bluuebunny/crossref_metadata_2025 huggingface dataset:
Clock-dependent chromatin accessibility rhythms regulate circadian transcription
Authors: Yuan Ye , Chen Qianqian , Brovkina Margarita , Clowney E. Josephine , Yadlapalli Swathi
Published: August 2023

Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms, how chromatin organization affects circadian rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible Chromatin with Sequencing) on FAC-sorted Drosophila clock neurons to assess genome-wide chromatin accessibility over the circadian cycle. We observed significant circadian oscillations in chromatin accessibility at promoter and enhancer regions of hundreds of genes, with enhanced accessibility either at dusk or dawn, which correlated with their peak transcriptional activity. Notably, genes with enhanced accessibility at dusk were enriched with E-box motifs, while those more accessible at dawn were enriched with VRI/PDP1-box motifs, indicating that they are regulated by the core circadian feedback loops, PER/CLK and VRI/PDP1, respectively. Further, we observed a complete loss of chromatin accessibility rhythms inper01null mutants, with chromatin consistently accessible throughout the circadian cycle, underscoring the critical role of Period protein in driving chromatin compaction during the repression phase. Together, this study demonstrates the significant role of chromatin organization in circadian regulation, revealing how the interplay between clock proteins and chromatin structure orchestrates the precise timing of biological processes throughout the day. This work further implies that variations in chromatin accessibility might play a central role in the generation of diverse circadian gene expression patterns in clock neurons.

Significance Statement

Chromatin organization plays a critical role in gene regulation in development and in disease. In this study, we discovered robust circadian oscillations in the chromatin accessibility of regulatory elements of clock-regulated genes inDrosophilaclock neurons, with enhanced accessibility either at dusk or dawn, which correlated with their peak transcriptional activity. We found enrichment of E-box motifs in genes that exhibited enhanced accessibility at dusk, and enrichment of VRI/PDP1-box motifs in genes that exhibited higher accessibility at dawn. Moreover, the complete loss of chromatin accessibility rhythms inper01mutants highlights the essential role of the Period protein in driving chromatin compaction during the repression phase. This study highlights the significance of chromatin organization in the generation of ∼24-hour circadian rhythms.
Bespoke conformation and antibody recognition distinguishes the streptococcal immune evasion factors EndoS and EndoS2
Authors: Sudol Abigail S. L. , Tews Ivo , Crispin Max
Published: August 2023

The IgG-specific endoglycosidases EndoS and EndoS2 fromStreptococcus pyogenesablate IgG function by removing the conserved N-linked glycans present on the Fc region. Their role in immune evasion, by inactivation of IgG antibodies, has led these enzymes to be investigated as therapeutics for suppressing unwanted immune activation. Their activity and precise substrate specificity has also prompted the development of these enzymes as tools for engineering IgG glycosylation. Recent structural studies have revealed how EndoS drives specificity for IgG by binding the Fc peptide surface with a domain that has homology for a carbohydrate-binding module (CBM). Here, we present the crystal structure of the EndoS2-IgG1 Fc complex at 3.0 Å resolution. Comparison with the EndoS-IgG1 Fc structure reveals a similar mode of interaction, but slightly different orientations resulting from different interfaces with glycosidase and CBM domains, leading to recognition of distinct Fc surfaces. These findings rationalise previous observations that non-catalytic domains cannot readily be substituted. The structural information presented here will guide the continued development of IgG-specific endoglycosidases in antibody glycoengineering and immunotherapy.
Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states
Authors: Morton Lorena , Arndt Philipp , Garza Alejandra P. , Henneicke Solveig , Mattern Hendrik , Gonzalez Marilyn , Dityatev Alexander , Yilmazer-Hanke Deniz , Schreiber Stefanie , Dunay Ildiko R.
Published: August 2023

