bluuebunny/crossref_metadata_2025_split huggingface dataset:
An indispensable role for dynamin-related protein 1 (DRP1) in adipogenesis
Authors: Reddy Mooli Raja Gopal , Mukhi Dhanunjay , Chen Zhonghe , Buckner Nia , Ramakrishnan Sadeesh K. 
Published: April 2020

AbstractEmerging evidence indicates that proper mitochondrial dynamics is critical for adipocyte differentiation and functional thermogenic capacity. We found that mitochondrial fission protein dynamin-related protein 1 (DRP1) is highly expressed in brown adipose tissue compared to white adipose tissue and their levels increase during brown adipocyte differentiation. Our results reveal that the inhibition of DRP1 using Mdivi-1 mitigates adipocyte differentiation and differentiation-associated mitochondrial biogenesis. We found that DRP1 is essential for the induction of the early phase of adipogenic transcriptional program. Intriguingly, inhibition of DRP1 is dispensable following the induction of adipogenesis and adipogenesis-associated mitochondrial biogenesis. Together, we demonstrate that DRP1 in the preadipocytes plays an essential role in brown and beige adipogenesis.
Control of mammalian brain aging by the unfolded protein response (UPR)
Authors: Cabral-Miranda Felipe , Tamburini Giovani , Martinez Gabriela , Medinas Danilo , Gerakis Yannis , Miedema Tim , Duran-Aniotz Claudia , Ardiles Alvaro O. , Gonzalez Cristobal , Sabusap Carleen , Bermedo-Garcia Francisca , Adamson Stuart , Vitangcol Kaitlyn , Huerta Hernan , Zhang Xu , Nakamura Tomohiro , Sardi Sergio Pablo , Lipton Stuart A. , Kenedy Brian K. , Cárdenas Julio Cesar , Palacios Adrian G. , Plate Lars , Henriquez Juan Pablo , Hetz Claudio 
Published: April 2020

AbstractAging is the major risk factor for the development of dementia and neurodegenerative disorders, and the aging brain manifests severe deficits in buffering capacity by the proteostasis network. Accordingly, we investigated the significance of the unfolded protein response (UPR), a major signaling pathway that copes with endoplasmic reticulum (ER) stress, to normal mammalian brain aging. Genetic disruption of ER stress sensor IRE1α accelerated cognitive and motor dysfunction during aging. Exogenous bolstering of the UPR by overexpressing an active form of the transcription factor XBP1 restored synaptic and cognitive function in addition to reducing cell senescence. Remarkably, proteomic profiling of hippocampal tissue indicated that XBP1s expression corrected age-related alterations in synaptic function. Collectively, our data demonstrate that strategies to manipulate the UPR sustain healthy brain aging.One Sentence SummaryThe IRE1/XBP1 pathway dictates when and how brain function declines during aging.
Rapid, precise quantification of large DNA excisions and inversions by ddPCR
Authors: Watry Hannah L. , Feliciano Carissa M. , Gjoni Katie , Takahashi Gou , Miyaoka Yuichiro , Conklin Bruce R. , Judge Luke M. 
Published: April 2020

AbstractThe excision of genomic sequences using paired CRISPR-Cas nucleases is a powerful tool to study gene function, create disease models and holds promise for therapeutic gene editing. However, our understanding of the factors that favor efficient excision is limited by the lack of a rapid, accurate measurement of DNA excision outcomes that is free of amplification bias. Here, we introduce ddXR (droplet digital PCR eXcision Reporter), a method that enables the accurate and sensitive detection of excisions and inversions independent of length. The method can be completed in a few hours without the need for next-generation sequencing. The ddXR method uncovered unexpectedly high rates of large (>20 kb) excisions and inversions, while also revealing a surprisingly low dependence on linear distance, up to 170 kb. We further modified the method to measure precise repair of excision junctions and allele-specific excision, with important implications for disease modeling and therapeutic gene editing.
Exogenous L-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice
Authors: Lundquist Adam J. , Gallagher Tyler J. , Petzinger Giselle M. , Jakowec Michael W. 
Published: April 2020

