bluuebunny/crossref_metadata_2025 huggingface dataset:
An Ancient Church
Authors: Hamilton Alastair
Published: October 2023

The legends surrounding the foundation and the early years of Egyptian Christianity have been a source of both contention and fascination for the Christians of the West. The Church of Alexandria was allegedly established by Mark the Evangelist on one of his visits to the Roman province of Egypt. St Mark thus became the first patriarch in an uninterrupted line of apostolic succession proudly recorded by the Coptic chronologists. Based largely on the authority of Eusebius of Caesarea in the early fourth century, and of the slightly later apocryphal Acts of Mark, the legend of the founder-evangelist became a hallowed part of Coptic tradition.1
The First Jesuit Mission
Authors: Hamilton Alastair
Published: October 2023

It was on the occasion of the first major mission to Egypt that the relatively young Society of Jesus started to play a leading part in the papal policy towards the Copts. Approved by the papacy in 1540, it was a society of clerks regular who took vows of poverty and chastity. Obedient to the papacy, they devoted themselves to works of charity, to education, and to the propagation of Catholicism throughout the world. The founder of the Society, Ignatius Loyola, had first wished to settle in Jerusalem and to dedicate himself to the service of the Church in the Holy Land.
Jansenists and Jesuits
Authors: Hamilton Alastair
Published: October 2023

Thanks to the manuscripts Wansleben collected, from the 1670s onwards France, of all countries north of the Alps, was at a unique advantage for research into the Church of Alexandria. When one of the greatest French orientalists of the late seventeenth and early eighteenth centuries, Euse`be Renaudot, produced by far the most important work on the early history of the Egyptian Church, an invaluable supplement to Wansleben’s study of Coptic practices, he denied any debt to Wansleben’s study, but admitted depending on the manuscripts which Wansleben sent back to France and which he consulted as soon as they arrived in Paris.1
Biblical Studies
Authors: Hamilton Alastair
Published: October 2023

The sixteenth and seventeenth centuries were the time of the triumph of the polyglot Bible. What had become the current Latin translation of the Bible sanctioned by the Church of Rome, the Vulgate attributed to Jerome, had come under increasing criticism as the humanists discovered Greek versions of the New Testament which differed substantially from the accepted Latin rendering.1 As the study of Eastern languages started to spread in scholarly circles the whole of the Bible was subjected to a closer inspection, which raised doubts about the reliability of the Vulgate.
Consilience, Crime Control, and Community Safety
Authors: Hawley Michael
Published: October 2023

This chapter provides an Australian perspective on effective intelligence through the development of consilient relationships. It examines the relationship between criminal-intelligence units and their most significant clients: policing, executive, and operational units. It also examines the reasons behind what can often be a fractured relationship, the harm that this can cause to effective crime control and community safety, and how the Australian Federal Police (AFP) is attempting to build a consilient relationship with its most significant clients through an initiative known as the Leadership in Criminal Intelligence Program (LCIP).
Market failures in payment and settlement systems
Authors: Manning Mark , Nier Erlend , Schanz Jochen
Published: October 2023

Given the importance of payments and financial market infrastructure for the real economy, it is unsurprising that public authorities have taken a close interest in their development. This chapter briefly reviews the market failures that have led to close public-sector involvement in the provision of financial market infrastrucure, some of which have been examined already in Part II of this book. The various forms of public-sector intervention are then described in more detail in Chapter 8. We defined systemic risk in Part II as ‘the risk that the failure of one participant in a transfer system, or in financial markets generally, to meet its obligations will cause other participants or financial institutions to be unable to meet their obligations (including settlement obligations in a transfer system) when due’ (CPSS, 2003c).
Banks providing infrastructure services
Authors: Manning Mark , Nier Erlend , Schanz Jochen
Published: October 2023

A bank may choose not to participate directly in all of the large-value payment systems for currencies in which it needs to make and receive payments. In some cases, even if it has a domestic presence, a bank may choose to access a payment system indirectly via another bank. The ratio of indirect to total participation in a payment system is often referred to as the degree of ‘tiering’. When a settlement bank becomes sufficiently large it becomes, in essence, a system itself, performing the same functions for its customer banks as a payment system provides for its direct members. Thus, the services provided by settlement banks can generate similar risks to those discussed in previous chapters in relation to dedicated systems.
The evolving infrastructure landscape and challenges for central banks
Authors: Manning Mark , Nier Erlend , Schanz Jochen
Published: October 2023

At the time of writing, financial innovation, globalization and regulatory change are transforming the structure of trading and post-trade services (see Jenkinson, 2007). Stresses in the financial system during 2007 and 2008 have also presented challenges for infrastructure providers and their participants, which may shape the evolution. Section 11.1 traces out how the trading landscape has responded to the challenges of financial globalization and regulatory change. We then consider how developments at this level might in turn influence the evolution of payment and settlement systems. Sections 11.2 and 11.3 consider the implications for financial and monetary stability, and how central banks might respond.
Corneal Irregularity Induced by Transepithelial Photorefractive Keratectomy in a Patient With Partial Limbal Stem Cell Deficiency
Authors: Vakalopoulos Dionysios G. , Chatzea Marina S. , Chronopoulou Konstantina , Katsimpras Marios , Tsopouridou Rodopi D. , Kymionis George D.
Published: October 2023

Purpose:

The aim of this study was to present a case of transepithelial photorefractive keratectomy (trans-PRK) laser ablation in a patient with partial limbal stem cell deficiency (LSCD) that resulted in corneal irregularity.

