bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Correlation: Optimal Transport Metrics For Characterizing Representational Stability and Remapping in Neurons Encoding Spatial Memory
Authors: Aoun Andrew , Shetler Oliver , Raghuraman Radha , Rodriguez Gustavo A. , Hussaini S. Abid
Published: July 2023

Spatial representations in the entorhinal cortex (EC) and hippocampus (HPC) are fundamental to cognitive functions like navigation and memory. These representations, embodied in spatial field maps, dynamically remap in response to environmental changes. However, current methods, such as Pearson’s correlation coefficient, struggle to capture the complexity of these remapping events, especially when fields do not overlap, or transformations are non-linear. This limitation hinders our understanding and quantification of remapping, a key aspect of spatial memory function. To address this, we propose a family of metrics based on the Earth Mover’s Distance (EMD) as a versatile framework for characterizing remapping. Applied to both normalized and unnormalized distributions, the EMD provides a granular, noise-resistant, and rate-robust description of remapping. This approach enables the identification of specific cell types and the characterization of remapping in various scenarios, including disease models. Furthermore, the EMD’s properties can be manipulated to identify spatially tuned cell types and to explore remapping as it relates to alternate information forms such as spatiotemporal coding. By employing approximations of the EMD, we present a feasible, lightweight approach that complements traditional methods. Our findings underscore the potential of the EMD as a powerful tool for enhancing our understanding of remapping in the brain and its implications for spatial navigation, memory studies and beyond.
The Microspherule protein 1(MCRS1) homolog interacts with the Myb-like transcription factor DRMY1 and is essential for embryogenesis inArabidopsis thaliana
Authors: Huo Huan Howard , Luo Ming , Lee Yuh-Ru Julie , Liu Bo
Published: July 2023

The evolutionarily conserved Microspherule protein 1 (MCRS1) has diverse functions from transcriptional regulation to stabilization of microtubule minus ends in acentrosomal spindles in mammals. A previous study suggested that in the model plantArabidopsis thaliana, inactivation of an MCRS1 homolog gene led to aborted embryogenesis. To test whether this lethality was caused by defects associated with transcription or mitosis, we used the heterozygousmcrs1mutant to examine whether the gene was required for mitosis during gametogenesis. Results of reciprocal crosses between themcrs1mutant and the wild-type plant showed that theMCRS1gene was dispensable for mitotic cell divisions associated with the development of both male and female gametophytes. An MCRS1-GFP fusion protein was expressed in themcrs1mutant and suppressed the mutation as reported by restored growth. This functional fusion protein exclusively localized to interphase nuclei and became undetectable during mitosis before returning to the reforming daughter nuclei. Affinity purification of the MCRS1-GFP protein resulted in consistent recovery of the Myb-like transcription factor DRMY1 (Developmentally Regulated Myb-like1) but not microtubule-associated factors. The association was further supported by the evidence of a direct interaction in living cells. Hence, the plant MCRS1 was concluded to play a role in the gene transcription in sporophyte development.
How climate change and population growth will shape attendance and human-wildlife interactions at British Columbia parks
Authors: Weststrate Dayna K , Chhen Aimee , Mezzini Stefano , Safford Kirk , Noonan Michael J
Published: July 2023

Protected areas are important for ecological conservation while simultaneously supporting culturally, and economically valuable tourism. However, excessive guest volumes strain operations and risk human-wildlife conflict, threatening the sustainability of nature-based tourism. Thus, park managers need to know what factors underpin attendance and how these might interact to shape future attendance. Using a decade of attendance records from 249 provincial parks, in British Columbia (BC), Canada, as well as 12 years of human-wildlife interactions (HWI) records at five national parks in BC, we modelled the impacts of weather conditions and population growth interact on park attendance and HWIs. We paired these models with climate change and population growth scenarios to generate projections of how attendance and HWIs will change throughout the century. Climate change is projected to result in more precipitation and higher temperatures, and, over this same time span, BC’s population is expected to grow substantially. Based on the observed relationship between attendance and weather, parks should anticipate a marked rise in visitors and HWIs especially during their respective peak seasons. These projections provide park managers with the information required for proactive management, ultimately contributing to the sustainability of recreation and tourism in protected areas.
Propagation path of a flowering cherry (Cerasus×yedoensis) cultivar ‘Somei-Yoshino’ traced by somatic mutations
Authors: Shirasawa Kenta , Esumi Tomoya , Itai Akihiro , Hatakeyama Katsunori , Takashina Tadashi , Yakuwa Takuji , Sumitomo Katsuhiko , Kurokura Takeshi , Fukai Eigo , Sato Keiichi , Shimada Takehiko , Shiratake Katsuhiro , Hosokawa Munetaka , Monden Yuki , Kusaba Makoto , Ikegami Hidetoshi , Isobe Sachiko
Published: July 2023

