bluuebunny/crossref_metadata_2025 huggingface dataset:
Television in the Streaming Era
Authors: Chalaby Jean
Published: March 2023

This ground-breaking study explores transformations in the TV industry under the impact of globalizing forces and digital technologies. Chalaby investigates the making of a digital value chain and the distinct value-adding segments which form the new video ecosystem. He provides a full account of the industry's global shift from the development of TV formats and transnational networks to the emergence of tech giants and streaming platforms. The author takes a deep dive into the infrastructure (communication satellites, subsea cable networks, data centres) and technology (cloud computing, machine learning and artificial intelligence) underpinning this ecosystem through the prism of global value chain theory. The book combines empirical data garnered over 20 years of researching the industry and offers unique insights from television and tech executives.
Ancient and Pre-modern Economies of the North American Pacific Northwest
Authors: Prentiss Anna Marie
Published: March 2023

This Element provides an overview of pre-modern and ancient economies of the Pacific Northwest region of North America. The region is widely known for its densely occupied semisedentary villages, intensive production economies, dramatic ritual life, and complex social relations. Scholars recognize significant diversity in the structure of subsistence and goods production in the service of domestic groups and institutional entities throughout the region. Here, domestic and institutional economies, specialization, distribution, economic development, and future directions are reviewed. The Element closes with thoughts on the processes of socio-economic change on the scales of houses, villages, and regional strategies.
The Songs of Clara Schumann
Authors: Rodgers Stephen
Published: March 2023

Focusing on Clara Schumann's central contributions to the genre of the Lied (or German art song), this is the first book-length critical study of her songs. Although relatively few in number, they were published and reviewed favorably in the press during her lifetime, and they continue to be programmed regularly in recitals by professional and amateur performers alike. Highlighting the powerful and distinctive features of the songs, the book treats them as a prism, casting light not just on them but also through them to explore questions that foster a deeper understanding of the work of female composers. The author argues for the importance of taking Clara Schumann's music on its own terms, the intimate relationship between text and musical form, and the vital role of musical analysis in recuperating the contributions of previously understudied composers.
Russian Economic Sanctions
Authors: Butler William E.
Published: March 2023

Over the years, Soviet and post-Soviet Russian legal practice has responded to foreign and international economic sanctions reactively. As a rule, Russia has not initiated economic sanctions as an assertive measure against other countries, will apply sanctions authorized by an international organization of which it is a member and for which sanctions it has voted, and retaliates almost reflexively against economic sanctions imposed by others specifically against Russia, seemingly with little regard for the self-imposed consequences of its actions. The Civil Code of the Russian Federation authorizes (Article 1194), as did its predecessor the 1964 Civil Code of the RSFSR, the introduction of retaliatory measures (retorsion) in response to similar measures against Russian citizens and juridical persons in other states.
The benefits of deciding now and not later: The influence of the timing between acquiring knowledge and deciding on decision confidence, omission neglect bias, and choice deferral
Authors: Hernandez José Mauro C. , Costa Filho Murilo Carrazedo M. , Gaffney Donald R. , Kardes Frank R.
Published: March 2023

Consumers often spend time searching before making a purchasing decision to acquire knowledge about products. If the purchasing decision is delayed, recall of acquired knowledge is likely to be impaired. Because products in the marketplace are rarely described completely, consumers who take too long to decide may fail to notice the absence of information relevant to a purchasing decision and fall prey to a phenomenon called ‘omission neglect’, an inability to detect missing information and form extreme and confidently held judgments. Omission neglect may be corrected by acquiring knowledge about the target product before making the choice. In the present research, we examine consumer decisions in the context of choice sets described incompletely and presented either immediately or a week after the acquisition of relevant information about a target product. Specifically, we investigate how the timing between product knowledge acquisition and decision-making affects the detection of missing information, decision confidence, and choice deferral. Across three experiments, we find that, after acquiring knowledge, when consumers have their decision delayed, they are less able to detect missing information, feel more confident, and defer choices less.
Aging the gap: the compensation among men and women executives
Authors: Elvira Marta M. , Quintana-García Cristina , Villamor Isabel
Published: March 2023

In this study, we explore how early career advancement affects the gender pay gap among top executives and argue that an employee's age at attainment of an executive position serves as a signal that helps reduce biases toward women, thereby lowering gender pay differentials. We analyze career data of 803 executives from public high-technology manufacturing firms in the United States by collecting information from ExecuComp, Marquis Who's Who, LinkedIn, and Bloomberg. Our results indicate that attaining a top management position at a young age has a positive effect on pay, particularly among women, and this effect is due to the variable portion of compensation, which represents a large proportion of compensation among top executives. Further, recent research has identified a pay premium among high-potential female managers, although its key drivers remain unclear. This paper explores age as an observable signal that influences this premium and reduces the gender pay gap.
Path-following and collision-avoidance guidance of unmanned sailboats based on beetle antennae search optimization
Authors: Deng Yingjie , Ni Tao , Zhang Zhuxin , Wang Jianwei
Published: March 2023

