bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shadows over Caribbean reefs: Identification of a new invasive soft coral species,Xenia umbellata, in southwest Puerto Rico
Authors: Toledo-Rodriguez Daniel A. , Veglia Alex , Jimenez Marrero Nilda M. , Gomez-Samot Joyce M. , McFadden Catherine S. , Weil Ernesto , Schizas Nikolaos V. 
Published: May 2024

AbstractIn October 2023, several colonies of an alien soft coral species were reported on shallow reefs in southwest Puerto Rico. The soft coral was identified as a xeniid octocoral (species undetermined), resembling the octocoralUnomia stolonifera, which has invaded and overgrown reefs in Venezuela in recent years. To conclusively characterize the species of the invading xeniid, we employed multilocus barcoding targeting four genes (ND2, mtMutS, COI, and 28S) of three separate colonies across three locations in southwest Puerto Rico. Sequence comparisons with xeniid sequences from GenBank, including those from the generaXeniaandUnomia, indicated a 100% sequence identity (>3,000 bp combined) with the speciesXenia umbellata(Octocorallia : Malacalcyonacea : Xeniidae).Xenia umbellatais native to the Red Sea and to our knowledge, this represents the first confirmed case of this species as an invader on Caribbean reefs. Similar toU. stolonifera, X. umbellatais well known for its ability to rapidly overgrow substrate as well as tolerate environmental extremes. In addition,X. umbellatahas recently been proposed as a model system for tissue regeneration having the ability to regenerate completely from a single tentacle. These characteristics greatly amplifyX. umbellata’s potential to adversely affect any reef it invades. Our findings necessitate continued collaborative action between local management agencies and stakeholders in Puerto Rico, as well as neighboring islands, to monitor and control this invasion prior to significant ecological perturbation.
Embryo spatial 3D genomics
Authors: Ma Yuang , Gou Bo , Xu Yuetong , Shu Muya , Lu Falong , Li Xiang 
Published: May 2024

AbstractThe 3D architecture of the genome is crucial for controlling gene expression and organ development. Here, we introduce a spatial 3D genomics approach for assessing chromatin conformationin-situin tissue sections, by integrating microfluidic deterministic barcoding and SPRITE procedures. This method was applied to mouse embryo sections, revealing a hierarchical model of chromatin interactions within and between compartments in various organs. The intra-compartment interactions vary among organs to orchestrate gene expressions, while the inter-compartment interactions remain identical in the most organs. Beyond this, the liver exhibits overwhelmingly packed chromatin with enhanced adjacent-compartment interactions, possibly related to its physiology. These findings highlight the importance of tissue-spatial information in understanding embryonic chromatin organization. The approach presents a powerful tool for investigating these processes in tissues with high heterogeneity.One Sentence SummaryA spatial 3D genomics approach was developed that accesses hierarchical chromatin conformationin-situin tissue sections.
Characterization of a Biochemical Mouse Model of Primary Aldosteronism for Thermal Therapies
Authors: Timmerman Sarah A. , Mullen Nathan , Taylor Angela E , Gilligan Lorna C , Pyle Marla , Shrestha Tej B. , Sebek Jan , Highland Margaret A. , Challapalli Ritihaas , Arlt Wiebke , Bossmann Stefan H. , Dennedy Michael Conall , Prakash Punit , Basel Matthew T. 
Published: May 2024

AbstractIntroductionAldosterone-producing adenoma (APA) is the most common cause of endocrine-related hypertension but surgery is not always feasible. Current medical interventions are associated with significant side effects and poor patient compliance. New APA animal models that replicate basic characteristics of APA and give physical and biochemical feedback are needed to test new non-surgical treatment methods, such as image-guided thermal ablation,MethodsA model of APA was developed in nude mice using HAC15 cells, a human adrenal carcinoma cell line. Tumor growth, aldosterone production, and sensitivity to angiotensin II were characterized in the model. The utility of the model was validated via treatment with microwave ablation and characterization of the resulting physical and biochemical changes in the tumor.ResultsThe APA model showed rapid and relatively homogeneous growth. The tumors produced aldosterone and steroid precursors in response to angiotensin II challenge, and plasma aldosterone levels were significantly higher in tumor bearing mice two hours after challenge verses non-tumor bearing mice. The model was useful for testing microwave ablation therapy, reducing aldosterone production by 80% in treated mice.ConclusionThe HAC15 model is a useful tumor model to study and develop localized treatment methods for APA.
Improved differential expression analysis of miRNA-seq data by modeling competition to be counted
Authors: Jun Seong-Hwan , Halushka Marc K. , McCall Matthew N. 
Published: May 2024

