TTF2 promotes replisome eviction from stalled forks in mitosis.

When cells enter mitosis with under-replicated DNA, sister chromosome segregation is compromised, which can lead to massive genome instability. The replisome-associated E3 ubiquitin ligase TRAIP mitigates this threat by ubiquitylating the CMG helicase in mitosis, leading to disassembly of stalled replisomes, fork cleavage, and restoration of chromosome structure by alternative end-joining. Here, we show that replisome disassembly requires TRAIP phosphorylation by the mitotic Cyclin B-CDK1 kinase, as well as TTF2, a SWI/SNF ATPase previously implicated in the eviction of RNA polymerase from mitotic chromosomes.

Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model.

Mucosal healing is associated with better clinical outcomes in patients with inflammatory bowel disease. But the epithelial-specific contribution to mucosal healing in vivo is poorly understood. We evaluated mucosal healing in an acute dextran sulfate sodium mouse model that shows an alleviated colitis response after epithelial-specific loss of Smad4.

USP37 prevents premature disassembly of stressed replisomes by TRAIP.

The E3 ubiquitin ligase TRAIP associates with the replisome and helps this molecular machine deal with replication stress. Thus, TRAIP promotes DNA inter-strand crosslink repair by triggering the disassembly of CDC45-MCM2-7-GINS (CMG) helicases that have converged on these lesions. However, disassembly of single CMGs that have stalled temporarily would be deleterious, suggesting that TRAIP must be carefully regulated.

False-Negative PET/CT scan with Metastatic Sebaceous Carcinoma: An Important Diagnostic Consideration.

Unlabelled: Positron emission tomography (PET) has gained widespread acceptance as a valuable diagnostic tool for cancer. It is rare for a PET/CT scan to overlook the presence of metastatic disease. Sebaceous carcinoma is an uncommon malignant tumour that typically originates in the skin of the eyelid.

Smad4 Loss in the Mouse Intestinal Epithelium Alleviates the Pathological Fibrotic Response to Injury in the Colon.

Unlabelled: Mucosal healing is associated with better clinical outcomes in patients with inflammatory bowel diseases (IBDs). Unresolved injury and inflammation, on the other hand, increases pathological fibrosis and the predisposition to cancer. Loss of Smad4, a tumor suppressor, is known to increase colitis-associated cancer in mouse models of chronic IBD.

Design and Evaluation of ZD06519, a Novel Camptothecin Payload for Antibody Drug Conjugates.

In recent years, the field of antibody drug conjugates (ADC) has seen a resurgence, largely driven by the clinical benefit observed in patients treated with ADCs incorporating camptothecin-based topoisomerase I inhibitor payloads. Herein, we present the development of a novel camptothecin ZD06519 (FD1), which has been specifically designed for its application as an ADC payload. A panel of camptothecin analogs with different substituents at the C-7 and C-10 positions of the camptothecin core was prepared and tested in vitro.

Contrasting leaf-scale photosynthetic low-light response and its temperature dependency are key to differences in crop-scale radiation use efficiency.

Radiation use efficiency (RUE) is a key crop adaptation trait that quantifies the potential amount of aboveground biomass produced by the crop per unit of solar energy intercepted. But it is unclear why elite maize and grain sorghum hybrids differ in their RUE at the crop level. Here, we used a non-traditional top-down approach via canopy photosynthesis modelling to identify leaf-level photosynthetic traits that are key to differences in crop-level RUE.

Hierarchical integration of DNA nanostructures and NanoGold onto a microchip facilitates covalent chemistry-mediated purification of circulating tumor cells in head and neck squamous cell carcinoma.

It is well-established that the combined use of nanostructured substrates and immunoaffinity agents can enhance the cell-capture performance of the substrates, thus offering a practical solution to effectively capture circulating tumor cells (CTCs) in peripheral blood. Developing along this strategy, this study first demonstrated a top-down approach for the fabrication of tetrahedral DNA nanostructure (TDN)-NanoGold substrates through the hierarchical integration of three functional constituents at various length-scales: a macroscale glass slide, sub-microscale self-organized NanoGold, and nanoscale self-assembled TDN. The TDN-NanoGold substrates were then assembled with microfluidic chaotic mixers to give TDN-NanoGold Click Chips.

The murine metastatic microenvironment of experimental brain metastases of breast cancer differs by host age in vivo: a proteomic study.

Breast cancer in young patients is known to exhibit more aggressive biological behavior and is associated with a less favorable prognosis than the same disease in older patients, owing in part to an increased incidence of brain metastases. The mechanistic explanations behind these findings remain poorly understood. We recently reported that young mice, in comparison to older mice, developed significantly greater brain metastases in four mouse models of triple-negative and luminal B breast cancer.

Critical examination of the characterization techniques, and the evidence, for the existence of extra-long amylopectin chains.

It has been suggested that amylopectin can contain small but significant amounts of extra-long chains (ELCs), which could affect functional properties, and also would have implications for the mechanism of starch biosynthesis. However, current evidence for the existence of ELCs is ambiguous. The amylose/amylopectin separation and the characterization techniques used for the investigation of ELCs are reviewed, problems in those techniques are examined, and studies of ELCs of amylopectin are discussed.

Habituation for professional learning: a qualitative study of physiotherapy students' experiences working with anatomy cadavers.

Introduction: Cadaveric dissection shapes the ways in which healthcare students understand the human body and the attitudes, identities and behaviors they exhibit as health professionals. There is however a paucity of related research with physiotherapy (PT) students.

Purpose: The purpose of this interpretivist study was to investigate PT students' conceptions of the human body in relation to experiences with human cadavers in anatomy education.

Complementary and Alternative Medicine Use in Patients With Cancer and Immigration Background.

Purpose: Studies have shown that patients with cancer are more likely to use complementary and alternative medicine (CAM) than noncancer patients for symptom relief and hope. We aimed to evaluate factors of race, ethnic groups, and immigration status in attitude of patients with cancer in seeking out CAM.

Patients And Methods: This is a prospective questionnaire study where information on demographics, cancer information, race/ethnicity, immigration duration, and psychosocial factors was correlated with the CAM use in a community cancer center located in the borough of Brooklyn, at New York City.

Tumor stromal topography promotes chemoresistance in migrating breast cancer cell clusters.

Multicellular clustering provides cancer cells with survival advantages and facilitates metastasis. At the tumor migration front, cancer cell clusters are surrounded by an aligned stromal topography. It remains unknown whether aligned stromal topography regulates the resistance of migrating cancer cell clusters to therapeutics.

Modelling plants across scales of biological organisation for guiding crop improvement.

Grain yield improvement in globally important staple crops is critical in the coming decades if production is to keep pace with growing demand; so there is increasing interest in understanding and manipulating plant growth and developmental traits for better crop productivity. However, this is confounded by complex cross-scale feedback regulations and a limited ability to evaluate the consequences of manipulation on crop production. Plant/crop modelling could hold the key to deepening our understanding of dynamic trait-crop-environment interactions and predictive capabilities for supporting genetic manipulation.

Matrix Anisotropy Promotes a Transition of Collective to Disseminated Cell Migration via a Collective Vortex Motion.

Cells detached and disseminated away from collectively migrating cells are frequently found during tumor invasion at the invasion front, where extracellular matrix (ECM) fibers are parallel to the cell migration direction. However, it remains unclear how anisotropic topography promotes the transition of collective to disseminated cell migration. This study applies a collective cell migration model with and without 800 nm wide aligned nanogrooves parallel, perpendicular, or diagonal to the cell migration direction.

Prospective randomized multicenter noninferiority clinical trial evaluating the use of TFN-advanced proximal femoral nailing system (TFNA) for the treatment of proximal femur fracture in a Chinese population.