AbstractL-lactate is an energetic and signaling molecule that is key to the metabolic and neuroplastic connection between astrocytes and neurons and may be involved in exercise-induced neuroplasticity. This study sought to explore the role of L-lactate in astrocyte reactivity and neuroplasticity. Using in vitro cultures of primary astrocytes, we show L-lactate increased expression of plasticity-related genes, including neurotrophic factors,Bdnf, Gdnf, Cntfand the immediate early genecFos. L-lactate’s promotion of neurotrophic factor expression may be mediated in part by the lactate receptor HCAR1 since application of the HCAR1 agonist 3,5-DHBA also increased expression ofBdnfin primary astrocytes. In vivo L-lactate administration to healthy mice caused a similar increase in the expression of plasticity-related genes as well as increased astrocyte morphological complexity in a region-specific manner, with increased astrocytic response found in the striatum but not the ectorhinal cortex, regions of the brain where increases in regional cerebral blood flow are increased or unaltered, respectively, with motor behavior. Additionally, L-lactate administration did not cause synaptogenesis or improve motor behavior based on the latency to fall on the accelerating rotarod, suggesting that L-lactate administration can initiate astrocyte-specific gene expression, but the activation of motor circuits is necessary to initiate striatal neuroplasticity. These results suggest that peripheral L-lactate is likely an important molecular component of exercise-induced neuroplasticity by acting in an astrocyte-specific manner to prime the brain for neuroplasticity.
Correcting False Memories: The Effect of Mnemonic Generalization on Original Memory Traces
Authors: Muncy Nathan M. , Kirwan C. Brock 
Published: April 2020

AbstractFalse memories are a common occurrence but the impact of misremembering on the original memory trace is ill-described. While the original memory may be overwritten, it is also possible for a second false memory to exist concurrently with the original, and if a false memory exists concurrently then recovery of the original information should be possible. This study investigates first, whether false recognition overwrites the original memory representation using a mnemonic discrimination task, and second, which neural processes are associated with recovering the original memory following a false memory. Thirty-five healthy, young adults performed multiple recognition memory tests, where the design of the experiment induced participants to make memory errors in the first recognition memory test and then allowed us to determine whether the memory error would be corrected in the second test. FMRI signal associated with the encoding and retrieval processes during the experiment were investigated in order to determine the important regions for false memory correction. We found that false memories do not overwrite the original trace in all instances, as recovery of the original information was possible. Critically, we determined that recovery of the original information was dependent on higher-order processes during the formation of the false memory during the first test, and not on processing at the time of encoding nor the second test.
Zinc Oxide Nanoparticles (ZnONPs) as Nanofertilizer: Improvement on Seed Yield and Antioxidant Defense System in Soil Grown Soybean (Glycine maxcv. Kowsar)
Authors: Yusefi-Tanha Elham , Fallah Sina , Rostamnejadi Ali , Pokhrel Lok Raj 
Published: April 2020

AbstractHerein, we investigated potential phytotoxicity of zinc oxide nanoparticles (ZnONPs) on seed yield, focusing on particle size-, morphology-, and concentration-dependent responses of multiple antioxidant defense biomarkers, in soil-grown soybean (Glycine maxcv. Kowsar) during its lifecycle. To this end, we synthesized three types of morphologically unique ZnONPs (spherical/ 38nm, floral-like/ 59nm, and rod-like/ >500nm); all with high purity, triclinic crystal structure and negative surface charge; and compared the toxicity with Zn2+ions. Each pot received two seeds, placed in soil inoculated with N-fixing bacteria (Rhizobium japonicum) and grown outdoor for 120 days. Our findings demonstrated a significant particle size-, morphology-, and concentration-dependent influence of ZnONPs on seed yield, lipid peroxidation, and various antioxidant biomarkers in soybean. Our spherical 38nm ZnONPs were the most protective compared to the floral-like 59nm ZnONPs, rod-like >500nm ZnONPs, and Zn2+ions, particularly up to 160 mg/kg. However, at the highest concentration of 400 mg/kg, spherical 38nm ZnONPs elicited the highest oxidative stress responses (H2O2synthesis, MDA, SOD, CAT, POX) in soybean compared to the other two morphologically different ZnONPs tested. The concentrationresponse curves for the three types of ZnONPs and Zn2+ions were nonlinear (nonmonotonous) for all the endpoints evaluated. The results also suggest differential nano-specific toxicity of ZnONPs compared to ionic Zn2+toxicity in soybean. Our higher NOAEL value of 160 mg/kg indicates the potential for ZnONPs to be used as a nanofertilizer for crops grown in Zn-deficient soils to improve crop yield, food quality and address malnutrition, globally.HighlightsParticle size-, morphology-, and concentration-dependent effects of ZnONPs tested.All Zn compounds (ZnONPs, Zn2+) promoted seed yield up to 160 mg/kg.Spherical 38nm ZnONPs elicited the least oxidative stress, except at 400 mg/kg.Concentration-response curves for all Zn compounds were non-linear.ZnONPs may serve as nanofertilizer for enriching Zn-deficit soil with Zn.Abstract FigureTOC Art
Specific PIP2Binding Promotes Calcium Activation of TMEM16A Chloride Channels
Authors: Jia Zhiguang , Chen Jianhan 
Published: April 2020

