Genetic parameters for carnitine, creatine, creatinine, carnosine, and anserine concentration in longissimus muscle and their association with palatability traits in Angus cattle

The objective of this study was to estimate genetic parameters for carnitine, creatine, creatinine, carnosine, and anserine concentration in LM and to evaluate their associations with Warner-Bratzler shear force (WBSF) and beef palatability traits. Longissimus muscle samples from 2,285 Angus cattle were obtained and fabricated into steaks for analysis of carnitine, creatine, creatinine, carnosine, anserine, and other nutrients, and for trained sensory panel and WBSF assessments. Restricted maximum likelihood procedures were used to obtain estimates of variance and covariance components under a multiple-trait animal model. Estimates of heritability for carnitine, creatine, creatinine, carnosine, and anserine concentrations in LM from Angus cattle were 0.015, 0.434, 0.070, 0.383, and 0.531, respectively. Creatine, carnosine, and anserine were found to be moderately heritable, whereas almost no genetic variation was observed in carnitine and creatinine. Moderate positive genetic (0.25, P \u3c 0.05) and phenotypic correlations (0.25, P \u3c 0.05) were identified between carnosine and anserine. Medium negative genetic correlations were identified between creatine and both carnosine (-0.53, P\u3c 0.05) and anserine (-0.46, P \u3c 0.05). Beef and livery/metallic flavor were not associated with any of the 5 compounds analyzed (P \u3e 0.10), and carnitine concentrations were not associated (P \u3e 0.10) with any of the meat palatability traits analyzed. Carnosine was negatively associated with overall tenderness as assessed by trained sensory panelists. Similar negative associations with overall tenderness were identified for creatinine and anserine. Painty/fishy was the only flavor significantly and negatively associated with creatinine and carnosine. These results provide information regarding the concentration of these compounds, the amount of genetic variation, and evidence for negligible associations with beef palatability traits in LM of beef cattle

High (but Not Low) Urinary Iodine Excretion Is Predicted by Iodine Excretion Levels from Five Years Ago

Background: It has not been investigated whether there are associations between urinary iodine (UI) excretion measurements some years apart, nor whether such an association remains after adjustment for nutritional habits. The aim of the present study was to investigate the relation between iodine-creatinine ratio (ICR) at two measuring points 5 years apart. Methods: Data from 2,659 individuals from the Study of Health in Pomerania were analyzed. Analysis of covariance and Poisson regressions were used to associate baseline with follow-up ICR. Results: Baseline ICR was associated with follow-up ICR. Particularly, baseline ICR >300 mu g/g was related to an ICR >300 mu g/g at follow-up (relative risk, RR: 2.20; p < 0.001). The association was stronger in males (RR: 2.64; p < 0.001) than in females (RR: 1.64; p = 0.007). In contrast, baseline ICR <100 mu g/g was only associated with an ICR <100 mu g/g at follow-up in males when considering unadjusted ICR. Conclusions: We detected only a weak correlation with respect to low ICR. Studies assessing iodine status in a population should take into account that an individual with a low UI excretion in one measurement is not necessarily permanently iodine deficient. On the other hand, current high ICR could have been predicted by high ICR 5 years ago. Copyright (C) 2011 S. Karger AG, Base

Chris Brown’s Liberal Conservatism, the Process of Moral Learning and Global Institutional Transformations

In the normative theory of International Relations, the major debate has been between the state-centric view and cosmopolitanism. A quarter of century ago I attempted to deconstruct one round of this debate – between Chris Brown and Mark Hoffman – by showing that the debate is both utopian and has an other-negating character. With the help of epistemological discussions and an analysis of two “case studies”, I built a case for a contextualist and dialogical morality, grounded on the concept of judgement. Interestingly, Brown’s 2010 collection of essays is entitled Practical Judgement in International Political Theory. In this paper I first explore whether similar or analogical deconstruction would anymore be possible. Second, I discuss Brown’s ideas about global civil society, democracy and justice, particularly in light of world-historical developments since the early 1990s and in relation to the development of my own thinking on the topic. While Brown has tried to overcome the dichotomy between the state-centric view and cosmopolitanism, I examine whether the idea of universal ethico-political learning and its cosmopolitan implications might explain the divergence in our practical judgements. I conclude by arguing any area of activities in international relations and world society, from property and contract to nuclear safety and global warming, can be subject to normative debates and potentially democratic politics. Good normative arguments often involve designs for better institutions, but they must be realizable by virtue of being connected to real causal processes.Peer reviewe

Cosmopolitanism, Self-Interest and World Government

Cosmopolitans, if they are interested in seeing their principles realised, must hope that persons worldwide can become motivated to act in accordance with what those principles demand. But although it is important that genuinely moral motives are developed, we should not ignore the potential pragmatic value of self-interested motives to the realisation of cosmopolitan ends. This article considers three such motives: economic self-interest, prudent self-interest and democratic self-interest. I argue that in each case, usefully harnessing these motivations implies or requires global political integration that amounts to ‘world government’. This argument has the effect of reinforcing the already popular view that realising cosmopolitan principles entails global political integration. For those who already endorse that view, my argument will act as supporting evidence; by contrast it represents a challenge to those cosmopolitans who have remained ambivalent about, or indeed have explicitly rejected, the need for global political integration

