Data on 10148 Black Bengal kids recorded from 2008 to 2019 and maintained at farmer’s fields at different agroclimatic clusters of West Bengal under the project “AICRP on Goat Improvement, Black ...Bengal Field Unit- Kolkata” were used to study the effect of non-genetic factors on body weight from birth to 12 months of age. The data were analysed using least squares analysis technique. The average birth weights of Black Bengal goats obtained under four different agro-climatic clusters revealed that there was a significant variation in body weight (kg) of all ages. The effect of year of kidding, influence of season and parity of the dam on body weight of Black Bengal kids at different ages were significant. But a non-significant result was found at the body weight in all the seasons as well as in all the parities at 9 and 12 months of age. Sex of the kid and type of birth had significant effect on body weights from birth to 12 months of age. Significantly higher body weight at birth was recorded in single born kid, followed by twin and triplets. The study concluded that it is possible to improve non-genetic elements in the field, particularly by providing excellent housing, reducing stress, having access to grazing pasture, and doing routine deworming and vaccinations. The findings supported the need for environmental changes that can aid in the development of management strategies and decision making regarding the selection.
The immunology of multiple sclerosis Attfield, Kathrine E; Jensen, Lise Torp; Kaufmann, Max ...
Nature reviews. Immunology,
12/2022, Letnik:
22, Številka:
12
Journal Article
Recenzirano
Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. ...Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings presented here begin to question the exclusivity of an antigen-specific cause and highlight how seemingly distinct immune cell types can share common functions that drive disease. Innovative techniques further expose new disease-associated immune cell populations and reinforce how environmental context is critical to their phenotype and subsequent role in disease. Importantly, the differentiation of immune cells into a pathogenic state is potentially reversible through therapeutic manipulation. As such, understanding the mechanisms that provide plasticity to causal cell types is likely key to uncoupling these disease processes and may identify novel therapeutic targets that replace the need for cell ablation.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver diseases in high-income countries and the burden of NAFLD is increasing at an alarming rate. The risk of developing NAFLD and ...related complications is highly variable among individuals and is determined by environmental and genetic factors. Genome-wide association studies have uncovered robust and reproducible associations between variations in genes such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B13 and the natural history of NAFLD. These findings have provided compelling new insights into the biology of NAFLD and highlighted potentially attractive pharmaceutical targets. More recently the development of polygenic risk scores, which have shown promising results for the clinical risk prediction of other complex traits (such as cardiovascular disease and breast cancer), have provided new impetus for the clinical validation of genetic variants in NAFLD risk stratification. Herein, we review current knowledge on the genetic architecture of NAFLD, including gene-environment interactions, and discuss the implications for disease pathobiology, drug discovery and risk prediction. We particularly focus on the potential clinical translation of recent genetic advances, discussing methodological hurdles that must be overcome before these discoveries can be implemented in everyday practice.
The incidence of type 2 diabetes (T2D) has rapidly increased over recent decades, and T2D has become a leading public health challenge in China. Compared with European descents, Chinese patients with ...T2D are diagnosed at a relatively young age and low BMI. A better understanding of the factors contributing to the diabetes epidemic is crucial for determining future prevention and intervention programs. In addition to environmental factors, genetic factors contribute substantially to the development of T2D. To date, more than 100 susceptibility loci for T2D have been identified. Individually, most T2D genetic variants have a small effect size (10-20% increased risk for T2D per risk allele); however, a genetic risk score that combines multiple T2D loci could be used to predict the risk of T2D and to identify individuals who are at a high risk. Furthermore, individualized antidiabetes treatment should be a top priority to prevent complications and mortality. In this article, we review the epidemiological trends and recent progress in the understanding of T2D genetic etiology and further discuss personalized medicine involved in the treatment of T2D.
Metabolic reprogramming and cancer progression Faubert, Brandon; Solmonson, Ashley; DeBerardinis, Ralph J
Science (American Association for the Advancement of Science),
04/2020, Letnik:
368, Številka:
6487
Journal Article
Recenzirano
Odprti dostop
Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of tumor metabolism. Metabolic ...heterogeneity among human tumors poses a challenge to developing therapies that exploit metabolic vulnerabilities. Recent work also demonstrates that the metabolic properties and preferences of a tumor change during cancer progression. This produces distinct sets of vulnerabilities between primary tumors and metastatic cancer, even in the same patient or experimental model. We review emerging concepts about metabolic reprogramming in cancer, with particular attention on why metabolic properties evolve during cancer progression and how this information might be used to develop better therapeutic strategies.
IMPORTANCE: Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown. OBJECTIVE: To investigate whether a healthy lifestyle is associated ...with lower risk of dementia regardless of genetic risk. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. EXPOSURES: A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. MAIN OUTCOMES AND MEASURES: Incident all-cause dementia, ascertained through hospital inpatient and death records. RESULTS: A total of 196 383 individuals (mean SD age, 64.1 2.9 years; 52.7% were women) were followed up for 1 545 433 person-years (median interquartile range follow-up, 8.0 7.4-8.6 years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 95% CI, 1.64-2.23). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 95% CI, 2.09-3.83). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 95% CI, 0.51-0.90). CONCLUSIONS AND RELEVANCE: Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.
Parkinson's disease (PD) is the second most common cause of neurodegeneration. Over the last two decades, various hypotheses have been proposed to explain the etiology of PD. Among these is the ...oxidant-antioxidant theory, which asserts that local and systemic oxidative damage triggered by reactive oxygen species and other free radicals may promote dopaminergic neuron degeneration. Excessive reactive oxygen species formation, one of the underlying causes of pathology in the course of PD has been evidenced by various studies showing that oxidized macromolecules including lipids, proteins, and nucleic acids accumulate in brain tissues of PD patients. DNA oxidation may produce various lesions in the course of PD. Mutations incurred as a result of DNA oxidation may further enhance reactive oxygen species production in the brains of PD patients, exacerbating neuronal loss due to defects in the mitochondrial electron transport chain, antioxidant depletion, and exposure to toxic oxidized dopamine. The protein products of SNCA, PRKN, PINK1, DJ1, and LRRK2 genes are associated with disrupted oxidoreductive homeostasis in PD. SNCA is the first gene linked with familial PD and is currently known to be affected by six mutations correlated with the disorder: A53T, A30P, E46K, G51D, H50Q and A53E. PRKN encodes Parkin, an E3 ubiquitin ligase which mediates the proteasome degradation of redundant and disordered proteins such as glycosylated α-synuclein. Over 100 mutations have been found among the 12 exons of PRKN. PINK1, a mitochondrial kinase highly expressed in the brain, may undergo loss of function mutations which constitute approximately 1-8% of early onset PD cases. More than 50 PD-promoting mutations have been found in PINK1. Mutations in DJ-1, a neuroprotective protein, are a rare cause of early onset PD and constitute only 1% of cases. Around 20 mutations have been found in DJ1 among PD patients thus far. Mutations in the LRRK2 gene are the most common known cause of familial autosomal dominant PD and sporadic PD. Treatment of PD patients, especially in the advanced stages of the disease, is very difficult. The first step in managing progressive PD is to optimize dopaminergic therapy by increasing the doses of dopamine agonists and L-dopa. The next step is the introduction of advanced therapies, such as deep brain stimulation. Genetic factors may influence the response to L-dopa and deep brain stimulation therapy and the regulation of oxidative stress. Consequently, research into minimally invasive surgical interventions, as well as therapies that target the underlying etiology of PD is warranted.
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