AbstractTMEM16A is a widely expressed Ca2+-activated Cl-channel that regulates crucial physiological functions including fluid secretion, neuronal excitability, and smooth muscle contraction. There is a critical need to understand the molecular mechanisms of TMEM16A gating and regulation. However, high-resolution TMEM16A structures have failed to reveal an activated state with unobstructed permeation pathway even with saturating Ca2+. This has been attributed to the requirement of PIP2for preventing TMEM16A desensitization. Here, we show that specific binding PIP2to TMEM16A can lead to spontaneous opening of the permeation pathway in the Ca2+-bound state. The predicted activated state is highly consistent with a wide range of mutagenesis and functional data. It yields a maximal Cl-conductance of ~1 pS, similar to experimental estimates, and recapitulates the selectivity of larger SCN-over Cl-. The resulting molecular mechanism of activation provides a basis for understanding the interplay of multiple signals in controlling TMEM16A channel function.
Synaptotagmin-7 participates in the regulation of acetylcholine release and short-term presynaptic facilitation in splanchnic nerve terminals
Authors: Caballero-Florán René N. , Bendahmane Mounir , Philippe Julie M. , Morales Alina , Anantharam Arun , Jenkins Paul M. 
Published: April 2020

AbstractDisturbances that threaten homeostasis elicit activation of the sympathetic nervous system (SNS) and the adrenal medulla. The effectors discharge as a unit to drive global and immediate changes in whole-body physiology. Descending sympathetic information is conveyed to the adrenal medulla via preganglionic splanchnic fibers. These fibers pass into the gland and synapse onto chromaffin cells, which synthesize, store, and secrete catecholamines and vasoactive peptides. While the importance of the sympatho-adrenal branch of the autonomic nervous system has been appreciated for many decades, the mechanisms underlying transmission between presynaptic splanchnic neurons and postsynaptic chromaffin cells have remained obscure. In contrast to chromaffin cells, which have enjoyed sustained attention as a model system for exocytosis, even the Ca2+sensors that are expressed within splanchnic terminals have not yet been identified. This study shows that a ubiquitous Ca2+-binding protein, synaptotagmin-7 (Syt7), is expressed within the fibers that innervate the adrenal medulla, and that its absence can alter synaptic transmission in the preganglionic terminals of chromaffin cells. The prevailing impact in presynapses that lack Syt7 is a decrease in synaptic strength and neuronal short-term plasticity. Evoked excitatory postsynaptic currents (EPSCs) in Syt7 KO preganglionic terminals are smaller in amplitude than in wild-type synapses stimulated in an identical manner. Splanchnic inputs also display robust short-term presynaptic facilitation, which is compromised in the absence of Syt7. These data reveal, for the first time, a role for any synaptotagmin at the splanchnic-chromaffin cell synapse. They also suggest that Syt7 has actions at synaptic terminals that are conserved across central and peripheral branches of the nervous system.
Proteogenomic Analysis of Pancreatic Cancer Subtypes
Authors: Kafita Doris , Nkhoma Panji , Zulu Mildred , Sinkala Musalula 
Published: April 2020

