perception of influencer transparency, product efficacy and purchase intentions. Further, this research demonstrates the applicability of the persuasion knowledge model in the domain of influencer marketing.
Red cabbage anthocyanins content as a natural colorant for obtaining different color on wool fibers
Authors: Barani Hossein , Maleki Homa 
Published: January 2020

Purpose
Finding blue colorants from natural sources is extremely difficult and, usually, the anthocyanin compounds are used for producing the blue color. This study aims to apply the Red Cabbage as a natural colorant to obtain different colors on wool yarn, as well as specify the optimum dyeing condition by response surface methodology for obtaining a blue color.

Design/methodology/approach
The effect of dyeing process parameters such as mordant concentration, dyeing time, pH of dyeing bath and dyeing temperature examined in the color characteristics of the dyed wool samples.

Findings
The obtained results indicated that the diverse colors achieve by varying the dyeing process parameters, which is in the range of 26° up to 271°. The non-mordanted dyed wool samples showed a red and red brownish color (Hue angle = 26° up to 70°), and the mordanted dyed wool samples showed a blue and blue-greenish color (Hue angle = 230° up to 271°). The obtained blue color with the optimized dyeing condition presented a considerable good wash and lightfastness.

Originality/value
This study provides a promising application of Red Cabbage as a natural colorant for obtaining different colors by varying the dyeing process parameters such as pH and stannous ion concentrations. The stannous ions yielded a co-pigmentation and presented a blue color on wool fibers, which is extremely difficult to obtain with natural colorant.
Single bath dyeing of modified nylon/cotton blended fabrics using direct/acid dyes
Authors: Iqbal Kashif , Javid Amjed , Rehman Abdur , Rehman Aisha , Ashraf Munir , Abid Hafiz Affan 
Published: January 2020

Purpose
This study aims to deal with the dyeing of nylon-/cotton-blended fabric in one bath using direct and acid dyes.

Design/methodology/approach
The cellulose in cotton/nylon-blended fabric was chemically modified using 3-chloro-2-hydroxypropyl tri-methyl ammonium chloride (CHPTAC) as cationizing agent to impart positive charge on the cellulose. The modified and unmodified blended fabrics were dyed in a single bath with direct and acid dyes under various concentrations of 0.5, 1, 2, 4 and 6 per cent on the weight of fabric by exhaust method. The dyeing of modified and unmodified fabrics was characterized through the properties such as K/S and colorfastness to washing, rubbing and light.

Findings
The modified fabric exhibited higher color yield, comparable rubbing fastness and good washing fastness.

Originality/value
The dye uptake was maximum in a single-bath dyeing process of nylon-/cotton-blended fabrics without electrolyte addition, which minimizes the impact of dyes on environment.
Substrate quality and not dominant plant community determines the vertical distribution and C assimilation of enchytraeids in peatlands
Authors: Briones María Jesús Iglesias , Carrera Noela , Huang Jinhua , Barreal Maria Esther , Schmelz Rüdiger Maria , Garnett Mark H. 
Published: January 2020

AbstractPeatlands are important carbon (C) stores as a result of acidity, waterlogging conditions and low temperatures slowing decomposition rates. However, climate change is predicted to bring not only changes in abiotic conditions but also the replacement of peat‐forming vegetation, such asSphagnummosses, with vascular plants. In these systems, enchytraeid worms represent the dominant mesofaunal group, and previous climate change manipulations have shown that their abundances and vertical distribution are strongly influenced by temperature and moisture gradients, with important implications for C cycling. Therefore, determining their behavioural responses to changes in both abiotic and biotic factors is crucial to quantify their contribution to decomposition processes.We investigated the importance of vertical edaphic gradients (soil moisture and labile C) on enchytraeids total numbers, vertical distribution and feeding activities by inverting intact soil cores and hence, reversing both substrate quality but leaving the microclimatic gradients intact. This manipulative experiment was set up in two different peatland areas, one dominated by heather (Erica mackaiana) and another by mosses (Sphagnumsp.) to determine the influence of different plant functional growth forms on these responses.Our results showed that most enchytraeid species were ‘stayers’ (i.e. in the ‘Upturned cores’, they remained in the same layer where they are ‘Normally’ located), and hence, their vertical distribution was more dependent on substrate quality than a change in microclimate. This response was more evident under drier conditions (i.e. the highest locations of the height gradient at the heather site) than at the wettest locations (i.e. the bottom of the slope and under mosses) due to more pronounced vertical gradients in substrate quality. Furthermore, radiocarbon measurements on enchytraeid tissues showed that to avoid competition among the growing populations for the limited labile resources present in the top layers, enchytraeids selected older C sources.These findings indicate that future climate change scenarios will not only bring important changes in the abiotic conditions (temperature and moisture) and biotic properties of peatlands (both vegetation composition and below‐ground soil biota community structure and vertical distribution) but also alterations in the feeding preferences of key decomposers that could result in the mobilization of previously unavailable C pools.A freePlain Language Summarycan be found within the Supporting Information of this article.