There are few studies on the intelligent guidance of unmanned sailboats, which should coordinate pluralistic tasks at sea in the nature of its maneuvring intractability. To ensure the algorithmic practicability, this paper proposes a path-following and collision-avoidance guidance approach of unmanned sailboats with total formulaic description. The risk-detecting mechanism is fabricated by setting a circular detecting zone and using the time to the closest point of approach. Then, the risk of collision, the path deviation, the speed loss, and the course loss can be judged by constructing the cost functions and applying the distance to closest point of approach. The optimized heading angle is deemed as the one minimizing the aggregate cost functions, which is sought by applying and improving the beetle antennae search (BAS) algorithm. In the proposed modified BAS, the searching step is redesigned to enhance the searching efficiency. To ensure the convergence of the real heading angle to the reference, the backstepping-based control law is fabricated for the high-order sailboat model and in the linear form. The control parameters are offline optimized through the modified BAS. Compared with the adaptive control, this controller can guarantee more computation simplicity and the optimized control performance. Finally, simulation corroborates that the sailboat can successfully complete path following and collision avoidance while encountering multiple static and moving obstacles under the proposed schemes.
Oceanic Mobility and the Empire of the Pass System
Authors: Raman Bhavani
Published: March 2023

From the age of empires to the apartheid regime in South Africa, pass laws have defined the scope of the mobility of subjects by relying on a paper document, the pass. This essay focusses on the pass document to understand the governance of mobility in the Indian ocean. In doing so, it shows how the pass document in its various forms through many centuries in fact, illuminates a form of inter-legal governance through which racialized life came to be constituted via convention and statute.
The use of sentiment and emotion analysis and data science to assess the language of nutrition-, food- and cooking-related content on social media: a systematic scoping review
Authors: Molenaar Annika , Jenkins Eva L , Brennan Linda , Lukose Dickson , McCaffrey Tracy A
Published: March 2023

Social media data are rapidly evolving and accessible, which presents opportunities for research. Data science techniques, such as sentiment or emotion analysis which analyse textual emotion, provide an opportunity to gather insight from social media. This paper describes a systematic scoping review of interdisciplinary evidence to explore how sentiment or emotion analysis methods alongside other data science methods have been used to examine nutrition, food and cooking social media content. A PRISMA search strategy was used to search nine electronic databases in November 2020 and January 2022. Of 7325 studies identified, thirty-six studies were selected from seventeen countries, and content was analysed thematically and summarised in an evidence table. Studies were published between 2014 and 2022 and used data from seven different social media platforms (Twitter, YouTube, Instagram, Reddit, Pinterest, Sina Weibo and mixed platforms). Five themes of research were identified: dietary patterns, cooking and recipes, diet and health, public health and nutrition and food in general. Papers developed a sentiment or emotion analysis tool or used available open-source tools. Accuracy to predict sentiment ranged from 33·33% (open-source engine) to 98·53% (engine developed for the study). The average proportion of sentiment was 38·8% positive, 46·6% neutral and 28·0% negative. Additional data science techniques used included topic modelling and network analysis. Future research requires optimising data extraction processes from social media platforms, the use of interdisciplinary teams to develop suitable and accurate methods for the subject and the use of complementary methods to gather deeper insights into these complex data.
The Ligue des Droits de l'Homme and the ‘Right to Life’ in the 1930s
Authors: Burgess Greg
Published: March 2023

This article examines the debates within the French Ligue des Droits de l'Homme on the adoption in 1936 of a Complément (Complement) to the 1789 Declaration of the Rights of Man and the Citizen. The Ligue questioned the relevance of the 1789 Declaration when social dislocation, economic distress and fascism challenged democracy. New rights, principally the ‘right to life’ (droit à la vie), the fundamental right from which all others flowed, were pronounced. The article examines the values and principles informing the Complément to address why a declaration of new rights was seen as a proper response to these crises. Aspirations for a radical transformation of the social, political and economic order were expressed in a genre and a language of rights deeply embedded in French history. The Complément continued the work of 1789, assuming a form through which this transformation could be imagined.
Pandemic grief risk factors and prolonged grief disorder in bereaved young adults during COVID-19
Authors: Schneider Sydnie , Rerick Peter O. , Cummings Caroline , McLean Elisabeth , Breen Lauren J. , Singer Jonathan
Published: March 2023

Objectives

This study evaluated whether COVID-19-specific risk factors (e.g., feeling guilty for not being present with the deceased at the time of the loss and feeling emotionally distant from the deceased prior to the loss) were associated with prolonged grief disorder (PGD) symptomatology or diagnosis among young adults bereaved due to any cause (e.g., illness and violent loss).

