Pathophysiology of Angiotensin II-Mediated Hypertension, Cardiac Hypertrophy, and Failure: A Perspective from Macrophages.

Heart failure is a complex syndrome characterized by cardiac hypertrophy, fibrosis, and diastolic/systolic dysfunction. These changes share many pathological features with significant inflammatory responses in the myocardium. Among the various regulatory systems that impact on these heterogeneous pathological processes, angiotensin II (Ang II)-activated macrophages play a pivotal role in the induction of subcellular defects and cardiac adverse remodeling during the progression of heart failure.

International Initiatives of the American Heart Association: Original Concepts, Present Programs, and Future Focus: A Science Advisory From the American Heart Association.

The American Heart Association (AHA), founded in 1924, is anchored in the core belief that scientific research can lead the way to better prevention, treatment, recovery, and ultimately a cure for cardiovascular disease. Historically, the association's involvement in international efforts centered on scientific cooperation. Activities mostly involved AHA leadership presenting at international scientific meetings and leaders from other countries sharing scientific and medical information at AHA meetings.

Integrating rapid habitat mapping with community metrics and functional traits to assess estuarine ecological conditions: A New Zealand case study.

Estuarine ecosystems are under pressure from anthropogenic stressors in many parts of the world. In a New Zealand estuary, we integrated rapid habitat mapping, univariate and multivariate benthic community metrics and functional traits-based metrics to provide a holistic assessment of its ecological condition. Our integrative approach identified 11 different habitat classes across the study estuary and revealed how univariate, multivariate, and functional traits-based metrics varied spatially.

Evaluating the utility of promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).

While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of promoter hypermethylation (m) as a prognostic and predictive marker in colon cancer. We examined the association of m with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803).

Climatic, oceanic, freshwater, and local environmental drivers of New Zealand estuarine macroinvertebrates.

Understanding the responses of organisms to different environmental drivers is critical for improving ecosystem management and conservation. Estuarine ecosystems are under pressure from multiple anthropogenic stressors (e.g.

Mapping the core senescence phenotype of primary human colon fibroblasts.

Advanced age is the largest risk factor for many diseases and several types of cancer, including colorectal cancer (CRC). Senescent cells are known to accumulate with age in various tissues, where they can modulate the surrounding tissue microenvironment through their senescence associated secretory phenotype (SASP). Recently, we showed that there is an increased number of senescent cells in the colons of CRC patients and demonstrated that senescent fibroblasts and their SASP create microniches in the colon that are conducive to CRC onset and progression.

Elevated EVL Methylation Level in the Normal Colon Mucosa Is a Potential Risk Biomarker for Developing Recurrent Adenomas.

Background: Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent adenomas. Better methods to evaluate who benefits from increased surveillance are needed.

DNA methylation profile in CpG-depleted regions uncovers a high-risk subtype of early-stage colorectal cancer.

Background: The current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. We aimed to investigate whether DNA methylation could serve as a novel biomarker for predicting prognosis in early-stage CRC patients.

Methods: We analyzed the genome-wide methylation status of CpG loci using Infinium MethylationEPIC array run on primary tumor tissues and normal mucosa of early-stage CRC patients to identify potential methylation markers for prognosis.

Video speeding can be efficient and speeding-induced preference cost can be lessened by selective speeding.

Over the past decade, screen-captured instructional videos have become popular tools for learning. Viewers wanting to learn efficiently can play these videos at faster-than-normal speeds, a feature offered by hosting services such as YouTube. Although previous research suggests that moderate speeding may not lessen learning, little research has tested this form of media for speeding-induced learning impairments.

Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia.

Purpose: Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE).

Experimental Design: DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing.

Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon.

Unlabelled: Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (<0.001) in normal colon from patients with and without colorectal cancer.

Evaluation of methylated DCR1 as a biomarker for response to adjuvant irinotecan-based therapy in stage III colon cancer: cancer and leukaemia Group B 89803 (Alliance).

Aberrantly methylated genes contribute to the landscape of epigenetic alterations in colorectal adenocarcinoma. The global CpG Island methylator phenotype (CIMP) and individually methylated genes are potential prognostic/predictive biomarkers. Research suggests an association between methylated (m) and lack of benefit with irinotecan (IFL) treatment.

The Incomplete Tyranny of Dynamic Stimuli: Gaze Similarity Predicts Response Similarity in Screen-Captured Instructional Videos.

