Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism

Degradability of cross-linked polyurethanes based on synthetic polyhydroxybutyrate and modified with polylactide

In many areas of application of conventional non-degradable cross-linked polyurethanes (PUR), there is a need for their degradation under the influence of specific environmental factors. It is practiced by incorporation of sensitive to degradation compounds (usually of natural origin) into the polyurethane structure, or by mixing them with polyurethanes. Cross-linked polyurethanes (with 10 and 30%wt amount of synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments) and their physical blends with poly([d,l]-lactide) (PDLLA) were investigated and then degraded under hydrolytic (phosphate buffer solution) and oxidative (CoCl2/H2O2) conditions. The rate of degradation was monitored by changes of samples mass, morphology of surface and their thermal properties. Despite the small weight losses of samples, the changes of thermal properties of polymers and topography of their surface indicated that they were susceptible to gradual degradation under oxidative and hydrolytic conditions. Blends of PDLLA and polyurethane with 30 wt% of R,S-PHB in soft segments and PUR/PDLLA blends absorbed more water and degraded faster than polyurethane with low amount of R,S-PHB

Biodegradable Copolymers Obtained by Solution Polymerization

This study aims the synthesis of copolymers of poly (l-lactic acid) and polycaprolactone by ring opening polymerization. The reactions between l-lactide (LLA) and ε-caprolactone (CL) monomers, in 100/0, 95/5, 90/10 and 80/20 LLA/CL mass ratios, were conducted in refluxing toluene, using Stannous octoate as iniciator, methanol as co-iniciator and inert atmosphere (N2). The reaction medium was maintained under stirring at 120 °C for 24 hours. The samples were characterized by carbon-13 and proton nuclear magnetic resonance (C13-NMR and H1-NMR), and gel permeation chromatography (GPC). Monomers were characterized by thermogravimetry (TG). Copolymers were formed only in samples containing 20 wt% ε-caprolactone. NMR spectra of the other samples showed no evidence of CL units. This fact may be associated with the low-temperature volatilization of monomers. The GPC analysis showed that the increase of CL concentration decrease the molecular weight of copolymers

Curved membrane structures induced by native lipids in giant vesicles

Native lipids in cell-membrane support crucial functions like intercell communication via their ability to deform into curved membrane structures. Cell membrane mimicking Giant unilamellar vesicles (GUV) is imperative in understanding native lipid's role in membrane transformation however remains challenging to assemble. We construct two giant vesicle models mimicking bacterial inner-membrane (IM) and outer-membrane (OM) under physiological conditions using single-step gel-assisted lipid swelling. IM vesicles composed of native bacterial lipids undergo small-scale membrane remodeling into bud and short-nanotube structures. In contrast, OM vesicles asymmetrically assembled from Lipopolysaccharide (LPS) and bacterial lipids underwent global membrane deformation under controlled osmotic stress. Remarkably, highly-curved structures mimicking cell-membrane architectures, including daughter vesicle networks interconnected by necks and nano-tubes ranging from micro to nanoscale, are generated in OM vesicles at osmotic stress comparable to that applied in IM vesicles. Further, we provide a quantitative description of the membrane structures by experimentally determining membrane elastic parameters, i.e., neck curvature and bending rigidity. We can conclude that a larger spontaneous curvature estimated from the neck curvature and softer membranes in OM vesicles is responsible for large-scale deformation compared to IM vesicles. Our findings will help comprehend the shape dynamics of complex native bacterial lipid membranes

Application of a new xylanase activity from Bacillus amyloliquefaciens XR44A in brewer's spent grain saccharification

Cellulases and xylanases are the key enzymes involved in the conversion of lignocelluloses into fermentable sugars. Western Ghat region (India) has been recognized as an active hot spot for the isolation of new microorganisms. The aim of this work was to isolate new microorganisms producing cellulases and xylanases to be applied in brewer's spent grain saccharification

Hydrogel formation by the 'topological conversion' of cyclic PLA-PEO block copolymers

An amphiphilic cyclic block copolymer consisting of poly(L- or D-lactide) and poly(ethylene oxide), that is, PLLA-PEO or PDLA-PEO, was synthesized from its corresponding linear triblock precursor, PLLA-PEO-PLLA or PDLA-PEO-PDLA, respectively, with alkenyl end groups. A mixture of the micellar dispersions of linear PLLA-PEO-PLLA and linear PDLA-PEO-PDLA formed a gel upon heating, whereas a mixture of the cyclic counterparts did not undergo this phase transition. These results suggest that the gelation behavior is directed by the topology of the polymer components. Furthermore, cyclic PLLA-PEO and cyclic PDLA-PEO block copolymers incorporating photocleavable o-nitrobenzyl units were synthesized. A mixture of the micellar dispersions of these block copolymers formed a gel upon ultraviolet irradiation via the 'topological conversion'