Methods:

A 23-year-old man with bilateral partial LSCD underwent trans-PRK for myopia correction 2 months before presentation to our department. Trans-PRK ablation was performed with a phototherapeutic keratectomy ablation profile set at 60 μm in the OD and 57 μm in the OS and 8 mm zone. At the time of presentation, the patient complained of decreased visual acuity. Corrected distant visual acuity was 20/20 (−3.25, −0.75 × 180 degrees) and 20/50 (−3.00, −3.00 × 180 degrees) in the OD and the OS, respectively. No further ocular history was reported other than prolonged soft contact lens use for myopia. Pre–trans-PRK tomography (WaveLight Oculyzer II diagnostic system, WaveLight GmbH, Germany) revealed bilateral superior steepening with corresponding epithelial thinning as obtained by the epithelial map using Optovue optical coherence tomography (Visionix Luneau technology). Slit-lamp examination showed bilateral superficial neovascularization, suggestive of early-stage LSCD.

Results:

A nonuniform laser stromal ablation resulting in corneal irregularity and decreased visual acuity was observed 2 months postoperatively. During the 6-month follow-up, corneal tomography was stable with only minimal improvement. At that time, corrected distant visual acuity remained 20/20 (−2.75, −0.75 × 160 degrees) in the OD and 20/50 (−3.00, −3.00 × 180 degrees) in the OS.

Conclusions:

Trans-PRK seems to be a contraindication in cases with corneal epithelial irregularities and could lead to abnormal and nonuniform stromal ablation.
Malignant Mimicry in a Rare Case of Hepatic Malakoplakia
Authors: Strayve Daniel , Ruby Jarom , Abidalhassan Mustafa , Hutfles Gerald J. , Schaberg Kurt B. , Wei Dongguang , Corwin Michael , Gholami Sepideh
Published: October 2023

We report a rare case of hepatic malakoplakia mimicking malignancy both in its clinical presentation and appearance on 4-phase computed tomography. This case highlights both an interesting variation by which this disease process can manifest and a multidisciplinary approach, which may be used to identify and treat future patients.
Light pollution in complex ecological systems
Authors: Hirt Myriam R. , Evans Darren M. , Miller Colleen R. , Ryser Remo
Published: October 2023

Light pollution has emerged as a burgeoning area of scientific interest, receiving increasing attention in recent years. The resulting body of literature has revealed a diverse array of species-specific and context-dependent responses to artificial light at night (ALAN). Because predicting and generalizing community-level effects is difficult, our current comprehension of the ecological impacts of light pollution on complex ecological systems remains notably limited. It is critical to better understand ALAN's effects at higher levels of ecological organization in order to comprehend and mitigate the repercussions of ALAN on ecosystem functioning and stability amidst ongoing global change. This theme issue seeks to explore the effects of light pollution on complex ecological systems, by bridging various realms and scaling up from individual processes and functions to communities and networks. Through this integrated approach, this collection aims to shed light on the intricate interplay between light pollution, ecological dynamics and humans in a world increasingly impacted by anthropogenic lighting.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
Spectral composition of light-emitting diodes impacts aquatic and terrestrial invertebrate communities with potential implications for cross-ecosystem subsidies
Authors: Parkinson Elizabeth , Tiegs Scott D.
Published: October 2023

Resource exchanges in the form of invertebrate fluxes are a key component of aquatic-terrestrial habitat coupling, but this interface is susceptible to human activities, including the imposition of artificial light at night. To better understand the effects of spectral composition of light-emitting diodes (LEDs)—a technology that is rapidly supplanting other lighting types—on emergent aquatic insects and terrestrial insects, we experimentally added LED fixtures that emit different light spectra to the littoral zone and adjacent riparian habitat of a pond. We installed four replicate LED treatments of different wavelengths (410, 530 and 630 nm), neutral white (4000 k) and a dark control, and sampled invertebrates in both terrestrial and over-water littoral traps. Invertebrate communities differed among light treatments and between habitats, as did total insect biomass and mean individual insect size. Proportional allochthonous biomass was greater in the riparian habitat and among some light treatments, demonstrating an asymmetrical effect of differently coloured LEDs on aquatic-terrestrial resource exchanges. Overall, our findings demonstrate that variation in wavelength from LEDs may impact the flux of resources between systems, as well as the communities of insects that are attracted to particular spectra of LED lighting, with probable implications for consumers.