Flowering cherry cultivar ‘Somei-Yoshino’ (Cerasus×yedoensis) has been clonally propagated and spread all around the world including Japan. ‘Somei-Yoshino’ is thought to be an interspecific hybrid derived fromC. spachianaandC. speciosa; however, its origin is unclear. Since somatic mutations are randomly induced in genomes and stably transmitted through generations, we aimed to identify somatic mutations in the genome of ‘Somei-Yoshino’ to trace its propagation path. A total of 46 ‘Somei-Yoshino’ clones were collected from all over Japan and subjected to whole-genome sequencing. The results revealed 684 single nucleotide variants, of which 71 were found in more than two clones. Clustering analysis of the 46 clones using these 71 variants revealed six groups, four of which contained 40 of the 46 clones. In addition, because each of the four clones closely planted in Ueno Park, Tokyo, Japan, clustered into the four different groups, we considered that these four clones could be the ancestors of the ‘Somei-Yoshino’ clones found in Japan. Furthermore, based on the comparison of mutant alleles with the genomes ofCerasusspecies, one of the four trees was concluded as the closest to the origin. Here, we propose that the origin of ‘Somei-Yoshino’ is a chimera derived from at least four somatic mutants.
Integration of variant annotations using deep set networks boosts rare variant association genetics
Authors: Clarke Brian , Holtkamp Eva , Öztürk Hakime , Mück Marcel , Wahlberg Magnus , Meyer Kayla , Munzlinger Felix , Brechtmann Felix , Hölzlwimmer Florian R. , Gagneur Julien , Stegle Oliver
Published: July 2023

Rare genetic variants can strongly predispose to disease, yet accounting for rare variants in genetic analyses is statistically challenging. While rich variant annotations hold the promise to enable well-powered rare variant association tests, methods integrating variant annotations in a data-driven manner are lacking. Here, we propose DeepRVAT, a model based on set neural networks that learns burden scores from rare variants, annotations, and phenotypes. In contrast to existing methods, DeepRVAT yields a single, trait-agnostic, nonlinear gene impairment score, enabling both risk prediction and gene discovery in a unified framework. On 34 quantitative and 26 binary traits, using whole-exome-sequencing data from UK Biobank, we find that DeepRVAT offers substantial increases in gene discoveries and improved replication rates in held-out data. Moreover, we demonstrate that the integrative DeepRVAT gene impairment score greatly improves detection of individuals at high genetic risk. Finally, we show that pre-trained DeepRVAT scores generalize across traits, opening up the possibility to conduct highly computationally efficient rare variant tests.
The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2
Authors: Pekar Jonathan E. , Lytras Spyros , Ghafari Mahan , Magee Andrew F. , Parker Edyth , Havens Jennifer L. , Katzourakis Aris , Vasylyeva Tetyana I. , Suchard Marc A. , Hughes Alice C. , Hughes Joseph , Robertson David L. , Dellicour Simon , Worobey Michael , Wertheim Joel O. , Lemey Philippe
Published: July 2023

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just ∼1–3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.
Biodiversity monitoring in Europe: user and policy needs
Authors: Moersberger Hannah , Valdez Jose , Martin Juliette G. C. , Junker Jessica , Georgieva Ivelina , Bauer Silke , Beja Pedro , Breeze Tom D. , Fernandez Miguel , Fernández Néstor , Brotons Lluís , Jandt Ute , Bruelheide Helge , Kissling W. Daniel , Langer Christian , Liquete Camino , Lumbierres Maria , Solheim Anne Lyche , Maes Joachim , Morán-Ordóñez Alejandra , Moreira Francisco , Pe’er Guy , Santana Joana , Shamoun-Baranes Judy , Smets Bruno , Capinha César , McCallum Ian , Pereira Henrique M. , Bonn Aletta
Published: July 2023

To implement the goals of the 2030 Global Biodiversity Framework, the European Biodiversity Strategy and the EU Green Deal, biodiversity monitoring is a pivotal instrument to achieve accountability and progress in conservation. Monitoring efforts in Europe, however, suffer from gaps and biases in taxonomy, spatial coverage, and temporal resolution, resulting in fragmented and disconnected data which does not provide sufficient evidence for policy making. To assess user and policy needs in biodiversity monitoring, we employed with EuropaBON a four-step user-centred stakeholder engagement process, including an international public stakeholder workshop, a standardised online survey, semi-structured interviews, and an expert meeting with representatives of EU member states, the European Commission and the European Environment Agency. The resulting insights into national and European biodiversity monitoring schemes identify policy needs, current challenges and potential solutions. Based on this in-depth policy and science stakeholder assessment, we recommend the establishment of a European Biodiversity Observation Network through a permanent Biodiversity Monitoring and Coordinating Centre to optimise existing observation efforts, harmonise data, and enhance our ability to predict and respond to key challenges related to biodiversity loss in a changing climate in Europe.
A mean-field theory for predicting single polymer collapse induced by neutral crowders
Authors: Chaboche Quentin , Campos-Villalobos Gerardo , Giunta Giuliana , Dijkstra Marjolein , Cosentino-Lagomarsino Marco , Scolari Vittore F.
Published: July 2023