AbstractMicroRNAs play a central role in regulating gene expression and modulating diseases. Despite the importance of microRNAs, statistical methods for analyzing them have received far less attention compared to messenger RNAs. Commonly, messenger RNA-seq methods are applied to microRNA-seq data, which may produce erroneous results due to the highly competitive nature of microRNA sequencing. This study critically examines and challenges the assumptions of messenger RNA-seq methods when applied to microRNA-seq data. We propose a Negative Binomial Softmax Regression (NBSR) method to model the unique characteristics of microRNA-seq data. On both simulated and experimental datasets, NBSR outperforms existing methods and offers a new perspective for analyzing microRNA-seq data. NBSR is implemented in Python and freely available as open-source software.
PhoCoil: An Injectable and Photodegradable Single-component Recombinant Protein Hydrogel for Localized Therapeutic Cell Delivery
Authors: Gregorio Nicole E. , DeForest Cole A. 
Published: May 2024

AbstractHydrogel biomaterials offer great promise for 3D cell culture and therapeutic delivery. Despite many successes, challenges persist in that gels formed from natural proteins are only marginally tunable while those derived from synthetic polymers lack intrinsic bioinstructivity. Towards the creation of biomaterials with both excellent biocompatibility and customizability, recombinant protein-based hydrogels have emerged as molecularly defined and user-programmable platforms that mimic the proteinaceous nature of the extracellular matrix. Here, we introduce PhoCoil, a dynamically tunable recombinant hydrogel formed from a single protein component with unique multi-stimuli responsiveness. Physical crosslinking through coiled-coil interactions promotes rapid shear-thinning and self-healing behavior, rendering the gel injectable, while an included photodegradable motif affords on-demand network dissolution via visible light. PhoCoil gel photodegradation can be spatiotemporally and lithographically controlled in a dose-dependent manner, through complex tissue, and without harm to encapsulated cells. We anticipate that PhoCoil will enable new applications in tissue engineering and regenerative medicine.
KF4 anti-CELA1 Antibody and Purified α1-Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine α1-Antitrypsin Deficiency
Authors: Devine Andrew J. , Smith Noah J. , Joshi Rashika , Brooks-Patton Brandon , Dunham Jenna , Varisco Ansley N. , Goodman Emily M. , Fan Qiang , Zingarelli Basilia , Varisco Brian M. 
Published: May 2024

AbstractAlpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like Elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression.Cela1-deficiency is protective in a murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in PPE and cigarette smoke models in wild type mice. We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lung, pancreas, small intestine, and spleen. In toxicity studies, mice treated with KF4 25 mg/kg weekly for four weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose IgG. In histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25 mg/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5 mg/kg reduced the lung elastase activity ofAAT-/-mice treated with 0.2 units of PPE. In this injury model,AAT-/-mice treated with KF4 1 mg/kg weekly, human purified AAT 60 mg/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1 mg/kg weekly. However, the efficacy of KF4, AAT, or KF4 & AAT was similar. While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.
Population genomics of a naturalCannabis sativaL. collection from Iran identifies novel genetic loci for flowering time, morphology, sex and chemotyping
Authors: Dehnavi Mahboubeh Mostafaei , Damerum Annabelle , Taheri Sadegh , Ebadi Ali , Panahi Shadab , Hodgin George , Brandley Brian , Salami Seyed Alireza , Taylor Gail 
Published: May 2024

