Identification of protein markers for extracellular vesicle (EV) subsets in cow’s milk

Extracellular vesicles (EVs), like exosomes, are small membrane vesicles involved in cell-to-cell communications that modulate numerous biological processes. We previously discovered a new EV subset in milk (sedimenting at 35,000 g; 35 K) that protected its cargo (RNAs and proteins) during simulated digestion and was more enriched in microRNAs than exosomes (sedimenting at 100 K). Here, we used LC-MS/MS to push further the comparison between these two pellets. Commonly used EV markers were not differentially enriched between the pellets, questioning their use with cow's milk EVs. Similarly, the majority of the quantified proteins were equally enriched between the two pellets. Nevertheless, 20 proteins were specific to 35 K, while 41 were specifically enriched in 100 K (p < 0.05), suggesting their potential use as specific markers. Loaded with these proteins, the EVs in these pellets might regulate translation, proliferation and cell survival for 35 K, and metabolism, extracellular matrix turnover and immunity for 100 K. This approach also brought new insights into milk EV-associated integrins and their possible role in specifically targeting recipient cell types. These findings may help better discriminate between milk EVs, improve our understanding of milk EV-associated protein function and their possible use as therapeutic tools for the management of immunity- and metabolism-associated disorders

Dietary intake of branched-chain amino acids in a mouse model of Alzheimer's disease: Effects on survival, behavior, and neuropathology

Introduction High levels of plasmatic branched-chain amino acids (BCAA), commonly used as dietary supplements, are linked to metabolic risk factors for Alzheimer's disease (AD). BCAA directly influence amino acid transport to the brain and, therefore, neurotransmitter levels. We thus investigated the impact of BCAA on AD neuropathology in a mouse model. Methods 3xTg-AD mice were fed either a control diet or a high-fat diet from 6 to 18 months of age. For the last 2 months, dietary BCAA content was adjusted to high (+50%), normal (+0%), or low (−50%). Results Mice fed a BCAA-supplemented high-fat diet displayed higher tau neuropathology and only four out of 13 survived. Mice on the low-BCAA diet showed higher threonine and tryptophan cortical levels while performing better on the novel object recognition task. Discussion These preclinical data underscore a potential risk of combining high-fat and high BCAA consumption, and possible benefits from BCAA restriction in AD

Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes

Poly(ADP-ribose) (pADPr) is a polymer assembled from the enzymatic polymerization of the ADP-ribosyl moiety of NAD by poly(ADP-ribose) polymerases (PARPs). The dynamic turnover of pADPr within the cell is essential for a number of cellular processes including progression through the cell cycle, DNA repair and the maintenance of genomic integrity, and apoptosis. In spite of the considerable advances in the knowledge of the physiological conditions modulated by poly(ADP-ribosyl)ation reactions, and notwithstanding the fact that pADPr can play a role of mediator in a wide spectrum of biological processes, few pADPr binding proteins have been identified so far. In this study, refined in silico prediction of pADPr binding proteins and large-scale mass spectrometry-based proteome analysis of pADPr binding proteins were used to establish a comprehensive repertoire of pADPr-associated proteins. Visualization and modeling of these pADPr-associated proteins in networks not only reflect the widespread involvement of poly(ADP-ribosyl)ation in several pathways but also identify protein targets that could shed new light on the regulatory functions of pADPr in normal physiological conditions as well as after exposure to genotoxic stimuli

Diverse perspectives on interdisciplinarity from the Members of the College of the Royal Society of Canada

Various multiple-disciplinary terms and concepts (although most commonly “interdisciplinarity”, which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the world’s complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demand thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paper—that interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues

Le codéveloppement professionnel en orientation : et si nous apprenions en échangeant sur notre pratique ?

