Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

The nutritional contribution and relationship with health of bread consumption: a narrative review.

Bread consumption dates back thousands of years, being one of the oldest and most widespread staple food worldwide. While bread is often associated with taste, pleasure, and tradition, its perception as a vehicle of nutrition and health remains complex. Today, there is no scientific consensus on whether bread consumption is beneficial or deleterious to human health.

In Vitro Human Gastrointestinal Digestibility and Colonic Fermentation of Wheat Sourdough and Yeast Breads.

Bread can vary in textural and nutritional attributes based on differences in the bread making process (e.g., flour type, fermentation agent, fermentation time).

Influence of sinusoidal forcing on the master FitzHugh-Nagumo neuron model and global dynamics of a unidirectionally coupled two-neuron system.

In this paper, we investigate a seven-parameter, five-dimensional dynamical system, specifically a unidirectional coupling of two FitzHugh-Nagumo neuron models, with one neuron being sinusoidally driven. This master-slave configuration features neuron N1 as the master, subjected to an external sinusoidal electrical current, and neuron N2 as the slave, interacting with N1 through an electrical force. We report numerical results for three distinct scenarios where N1 operates in (i) periodic, (ii) quasiperiodic, and (iii) chaotic regimes.

KaryoCreate: A CRISPR-based technology to study chromosome-specific aneuploidy by targeting human centromeres.

Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer. Here, we describe KaryoCreate (karyotype CRISPR-engineered aneuploidy technology), a system that enables the generation of chromosome-specific aneuploidies by co-expression of an sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to mutant KNL1. We design unique and highly specific sgRNAs for 19 of the 24 chromosomes.

Noninvasive Methods to Detect Reactive Oxygen Species as a Proxy of Seed Quality.

ROS homeostasis is crucial to maintain radical levels in a dynamic equilibrium within physiological ranges. Therefore, ROS quantification in seeds with different germination performance may represent a useful tool to predict the efficiency of common methods to enhance seed vigor, such as priming treatments, which are still largely empirical. In the present study, ROS levels were investigated in an experimental system composed of hydroprimed and heat-shocked seeds, thus comparing materials with improved or damaged germination potential.

Nutritional and lifestyle management of the aging journey: A narrative review.

With age, the physiological responses to occasional or regular stressors from a broad range of functions tend to change and adjust at a different pace and restoring these functions in the normal healthy range becomes increasingly challenging. Even if this natural decline is somehow unavoidable, opportunities exist to slow down and attenuate the impact of advancing age on major physiological processes which, when weakened, constitute the hallmarks of aging. This narrative review revisits the current knowledge related to the aging process and its impact on key metabolic functions including immune, digestive, nervous, musculoskeletal, and cardiovascular functions; and revisits insights into the important biological targets that could inspire effective strategies to promote healthy aging.

Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index.

Background: Subclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals.

Gender differences in fasting and postprandial metabolic traits predictive of subclinical atherosclerosis in an asymptomatic Chinese population.

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis.

A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage.

Glycine and cysteine are non-essential amino acids that are required to generate glutathione, an intracellular tripeptide that neutralizes reactive oxygen species and prevents tissue damage. During aging glutathione demand is thought to increase, but whether additional dietary intake of glycine and cysteine contributes towards the generation of glutathione in healthy older adults is not well understood. We investigated supplementation with glycine and n-acetylcysteine (GlyNAC) at three different daily doses for 2 weeks (low dose: 2.

Longitudinal Human Milk miRNA Composition over the First 3 mo of Lactation in a Cohort of Healthy Mothers Delivering Term Infants.

Background: MicroRNAs (miRNAs) are small noncoding RNAs involved in posttranscriptional regulation. miRNAs can be secreted and found in many body fluids, and although they are particularly abundant in breastmilk, their functions remain elusive. Human milk (HM) miRNAs start to raise considerable interest, but a comprehensive understanding of the repertoire and expression profiles along lactation has not been well characterized.

Clinical- and omics-based models of subclinical atherosclerosis in healthy Chinese adults: a cross-sectional exploratory study.

Background: Classical risk factors, such as fasting cholesterol, blood pressure (BP), and diabetes status are used today to predict the risk of developing cardiovascular disease (CVD). However, accurate prediction remains limited, particularly in low-risk groups such as women and younger individuals. Growing evidence suggests that biomarker concentrations following consumption of a meal challenge are better and earlier predictors of disease development than biomarker concentrations.

Endoplasmic reticulum stress response and bile acid signatures associate with multi-strain seroresponsiveness during elderly influenza vaccination.

The elderly are an important target for influenza vaccination, and the determination of factors that underlie immune responsiveness is clinically valuable. We evaluated the immune and metabolic profiles of 205 elderly Singaporeans administered with Vaxigrip. Despite high seroprotection rates, we observed heterogeneity in the response.

Funeral and Mortuary Operators: The Role of Stigma, Incivility, Work Meaningfulness and Work-Family Relation to Explain Occupational Burnout.

The funeral and mortuary sector, including funeral homes, cemeteries and crematoria, is a largely neglected sector in regard to the study of occupational factors that can affect the quality of working life. The present study aimed at overcoming this gap by investigating job demands and resources that may affect burnout levels. Data were collected through a self-report questionnaire involving funeral industry employees (N = 229) from cemetery, morgues, crematoria and funeral agencies in a Northern Italian region.

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD.

Malnutrition in Relation with Dietary, Geographical, and Socioeconomic Factors among Older Chinese.

Objective: Nutrition is closely related to the health of the elderly population. This study aimed to provide a comprehensive picture of the nutrition status of elderly Chinese and its related dietary, geographical, and socioeconomic factors.

Methods: A total of 13,987 ≥ 60-year-old persons from the 2010-2013 Chinese National Nutrition and Health Survey were included to evaluate various aspects of malnutrition, including underweight, overweight or obesity, and micronutrient inadequacy.

Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults.

Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described. To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance.

The aging gut microbiome and its impact on host immunity.

The microbiome plays a fundamental role in the maturation, function, and regulation of the host-immune system from birth to old age. In return, the immune system has co-evolved a mutualistic relationship with trillions of beneficial microbes residing our bodies while mounting efficient responses to fight invading pathogens. As we age, both the immune system and the gut microbiome undergo significant changes in composition and function that correlate with increased susceptibility to infectious diseases and reduced vaccination responses.

De novo assembly and delivery to mouse cells of a 101 kb functional human gene.

Design and large-scale synthesis of DNA has been applied to the functional study of viral and microbial genomes. New and expanded technology development is required to unlock the transformative potential of such bottom-up approaches to the study of larger mammalian genomes. Two major challenges include assembling and delivering long DNA sequences.

Preparing for a good death? Palliative care representations in the italian public television programming.

The difficulty in accepting death is a constant that transcends differences of time and place. The literature shows that the dying is often subjected to invasive procedures with significant consequences on individual wellbeing and public health. If death is hard to accept even for the practitioners, what happens in the broader population? What narratives surround the end of life? The study focuses on the Italian context and its transformations, the public's understanding of palliative care, and the television programs dealing with hospice and palliative care aired by the Italian public broadcasting company from the 1950s to the present day.