AbstractFuture breeding and selection ofCannabis sativaL. for drug production and industrial purposes require a source of germplasm with wide genetic variation, such as that found in wild relatives and progenitors of highly cultivated plants. Limited directional selection and breeding have occurred in this crop, especially informed by molecular markers. Here, we investigated the population genomics of a natural cannabis collection of male and female individuals from differing climatic zones in Iran. Using Genotyping-By-Sequencing (GBS), we sequenced 228 genotypes from 35 populations. The results obtained from GBS were used to perform association analysis identifying links between genotype and important phenotypes, including inflorescence characteristics, flowering time, plant morphology, tetrahydrocannabinol (THC) content, cannabidiol (CBD) content and sex. Approximately 23,266 significant SNPs of high quality were detected to establish associations between markers and traits, and population structure showed that Iranian cannabis plants fall into five groups. A comparison of Iranian samples from this study to global data suggests that the Iranian population is distinctive and, in general, is closer to marijuana than to hemp, although some populations in this collection are closer to hemp. The GWAS results showed that novel genetic loci, not previously identified, contribute to sex, yield and chemotype traits in cannabis and are worthy of further study.
Single cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization
Authors: Liu Fengshuo , Ding Yunfeng , Xu Zhan , Hao Xiaoxin , Pan Tianhong , Miles George , Wu Yi-Hsuan , Liu Jun , Bado Igor L. , Zhang Weijie , Wu Ling , Gao Yang , Yu Liqun , Edwards David G. , Chan Hilda L. , Aguirre Sergio , Dieffenbach Michael Warren , Chen Elina , Shen Yichao , Hoffman Dane , Dominguez Luis Becerra , Rivas Charlotte Helena , Chen Xiang , Wang Hai , Gugala Zbigniew , Satcher Robert L. , Zhang Xiang H.-F. 
Published: May 2024

SUMMARYBone represents congenial soil for metastatic seeds and is frequently affected by metastasis of multiple cancer types. The histological and molecular characteristics of bone metastases (BMs) are diverse but poorly understood. Herein, we performed single-cell RNA-seq on 34 BMs from 6 cancer types and identified 3 ecosystem archetypes characterized by enrichment of macrophages/osteoclasts (Mφ-OC), regulatory/exhausted T cells (Treg-Tex), and monocytes (Mono), respectively. Breast cancer BMs are mostly the Mφ-OC archetype driven by the osteolytic vicious cycle, whereas kidney cancers BMs mainly belong to the Treg-Tex archetype that lacks osteoclasts. Lung cancers BMs evenly distributed across all archetypes. Further analyses revealed parallel mechanisms of immunosuppression and bone remodeling. Elevated estrogen signaling distinguishes macrophages in the Mφ-OC subtype, which was investigated in a companion study. Together, we elucidated that divergent mechanisms toward bone colonization and that BMs of different origins can adopt the same mechanism through convergent evolution or adaptation.HIGHLIGHTSAnalyses of bone metastases from 6 cancer types revealed three immune archetypes.Archetypes diverge on immune trajectories, and features of tumor and stromal cells.Dominant cell type in each archetype undergoes convergent evolution.Regulatory networks converge on osteoclasts and Tregs to drive archetype formation.Graphic Abstract
Crosslinker Architectures Impact Viscoelasticity in Dynamic Covalent Hydrogels
Authors: Lin Yung-Hao , Lou Junzhe , Xia Yan , Chaudhuri Ovijit 
Published: May 2024

