A targetable developmental program co-regulates angiogenesis and immune evasion.

Ultraviolet (UV)-induced DNA mutations produce genetic drivers of cutaneous melanoma initiation and numerous neoantigens that can trigger anti-tumor immune responses in the host. Consequently, melanoma cells must rapidly evolve to evade immune detection by simultaneously modulating cell-autonomous epigenetic mechanisms and tumor-microenvironment interactions. Angiogenesis has been implicated in this process; although an increase of vasculature initiates the immune response in normal tissue, solid tumors manage to somehow enhance blood flow while preventing immune cell infiltration.

Pre-conception nutrition estimated from milk composition characterises the sex ratio of offspring in cattle.

In livestock breeding, offspring of a particular sex are often favoured. Various biological mechanisms influence the offspring sex ratio (OSR). It has been hypothesised that maternal body condition/nutritional status influence OSR.

Enrichments Adjusted to the Number of Litters: Simple Approach to Improve the Welfare of Weaned Piglets under Farm Conditions.

Environmental enrichment is one of the methods used to reduce conflicts at weaning, which erupt when mixing unknown litters and are known to negatively affect growth and welfare of piglets. Here we aimed to test a simple approach of increasing the amount of existing enrichment objects to mitigate post-weaning aggression. The experiment comprised ten groups of piglets (five controls, five tests) with 3-4 litters weaned in each of them.

Factors that determine cell type-specific CTCF binding in health and disease.

A number of factors contribute to cell type-specific CTCF chromatin binding, but how they act in concert to determine binding stability and functionality has not been fully elucidated. In this review, we tie together different layers of regulation to provide a holistic view of what is known. What emerges from these studies is a multifaceted system in which DNA sequence, DNA and chromatin accessibility, and cell type-specific transcription factors together contribute to CTCF binding profile and function.

Chronic viral infection alters PD-1 locus subnuclear localization in cytotoxic CD8 T cells.

During chronic infection, virus-specific CD8 cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice.

Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its ability to act as a chromatin organizer.

Although only a fraction of CTCF motifs are bound in any cell type, and approximately half of the occupied sites overlap cohesin, the mechanisms underlying cell-type specific attachment and ability to function as a chromatin organizer remain unknown. To investigate the relationship between CTCF and chromatin we applied a combination of imaging, structural and molecular approaches, using a series of brain and cancer associated CTCF mutations that act as CTCF perturbations. We demonstrate that binding and the functional impact of WT and mutant CTCF depend not only on the unique properties of each protein, but also on the genomic context of bound sites.

MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data.

Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover cis regulatory elements (CREs) in a 1 Mb region around every promoter in the genome.

Quality by design approach to improve quality and decrease cost of in vitro transcription of mRNA using design of experiments.

In vitro transcription (IVT) reaction is an RNA polymerase-catalyzed production of messenger RNA (mRNA) from DNA template, and the unit operation with highest cost of goods in the mRNA drug substance production process. To decrease the cost of mRNA production, reagents should be optimally utilized. Due to the catalytic, multicomponent nature of the IVT reaction, optimization is a multi-factorial problem, ideally suited to design-of-experiment approach for optimization and identification of design space.

Climate Change Curricula in Family Medicine Residency Programs: Program Directors' Perspectives From a CERA Survey.

Background And Objectives: Climate change is a major threat to the health of people worldwide. The health care system deals with the immediate health-related effects of climate change and, at the same time, is a major emitter of greenhouse gas. This study aimed to investigate (a) the awareness and perception of climate change among family medicine residency program directors, and (b) the state of climate change education in family medicine residency programs.

Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its contribution to gene regulation.

Here we used a series of CTCF mutations to explore CTCF's relationship with chromatin and its contribution to gene regulation. CTCF's impact depends on the genomic context of bound sites and the unique binding properties of WT and mutant CTCF proteins. Specifically, CTCF's signal strength is linked to changes in accessibility, and the ability to block cohesin is linked to its binding stability.

MethNet: a robust approach to identify regulatory hubs and their distal targets in cancer.

Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover novel cis regulatory elements (CREs) in a 1Mb region around every promoter in the genome.

Primary Care Clinicians' Attitude, Knowledge, and Willingness to Address Climate Change in Shared Decision-Making.

Background: Climate change poses a threat to the health of people worldwide. Little is known about the awareness of primary care clinicians toward climate change and if they are open and prepared to address climate change issues with their patients. As pharmaceuticals are the main source of carbon emissions in primary care, avoiding the prescription of particular climate-harmful medications is a meaningful contribution to the reduction of greenhouse gases.

What do we want? Training! When do we want it? Now? A training needs analysis for adaptive radiotherapy for therapeutic radiographers.

Introduction: Therapeutic radiographers (TRs) have adapted to the changing requirements and demands of the oncology service and in response to advanced techniques such as on-line adaptive MRI-guided radiotherapy (MRIgRT). The skills required for MRIgRT would benefit many TRs not just those involved in this technique. This study presents the results of a training needs analysis (TNA) for the required MRIgRT skills in readiness for training TRs for current and future practice.

Cell-type-specific prediction of 3D chromatin organization enables high-throughput in silico genetic screening.

Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.

Increasing yield of in vitro transcription reaction with at-line high pressure liquid chromatography monitoring.

The COVID-19 pandemic triggered an unprecedented rate of development of messenger ribonucleic acid (mRNA) vaccines, which are produced by in vitro transcription reactions. The latter has been the focus of intense development to increase productivity and decrease cost. Optimization of in vitro transcription (IVT) depends on understanding the impact of individual reagents on the kinetics of mRNA production and the consumption of building blocks, which is hampered by slow, low-throughput, end-point analytics.

Images and images: Current roles of therapeutic radiographers.

Introduction: Therapeutic radiography is a small profession and has adapted in response to advanced techniques. An increase in on-line adaptive MRI-guided radiotherapy (MRIgRT) will require role extension for therapeutic radiographers (TRs). This study will investigate the current role description for TRs and the activities they currently undertake with regards to MRIgRT.

The art of chromosome dynamics: an interview with Jane Skok.

In this interview, Professor Jane Skok speaks with Storm Johnson, commissioning editor for , on her work to date in the field of chromosome architecture and regulatory elements. Jane Skok's lab uses sophisticated microscopic techniques to visualize recombination in individual cells, tracing the dynamic changes in chromosome architecture and nuclear location at different stages of this complex process. This line of research unites two lifelong passions: science and art.

CRISPR and biochemical screens identify MAZ as a cofactor in CTCF-mediated insulation at Hox clusters.

CCCTC-binding factor (CTCF) is critical to three-dimensional genome organization. Upon differentiation, CTCF insulates active and repressed genes within Hox gene clusters. We conducted a genome-wide CRISPR knockout (KO) screen to identify genes required for CTCF-boundary activity at the HoxA cluster, complemented by biochemical approaches.

Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer.

Unlabelled: Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. "Drug-tolerant persisters" (DTP), a subpopulation of cancer cells that survive via reversible, nongenetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKI) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome.

Morphogenesis of digitate structures in hot spring silica sinters of the El Tatio geothermal field, Chile.

In silica-rich hot spring environments, internally laminated, digitate sinter deposits are often interpreted as bio-mediated structures. The organic components of microbial communities (cell surfaces, sheaths and extracellular polymeric substances) can act as templates for silica precipitation, therefore influencing digitate sinter morphogenesis. In addition to biologic surface-templating effects, various microenvironmental factors (hydrodynamics, local pH and fluctuating wind patterns) can also influence silica precipitation, and therefore the morphology of resulting digitate sinters.