bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence-based GWAS in 180 000 German Holstein cattle reveals new candidate genes for milk production traits
Authors: Križanac Ana-Marija , Reimer Christian , Heise Johannes , Liu Zengting , Pryce Jennie , Bennewitz Jörn , Thaller Georg , Falker-Gieske Clemens , Tetens Jens 
Published: December 2023

AbstractBackgroundThe use of genome-wide association studies (GWAS) has led to the identification of numerous quantitative trait loci and candidate genes in dairy cattle. To obtain sufficient power of GWAS and to identify quantitative trait nucleotides, whole-genome sequence data is required. Sequence data facilitates the identification of potential causal variants; however, sequencing of whole genomes is still expensive for a large number of animals. Imputation is a quick and efficient way of obtaining sequence data from large datasets. Milk production traits are complex and influenced by many genetic and environmental factors. Although extensive research has been performed for these traits, with many associations unveiled thus far, due to their crucial economic importance, complex genetic architecture, and the fact that causative variants in cattle are still scarce, there is a need for a better understanding of their genetic background. In this study, we aimed to identify new candidate loci associated with milk production traits in German Holstein cattle, the most important dairy breed in Germany and worldwide. For that purpose, 252,285 cattle were imputed to the sequence level and large-scale GWAS was carried out to identify new association signals.ResultsWe confirmed many known and identified 30 previously unreported candidate genes for milk, fat, and protein yield. While all of the genes were functionally associated with the traits, some showed pleiotropic effects as well. Specifically, association with mammary gland development, fatty acid synthesis, metabolism of lipids, or milk production QTLs in other farm animals has been reported. Variants associated with these genes explained a large percentage of genetic variance, compared to random ones.ConclusionsOur findings proved the power of large samples and sequence-based GWAS in detecting new association signals. In order to fully exploit the power of GWAS, one should aim at very large samples combined with whole-genome sequence data. Although milk production traits in cattle are comprehensively researched, the genetic background of these traits is still not fully understood, with the potential for many new associations to be revealed, as shown in our study. With constantly growing sample sizes, we expect more insights into the genetic architecture of production traits in the future.
Rapid Vacuolar Sorting of the Borate Transporter BOR1 Requires the Adaptor Protein Complex AP-4 in Arabidopsis
Authors: Yoshinari Akira , Shimizu Yutaro , Hosokawa Takuya , Nakano Akihiko , Uemura Tomohiro , Takano Junpei 
Published: December 2023

AbstractPlants maintain nutrient homeostasis by controlling the activities and abundance of nutrient transporters. InArabidopsis thaliana, the borate (B) transporter BOR1 plays a role in the efficient translocation of B under low-B conditions. BOR1 undergoes polyubiquitination in the presence of sufficient B and is then transported to the vacuole via multivesicular bodies (MVBs) to prevent B accumulation in tissues at a toxic level. A previous study indicated that BOR1 physically interacts with μ subunits of adaptor protein complexes AP-3 and AP-4, both involved in vacuolar sorting pathways. In this study, we investigated the roles of AP-3 and AP-4 subunits in BOR1 trafficking in Arabidopsis. The lack of AP-3 subunits did not affect either vacuolar sorting or polar localization of BOR1-GFP, whereas the absence of AP-4 subunits resulted in a delay in high-B-induced vacuolar sorting without affecting polar localization. Super-resolution microscopy revealed a rapid sorting of BOR1-GFP into AP-4-positive spots in thetrans-Golgi network (TGN) upon high-B supply. These results indicate that AP-4 is involved in sequestration of ubiquitinated BOR1 into a TGN-specific subdomain “vacuolar-trafficking zone,” and is required for efficient sorting to MVB and vacuole. Our findings elucidate the rapid vacuolar sorting process facilitated by AP-4 in plant nutrient transporters.Subject areas(7) Membrane and transport
Oligodendrocyte-specific expression ofPSG8-AS1suggests a role in myelination with prognostic value in oligodendroglioma
Authors: de los Angeles Becerra Rodriguez Maria , Gonzalez Muñoz Elena , Moore Tom 
Published: December 2023

