bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macromolecular crowding by hyaluronan: implications for binding reactions in the pericellular matrix and at the cell surface
Authors: Fernig David G. 
Published: January 2024

AbstractIn common with many glycosaminoglycan binding growth factors, the interactions of fibroblast growth factor-2 (FGF-2) with heparin/heparan sulfate regulate its biological activity. Consequently, much effort has been expended in characterising growth factor-glycoaminoglycan interactions. Many experiments are performedin vitroin dilute solution. However, the cell surface is an extremely crowded environment. We have, therefore, examined the parameters of FGF-2 binding to a heparin-derived tetradecasaccharide in the presence of two different crowding agents, dextran, a commonly used crowding agent, as well as hyaluronan (HA), which is normally present at the cell surface. The heparin tetradecassaccaride was immobilised through its reducing end onto a biosensor surface and the crowding agents were used in solution. The results show that the observed on-rate rate of association (kon) decreased over two-fold with increasing concentrations of both crowding agents. The slope of initial rate of association similarly decreased, indicating that as the solution became more crowded the diffusion of FGF-2 becomes increasingly limited. One thousand kDa HA was shown to be the most effective crowding agent, as diffusion became limited at concentrations above 0.5 mg/ml, compared to 1 mg/ml and 10 mg/ml for 100kDa HA and dextran, respectively. Such concentrations of hyaluronan are readily found extracellularly. The results, therefore, suggest that the effect of crowding at the cell surface and in the extracellular matrix may play an important role in governing the interactions of at least FGF-2 with its heparan sulfate co-receptor.
Complementation testing identifies causal genes at quantitative trait loci underlying fear related behavior
Authors: Chen Patrick B. , Chen Rachel , LaPierre Nathan , Chen Zeyuan , Mefford Joel , Marcus Emilie , Heffel Matthew G. , Soto Daniela C. , Ernst Jason , Luo Chongyuan , Flint Jonathan 
Published: January 2024

ABSTRACTKnowing the genes involved in quantitative traits provides a critical entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. Here we address a key step towards that goal by deploying a test that directly queries whether a gene mediates the effect of a quantitative trait locus (QTL). To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six QTLs, and identified six genes. Four genes,Lsamp, Ptprd, Nptx2andSh3gl,have known roles in synapse function; the fifth gene,Psip1,is a transcriptional co-activator not previously implicated in behavior; the sixth is a long non-coding RNA4933413L06Rikwith no known function. Single nucleus transcriptomic and epigenetic analyses implicated excitatory neurons as likely mediating the genetic effects. Surprisingly, variation in transcriptome and epigenetic modalities between inbred strains occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results open a bottleneck in using genetic mapping of QTLs to find novel biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.
Synaptic Proteomes of Cortical Interneuron Classes Revealed by Antibody Directed Proximity Labeling
Authors: Battison Alexandria S. , Liddle Jennifer C. , Sumsky Stefan L. , O’Connell Christopher B. , Balsbaugh Jeremy L. , LoTurco Joseph J. 
Published: January 2024

AbstractSubtypes of inhibitory interneurons play diverse roles within neural circuits in cerebral cortex. Defining the molecular underpinnings of interneuron functions within cortical circuits will require identification of interneuron synaptic proteomes. In this study, we first combined genetically directed expression of tdTomato-synaptophysin with antibody-directed proximity labeling and tandem mass spectrometry to identify synaptic proteomes of three major interneuron classes in mouse cortex: parvalbumin (PV), somatostatin (SS), and vasoactive intestinal peptide (VIP).After stringent filtering we identified 581 proteins: 228 identified in all cell classes and 353 in one or two of three classes. The PV class had the largest number of uniquely identified proteins (141), followed by VIP (30) and SST (20). Consistent with previously reported electrophysiological evidence, PV presynaptic proteomes were enriched for NMDA receptor subunits and scaffolding proteins. We used antibodies against synaptotagmin 2 (Syt2), a presynaptic protein present at PV synapses, to confirm NMDAR localization, and to find that the mu-opioid receptor agonist buprenorphine rapidly caused reorganization of the PV presynaptic proteome. Overall, our results reveal proteomes of PV, SST, and VIP interneurons in cortex that likely underlie distinct and dynamic interneuron synaptic properties.
A PACAP-activated network for secretion requires coordination of Ca2+influx and Ca2+mobilization
Authors: Chen Xiaohuan , Bell Nicole A. , Coffman Breanna L. , Rabino Agustin A. , Garcia-Mata Rafael , Kammermeier Paul J. , Yule David I. , Axelrod Daniel , Smrcka Alan V. , Giovannucci David R. , Anantharam Arun 
Published: January 2024

AbstractChromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for coupling cell stimulation to secretion are acetylcholine and pituitary adenylate activating polypeptide (PACAP). In contrast to acetylcholine, PACAP evokes a persistent secretory response from chromaffin cells. However, the mechanisms by which PACAP acts are poorly understood. Here, it is shown that PACAP induces sustained increases in cytosolic Ca2+which are disrupted when Ca2+influx through L-type channels is blocked or internal Ca2+stores are depleted. PACAP liberates stored Ca2+via inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER), thereby functionally coupling Ca2+mobilization to Ca2+influx and supporting Ca2+-induced Ca2+-release. These Ca2+influx and mobilization pathways are unified by an absolute dependence on phospholipase C epsilon (PLCε) activity. Thus, the persistent secretory response that is a defining feature of PACAP activity,in situ, is regulated by a signaling network that promotes sustained elevations in intracellular Ca2+through multiple pathways.
Standardized Parts for Activation of Small GTPase Signaling in Living Cells
Authors: He Yuchen , Faulkner Benjamin M. , Roberti Meaghan A. , Bassford Dana K. , Stains Cliff I. 
Published: January 2024

AbstractSmall GTPases comprise a superfamily of over 167 proteins in the human genome and are critical regulators of a variety of pathways including cell migration and proliferation. Despite the importance of these proteins in cell signaling, a standardized approach for controlling small GTPase activation within living cells is lacking. Herein, we report a split-protein-based approach to directly activate small GTPase signaling in living cells. Importantly, our fragmentation site can be applied across the small GTPase superfamily. We highlight the utility of these standardized parts by demonstrating the ability to directly modulate the activity of four different small GTPases with user-defined inputs, providing a plug and play system for direct activation of small GTPases in living cells.
Reinforcement Expectation in the Honey Bee (Apis mellifera): Can Downshifts in Reinforcement Show Conditioned Inhibition?
Authors: Mahoney Shawn , Hosler Jay , Smith Brian H 
Published: January 2024

ABSTRACTWhen animals learn the association of a Conditioned Stimulus with an Unconditioned Stimulus, later presentation of the CS invokes a representation of the US. When the expected US fails to occur, theoretical accounts predict that conditioned inhibition can accrue to any other stimuli that are associated with this change in the US. Empirical work with mammals has confirmed the existence of conditioned inhibition. But the way it is manifested, the conditions that produce it, and determining whether it is the opposite of excitatory conditioning, are important considerations. Invertebrates can make valuable contributions to this literature because of the well-established conditioning protocols and access to the central nervous system for studying neural underpinnings of behavior. Nevertheless, while conditioned inhibition has been reported, it has yet to be thoroughly investigated in invertebrates. Here we evaluate the role of the unconditioned stimulus (US) in producing conditioned inhibition by using Proboscis Extension Response conditioning of the honey bee (Apis mellifera). Specifically, using variations of a ‘feature-negative’ experimental design, we employ downshifts in US intensity relative to US intensity used during initial excitatory conditioning, to show that an odorant in an odor-odor mixture can become a conditioned inhibitor. We argue that some alternative interpretations to conditioned inhibition are unlikely. However, we show variation across individuals in how strongly they show Conditioned Inhibition, with some individuals possibly revealing a different means of learning about changes in reinforcement. We discuss how resolution of these differences is needed to fully understand whether and how Conditioned Inhibition is manifested in the honey bee, and whether it can be extended to investigate how it is encoded in the CNS. It is also important for extension to other insect models. In particular, work like this will be important as more is revealed of the complexity of the insect brain from connectome projects.
Fas2EB112: A Tale of Two Chromosomes
Authors: Finegan Tara M. , Cammarota Christian , Andrade Oscar Mendoza , Garoutte Audrey M. , Bergstralh Dan T. 
Published: January 2024

SummaryThe cell-cell adhesion molecule Fasciclin II (Fas2) has long been studied for its evolutionarily-conserved role in axon guidance. It is also expressed in the follicular epithelium, where together with a similar protein, Neuroglian (Nrg), it helps to drive the reintegration of cells born out of the tissue plane. Remarkably, one Fas2 protein null allele,Fas2G0336, demonstrates a mild reintegration phenotype, whereas work with the classic null alleleFas2EB112showed more severe epithelial disorganization. These observations raise the question of which allele (if either) causes abona fideloss of Fas2 protein function. The problem is not only relevant to reintegration but fundamentally important to understanding what this protein does and how it works:Fas2EB112has been used in at least 37 research articles, andFas2G0336in at least three. An obvious solution is that one of the two chromosomes carries a modifier that either suppresses (Fas2G0336) or enhances (Fas2EB112) phenotypic severity. We find not only the latter to be the case, but identify the enhancing mutation asNrg14, also a classic null allele.
A Genome-Wide CRISPR Screen Identifies Sortilin as the Receptor Responsible for Galectin-1 Lysosomal Trafficking
Authors: Donnelly Justin , Kamber Roarke A. , Wisnovsky Simon , Roberts David S. , Peltan Egan L. , Bassik Michael C. , Bertozzi Carolyn R. 
Published: January 2024