Dans un contexte où les psychologues de l’orientation font face à des problèmes de plus en plus complexes et variés, le codéveloppement professionnel est un dispositif d’analyse des pratiques qui peut contribuer à renforcer leur pouvoir d’agir. L’article est une illustration d’une démarche de codéveloppement professionnel mise en place en Suisse dans le cadre d’une formation postgrade en ressources humaines et orientation. Dans une première partie, nous décrivons la notion de codéveloppement, le cadre général et les objectifs de cette sorte d’intervention, ainsi que son application auprès de conseillers et conseillères en orientation au Québec. Dans une seconde partie, nous présentons et illustrons par une étude de cas les huit étapes ayant caractérisé la mise en place de cette intervention dans le contexte suisse. Le récit de pratique émergeant de cette illustration est enfin analysé et discuté.In a context where career counselors are facing increasingly complex and diverse issues, professional co-development is a means for analyzing professional practices that can contribute to their empowerment. The article is an illustration of a professional co-development intervention implemented in Switzerland as part of postgraduate training in human resources and career counseling. In the first part, we describe the notion of co-development, the framework and goals of this type of intervention, and its application to career counselors in Quebec, Canada. In the second part, we present and illustrate through a case study the eight steps that characterized the implementation of this intervention in the Swiss context. Finally, the narrative of practice emerging from this illustration is analyzed and discussed

Modulation of branched-chain amino acids dietary intake affects survival, behavior and neuropathology of the 3xTg-AD mouse model of Alzheimer's disease

International audienc

Re-Os Geochronological Evidence for Multiple Paleoproterozoic Gold Events at the Scale of the West African Craton

International audienc

Tetrahydrobiopterin as a potential treatment for Alzheimer's disease: A study in 3xTg-AD mice

Alzheimer’s disease (AD) is a multifactorial disease, thus multi-target treatments are needed. Tetrahydrobiopterin (BH4) has been shown to be decreased in elderly and in AD patients. BH4 is an enzymatic cofactor required for the synthesis of serotonin (5-HT), dopamine (DA) and nitric oxide. It also exerts strong antioxidant and anti-inflammatory effects. Thus, BH4 administration could ameliorate monoaminergic neurotransmission but also other key physiological processes such as vascularization, metabolism, inflammatory and oxidative status. Surprisingly, despite its crucial role in the CNS, the potential of BH4 as a treatment in AD has never been investigated. Thus, we hypothesized that BH4 administration can ameliorate both cognitive symptoms and AD neuropathology. Non-transgenic (NonTg) and 3xTg-AD mice, which display age-related behavior impairment, tau and Aβ neuropathologies, were subject to a high-fat diet (35% fat - HFD) or control diet (5% fat - CD) from 6 to 13 months in order to exacerbate inflammatory and metabolic disturbances. Then, mice were injected intraperitoneally with BH4 (15mg/kg) or control solution during ten days. To verify whether BH4 is a suitable therapeutic for the CNS, we first demonstrated that peripheral administration of BH4 (50mg/kg) was sufficient to double BH4 brain content within 3h. Using in-situ brain perfusion, we found that the brain uptake clearance (Clup) of BH4 was approximately 0.08μl/g/sec, consistent with a modest transfer across the BBB. For the first time, we report that ten days of chronic administration of BH4 induced a total rescue of memory impairment in 13-month-old 3xTg-AD mice as determined with the novel object recognition test. Interestingly, this improvement was observed even over a HFD background. Moreover, glucose intolerance induced by HFD in 3xTg-AD mice was completely reversed by BH4 treatment while no difference on diet consumption, mice weight and voluntary locomotion in open-field were observed. BH4 treatment had no effect on total or phosphorylated tau assessed in soluble and insoluble fractions extracted from the hippocampus. As BH4 is involved in monoamine synthesis, we also measured striatal DA and 5-HT content without detecting any significant changes. Amyloid pathology and pro-inflammatory cytokines measurements are currently ongoing. Overall, our data show that BH4 supplementation leads to a rescue in object recognition memory and metabolic impairments in the 3xTg-AD mouse model, without altering tau neuropathology