Although eye tracking has been used extensively to assess cognitions for static stimuli, recent research suggests that the link between gaze and cognition may be more tenuous for dynamic stimuli such as videos. Part of the difficulty in convincingly linking gaze with cognition is that in dynamic stimuli, gaze position is strongly influenced by exogenous cues such as object motion. However, tests of the gaze-cognition link in dynamic stimuli have been done on only a limited range of stimuli often characterized by highly organized motion.

The Utility of Expanded Conclusion Scales During Latent Print Examinations.

During fingerprint comparisons, a latent print examiner visually compares two impressions to determine whether or not they originated from the same source. They consider the amount of perceived detail in agreement or disagreement and accumulate evidence toward same source and different sources propositions. This evidence is then mapped to one of three conclusions: Identification, Inconclusive, or Exclusion.

The Role of the Veterinary Technician in End-of-Life Care.

In addressing end-of-life care in veterinary medicine, the role of the veterinary technician can have a profound impact on quality of life during the final days in a pet's life. The role of the veterinary technician in end-of-life care is multifaceted, as duties range from nursing care to social and emotional support for pet caregivers. Human hospice care is helpful as a a model to better understand the importance of palliative care in animals.

Dysfunctional epigenetic aging of the normal colon and colorectal cancer risk.

Background: Chronological age is a prominent risk factor for many types of cancers including colorectal cancer (CRC). Yet, the risk of CRC varies substantially between individuals, even within the same age group, which may reflect heterogeneity in biological tissue aging between people. Epigenetic clocks based on DNA methylation are a useful measure of the biological aging process with the potential to serve as a biomarker of an individual's susceptibility to age-related diseases such as CRC.

Senescence-associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15.

The risk of colorectal cancer (CRC) varies between people, and the cellular mechanisms mediating the differences in risk are largely unknown. Senescence has been implicated as a causative cellular mechanism for many diseases, including cancer, and may affect the risk for CRC. Senescent fibroblasts that accumulate in tissues secondary to aging and oxidative stress have been shown to promote cancer formation via a senescence-associated secretory phenotype (SASP).

Implications of Epigenetic Drift in Colorectal Neoplasia.

Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here, we identify and validate 781 CpG islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples. However, compared with normal colon, this drift advanced (∼3-4-fold) faster in neoplasia, consistent with increased cell proliferation during neoplastic progression.

A five-CpG DNA methylation score to predict metastatic-lethal outcomes in men treated with radical prostatectomy for localized prostate cancer.

Background: Prognostic biomarkers for localized prostate cancer (PCa) could improve personalized medicine. Our group previously identified a panel of differentially methylated CpGs in primary tumor tissue that predict disease aggressiveness, and here we further validate these biomarkers.

Methods: Pyrosequencing was used to assess CpG methylation of eight biomarkers previously identified using the HumanMethylation450 array; CpGs with strongly correlated (r >0.

Subtypes of Barrett's oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis.

Objective: To identify and characterise DNA methylation subtypes in oesophageal adenocarcinoma (EAC) and its precursor Barrett's oesophagus (BE).

Design: We performed genome-wide DNA methylation profiling on samples of non-dysplastic BE from cancer-free patients (n=59), EAC (n=23), normal squamous oesophagus (n=33) and normal fundus (n=9), and identified methylation subtypes using a recursively partitioned mixture model. We assessed genomic alterations for 9 BE and 22 EAC samples with massively parallel sequencing of 243 EAC-associated genes, and we conducted integrative analyses with transcriptome data to identify epigenetically repressed genes.

Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression.

Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome. Because restoration of MeCP2 expression in a mouse model reverses neurologic deficits in adult animals, reactivation of the wild-type copy of MeCP2 on the inactive X chromosome (Xi) presents a therapeutic opportunity in RS. To identify genes involved in MeCP2 silencing, we screened a library of 60,000 shRNAs using a cell line with a MeCP2 reporter on the Xi and found 30 genes clustered in seven functional groups.

Transposon mutagenesis identifies candidate genes that cooperate with loss of transforming growth factor-beta signaling in mouse intestinal neoplasms.

Colorectal cancer (CRC) results from the accumulation of gene mutations and epigenetic alterations in colon epithelial cells, which promotes CRC formation through deregulating signaling pathways. One of the most commonly deregulated signaling pathways in CRC is the transforming growth factor β (TGF-β) pathway. Importantly, the effects of TGF-β signaling inactivation in CRC are modified by concurrent mutations in the tumor cell, and these concurrent mutations determine the ultimate biological effects of impaired TGF-β signaling in the tumor.