Vascular risk factors such as chronic hypertension are well established major modifiable factors for the development of cerebral small vessel disease (cSVD). In the present study, our focus was the investigation of cSVD-related phenotypic changes in microglia in human disease and in the spontaneously hypertensive stroke-prone rat (SHRSP) model of cSVD. Our examination of cortical microglia in human post-mortem cSVD cortical tissue revealed distinct morphological microglial features specific to cSVD. We identified enlarged somata, an increase in the territory occupied by thickened microglial processes, and an expansion in the number of vascular-associated microglia. In parallel, we characterized microglia in a rodent model of hypertensive cSVD along different durations of arterial hypertension, i.e., early chronic and late chronic hypertension. Microglial somata were already enlarged in early hypertension, whereas at late-stage chronic hypertension they further exhibited elongat ed branches, thickened processes, and a reduced ramification index, mirroring the findings in human cSVD. An unbiased multidimensional flow cytometric analysis revealed phenotypic heterogeneit y among microglia cells within the hippocampus and cortex. At early-stage hypertension, hippocampal microglia exhibited upregulated CD11b/c, P2Y12R, CD200R, and CD86 surface markers. Detailed analysis of cell subpopulations revealed a unique microglial subset expressing CD11b/c, CD163, and CD86 exclusively in early hypertension. Notably, even at early-stage hypertension, microglia displayed a higher association with cerebral blood vessels. We identified several profound clusters of microglia expressing distinct marker profiles at late chronic hypertensive states. We further detected a temporal hypertension-related disturbances in blood-brain barrier integrity, accompanied by increased recruitment of leukocytes to the brain parenchyma in early hypertension. In summary, our findings demonstrate a higher vulnerability of the hippocampus, stage-specific microglial signatures based on morphological features, and cell surface protein expression in response to chronic arterial hypertension. These results indicate the diversity within microglia sub-populations and implicate the subtle involvement of microglia in cSVD pathogenesis.
Primary Human Cell-Derived Extracellular Matrix from Decellularized Fibroblast Microtissues with Tissue-Dependent Composition and Microstructure
Authors: Fonseca Vera C. , Van Vivian , Ip Blanche C.
Published: August 2023

Human extracellular matrix (ECM) exhibits complex protein composition and architecture depending on tissue and disease state, which remains challenging to reverse engineer. One promising approach is based on cell-secreted ECM from human fibroblasts, which can then be decellularized into an acellular biomaterial. However, fibroblasts initially seeded on rigid tissue culture plastic or biomaterial scaffolds experience aberrant mechanical cues that influence ECM deposition. Here, we show that engineered microtissues of primary human fibroblasts seeded in low-adhesion microwells can be decellularized to produce human, tissue-specific ECM. We investigate: 1) cardiac fibroblasts, as well as 2) lung fibroblasts from healthy, idiopathic fibrosis and chronic obstructive pulmonary disease donors. We demonstrate optimized culture and decellularization conditions, then characterize gene expression and protein composition. We further characterize ECM microstructure and mechanical properties. We envision that this method could be utilized for biomanufacturing of patient and tissue-specific ECM for organoid drug screening as well as implantable scaffolds.

Impact

In this study, we demonstrate a method for preparing decellularized matrix using primary human fibroblasts with tissue and disease-specific features. We aggregate single cell dispersions into engineered tissues using low adhesion microwells and show culture conditions that promote ECM deposition. We demonstrate this approach for cardiac fibroblasts as well as lung fibroblasts (both normal and diseased). We systematically investigate tissue morphology, matrix architecture, and mechanical properties, along with transcriptomic and proteomic analysis. This approach should be widely applicable for generating personalized ECM with features of patient tissues and disease state, relevant for culturing patient cells ex vivo as well as implantation for therapeutic treatments.
Laminar Dynamics of Target Selection in the Posterior Parietal Cortex of the Common Marmoset
Authors: Selvanayagam Janahan , Johnston Kevin D. , Everling Stefan
Published: August 2023

The lateral intraparietal area (LIP) plays a crucial role in target selection and attention in primates, but the laminar microcircuitry of this region is largely unknown. To address this, we used ultra-high density laminar electrophysiology with Neuropixels probes to record neural activity in the posterior parietal cortex (PPC) of two adult marmosets while they performed a simple visual target selection task. Our results reveal neural correlates of visual target selection in the marmoset, similar to those observed in macaques and humans, with distinct timing and profiles of activity across cell types and cortical layers. Notably, a greater proportion of neurons exhibited stimulus related activity in superficial layers whereas a greater proportion of infragranular neurons exhibited significant post-saccadic activity. Stimulus-related activity was first observed in granular layer putative interneurons, whereas target discrimination activity emerged first in supragranular layers putative pyramidal neurons, supporting a canonical laminar circuit underlying visual target selection in marmoset PPC. These findings provide novel insights into the neural basis of visual attention and target selection in primates.
Analyzing microbial evolution through gene and genome phylogenies
Authors: Teichman Sarah , Lee Michael D. , Willis Amy D.
Published: August 2023

Abstract

Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories. To address this challenge, we propose to treat estimated gene-level phylogenies as data objects, and present an interactive method for the analysis of a collection of gene phylogenies. We use a local linear approximation of phylogenetic tree space to visualize estimated gene trees as points in low-dimensional Euclidean space, and address important practical limitations of existing related approaches, allowing an intuitive visualization of complex data objects. We demonstrate the utility of our proposed approach through microbial data analyses, including by identifying outlying gene histories in strains ofPrevotella, and by contrastingStreptococcusphylogenies estimated using different gene sets. Our method is available as an open-source R package, and assists with estimating, visualizing and interacting with a collection of bacterial gene phylogenies. dimension reduction, microbiome, non-Euclidean, statistical genetics, visualization
New insights into functional divergence and adaptive evolution of uncultured bacteria in anammox community by complete genome-centric analysis
Authors: Wang Yi-Cheng , Mao Yanping , Fu Hui-Min , Wang Jin , Weng Xun , Liu Zi-Hao , Xu Xiao-Wei , Yan Peng , Fang Fang , Guo Jin-Song , Shen Yu , Chen You-Peng
Published: August 2023

