Subtilase SBT5.2 inactivates flagellin immunogenicity in the plant apoplast.

Most angiosperm plants recognise the 22-residue flagellin (flg22) epitope in bacterial flagellin via homologs of cell surface receptor FLS2 (flagellin sensitive-2) and mount pattern-triggered immune responses. However, flg22 is buried within the flagellin protein indicating that proteases might be required for flg22 release. Here, we demonstrate the extracellular subtilase SBT5.

A Robotic Clamped-Kinematic System to Study Knee Ligament Injury.

Knee ligament injury is among the most common sports injuries and is associated with long recovery periods and low return-to-sport rates. Unfortunately, the mechanics of ligament injury are difficult to study in vivo, and computational studies provide limited insight. The objective of this study was to implement and validate a robotic system capable of reproducing natural six degree-of-freedom clamped-kinematic trajectories on human cadaver knees (meaning that positions and orientations are rigidly controlled and resultant loads are measured).

Novel structural insights at the extracellular plant-pathogen interface.

Plant pathogens represent a critical threat to global agriculture and food security, particularly under the pressures of climate change and reduced agrochemical use. Most plant pathogens initially colonize the extracellular space or apoplast and understanding the host-pathogen interactions that occur here is vital for engineering sustainable disease resistance in crops. Structural biology has played important roles in elucidating molecular mechanisms underpinning plant-pathogen interactions but only few studies have reported structures of extracellular complexes.

Hypoxia represses pattern-triggered immune responses in Arabidopsis.

Biotic and abiotic stresses frequently co-occur in nature, yet relatively little is known about how plants coordinate the response to combined stresses. Protein degradation by the ubiquitin/proteasome system is central to the regulation of multiple independent stress response pathways in plants. The Arg/N-degron pathway is a subset of the ubiquitin/proteasome system that targets proteins based on their N-termini and has been specifically implicated in the responses to biotic and abiotic stresses, including hypoxia, via accumulation of group VII ETHYLENE RESPONSE FACTOR (ERF-VII) transcription factors that orchestrate the onset of the hypoxia response program.

Cytoskeleton-associated gelsolin responds to the midgut distention process in saline meal-fed Aedes aegypti and affects arbovirus dissemination from the midgut.

The mosquito, Aedes aegypti, is the principal vector for several arboviruses. The mosquito midgut is the initial tissue that gets infected with an arbovirus acquired along with a blood meal from a vertebrate host. Blood meal ingestion leads to midgut tissue distention thereby increasing the pore size of the surrounding basal lamina.

Bioengineering secreted proteases converts divergent Rcr3 orthologs and paralogs into extracellular immune co-receptors.

Secreted immune proteases "Required for Cladosporium resistance-3" (Rcr3) and "Phytophthora-inhibited protease-1" (Pip1) of tomato (Solanum lycopersicum) are both inhibited by Avirulence-2 (Avr2) from the fungal plant pathogen Cladosporium fulvum. However, only Rcr3 acts as a decoy co-receptor that detects Avr2 in the presence of the Cf-2 immune receptor. Here, we identified crucial residues in tomato Rcr3 that are required for Cf-2-mediated signaling and bioengineered various proteases to trigger Avr2/Cf-2-dependent immunity.

IMMUNOTAR - Integrative prioritization of cell surface targets for cancer immunotherapy.

Cancer remains a leading cause of mortality globally. Recent improvements in survival have been facilitated by the development of less toxic immunotherapies; however, identifying targets for immunotherapies remains a challenge in the field. To address this challenge, we developed IMMUNOTAR, a computational tool that systematically prioritizes and identifies candidate immunotherapeutic targets.

BIG enhances Arg/N-degron pathway-mediated protein degradation to regulate Arabidopsis hypoxia responses and suberin deposition.

BIG/DARK OVEREXPRESSION OF CAB1/TRANSPORT INHIBITOR RESPONSE3 is a 0.5 MDa protein associated with multiple functions in Arabidopsis (Arabidopsis thaliana) signaling and development. However, the biochemical functions of BIG are unknown.

Similar Medium-Term Revision Rates Following Acute Total Hip Arthroplasty Versus Open Reduction and Internal Fixation for Acetabular Fractures in the Elderly.

Background: The management of elderly acetabular fractures is complex, with high rates of conversion total hip arthroplasty (THA) after open reduction and internal fixation (ORIF), but potentially higher rates of complications after acute THA.

Methods: The California Office of Statewide Health Planning and Development database was queried between 2010 and 2017 for all patients aged 60 years or older who sustained a closed, isolated acetabular fracture and underwent ORIF, THA, or a combination. Chi-square tests and Student t tests were used to identify demographic differences between groups.

Reverse total shoulder arthroplasty with proximal bone loss: a biomechanical comparison of partially vs. fully cemented humeral stems.

Background: The appropriate amount of cementation at the time of reverse total shoulder arthroplasty with significant proximal bone loss or resection is unknown. Extensive cementation of a humeral prosthesis makes eventual revision arthroplasty more challenging, increasing the risk of periprosthetic fracture. We analyzed the degree of subsidence and torque tolerance of humeral components undergoing standard cementation technique vs.

Postoperative Care and Outcomes in Solid-Organ Transplant Patients Undergoing Lower Extremity Fracture Treatment.

Objectives: To determine the postoperative outcomes in solid-organ transplant (SOT) patients undergoing operative treatment of lower extremity fractures.

Design: Retrospective comparative study.

Setting: Academic Level 1 trauma center.