Macromolecular crowding can induce the collapse of a single long polymer into a globular form due to depletion forces of entropic nature. This phenomenon has been shown to play a significant role in compacting the genome within the bacteriumEscherichia coliinto a well-defined region of the cell known as the nucleoid. Motivated by the biological significance of this process, numerous theoretical and computational studies have searched for the primary determinants of the behavior of polymer-crowder phases. However, our understanding of this process remains incomplete and there is debate on a quantitatively unified description. In particular, different simulation studies with explicit crowders have proposed different order parameters as potential predictors for the collapse transition. In this work, we present a comprehensive analysis of published simulation data obtained from different sources. Based on the common behavior we find in this data, we develop a unified phenomenological model that we show to be predictive. Finally, to further validate the accuracy of the model, we conduct new simulations on polymers of various sizes, and investigate the role of jamming of the crowders.
In Vivo Monitoring of Cellular Senescence by Photoacoustic and Fluorescence Imaging Utilizing a Nanostructured Organic Probe
Authors: Baker Andrew G. , Ou Hui-Ling , Hartono Muhamad , Popov Andrea Bistrović , Brown Emma L. , Joseph James , Golinska Monika , Sanghera Chandan , González-Gualda Estela , Macias David , Else Thomas R. , Greer Heather F. , Vernet Aude , Bohndiek Sarah E. , Fruk Ljiljana , Muñoz-Espín Daniel
Published: July 2023

Senescent cells accumulate in multiple age-related disorders, including cancer, exacerbating the pathological manifestations, and the eradication of these cells has emerged as a promising therapeutic strategy. Despite the impact of senescence in diseases, the development of tools to monitor the senescent burdenin vivoremains a challenge due to their suboptimal specificity, translatability, and tissue penetrance. Here, we have designed a nanostructured organic probe (NanoJaggs) based on biocompatible indocyanine green dye (ICG) building blocks forming J-aggregates, which possess distinct spectral properties allowing both fluorescence and photoacoustic tomography (PAT) detection. We show that NanoJaggs are taken up by an active process of endocytosis and exhibit selective accumulation at the lysosomal compartment in severalin vitromodels for senescence. Finally, NanoJagg probe is validated in twoin vivostudies including live PAT imaging and shows remarkable specificity to tumours with chemotherapy-induced senescence compared to untreated proliferative tumors.In vitro, ex vivoandin vivoall indicate that NanoJaggs are a clinically translatable tool for detection of senescence and their robust PAT signal makes them suitable for longitudinal monitoring of the senescent burden in solid tumors after chemo or radiotherapy.
Identifying novel radioprotective drugs via salivary gland tissue chip screening
Authors: Piraino Lindsay , Chen Chiao Yun , Mereness Jared , Dunman P. M. , Ovitt Catherine , Benoit Danielle , DeLouise Lisa
Published: July 2023

During head and neck cancer treatment, off-target ionizing radiation damage to the salivary glands commonly causes a permanent loss of secretory function. Due to the resulting decrease in saliva production, patients have trouble eating, speaking and are predisposed to oral infections and tooth decay. While the radioprotective antioxidant drug Amifostine is approved to prevent radiation-induced hyposalivation, it has intolerable side effects that limit its use, motivating the discovery of alternative therapeutics. To address this issue, we previously developed a salivary gland mimetic (SGm) tissue chip platform. Here, we leverage this SGm tissue chip for high-content drug discovery. First, we developed in-chip assays to quantify glutathione and cellular senescence (β-galactosidase), which are biomarkers of radiation damage, and we validated radioprotection using WR-1065, the active form of Amifostine. Following validation, we tested other reported radioprotective drugs, including, Edaravone, Tempol, N-acetylcysteine (NAC), Rapamycin, Ex-Rad, and Palifermin, confirming that all drugs but NAC and Ex-Rad exhibited robust radioprotection. Next, a Selleck Chemicals library of 438 FDA-approved drugs was screened for radioprotection. We discovered 25 hits, with most of the drugs identified with mechanisms of action other than antioxidant activity. Hits were down-selected using EC50values and pharmacokinetics and pharmacodynamics data from the PubChem database leading to testing of Phenylbutazone (anti-inflammatory), Enoxacin (antibiotic), and Doripenem (antibiotic) forin vivoradioprotection in mice using retroductal injections. Results confirm that Phenylbutazone and Enoxacin exhibited equivalent radioprotection to Amifostine. This body of work demonstrates the development and validation of assays using a SGm tissue chip platform for high-content drug screening and the successfulin vitrodiscovery andin vivovalidation of novel radioprotective drugs with nonantioxidant primary indications pointing to possible, yet unknown novel mechanisms of radioprotection.
Prediction of protein-RNA interactions from single-cell transcriptomic data
Authors: Fiorentino Jonathan , Armaos Alexandros , Colantoni Alessio , Tartaglia Gian Gaetano
Published: July 2023

RNA-binding proteins play a crucial role in regulating RNA processing, yet our understanding of their interactions with coding and non-coding RNAs remains limited. Experimental studies are typically restricted to a small number of cell lines and a limited set of RNA-binding proteins (RBPs). Although computational methods based on sequence and structure can predict protein-RNA interactions accurately, they often lack the ability to consider cell-type-specific gene expression and the broader context of gene regulatory networks (GRNs).

In the present study, we assess the performance of several GRN inference algorithms in predicting protein-RNA interactions from single-cell transcriptomic data, and we propose a pipeline, called scRAPID (single-cell transcriptomic-based RnA Protein Interaction Detection), that integrates these methods with thecatRAPID algorithm, which can identify direct physical interactions between RBPs and RNA molecules.

Our approach demonstrates that RBP-RNA interactions can be inferred from single-cell transcriptomic data, with performances comparable or superior to those achieved for the well-established task of inferring transcription factor-target interactions. Notably, the incorporation ofcatRAPID significantly enhances the accuracy of identifying interactions, particularly with long non-coding RNAs, and enables the identification of hub RBPs and hub RNAs. Additionally, we show that interactions between RBPs can be detected based on their inferred RNA targets.

We have made the software freely available athttps://github.com/tartaglialabIIT/scRAPID.
Crk/Crklregulates early angiogenesis in mouse embryos by accelerating endothelial cell maturation
Authors: Shi Lijie , Song Hansoo , Zhou Bin , Morrow Bernice E.
Published: July 2023

Rationale

Ubiquitously expressed cytoplasmic adaptors CRK and CRKL mediate multiple signaling pathways in mammalian embryogenesis. They are also associated with cardiovascular defects occurring in Miller-Dieker syndrome and 22q11.2 deletion syndrome, respectively. The embryonic mesoderm contributes to the formation of the cardiovascular system, yet the roles thatCrkandCrklplay there are not understood on a single cell level.

Objectives

To determine functions ofCrkandCrklin the embryonic mesoderm during early mouse vascular development. Secondly, we will examine the molecular mechanisms responsible for early embryonic endothelial cell (EC) defects by performing single cell RNA-sequencing (scRNA-seq) andin vivovalidation experiments.

Methods and Results

Inactivation of bothCrkandCrkltogether usingMesp1Creresulted embryonic lethality with severe vascular defects. Although vasculogenesis appeared normal, angiogenesis was disrupted both in the yolk sac and embryo proper, leading to disorganized vascular networks. We performed scRNA-seq of theMesp1Cremesodermal lineage and found that there was upregulation of a great number of angiogenesis and cell migration related genes in ECs in the mutants, including NOTCH signaling genes such asDll4andHey1. Further bioinformatic analysis of EC subpopulations identified a relative increase in the number of more differentiated angiogenic ECs and decrease in EC progenitors. Consistent with this, we identified an expansion ofDll4expressing cells within abnormal arteries,in vivo. Also, our bioinformatic data indicates that there is dysregulated expression of lineage genes that promote EC differentiation causing accelerated cell fate progression during EC differentiation.

Conclusions

Our results show thatCrkandCrklare crucial for regulating early embryonic angiogenesis. Combined inactivation ofCrk/Crklcaused precocious EC maturation with an increase of atypical differentiated angiogenic ECs and failed vascular remodeling. This is in part due to increased NOTCH signaling and altered expression of cell migration genes.
Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates
Authors: Speed Doug , Evans David M.
Published: July 2023

We propose TetraHer, a method for estimating the liability heritability of binary phenotypes. TetraHer has five key features. Firstly, it can be applied to data from complex pedigrees, that contain multiple types of relationships. Secondly, it can correct for ascertainment of cases or controls. Thirdly, it can accommodate covariates. Fourthly, it can model the contribution of common environment. Fifthly, it produces a likelihood, that can be used for significance testing. We first demonstrate the validity of TetraHer on simulated data. We then use TetraHer to estimate liability heritability for 229 codes from the tenth International Classification of Diseases (ICD-10). We identify 118 codes with significant heritability (P<0.05/229), which can be used in future analyses for investigating the genetic architecture of human diseases.
A Conserved Electrostatic Membrane-Binding Surface in Synaptotagmin-Like Proteins Revealed Using Molecular Phylogenetic Analysis and Homology Modeling
Authors: Chon Nara L. , Tran Sherleen , Miller Christopher S. , Lin Hai , Knight Jefferson D.
Published: July 2023

Protein structure prediction has emerged as a core technology for understanding biomolecules and their interactions. Here, we combine homology-based structure prediction with molecular phylogenetic analysis to study the evolution of electrostatic membrane binding among vertebrate synaptotagmin-like proteins (Slps). Slp family proteins play key roles in the membrane trafficking of large dense-core secretory vesicles. Our previous experimental and computational study found that the C2A domain of Slp-4 (also called granuphilin) binds with high affinity to anionic phospholipids in the cytoplasmic leaflet of the plasma membrane through a large positively charged protein surface centered on a cluster of phosphoinositide-binding lysine residues. Because this surface contributes greatly to Slp-4 C2A domain membrane binding, we hypothesized that the net charge on the surface might be evolutionarily conserved. To test this hypothesis, the known C2A sequences of Slp-4 among vertebrates were organized by class (from mammalia to pisces) using molecular phylogenetic analysis. Consensus sequences for each class were then identified and used to generate homology structures, from which Poisson–Boltzmann electrostatic potentials were calculated. For comparison, homology structures and electrostatic potentials were also calculated for the five human Slp protein family members. The results demonstrate that the charge on the membrane-binding surface is highly conserved throughout the evolution of Slp-4, and more highly conserved than many individual residues among the human Slp family paralogs. Such molecular phylogenetic-driven computational analysis can help to describe the evolution of electrostatic interactions between proteins and membranes which are crucial for their function.