Methods

We surveyed 196 young adults who had a family member/close friend die during the COVID-19 pandemic. Participants completed the PGD-12 Questionnaire and the 10-item Pandemic Grief Risk Factors (PGRF) Questionnaire.

Results

More time spent with the deceased before the loss and greater endorsement of pandemic grief risk factors were associated with increased PGD symptoms and a greater likelihood of meeting the diagnostic criteria for PGD.

Significance of results

The COVID-19 pandemic created unique risk factors that affected the grieving process for bereaved individuals, regardless of whether the death was related to COVID-19 infection. These findings add to a growing body of literature examining grief and loss within the unique context of the COVID-19 pandemic and suggest that there may be detrimental long-term psychological outcomes for these bereaved individuals, regardless of the cause of death. Routine screening for these unique risk factors in medical and psychological clinics is warranted to help identify those individuals who could benefit from early intervention. Also, it will be important to understand and possibly modify evidence-based interventions and prevention programs to directly address the identified unique PGRF.
Population structure, genetic diversity and bakanae disease resistance among rice varieties
Authors: Raghu S. , Baite M. S. , Yadav M. K. , Prabhukarthikeyan S. R. , Keerthana U. , Anil Kumar C. , Jeevan B. , Lenka S. , Subudhi H. N. , Rath P. C.
Published: March 2023

Availability of resistance sources among cultivated varieties helps in easy utilization as donor owing to no deleterious linkage drag. In the present investigation, 121 rice varieties were screened for their resistance against a virulent isolate ofFusarium fujikuroi(Ff-10) and genotyped using reported microsatellite markers. Among 121 varieties, only eight varieties, namely Luna Sankhi, Improved Tapaswini, Sarasa, Sadabahar, CR-311, Kshira, Wifa-10 and Binadhan-8, were found to be highly resistant (HR), seven varieties were resistant (R), 31 were moderately resistant (MR), 10 were moderately susceptible (MS), 11 were susceptible (S) and the rest 54 were highly susceptible (HS). The allele diversity of molecular markers classified the population into three clusters. The highly resistant varieties were grouped in major clusters II and III, whereas the remaining genotypes were distributed in all three clusters. Analysis of molecular variance (AMOVA) resulted in 95% of the maximum diversity within the test population and 5% diversity between populations. Population structure analysis grouped the genotypes into two sub-populations based on relatedness, where most of the resistant genotypes were grouped into one sub-population and other genotypes were distributed among sub-populations. Re-examination of reported markers' trait associations with bakanae resistance in the experimental population identified marker RM-3698 as associated with resistance accounting 8.4% explained phenotypic variation. This study shows that simple sequence repeat markers can be used to assess allelic diversity and population structure of bakanae resistance in rice varieties. The highly resistant genotypes, along with resistance markers, could be used as donors in marker-assisted bakanae improvement breeding programmes.
Ot2Rec: A semi-automatic, extensible, multi-software tomographic reconstruction workflow
Authors: Yee Neville B.-Y. , Ho Elaine M. L. , Tun Win , Smith Jake L. R. , Dumoux Maud , Grange Michael , Darrow Michele C. , Basham Mark
Published: March 2023

Electron cryo-tomography is an imaging technique for probing 3D structures with at the nanometer scale. This technique has been used extensively in the biomedical field to study the complex structures of proteins and other macromolecules. With the advancement in technology, microscopes are currently capable of producing images amounting to terabytes of data per day, posing great challenges for scientists as the speed of processing of the images cannot keep up with the ever-higher throughput of the microscopes. Therefore, automation is an essential and natural pathway on which image processing—from individual micrographs to full tomograms—is developing. In this paper, we present Ot2Rec, an open-source pipelining tool which aims to enable scientists to build their own processing workflows in a flexible and automatic manner. The basic building blocks of Ot2Rec are plugins which follow a unified application programming interface structure, making it simple for scientists to contribute to Ot2Rec by adding features which are not already available. In this paper, we also present three case studies of image processing using Ot2Rec, through which we demonstrate the speedup of using a semi-automatic workflow over a manual one, the possibility of writing and using custom (prototype) plugins, and the flexibility of Ot2Rec which enables the mix-and-match of plugins. We also demonstrate, in the Supplementary Material, a built-in reporting feature in Ot2Rec which aggregates the metadata from all process being run, and output them in the Jupyter Notebook and/or HTML formats for quick review of image processing quality. Ot2Rec can be found at https://github.com/rosalindfranklininstitute/ot2rec.
Less‐Well‐Developed Crustal Channel‐Flow in the Central Tibetan Plateau Revealed by Receiver Function and Surface Wave Joint Inversion
Authors: Nie Shitan , Tian Xiaobo , Liang Xiaofeng , Wan Bo
Published: March 2023