AbstractPancreatic cancer remains a significant public health problem with an ever-rising incidence of disease. Cancers of the pancreas are characterised by various molecular aberrations, including changes in the proteomics and genomics landscape of the tumour cells. There is a need, therefore, to identify the proteomic landscape of pancreatic cancer and the specific genomic and molecular alterations associated with disease subtypes. Here, we carry out an integrative bioinformatics analysis of The Cancer Genome Atlas dataset that includes proteomics and whole-exome sequencing data collected from pancreatic cancer patients. We apply unsupervised clustering on the proteomics dataset to reveal the two distinct subtypes of pancreatic cancer. Using functional and pathway analysis, we demonstrate the different molecular processes and signalling aberrations of the pancreatic cancer subtypes. We explore the clinical characteristic of these subtypes to show differences in disease outcome. Using datasets of mutations and copy number alterations, we show that various signalling pathways are altered among pancreatic tumours, including the Wnt pathway, Notch pathway and PI3K-mTOR pathways. Altogether, we reveal the proteogenomic landscape of pancreatic cancer subtypes and the altered molecular processes which can be leveraged to devise more effective treatments.
Analysis of FGF20-regulated genes in organ of Corti progenitors by translating ribosome affinity purification
Authors: Yang Lu M. , Stout Lisa , Rauchman Michael , Ornitz David M. 
Published: April 2020

ABSTRACTBackgroundUnderstanding the mechanisms that regulate hair cell (HC) differentiation in the organ of Corti (OC) is essential to designing genetic therapies for hearing loss due to HC loss or damage. We have previously identified Fibroblast Growth Factor 20 (FGF20) as having a key role in HC and supporting cell differentiation in the mouse OC. To investigate the genetic landscape regulated by FGF20 signaling in OC progenitors, we employ Translating Ribosome Affinity Purification combined with Next Generation mRNA Sequencing (TRAPseq) in theFgf20lineage.ResultsWe show that TRAPseq targeting OC progenitors effectively enriched for mRNA within this rare cell population. TRAPseq identified differentially expressed genes downstream of FGF20, includingEtv4, Etv5, Etv1, Dusp6, Hey1, Hey2, Heyl, Tectb, Fat3, Cpxm2, Sall1, Sall3, and cell cycle regulators such asCdc20. Analysis ofCdc20conditional-null mice identified decreased cochlea length, while analysis ofSall1-ΔZn2-10mice, which harbor a mutation that causes Townes-Brocks syndrome, identified a decrease in outer hair cell number.ConclusionsWe present two datasets: genes with enriched expression in OC progenitors, and genes regulated by FGF20 in the embryonic day 14.5 cochlea. We validate select differentially expressed genes via in situ hybridization and in vivo functional studies in mice.Key findingsTranslating Ribosome Affinity Purification (TRAP) with Fgf20-Cre enriches for prosensory cell mRNATRAP combined with RNAseq identifies genes downstream of FGF20 during prosensory cell differentiationFGF20 regulates Sall1, gene implicated in human sensorineural hearing lossGrant Sponsor and NumberNational Institute on Deafness and Other Communication Disorders – DC017042 (DMO) Washington University Institute of Clinical and Translational Sciences and National Center for Advancing Translational Sciences – CTSA grant UL1TR002345 (JIT471 to DMO) March of Dimes – 6-FY13-127 (MR)
Insulin promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10
Authors: Brumfield Alexandria , Chaudhary Natasha , Molle Dorothee , Wen Jennifer , Graumann Johannes , McGraw Timothy E. 
Published: April 2020

ABSTRACTInsulin controls glucose uptake into muscle and fat cells by inducing a net redistribution of GLUT4 from intracellular storage to the plasma membrane (PM). The TBC1D4-RAB10 signaling module is required for insulin-stimulated GLUT4 translocation to the PM, although where it intersects GLUT4 traffic was unknown. Here we demonstrate that TBC1D4-RAB10 functions to control GLUT4 mobilization from a Trans Golgi Network (TGN) storage compartment, establishing that insulin, in addition to regulating the PM proximal effects of GLUT4-containing vesicles docking to and fusion with the PM, also directly regulates the behavior of GLUT4 deeper within the cell. We also show that GLUT4 is retained in an element/domain of the TGN from which newly synthesized lysosomal proteins are targeted to the late endosomes and the ATP7A copper transporter is translocated to the PM by elevated copper. Insulin does not mobilize ATP7A nor does copper mobilize GLUT4. Consequently, GLUT4 intracellular sequestration and mobilization by insulin is achieved, in part, through utilizing a region of the TGN devoted to specialized cargo transport in general rather than being specific for GLUT4. Our results define GLUT4-containing region of the TGN as a sorting and storage site from which different cargo are mobilized by distinct signals.
Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations
Authors: Bury Leah , Moodie Brittania , McKay Liliana S. , Miga Karen H. , Cheeseman Iain M. 
Published: April 2020