Impact statement

The interior surface of eukaryotic plasma membranes is negatively charged, and many proteins that bind to it have correspondingly evolved a positively charged face. Here, we use techniques from evolutionary biology and computational biophysics to study the conservation of this positively charged surface in an important protein family. We find that the overall surface charge is highly conserved, more so than individual amino acids, consistent with its important role in electrostatic interaction with the membrane.
The Role and Mechanism of TEAD4 in Preimplantation Embryonic Development in Mice and Cattle
Authors: Wu Xiaotong , Shi Yan , Hu Bingjie , Zhao Panpan , Li Shuang , Xiao Lieying , Wang Shaohua , Zhang Kun
Published: July 2023

Tead4, a critical transcription factor expressed during preimplantation development, is essential for the expression of trophectoderm-specific genes in mice. However, the functional mechanism ofTead4in mouse preimplantation development and its conservation across mammals remain unclear. Here, we report that Tead4 is a crucial transcription factor necessary for blastocyst formation in mice. Disruption ofTead4through base editing results in developmental arrest at the morula stage. Additionally, RNA-seq analysis reveals dysregulation of 670 genes inTead4knockout embryos. As anticipated,Tead4knockout leads to a decrease in trophectoderm genesCdx2andGata3. Intriguingly, we observed a reduction in Krt8, suggesting that Tead4 influences the integrity of the trophectoderm epithelium in mice. More importantly, we noted a dramatic decrease in nuclear Yap in outside cells forTead4-deficient morula, indicating that Tead4 directly regulates Hippo signaling. In contrast, bovine embryos withTEAD4depletion could still develop to blastocysts with normal expression ofCDX2,GATA3, andSOX2, albeit with a decrease in total cell number and ICM cell number. In conclusion, we propose that Tead4 regulates mouse blastocyst formation via Krt8 and Yap, both of which are critical regulators of mouse preimplantation development.
A Size Filter Regulates Apical Protein Sorting
Authors: de Caestecker Christian , Macara Ian G.
Published: July 2023

Despite decades of research, apical sorting of epithelial membrane proteins remains incompletely understood. We noted that apical cytoplasmic domains are smaller than those of basolateral proteins; however, the reason for this discrepancy is unknown. We investigated whether a size barrier at the trans-Golgi network (TGN) might hinder apical sorting of proteins with large cytoplasmic tails. We focused on Crb3 and Ace2 as representative apical proteins with short cytoplasmic tails. By incorporating a streptavidin-binding peptide, these proteins can be trapped in the endoplasmic reticulum (ER) until addition of biotin, which triggers synchronous release to the Golgi and subsequent transport to the apical cortex. Strikingly, departure from the Golgi could be significantly delayed simply by increasing cytoplasmic bulk. Moreover, large and small Crb3 segregated into spatially distinct Golgi regions as detected by super resolution imaging. Biologically, Crb3 forms a complex through its cytoplasmic tail with the Pals1 protein, which could also delay departure, but although associated at the ER and Golgi, we found that Pals1 disassociates prior to Crb3 departure. Notably, a non-dissociable mutant Pals1 hampers the exit of Crb3. We conclude that an unexpected mechanism involving a size filter at the TGN facilitates apical sorting of proteins with small cytoplasmic domains and that timely release of Pals1, to reduce cytoplasmic domain size, is essential for the normal kinetics of Crb3 sorting.
Face‐to‐face with the (animal) Other
Authors: Kavesh Muhammad A.
Published: July 2023

The imperial underpinning of the early anthropology of Pakistan constituted “the other” as a subject of comprehension, categorization, and containment. Later, with the post‐9/11 geopolitical backdrop, anthropologists focused on selected themes such as religious and ethnic disparity and political nationalism, eliding some topics or groups. What would it mean for the anthropology of Pakistan to consider alienated themes and groups while emphasizing the infinity of the Other? How would conceiving the Otherbeyonda political or religious other, or even beyond a human subject, create a possibility of decolonizing the anthropology of Pakistan while exploring multiple futures—emergent, imagined, and expected? Such an approach critically moots a reexamination of theoretical, methodological, and epistemological tenets and urges the discipline to engage with diverse lifeworlds. It brings the face of the Other face‐to‐face with anthropology beyond humanity to consider all beings, intersubjective and collaborative experiences, and shared values.
The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples
Authors: Feitosa Priscilla Mariana Freitas Aguiar , Hirth Carlos Gustavo , Silva‐Fernandes Isabelle Joyce De Lima , Dornelas Conceição Aparecida
Published: July 2023

