Psychological evaluation of candidates for the uterus transplantation French trial.

Introduction: Since 2017, women with absolute uterine infertility due to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome have been eligible to participate in a uterine transplantation clinical trial conducted by Foch Hospital in France. The aim of this study is to assess the psychological state of potential candidates, including recipients, their partners, and their living-related donors.

Material And Methods: Sixteen potential uterus transplant candidates, including recipients, partners, and living-related donors, participated in the study.

[Epidemiologic and histopathologic characteristics of 1280 uterine cervical cancers in Kinshasa].

Objective: Due to the lack of both cancer registry and large scale cervical screening in most african countries, only theoretical studies are available. The objective of our work was to provide epidemiological and histopathological characteristics of cervical cancer based on concrete observations.

Methods: This study was carried out on all cancers (n=5801) collected in the last 10 years from 5 pathology laboratories of Kinshasa; the histologic slides of the cervical cancers (n=1280) were reviewed by at least two pathologists and classified according to the 2014 OMS classification.

Power of protein/tRNA functional assembly against aberrant aggregation.

Understanding the mechanisms of protein oligomerization and aggregation is a major concern for biotechnology and medical purposes. However, significant challenges remain in determining the mechanism of formation of these superstructures and the environmental factors that can precisely modulate them. Notably the role that a functional ligand plays in the process of protein aggregation is largely unexplored.

A chemical chaperone induces inhomogeneous conformational changes in flexible proteins.

Organic osmolytes also known as chemical chaperones are major cellular compounds that favor, by an unclear mechanism, protein's compaction and stabilization of the native state. Here, we have examined the chaperone effect of the naturally occurring trimethylamine N-oxide (TMAO) osmolyte on a loosely packed protein (LPP), known to be a highly flexible form, using an apoprotein mutant of the flavin-dependent RNA methyltransferase as a model. Thermal and chemical denaturation experiments showed that TMAO stabilizes the structural integrity of the apoprotein dramatically.

Peptide-binding dependent conformational changes regulate the transcriptional activity of the quorum-sensor NprR.

The transcriptional regulator NprR controls the expression of genes essential for the adaptative response of Bacillus cereus. NprR belongs to the RNPP family of directly regulated quorum sensors from Gram-positive bacteria. It is activated by the re-imported signaling peptide NprX.

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR.

The quorum-sensing regulator PlcR is the master regulator of most known virulence factors in Bacillus cereus. It is a helix-turn-helix (HTH)-type transcription factor activated upon binding of its cognate signaling peptide PapR on a tetratricopeptide repeat-type regulatory domain. The structural and functional properties of PlcR have defined a new family of sensor regulators, called the RNPP family (for Rap, NprR, PrgX, and PlcR), in Gram-positive bacteria.

Multiple myeloma presenting as hepatic nodular lesion.

The diffuse infiltration by plasma cells in the liver is not uncommon in multiple myeloma (MM). However, a MM with hepatic mass is very unusual. We report a case of a 75-year-old male with hepatomegaly and a lesion occupying a voluminous space in the liver.

Biophysical studies of the interaction between calmodulin and the R²⁸⁷-T³¹¹ region of human estrogen receptor α reveals an atypical binding process.

The transcriptional activity of human estrogen receptor ERα is modulated by a number of coregulatory proteins among which calmodulin (CaM). Segment 295-311 in the hinge region of ERα has previously been proposed to be the CaM binding site. In this work, we investigate the molecular mechanism of the interaction of CaM with peptides derived from the hinge region of ERα, using a biophysical approach combining isothermal titration calorimetry, fluorescence, CD and NMR.

Dissection of Dom34-Hbs1 reveals independent functions in two RNA quality control pathways.

Eukaryotic cells have several quality control pathways that rely on translation to detect and degrade defective RNAs. Dom34 and Hbs1 are two proteins that are related to translation termination factors and are involved in no-go decay (NGD) and nonfunctional 18S ribosomal RNA (rRNA) decay (18S NRD) pathways that eliminate RNAs that cause strong ribosomal stalls. Here we present the structure of Hbs1 with and without GDP and a low-resolution model of the Dom34-Hbs1 complex.

