Inserting Oneself in the Story: Queer Literacy, Comics, and an Admonition to Move

Inserting Oneself in the Story: Queer Literacy, Comics, and an Admonition to Mov

Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.

Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms

Cellular delivery of antibodies: effective targeted subcellular imaging and new therapeutic tool

It is already more than a century since the pioneering work of the Nobel Laureate Ehrlich gave birth to the side chain theory1, which helped to define antibodies and their ability to target specific biological sites. However, the use of antibodies is still restricted to the extracellular space due to the lack of a suitable delivery vehicle for the efficient transport of antibodies into live cells without inducing toxicity. In this work, we report the efficient encapsulation and delivery of antibodies into live cells with no significant loss of cell viability or any deleterious affect on the cell metabolic activity. This delivery system is based on poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-(2-(diisopropylamino)ethyl methacrylate), (PMPC-PDPA), a pH sensitive diblock copolymer that self-assembles to form nanometer-sized vesicles, also known as polymersomes, at physiological pH. These polymersomes can successfully deliver relatively high antibody payloads within live cells. Once inside the cells, we demonstrate that these antibodies can target their epitope by immune-labelling of cytoskeleton, Golgi, and transcription factor proteins in live cells. We also demonstrate that this effective antibody delivery mechanism can be used to control specific subcellular events, as well as modulate cell activity and pro-inflammatory process

Intranasal administration of NDV-HXP-S COVID19 vaccines induces robust protective mucosal and systemic immunity in mice

With the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually changing and no end of this pandemic in sight, a next generation of vaccines preventing transmission and an equitable allocation is needed in order to reduce global disease burden. The NDV-HXP-S vaccine is based on recombinant Newcastle disease virus (NDV) stably expressing a membrane-anchored, optimized (with six proline mutations – Hexa Pro) spike protein1. Using the current influenza virus vaccine manufacturing facilities, this vaccine can be produced in embryonated eggs and thereby can meet the demands on a global scale at a low cost. Here, we report that mice vaccinated intranasally (i.n.) with different designs and regimens of our live NDV-HXP-S induced strong antibody response, displaying good systemic as well as mucosal immunity. Furthermore, the T and B cell responses in the lung were characterized via flow cytometry. It is important to emphasize, that we have been able to quickly adapt the vaccine to newly emerging variants of concern (VOC) of SARS-CoV-2. Please click Download on the upper right corner to see the full abstract

SIRT1 in astrocytes regulates glucose metabolism and reproductive function

Sirtuin 1 (Sirt1) is an NAD-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, evidence suggests that SIRT1 in neurons plays a role in the central regulation of energy balance and reproduction, but no studies have addressed the contribution of astrocytes. We show here that overexpression of SIRT1 in astrocytes causes markedly increased food intake, body weight gain, and glucose intolerance, but expression of a deacetylase-deficient SIRT1 mutant decreases food intake and body weight and improves glucose tolerance, particularly in female mice. Paradoxically, the effect of these SIRT1 mutants on insulin tolerance was reversed, with overexpression showing greater insulin sensitivity. The mice overexpressing SIRT1 were more active, generated more heat, and had elevated oxygen consumption, possibly in compensation for the increased food intake. The female overexpressing mice were also more sensitive to diet-induced obesity. Reproductively, the mice expressing the deacetylase-deficient SIRT1 mutant had impaired estrous cycles, decreased LH surges, and fewer corpora lutea, indicating decreased ovulation. The GnRH neurons were responsive to kisspeptin stimulation, but hypothalamic expression of Kiss1 was reduced in the mutant mice. Our results showed that SIRT1 signaling in astrocytes can contribute to metabolic and reproductive regulation independent of SIRT1 effects in neurons.Fil: Choi, Irene. VA San Diego Healthcare System; Estados UnidosFil: Rickert, Emily. University of California at San Diego; Estados UnidosFil: Fernandez, Marina Olga. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Webster, Nicholas J.G.. VA San Diego Healthcare System; Estados Unidos. University of California at San Diego; Estados Unido

The neural basis of intuitive and counterintuitive moral judgment

Neuroimaging studies on moral decision-making have thus far largely focused on differences between moral judgments with opposing utilitarian (well-being maximizing) and deontological (duty-based) content. However, these studies have investigated moral dilemmas involving extreme situations, and did not control for two distinct dimensions of moral judgment: whether or not it is intuitive (immediately compelling to most people) and whether it is utilitarian or deontological in content. By contrasting dilemmas where utilitarian judgments are counterintuitive with dilemmas in which they are intuitive, we were able to use functional magnetic resonance imaging to identify the neural correlates of intuitive and counterintuitive judgments across a range of moral situations. Irrespective of content (utilitarian/deontological), counterintuitive moral judgments were associated with greater difficulty and with activation in the rostral anterior cingulate cortex, suggesting that such judgments may involve emotional conflict; intuitive judgments were linked to activation in the visual and premotor cortex. In addition, we obtained evidence that neural differences in moral judgment in such dilemmas are largely due to whether they are intuitive and not, as previously assumed, to differences between utilitarian and deontological judgments. Our findings therefore do not support theories that have generally associated utilitarian and deontological judgments with distinct neural systems

The status of sustainable social innovation in Malta

Governments are increasingly using social innovation to stimulate economic growth and address social issues sustainably. Unfortunately, due to its size, Malta faces a very different challenge to sustainably kick-start high-value-added innovative ecosystems compared to larger states. This is due to a number of issues, including diseconomies of scale, that tend to impede conventional innovation policy efforts. Based on grassroots data, this paper presents the results of a study which determined the status of social innovation in Malta and presents a few recommended measures that can be implemented in order to stimulate social innovation sustainably in Malta and possibly in similar small jurisdictions.peer-reviewe