This article is part of the theme issue ‘Light pollution in complex ecological systems’.
A Biallelic Variant of the RNA Exosome GeneEXOSC4Causes Translational Defects Associated with a Neurodevelopmental Disorder
Authors: Fasken Milo B. , Leung Sara W. , Cureton Lauryn A. , Al-Awadi Maha , Al-Kindy Adila , Khoshnevis Sohail , Ghalei Homa , Al-Maawali Almundher , Corbett Anita H.
Published: October 2023

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Mutations inEXOSCgenes encoding structural subunits of the complex are linked to several autosomal recessive disorders. Here, we describe a missense allele of theEXOSC4gene, which causes a collection of clinical features in two affected siblings. This missense mutation (NM_019037.3: exon3:c.560T>C), changes a leucine residue within a highly conserved region of EXOSC4 to proline (p.Leu187Pro). The two affected individuals presented with prenatal growth restriction, failure to thrive, global developmental delay, intracerebral and basal ganglia calcifications, and kidney failure. Homozygosity for the damaging variant was identified through exome sequencing and Sanger sequencing confirmed segregation. To explore the functional consequences of this amino acid change, we modeled EXOSC4-L187P in the corresponding budding yeast protein, Rrp41 (Rrp41-L187P). Cells that express Rrp41-L187P as the sole copy of the essential Rrp41 protein show significant growth defects. The steady-state level of both the Rrp41-L187P and the EXOSC4-L187P proteins is significantly decreased compared to control Rrp41/EXOSC4. Consistent with this observation, targets of the RNA exosome accumulate inrrp41-L187Pcells, including the 7S precursor of 5.8S rRNA. Polysome profiles show a significant decrease in translation inrrp41-L187Pcells as compared to control cells with apparent incorporation of 7S pre-rRNA into polysomes. Taken together, this work adds the EXOSC4 subunit of the RNA exosome to the structural subunits of this complex that have been linked to human disease and defines foundational molecular defects that could contribute to the adverse growth phenotypes caused by this novel EXOSC4 pathogenic variant.
DREDge: robust motion correction for high-density extracellular recordings across species
Authors: Windolf Charlie , Yu Han , Paulk Angelique C. , Meszéna Domokos , Muñoz William , Boussard Julien , Hardstone Richard , Caprara Irene , Jamali Mohsen , Kfir Yoav , Xu Duo , Chung Jason E. , Sellers Kristin K. , Ye Zhiwen , Shaker Jordan , Lebedeva Anna , Raghavan Manu , Trautmann Eric , Melin Max , Couto João , Garcia Samuel , Coughlin Brian , Horváth Csaba , Fiáth Richárd , Ulbert István , Movshon J. Anthony , Shadlen Michael N. , Churchland Mark M. , Churchland Anne K. , Steinmetz Nicholas A. , Chang Edward F. , Schweitzer Jeffrey S. , Williams Ziv M. , Cash Sydney S. , Paninski Liam , Varol Erdem
Published: October 2023

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.
AI-Powered Smart Glasses for Sensing and Recognition of Human-Robot Walking Environments
Authors: Rossos Daniel , Mihailidis Alex , Laschowski Brokoslaw
Published: October 2023

Environment sensing and recognition can allow humans and robots to dynamically adapt to different walking terrains. However, fast and accurate visual perception is challenging, especially on embedded devices with limited computational resources. The purpose of this study was to develop a novel pair of AI-powered smart glasses for onboard sensing and recognition of human-robot walking environments with high accuracy and low latency. We used a Raspberry Pi Pico microcontroller and an ArduCam HM0360 low-power camera, both of which interface with the eyeglass frames using 3D-printed mounts that we custom-designed. We trained and optimized a lightweight and efficient convolutional neural network using a MobileNetV1 backbone to classify the walking terrain as either indoor surfaces, outdoor surfaces (grass and dirt), or outdoor surfaces (paved) using over 62,500 egocentric images that we adapted and manually labelled from the Meta Ego4D dataset. We then compiled and deployed our deep learning model using TensorFlow Lite Micro and post-training quantization to create a minimized byte array model of size 0.31MB. Our system was able to accurately predict complex walking environments with 93.6% classification accuracy and had an embedded inference speed of 1.5 seconds during online experiments using the integrated camera and microcontroller. Our AI-powered smart glasses open new opportunities for visual perception of human-robot walking environments where embedded inference and a low form factor is required. Future research will focus on improving the onboard inference speed and miniaturization of the mechatronic components.
Resolving spatiotemporal electrical signaling within the islet via CMOS microelectrode arrays
Authors: Gresch Anne , Hüwel Jan D. , Briggs Jennifer , Berger Tim , Koch Ruben , Deickert Thomas , Beecks Christian , Benninger Richard , Düfer Martina
Published: October 2023

Glucose-stimulated beta-cells synchronize calcium waves across the islet to recruit more beta-cells for insulin secretion. Compared to calcium dynamics, the formation and cell-to-cell propagation of electrical signals within the islet are poorly characterized. To determine factors that influence the propagation of electrical activity across the islet underlying calcium oscillations and beta-cell synchronization, we used high-resolution CMOS multielectrode arrays (MEA) to measure voltage changes associated with the membrane potential of individual cells within intact mouse islets. We measured both fast (milliseconds, spikes) and slow (seconds, waves) voltage changes and analyzed the spatiotemporal voltage dynamics. Treatment of islets from C57BL6 mice with increasing glucose concentrations revealed that single spike activity and wave signal velocity were both glucose-dependent. A repeated glucose stimulus involved a highly active subset of cells in terms of spike activity. When islets were pretreated for 72 hours with glucolipotoxic medium, the wave velocity was significantly reduced. Network analysis confirmed that the synchrony of islet cells was affected due to slower propagating electrical waves and not due to altered spike activity. In summary, this approach provided novel insight regarding the propagation of electrical activity and opens a wide field for further studies on signal transduction in the islet cell network.