A crustal channel‐flow model has been previously used to explain the formation of crustal extensional structures in the Tibetan Plateau. However, the existence of massive crustal channel‐flow in the central plateau is still controversial. To reveal the crustal S‐wave velocity structure with high vertical resolution, we conducted a joint inversion of receiver functions and surface wave dispersions from the 2‐D broadband seismic array SANDWICH deployed in the central plateau. Our results show a low‐velocity layer (LVL) in the middle‐lower crust beneath all stations. The minimum S‐wave velocity in each LVL is mostly within 3.0–3.4 km/s, which result in the maximum velocity reductions are less than 17.5%. It deduces a melt volume percentage (MVP) less than 7% even attributing all velocity reduction to partial melting of rocks. Our study suggests that there is not a high enough melt volume in central Tibet to develop crustal channel‐flow, which requires a larger MVP to decrease rock strength more than an order of magnitude. The formation of extensional structures in the central plateau may contribute to ductile deformation in the middle‐lower crust but not crustal channel‐flow.
Timing and Consequences of Bering Strait Opening: New Insights From40Ar/39Ar Dating of the Barmur Group (Tjörnes Beds), Northern Iceland
Authors: Hall Jonathan R. , Allison Matthew S. , Papadopoulos Max T. , Barfod Dan N. , Jones Stephen M.
Published: March 2023

The Barmur Group (informally Tjörnes beds) sedimentary succession of northern Iceland is key to reconstructing the opening of the Bering Strait oceanic gateway because these rocks record migration of bivalve molluscs from the Pacific to the Atlantic via the Arctic. However, the timing of the migration event is poorly constrained owing to a lack of reliable absolute ages. To address this problem, we present the first Ar‐Ar radiometric dates from four basaltic lavas that underlie, are intercalated with, and overlie the Barmur Group, and integrate them with existing paleomagnetic records. We show that the Barmur Group has a latest Miocene to early Pliocene age range (c. 6.0–4.4 Ma; C3r–C3n.2n), older than all previous age models. Thus, the Barmur Group does not record the mid‐Piacenzian Warm Period, contra some previous suggestions. Abundant Pacific bivalve molluscs appeared in the Barmur Group during subchrons C3n.4n–C3n.3r at 5.235–4.896 Ma, over 1.3 million years earlier than previously suggested. Appearance of Pacific bivalves in the northern Atlantic occurred shortly after the 5.6–5.4 Ma age previously inferred for first appearance of Arctic bivalves in the Pacific. Thus, our data suggest that first opening of the Bering Strait gateway by the latest Miocene (c. 5.5 Ma) was soon followed by bidirectional trans‐Arctic faunal exchange, and argue against a hypothesized two‐stage faunal exchange process spanning c. 2 million years. Our results also confirm that first opening of the Bering Strait gateway was not directly associated with the growth of large northern hemisphere icesheets, which occurred several million years later.
Direct extraction of topological Zak phase with the synthetic dimension
Authors: Li Guangzhen , Wang Luojia , Ye Rui , Zheng Yuanlin , Wang Da-Wei , Liu Xiong-Jun , Dutt Avik , Yuan Luqi , Chen Xianfeng
Published: March 2023

Measuring topological invariants is an essential task in characterizing topological phases of matter. They are usually obtained from the number of edge states due to the bulk-edge correspondence or from interference since they are integrals of the geometric phases in the energy band. It is commonly believed that the bulk band structures could not be directly used to obtain the topological invariants. Here, we implement the experimental extraction of Zak phase from the bulk band structures of a Su-Schrieffer-Heeger (SSH) model in the synthetic frequency dimension. Such synthetic SSH lattices are constructed in the frequency axis of light, by controlling the coupling strengths between the symmetric and antisymmetric supermodes of two bichromatically driven rings. We measure the transmission spectra and obtain the projection of the time-resolved band structure on lattice sites, where a strong contrast between the non-trivial and trivial topological phases is observed. The topological Zak phase is naturally encoded in the bulk band structures of the synthetic SSH lattices, which can hence be experimentally extracted from the transmission spectra in a fiber-based modulated ring platform using a laser with telecom wavelength. Our method of extracting topological phases from the bulk band structure can be further extended to characterize topological invariants in higher dimensions, while the exhibited trivial and non-trivial transmission spectra from the topological transition may find future applications in optical communications.
The role of N-glycosylation modification in the pathogenesis of liver cancer
Authors: Hu Mengyu , Zhang Rui , Yang Jiaren , Zhao Chenshu , Liu Wei , Huang Yuan , Lyu Hao , Xiao Shuai , Guo Dong , Zhou Cefan , Tang Jingfeng
Published: March 2023

