An intact C-terminal end of albumin is required for its long half-life in humans.

Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics

Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex

"Truth" has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning

Integrated Brain Atlas for Unbiased Mapping of Nervous System Effects Following Liraglutide Treatment

Light Sheet Fluorescence Microscopy (LSFM) of whole organs, in particular the brain, offers a plethora of biological data imaged in 3D. This technique is however often hindered by cumbersome non-Automated analysis methods. Here we describe an approach to fully automate the analysis by integrating with data from the Allen Institute of Brain Science (AIBS), to provide precise assessment of the distribution and action of peptide-based pharmaceuticals in the brain. To illustrate this approach, we examined the acute central nervous system effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Peripherally administered liraglutide accessed the hypothalamus and brainstem, and led to activation in several brain regions of which most were intersected

Chronic stress does not impair liver regeneration in rats

Background: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. Methods: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. Result: None of the animals died during the study. There were no differences between in body weight, liver weight, liver regeneration rate or biochemical markers at any time during the study. Conclusion: The results of this study indicate that stress and the induction of depression-like state do not affect the process of liver regeneration after 70 % hepatectomy in rats

Ambivalence, equivocation and the politics of experimental knowledge: a transdisciplinary neuroscience encounter

This article is about a transdisciplinary project between the social, human and life sciences, and the felt experiences of the researchers involved. ‘Transdisciplinary’ and ‘interdisciplinary’ research-modes have been the subject of much attention lately – especially as they cross boundaries between the social/humanistic and natural sciences. However, there has been less attention, from within science and technology studies, to what it is actually like to participate in such a research-space. This article contributes to that literature through an empirical reflection on the progress of one collaborative and transdisciplinary project: a novel experiment in neuroscientific lie detection, entangling science and technology studies, literary studies, sociology, anthropology, clinical psychology and cognitive neuroscience. Its central argument is twofold: (1) that, in addition to ideal-type tropes of transdisciplinary conciliation or integration, such projects may also be organized around some more subterranean logics of ambivalence, reserve and critique; (2) that an account of the mundane ressentiment of collaboration allows for a more careful attention to the awkward forms of ‘experimental politics’ that may flow through, and indeed propel, collaborative work more broadly. Building on these claims, the article concludes with a suggestion that such subterranean logics may be indissociable from some forms of collaboration, and it proposes an ethic of ‘equivocal speech’ as a way to live with and through these kinds of transdisciplinary experiences