Article Highlights

This study presents a new method for characterizing islet spatiotemporal electrical dynamics and subpopulations of beta-cells. We asked whether a high-resolution CMOS-MEA is suited to detect electrical signals on a level close to single cells, and whether we can track the propagation of electrical activity through the islet on a cellular scale. A highly active subpopulation of islet cells was identified by action potential-like spike activity, whereas slower waves were a measure for synchronized electrical activity. Further, propagating waves were slowed by glucolipotoxicity. The technique is a useful tool for exploring the pancreatic islet network in health and disease.
DAP12 deficiency alters microglia-oligodendrocyte communication and enhances resilience against tau toxicity
Authors: Chen Hao , Fan Li , Guo Qi , Wong Man Ying , Yu Fangmin , Foxe Nessa , Wang Winston , Nessim Aviram , Carling Gillian , Liu Bangyan , Lopez-Lee Chloe , Huang Yige , Amin Sadaf , Patel Tark , Mok Sue-Ann , Song Won-min , Zhang Bin , Ma Qin , Fu Hongjun , Gan Li , Luo Wenjie
Published: October 2023

Pathogenic tau accumulation fuels neurodegeneration in Alzheimer’s disease (AD). Enhancing aging brain’s resilience to tau pathology would lead to novel therapeutic strategies. DAP12 (DNAX-activation protein 12) is critically involved in microglial immune responses. Previous studies have showed that mice lacking DAP12 in tauopathy mice exhibit higher tau pathology but are protected from tau-induced cognitive deficits. However, the exact mechanism remains elusive. Our current study uncovers a novel resilience mechanism via microglial interaction with oligodendrocytes. Despite higher tau inclusions, Dap12 deletion curbs tau-induced brain inflammation and ameliorates myelin and synapse loss. Specifically, removal of Dap12 abolished tau-induced disease-associated clusters in microglia (MG) and intermediate oligodendrocytes (iOli), which are spatially correlated with tau pathology in AD brains. Our study highlights the critical role of interactions between microglia and oligodendrocytes in tau toxicity and DAP12 signaling as a promising target for enhancing resilience in AD.
Integration of QTL and transcriptome approaches for the identification of genes involved in tomato response to nitrogen deficiency
Authors: Desaint H. , Héreil A. , Belinchon-Moreno J. , Carretero Y. , Pelpoir E. , Pascal M. , Brault M , Dumont D. , Lecompte F. , Laugier P. , Duboscq R. , Bitton F. , Grumic M. , Giraud C. , Ferrante P. , Giuliano G , Sunseri F. , Causse M.
Published: October 2023

Optimising plant nitrogen (N) usage and inhibiting N leaching loss in the soil-crop system is crucial to maintain crop yield and reduce environmental pollution. This study aimed at identifying quantitative trait loci (QTL) and differential expressed genes (DEGs) between two N treatments in order to list candidate genes related to nitrogen-related contrasting traits in tomato varieties. We characterised a genetic diversity core-collection (CC) and a multi-parental advanced generation intercross (MAGIC) tomato population grown in greenhouse under two nitrogen levels and assessed several N-related traits and mapped QTLs. Transcriptome response under the two N conditions was also investigated through RNA sequencing of fruit and leaves in four parents of the MAGIC population.

Significant differences in response to N input reduction were observed at the phenotypic level for biomass and N-related traits. Twenty-seven (27) QTLs were detected for three target traits (Leaf N content, leaf Nitrogen Balance Index and petiole NO3-content), ten and six at low and high N condition, respectively; while 19 QTLs were identified for plasticity traits. At the transcriptome level, 4,752 and 2,405 DEGs were detected between the two N conditions in leaves and fruits, respectively, among which 3,628 (50.6%) in leaves and 1,717 (71.4%) in fruit were genotype specific. When considering all the genotypes, 1,677 DEGs were shared between organs or tissues.

Finally, we integrated DEGs and QTLs analyses to identify the most promising candidate genes. The results highlighted a complex genetic architecture of N homeostasis in tomato and novel putative genes useful for breeding improved-NUE tomato.

Highlight

Tomato response to nitrogen deficiency is genetically controlled by a few QTLs and impacts the expression of a large number of genes, among which some are good targets for breeding sober varieties.
Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan
Authors: Zhang Yizhong , Naaz Arshia , Cheng Trishia Yi Ning , Lin Jovian Jing , Alfatah Mohammad
Published: October 2023