The Pih1-Tah1 cochaperone complex inhibits Hsp90 molecular chaperone ATPase activity.

Hsp90 (heat shock protein 90) is an ATP-dependent molecular chaperone regulated by collaborating proteins called cochaperones. This machinery is involved in the conformational activation of client proteins like signaling kinases, transcription factors, or ribonucleoproteins (RNP) such as telomerase. TPR (TetratricoPeptide Repeat)-containing protein associated with Hsp90 (Tah1) and protein interacting with Hsp90 (Pih1) have been identified in Saccharomyces cerevisiae as two Hsp90 cochaperones involved in chromatin remodeling complexes and small nucleolar RNP maturation.

A conserved mechanism of GABA binding and antagonism is revealed by structure-function analysis of the periplasmic binding protein Atu2422 in Agrobacterium tumefaciens.

Bacterial periplasmic binding proteins (PBPs) and eukaryotic PBP-like domains (also called as Venus flytrap modules) of G-protein-coupled receptors are involved in extracellular GABA perception. We investigated the structural and functional basis of ligand specificity of the PBP Atu2422, which is implicated in virulence and transport of GABA in the plant pathogen Agrobacterium tumefaciens. Five high-resolution x-ray structures of Atu2422 liganded to GABA, Pro, Ala, and Val and of point mutant Atu2422-F77A liganded to Leu were determined.

High affinity binding between Hsp70 and the C-terminal domain of the measles virus nucleoprotein requires an Hsp40 co-chaperone.

The major inducible 70 kDa heat shock protein (hsp70) binds the measles virus (MeV) nucleocapsid with high affinity in an ATP-dependent manner, stimulating viral transcription and genome replication, and profoundly influencing virulence in mouse models of brain infection. Binding is mediated by two hydrophobic motifs (Box-2 and Box-3) located within the C-terminal domain (N(TAIL)) of the nucleocapsid protein, with N(TAIL) being an intrinsically disordered domain. The current work showed that high affinity hsp70 binding to N(TAIL) requires an hsp40 co-chaperone that interacts primarily with the hsp70 nucleotide binding domain (NBD) and displays no significant affinity for N(TAIL).

Identification of a human estrogen receptor alpha-derived antiestrogenic peptide that adopts a polyproline II conformation.

Polyproline II (PPII) helix is an extended secondary structure present in a number of proteins. PPII-containing sequences mediate specific protein-protein interactions with partners containing appropriate cognate domains called PPII-recognizing domains (PRDs) and are involved in the activation of intracellular signaling pathways. Thus, the identification of PPII structures in proteins is of great interest, not only to explore molecular and physiological mechanisms, but also to elaborate new potential drugs.

Disulfide bond substitution by directed evolution in an engineered binding protein.

Breaking ties: The antitumour protein, neocarzinostatin (NCS), is one of the few drug-carrying proteins used in human therapeutics. However, the presence of disulfide bonds limits this protein's potential development for many applications. This study describes a generic directed-evolution approach starting from NCS-3.

High affinity Grb2-SH3 domain ligand incorporating Cbeta-substituted prolines in a Sos-derived decapeptide.

Peptide ligands that disrupt MAPK pathways are of great interest for a better understanding of these signalling cascades and represent therefore an attractive target to control cell degenerative processes. In that context, selective disruption of the upstream Grb2/Sos complex in the Ras/MAPK cascade has focused extensive work. The Sos PPII decapeptide, which interacts with the Grb2-SH3 domains, has been modified in various positions and the best inhibitors designed so far are either dimeric ligands or peptoid analogues of the VPPPVPPRRR sequence.

Cross-sectional anatomy and comparative ultrasonography of the equine medial femorotibial joint and its related structures.