AbstractThe segmentally duplicated Pregnancy-specific glycoprotein (PSG) locus on chromosome 19q13 may be one of the most rapidly evolving in the human genome. It comprises ten coding genes (PSG1-9, 11) and one predominantly non-coding gene (PSG10) that are expressed in the placenta and gut, in addition to several poorly characterized long non-coding RNAs. We report that long non-coding RNAPSG8-AS1has an oligodendrocyte-specific expression pattern and is co-expressed with genes encoding key myelin constituents.PSG8-AS1exhibits two peaks of expression during human brain development coinciding with the most active periods of oligodendrogenesis and myelination.PSG8-AS1orthologs were found in the genomes of several primates but significant expression was found only in the human, suggesting a recent evolutionary origin of its proposed role in myelination. Additionally, because co-deletion of chromosomes 1p/19q is a genomic marker of oligodendroglioma, expression ofPSG8-AS1was examined in these tumors.PSG8-AS1may be a promising diagnostic biomarker for glioma, with prognostic value in oligodendroglioma.
Circuit dynamics of superficial and deep CA1 pyramidal cells and inhibitory cells in freely-moving macaques
Authors: Abbaspoor S. , Hoffman K.L. 
Published: December 2023

AbstractDiverse neuron classes in hippocampal CA1 have been identified through the heterogeneity of their cellular/molecular composition. How these classes relate to hippocampal function and the network dynamics that support cognition in primates remains unclear. Here we report inhibitory functional cell groups in CA1 of freely-moving macaques whose diverse response profiles to network states and each other suggest distinct and specific roles in the functional microcircuit of CA1. In addition, pyramidal cells that were segregated into superficial and deep layers differed in firing rate, burstiness, and sharp-wave ripple-associated firing. They also showed strata-specific spike-timing interactions with inhibitory cell groups, suggestive of segregated neural populations. Furthermore, ensemble recordings revealed that cell assemblies were preferentially organized according to these strata. These results suggest sublayer-specific circuit organization in hippocampal CA1 of the freely-moving macaques that may underlie its role in cognition.
Single cell transcriptional changes across the blood stages of artemisinin resistant K13580YPlasmodium falciparumupon dihydroartemisinin exposure
Authors: Oduor Cliff I. , Connelly Sean V. , Cunningham Clark , Rustamzade Nazrin , Zuromski Jenna , Chin Deborah M. , Nixon Chris , Kurtis Jonathan , Juliano Jonathan J. , Bailey Jeffrey A 
Published: December 2023

ABSTRACTArtemisinins have been a cornerstone of malaria control, but resistance inPlasmodium falciparum, due to mutations in the Kelch13 (K13) protein, threaten these advances. Artemisinin exposure results in a dynamic transcriptional response across multiple pathways, but most work has focused on ring stages andex vivotranscriptional analysis. We applied single cell RNAseq to two unsynchronized coisogenic parasite lines (K13C580and K13580Y) over 6 hrs after a pulse exposure to dihydroartemisinin (DHA). Transcription was altered across all stages, with the greatest occurring at the trophozoite and ring stage in both lines. This response involved the arrest of metabolic processes, support for a dormancy phenomenon upon treatment, and the enhancement of protein trafficking and the unfolded protein response. While similar, the response was consistent across stages in K13580Y, with enhanced parasite survival to drug induced stress. Increased surface protein expression was seen in K13580Yparasites at baseline and upon drug exposure, highlighted by the increased expression ofPfEMP1andGARP,a potential therapeutic target. Antibody targeting GARP maintained anti-parasitic efficacy in K13580Yparasites. This work provides single cell insight of gene transcription across all life cycle stages revealing transcriptional changes that could initiate a dormancy state and mediate survival upon treatment.IMPORTANCESingle cell RNA sequencing allows deconvolution of the cellular stages of malaria and investigation of their response to treatment conditions. Utilizing two different genetic backgrounds of a key resistance marker to artemisinin treatment, we compared the response to dihydroartemisinin between these genetic backgrounds. We found a distinct transcriptional profile post treatment in both genetic backgrounds, with downregulation of metabolic process genes and upregulation of stress response genes. Comparing these two genetic backgrounds post treatment using traditional differential expression, and a novel computational method called MELD, we found consistent increased expression of GARP and pathogenesis related genes, likePfEMP1. This study identifies possible gene dependencies of parasite survival post artemisinin treatment, providing targets for inhibiting the dormancy state.
A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts
Authors: Johnson Ben , Iuliano Maria , Lam TuKiet , Biederer Thomas , De Camilli Pietro 
Published: December 2023