N-glycosylation is one of the most common types of protein modifications and it plays a vital role in normal physiological processes. However, aberrant N-glycan modifications are closely associated with the pathogenesis of diverse diseases, including processes such as malignant transformation and tumor progression. It is known that the N-glycan conformation of the associated glycoproteins is altered during different stages of hepatocarcinogenesis. Characterizing the heterogeneity and biological functions of glycans in liver cancer patients will facilitate a deeper understanding of the molecular mechanisms of liver injury and hepatocarcinogenesis. In this article, we review the role of N-glycosylation in hepatocarcinogenesis, focusing on epithelial-mesenchymal transition, extracellular matrix changes, and tumor microenvironment formation. We highlight the role of N-glycosylation in the pathogenesis of liver cancer and its potential applications in the treatment or diagnosis of liver cancer.
Death of tonsillar B cells by NETosis
Authors: Bukhari Ameera , Kalinina Olga , Knight Katherine L.
Published: March 2023

Regulating B cell death is essential for generating antibodies and maintaining immune tolerance. B cells can die by apoptosis, and we report that human tonsil B cells, but not peripheral blood B cells also die by NETosis. This cell death is density-dependent, characterized by the loss of cell and nuclear membrane integrity, release of reactive oxygen species, and chromatin decondensation. Tonsil B cells secrete high levels of TNF, and inhibiting TNF prevented chromatin decondensation. By in situ fluorescence microscopy, B cell NETosis, as identified by the hyper citrullination of Histone-3, was localized to the light zone (LZ) of germinal centers in normal tonsil and overlapped with the B cell marker CD19/IgM. We propose a model in which stimulation of B cells in the LZ induces NETosis, driven in part by TNF. We also provide evidence that NETosis of tonsil B cells may be inhibited by an unidentified factor in tonsil. The results describe a previously unidentified form of B cell death and suggest a new mechanism to maintain B cell homeostasis during immune responses.
The plant unique ESCRT component FREE1 regulates autophagosome closure
Authors: Zeng Yonglun , Li Baiying , Huang Shuxian , Li Hongbo , Cao Wenhan , Chen Yixuan , Liu Guoyong , Li Zhenping , Yang Chao , Feng Lei , Gao Jiayang , Lo Sze Wan , Zhao Jierui , Shen Jinbo , Guo Yan , Gao Caiji , Dagdas Yasin , Jiang Liwen
Published: March 2023

The energy sensor AMP-activated protein kinase (AMPK) can activate autophagy when cellular energy production becomes compromised. However, the degree to which nutrient sensing impinges on the autophagosome closure remains unknown. Here, we provide the mechanism underlying a plant unique protein FREE1, upon autophagy-induced SnRK1α1-mediated phosphorylation, functions as a linkage between ATG conjugation system and ESCRT machinery to regulate the autophagosome closure upon nutrient deprivation. Using high-resolution microscopy, 3D-electron tomography, and protease protection assay, we showed that unclosed autophagosomes accumulated in free1 mutants. Proteomic, cellular and biochemical analysis revealed the mechanistic connection between FREE1 and the ATG conjugation system/ESCRT-III complex in regulating autophagosome closure. Mass spectrometry analysis showed that the evolutionary conserved plant energy sensor SnRK1α1 phosphorylates FREE1 and recruits it to the autophagosomes to promote closure. Mutagenesis of the phosphorylation site on FREE1 caused the autophagosome closure failure. Our findings unveil how cellular energy sensing pathways regulate autophagosome closure to maintain cellular homeostasis.
A Vaccinia-based system for directed evolution of GPCRs in mammalian cells
Authors: Klenk Christoph , Scrivens Maria , Niederer Anina , Shi Shuying , Mueller Loretta , Gersz Elaine , Zauderer Maurice , Smith Ernest S. , Strohner Ralf , Plückthun Andreas
Published: March 2023

Directed evolution in bacterial or yeast display systems has been successfully used to improve stability and expression of G protein-coupled receptors for structural and biophysical studies. Yet, several receptors cannot be tackled in microbial systems due to their complex molecular composition or unfavorable ligand properties. Here, we report an approach to evolve G protein-coupled receptors in mammalian cells. To achieve clonality and uniform expression, we develop a viral transduction system based on Vaccinia virus. By rational design of synthetic DNA libraries, we first evolve neurotensin receptor 1 for high stability and expression. Second, we demonstrate that receptors with complex molecular architectures and large ligands, such as the parathyroid hormone 1 receptor, can be readily evolved. Importantly, functional receptor properties can now be evolved in the presence of the mammalian signaling environment, resulting in receptor variants exhibiting increased allosteric coupling between the ligand binding site and the G protein interface. Our approach thus provides insights into the intricate molecular interplay required for GPCR activation.
Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes
Authors: Li Lingling , Jiang Dongxian , Liu Hui , Guo Chunmei , Zhao Rui , Zhang Qiao , Xu Chen , Qin Zhaoyu , Feng Jinwen , Liu Yang , Wang Haixing , Chen Weijie , Zhang Xue , Li Bin , Bai Lin , Tian Sha , Tan Subei , Yu Zixiang , Chen Lingli , Huang Jie , Zhao Jian-Yuan , Hou Yingyong , Ding Chen
Published: March 2023

The subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage. Proteome-based analysis elucidates stage-specific molecular characterizations and carcinogenesis tracks, and defines the cancer-driving waves of the adenocarcinoma and Brunner’s gland subtypes. The drug-targetable alanyl-tRNA synthetase (AARS1) in the high tumor mutation burden/immune infiltration is significantly enhanced in DC progression, and catalyzes the lysine-alanylation of poly-ADP-ribose polymerases (PARP1), which decreases the apoptosis of cancer cells, eventually promoting cell proliferation and tumorigenesis. We assess the proteogenomic landscape of early DC, and provide insights into the molecular features corresponding therapeutic targets.
Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice
Authors: Cope Elise C. , Wang Samantha H. , Waters Renée C. , Gore Isha R. , Vasquez Betsy , Laham Blake J. , Gould Elizabeth
Published: March 2023

Mutation or deletion of theSHANK3gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments.Shank3Bknockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 inShank3Bknockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype andShank3Bknockout mice. However, activation of the CA2 enhanced vCA1 theta power inShank3Bknockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function.
The RNA-binding protein hnRNP F is required for the germinal center B cell response
Authors: Huang Hengjun , Li Yuxing , Zhang Gaopu , Ruan Gui-Xin , Zhu Zhijian , Chen Wenjing , Zou Jia , Zhang Rui , Wang Jing , Ouyang Yu , Xu Shengli , Ou Xijun
Published: March 2023

The T cell-dependent (TD) antibody response involves the generation of high affinity, immunoglobulin heavy chain class-switched antibodies that are generated through germinal center (GC) response. This process is controlled by coordinated transcriptional and post-transcriptional gene regulatory mechanisms. RNA-binding proteins (RBPs) have emerged as critical players in post-transcriptional gene regulation. Here we demonstrate that B cell-specific deletion of RBP hnRNP F leads to diminished production of class-switched antibodies with high affinities in response to a TD antigen challenge. B cells deficient in hnRNP F are characterized by defective proliferation and c-Myc upregulation upon antigenic stimulation. Mechanistically, hnRNP F directly binds to the G-tracts of Cd40 pre-mRNA to promote the inclusion of Cd40 exon 6 that encodes its transmembrane domain, thus enabling appropriate CD40 cell surface expression. Furthermore, we find that hnRNP A1 and A2B1 can bind to the same region of Cd40 pre-mRNA but suppress exon 6 inclusion, suggesting that these hnRNPs and hnRNP F might antagonize each-other’s effects on Cd40 splicing. In summary, our study uncovers an important posttranscriptional mechanism regulating the GC response.
White matter disconnection of left multiple demand network is associated with post-lesion deficits in cognitive control
Authors: Jiang Jiefeng , Bruss Joel , Lee Woo-Tek , Tranel Daniel , Boes Aaron D.
Published: March 2023

Cognitive control modulates other cognitive functions to achieve internal goals and is important for adaptive behavior. Cognitive control is enabled by the neural computations distributed over cortical and subcortical areas. However, due to technical challenges in recording neural activity from the white matter, little is known about the anatomy of white matter tracts that coordinate the distributed neural computations that support cognitive control. Here, we leverage a large sample of human patients with focal brain lesions (n = 643) and investigate how lesion location and connectivity profiles account for variance in cognitive control performance. We find that lesions in white matter connecting left frontoparietal regions of the multiple demand network reliably predict deficits in cognitive control performance. These findings advance our understanding of the white matter correlates of cognitive control and provide an approach for incorporating network disconnection to predict deficits following lesions.
Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats
Authors: Subramanian Keshav S. , Lauer Logan Tierno , Hayes Anna M. R. , Décarie-Spain Léa , McBurnett Kara , Nourbash Anna C. , Donohue Kristen N. , Kao Alicia E. , Bashaw Alexander G. , Burdakov Denis , Noble Emily E. , Schier Lindsey A. , Kanoski Scott E.
Published: March 2023

The lateral hypothalamic area (LHA) integrates homeostatic processes and reward-motivated behaviors. Here we show that LHA neurons that produce melanin-concentrating hormone (MCH) are dynamically responsive to both food-directed appetitive and consummatory processes in male rats. Specifically, results reveal that MCH neuron Ca2+ activity increases in response to both discrete and contextual food-predictive cues and is correlated with food-motivated responses. MCH neuron activity also increases during eating, and this response is highly predictive of caloric consumption and declines throughout a meal, thus supporting a role for MCH neurons in the positive feedback consummatory process known as appetition. These physiological MCH neural responses are functionally relevant as chemogenetic MCH neuron activation promotes appetitive behavioral responses to food-predictive cues and increases meal size. Finally, MCH neuron activation enhances preference for a noncaloric flavor paired with intragastric glucose. Collectively, these data identify a hypothalamic neural population that orchestrates both food-motivated appetitive and intake-promoting consummatory processes.
Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response
Authors: Santa Cruz André , Mendes-Frias Ana , Azarias-da-Silva Marne , André Sónia , Oliveira Ana Isabel , Pires Olga , Mendes Marta , Oliveira Bárbara , Braga Marta , Lopes Joana Rita , Domingues Rui , Costa Ricardo , Silva Luís Neves , Matos Ana Rita , Ângela Cristina , Costa Patrício , Carvalho Alexandre , Capela Carlos , Pedrosa Jorge , Castro António Gil , Estaquier Jérôme , Silvestre Ricardo
Published: March 2023

Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+β7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.
Screw sense excess and reversals of helical polymers in solution
Authors: Rey-Tarrío Francisco , Rodríguez Rafael , Quiñoá Emilio , Freire Félix
Published: March 2023

The helix reversal is a structural motif found in helical polymers in the solid state, but whose existence is elusive in solution. Herein, we have shown how the photochemical electrocyclization (PEC) of poly(phenylacetylene)s (PPAs) can be used to determine not only the presence of helix reversals in polymer solution, but also to estimate the screw sense excess. To perform these studies, we used a library of well folded PPAs and different copolymers series made by enantiomeric comonomers that show chiral conflict effect. The results obtained indicate that the PEC of a PPA will depend on the helical scaffold adopted by the PPA backbone and on its folding degree. Then, from these studies it is possible to determine the screw sense excess of a PPA, highly important in applications such as chiral stationary phases in HPLC or asymmetric synthesis.
A-MYB and BRDT-dependent RNA Polymerase II pause release orchestrates transcriptional regulation in mammalian meiosis
Authors: Alexander Adriana K. , Rice Edward J. , Lujic Jelena , Simon Leah E. , Tanis Stephanie , Barshad Gilad , Zhu Lina , Lama Jyoti , Cohen Paula E. , Danko Charles G.
Published: March 2023

During meiotic prophase I, spermatocytes must balance transcriptional activation with homologous recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state. We explored the interplay between chromatin accessibility and transcription through prophase I of mammalian meiosis by measuring genome-wide patterns of chromatin accessibility, nascent transcription, and processed mRNA. We find that Pol II is loaded on chromatin and maintained in a paused state early during prophase I. In later stages, paused Pol II is released in a coordinated transcriptional burst mediated by the transcription factors A-MYB and BRDT, resulting in ~3-fold increase in transcription. Transcriptional activity is temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings reveal mechanisms underlying chromatin specialization in either transcription or recombination in meiotic cells.
MS2Query: reliable and scalable MS2 mass spectra-based analogue search
Authors: de Jonge Niek F. , Louwen Joris J. R. , Chekmeneva Elena , Camuzeaux Stephane , Vermeir Femke J. , Jansen Robert S. , Huber Florian , van der Hooft Justin J. J.
Published: March 2023

Metabolomics-driven discoveries of biological samples remain hampered by the grand challenge of metabolite annotation and identification. Only few metabolites have an annotated spectrum in spectral libraries; hence, searching only for exact library matches generally returns a few hits. An attractive alternative is searching for so-called analogues as a starting point for structural annotations; analogues are library molecules which are not exact matches but display a high chemical similarity. However, current analogue search implementations are not yet very reliable and relatively slow. Here, we present MS2Query, a machine learning-based tool that integrates mass spectral embedding-based chemical similarity predictors (Spec2Vec and MS2Deepscore) as well as detected precursor masses to rank potential analogues and exact matches. Benchmarking MS2Query on reference mass spectra and experimental case studies demonstrate improved reliability and scalability. Thereby, MS2Query offers exciting opportunities to further increase the annotation rate of metabolomics profiles of complex metabolite mixtures and to discover new biology.
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Authors: Onuchic Laura , Padovano Valeria , Schena Giorgia , Rajendran Vanathy , Dong Ke , Shi Xiaojian , Pandya Raj , Rai Victoria , Gresko Nikolay P. , Ahmed Omair , Lam TuKiet T. , Wang Weiwei , Shen Hongying , Somlo Stefan , Caplan Michael J.
Published: March 2023

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in the PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid (aa) residues of PC1 in two Pkd1-KO orthologous murine models of ADPKD suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function, and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.
Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan
Authors: Alder Laura , Trapani Dario , Bradbury Claire , Van Swearingen Amanda E. D. , Tolaney Sara M. , Khasraw Mustafa , Anders Carey K. , Lascola Christopher D. , Hsu Liangge , Lin Nancy U. , Sammons Sarah
Published: March 2023