Prostate cancer is the world's most frequently diagnosed malignancy in men. Recent work suggests that patients with high ERG expression intensity are significantly more likely to develop biochemical relapse and metastasis, and die of prostate cancer. The objective of this study was to determine the relationship between the intensity of ERG protein expression and the staging of prostate cancer and the formation of metastases in 635 samples. A retrospective cohort analysis was performed using immunohistochemistry reactions in tissue microarray samples taken from non‐neoplastic and neoplastic prostate tissue from patients who underwent radical prostatectomies at a reference hospital from 2009 to 2016. For the ERG marker analysis, the samples were scored for the presence or absence of nuclear signals. Weak, moderate, or strong intensity of the nuclei of the observable tumor cells was considered to be positive markers. All told, 635 samples were evaluated, and the ERG expression was inconclusive in 9% of cases, while 30% were positive and 61% were negative. Of the samples with positive result: 25.8% were weak and focal, 53.2% were moderate, and 21% were strong. Finally, 21% of the cases with a positive ERG had a high Gleason score. Metastasis was detected in 41% of the patients who were ERG positive, and of these, the majority had moderate marking and were aged older than 60 years, although there was no statistically significant difference between the older and younger age groups. Patients with moderate to strong ERG staining had higher staging compared to the others, and no increase in metastasis was detected in patients with more intense ERG expression. More studies should be carried out to corroborate these results and to reach a consensus on the intensity and scoring of the expression levels of ERG markers.
Comparison of morbidity‐related parameters between autologous and allogeneic bone grafts for alveolar ridge augmentation from patients' perspective—A questionnaire‐based cohort study
Authors: Heimes Diana , Pabst Andreas , Becker Philipp , Hartmann Amely , Kloss Frank , Tunkel Jochen , Smeets Ralf , Kämmerer Peer W.
Published: July 2023

Introduction

Alveolar ridge augmentation is often required before dental implant placement. In this context, autologous bone grafts are considered the biological gold standard. Still, bone block harvesting is accompanied by some serious potential disadvantages and possible complications, such as pain, bleeding, and nerve irritation. Several studies aimed to compare autologous to allogeneic bone grafts concerning bone quality and implant survival rates; this is the first prospective study analyzing and comparing morbidity‐related parameters after alveolar ridge augmentation using autogenous and allogeneic bone blocks from patients' perspective.

Methods

Using a questionnaire, 36 patients were asked to evaluate the surgery as well as the post‐operative period concerning pain, stress, sensibility deficits, satisfaction with, and consequences from the surgery as well as the preferred procedure for future alveolar ridge augmentations.

Results

No significant differences were shown regarding stress and pain during and after surgery, whereas the rate of nerve irritations was twice as high in the autologous group. The swelling was significantly higher in patients with autologous bone blocks (p = 0.001). Nevertheless, the overall satisfaction of patients of both groups was very high, with over 8/10 points.

Conclusions

The swelling was the main reason for patients' discomfort in both groups and was significantly higher after autologous bone augmentation. Since this side effect seems to be a highly relevant factor for patients' comfort and satisfaction, it needs to be discussed during preoperative consultation to allow shared decision‐making considering the anticipated morbidity.
Trait‐environment associations diverge between native and alien breeding bird assemblages on the world's oceanic islands
Authors: Rault Charlotte , Leprieur Fabien , Barbaro Luc , Kreft Holger , Mouquet Nicolas , Papaïx Julien , Şekercioğlu Çağan H. , Violle Cyrille , Barnagaud Jean‐Yves
Published: July 2023

Aim

To investigate spatial variations in the ecological trait structure of breeding bird assemblages on oceanic islands. To test the hypothesis that native and naturalized alien bird species are filtered by different processes, leading to diverging associations between traits and insular environmental gradients.

Location

Oceanic islands worldwide.

Time Period

Current.

Major Taxa Studied

Terrestrial breeding birds.

Methods

We assessed the composition of breeding terrestrial bird assemblages from the extent‐of‐occurrence maps of 3170 native and 169 naturalized alien species on 4660 oceanic islands. We quantified their ecological trait structures with respect to diet, mobility and body mass as the standardized distance between a mean pairwise trait distance index and its expectation from a null model. We used spatial generalized additive models to relate trait structures to proxies of environmental conditions and human impact on land, accounting for all species, native species only and alien species only.

Results

Diet and mobility traits tended to be more diverse than expected by a null model, while body mass tended towards clustering. Trait‐environment associations were idiosyncratic, but environmental variables tended to explain trait structures better than human impacts on habitats. Islands invaded by alien species had similar trait structures as noninvaded ones, although they hosted assemblages with more clustered body masses. However, trait‐environment relationships diverged when considering all islands and all species, invaded islands only or alien species only.

Main Conclusions

Despite their ecosystem‐level influences, alien species have a limited effect on the global patterns of trait structures in the breeding bird assemblages of the world's islands, either because they account for a low proportion of species or because successful invaders and native species have similar trait suites. Trait‐environment associations suggest that filters related to the conditions of alien species' introductions explain their distributions in island assemblages better than the constraints associated with isolated environments.
Age trajectories in extra-pair siring success suggest an effect of maturation or early-life experience
Authors: Schlicht Emmi , Kempenaers Bart
Published: July 2023