Pilot Study of a Mobile Phone Chatbot for Medication Adherence and Toxicity Management Among Patients With GI Cancers on Capecitabine.

Purpose: Capecitabine is an oral chemotherapy used to treat many gastrointestinal cancers. Its complex dosing and narrow therapeutic index make medication adherence and toxicity management crucial for quality care.

Methods: We conducted a pilot study of PENNY-GI, a mobile phone text messaging-based chatbot that leverages algorithmic surveys and natural language processing to promote medication adherence and toxicity management among patients with gastrointestinal cancers on capecitabine.

Surface and Global Proteome Analyses Identify ENPP1 and Other Surface Proteins as Actionable Immunotherapeutic Targets in Ewing Sarcoma.

Purpose: Ewing sarcoma is the second most common bone sarcoma in children, with 1 case per 1.5 million in the United States. Although the survival rate of patients diagnosed with localized disease is approximately 70%, this decreases to approximately 30% for patients with metastatic disease and only approximately 10% for treatment-refractory disease, which have not changed for decades.

ATP-sensitive inward rectifier potassium channels regulate secretion of pro-feeding salivary proteins in the lone star tick (Amblyomma americanum).

Understanding the physiological and molecular regulation of tick feeding is necessary for developing intervention strategies to curb disease transmission by ticks. Pharmacological activation of ATP-gated inward rectifier potassium (K) channels reduced fluid secretion from isolated salivary gland and blood feeding in the lone star tick, Amblyomma americanum, yet the temporal expression pattern of K channel proteins remained unknown. K channels were highly expressed in type II and III acini in off-host stage and early feeding phase ticks, yet expression was reduced in later stages of feeding.

Modifiable and non-modifiable risk factors for failure of non-operative treatment of pediatric forearm fractures: Where can we do better?

Introduction: Distal third forearm fractures are common fractures in children. While outcomes are generally excellent, some patients fail initial non-operative management and require intervention. The purpose of this study is to identify independent risk factors associated with failure of closed reduction.

Surgeon and Radiologist Evaluation of Electromagnetic Chip Localization for Benign and Malignant Breast Lesions.

Background: SmartClip is a food and drug administration-approved, electromagnetic chip (EMC) localization system that provides three-dimensional navigation for the excision of soft tissue lesions. The purpose of this study was to analyze the accuracy and feasibility of EMC radiologic and surgical localization for benign and malignant breast lesions.

Patients And Methods: An institutional review board-approved, single institution, prospective study from October 2020 to September 2022 of 38 women undergoing breast conserving surgery with EMC localization of a single lesion > 5 mm on mammogram (MMG) or ultrasound (US) imaging.

Basophil responses in susceptible AKR mice upon infection with the intestinal helminth parasite Trichuris muris.

Intestinal helminth infection promotes a Type 2 inflammatory response in resistant C57BL/6 mice that is essential for worm clearance. The study of inbred mouse strains has revealed factors that are critical for parasite resistance and delineated the role of Type 1 versus Type 2 immune responses in worm clearance. In C57BL/6 mice, basophils are key innate immune cells that promote Type 2 inflammation and are programmed via the Notch signalling pathway during infection with the helminth Trichuris muris.

Cardiovascular Protective Effects of NP-6A4, a Drug with the FDA Designation for Pediatric Cardiomyopathy, in Female Rats with Obesity and Pre-Diabetes.

Background: Obese and pre-diabetic women have a higher risk for cardiovascular death than age-matched men with the same symptoms, and there are no effective treatments. We reported that obese and pre-diabetic female Zucker Diabetic Fatty (ZDF-F) rats recapitulate metabolic and cardiac pathology of young obese and pre-diabetic women and exhibit suppression of cardio-reparative AT2R. Here, we investigated whether NP-6A4, a new AT2R agonist with the FDA designation for pediatric cardiomyopathy, mitigate heart disease in ZDF-F rats by restoring AT2R expression.

Insurance-Based Disparities in Congenital Cardiac Operations in the Era of the Affordable Care Act.

A body of literature has previously highlighted the impact of health insurance on observed disparities in congenital cardiac operations. With aims of improving access to healthcare for all patients, the Affordable Care Act (ACA) expanded Medicaid coverage to nearly all eligible children in 2010. Therefore, the present population-based study aimed to examine the association of Medicaid coverage with clinical and financial outcomes in the era the ACA.

Human antibodies targeting ENPP1 as candidate therapeutics for cancers.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein expressed in many tissues. High expression levels of ENPP1 have been observed in many cancer types such as lung cancer, ovarian cancer, and breast cancer. Such overexpression has been associated with poor prognosis in these diseases.

Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial.

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ).

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Objective: To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR).

Methods: Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer.

Glycoproteomic Analyses of Influenza A Viruses Using timsTOF Pro MS.

-Linked glycosylation in hemagglutinin and neuraminidase glycoproteins of influenza viruses affects antigenic and receptor binding properties, and precise analyses of site-specific glycoforms in these proteins are critical in understanding the antigenic and immunogenic properties of influenza viruses. In this study, we developed a glycoproteomic approach by using a timsTOF Pro mass spectrometer (MS) to determine the abundance and heterogeneity of site-specific glycosylation for influenza glycoproteins. Compared with a Q Exactive HF MS, the timsTOF Pro MS method without the hydrophilic interaction liquid chromatography column enrichment achieved similar glycopeptide coverage and quantities but was more effective in identifying low-abundance glycopeptides.