AbstractDynamic covalent crosslinked (DCC) hydrogels represent a significant advance in biomaterials for regenerative medicine and mechanobiology. These gels typically offer viscoelasticity and self-healing properties that more closely mimicin vivotissue mechanics than traditional, predominantly elastic, covalent crosslinked hydrogels. Despite their promise, the effects of varying crosslinker architecture – side chain versus telechelic crosslinks – on the viscoelastic properties of DCC hydrogels have not been thoroughly investigated. This study introduces hydrazone-based alginate hydrogels and examines how side-chain and telechelic crosslinker architectures impact hydrogel viscoelasticity and stiffness. In hydrogels with side-chain crosslinking (SCX), higher polymer concentrations enhance stiffness and decelerates stress relaxation, while an off-stoichiometric hydrazine-to-aldehyde ratio leads to reduced stiffness and shorter relaxation time. In hydrogels with telechelic crosslinking, maximal stiffness and slowest stress relaxation occurs at intermediate crosslinker concentrations for both linear and star crosslinkers, with higher crosslinker valency further increasing stiffness and relaxation time. Our result suggested different ranges of stiffness and stress relaxation are accessible with the different crosslinker architectures, with SCX hydrogels leading to slower stress relaxation relative to the other architectures, and hydrogels with star crosslinking (SX) providing increased stiffness and slower stress relaxation relative to hydrogels with linear crosslinking (LX). The mechanical properties of SX hydrogels are more robust to changes induced by competing chemical reactions compared to LX hydrogels. Our research underscores the pivotal role of crosslinker architecture in defining hydrogel stiffness and viscoelasticity, providing crucial insights for the design of DCC hydrogels with tailored mechanical properties for specific biomedical applications.
A method for filtering abnormal modified base calling in Oxford Nanopore Technologies sequencing
Authors: Jia Ruikai , Wang Yusha , Ye Hua , Ma Xiaoshu 
Published: May 2024

AbstractBackgroundgene synthesis sequencing using the long-read Oxford Nanopore Technologies (ONT) provides a cost-effective option for gene synthesis quality control. Despite the advantage of using long reads, however, accurate base calling is influenced by modified bases.ResultsWe introduce a method for filtering abnormal modified base calling in Oxford Nanopore Technologies sequencing. This method is based on the mapping results and perform an exact binomial test on the proportion of single base forward and reverse chain depth to determine the presence of abnormal modified base calling. Based on Sanger sequencing results, this method detected 96.79% of effective abnormal modified base calling, and the accuracy of gene synthesis sequencing increased from 99.40% before calibration to 99.98% after calibration, significantly reducing the proportion of requiring secondary gene synthesis sequencing.ConclusionThis method can accurately filter abnormally modified base calling sites, reduce the proportion of using Sanger for secondary sequencing, thereby saving costs, and improving efficiency.
A pressure-jump EPR system to monitor millisecond conformational exchange rates of spin-labeled proteins
Authors: Grosskopf Julian D. , Sidabras Jason W. , Altenbach Christian , Anderson Jim R. , Mett Richard R. , Strangeway Robert A. , Hyde James S. , Hubbell Wayne L. , Lerch Michael T. 
Published: May 2024

AbstractSite-directed spin labeling electron paramagnetic resonance (SDSL-EPR) using nitroxide spin labels is a well-established technology for mapping site-specific secondary and tertiary structure and for monitoring conformational changes in proteins of any degree of complexity, including membrane proteins, with high sensitivity. SDSL-EPR also provides information on protein dynamics in the time scale of ps-μs using continuous wave lineshape analysis and spin lattice relaxation time methods. However, the functionally important time domain of μs-ms, corresponding to large-scale protein motions, is inaccessible to those methods. To extend SDSL-EPR to the longer time domain, the perturbation method of pressure-jump relaxation is implemented. Here, we describe a complete high-pressure EPR system at Q-band for both static pressure and millisecond-timescale pressure-jump measurements on spin-labeled proteins. The instrument enables pressure jumps both up and down from any holding pressure, ranging from atmospheric pressure to the maximum pressure capacity of the system components (∼3500 bar). To demonstrate the utility of the system, we characterize a local folding-unfolding equilibrium of T4 lysozyme. The results illustrate the ability of the system to measure thermodynamic and kinetic parameters of protein conformational exchange on the millisecond timescale.
Activation of PKR by a short-hairpin RNA
Authors: Cottrell Kyle A. , Ryu Sua , Donelick Helen , Mai Hung , Pierce Jackson R. , Bass Brenda L. , Weber Jason D. 
Published: May 2024