Across birds, male age is the most consistent predictor of extra-pair siring success, yet little is known about age effects on paternity over the lifetime of individuals. Here, we use data from a 13-year study of a population of blue tits (Cyanistes caeruleus) to investigate how extra-pair siring success changes with age within individuals. Our results indicate that extra-pair siring success does not continuously increase with male age. Instead, siring success was related to male age in a threshold fashion, whereby yearling males were less likely to gain paternity than older males. This effect was independent of the age of the social partner, but influenced by the age of the extra-pair female: success of yearlings at siring extra-pair young (EPY) with older females was even lower. Among males that sired at least one EPY, the number of extra-pair mates and the proportion of EPY sired were unrelated to male age. We found no evidence for an influence of selective disappearance on extra-pair reproduction. Senescence, if anything, only occurs at ages blue tits rarely reach. A literature review indicates that an effect of male age on extra-pair siring success may be limited to the switch from yearling to older in many species. Thus, the generally observed age effect on male extra-pair siring success may be linked to age class rather than continuous ageing. This suggests that lack of experience or not fully completed maturation are important drivers of age patterns in extra-pair paternity.

Abstract

In the blue tit, success at gaining paternity in nests of other males (extra-pair paternity) is related to male age in a threshold fashion: yearlings are less successful than older males. Yearling males may be losing out in competition with older males due to incomplete maturation, a lack of experience, or a female preference for older males.
Human β‐defensins are correlated with the immune infiltration and regulated by vitamin D3 in periodontitis
Authors: Zhang Churen , Han Ye , Miao Lili , Yue Zhaoguo , Xu Min , Liu Kaining , Hou Jianxia
Published: July 2023

Objective

Exploring the correlation between human β‐defensins (HBDs) and immune infiltration in periodontitis, and whether it is regulated by vitamin D3.

Background

The human body produces essential antimicrobial peptides called HBDs, which are associated with periodontitis. There is a strong link between periodontal tissue destruction and the immune cell infiltration. Moreover, vitamin D3 has been reported to regulate the expression of immune cell chemokines. However, the relationship between vitamin D3, HBDs, and immune infiltration in periodontitis remains to be investigated.

Methods

The Gene Expression Omnibus database was accessed to obtain transcriptomic information of gingival samples taken from periodontitis patients. The expression value of HBD‐2 and HBD‐3 was calculated. Additionally, using the online program ImmuCellAl, 10 immune cells were scored for immune infiltration in the high‐HBDs‐expression group and the low‐HBDs‐expression group, separately. After that, transcriptome sequencing was done based on human gingival fibroblasts that had received vitamin D3 treatment. Furthermore, hGFs were treated by vitamin D3, tumor necrosis factor‐α (TNF‐α), and Porphyromonas gingivalis lipopolysaccharide (Pg‐LPS). The expressions of HBD‐2, HBD‐3, interleukin‐8 (IL‐8), and monocyte chemoattractant protein‐1 (MCP‐1) were detected. To seek the potential mechanism, CYP27A1 siRNA was employed to reduce the expression of CYP27A1, and nuclear factor‐gene binding protein 65 (NF‐κB p65) was examined.

Results

In GSE10334, the expressions of HBD‐2 and HBD‐3 were down‐regulated in periodontitis group. Meanwhile, monocyte, macrophage, and CD4_T cell were less infiltrated in low‐HBD‐2‐expression group, while less Gamma‐delta T‐cell infiltration was found in low‐HBD‐3‐expression group. Transcriptome sequencing found that 21 genes were significantly expressed, of which the function was enriched in response to bacterial origin and TNF signal pathway. Vitamin D3 could significantly up‐regulate the expression of HBD‐2 and HBD‐3, which could be controlled by knocking down CYP27A1 mRNA expression. With prolonged vitamin D3 stimulation, the expression of HBD‐2 and HBD‐3 increased. TNF‐α/Pg‐LPS could significantly increase the expression of HBD‐2, HBD‐3, IL‐8, MCP‐1, and p65, all of which were reduced by vitamin D3.

Conclusion

HBDs are correlated with immune infiltration in periodontitis. Vitamin D3 inhibits the expression of HBDs and chemokines induced by TNF‐α/Pg‐LPS, possibly through NF‐κB pathway, in human gingival fibroblasts.
Pediatric risk to orthotopic heart transplant (PRO) score: Insights from United Network for Organ Sharing (UNOS) waitlist mortality findings
Authors: Raymundo Stephanie , Wilhalme Holly , Chaudhary Anila , Karunungan Krystal , Alejos Juan , Srivastava Neeraj
Published: July 2023

Background

Pediatric heart transplant candidates on the waitlist have the highest mortality rate among all solid organ transplants. A risk score incorporating a candidate's individual risk factors may better predict mortality on the waitlist and optimize organ allocation to the sickest of those awaiting transplant.

Methods

Using the United Network for Organ Sharing (UNOS) database, we evaluated a total of 5542 patients aged 0–18 years old on the waitlist for a single, first time, heart transplant from January 2010 to June 2019. We performed a univariate analysis on two‐thirds (N = 3705) of these patients to derive the factors most associated with waitlist mortality or delisting secondary to deterioration within 1 year. Those with a p <0.2 underwent a multivariate analysis and the resulting factors were used to build a prediction model using the Fine‐Grey model analysis. This predictive scoring model was then validated on the remaining one‐third of the patients (N = 1852).