Reasons For Performing Study: Injuries of the equine stifle are frequent causes of hindlimb lameness. Ultrasonography is useful for the diagnosis of many soft tissue lesions but, until recently, its application to the equine stifle has been limited to a description of normal and abnormal structures. A comparative study using gross anatomical sections to identify all structures visible on ultrasonographic images of the equine stifle has not previously been reported.

Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin PA-IIL of Pseudomonas aeruginosa.

One of the mechanisms contributing to the protection by breast-feeding of the newborn against enteric diseases is related to the ability of human milk oligosaccharides to prevent the attachment of pathogenic bacteria to the duodenual epithelium. Indeed, a variety of fucosylated oligosaccharides, specific to human milk, form part of the innate immune system. In the present study, we demonstrate the specific blocking of PA-IIL, a fucose-binding lectin of the human pathogen Pseudomonas aeruginosa, by milk oligosaccharides.

Affinity transfer by CDR grafting on a nonimmunoglobulin scaffold.

Neocarzinostatin (NCS) is a small "all beta" protein displaying the same overall fold as immunoglobulins. This protein possesses a well-defined hydrophobic core and two loops structurally equivalent to the CDR1 and CDR3 of immunoglobulins. NCS is the most studied member of the enediynechromoprotein family, and is clinically used as an antitumoral agent.

Role of the tyrosine corner motif in the stability of neocarzinostatin.

Although the immunoglobulin-like beta-sandwich fold has no specifically conserved function, some common structural features have been observed, in particular a structural motif, the tyrosine corner. Such a motif was described in neocarzinostatin (NCS), a bacterial protein the structure of which is very similar to that of the immunoglobulin domain. Compared with the other beta-sheet proteins, the NCS 'tyrosine corner' presents non-standard structural features.

Histones: a novel class of lipopolysaccharide-binding molecules.

Unlike soluble and membrane forms of lipopolysaccharide (LPS)-binding proteins, intracellular LPS-binding molecules are poorly documented. We looked for such molecules in a murine lung epithelial cell line. Two proteins with LPS-binding activity were isolated and unambiguously identified as histones H2A.

Key interactions in neocarzinostatin, a protein of the immunoglobulin fold family.

Neocarzinostatin (NCS) is a seven-stranded beta-sandwich protein, the folding of which is similar to that of the variable domains of immunoglobulins (Ig). The investigation of the backbone dynamics of apo-NCS [Izadi-Pruneyre et al. (2001) Protein Sci.

Protection by glutathione against the antiproliferative effects of nitric oxide. Dependence on kinetics of no release.

Pretreatment by L-buthionine sulfoximine (BSO), which inactivates gamma-glutamylcysteine synthetase and, therefore, inhibits glutathione (GSH) synthesis, greatly increased the sensitivity of tumor cells to the antiproliferative effects of several NO-donating compounds. The sensitization that resulted from depletion of cellular GSH pools was observed in tumor cells exhibiting different degrees of resistance to NO. In contrast, GSH depletion of tumor target cells did not affect their sensitivity to the cytostatic activity of activated macrophages and other NO-producing cells (EMT6 cells treated by interferon gamma and LPS).

Morphological study of the development of the disseminate prostate in intact and castrated male pigs aged two to six months.

The light-microscopical and ultrastructural differentiation of the disseminate prostate was studied in 12 boars and 8 barrows, ranging in age from 8 to 28 and 12 to 27 weeks, respectively. The barrows had been castrated at the age of 8 weeks. In young boars the prostate is organized in an inner zone and an outer zone.

A simple and inexpensive device for applying a calibration pulse when performing intracellular recording.

A simple and low-cost device is described which facilitates the calibration of intracellular DC recordings in amplitude and time. A current source, optically coupled to a conventional stimulator, injects a pulse of current, across a 1-omega resistor connecting the preparation to ground. Amplitude and duration of the current pulse are determined by adjusting the voltage output of the conventional stimulator.