An inability to replicate the genome can cause replication stress and genome instability. Here, we develop BLOCK-ID, a proteomic method to identify and visualize proteins at stressed replication forks. This approach successfully identified novel mediators of the replication stress response, including the chromatin acetylation reader protein TRIM24.
View Article and Find Full Text PDFBackground: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder often misdiagnosed as Parkinson's Disease (PD) due to shared symptoms. PSP is characterized by the accumulation of tau protein in specific brain regions, leading to loss of balance, gaze impairment, and dementia. Diagnosing PSP is challenging, and there is a significant demand for reliable biomarkers.
View Article and Find Full Text PDFLipids are a concentrated source of energy with at least twice as much energy as the same amount of carbohydrates and protein. Dietary lipids provide a practical alternative toward increasing the dietary energy density of feeds for high-performing modern broilers. However, the digestion and absorption of dietary lipids are much more complex than that of the other macronutrients.
View Article and Find Full Text PDFObjective: This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of mild cognitive impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined.
Methods: CSF was collected longitudinally from 269 cognitively normal BIOCARD Study participants (mean baseline age = 57.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons, which eventually may lead to death. Critical to the mission of developing effective therapies for ALS is the discovery of biomarkers that can illuminate mechanisms of neurodegeneration and have diagnostic, prognostic, or pharmacodynamic value. Here, we merged unbiased discovery-based approaches and targeted quantitative comparative analyses to identify proteins that are altered in cerebrospinal fluid (CSF) from patients with ALS.
View Article and Find Full Text PDFTwo experiments were conducted to evaluate the effects of dietary sophorolipids (SLs) supplementation as antibiotic alternatives on growth performance and gut health of chickens infected with Eimeria maxima. In experiment 1, 336 (zero-day-old) male broilers were used. The chickens were weighed and randomly allocated to the following 6 treatments groups with 7 chickens/cage and 8 cages/treatment: control group that received a basal diet (NC), positive control group that received a basal diet and was challenged with E.
View Article and Find Full Text PDFThe in vitro antimicrobial activity of sophorolipids (SLs) against Eimeria maxima and Clostridium perfringens, and the in vivo effects of SLs on growth performance and gut health in necrotic enteritis (NE)-afflicted broiler chickens were studied. To test the direct killing effects of SLs on enteric pathogens, 2.5 × 10 freshly prepared sporozoites of each Eimeria acervulina, E.
View Article and Find Full Text PDFThere is a need for targeted analysis of biological fluids for diagnosis, prognosis, or monitoring the progression of diseases. Cerebrospinal fluid (CSF) and serum have been widely used for the development of protein analysis for neurodegenerative diseases and other diseases, respectively. Recently, data-independent acquisition (DIA) mass spectrometry (MS) has been developed to increase the throughput over data-dependent acquisition (DDA) on screening of a large number of samples and discovery of candidate targets.
View Article and Find Full Text PDFAccumulation of the parkin-interacting substrate (PARIS; ), due to inactivation of parkin, contributes to Parkinson's disease (PD) through repression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α; ) activity. Here, we identify farnesol as an inhibitor of PARIS. Farnesol promoted the farnesylation of PARIS, preventing its repression of PGC-1α via decreasing PARIS occupancy on the promoter.
View Article and Find Full Text PDFThe haploinsufficiency of C9orf72 is implicated in the most common forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the full spectrum of C9orf72 functions remains to be established. Here, we report that C9orf72 is a mitochondrial inner-membrane-associated protein regulating cellular energy homeostasis via its critical role in the control of oxidative phosphorylation (OXPHOS). The translocation of C9orf72 from the cytosol to the inter-membrane space is mediated by the redox-sensitive AIFM1/CHCHD4 pathway.
View Article and Find Full Text PDFMagnolia bark extract administered as a dietary supplement to poultry confers a performance and health benefit, but the mechanisms are unknown. Here, a metabolomics approach was used to identify changes in intestinal metabolite levels in chickens fed an unsupplemented diet or a diet supplemented with magnolia bark extract. Total body weight gains of chickens fed magnolia bark-supplemented diets were increased 2% (from 861 to 878 g/chicken), compared with chickens fed an unsupplemented diet.
View Article and Find Full Text PDFThe present study was conducted to evaluate the encapsulated essential oils (EEO) as an alternative to anticoccidials using a coccidiosis vaccine challenged model in broiler chickens. A total of 600 one-day-old male broiler chicks were provided with no added corn/soybean-meal-based control diet or diets that contained either salinomycin (SAL) or thymol- and carvacrol-based EEO at 60 and 120 mg per kg of diet. Before challenge at 21 days, each treatment had 10 replicates except for the no-added control group, which had 20 replicates.
View Article and Find Full Text PDFSubtherapeutic levels of dietary antibiotics increase growth performance in domestic animals, but the mechanisms are poorly understood. Here, 1-week-old broiler chickens were challenged with LPS (experiment 1), or co-infected with and as an experimental model of necrotic enteritis (experiment 2), and fed a standard basal diet or a basal diet supplemented with virginiamycin or bacitracin methylene disalicylate. In experiment 1, LPS-challenged chickens fed the unsupplemented diet had decreased body weight gains, compared with unsupplemented controls given the PBS control.
View Article and Find Full Text PDFThere are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2 International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance.
View Article and Find Full Text PDFBackground: Magnolia tree bark has been widely used in traditional Asian medicine. However, to our knowledge, no studies have been reported investigating the effects of dietary supplementation with magnolia bark extract in chickens.
Objective: We tested the hypothesis that dietary supplementation of chickens with a bark extract would increase growth performance in uninfected and / co-infected chickens.
The objective of this experiment was to evaluate the antioxidant potential of Allium hookeri (AH) root in two forms, powdered AH root and fermented powdered AH root, to demonstrate its value as an antibiotic alternative feed additive for broiler chickens. A total of 125 male Ross-708 broiler chickens were randomly assigned to five groups (n = 25 birds/group) and fed standard diets supplemented with root or fermented root of AH at two different levels (1% or 5%). Control birds were provided with non-supplemented basal diets.
View Article and Find Full Text PDFAlthough dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet.
View Article and Find Full Text PDFAvian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens against different species of Eimeria using a single vaccine will have a major beneficial impact on commercial poultry production.
View Article and Find Full Text PDFNecrotic enteritis (NE) is an important enteric disease in poultry, and Clostridium perfringens (CP) type A strains are the primary etiology. NE is responsible for annual losses of US $6 billion to the poultry industry in the United States. An increase in the incidence of NE has been also associated with withdrawal of antibiotic growth promoters from poultry feed.
View Article and Find Full Text PDFThis study investigated the effects of Bacillus subtilis-based probiotics on the performance, modulation of host inflammatory responses and intestinal barrier gene expression of broilers subjected to LPS challenge. Chickens were randomly allocated to one of the 3 dietary treatment groups - control, antibiotic, or probiotic. At 14days, half of the chickens in each treatment were injected with LPS (1mg/kg body weight), and the other half injected with sterile PBS.
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