AbstractGalectins are a family of mammalian glycan-binding proteins that have been implicated as regulators of myriad cellular processes including cell migration, apoptosis, and immune modulation. Several members of this family, such as galectin-1, exhibit both cell-surface and intracellular functions. Interestingly, galectin-1 can be found in the endomembrane system, nucleus, or cytosol, as well as on the cell surface. The mechanisms by which galectin-1 traffics between cellular compartments, including its unconventional secretion and internalization processes, are poorly understood. Here, we determined the pathways by which exogenous galectin-1 enters cells and explored its capacity as a delivery vehicle for protein and siRNA therapeutics. We used a galectin-1-toxin conjugate, modelled on antibody-drug conjugates, as a selection tool in a genome-wide CRISPR screen. We discovered that galectin-1 interacts with the endosome-lysosome trafficking receptor sortilin in a glycan-dependent manner, which regulates galectin-1 trafficking to the lysosome. Further, we show that this pathway can be exploited for delivery of a functional siRNA. This study sheds light on the mechanisms by which galectin-1 is internalized by cells and suggests a new strategy for intracellular drug delivery via galectin-1 conjugation.
Multi-omic characterization of allele-specific regulatory variation in hybrid pigs
Authors: Quan Jianping , Yang Ming , Wang Xingwang , Cai Gengyuan , Ding Rongrong , Zhuang Zhanwei , Zhou Shenping , Tan Suxu , Ruan Donglin , Wu Jiajing , Zheng Enqin , Zhang Zebin , Liu Langqing , Meng Fanming , Wu Jie , Xu Cineng , Qiu Yibin , Wang Shiyuan , Lin Meng , Li Shaoyun , Ye Yong , Zhou Fuchen , Lin Danyang , Li Xuehua , Deng Shaoxiong , Zhang Yuling , Yao Zekai , Gao Xin , Yang Yingshan , Liu Yiyi , Zhan Yuexin , Liu Zhihong , Zhang Jiaming , Ma Fucai , Yang Jifei , Chen Qiaoer , Yang Jisheng , Ye Jian , Dong Linsong , Gu Ting , Huang Sixiu , Xu Zheng , Li Zicong , Yang Jie , Huang Wen , Wu Zhenfang 
Published: January 2024

AbstractGenetic variation in the regulation of gene expression contributes substantially to phenotypic variation. Understanding how variation in DNA sequences and epigentic modifications leads to gene expression variation remains a challenging task. In hybrid animals where cellular environments are homogeneous, differences between the expression of paternal and maternal alleles must be due tocissequence or epigenic differences. Therefore, hybrid mapping is a powerful approach to efficiently identify and characterize genes under regulation through mechanisms incis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we performed a comprehensive multi-omic characterization of regulatory variation across brain, liver, muscle, and placenta in four developmental stages. We produced one of the largest multi-omic datasets to date in pigs, including 16 whole genome sequenced genomes, 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We developed a novel read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We showed that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identified 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. By integrating methylation, chromatin accessibility, and gene expression data, many of these allele specific expression can be explained by allele specific methylation and/or chromatin accessibility. This study provides one of the most comprehensive characterizations of regulatory variation across multiple tissues and developmental stages in pigs and offers new opportunity of genetic improvement for this important food animal species.
Normal and Aberrant Cell Cycles Characterized by a Continuous-Time Stochastic Boolean Model of Cell Cycle Regulation in Budding Yeast
Authors: Taoma Kittisak , Tyson John J. , Laomettachit Teeraphan , Kraikivski Pavel 
Published: January 2024

AbstractThe cell cycle of budding yeast is governed by an intricate protein regulatory network whose dysregulation can lead to lethal mistakes or aberrant cell division cycles. In this work, we model this network in a Boolean framework for stochastic simulations. Our model is sufficiently detailed to account for the phenotypes of 41 mutant yeast strains (85% of the experimentally characterized strains that we simulated) and also to simulate an endoreplicating strain (multiple rounds of DNA synthesis without mitosis) and a strain that exhibits ‘Cdc14 endocycles’ (periodic transitions between metaphase and anaphase). Because our model successfully replicates the observed properties of both wild-type yeast cells and many mutant strains, it provides a reasonable, validated starting point for more comprehensive stochastic-Boolean models of cell cycle controls. Such models may provide a better understanding of cell cycle anomalies in budding yeast and ultimately in mammalian cells.
Microvilli regulate the release modes of alpha-tectorin to organize the domain-specific matrix architecture of the tectorial membrane
Authors: Niazi Ava , Kim Ju Ang , Kim Dong-Kyu , Lu Di , Sterin Igal , Park Joosang , Park Sungjin 
Published: January 2024