Anaerobic ammonium-oxidation (anammox) bacteria play a crucial role in global nitrogen cycling and wastewater nitrogen removal, but they share symbiotic relationships with various other microorganisms. No pure culture is available for anammox bacteria so far. Although shotgun metagenomics based on short reads has been widely used in anammox research, metagenome-assembled genomes (MAGs) are often discontinuous and highly contaminated, which limits in-depth analyses of anammox communities. Here, for the first time, we performed Pacific Biosciences high-fidelity (HiFi) long-read sequencing on the anammox granule sludge sample from a lab-scale bioreactor, and obtained 30 accurate and complete metagenome-assembled genomes (cMAGs). These cMAGs were obtained by selecting high-quality circular contigs from initial assemblies of long reads generated by HiFi sequencing, eliminating the need for Illumina short reads, binning, and reassembly. One new anammox species and species from three novel families were found in this anammox community. cMAG-centric analysis revealed divergences in general and nitrogen metabolism among members of the anammox community. Furthermore, we identified mobile genetic elements (MGEs) and putative horizontal gene transfer (HGT) events within these cMAGs to explore the adaptive evolution of the community. The results suggest that MGEs and HGT events, particularly transposons containingtnpAin anammox bacteria, might play important roles in the adaptive evolution of this anammox community. The cMAGs generated in the present study could be used to establish of a comprehensive database for anammox bacteria and associated microorganisms. Our findings highlight the advantages of HiFi sequencing for the studies of complex mixed cultures such as anammox communities and advance our understanding of anammox communities.
Coronaviruses Spike glycoprotein endodomains: the sequence and structure-based comprehensive study
Authors: Kumar Prateek , Bhardwaj Aparna , Mukherjee Bodhidipra , Joshi Richa , Giri Rajanish
Published: August 2023

The flexibility of proteins makes them available to interact with many biomolecules in the cell. Specifically, such interactions in viruses help them to perform more functions despite having a smaller genome. Therefore, these flexible regions can be exciting and essential targets to be explored for their role in pathogenicity and therapeutic developments as they achieve essential interactions. In the continuation with our previous study on disordered analysis of SARS-CoV-2 spike cytoplasmic tail (CTR), or endodomain, here we have explored the disordered potential endodomains of six other coronaviruses using multiple bioinformatics approaches and molecular dynamics simulations. Based on the comprehensive analysis of its sequence and structural composition, we report the varying disorder propensity in endodomains of spike proteins of coronaviruses. The observations of this study may help to understand the importance of spike glycoprotein endodomain and creating therapeutic interventions against them.
Differences in personality within and between five species of ants in open field tests
Authors: Pedraza Alexandra Rodriguez
Published: August 2023

When confronted to new situations individuals may express different kinds of behaviors. They can be atracted, explore, get immobile, attack, hide or increase their motor activity in order to confront or avoid this situation. Several studies have been conducted on vertebrate species and different patterns have been observed depending on factors as genetic or environmental ones as well as cases of rigidity or flexibility in behaviorl reaction. Less studies have been conducted on insects personalities but the current research is improving in this aspect. Here I present the case of five ant species that I tested in open field tests in order to detect if they present different response profiles when confronted to a novel environment and how these profiles can vary depending on factors as species, ambient conditions or ecological realities of the studied populations. In this article I expose hypothesis to explain you how they react in these circumstancies and how the observed differences can subtend some of their living realities.
The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation
Authors: Moore Madeleine , Pardo-Fernandez Luis , Mitchell Louise , Schmidt Tobias , Waldron Joseph A , May Stephanie , Muller Miryam , Smith Rachael C. L. , Strathdee Douglas , Bryson Sheila , Hodge Kelly , Lilla Sergio , Wilczynska Ania , McGarry Lynn , Gillen Sarah , Peter-Durairaj Ruban , Kanellos Georgios , Nixon Colin , Zanivan Sara , Sansom Owen J. , Bird Thomas G. , Bushell Martin , Norman Jim C.
Published: August 2023

