Once experimentally prohibitive, structural studies of individual missense variants in proteins are increasingly feasible, and can provide a new level of insight into human genetic disease. One example of this is the recently identified inborn error of metabolism known as phosphoglucomutase-1 (PGM1) deficiency. Just as different variants of a protein can produce different patient phenotypes, they may also produce distinct biochemical phenotypes, affecting properties such as catalytic activity, protein stability, or 3D structure/dynamics. Experimental studies of missense variants, and particularly structural characterization, can reveal details of the underlying biochemical pathomechanisms of missense variants. Here, we review four examples of enzyme dysfunction observed in disease-related variants of PGM1. These studies are based on 11 crystal structures of wild-type (WT) and mutant enzymes, and multiple biochemical assays. Lessons learned include the value of comparing mutant and WT structures, synergy between structural and biochemical studies, and the rich understanding of molecular pathomechanism provided by experimental characterization relative to the use of predictive algorithms. We further note functional insights into the WT enzyme that can be gained from the study of pathogenic variants.The homeostasis of mitochondrial functional state is intimately in relation with SIRT3 (sirtuin3). SIRT3, the deacetylase mainly anchored in mitochondria, acts as a modulator of metabolic regulation via manipulating the activity and function of downstream targets at post-translational modification levels. The features of energy sensing and ADP-ribose transference of SIRT3 have also been reported. Recently, accumulating SIRT3-focusing evidences have suggested its complicated role in a series of adverse events such as metabolic disorders, aging-related diseases, coupled with tumors, in which SIRT3 regulates the progress of corresponding biochemical reactions by targeting key mediators. By systematically summarizing the downstream deacetylated proteins of the SIRT3 axis, this review aims to give a comprehensive introduction to the main metabolic pathways and diseases of the molecules involved in acetylation modification, which is expected to provide a direction for further exploration of the pathogenesis and therapeutic targets of the above diseases.Huntington’s disease (HD) is an inherited neurodegenerative disorder that usually starts during midlife with progressive alterations of motor and cognitive functions. The disease is caused by a CAG repeat expansion within the huntingtin gene leading to severe striatal neurodegeneration. Recent studies conducted on pre-HD children highlight early striatal developmental alterations starting as soon as 6 years old, the earliest age assessed. These findings, in line with data from mouse models of HD, raise the questions of when during development do the first disease-related striatal alterations emerge and whether they contribute to the later appearance of the neurodegenerative features of the disease. this website In this review we will describe the different stages of striatal network development and then discuss recent evidence for its alterations in rodent models of the disease. We argue that a better understanding of the striatum’s development should help in assessing aberrant neurodevelopmental processes linked to the HD mutation.After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.Double contingency-each of us (Ego) expects others (Alter) to entertain expectations as we entertain them ourselves-can be considered as the micro-operation of an above-individual (i.e., social) logic of expectations. Meaning is provided to events from the perspective of hindsight, but with reference to horizons of meaning. Whereas “natural selection” is based on genotypes that are observable (like DNA), cultural selection mechanisms are not hard-wired, but evolve. The “genotypes” of cultural evolution are codes in the communication which can operate as selections upon one another. Local instantiations shape trajectories; regimes operate as selection pressure with reference to the next-order horizons of meaning. These orders of expectations can operate incursively and hyper-incursively against the arrow of time and thus generate redundancies (i) horizons of meaning can be expected to overlap and (ii) distinctions generate new options enlarging the maximum capacities. Information theory and the theory of anticipatory systems can be used for the elaboration of operations against the arrow of time. New options can be a synergetic effect of interactions among codes in the communication and serve as sources of wealth in a knowledge-based economy.