Lipids, fatty acids and flavor of beef from steers grazed on different pastures or fed up to 112 days on a corn based finishing ration

Sixty-eight Angus steers were separated into five treatment groups, each of which grazed a different type of pasture prior to grain feeding. Each pasture was composed of different mixtures of grasses. The grasses included fescue, clover, sudan grass, sorghum, bermuda grass, and orchard grass. Three steers from each treatment were slaughtered off grass (0-day feed group). The remainder were divided into feeding groups where at least two steers from each treatment were in each group, and all were ad-justed to a corn diet for two weeks. After adjustment a group was slaughtered every 28 days up to 112 days on corn. Total lipid content, fatty acid composition, tocopherol content and sensory evaluation of flavor by Quantitative Descriptive Analysis were determined on the longissimus muscle from each steer carcass that was aged 10 days at 6°C. The muscle was stored in double-wrapped polyethylene coated freezer paper at -18°C until analyzed. Grasses from each pasture also were analyzed for moisture, total lipid and fatty acid composition. Across time on feed, milky-oily flavor and aroma decreased linearly in intensity; beef fat flavor and aroma increased linearly in intensity, and total lipid content increased curvilinearly. Beef from steers off grass had lower levels of monounsaturated and higher levels of saturated and polyunsaturated fatty acids than beef produced by grain. Fatty acids deposited in increasing lipid content across days on feed included 14:0, 14:1, 16:0, 16:1, 17:1, 18:1, 18:2ω6, and 20:1. Beef produced by grass had higher levels of ω3 fatty acids (18:3, 20:3, 20:5, 22:5, and 22:6) and lower levels of ω6 fatty acids (18:2, 20:3, and 20:4 than beef produced by corn. High levels of 18:3ω3 in all pastures was pro-bably the source of the ω3 acids, and the high levels of 18:2ω6 in corn, the source of the ω6 acids. Tocopherol (α and r) content in muscle decreased over time on feed, and the change in α-tocopherol content could be explained by the change in its dietary levels. Flavor of the beef was correlated with chemical characteristics of the beef. Fatty acids positively correlated with milky-oily flavor included 13:0, 15:0, 19:0, 19:1, 20:1, 20:3ω3, 20:3ω6, 20:5ω3, and the sum of the ω3 fatty acids. Fatty acids positively correlated with beef fat flavor included 12:0, 14:0, 14:1, and 16:1. Of all chemical characteristics, α-tocopherol had the highest positive correlation coefficient (0.58) with milky-oily flavor. Total lipid content and moisture content of the grasses in the different treatments were within reported literature levels. There were no significant differences among pastures in the fatty acid composition. All pastures had high levels of 18:2ω6 (23-38%) and 18:3ω3 (23-43%). Pasture type did not significantly affect the flavor of the beef or the lipid or tocopherol contents, but did affect a few fatty acids expressed in mg/100 g beef: 14:0 20:3ω3, 20:4ω6, 22:6ω3, and an unknown which was possibly a branched chain 18 carbon acid

Activation of the ATR kinase by the RPA-binding protein ETAA1

Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically, this requires a conserved domain in ETAA1 that potently and directly stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 gives rise to synthetic lethality characterized by massive genome instability and abrogation of ATR-dependent signalling. Our findings demonstrate that parallel TopBP1-and ETAA1-mediated pathways underlie ATR activation and that their combined action is essential for coping with replication stress

Public International Law: Environmental Law

Noteworthy international activity relating to the environment occurred in a wide variety of fora in 2000. This chapter provides brief updates on some of the most significant developments. Though by no means a comprehensive review, the chapter reflects the wide sweep of issues and large number of entities now involved in the development of international environmental law, at the start of this new century. It also reflects how critical and complex this international work is, and how much remains to be done

Gene Expression Signature of Cigarette Smoking and Its Role in Lung Adenocarcinoma Development and Survival

Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure.We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change >1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p = 0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers

Acetylcholine Neurotransmitter Receptor Densities in the Striatum of Hemiparkinsonian Rats Following Botulinum Neurotoxin-A Injection

Cholinergic neurotransmission has a pivotal function in the caudate-putamen, and is highly associated with the pathophysiology of Parkinson's disease. Here, we investigated long-term changes in the densities of the muscarinic receptor subtypes M1, M2, M3 (mAchRs) and the nicotinic receptor subtype α4β2 (nAchRs) in the striatum of the 6-OHDA-induced hemiparkinsonian (hemi-PD) rat model using quantitative in vitro receptor autoradiography. Hemi-PD rats exhibited an ipsilateral decrease in striatal mAchR densities between 6 and 16%. Moreover, a massive and constant decrease in striatal nAchR density by 57% was found. A second goal of the study was to disclose receptor-related mechanisms for the positive motor effect of intrastriatally injected Botulinum neurotoxin-A (BoNT-A) in hemi-PD rats in the apomorphine rotation test. Therefore, the effect of intrastriatally injected BoNT-A in control and hemi-PD rats on mAchR and nAchR densities was analyzed and compared to control animals or vehicle-injected hemi-PD rats. BoNT-A administration slightly reduced interhemispheric differences of mAchR and nAchR densities in hemi-PD rats. Importantly, the BoNT-A effect on striatal nAchRs significantly correlated with behavioral testing after apomorphine application. This study gives novel insights of 6-OHDA-induced effects on striatal mAchR and nAchR densities, and partly explains the therapeutic effect of BoNT-A in hemi-PD rats on a cellular level

A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases

A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi)genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology

A Belief System's Organization Based on a Computational Model of the Dynamic Context: First Approximation

In this article we present a model of organization of a belief system based on a set of binary recursive functions that characterize the dynamic context that modifies the beliefs. The initial beliefs are modeled by a set of two-bit words that grow, update, and generate other beliefs as the different experiences of the dynamic context appear. Reason is presented as an emergent effect of the experience on the beliefs. The system presents a layered structure that allows a functional organization of the belief system. Our approach seems suitable to model different ways of thinking and to apply to different realistic scenarios such as ideologies

Ancient human genomes and environmental DNA from the cement attaching 2,000 year-old head lice nits

Over the past few decades there has been an increased demand for genome analysis of ancient human remains. Destructive sampling is increasingly difficult for ethical reasons, and previous methods of breaking the skull to access the petrous bone are often forbidden for curatorial reasons, together with teeth which may be missing or too precious to sample. However, most ancient humans carried head lice, and their eggs abound in historical hair specimens. Here we show that host DNA is protected by the cement that glues head lice eggs (nits) to the hair of ancient Argentinian mummies, 1,500–2,000 years old. The cement also preserves ancient environmental DNA of the skin, including the earliest recorded case of Merkel Cell Polyomavirus. We also show that human DNA obtained from nit cement can equal human genome assessment from tooth DNA, can increase assessment from petrous bone by two-fold, and by four-fold DNA over bloodmeal of adult lice a millennium younger. Genome-wide analyses from nit cement DNA also enables identification of the population genetic affinities of ancient humans. In metric studies of the sheaths, the length of the cement tube negatively correlated with the age of the specimens, while hair linear distance between nit and scalp informed about environmental conditions at the time before death. Ectoparasitic lice sheaths on hair, feathers, skins, or mummified remains can offer an alternative, non-destructive source of high-quality ancient DNA from a variety of host taxa and reveal details of their historical environment