Increased protein synthesis supports growth of established tumours. However, how mRNA translation contributes to early tumorigenesis remains unclear. Here we show that following oncogene activation, hepatocytes enter a non-proliferative/senescent-like phase characterized by α5β1 integrin-dependent deposition of fibronectin-rich extracellular matrix (ECM) niches. These niches then promote exit from oncogene-induced senescence to permit progression to proliferating hepatocellular carcinoma (HCC). Removal of eIF4A2, a negative regulator of mRNA translation, boosts the synthesis of membrane/secretory proteins which drives a compensatory increase in the turnover/degradation of membrane proteins including α5β1 integrin. This increased membrane protein degradation, in turn, compromises generation of ECM-rich tumour initiation niches, senescence-exit and progression to proliferating HCC. Consistently, pharmacological inhibition of mRNA translation following eIF4A2 loss restores ECM deposition and reinstates HCC progression. Thus, although inhibition of protein synthesis may be an effective way to reduce tumour biomass and the growth of established tumours, our results highlight how agents which reduce mRNA translation, if administered during early tumorigenesis, may awaken senescent cells and promote tumour progression.
TroR is the primary regulator of the iron homeostasis transcription network in the halophilic archaeonHaloferax volcanii
Authors: Pastor Mar Martinez , Sakrikar Saaz , Hwang Sungmin , Hackley Rylee , Soborowski Andrew , Maupin-Furlow Julie A. , Schmid Amy
Published: August 2023

Maintaining intracellular iron concentration within the homeostatic range is vital to meet cellular metabolic needs and reduce oxidative stress. Previous research revealed that the haloarchaeonHalobacterium salinarumencodes four diphtheria toxin repressor (DtxR) family transcription factors (TFs) that together regulate the iron response through an interconnected transcriptional regulatory network (TRN). However, the metal specificity of DtxR TFs and the conservation of the TRN remained poorly understood. Here we identified and characterized the TRN ofHaloferax volcaniifor comparison. Genetic analysis demonstrated thatHfx. volcaniirelies on three DtxR transcriptional regulators (Idr, SirR, and TroR), with TroR as the primary regulator of iron homeostasis. Bioinformatics and molecular approaches revealed that TroR binds a conservedcis-regulatory motif located ∼100 nt upstream of the start codon of iron-related target genes. Transcriptomics analysis demonstrated that, under conditions of iron sufficiency, TroR repressed iron uptake and induced iron storage mechanisms. TroR repressed the expression of one other DtxR TF, Idr. This reduced DtxR TRN complexity relative to that ofHbt. salinarumappeared correlated with natural variations in iron availability. Based on these data, we hypothesize that increasing TRN complexity appears selected for under variable environmental conditions such as iron availability.
Assessing the construction site supervisory attributes in effectuating mathematical theories and applications to construction operations
Authors: Manoharan Kesavan , Dissanayake Pujitha , Pathirana Chintha , Deegahawature Dharsana , Silva Renuka
Published: August 2023

Purpose

Site supervision features largely influence the productivity status of construction operational processes. This study aims to use a case study containing mixed methods to test the site supervisory traits in applying mathematical theories to construction operations for directing supervisory capabilities under various operational characteristics.

Design/methodology/approach

A total of 62 construction site supervisors were trained as part of a new apprenticeship programme. Through literature reviews and expert consultations, grading criteria were designed with various degrees of descriptions and score ratings. The supervisory attributes were evaluated under seven competency element characteristics mapped with the relevant learning domains.

Findings

The results demonstrate a detailed sectional view of performance ratings of supervisors under different characteristics of competency factors with the validity, reliability, applicability and generalisability assurance of the research findings using relevant statistical tests and expert evaluations.

Research limitations/implications

Though the research applications were engaged directly with the construction industry in the Sri Lankan setting, other developing countries and emerging industries can also employ equivalent tactics to attain similar outcomes in their industry-based operations.

Originality/value

The research findings have led to producing a new guide that makes significant impacts on deciding the capability levels in construction supervisory attributes while executing problem-solving applications in construction planning and operational processes. Accordingly, the findings push to open a gate to intake advanced cognitive attributes towards addressing the industry's knowledge gap on how the problem-solving-based apprenticeship protocols need to be linked with the supervision features.
How to build rapport in online space: using online chat emoticons for qualitative interviewing in feminist research
Authors: Park Jiyea
Published: August 2023

Purpose

This study draws on the author's experiences building rapport through online chat for data collection for the author's doctoral dissertation. The author contacted ten Korean women via online chat to recruit and faced the most challenging situation; building rapport. As the Millennial generation is known as being tech-savvy or digital natives, the author actively used emoticons (pictorial representations of facial expressions using characters) with potential interviewees and completed ten interviews. Therefore, this paper offers a new qualitative interviewing method in feminist research.

Design/methodology/approach

The paper briefly reviews the works of literature on interviewing women on sensitive topics and building rapport before the interview. Then, the author introduced using emoticons to create rapport during the data collection process and how a non-traditional approach positively impacts the interviewer and interviewee before, during and even after the interview.

Findings

Women participants' responses and behaviors differed after building a rapport through an online chat. They were willing to share their personal stories and memories with the interviewer even though the interviewer did not ask.

Research limitations/implications

This study provides a stepping stone for developing an account of the new qualitative methodological approach, specifically feminist qualitative research.