ABSTRACTJunctions between the ER and the plasma membrane (ER/PM junctions) are implicated in calcium homeostasis, non-vesicular lipid transfer and other cellular functions. Two ER proteins that function both as membrane tethers to the PM via a polybasic motif in their C-terminus and as phospholipid transporters are brain-enriched TMEM24 (C2CD2L) and its paralog C2CD2. Based on an unbiased proximity ligation analysis, we found that both proteins can also form a complex with band 4.1 family members, which in turn can bind a variety of plasma membrane proteins including cell adhesion molecules such as SynCAM 1. This complex results in the enrichment of TMEM24 and C2CD2 containing ER/PM junctions at sites of cell contacts. Dynamic properties of TMEM24-dependent ER/PM contacts are impacted when in complex as TMEM24 present at cell adjacent junctions is not shed by calcium rise, unlike TMEM24 at non-cell adjacent junctions. These findings suggest that cell-contact interactions control ER/PM junctions via TMEM24 complexes involving band 4.1 proteins.SUMMARYThe ER-anchored lipid transfer proteins TMEM24/C2CD2L and its paralog C2CD2 mediate formation of ER-plasma membrane junctions at sites of cell-cell contacts by interacting with band 4.1 family members and indirectly with cell adhesion proteins.
Neuropilin-1 is a co-receptor for Nerve Growth Factor-evoked pain
Authors: Peach Chloe J. , Tonello Raquel , Damo Elisa , Gomez Kimberly , Calderon-Rivera Aida , Bruni Renato , Bansia Harsh , Maile Laura , Manu Ana-Maria , Hahn Hyunggu , Thomsen Alex R.B. , Schmidt Brian L. , Davidson Steve , des Georges Amedee , Khanna Rajesh , Bunnett Nigel W. 
Published: December 2023

AbstractNerve growth factor (NGF) monoclonal antibodies inhibit chronic pain yet, failed to gain approval due to worsened joint damage in osteoarthritis patients. We report that neuropilin-1 (NRP1) is a co-receptor for NGF and tropomyosin-related kinase A (TrkA) pain signaling. NRP1 is coexpressed with TrkA in human and mouse nociceptors. NRP1 inhibitors suppress NGF-stimulated excitation of human and mouse nociceptors and NGF-evoked nociception in mice. NRP1 knockdown inhibits NGF/TrkA signaling, whereas NRP1 overexpression enhances signaling. NGF binds NRP1 with high affinity and interacts with and chaperones TrkA from the biosynthetic pathway to the plasma membrane and endosomes, enhancing TrkA signaling. Molecular modeling suggests that C-terminal R/KXXR/K NGF motif interacts with extracellular “b” NRP1 domain within a plasma membrane NGF/TrkA/NRP1 of 2:2:2 stoichiometry. G Alpha Interacting Protein C-terminus 1 (GIPC1) scaffolds NRP1 and TrkA to myosin VI and colocalizes in nociceptors with NRP1/TrkA. GIPC1 knockdown abrogates NGF-evoked excitation of nociceptors and pain-like behavior. NRP1 is a nociceptor-enriched co-receptor that facilitates NGF/TrkA pain signaling. NRP binds NGF and chaperones TrkA to the plasma membrane and signaling endosomes via the GIPC1 adaptor. NRP1 and GIPC1 antagonism in nociceptors offers a long-awaited non-opioid alternative to systemic antibody NGF sequestration for the treatment of chronic pain.SummaryNeuropilin-1 and G Alpha Interacting Protein C-terminus 1 are necessary for nerve growth factor-evoked pain and are non-opioid therapeutic targets for chronic pain.
Fluorescent tagging of endogenous IRS2 with an auxin-dependent degron to assess dynamic intracellular localization and function
Authors: Jo Minjeong , Lee Ji-Sun , Lero Michael W. , Morgan Jennifer S. , Shaw Leslie M. 
Published: December 2023