Aging is a multifaceted biological process marked by the decline in both mitotic and postmitotic cellular function, often central to the development of age-related diseases. In the pursuit of slowing or even reversing the aging process, a prominent strategy of significant interest is calorie restriction (CR), also known as dietary restriction, and the potential influence of a drug called rapamycin (RM). Both CR and RM have demonstrated the capacity to extend healthspan and lifespan across a diverse array of species, including yeast, worms, flies, and mice. Nevertheless, their individual and combined effects on mitotic and postmitotic cells, as well as their comparative analysis, remain areas that demand a thorough investigation. In this study, we employ RNA-sequencing methodologies to comprehensively analyze the impact of CR, RM, and their combination (CR+RM) on gene expression in yeast cells. Our analysis uncovers distinctive, overlapping, and even contrasting patterns of gene regulation, illuminating the unique and shared effects of CR and RM. Most notably, our findings reveal a synergistic effect of CR+RM in extending the lifespan of postmitotic cells, a result validated in both yeast and human cells. This research offers valuable insights into the processes of aging and presents potential strategies for enhancing healthspan and delaying the onset of age-related diseases. These findings have the potential to revolutionize our approach to implementing these interventions under specific conditions and within the context of age-related diseases.
Single-nucleus RNA sequencing provides insights into the GL261-GSC syngeneic mouse model of glioblastoma
Authors: García-Vicente Laura , Borja Michael , Tran Vanessa , Álvarez-Vázquez Andrea , Flores-Hernández Raquel , Granados Alejandro , McGeever Aaron , Kim Yang-Joon , Dorman Leah , Detweiler Angela , Mekonen Honey , Paul Sheryl , Pisco Angela O , Neff Norma F , Tabernero Arantxa
Published: October 2023

Glioblastoma (GBM) is an aggressive tumor with very bad prognosis. The urgent need to find new effective therapies is challenged by the unique characteristics of GBM, including high intra and intertumoral heterogeneity. Using single-nucleus transcriptomics (snRNA-seq), we characterized the panorama of a preclinical immunocompetent murine model based in the implantation of mouse glioblastoma stem cells (GL261-GSCs) into the brain parenchyma. Additionally, we performed Visium spatial transcriptomics in the in vivo model to confirm the location of annotated cells. To understand the technical bias of this approach, we performed two scRNA-seq methods in GBM cells. We thoroughly characterized the tumor microenvironment (TME) at early and late stages of tumor development and upon treatment with temozolomide (TMZ), the standard of care for patients with GBM, and with Tat-Cx43266-283, a promising experimental treatment. We identified prominent GBM targets that can be addressed using this preclinical model, such asGrik2,Nlgn3,Gap43orKcnn4, which are involved in electrical and synaptic integration of GBM cells into neural circuits, as well as the expression ofNt5e,Cd274orIrf8, which indicates the development of immune evasive properties in these GBM cells. In agreement, snRNA-seq unveiled high expression of several immunosuppressive-associated molecules in immune cells, such asCsf1r, Arg1, Mrc1andTgfb1, suggesting the development of an immunosuppressive microenvironment. We also show the landscape of cytokines, cytokine receptors, checkpoint ligands and receptors in tumor and TME cells, which are crucial data for a rational design of immunotherapy studies. Thus, Mrc1, PD-L1, TIM-3 or B7-H3 are among the immunotherapy targets that can be addressed in this model. Finally, the comparison of the preclinical GL261-GSC GBM model with human GBM subtypes unveiled important similarities with the recently identified TMEmed human GBM, indicating that preclinical data obtained in GL261-GSC GBM model might be applied to TMEmed human GBM, improving patient stratification in clinical trials. In conclusion, this work provides crucial information for future preclinical studies in GBM improving their clinical application.
Thalamocortical Spindles occur during Rapid Eye Movement Sleep in Mouse Somatosensory Pathway
Authors: Boscher Flore , Jumel Katlyn , Dvořáková Tereza , Gentet Luc , Urbain Nadia
Published: October 2023

Rapid eye movement sleep (REM) is often considered as a homogeneous state of sleep. However, the frequent occurrence of transient events indicates that it may be separated into two distinct, phasic and tonic, substates. During tonic REM, we found local appearances of spindle waves in the barrel cortex concomitant with strong delta power on the local field potential. Subthreshold spindle oscillations in neurons of the ventral posterior medial nucleus further confirmed the thalamic origin of these cortical spindles. Spindle oscillations were suppressed in phasic REM, while thalamus spike firing increased associated with rapid whisker movements of mice and cortical activity transitioned to an activated state. During REM, sensory thalamus and barrel cortex therefore alternate between high (wake-like) and low (non-REM sleep-like) activation states, possibly allowing transient sensory integration windows to emerge throughout this paradoxical sleep stage.
Pre-Cambrian origin ofenvelope-carrying endogenous retroviruses in metazoans
Authors: Chary Shashank , Hayashi Rippei
Published: October 2023

Retrotransposons or endogenous retroviruses (ERVs) essentially carry open reading frames ofgagandpol, which are utilized to selfishly replicate themselves in the host’s germline genome. One rare example of ERVs that additionally carryenvelopegenes, are Ty3/gypsyerrantiviruses in Drosophila. Though they are structurally analogous to vertebrate retroviruses, their evolutionary relationship as well as the origin ofenvelopegenes remain elusive. We systematically searched for intactenvelope-containing ERVs that are homologous to Ty3/gypsyand vertebrate retroviruses in metazoan genomes and found that they are widespread across taxa including ancient animals such as Cnidarians, Ctenophores and Tunicates. Most elements are multiplied in their respective genomes, implying recent germline expansion.Envelopegenes are classified into those that resemble glycoprotein F from paramyxoviruses (F-type), glycoprotein B from herpesviruses (HSV/gB-type), and GP2 glycoprotein from retroviruses and Ebolavirus (GP2-type). Both F-type and HSV/gB-type ERVs are ubiquitously found in invertebrate genomes while vertebrate genomes carry F-type and GP2-type ERVs. Interestingly, vertebrate ERVs share a distinct and structurally conserved domain of POL with Ty3/gypsyelements from insects and ancient animals, suggesting that they share common origins. Furthermore, phylogenetic and structural analyses revealed thatenvelopegenes have largely diverged withpolgenes as well as with the host organisms throughout their evolutionary history and recombined infrequently, suggesting that theenvelopeacquisition to ERVs is ancient and likely dates to before the split of bilaterian and non-bilaterian animals in Pre-Cambrian era.
VisualR: a novel and scalable solution for assessing visual function using virtual reality
Authors: Sozzi Federica , Groß Henning , Ljubisic Bratislav , Adams Jascha , Gyacsok Andras , Graziano Giuseppe , Weiß Steffen , Pires Nuno D.
Published: October 2023

Background

Diagnosis and treatment of progressive eye diseases require effective monitoring of visual structure and function. However, current methods for measuring visual function are limited in accuracy, reliability, and usability. We propose a novel approach that leverages virtual reality (VR) technology to overcome these challenges, enabling more comprehensive measurements of visual function endpoints.

Results

We developed VisualR, a low-cost VR-based application that consists of a smartphone app and a simple VR headset. The virtual environment allows precise control of visual stimuli, full control over the field of view, separating visual input to the left and right eyes, controlling visual angles and blocking background visual noise. We developed novel tests for metamorphopsia, contrast sensitivity and reading speed that can be performed by following simple instructions and providing verbal responses to visual cues, without the need for expert supervision. The smartphone app does not require an internet connection, handles all data processing and image display, and all data is stored locally and owned by the user.

Conclusion

VisualR demonstrates the feasibility of building a visual function test device using consumer-grade hardware. Eventually, this technology could be used to measure visual function endpoints during clinical development of new treatments and to support disease diagnosis and monitoring. We open-sourced the application code and provide guidelines for creating reliable and user-friendly VR-based tests. We believe VR can open a new paradigm in visual function testing, and invite the wider community to build upon our work.
Associations Between Polygenic Scores for Cognitive and Non-cognitive Factors of Educational Attainment and Measures of Behavior, Psychopathology, and Neuroimaging in the Adolescent Brain Cognitive Development Study
Authors: Gorelik Aaron J. , Paul Sarah E. , Miller Alex P. , Baranger David A.A. , Lin Shuyu , Zhang Wei , Elsayed Nourhan M. , Modi Hailey , Addala Pooja , Bijsterbosch Janine , Barch Deanna M. , Karcher Nicole R. , Hatoum Alexander S. , Agrawal Arpana , Bogdan Ryan , Johnson Emma C.
Published: October 2023

Background

Both cognitive and non-cognitive (e.g., traits like curiosity) factors are critical for social and emotional functioning and independently predict educational attainment. These factors are heritable and genetically correlated with a range of health-relevant traits and behaviors in adulthood (e.g., risk-taking, psychopathology). However, whether these associations are present during adolescence, and to what extent these relationships diverge, could have implications for adolescent health and well-being.

Methods

Using data from 5,517 youth of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSMStudy, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and outcomes related to cognition, socioeconomic status, risk tolerance and decision-making, substance initiation, psychopathology, and brain structure.

Results

Cognitive and non-cognitive PGSs were both positively associated with cognitive performance and family income, and negatively associated with ADHD and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk-taking, delayed discounting, and anorexia, as well as lower likelihood of nicotine initiation. The cognitive PGS was further associated with cognition scores and anorexia inwithin-siblinganalyses, suggesting these results do not solely reflect the effects of assortative mating or passive gene-environment correlations. The cognitive PGS showed significantly stronger associations with cortical volumes than the non-cognitive PGS and was associated with right hemisphere caudal anterior cingulate and pars-orbitalis inwithin-siblinganalyses, while the non-cognitive PGS showed stronger associations with white matter fractional anisotropy and a significantwithin-siblingassociation for right superior corticostriate-frontal cortex.

Conclusions

Our findings suggest that PGSs for cognitive and non-cognitive factors show similar associations with cognition and socioeconomic status as well as other psychosocial outcomes, but distinct associations with regional neural phenotypes in this adolescent sample.
Outcomes of Percutaneous Coronary Intervention for Protected versus Unprotected Left Main Coronary Artery Disease: Insights from the VA CART Program
Authors: Gonzalez Pedro Engel , Hebbe Annika , Hussain Yasin , Khera Rohan , Banerjee Subhash , Plomondon Mary E , Waldo Stephen W. , Pfau Steven E. , Curtis Jeptha P. , Shah Samit M.
Published: October 2023

Background

Practice patterns and outcomes of protected left main (PLM) and unprotected left main (ULM) percutaneous coronary intervention (PCI), as well as the differences between these types of PCI, are not well defined in real-world clinical practice.