Originality/value

Few studies have described how qualitative researchers create a rapport in virtual space, specifically using emoticons. Also, this study suggests a new methodological approach since nonverbal communication in online chat is inevitable when interviewing people in qualitative research.
The dynamic trade-off theory of capital structure: evidence from a panel of US industrial companies
Authors: Esghaier Ridha
Published: August 2023

Purpose

This paper aims to test the empirical validity of the dynamic trade-off theory in its symmetric and asymmetric versions in explaining the capital structure of a panel of publicly listed US industrial firms over the period from 2013 to 2019. It analyzes the existence of an adjustment of leverage toward its target level and whether the speed of this adjustment is influenced by the debt measure, the model specification or/and the fact that the actual debt ratio is higher or lower than its long-term target level.

Design/methodology/approach

This paper uses a quantitative research methodology using panel data analysis under the partial adjustment model and the error correction model using the generalized moment method in first differences and in systems to explore the dynamic nature of firms’ capital structure behavior.

Findings

The results show that the effects of the conventional determinants of leverage are globally consistent with the trade-off theory predictions. The dynamic versions confirm that firms exhibit leverage-targeting behavior. Although this speed of adjustment (SOA) depends on the debt and model specifications, it is around 60% on average. The estimated SOA is higher for the market leverage measure compared to the book leverage. The asymmetric adjustment model reveals that firms are more sensitive to reducing leverage than increasing it when they are away from their target; overleveraged firms exhibit approximately 5% faster adjustment than underleveraged firms when book leverage is used.

Originality/value

The originality of this research paper lies in its development and test of an asymmetric model to allow the leverage adjustment speed to vary depending on whether the firm’s debt ratio is above or below its target level and the methodological approach as well as the different model specifications used and the insights generated through the application of rigorous econometric techniques.
Rural development and digital technologies: a collaborative framework for policy-making
Authors: Monda Antonella , Feola Rosangela , Parente Roberto , Vesci Massimiliano , Botti Antonio
Published: August 2023

Purpose

The paper aims to define a model for rural development, able to stimulate collaborations between actors involved in the agrifood chain and based on digital technologies as enabling factors for such collaborations.

Design/methodology/approach

An exploratory research, based on a qualitative approach, is conducted, using both constructivist grounded theory and Gioia methodology. Data were collected through semi-structured interviews and roundtables administered to Italian key players.

Findings

The authors identify five actions (definition of territorial identity, involvement of internal and external supply chain actors, definition of quality standards, cooperation intra and infra supply chains, communication through technology) for collaboration in the development of rural areas that policymakers should encourage and actors in the supply chains must implement. The paper also entails both theoretical and practical implications. From the theoretical point of view, this study contributes to the literature on the relationship between agrifood, local development and the role of technologies. From the managerial point of view, this paper provides insights for policymakers to define strategies and actions aimed at developing collaborations between actors involved in the agrifood chain and leveraging digital technologies to support rural development.

Originality/value

The paper proposes a framework for the collaboration of the actors of the agrifood sector and related food tourism that could be the basis for the development of a digital platform able to connect all the subjects involved in rural development.
Making Global Governance Accountable: Civil Society, States, and the Politics of Reform
Authors: Lall Ranjit
Published: August 2023

Recent decades have witnessed the adoption of unprecedentedly broad and inclusive accountability mechanisms by many major international institutions, from grievance redress systems to transparency policies. What explains the establishment of these mechanisms—and why have only some institutions embraced them? I argue that adoption is more likely when member states, in particular the most powerful, face “bottom‐up” pressures for accountability from dense transnational civil society networks—networks with the capacity to build leverage through agenda setting, coalition building, and advocacy strategies—and when institutions perform governance tasks that are costly to monitor. Analysis of a rich new dataset shows that adoption is positively related to the density of international nongovernmental organizations in an institution's issue area—including only those based in powerful member countries—and that this relationship is stronger when governance tasks entail high monitoring costs. Statistical tests are complemented by qualitative evidence from interviews and other primary sources.
Intraoral digital implant scans: Parameters to improve accuracy
Authors: Revilla‐León Marta , Lanis Alejandro , Yilmaz Burak , Kois John C. , Gallucci German O.
Published: August 2023

Purpose

To report the means to maximize the predictability and accuracy of intraoral digital implant scans through the evaluation of operator and patient‐related factors.

Materials and Methods

A search of published articles related to factors that can decrease the scanning accuracy of intraoral digital implant scans was completed in four data sources:MEDLINE, EMBASE, EBSCO, and Web of Science. All studies related to variables that can influence the accuracy of intraoral digital implant scans obtained by using intraoral scanners (IOSs) were considered. These variables included ambient lighting, scanning pattern, implant scan body (ISB) design, techniques for splinting ISBs, arch location, implant position, and inter‐implant distance.

