Enhancing Oral Delivery of Biologics: A Non-Competitive and Cross-Reactive Anti-Leptin Receptor Nanofitin Demonstrates a Gut-Crossing Capacity in an Ex Vivo Porcine Intestinal Model.

Biotherapeutics exhibit high efficacy in targeted therapy, but their oral delivery is impeded by the harsh conditions of the gastrointestinal (GI) tract and limited intestinal absorption. This article presents a strategy to overcome the challenges of poor intestinal permeability by using a protein shuttle that specifically binds to an intestinal target, the leptin receptor (LepR), and exploiting its capacity to perform a receptor-mediated transport. Our proof-of-concept study focuses on the characterization and transport of robust affinity proteins, known as Nanofitins, across an ex vivo porcine intestinal model.

The N-terminal domain of TET1 promotes the formation of dense chromatin regions refractory to transcription.

TET (ten-eleven translocation) enzymes initiate active cytosine demethylation via the oxidation of 5-methylcytosine. TET1 is composed of a C-terminal domain, which bears the catalytic activity of the enzyme, and a N-terminal region that is less well characterized except for the CXXC domain responsible for the targeting to CpG islands. While cytosine demethylation induced by TET1 promotes transcription, this protein also interacts with chromatin-regulating factors that rather silence this process, the coordination between these two opposite functions of TET1 being unclear.

3D architecture and structural flexibility revealed in the subfamily of large glutamate dehydrogenases by a mycobacterial enzyme.

Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies.

20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition.

Intellectual disability (ID) is characterized by an extraordinary genetic heterogeneity, with >250 genes that have been implicated in monogenic forms of ID. Because this complexity precluded systematic testing for mutations and because clinical features are often non-specific, for some of these genes only few cases or families have been unambiguously documented. It is the case of the X-linked gene encoding monoamine oxidase A (MAOA), for which only one nonsense mutation has been identified in Brunner syndrome, characterized in a single family by mild non-dysmorphic ID and impulsive, violent and aggressive behaviors.

The porcine trophoblastic interferon-gamma, secreted by a polarized epithelium, has specific structural and biochemical properties.

At the time of implantation in the maternal uterus, the trophectoderm of the pig blastocyst is the source of a massive secretion of interferon-gamma (IFN-gamma), together with lesser amounts of IFN-delta, a unique species of type I IFN. This trophoblastic IFN-gamma (TrIFN-gamma) is an unprecedented example of IFN-gamma being produced spontaneously by an epithelium. We therefore studied some of its structural and biochemical properties, by comparison with pig IFN-gamma from other sources, either natural LeIFN-gamma (from adult leucocytes), or recombinant.

Crystallization and preliminary X-ray diffraction studies of beta-cryptogein, a toxic elicitin secreted by the phytopathogenic fungus Phytophthora cryptogea.

Crystals of the basic elicitin secreted by Phytophthora cryptogea have been obtained by the hanging-drop method of vapor diffusion from sodium chloride solutions. The crystals belong to the tetragonal space group P4(1)22 (or enantiomorph P4(3)22), with unit cell dimensions a = b = 47 A, c = 137 A and probably contain two molecules per asymmetric unit. The crystals are very stable to X-rays and diffract to 2.

[Purification and characterization of presumed thyrotropic hormone subunits of a teleost fish, the eel (Anguilla anguilla)].

We have only a partial knowledge of fish thyrotropins (TSH) and no data about peptide sequence are available. Various HPLC techniques allowed us to purify a 31.4 kDa, heterodimeric protein from saline eel pituitary extracts containing TSH activity.

Molecular forms of Electrophorus acetylcholinesterase. Molecular weight and composition.

Molecular weights for the series of six Electrophorus acetylcholinesterase forms have been determined either by the sedimentation-diffusion equilibrium method or, particularly in the case of the very scarce G' and G inches forms, from their Stokes radius and sedimentation coefficient values. Both methods are in excellent agreement. The results provide good evidence for the model previously proposed, G inches, G' and G containing one, two and four subunits, whereas A, C and D possess, in addition to respectively one, two and three tetrameric sets of such subunits, a structural element, the tail.