AbstractRecognition of viral infection often relies on the detection of double-stranded RNA (dsRNA), a process that is conserved in many different organisms. In mammals, proteins such as MDA5, RIG-I, OAS, and PKR detect viral dsRNA, but struggle to differentiate between viral and endogenous dsRNA. This study investigates an shRNA targeting DDX54’s potential to activate PKR, a key player in the immune response to dsRNA. Knockdown of DDX54 by a specific shRNA induced robust PKR activation in human cells, even when DDX54 is overexpressed, suggesting an off-target mechanism. Activation of PKR by the shRNA was enhanced by knockdown of ADAR1, a dsRNA binding protein that suppresses PKR activation, indicating a dsRNA-mediated mechanism. In vitro assays confirmed direct PKR activation by the shRNA. These findings emphasize the need for rigorous controls and alternative methods to validate gene function and minimize unintended immune pathway activation.
Sexual display behaviour follows consistent sex-specific reaction norms across latitude in response to operational sex-ratio
Authors: Martinossi-Allibert Ivain , Wacker Sebastian , Aparicio Estalella Claudia , Kvarnemo Charlotta , Amundsen Trond 
Published: May 2024

AbstractPredicting the strength and direction of sexual selection is a challenging task for evolutionary theory, as the effects of ecological factors, social environment, and behavioural plasticity, all need to be taken into account. The Operational Sex Ratio (OSR) is a key variable, which has been shown to (i) affect the strength and direction of mating competition, as a social environment cue, and (ii) be affected itself by ecological conditions through sex-specific environmental effects. Yet, gaining a global view of (i) and (ii) in wild populations represents an arduous but necessary step to further our understanding of sexual selection dynamics in the wild. Here, we address this challenge by using reaction norms. We conducted an extensive field study on the two-spotted gobyPomatoschistus flavescens, monitoring six populations along a latitudinal gradient during an entire breeding season. Doing so, we compared across populations the temporal trajectories in social environment and sexual displays, which is unprecedented. We develop a reaction norm framework based on OSR theory to analyse the data. We show that what appears to be tremendous variation in sexual displays across populations and sampling times, follows consistent rules: sexual display behaviour follows behavioural reaction norms in response to the social environment that are consistent across populations, but social environment fluctuations are specific to each population. Recording behaviour not only over time, but also along a latitudinal gradient where ecological conditions change and in turn affect OSR, was necessary to gain insight into the relationship between social environment and sexual displays, which in turn contributes to sexual selection dynamics.
Assessing Immune Microenvironment in TCGA-LUAD via CIBERSORTx Using Single-Cell Derived Signature Matrix and ESTIMATE Algorithm
Authors: Verma Madhulika 
Published: May 2024

AbstractLung cancer (LC) remains a significant global health concern, affecting millions worldwide each year. Tumor-infiltrating immune cells (TIICs) play a crucial role in Lung Cancer progression and prognosis, with various immune cell types infiltrating the tumor microenvironment. Traditional methods like immunohistochemistry and flow cytometry have limitations in accurately profiling TIIC subtypes. However, recent advancements in single-cell RNA sequencing and computational algorithms like CIBERSORTx offer a promising approach for characterizing TIICs in bulk tumor samples.In this study, we undertook the validation of the signature matrix comprising 14 distinct immune cell types and subtypes, which was originally derived from PBMC single-cell RNA-seq data, in our previous work (Verma, 2024). The positive controls included 8 bulk RNA-seq samples of whole blood and specific immune cell bulk RNA-seq samples, while the negative control comprised neuroblastoma cell lines lacking immune content. Subsequently, we applied this signature matrix to deconvolute TCGA-LUAD data (n = 598), and assessed tumor purity and immune-stromal content using the ESTIMATE algorithm.Our findings indicate that the signature matrix accurately reflected flow cytometry-derived fractions, supported by correlation analysis. Specifically, the second positive control and negative control accurately reflected immune and non-immune sample fractions, respectively, further validating the efficacy of our approach. This study also provide insights into the invasion of immunocytes in lung adenocarcinoma and highlight the potential of computational tools like CIBERSORTx and ESTIMATE in characterizing the immune microenvironment of LC.