Leptomeningeal metastases (LM) are a devastating complication of HER2 + metastatic breast cancer (MBC), with no effective treatments. In a case series of 8 patients with heavily pretreated HER2 + MBC and progressing LM, all 8 patients (100%) derived clinical benefit from Trastuzumab deruxtecan (TDXd), and 4 patients (50%) had an objective partial response based on formal neuroradiology MRI reads using the EORTC/RANO-LM Revised-Scorecard. T-DXd warrants further study in LM in HER2 + MBC and solid tumors where T-DXd may be active.
GazeBaseVR, a large-scale, longitudinal, binocular eye-tracking dataset collected in virtual reality
Authors: Lohr Dillon , Aziz Samantha , Friedman Lee , Komogortsev Oleg V.
Published: March 2023

We present GazeBaseVR, a large-scale, longitudinal, binocular eye-tracking (ET) dataset collected at 250 Hz with an ET-enabled virtual-reality (VR) headset. GazeBaseVR comprises 5,020 binocular recordings from a diverse population of 407 college-aged participants. Participants were recorded up to six times each over a 26-month period, each time performing a series of five different ET tasks: (1) a vergence task, (2) a horizontal smooth pursuit task, (3) a video-viewing task, (4) a self-paced reading task, and (5) a random oblique saccade task. Many of these participants have also been recorded for two previously published datasets with different ET devices, and 11 participants were recorded before and after COVID-19 infection and recovery. GazeBaseVR is suitable for a wide range of research on ET data in VR devices, especially eye movement biometrics due to its large population and longitudinal nature. In addition to ET data, additional participant details are provided to enable further research on topics such as fairness.
Alternative culture medium design for biomass production of autochthonous meat starter Latilactobacillus sakei sp. sakei ACU-2
Authors: Galante Nadia , Palavecino Prpich Noelia , Campos Carmen , Cayré María Elisa , Castro Marcela
Published: March 2023

The autochthonous strain Latilactobacillus sakei sp. sakei ACU-2 was selected as a meat starter culture for dry sausage production. Transferring this strain from laboratory scale to industry requires an increase in biomass production, while lowering process costs. In this study, a combination of techniques was applied in order to optimize the culture medium composition to enhance biomass production of L. sakei ACU-2. One variable at a time experiments, Plackett–Burman design, and mixture design were performed to fulfill the strain nutritional requirements. Eventually, the optimized formulation contained 19.46 g/L yeast extract; 8.28 g/L whey protein concentrate; 2.26 g/L soy peptone; 30 g/L cerelose; 1 g/L Tween 80; 5 g/L sodium acetate; 0.2 g/L magnesium sulfate and 0.05 g/L manganese sulfate. When L. sakei ACU-2 was cultivated in a bioreactor using the alternative medium, an enhancement of 75.5% of biomass production was achieved, in comparison to its growth in the commercial de Man, Rogosa, and Sharpe medium. Furthermore, a reduction of 62–86% of the cost was also attained. These results support a promising large-scale application of the designed medium for high biomass yields of the starter culture at minor costs.
Results from a living systematic review of the prevalence of mood and anxiety disorders and factors associated with symptoms in systemic sclerosis
Authors: Nassar Elsa-Lynn , Abdulkareem Dalal A. , Thombs Brett D.
Published: March 2023

We aimed to synthesize evidence on (1) the prevalence of mood and anxiety disorders and (2) factors associated with symptoms in systemic sclerosis (SSc). We searched MEDLINE, CINAHL, EMBASE, Cochrane CENTRAL, and PsycINFO via an ongoing living systematic review with automated monthly searches. We identified 6 eligible studies through March 1, 2023. Based on 3 studies (N = 93 to 345), current or 30-day major depressive disorder prevalence was 4% (95% confidence interval [CI] 2%, 6%) in a sample of Canadian outpatients (N = 345), 18% (95% CI 12%, 27%) in a study of Indian outpatients (N = 93), 10% (95% CI 4%, 21%) for French patient conference attendees (N = 51), and 29% (95% CI 18%, 42%) for French inpatients (N = 49). Current or 30-day prevalence of any anxiety disorder was 49% (95% CI 36%, 62%) for French conference attendees and 51% (95% CI 38%, 64%) for French inpatients; current or 30-day prevalence of generalized anxiety disorder was 3% for Indian outpatients (95% CI 1%, 9%; N = 93). In 3 studies (N = 114 to 376) that examined factors associated with depressive symptoms, higher education and being married or living as married were associated with lower symptoms and pulmonary involvement, breathing problems, and tender joint counts with higher symptoms; age and disease severity markers were not associated. Only 1 study (N = 114) assessed factors associated with anxiety symptoms and found no statistically significant associations. Limitations included heterogeneous populations and assessment methods, small samples, and substantial risk of bias concerns. Mood and anxiety disorder prevalence appear high in SSc, but estimates vary, and existing studies have important limitations. Future research should assess mood and anxiety prevalence and factors associated with symptoms using large representative samples and validated classification and assessment methods.

Review registration: PROSPERO (CRD 42021251339).