Results

Among operator‐related factors, ambient lighting conditions, scanning pattern, and ISB design (material, geometry, and retention design) can impact the accuracy of intraoral digital implant scans. The optimal ISB for maximizing IOS accuracy is unclear; however, polymer ISB can wear with multiple reuse and sterilization methods. Among patient‐related factors, additional variables should be considered, namely arch (maxillary vs. mandibular arch), implant position in the arch, inter‐implant distance, implant depth, and angulation.

Conclusions

Ambient lighting conditions should be established based on the IOS selected to optimize the accuracy of intraoral digital implant scans. The optimal scanning pattern may vary based on the IOS, clinical situation, and the number of implants. The optimal ISB design may vary depending on the IOS used. Metallic implant scan bodies are preferred over polymer ISB designs to minimize wear due to multiple use and sterilization distortion. Among patient‐related factors, additional variables should be considered namely the arch scanned, implant position in the arch, inter‐implant distance, implant depth, and angulation. The impact of these factors may vary depending on the IOS selected.
After string of failures, Japan aims to launch x-ray telescope
Authors: Clery Daniel
Published: August 2023

Groundbreaking XRISM will capture spectra, revealing the motion and composition of million-degree gases
Yolk sac cell atlas reveals multiorgan functions during human early development
Authors: Goh Issac , Botting Rachel A. , Rose Antony , Webb Simone , Engelbert Justin , Gitton Yorick , Stephenson Emily , Quiroga Londoño Mariana , Mather Michael , Mende Nicole , Imaz-Rosshandler Ivan , Yang Lu , Horsfall Dave , Basurto-Lozada Daniela , Chipampe Nana-Jane , Rook Victoria , Lee Jimmy Tsz Hang , Ton Mai-Linh , Keitley Daniel , Mazin Pavel , Vijayabaskar M. S. , Hannah Rebecca , Gambardella Laure , Green Kile , Ballereau Stephane , Inoue Megumi , Tuck Elizabeth , Lorenzi Valentina , Kwakwa Kwasi , Alsinet Clara , Olabi Bayanne , Miah Mohi , Admane Chloe , Popescu Dorin-Mirel , Acres Meghan , Dixon David , Ness Thomas , Coulthard Rowen , Lisgo Steven , Henderson Deborah J. , Dann Emma , Suo Chenqu , Kinston Sarah J. , Park Jong-eun , Polanski Krzysztof , Marioni John , van Dongen Stijn , Meyer Kerstin B. , de Bruijn Marella , Palis James , Behjati Sam , Laurenti Elisa , Wilson Nicola K. , Vento-Tormo Roser , Chédotal Alain , Bayraktar Omer , Roberts Irene , Jardine Laura , Göttgens Berthold , Teichmann Sarah A. , Haniffa Muzlifah
Published: August 2023

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.
Overcoming losses in superlenses with synthetic waves of complex frequency
Authors: Guan Fuxin , Guo Xiangdong , Zeng Kebo , Zhang Shu , Nie Zhaoyu , Ma Shaojie , Dai Qing , Pendry John , Zhang Xiang , Zhang Shuang
Published: August 2023

Superlenses made of plasmonic materials and metamaterials can image features at the subdiffraction scale. However, intrinsic losses impose a serious restriction on imaging resolution, a problem that has hindered widespread applications of superlenses. Optical waves of complex frequency that exhibit a temporally attenuating behavior have been proposed to offset the intrinsic losses in superlenses through the introduction of virtual gain, but experimental realization has been lacking because of the difficulty of imaging measurements with temporal decay. In this work, we present a multifrequency approach to constructing synthetic excitation waves of complex frequency based on measurements at real frequencies. This approach allows us to implement virtual gain experimentally and observe deep-subwavelength images. Our work offers a practical solution to overcome the intrinsic losses of plasmonic systems for imaging and sensing applications.
Human POT1 protects the telomeric ds-ss DNA junction by capping the 5′ end of the chromosome
Authors: Tesmer Valerie M. , Brenner Kirsten A. , Nandakumar Jayakrishnan
Published: August 2023

Protection of telomeres 1 (POT1) is the 3′ single-stranded overhang-binding telomeric protein that prevents an ataxia telangiectasia and Rad3–related (ATR) DNA damage response (DDR) at chromosome ends. What precludes the DDR machinery from accessing the telomeric double-stranded–single-stranded junction is unknown. We demonstrate that human POT1 binds this junction by recognizing the phosphorylated 5′ end of the chromosome. High-resolution crystallographic structures reveal that the junction is capped by POT1 through a “POT-hole” surface, the mutation of which compromises junction protection in vitro and telomeric 5′-end definition and DDR suppression in human cells. Whereas both mouse POT1 paralogs bind the single-stranded overhang, POT1a, not POT1b, contains a POT-hole and binds the junction, which explains POT1a’s sufficiency for end protection. Our study shifts the paradigm for DDR suppression at telomeres by highlighting the importance of protecting the double-stranded–single-stranded junction.
In silico protein interaction screening uncovers DONSON’s role in replication initiation
Authors: Lim Yang , Tamayo-Orrego Lukas , Schmid Ernst , Tarnauskaite Zygimante , Kochenova Olga V. , Gruar Rhian , Muramatsu Sachiko , Lynch Luke , Schlie Aitana Verdu , Carroll Paula L. , Chistol Gheorghe , Reijns Martin A. M. , Kanemaki Masato T. , Jackson Andrew P. , Walter Johannes C.
Published: August 2023