Methods

Data collected from all Veteran Affairs (VA) catheterization laboratories participating in the Clinical Assessment Reporting and Tracking Program between 2009 and 2019. The analysis included 4,351 patients undergoing left main PCI, of which 1,306 pairs of PLM and ULM PCI were included in a propensity matched cohort. Patients and procedural characteristics were compared between PLM and ULM PCI. Temporal trends were also assessed. Peri-procedural and one-year major adverse cardiovascular events (MACE) were compared using cumulative incidence plots. The primary outcome was MACE outcomes at 1-year, which was defined as a composite of all-cause mortality, rehospitalization for myocardial infarction (MI), rehospitalization for stroke or urgent revascularization.

Results

ULM PCI patients in comparison to PLM PCI were older (71.5 vs 69.2; P < 0.001), more clinically complex and more likely to present with ACS. In the propensity matched cohort, radial access was used more often for ULM PCI (21% [273] vs. 14% [185], P < 0.001), and ULM PCI was more likely to involve the LM bifurcation (22% vs 14%; P = 0.003) and require mechanical circulatory support (10% [134] vs 1% [17]; P <0.001). One-year MACE occurred more frequently with ULM PCI compared to PLM PCI (22% [289] vs. 16% [215]; P = < 0.001) and all-cause mortality was also higher (16% [213] vs. 10% [125]; P = < 0.001). In the matched cohort there was a low incidence of rehospitalization for MI (4% [48] ULM vs. 4% [48] PLM; P = 1.000) or revascularization (7% [94] ULM vs. 6% [84] PLM; P = 0.485).

Conclusions

Veterans undergoing PLM PCI had better one-year outcomes than those undergoing ULM PCI, but in both groups there was a high rate of mortality and MACE at one-year despite a relatively low rate of MI or revascularization.
FAK family proteins regulatein vivobreast cancer metastasisviadistinct mechanisms
Authors: Genna Alessandro , Alter Joel , Poletti Martina , Meirson Tomer , Sneh Tal , Gendler Michal , Saleev Natalia , Karagiannis George S. , Wang Yarong , Cox Dianne , Entenberg David , Oktay Maja H. , Korcsmaros Tamas , Condeelis John S. , Gil-Henn Hava
Published: October 2023

Breast cancer is the most commonly diagnosed malignancy and the major leading cause of tumor-related deaths in women. It is estimated that the majority of breast tumor-related deaths are a consequence of metastasis, to which no cure exists at present. The FAK family proteins Proline-rich tyrosine kinase (PYK2) and focal adhesion kinase (FAK) are highly expressed in breast cancer, but the exact cellular and signaling mechanisms by which they regulatein vivotumor cell invasiveness and consequent metastatic dissemination are mostly unknown. Using a PYK2 and FAK knockdown xenograft model we show here, for the first time, that ablation of either PYK2 or FAK decreases primary tumor size and significantly reduces Tumor MicroEnvironment of Metastasis (TMEM) doorway activation, leading to decreased intravasation and reduced spontaneous lung metastasis. Intravital imaging analysis further demonstrates that PYK2, but not FAK, regulates a motility phenotype switch between focal adhesion-mediated fast motility and invadopodia-dependent, ECM-degradation associated slow motility within the primary tumor. Furthermore, we validate ourin vivoand intravital imaging results with integrated transcriptomic and proteomic data analysis from xenograft knockdown tumors and reveal new and distinct pathways by which these two homologous kinases regulate breast tumor cell invasiveness and consequent metastatic dissemination. Our findings identify PYK2 and FAK as novel mediators of mammary tumor progression and metastasis and as candidate therapeutic targets for breast cancer metastasis.
TheMarchantiapangenome reveals ancient mechanisms of plant adaptation to the environment
Authors: Beaulieu Chloé , Libourel Cyril , Mbadinga Zamar Duchesse Lacourt , Mahboubi Karima El , Hoey David J. , Keller Jean , Girou Camille , Clemente Helene San , Diop Issa , Amblard Emilie , Théron Anthony , Cauet Stéphane , Rodde Nathalie , Zachgo Sabine , Halpape Wiebke , Meierhenrich Anja , Laker Bianca , Brautigam Andrea , Greiff George RL ,   The SLCU Outreach Consortium, Szovenyi Peter , Cheng Shifeng , Tanizawa Yasuhiro , Leebens-Mack James H. , Schmutz Jeremy , Webber Jenel , Grimwood Jane , Jacquet Christophe , Dunand Christophe , Nelson Jessica M. , Roux Fabrice , Philippe Hervé , Schornack Sebastian , Bonhomme Maxime , Delaux Pierre-Marc
Published: October 2023

Plant adaptation to a terrestrial life 450 million years ago played a major role in the evolution of life on Earth. This shift from an aquatic environment has been mostly studied by focusing on flowering plants. Here, we gathered a collection of 133 accessions of the non-vascular plantsMarchantia polymorphaand studied its intraspecific diversity using selection signature analyses, genome-environment association study and a gene-centered pangenome. We identified adaptive features shared with flowering plants, such as peroxidases or nucleotide-binding and leucine-rich repeat (NLR), which likely played a role in the adaptation of the first land plants to the terrestrial habitat. TheM. polymorphapangenome also harbored lineage-specific accessory genes absent from seed plants. We conclude that different land plants lineages still share many elements from the genetic toolkit evolved by their most recent common ancestor to adapt to the terrestrial habitat, refined by lineage specific polymorphisms and gene family evolutions.
Hybridde novoand haplotype resolved genome assembly of Vechur cattle - elucidating genetic variation
Authors: Muthusamy Poorvishaa V. , Mani Rajesh Vakayil , Kumari Shivani , Kaur Manpreet , Bhaskar Balu , Pillai Rajeev Raghavan , Kumar Thankappan Sajeev , Anilkumar Thapasimuthu Vijayamma , Singh N. Sadananda
Published: October 2023

