Brain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: achievements and weaknesses.

Mitochondrial diseases are a group of severe pathologies that cause complex neurodegenerative disorders for which, in most cases, no therapy or treatment is available. These organelles are critical regulators of both neurogenesis and homeostasis of the neurological system. Consequently, mitochondrial damage or dysfunction can occur as a cause or consequence of neurodevelopmental or neurodegenerative diseases.

The mid-secretory endometrial transcriptomic landscape in endometriosis: a meta-analysis.

Study Question: Do women with endometriosis have a different endometrial gene expression profile at the time of embryo implantation than women without endometriosis?

Summary Answer: The endometrial gene expression profile of women with endometriosis differs from that of women without endometriosis at the mid-secretory phase, although the differences are small.

What Is Known Already: About 50% of women with endometriosis suffer infertility. Several molecular studies have suggested impaired endometrial receptivity in women with endometriosis, while others have detected no dysregulation of endometrial receptivity.

Toward the computational design of protein crystals with improved resolution.

Substantial advances have been made in the computational design of protein interfaces over the last 20 years. However, the interfaces targeted by design have typically been stable and high-affinity. Here, we report the development of a generic computational design method to stabilize the weak interactions at crystallographic interfaces.

Dielectric Properties of a Protein Probed by Reversal of a Buried Ion Pair.

Thirty years ago, Hwang and Warshel suggested that a microenvironment preorganized to stabilize an ion pair would be incapable of reorganizing to stabilize the reverse ion pair. The implications were that (1) proteins have a limited capacity to reorganize, even under the influence of strong interactions, such as those present when ionizable groups are buried in the hydrophobic interior of a protein, and (2) the inability of proteins to tolerate the reversal of buried ion pairs demonstrates the limitations inherent to continuum electrostatic models of proteins. Previously we showed that when buried individually in the interior of staphylococcal nuclease, Glu23 and Lys36 have p K values near pH 7, but when buried simultaneously, they establish a strong interaction of ∼5 kcal/mol and have p K values shifted toward more normal values.

Anomalous Properties of Lys Residues Buried in the Hydrophobic Interior of a Protein Revealed with N-Detect NMR Spectroscopy.

Ionizable residues buried in hydrophobic environments in proteins are essential for many fundamental biochemical processes. These residues titrate with anomalous pK values that are challenging to reproduce with structure-based calculations owing to the conformational reorganization coupled to their ionization. Detailed characterization of this conformational reorganization is of interest; unfortunately, the properties of buried Lys residues are difficult to study experimentally.