AbstractInsulin Receptor Substrate 2 (IRS2) is a signaling adaptor protein for the insulin (IR) and Insulin-like Growth Factor-1 (IGF-1R) receptors. In breast cancer, IRS2 contributes to both initiation of primary tumor growth and establishment of secondary metastases through regulation of cancer stem cell (CSC) function and invasion. However, how IRS2 mediates its diverse functions is not well understood. We used CRISPR/Cas9-mediated gene editing to modify endogenous IRS2 to study the expression, localization, and function of this adaptor protein. A cassette containing an auxin inducible degradation (AID) sequence, 3X-FLAG tag and mNeon-green was introduced at the N-terminus of the IRS2 gene to provide rapid and reversible control of IRS2 protein degradation and analysis of endogenous IRS2 expression and localization. Live fluorescence imaging of these cells revealed that IRS2 shuttles between the cytoplasm and nucleus in response to growth regulatory signals, and deletion of a putative nuclear export sequence in the C-terminal tail promotes nuclear retention of IRS2. Moreover, acute induction of IRS2 degradation reduces CSC function, similar to the constitutive knockout of IRS2. Our data highlight the value of our model of endogenously tagged IRS2 as a tool to elucidate IRS2 localization and function.
Diverse 3D cellular patterns underlie the development ofCardamine hirsutaandArabidopsis thalianaovules
Authors: Mody Tejasvinee Atul , Rolle Alexander , Stucki Nico , Roll Fabian , Bauer Ulrich , Schneitz Kay 
Published: December 2023

AbstractA fundamental question in biology is how organ morphogenesis comes about. The ovules ofArabidopsis thalianahave been established as a successful model to study numerous aspects of tissue morphogenesis; however, little is known regarding the relative contributions and dynamics of differential tissue and cellular growth and architecture in establishing ovule morphogenesis in different species. To address this issue, we generated a 3D digital atlas ofCardamine hirsutaovule development with full cellular resolution. We combined quantitative comparative morphometrics and topological analysis to explore similarities and differences in the 3D cellular architectures underlying ovule development of the two species. We discovered that they show diversity in the way the three radial cell layers of the primordium contribute to its growth, in the formation of a new cell layer in the inner integument and, in certain cases, in the topological properties of the 3D cell architectures of homologous tissues despite their similar shape. Our work demonstrates the power of comparative 3D cellular morphometry and the importance of internal tissues and their cellular architecture in organ morphogenesis.Summary StatementQuantitative morphometric comparison of 3D digital ovules at full cellular resolution reveals diversity in internal 3D cellular architectures between similarly shaped ovules ofCardamine hirsutaandArabidopsis thaliana.
The vestibulospinal nucleus is a locus of balance development
Authors: Hamling Kyla R. , Harmon Katherine , Kimura Yukiko , Higashijima Shin-ichi , Schoppik David 
Published: December 2023

