[Why (and how) to think of care beyond the sexuation of bodies]. / Pourquoi (et comment) penser le soin au-delà de la sexuation des corps.

More and more young people identify as transgender or non-binary today. This can be attributed to the increased availability of vocabulary regarding gender as well as the diverse representations of trans and non-binary people in media and on social networking sites. However, medical or educational institutions are slow to change and many trans individuals still feel uncomfortable in the presence of health care providers, regardless of their specialty.

Antibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth.

Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study, we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O antigen of a second lipopolysaccharide (LPS) type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane.

Structural basis for selective cross-reactivity in a bactericidal antibody against inner core lipooligosaccharide from Neisseria meningitidis.

The structure of a antigen-binding fragment (Fab) from the bactericidal monoclonal antibody LPT3-1 specific to lipooligosaccharide (LOS) inner cores from Neisseria meningitidis has been solved in complex with an eight-sugar inner core fragment NmL3 galE lpt3 KOH to 2.69 Å resolution. The epitope is centered about an inner core N-acetylglucosamine residue unique to N. meningitidis and does not include the lipid A moiety, which is disordered in the structure, but is positioned to allow the binding of free and membrane-anchored full-length LOS. All the amino acid residues that contact antigen are of germline origin but, remarkably, two consecutive somatic mutations of serine to glycine in the heavy chain at residues 52 and 52a are positioned to deprive the antibody of advantageous interactions and so weaken binding. However, these mutations are key to allowing selective cross-reactivity with the HepII-3-PEtn inner core variant expressed by 70% of strains. Neisseria meningitidis is a leading cause of disease in the developed world and is especially dangerous to children, who lack the necessary protective antibodies. The structure of Fab LPT3-1 in complex with LOS provides insight into the antibody's selective ability to recognize multiple clinically relevant variations of the LOS inner core from N. meningitidis.

In vivo neutralization of α-cobratoxin with high-affinity llama single-domain antibodies (VHHs) and a VHH-Fc antibody.

Small recombinant antibody fragments (e.g. scFvs and VHHs), which are highly tissue permeable, are being investigated for antivenom production as conventional antivenoms consisting of IgG or F(ab')2 antibody fragments do not effectively neutralize venom toxins located in deep tissues. However, antivenoms composed entirely of small antibody fragments may have poor therapeutic efficacy due to their short serum half-lives. To increase serum persistence and maintain tissue penetration, we prepared low and high molecular mass antivenom antibodies. Four llama VHHs were isolated from an immune VHH-displayed phage library and were shown to have high affinity, in the low nM range, for α-cobratoxin (α-Cbtx), the most lethal component of Naja kaouthia venom. Subsequently, our highest affinity VHH (C2) was fused to a human Fc fragment to create a VHH2-Fc antibody that would offer prolonged serum persistence. After in planta (Nicotiana benthamiana) expression and purification, we show that our VHH2-Fc antibody retained high affinity binding to α-Cbtx. Mouse α-Cbtx challenge studies showed that our highest affinity VHHs (C2 and C20) and the VHH2-Fc antibody effectively neutralized lethality induced by α-Cbtx at an antibody:toxin molar ratio as low as ca. 0.75×:1. Further research towards the development of an antivenom therapeutic involving these anti-α-Cbtx VHHs and VHH2-Fc antibody molecules should involve testing them as a combination, to determine whether they maintain tissue penetration capability and low immunogenicity, and whether they exhibit improved serum persistence and therapeutic efficacy.

Measuring tongue shapes and positions with ultrasound imaging: a validation experiment using an articulatory model.

OBJECTIVE: The goal of this paper is to assess the validity of various metrics developed to characterize tongue shapes and positions collected through ultrasound imaging in experimental setups where the probe is not constrained relative to the subject's head. PATIENTS AND METHODS: Midsagittal contours were generated using an articulatory-acoustic model of the vocal tract. Sections of the tongue were extracted to simulate ultrasound imaging. Various transformations were applied to the tongue contours in order to simulate ultrasound probe displacements: vertical displacement, horizontal displacement, and rotation. The proposed data analysis method reshapes tongue contours into triangles and then extracts measures of angles, x and y coordinates of the highest point of the tongue, curvature degree, and curvature position. RESULTS: Parameters related to the absolute tongue position (tongue height and front/back position) are more sensitive to horizontal and vertical displacements of the probe, whereas parameters related to tongue curvature are less sensitive to such displacements. CONCLUSION: Because of their robustness to probe displacements, parameters related to tongue shape (especially curvature) are particularly well suited to cases where the transducer is not constrained relative to the head (studies with clinical populations or children).

Articulatory and acoustic adaptation to palatal perturbation.

Previous work has established that speakers have difficulty making rapid compensatory adjustments in consonant production (especially in fricatives) for structural perturbations of the vocal tract induced by artificial palates with thicker-than-normal alveolar regions. The present study used electromagnetic articulography and simultaneous acoustic recordings to estimate tongue configurations during production of [s s t k] in the presence of a thin and a thick palate, before and after a practice period. Ten native speakers of English participated in the study. In keeping with previous acoustic studies, fricatives were more affected by the palate than were the stops. The thick palate lowered the center of gravity and the jaw was lower and the tongue moved further backwards and downwards. Center of gravity measures revealed complete adaptation after training, and with practice, subjects' decreased interlabial distance. The fact that adaptation effects were found for [k], which are produced with an articulatory gesture not directly impeded by the palatal perturbation, suggests a more global sensorimotor recalibration that extends beyond the specific articulatory target.

Selection of single chain variable fragment (scFv) antibodies from a hyperimmunized phage display library for the detection of the antibiotic monensin.

Concerns over the occurrence of the veterinary antibiotic monensin (MW 671Da) in animal food products and water have given rise to the need for a sensitive and rapid detection method. In this study, four monensin-specific single chain variable fragments (scFvs) were isolated from a hyperimmunized phage-displayed library originating from splenocytes of a mouse immunized with monensin conjugated to bovine serum albumin (BSA). The coding sequences of the scFvs were engineered in the order 5'-V(L)-linker-V(H)-3', where the linker encodes for Gly(10)Ser(7)Arg. Three rounds of selection were performed against monensin conjugated to chicken ovalbumin (OVA) and keyhole limpet hemocyanin (KLH), alternately. In the third round of selection, two different strategies, which differed in the number of washes and the concentration of the coating conjugates, were used to select for specific binders to monensin. A total of 376 clones from round two and three were screened for their specific binding to monensin conjugates and positive clones were sequenced. It was found that 80% of clones from round three contained a stop codon. After removing the stop codon by site-directed mutagenesis, ten binders with different amino acid sequences were subcloned into the vector pMED2 for soluble expression in Escherichia coli HB2151. Four of these scFvs bound to free monensin as determined using competitive fluorescence polarization assays (C-FPs). IC(50) values ranged from 0.031 and 231 microM. A cross-reactivity assay against salinomycin, lasalocid A, kanamycin and ampicillin revealed that the two best binders were highly specific to monensin.