CDC45-MCM2-7-GINS (CMG) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit “pre-loading complex” (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a vertebrate pre-LC containing GINS, TOPBP1, and DNA pol ε. Our evidence suggests that DONSON docks the pre-LC onto MCM2-7, delivering GINS to its binding site in CMG. A patient-derived DONSON mutation compromises CMG assembly and recapitulates microcephalic dwarfism in mice. These results unify our understanding of eukaryotic replication initiation, implicate defective CMG assembly in microcephalic dwarfism, and illustrate how in silico protein-protein interaction screening accelerates mechanistic discovery.
Synthesis of Monodisperse Silica Particles by Controlled Regrowth
Authors: Khlebtsov B. N. , Burov A. M.
Published: August 2023

The development of a simple and reproducible method for the synthesis of monodisperse silica particles is of considerable interest from the point of view of their numerous applications in photonics, biosensing, and biomedicine. When using the well-known Stober method, there is a continuous formation and growth of seeds, which leads to the synthesis of polydisperse colloids. In this work, we used the method of successive growth of silica particles obtained by hydrolytic condensation of tetraethylorthosilicate in an alcoholic-aqueous medium using an alkaline catalyst. It is shown that this technique makes it possible to obtain colloids with a particle size from 50 nm to 3 μm and a standard deviation of less than 5%. An additional advantage of the developed method of stepwise growth is the possibility to include fluorophores and SERS tags into the silica matrix.
Closure of a distal splenorenal shunt as a therapy for refractory hyperammonaemia in setting of neuropsychiatric symptoms
Authors: Miller Alexander , Bernshteyn Michelle , Achakzai Basit , Macfie Rebekah
Published: August 2023

Before the widespread use of the transjugular intrahepatic portosystemic shunt, portal hypertension was addressed by the creation of an operative distal splenorenal shunt (DSRS). DSRS was largely regarded as a safe and effective therapy, though it did have a risk of precipitating hyperammonaemia and hepatic encephalopathy.

A woman suffered a gunshot wound to the abdomen. This trauma led to portal vein thrombosis, cavernous transformation of the vein and eventually bleeding oesophageal varices from portal hypertension. A DSRS was created to decrease portal hypertension. Years later, she had profound depression with psychomotor slowing in the setting of hyperammonaemia. To reduce hepatic encephalopathy as a contributor to her neuropsychiatric condition, her shunt was closed. The hyperammonaemia resolved and neuropsychiatric symptoms improved.

This case highlights several interesting clinical features, including portal hypertension due to chronic portal vein occlusion, cavernous transformation, a surgical DSRS causing hyperammonaemia and hepatic encephalopathy manifesting as neuropsychiatric symptoms.
Preexercise intermittent passive stretching and vascular function after treadmill exercise
Authors: Caldwell Jacob T. , Fenn Sarah A. , Bekkedal Lukas M. , Dodge Christopher , Muller-Delp Judy
Published: August 2023

We demonstrate for the first time that popliteal artery and gastrocnemius microvascular responsiveness after acute aerobic exercise are reduced. The decline in vascular function was mitigated in those who performed intermittent passive stretching before the exercise bouts. Collectively, these findings suggest that intermittent passive stretching is a novel method to increase vascular resiliency before aerobic activity.
Mesenchymal stromal cells for improvement of cardiac function following acute myocardial infarction: a matter of timing
Authors: Barrère-Lemaire Stéphanie , Vincent Anne , Jorgensen Christian , Piot Christophe , Nargeot Joël , Djouad Farida
Published: August 2023

Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.
Comparison of Different Chronic Maintenance Antithrombotic Strategies in Patients with Coronary Artery Disease: A Systematic Review and Network Meta-Analysis
Authors: Zhang Junyan , Chen Zhongxiu , Cai Yujia , Li Chen , He Yong
Published: August 2023