Purpose: To evaluate whether the 24-weeks postoperative fracture union rate for the investigational TFNA intramedullary nail was non-inferior compared to the control product PFNA-II.

Methods: The study was a prospective, randomized, single-blind, noninferiority dual-arm study drawing from 9 trauma centers across China, between November 2018 and September 2020, with follow-up measurements at 24 weeks after internal fixation. The full analysis data set (FAS [Intent-to-Treat]) was analyzed and is summarized here.

Outcomes of surgical versus nonsurgical treatment for multiple rib fractures: A US hospital matched cohort database analysis.

Background: Treatment for multiple rib fractures includes surgical stabilization of rib fractures (SSRF) or nonoperative management (NOM). Meta-analyses have demonstrated that SSRF results in faster recovery and lower long-term complication rates versus NOM. Our study evaluated postoperative outcomes for multiple rib fracture patients following SSRF versus NOM in a real-world, all-comer study design.

A cross-scale analysis to understand and quantify the effects of photosynthetic enhancement on crop growth and yield across environments.

Photosynthetic manipulation provides new opportunities for enhancing crop yield. However, understanding and quantifying the importance of individual and multiple manipulations on the seasonal biomass growth and yield performance of target crops across variable production environments is limited. Using a state-of-the-art cross-scale model in the APSIM platform we predicted the impact of altering photosynthesis on the enzyme-limited (A ) and electron transport-limited (A ) rates, seasonal dynamics in canopy photosynthesis, biomass growth, and yield formation via large multiyear-by-location crop growth simulations.

PDMS-PEG Block Copolymer and Pretreatment for Arresting Drug Absorption in Microphysiological Devices.

Poly(dimethylsiloxane) (PDMS) is a commonly used polymer in organ-on-a-chip devices and microphysiological systems. However, due to its hydrophobicity and permeability, it absorbs drug compounds, preventing accurate drug screening applications. Here, we developed an effective and facile method to prevent the absorption of drugs by utilizing a PDMS-PEG block copolymer additive and drug pretreatment.

Genetic basis of sorghum leaf width and its potential as a surrogate for transpiration efficiency.

Leaf width was correlated with plant-level transpiration efficiency and associated with 19 QTL in sorghum, suggesting it could be a surrogate for transpiration efficiency in large breeding program. Enhancing plant transpiration efficiency (TE) by reducing transpiration without compromising photosynthesis and yield is a desirable selection target in crop improvement programs. While narrow individual leaf width has been correlated with greater intrinsic water use efficiency in C species, the extent to which this translates to greater plant TE has not been investigated.

Estimating Photosynthetic Attributes from High-Throughput Canopy Hyperspectral Sensing in Sorghum.

Sorghum, a genetically diverse C cereal, is an ideal model to study natural variation in photosynthetic capacity. Specific leaf nitrogen (SLN) and leaf mass per leaf area (LMA), as well as, maximal rates of Rubisco carboxylation ( ), phosphoenolpyruvate (PEP) carboxylation ( ), and electron transport ( ), quantified using a C photosynthesis model, were evaluated in two field-grown training sets ( = 169 plots including 124 genotypes) in 2019 and 2020. Partial least square regression (PLSR) was used to predict ( = 0.

Calcium handling genes are regulated by promoter DNA methylation in colorectal cancer cells.

Calcium signaling regulates various cellular processes, including proliferation and cell death. DNA methylation of gene promoters is an epigenetic modification that facilitates transcriptional suppression. Disruption of calcium homeostasis and DNA methylation in cancer are each linked to tumor development and progression.

Genetic control of leaf angle in sorghum and its effect on light interception.

Developing sorghum genotypes adapted to different light environments requires understanding of a plant's ability to capture light, determined through leaf angle specifically. This study dissected the genetic basis of leaf angle in 3 year field trials at two sites, using a sorghum diversity panel (729 accessions). A wide range of variation in leaf angle with medium heritability was observed.