ABSTRACTMature vertebrates maintain posture using vestibulospinal neurons that transform sensed instability into reflexive commands to spinal motor circuits. Postural stability improves across development. However, due to the complexity of terrestrial locomotion, vestibulospinal contributions to postural refinement in early life remain unexplored. Here we leveraged the relative simplicity of underwater locomotion to quantify the postural consequences of losing vestibulospinal neurons during development in larval zebrafish of undifferentiated sex. By comparing posture at two timepoints, we discovered that later lesions of vestibulospinal neurons led to greater instability. Analysis of thousands of individual swim bouts revealed that lesions disrupted movement timing and corrective reflexes without impacting swim kinematics, and that this effect was particularly strong in older larvae. Using a generative model of swimming, we showed how these disruptions could account for the increased postural variability at both timepoints. Finally, late lesions disrupted the fin/trunk coordination observed in older larvae, linking vestibulospinal neurons to postural control schemes used to navigate in depth. Since later lesions were considerably more disruptive to postural stability, we conclude that vestibulospinal contributions to balance increase as larvae mature. Vestibulospinal neurons are highly conserved across vertebrates; we therefore propose that they are a substrate for developmental improvements to postural control.SIGNIFICANCE STATEMENTMany animals experience balance improvements during early life. Mature vertebrates use vestibulospinal neurons to transform sensed instability into postural corrections. To understand if/how these neurons shape postural development, we ablated them at two developmentally important timepoints in larval zebrafish. Loss of vestibulospinal neurons disrupted specific stabilizing behaviors (swim timing, tilt correction, and fin/body coordination) more profoundly in older fish. We conclude that postural development happens in part by changes to vestibulospinal neurons — a significant step towards understanding how developing brains gain the ability to balance.
Learning experience network analysis for design-based research
Authors: Donaldson Jonan Phillip , Han Ahreum , Yan Shulong , Lee Seiyon , Kao Sean 
Published: December 2023

Purpose
Design-based research (DBR) involves multiple iterations, and innovations are needed in analytical methods for understanding how learners experience a learning experience in ways that both embrace the complexity of learning and allow for data-driven changes to the design of the learning experience between iterations. The purpose of this paper is to propose a method of crafting design moves in DBR using network analysis.

Design/methodology/approach
This paper introduces learning experience network analysis (LENA) to allow researchers to investigate the multiple interdependencies between aspects of learner experiences, and to craft design moves that leverage the relationships between struggles, what worked and experiences aligned with principles from theory.

Findings
The use of network analysis is a promising method of crafting data-driven design changes between iterations in DBR. The LENA process developed by the authors may serve as inspiration for other researchers to develop even more powerful methodological innovations.

Research limitations/implications
LENA may provide design-based researchers with a new approach to analyzing learner experiences and crafting data-driven design moves in a way that honors the complexity of learning.

Practical implications
LENA may provide novice design-based researchers with a structured and easy-to-use method of crafting design moves informed by patterns emergent in the data.

Originality/value
To the best of the authors’ knowledge, this paper is the first to propose a method for using network analysis of qualitative learning experience data for DBR.
Information security risks and sharing behavior on OSN: the impact of data collection awareness
Authors: Pham Thi Huyen , Phan Thuy-Anh , Trinh Phuong-Anh , Mai Xuan Bach , Le Quynh-Chi 
Published: December 2023

Purpose
This study aims to ascertain the impact of data collecting awareness on perceived information security concerns and information-sharing behavior on social networking sites.

Design/methodology/approach
Based on communication privacy management theory, the study forecasted the relationship between information-sharing behavior and awareness of data collecting purposes, data collection tactics and perceived security risk using structural equation modeling analysis and one-way ANOVA. The sample size of 521 young social media users in Vietnam, ages 18 to 34, was made up of 26.7% men and 73.3% women. When constructing the questionnaire survey method with lone source respondents, the individual’s unique awareness and experiences with using online social networks (OSNs) were taken into account.

Findings
The results of the investigation demonstrate a significant relationship between information-sharing and awareness of data collecting, perceptions of information security threats and behavior. Social media users have used OSN privacy settings and paid attention to the sharing restriction because they are concerned about data harvesting.

Research limitations/implications
This study was conducted among young Vietnamese social media users, reflecting specific characteristics prevalent in the Vietnamese environment, and hence may be invalid in other nations’ circumstances.

Practical implications
Social media platform providers should improve user connectivity by implementing transparent privacy policies that allow users to choose how their data are used; have clear privacy statements and specific policies governing the use of social media users’ data that respect users’ consent to use their data; and thoroughly communicate how they collect and use user data while promptly detecting any potential vulnerabilities within their systems.

Originality/value
The authors ascertain that the material presented in this manuscript will not infringe upon any statutory copyright and that the manuscript will not be submitted elsewhere while under Journal of Information, Communication and Ethics in Society review.