Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages

Infertility is a growing problem worldwide. Currently, in vitro fertilization (IVF) is widely performed to treat infertility. However, a high percentage of IVF cycles fails, due to the poor developmental potential of the retrieved oocyte to generate viable embryos. Fatty acid content of the follicular microenvironment can affect oocyte maturation and the subsequent developmental competence. Saturated and monounsaturated fatty acids are mainly used by follicle components as primary energy sources whereas polyunsaturated fatty acids (PUFAs) play a wide range of roles. A large body of evidence supports the beneficial effects of n-3 PUFAs in prevention, treatment, and amelioration of some pathophysiological conditions including heart diseases, cancer, diabetes, and psychological disorders. Nevertheless, current findings regarding the effects of n-3 PUFAs on reproductive outcomes in general and on oocyte quality more specifically are inconsistent. This review attempts to provide a comprehensive overview of potential molecular mechanisms by which n-3 PUFAs affect oocyte maturation and developmental competence, particularly in the setting of IVF and thereby aims to elucidate the reasons behind current discrepancies around this topic.     

Actions,Action Sequences and Habits: Evidence That Goal-Directed and Habitual Action Control Are Hierarchically Organized

Behavioral evidence suggests that instrumental conditioning is governed by two forms of action control: a goal-directed and a habit learning process. Model-based reinforcement learning (RL) has been argued to underlie the goal-directed process; however, the way in which it interacts with habits and the structure of the habitual process has remained unclear. According to a flat architecture, the habitual process corresponds to model-free RL, and its interaction with the goal-directed process is coordinated by an external arbitration mechanism. Alternatively, the interaction between these systems has recently been argued to be hierarchical, such that the formation of action sequences underlies habit learning and a goal-directed process selects between goal-directed actions and habitual sequences of actions to reach the goal. Here we used a two-stage decision-making task to test predictions from these accounts. The hierarchical account predicts that, because they are tied to each other as an action sequence, selecting a habitual action in the first stage will be followed by a habitual action in the second stage, whereas the flat account predicts that the statuses of the first and second stage actions are independent of each other. We found, based on subjects'' choices and reaction times, that human subjects combined single actions to build action sequences and that the formation of such action sequences was sufficient to explain habitual actions. Furthermore, based on Bayesian model comparison, a family of hierarchical RL models, assuming a hierarchical interaction between habit and goal-directed processes, provided a better fit of the subjects'' behavior than a family of flat models. Although these findings do not rule out all possible model-free accounts of instrumental conditioning, they do show such accounts are not necessary to explain habitual actions and provide a new basis for understanding how goal-directed and habitual action control interact.     

Human SIRT1 Multispecificity Is Modulated by Active-Site Vicinity Substitutions during Natural Evolution

Many enzymes that catalyze protein post-translational modifications can specifically modify multiple target proteins. However, little is known regarding the molecular basis and evolution of multispecificity in these enzymes. Here, we used a combined bioinformatics and experimental approaches to investigate the evolution of multispecificity in the sirtuin-1 (SIRT1) deacetylase. Guided by bioinformatics analysis of SIRT1 orthologs and substrates, we identified and examined important amino acid substitutions that have occurred during the evolution of sirtuins in Metazoa and Fungi. We found that mutation of human SIRT1 at these positions, based on sirtuin orthologs from Fungi, could alter its substrate specificity. These substitutions lead to reduced activity toward K382 acetylated p53 protein, which is only present in Metazoa, without affecting the high activity toward the conserved histone substrates. Results from ancestral sequence reconstruction are consistent with a model in which ancestral sirtuin proteins exhibited multispecificity, suggesting that the multispecificity of some metazoan sirtuins, such as hSIRT1, could be a relatively ancient trait.     

The roles of signaling pathways in liver repair and regeneration

The liver has remarkable regeneration potency that restores liver mass and sustains body hemostasis. Liver regeneration through signaling pathways following resection or moderate damages are well studied. Various cell signaling, growth factors, cytokines, receptors, and cell types implicated in liver regeneration undergo controlled hypertrophy and proliferation. Some aspects of liver regeneration have been discovered and many investigations have been carried out to identify its mechanisms. However, for optimizing liver regeneration more should be understood about mechanisms that control the growth of hepatocytes and other liver cell types in adults. The current paper deals with the possible applicability of liver regeneration signaling pathways as a target for therapeutic approaches and preventing various liver damages. Furthermore, the latest findings of spectrum-specific signaling pathway mechanisms that underlie liver regeneration are briefly described.     

Employing directed evolution for the functional analysis of multi-specific proteins

Multi-specific proteins located at the heart of complex protein–protein interaction (PPI) networks play essential roles in the survival and fitness of the cell. In addition, multi-specific or promiscuous enzymes exhibit activity toward a wide range of substrates so as to increase cell evolvability and robustness. However, despite their high importance, investigating the in vivo function of these proteins is difficult, due to their complex nature. Typically, deletion of these proteins leads to the abolishment of large PPI networks, highlighting the difficulty in examining the contributions of specific interactions/activities to complex biological processes and cell phenotypes. Protein engineering approaches, including directed evolution and computational protein design, allow for the generation of multi-specific proteins in which certain activities remain intact while others are abolished. The generation and examination of these mutants both in vitro and in vivo can provide high-resolution analysis of biological processes and cell phenotypes and provide new insight into the evolution and molecular function of this important protein family.