Results

The Pediatric Risk to OHT (PRO) scoring model utilizes the following unique patient variables: blood type, diagnosis of congenital heart disease, weight, presence of ventilator support, presence of inotropic support, extracorporeal membrane oxygenation (ecmo) status, creatinine level, and region. A higher score indicates an increased risk of mortality. The PRO score had a predictive strength of 0.762 as measured by area under the ROC curve at 1 year.

Conclusion

The PRO score is an improved predictive model with the potential to better assess mortality for patients awaiting heart transplant.
El juego de las diferencias: la gestión indígena de la interculturalidad en Baja California
Authors: Chávez Valencia José Atahualpa
Published: July 2023

El objetivo del artículo se enfoca en evidenciar las gestiones emprendidas por los agentes indígenas buscando crear las condiciones necesarias, para establecer un diálogo intercultural efectivo, tendiente a modificar sus condiciones económicas, políticas y culturales imperantes, a través de solicitudes y exigencias de reconocimiento legal, políticas públicas, instituciones educativas y de atención diferenciada, así como espacios en las estructuras de gobierno. La investigación se enfoca en dos experiencias concretas de gestión en Baja California: las escuelas bilingües para indígenas purhépechas, en Playas de Rosarito; y la Casa de la Mujer Indígena “Donají, en Tijuana.
Correlating the charge-transfer gap to the maximum transition temperature in Bi
2
Sr
2
Ca

n

-1
Cu

n

O
2

n

+4+δ
Authors: Wang Zechao , Zou Changwei , Lin Chengtian , Luo Xiangyu , Yan Hongtao , Yin Chaohui , Xu Yong , Zhou Xingjiang , Wang Yayu , Zhu Jing
Published: July 2023

As the number of CuO
2
layers,
n
, in each unit cell of a cuprate family increases, the maximum transition temperature (
T
c,max
) exhibits a universal bell-shaped curve with a peak at
n
= 3. The microscopic mechanism of this trend remains elusive. In this study, we used advanced electron microscopy to image the atomic structure of cuprates in the Bi
2
Sr
2
Ca

n

-1
Cu

n

O
2

n

+4+δ
family with 1 ≤
n
≤ 9; the evolution of the charge-transfer gap size (Δ) with
n
can be measured simultaneously. We determined that the
n
dependence of Δ follows an inverted bell-shaped curve with the minimum Δ value at
n
= 3. The correlation between Δ,
n
, and
T
c,max
may clarify the origin of superconductivity in cuprates.
Leveraging artificial intelligence in the fight against infectious diseases
Authors: Wong Felix , de la Fuente-Nunez Cesar , Collins James J.
Published: July 2023

Despite advances in molecular biology, genetics, computation, and medicinal chemistry, infectious disease remains an ominous threat to public health. Addressing the challenges posed by pathogen outbreaks, pandemics, and antimicrobial resistance will require concerted interdisciplinary efforts. In conjunction with systems and synthetic biology, artificial intelligence (AI) is now leading to rapid progress, expanding anti-infective drug discovery, enhancing our understanding of infection biology, and accelerating the development of diagnostics. In this Review, we discuss approaches for detecting, treating, and understanding infectious diseases, underscoring the progress supported by AI in each case. We suggest future applications of AI and how it might be harnessed to help control infectious disease outbreaks and pandemics.
RHINO directs MMEJ to repair DNA breaks in mitosis
Authors: Brambati Alessandra , Sacco Olivia , Porcella Sarina , Heyza Joshua , Kareh Mike , Schmidt Jens C. , Sfeir Agnel
Published: July 2023

Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are the primary pathways for repairing DNA double-strand breaks (DSBs) during interphase, whereas microhomology-mediated end-joining (MMEJ) has been regarded as a backup mechanism. Through CRISPR-Cas9–based synthetic lethal screens in cancer cells, we identified subunits of the 9-1-1 complex (RAD9A-RAD1-HUS1) and its interacting partner, RHINO, as crucial MMEJ factors. We uncovered an unexpected function for RHINO in restricting MMEJ to mitosis. RHINO accumulates in M phase, undergoes Polo-like kinase 1 (PLK1) phosphorylation, and interacts with polymerase θ (Polθ), enabling its recruitment to DSBs for subsequent repair. Additionally, we provide evidence that MMEJ activity in mitosis repairs persistent DSBs that originate in S phase. Our findings offer insights into the synthetic lethal relationship between the genes
POLQ
and
BRCA1
and
BRAC2
and the synergistic effect of Polθ and poly(ADP-ribose) polymerase (PARP) inhibitors.
Microbially Induced Calcium Carbonate Precipitation by
Sporosarcina pasteurii
: a Case Study in Optimizing Biological CaCO
3
Precipitation
Authors: Carter Michael S. , Tuttle Matthew J. , Mancini Joshua A. , Martineau Rhett , Hung Chia-Suei , Gupta Maneesh K.
Published: July 2023

Current production of traditional concrete requires enormous energy investment that accounts for approximately 5 to 8% of the world’s annual CO
2
production. Biocement is a building material that is already in industrial use and has the potential to rival traditional concrete as a more convenient and more environmentally friendly alternative.