AbstractThe tectorial membrane (TM) is an apical extracellular matrix (ECM) in the cochlea essential for auditory transduction. The TM exhibits highly ordered domain-specific architecture. Alpha-tectorin/TECTA is a glycosylphosphatidylinositol (GPI)-anchored ECM protein essential for TM organization. Here, we identified that TECTA is released by distinct modes: proteolytic shedding by TMPRSS2 and GPI-anchor-dependent release from the microvillus tip. In the medial/limbal domain, proteolytically shed TECTA forms dense fibers. In the lateral/body domain produced by the supporting cells displaying dense microvilli, the proteolytic shedding restricts TECTA to the microvillus tip and compartmentalizes the collagen-binding site. The tip-localized TECTA, in turn, is released in a GPI-anchor-dependent manner to form collagen-crosslinking fibers, required for maintaining the spacing and parallel organization of collagen fibrils. Overall, we showed that distinct release modes of TECTA determine the domain-specific organization pattern, and the microvillus coordinates the release modes along its membrane to organize the higher-order ECM architecture.Abstract FigureGraphical Abstract
Does state-led urbanization come at the cost of agriculture? Evidence from China
Authors: Liu Wenhua , He Zekai , Wang Qi 
Published: January 2024

PurposeThis paper explores the relationship between state-led urbanization and primary industry development using the difference-in-differences (DiD) method.Design/methodology/approachThe study uses the DiD method.FindingsExploiting county-city mergers during 2010–2018, the key strategy to expand the city outward and promote urbanization on the urban fringe by local government, the authors find that county-city mergers led to the growth of primary industry decline by 4.23%. The result can be explained by the loss of essential production factors, including land and labor used for farming. In addition, the negative effect is more pronounced for counties with more substantial manufacturing. The results indicate that urbanization in China relocates land and labor; however, it does not improve the efficiency of agricultural output.Originality/valueThis paper contributes to the understanding of urbanization and rural development from the perspective of the primary industry by showing production factor redistribution. Second, this study complements the literature on local government mergers.
Harnessing digital power for relevance: status of digital transformation in selected university libraries in Uganda
Authors: Nakaziba Sarah , Ngulube Patrick 
Published: January 2024

Purpose
This study aims to assess the extent to which Uganda university libraries have implemented digital transformation technologies and to determine the facilitators and barriers affecting the implementation of digital transformation in selected university libraries in Uganda.

Design/methodology/approach
This study used a convergent parallel mixed methods design. It was conducted in six selected university libraries in Uganda, which were in three private and three public universities. The study sample included 103 librarians with a minimum qualification of a bachelor’s degree and six library directors.

Findings
The findings indicated that there was an average (n = 37, 48.7%) implementation of digital transformation in the selected university libraries in Uganda. Some of the barriers hindering digital transformation included inadequate funding, lack of awareness of digital technologies, inadequate ICT skills, insufficient ICT infrastructure and limited staff among others. There is a need for library management to provide support in the form of funds, policies and human resources to implement such digital transformation.

Research limitations/implications
The criteria for choosing universities were those that have been around for at least 10 years. The reason for this was that it was assumed that these universities would have well-established staff development programmes and procedures as well as be likely to have incorporated technology into their services, including libraries. This study’s limitations stem from the fact that this criterion for selection might not apply to all Ugandan university libraries, particularly those that are less than 10 years old and may not have been well represented in this study.

Originality/value
The magnitude of the problem of digital transformation in university libraries in Uganda is unclear because of the limited research available in the Uganda library and information science field. This study presents the status of digital transformation in Uganda university libraries.
Shearling: tackling competition
Authors: Ghosh Dastidar Surajit , Das Manoj , Priyadarshini Shabnam 
Published: January 2024

Learning outcomes
After completion of the case study, students will be able to analyze the marketing mix strategy of a firm, discuss the importance of a generic strategy to gain a competitive advantage, analyze the basis of consumer segmentation in furniture and highlight the importance of positioning in influencing the overall marketing mix strategy of a firm.

Case overview/synopsis
It was April 18, 2022. Puneet Singh Seehra (Seehra), the owner and director of Shearling Skins Private Limited (Shearling), was visibly worried as he was looking at the recent sales report. Shearling was in the business of manufacturing premium-quality furniture for corporate clients. Seehra was happy about the growth of his company. However, he was lately concerned about the declining sales figures. Some important questions were troubling Seehra. Was competition eating into his business? How could he differentiate Shearling from competition? What was the right marketing strategy for a market dominated by unorganized competitors and a few major players? His head spinning, he leaned back on his chair as he looked out of his office window.

Complexity academic level
The case study can be taught in a graduate-level course in marketing or strategy.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS: 8 Marketing