Framing Social Justice: The Ties That Bind a Multinational Occupational Community

The notion of a frame is central to the conceptualisation of social justice and the grounding of social justice claims. Influential theories of social justice are typically grounded in national or cosmopolitan framings. Those entitled to raise claims of injustice are identified as citizens of states or the globe, respectively. The re-visioning of understandings of space and belonging, incumbent in the processes of globalisation, problematises static geographical framings. We offer an alternative lens and argue for the inclusion of sociological data in accounts of social justice to identify the relevant framing of the community of entitlement. Drawing on secondary analysis of a qualitative dataset, we explore the case of multinational seafarers caught at the intersection of competing appeals to nationality and commonality as an exemplar of transnational workers. And, argue that there are compelling grounds to treat this group of multinational seafarers as a community of entitlement

Supervised multivariate analysis of sequence groups to identify specificity determining residues

<p>Abstract</p> <p>Background</p> <p>Proteins that evolve from a common ancestor can change functionality over time, and it is important to be able identify residues that cause this change. In this paper we show how a supervised multivariate statistical method, Between Group Analysis (BGA), can be used to identify these residues from families of proteins with different substrate specifities using multiple sequence alignments.</p> <p>Results</p> <p>We demonstrate the usefulness of this method on three different test cases. Two of these test cases, the Lactate/Malate dehydrogenase family and Nucleotidyl Cyclases, consist of two functional groups. The other family, Serine Proteases consists of three groups. BGA was used to analyse and visualise these three families using two different encoding schemes for the amino acids.</p> <p>Conclusion</p> <p>This overall combination of methods in this paper is powerful and flexible while being computationally very fast and simple. BGA is especially useful because it can be used to analyse any number of functional classes. In the examples we used in this paper, we have only used 2 or 3 classes for demonstration purposes but any number can be used and visualised.</p

The Naturally Processed CD95L Elicits a c-Yes/Calcium/PI3K-Driven Cell Migration Pathway

Patients affected by chronic inflammatory disorders display high amounts of soluble CD95L. This homotrimeric ligand arises from the cleavage by metalloproteases of its membrane-bound counterpart, a strong apoptotic inducer. In contrast, the naturally processed CD95L is viewed as an apoptotic antagonist competing with its membrane counterpart for binding to CD95. Recent reports pinpointed that activation of CD95 may attract myeloid and tumoral cells, which display resistance to the CD95-mediated apoptotic signal. However, all these studies were performed using chimeric CD95Ls (oligomerized forms), which behave as the membrane-bound ligand and not as the naturally processed CD95L. Herein, we examine the biological effects of the metalloprotease-cleaved CD95L on CD95-sensitive activated T-lymphocytes. We demonstrate that cleaved CD95L (cl-CD95L), found increased in sera of systemic lupus erythematosus (SLE) patients as compared to that of healthy individuals, promotes the formation of migrating pseudopods at the leading edge of which the death receptor CD95 is capped (confocal microscopy). Using different migration assays (wound healing/Boyden Chamber/endothelial transmigration), we uncover that cl-CD95L promotes cell migration through a c-yes/Ca2+/PI3K-driven signaling pathway, which relies on the formation of a CD95-containing complex designated the MISC for Motility-Inducing Signaling Complex. These findings revisit the role of the metalloprotease-cleaved CD95L and emphasize that the increase in cl-CD95L observed in patients affected by chronic inflammatory disorders may fuel the local or systemic tissue damage by promoting tissue-filtration of immune cells

Phase II trial of imatinib mesylate in patients with metastatic melanoma

Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined

Tradeoff Between Stability and Multispecificity in the Design of Promiscuous Proteins

Natural proteins often partake in several highly specific protein-protein interactions. They are thus subject to multiple opposing forces during evolutionary selection. To be functional, such multispecific proteins need to be stable in complex with each interaction partner, and, at the same time, to maintain affinity toward all partners. How is this multispecificity acquired through natural evolution? To answer this compelling question, we study a prototypical multispecific protein, calmodulin (CaM), which has evolved to interact with hundreds of target proteins. Starting from high-resolution structures of sixteen CaM-target complexes, we employ state-of-the-art computational methods to predict a hundred CaM sequences best suited for interaction with each individual CaM target. Then, we design CaM sequences most compatible with each possible combination of two, three, and all sixteen targets simultaneously, producing almost 70,000 low energy CaM sequences. By comparing these sequences and their energies, we gain insight into how nature has managed to find the compromise between the need for favorable interaction energies and the need for multispecificity. We observe that designing for more partners simultaneously yields CaM sequences that better match natural sequence profiles, thus emphasizing the importance of such strategies in nature. Furthermore, we show that the CaM binding interface can be nicely partitioned into positions that are critical for the affinity of all CaM-target complexes and those that are molded to provide interaction specificity. We reveal several basic categories of sequence-level tradeoffs that enable the compromise necessary for the promiscuity of this protein. We also thoroughly quantify the tradeoff between interaction energetics and multispecificity and find that facilitating seemingly competing interactions requires only a small deviation from optimal energies. We conclude that multispecific proteins have been subjected to a rigorous optimization process that has fine-tuned their sequences for interactions with a precise set of targets, thus conferring their multiple cellular functions