Cattle contribute to the nutritional needs and economy of a place. Performance and fitness depends on the response and adaptation to local climatic conditions. Genomic and genetic studies are important for advancing cattle breeding and availability of relevant reference genomes are essential. In the present study, the genome of a Vechur calf was sequenced on both short-read illumina and long-read nanopore platforms. Hybridde novoassembly approach was deployed to obtain an average contigs length of 1.97 Mbp and N50 of 4.94 Mbp. Using a short-read genome sequence of the corresponding sire and dam, a haplotype-resolved genome was also assembled. In comparison to the taurine reference genome, we found 28982 autosomal structural variants, 16926990 SNVs with 883544 SNVs homozygous in the trio samples suggesting high prevalence of these SNPs in the population. Many of these SNPs have been reported to be associated with various QTLs including growth, milk yield and milk fat content which are crucial determinants of cattle production. Further, population genotype data analysis indicated that the present sample belongs to an Indian cattle breed forming a unique cluster ofBos indicus. Subsequent FSTanalysis revealed differentiation of Vechur cattle genome at multiple loci, especially those regions related to whole body growth and cell division especially IGF1, HMGA2, RRM2 and CD68 loci suggesting a possible role of these genes in its small stature and better disease resistance capabilities in comparison with the local crossbreeds. This provides an opportunity to select and engineer cattle breeds optimized for local conditions.
4D Crystallography Captures Transient IF1-Ribosome Dynamics in Translation Initiation
Authors: Yapici Ilkin , Dao E. Han , Yokoi Shun , Destan Ebru , Ayan Esra , Shafei Alaleh , Ertem Fatma Betul , Kulakman Cahine , Yilmaz Merve , Tosun Bilge , Ciftci Halilibrahim , Kepceoglu Abdullah , Johnson Jerome , Guven Omur , Ergul Ali , Hayes Brandon , Rao Yashas , Kupitz Christopher , Poitevin Frederic P. , Liang Mengling , Hunter Mark S. , Milon Pohl , Mitsutake Ayori , Sierra Raymond G. , Wakatsuki Soichi , DeMirci Hasan
Published: October 2023

Initiation factor 1 (IF1) is one of multiple key ligands involved in the initiation of mRNA translation, a highly dynamic and carefully-orchestrated process. However, details surrounding IF1 transient interactions with the small 30S ribosomal subunit remain incompletely understood despite characterization of unbound and fully-bound 30S states. Improvements in X-ray light sources and crystallographic techniques are now enabling time-resolved structural studies at near-physiological temperature and near-atomic resolution and thus the structural investigation of such dynamic processes. Here, we employed time-resolved serial femtosecond X-ray crystallography (TR-SFX) to probe the binding of IF1 to the small 30S ribosomal subunit in real time. Our time-resolved structural data demonstrates transient cryptic short-, mid-, and long-range allostery among different regions of the small 30 ribosomal subunit during IF1 binding, revealing small- and large-scale protein-target interactions and dynamics within intermediate macromolecular states at unprecedented temporal and spatial resolution. These data represent one of the first such 4D crystallographic studies assessing protein-protein and protein-RNA interactions and could serve as the basis for subsequent studies of the ribosome and of the multitudinous dynamic processes which underpin biology, and therefore, of life.
Determining the defining lengths between mature microRNAs/small interfering RNAs and tinyRNAs
Authors: Sim GeunYoung , Kehling Audrey C. , Park Mi Seul , Divoky Cameron , Zhang Huaqun , Malhotra Nipun , Secor Jackson , Nakanishi Kotaro
Published: October 2023

MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are loaded into Argonaute (AGO) proteins, forming RNA-induced silencing complexes (RISCs). The assembly process establishes the seed, central, 3′ supplementary, and tail regions across the loaded guide, enabling the RISC to recognize and cleave target RNAs. This guide segmentation is caused by anchoring the 3′ end at the AGO PAZ domain, but the minimum guide length required for the conformation remains to be studied because there was no method by which to do so. Using a 3′→5′ exonuclease ISG20, we determined the lengths of AGO-associated miR-20a and let-7a with 3′ ends that no longer reach the PAZ domain. Unexpectedly, miR-20a and let-7a needed different lengths, 19 and 20 nt, respectively, to maintain their RISC conformation. This difference can be explained by the low affinity of the PAZ domain for the adenosine at g19 of let-7a, suggesting that the tail-region sequence slightly alters the minimum guide length. We also present that 17-nt guides are sufficiently short enough to function as tinyRNAs (tyRNAs) whose 3’ ends are not anchored at the PAZ domain. Since tyRNAs do not have the prerequisite anchoring for the standardized guide segmentation, they would recognize targets differently from miRNAs and siRNAs.