AbstractCentromeres play a fundamental role in chromosome segregation. Although originally thought to be silent chromosomal regions, centromeres are actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA smFISH foci fluctuate in their levels over the cell cycle and do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Our results demonstrate that alpha-satellite expression occurs through RNA Polymerase II-dependent transcription, but does not require centromere proteins and other cell division components. Instead, our work implicates centromere-nucleolar associations as the major factor regulating alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels, explaining variations in alpha-satellite RNA between cell lines. In addition, alpha-satellite transcript levels increase substantially when the nucleolus is disrupted. Together, our results are inconsistent with a direct, physical role for alpha-satellite transcripts in cell division processes, and instead support a role for ongoing transcription in promoting centromere chromatin dynamics. The control of alpha-satellite transcription by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.
Discussion of (dis)aggregated earnings guidance and acquisition financing
Authors: Zhang Joseph H. 
Published: April 2020

PurposeThe author discusses the paper by Ordyna (2020) and suggests a few areas for improvement. First, the author could think more about the financing scheme of the acquisition including hybrid debt securities. Second, the author could consider forecast reputation, the timing and frequency of earnings guidance. Third, the author may consider the difference-in-differences research design and identification strategy. Other model designs, robustness checks and alternative measures of key variables are discussed.
“Yes Madam”: digitized services right here and right now
Authors: Singh Shikha , Mittal Shweta 
Published: April 2020

Learning outcomes
The case helps to understand: the working mechanisms of a digitized salon service, with a focus on the lower- and middle-income strata. The changing scenario of the service marketing model, with the growth in digital service models. To investigate the organisational challenges of a digitally facilitated/based start-up and find solutions to overcome the challenges.

Case overview/synopsis
“Yes Madam”-salon at home was a business enterprise, providing beauty and wellness services at the doorstep through a mobile application and web-based platform. The case describes the reason for opening the doorstep beauty services, its revenue model and aims to provide quality services to lower- and middle-income strata. The case will help students to understand the working mechanism of digitized salon services and associated challenges; prominent ones being attracting, selecting and retaining the beauticians and providing the standardised services. The case has examined the low-price services for the consumers delivered by the company. The case also discussed their plans for diversification and penetration into the untapped markets.

Complexity academic level
Graduates and postgraduates.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.
An examination of the effects of outsourcing ticket sales force management
Authors: Popp Nels , Jensen Jonathan A. , McEvoy Chad D. , Weiner James F. 
Published: April 2020

PurposeThe purpose of the study is to ascertain whether sport organizations which outsource ticket sales force management outperform sports organizations which manage their ticket sales force internally, relative to ticket revenue and attendance.Design/methodology/approachThirteen years of ticket revenue and football attendance data were collected for National Collegiate Athletic Association (NCAA) Football bowl subdivision (FBS) Division I Athletics Departments (n = 126), as well as data on whether the organization employed an external (outsourced), internal or no ticket sales force. The number of salespeople employed was also captured. Within-subjects, fixed effects regression models, which included several control variables such as number of home contests, prior season attendance, team success and population, were run to assess the relationship between sales force type and both ticket revenue and attendance, for one year, two years and three years after sales force establishment.FindingsAll models were significant. While both internally managed ticket sales forces and those managed by outsourced firms saw significant increases in ticket revenue (compared to not employing a sales force), internally managed departments outperformed third parties. In addition, departments utilizing outsourcing companies reported lower attendance for the first two years after outsourcing, but attendance differences were negligible by the third year of outsourcing.Practical implicationsThe results of the study provide data to help sport managers determine whether outsourcing sales functions within an organization will lead to greater ticket revenue and/or attendance.Originality/valueWhile several sport management studies have examined the decision-making process of outsourcing organizational functions, no prior studies have examined the financial implications of doing so.