Ketogenic diet modulates NAD\u3csup\u3e+\u3c/sup\u3e-dependent enzymes and reduces DNA damage in hippocampus

© 2018 Elamin, Ruskin, Masino and Sacchetti. The ketogenic diet’s (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking. We previously showed that feeding rats a KD produced an early (within 2 days) and persistent elevation of hippocampal nicotinamide adenine dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule. NAD+ is a marker of cellular health and a substrate for enzymes implicated in longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1 (PARP-1). As a result, activation of NAD+-dependent enzymes’ downstream pathways could be the origin of KD’s broad beneficial effects. Here rats were fed ad libitum regular chow or KD for 2 days or 3 weeks and the levels of hippocampal sirtuins, PARP-1, and the oxidative DNA damage marker 8-hydroxy-2’-deoxyguanosine were quantified. We found a significant immediate and persistent increase in the collective activity of nuclear sirtuin enzymes, and a significant augmentation of Sirt1 mRNA at 2 days. Levels of PARP-1 and 8-hydroxy-2’- deoxyguanosine decreased after 2 days of treatment and further declined at 3 weeks. Our data show that a KD can rapidly modulate energy metabolism by acting on NAD+-dependent enzymes and their downstream pathways. Thus, therapy with a KD can potentially enhance brain health and increase overall healthspan via NAD+- related mechanisms that render cells more resilient against DNA damage and a host of metabolic, epileptic, neurodegenerative, or neurodevelopmental insults

Ketogenic Diet Modulates NAD+-Dependent Enzymes and Reduces DNA Damage in Hippocampus

The ketogenic diet’s (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking. We previously showed that feeding rats a KD produced an early (within 2 days) and persistent elevation of hippocampal nicotinamide adenine dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule. NAD+ is a marker of cellular health and a substrate for enzymes implicated in longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1 (PARP-1). As a result, activation of NAD+-dependent enzymes’ downstream pathways could be the origin of KD’s broad beneficial effects. Here rats were fed ad libitum regular chow or KD for 2 days or 3 weeks and the levels of hippocampal sirtuins, PARP-1, and the oxidative DNA damage marker 8-hydroxy-2’-deoxyguanosine were quantified. We found a significant immediate and persistent increase in the collective activity of nuclear sirtuin enzymes, and a significant augmentation of Sirt1 mRNA at 2 days. Levels of PARP-1 and 8-hydroxy-2’-deoxyguanosine decreased after 2 days of treatment and further declined at 3 weeks. Our data show that a KD can rapidly modulate energy metabolism by acting on NAD+-dependent enzymes and their downstream pathways. Thus, therapy with a KD can potentially enhance brain health and increase overall healthspan via NAD+-related mechanisms that render cells more resilient against DNA damage and a host of metabolic, epileptic, neurodegenerative, or neurodevelopmental insults

Orientation of the central domains of KSRP and its implications for the interaction with the RNA targets

KSRP is a multi-domain RNA-binding protein that recruits the exosome-containing mRNA degradation complex to mRNAs coding for cellular proliferation and inflammatory response factors. The selectivity of this mRNA degradation mechanism relies on KSRP recognition of AU-rich elements in the mRNA 3′UTR, that is mediated by KSRP’s KH domains. Our structural analysis shows that the inter-domain linker orients the two central KH domains of KSRP—and their RNA-binding surfaces—creating a two-domain unit. We also show that this inter-domain arrangement is important to the interaction with KSRP’s RNA targets

A Woman’s Loss of Imagination: Paola Masino’s Magical Realism in Nascita e morte della Massaia

Criticism on Paola Masino has flourished since the early 2000s. This increased attention has contributed towards reclaiming an author often overshadowed by the attention received by her partner, Massimo Bontempelli, the father of realismo magico. Masino experimented with a variety of styles—realismo magico was one of them—as she rejected strictly naturalistic forms of representation, preferring to co-opt myths and the supernatural. Nascita e morte della Massaia (1945) is Masino’s most renowned literary effort, both for its critique of Fascist Italy and for its sophisticated stylistic effects. Nascita, while indebted to Bontempelli’s theorizations, features all the chief characteristics listed in Faris’s analysis of magical realism as an international phenomenon, and illustrates how magical realism offers strategies for evading censorship to those writing against totalitarianism regimes. At the same time, it is an example of how magical realism can be used to denounce socially imposed gender roles. My analysis shows how this narrative mode emerges on multiple levels within Masino’s text

Venezia Novecento. Le voci di Paola Masino e Milena Milani

In questi Atti di Convegno, Paola Masino, Milena Milani e Venezia si propongono come tre poli di un dialogo a più voci. Alcuni dei volti e delle trame della vita in città, negli anni Trenta e Quaranta e nei decenni successivi, sono infatti riuniti attorno a due autrici che hanno saputo fare della scrittura un mestiere fecondo. Il loro contributo, evidenziato nel volume da nove relatrici, ridisegna il volto della laguna con particolare attenzione ai luoghi e ai tempi, cogliendo, di decennio in decennio, peculiarità e variazioni. Un profilo, quello di Venezia Novecento, poco o per nulla narrato dalle donne, che trova in questi saggi un timbro di autenticità

Violencia obstétrica en México: La consolidación disputada de un nuevo paradigma

<p>A partir de múltiples investigaciones antropológicas y salubristas sobre problemas de salud y mortalidad materna en México, surge mi interés en la problemática de la violencia obstétrica, tanto como una categoría epistémica que nombra de manera innovadora una problemática institucional de viejo cuño, así como su uso —en la práctica— en disputas legales y sociopolíticas que se han desarrollado en el país en los últimos años. En particular, el texto explora cómo y hasta qué punto violencia obstétrica, como un marco conceptual de reciente creación, se está arraigando en la legislación mexicana y en la defensoría de los derechos humanos, al mismo tiempo que continúaenfrentándose a resistencias diversas dentro del sistema de salud y por distintos actores.</p&gt