Background. Optimal antithrombotic therapy during the chronic maintenance period in patients with coronary artery disease (CAD) is unknown. We compared five kinds of mainstream chronic maintenance antithrombotic strategies at least one year after the acute phase: aspirin alone, clopidogrel alone, ticagrelor alone, continued dual antiplatelet therapy (DAPT) for a period of time, and maintenance with aspirin combined with a low-dose anticoagulant such as rivaroxaban. Methods. Ten randomized, controlled trials were selected using PubMed, Ovid MEDLINE, Embase, and Cochrane library through February 2023. The primary outcome was main adverse cardiac events (MACEs), and secondary outcomes include net adverse clinical events (NACEs), cardiac death, all-cause death, ischemic stroke, stent thrombosis, total bleeding, and major bleeding. A network meta-analysis was conducted with a random-effects model. Data extraction was performed by three independent reviewers. Results. Our search identified ten eligible randomized controlled trials enrolling a total of 82,084 patients comparing different chronic maintenance antithrombotic strategies. As for the primary endpoint, there was no statistical difference in MACE outcomes between any two of the five methods. As for the secondary endpoint, there was no statistical difference in NACE, major bleeding, all-cause death, cardiac death, and stent thrombosis between any two methods. The aspirin plus low-dose rivaroxaban group had a lower incidence of ischemic stroke compared to the aspirin group (

OR
=
0.49

, 95% CrI 0.26-0.91). And the prolonged DAPT group had a higher total bleeding rate compared to aspirin group (

OR
=
2.4

, 95% CrI 1.1-5.9). Conclusions. In terms of MACE, NACE, all-cause death, cardiac death, stent thrombosis, and major bleeding, there were no significant differences between using aspirin alone, clopidogrel alone, and ticagrelor alone; extending DAPT duration; and using aspirin combined with low-dose rivaroxaban for chronic maintenance antithrombotic regimens. However, choosing aspirin combined with low-dose rivaroxaban can reduce the incidence of ischemic stroke, and prolonged DAPT may have a higher rate of total bleeding. However, it is important to note that this study is based on indirect comparisons, and there is currently a lack of direct evidence comparing various maintenance antiplatelet therapy regimens. Further high-quality studies are needed to address this gap and provide more conclusive evidence on the comparative effectiveness of different maintenance antiplatelet strategies.
Ser professor em tempo de reconstrução: manter o foco e reluzir o brilho da alegria motivadora
Authors: Pereira Alexander
Published: August 2023

O artigo reflete a percepção de um professor que acredita que estamos vivendo um momento nebuloso no Brasil. O autor encontra ressonância em Ressa quando afirma que as fake news e as plataformas digitais alimentadas por mentiras causam grande destruição. Ele acredita que o brilho do conhecimento oferecido pela escola é parte importante do antídoto que pode erradicar esse mal. E encontra respaldo em Csikzentmihalyi, Gardner, Freire e Gainza.
Diagnostic Approach for Suspected Acute Myocarditis: Considerations for Standardization and Broadening Clinical Spectrum
Authors: Martens Pieter , Cooper Leslie T. , Tang W. H. Wilson
Published: August 2023

Myocarditis is most recognized in patients with moderate to severe, recent‐onset heart failure. However, less typical presentations including myocardial infarction with normal coronary arteries and arrhythmias are important manifestations but less commonly recognized to be caused by myocarditis. Most cases of myocarditis can be self‐limiting without specific treatment; however, appropriate identification of risk during the diagnostic process of myocarditis and once a diagnosis is established is of primordial importance to identify patients in need for more specific follow‐up and management. We propose a flexible, multitiered approach to the diagnostic process, allowing for capturing of the spectrum of myocarditis at an early time‐point, individualized use of diagnostic resources through disease severity phenotyping, and providing structured follow‐up care once myocarditis is confirmed. Such diagnostic processes allow for identification of specific etiologies with potential therapeutic consequences or allows for the comprehension of disease chronicity by understanding genetic contributions or elements of persistent immune dysregulation and degree of cardiac damage. The article highlights the evolving field of immunophenotyping in myocarditis, generating a potential for the development of targeted therapeutic approaches. Currently long‐term follow‐up should be titrated to the refined risk assessments of patients with a diagnosis of myocarditis and includes arrhythmia monitoring and imaging when the results will likely impact management. Genetic testing should be considered in selected cases, and histologic diagnosis may be considered in nonresponders even at later stages.
From Postal Scale to Psychological Apparatus
Authors: Cristalli Claudia , Jackson Rebecca L.
Published: August 2023

This paper describes our reconstruction of the apparatus used in C.S. Peirce and Joseph Jastrow’s 1885 psychophysical experiment, “On Small Differences of Sensation” and how it relates to persistent questions in scientific theories of measurement. We situate Peirce and Jastrow’s work in the broader context of nineteenth-century discussions about the status of psychology as a science and emphasize the role of measurement and experiment in determining that status. Through our re-enactment of the experiment, we analyze the experiment’s methodology, which features blinding, randomization, noise control, and a technology for data recording. Our claims are illustrated by images of historical and reconstructed apparatuses, as well as graphs of the data collected in our reproduction. Our findings exemplify the relevance of history of psychology for contemporary philosophy of science and theories of measurement, and defend experimental reconstructions as a particularly fertile method of inquiry in the history of psychophysical sciences.