Repairing a deleterious domestication variant in a floral regulator gene of tomato by base editing.

Crop genomes accumulate deleterious mutations-a phenomenon known as the cost of domestication. Precision genome editing has been proposed to eliminate such potentially harmful mutations; however, experimental demonstration is lacking. Here we identified a deleterious mutation in the tomato transcription factor SUPPRESSOR OF SP2 (SSP2), which became prevalent in the domesticated germplasm and diminished DNA binding to genome-wide targets.

Roughness integration across fingers within compared with across the hands.

Feeling a texture typically involves sliding the fingers of a hand across that surface or rubbing the surface between the thumb and another digit. Texture signals appear to be integrated across the digits of a hand with perceived roughness at one finger swayed in the direction of texture touched by another finger of the same hand. To date, one study has reported similar integrative effects when the pairs of digits belong to different hands.

Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement.

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations.

Is increased mutation driving genetic diversity in dogs within the Chornobyl exclusion zone?

Environmental contamination can have lasting impacts on surrounding communities, though the long-term impacts can be difficult to ascertain. The disaster at the Chornobyl Nuclear Power Plant in 1986 and subsequent remediation efforts resulted in contamination of the local environment with radioactive material, heavy metals, and additional environmental toxicants. Many of these are mutagenic in nature, and the full effect of these exposures on local flora and fauna has yet to be understood.

Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma.

Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor () to the proliferative isoform.

Hearing aid adoption rates among adults without hearing aid experience in an audiology clinic before and after price unbundling.

Objectives: The purpose of this study was to investigate a policy-related factor and patient-related factors that might affect hearing aid adoption for adults, specifically price unbundling, and demographic and audiologic factors, respectively.

Design: Retrospective data from hearing aid consultation appointments in an audiology clinic in a medical centre were examined. Appointments were conducted between 2019 and 2023, capturing visits when services and devices were charged using a model that was bundled (2019-2022) and unbundled (2023).

Evaluation of Pharmacist Involvement in Emergency Response.

: Emergency response teams are designed to promptly deliver care to hospitalized patients experiencing acute decompensation events. Pharmacists are an integrated part of emergency response teams and their presence at emergency response events has been shown to improve adherence to institutional and advanced cardiac life support (ACLS) guidelines. This study assesses the impact of pharmacist involvement at emergency responses and time clinical pharmacists dedicate to emergency response.

The interaction between values and self-identity on fairtrade consumption: The value-identity-behavior model.

The interplay between egoistic and altruistic values, self-identity, and ethical behaviors remains underexplored, despite its significance in ethical consumption. This study investigates these dynamics by developing and testing the Value-Identity-Behavior model using a robust dataset of 3023 participants from three leading fairtrade markets in Europe: the U.K.

Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children.

Background: Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for Plasmodium falciparum malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.

Domainator, a flexible software suite for domain-based annotation and neighborhood analysis, identifies proteins involved in antiviral systems.

The availability of large databases of biological sequences presents an opportunity for in-depth exploration of gene diversity and function. Bacterial defense systems are a rich source of diverse but difficult to annotate genes with biotechnological applications. In this work, we present Domainator, a flexible and modular software suite for domain-based gene neighborhood and protein search, extraction and clustering.

Small and Long Non-Coding RNA Analysis for Human Trophoblast-Derived Extracellular Vesicles and Their Effect on the Transcriptome Profile of Human Neural Progenitor Cells.

In mice, the fetal brain is dependent upon the placenta for factors that guide its early development. This linkage between the two organs has given rise to the term, the placenta-brain axis. A similar interrelationship between the two organs may exist in humans.

Tomato roots exhibit distinct, development-specific responses to bacterial-derived peptides.

Plants possess cell-surface recognition receptors that detect molecular patterns from microbial invaders and initiate an immune response. Understanding the conservation of pattern-triggered immunity within different plant organs and across species is crucial to its sustainable and effective use in plant disease management but is currently unclear.We examined the activation and immune response patterns of three pattern recognition receptors (PRRs: FLS2, FLS3, and CORE) in different developmental regions of roots and in leaves of multiple accessions of domesticated and wild tomato ( and ) using biochemical and genetic assays.

TIA1 Mediates Divergent Inflammatory Responses to Tauopathy in Microglia and Macrophages.

The RNA binding protein TIA1 is known to regulate stress responses. Here we show that TIA1 plays a much broader role in inflammatory cells, being required for the microglial sensome. We crossed TIA1 cKO mice (using a CX3CR1 driven cre element) to PS19 MAPT P301S tauopathy mice.

Information Needs of Australian Families Living with Craniosynostosis: A Qualitative Study.

Objective: Craniosynostosis is considered a lifelong condition, yet relatively little focus has been directed toward ascertaining the information needs of Australian families. Thus, the aim of this study was to explore the information needs of Australian parents whose child has been diagnosed with nonsyndromic or syndromic craniosynostosis.

Design: Twenty-one online narrative interviews were conducted with parents of children with craniosynostosis (aged between 4 months and 20 years).

Eurasian spruce bark beetle detects lanierone using a highly expressed specialist odorant receptor, present in several functional sensillum types.

Background: Insects detect odours using odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) in the antennae. Ecologically important odours are often detected by selective and abundant OSNs; hence, ORs with high antennal expression. However, little is known about the function of highly expressed ORs in beetles, since few ORs have been functionally characterized.

'For Youth by Youth': Distributive Leadership in Action With a Youth Codesign Team.

Background: Integrated youth services are an emerging delivery model in Canada that addresses siloed and fragmented youth mental health and other services. Youth engagement is viable for developing integrated youth services when purposefully built. However, it is not always clear how youth are involved in service transformation as decision-makers, and it requires an exploration of how to work with youth authentically and intentionally in the codesign process.

Aberrant activation of wound healing programs within the metastatic niche facilitates lung colonization by osteosarcoma cells.

Purpose: Lung metastasis is responsible for most deaths caused by osteosarcoma. How malignant bone cells coerce the lung microenvironment to support metastatic growth remains unclear. We sought to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms essential to metastatic niche formation in the lung.

Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn's Disease.

Background And Aims: Management of Crohn's disease (CD) requires frequent monitoring for disease activity and response to therapy. In this study, we examined the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic in patients with CD.

Methods: Stool samples were collected from 68 individuals for up to 3 time points prior to, and after initiation of an advanced therapy.

Matching excellence: Oxford Nanopore Technologies' rise to parity with Pacific Biosciences in genome reconstruction of non-model bacterium with high G+C content.

The reconstruction of complete bacterial genomes is essential for microbial research, offering insights into genetic content, ontology and regulation. While Pacific Biosciences (PacBio) provides high-quality genomes, its cost remains a limitation. Oxford Nanopore Technologies (ONT) offers long reads at a lower cost, yet its error rate raises scepticism.

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Purpose: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

Methods: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles.

Treatment with novel topoisomerase inhibitors in Ewing sarcoma models reveals heterogeneity of tumor response.

Introduction: The topoisomerase 1 (TOP1) inhibitor irinotecan is a standard-of-care agent for relapsed Ewing sarcoma (EWS), but its efficacy is limited by chemical instability, rapid clearance and reversibility, and dose-limiting toxicities, such as diarrhea. Indenoisoquinolines (IIQs) represent a new class of clinical TOP1 inhibitors designed to address these limitations.

Methods: In this study, we evaluated the preclinical efficacy of three IIQs (LMP400, LMP744, and LMP776) in relevant models of EWS.

Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma.

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection.