Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins.

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic datasets, we identified lysosomal leucine aminopeptidase (LyLAP; formerly phospholipase B domain-containing 1) as the hydrolase most tightly associated with elevated endocytosis. Untargeted metabolomics and biochemical reconstitution demonstrated that LyLAP is a processive monoaminopeptidase with preference for amino-terminal leucine. This activity was necessary and sufficient for the breakdown of hydrophobic transmembrane domains. LyLAP was up-regulated in pancreatic ductal adenocarcinoma (PDA), which relies on macropinocytosis for nutrient uptake. In PDA cells, LyLAP ablation led to the buildup of undigested hydrophobic peptides, lysosomal membrane damage, and growth inhibition. Thus, LyLAP enables lysosomal degradation of membrane proteins and protects lysosomal integrity in highly endocytic cancer cells

Gliding Arc Plasma Synthesis of MnO2 Nanomaterials for Catalytic Oxidation of Benzene: Effect of Plasmagenic Gas

MnO2 nanostructures were successfully synthesized via the reduction of KMnO4 solutions using the gliding arc plasma (Plasma Glidarc) approach. Here, we highlight the effect of different plasmagenic gases, such as moist air (atmospheric air), dry air, nitrogen (N2) or oxygen (O2). The obtained materials were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), nitrogen physisorption and scanning electron microscopy (SEM). The crystalline structures of obtained MnO2 polymorphs are mainly γ-MnO2 and α-MnO2, regardless of the feeding gas. The main reactive species, in addition to nitrogenous species like NO· radical generated with moist air, dry air or N2 gas, other oxygenated species such as H2O2 (E°(O2/H2O2) = 0.69 V) are produced with O2 able to reduce KMnO4 solution (E°(KMnO4/MnO2) = 1.70 V). Helium gas did not allow for the plasma reduction of the KMnO4 solution, even after 60 min of exposure. Furthermore, gas humidification did not significantly affect the precipitation time or the properties of plasma-synthesized MnO2. Atmospheric humidified air appears to be the best plasmagenic gas, as it allows for a shorter synthesis time and leads to a large specific surface area. All plasma-synthesized MnO2 showed good activity during the catalytic oxidation of benzene. The use of different MnO2 polymorphs (α-, δ- and γ-MnO2) showed that, in addition to the specific surface area, the crystalline structure significantly affects the catalytic oxidation of benzene. K+ species inserted within the MnO2 structure allow for their stability during the catalytic process. This work highlights the possibility to use different plasmagenic gases to prepare MnO2 nanostructures through plasma glidarc for the catalytic oxidation of benzene

Hormonal disruption from plastic ingestion in northern fulmars: Activation and inhibition of estrogen receptors

Plastic pollution is of global concern, yet documented harmful effects from plastic ingestion in wild species is limited. Procellariiformes, such as northern fulmars (Fulmarus glacialis, fulmar), have high levels of plastic ingestion, and we investigated their potential hormonal disruption. As human estrogen receptors (ERs) are commonly used to assess risk of hormonal disruption for wild species, we first compared human and fulmar ER responses to plastic-associated chemicals using a luciferase-reporter gene assay. ERs from both species were activated by bisphenol-A (BPA), bisphenol-S (BPS), 4-octylphenol (4-OP), and benzyl butyl phthalate (BBP), and inhibited by tetrabromobisphenol-A (TBBPA), 2,5,2',5'tetrachloro-biphenyl (PCB-52), and 2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138), although we observed species-specific differences in sensitivity. To assess if ingested plastic had the potential to alter fulmar hormone function, plastic recovered from fulmar stomachs (n = 27) were leached for 14 days with daily solvent renewal and leachates were exposed to fulmar ERs. Almost 50 % of the birds (13 out of 27) had ingested plastic that leached chemicals which caused ER activation and/or inhibition on day 1, with ∼70 % of these (9 out of 13) also showing a response on day 5 and/or 14. The polymer composition of the recovered plastic pieces (n = 142) was identified with infrared spectroscopy. Polyethylene (PE) (60 %) was the most abundant polymer, followed by polypropylene (PP) (35 %), polyethylene terephthalate (PET) (3 %) and unidentifiable (2 %). Polymer type was not associated with ER response, suggesting that chemical additives, not polymer composition, were responsible for the observed hormonal disruption. To our knowledge, we provide the first data on a seabird's ER response to plastic-associated chemicals. Overall, we highlight the potential for plastic ingestion to disrupt fulmar hormone function, providing important information about the harmful effects of plastic pollution

Nephrotoxicity and Modern Volatile Anesthetics: A Narrative Review.

Volatile anesthetics, while increasingly utilized in intensive care medicine, are associated with significant renal adverse effects. A critical safety concern-particularly with sevoflurane-involves its potential impact on renal function. Pathophysiologically, inorganic fluoride levels exceeding 50 µmol/L are recognized as a threshold for nephrogenic diabetes insipidus, a condition generally considered reversible. Additionally, the sevoflurane degradation product "compound A" has been implicated in direct renal tubular and glomerular toxicity. Specifically, exposure has been correlated with glomerular damage, evidenced by albuminuria, as well as injury to both proximal and distal tubules, indicated by elevated levels of α-glutathione-S-transferase. Postprandial glycosuria may also be observed. Unlike nephrogenic diabetes insipidus, the structural damage induced by compound A may result in irreversible renal impairment

Classes cléricales et prohibitions musicales chez les chanoines réguliers de San Salvatore. Une lecture politique (Italie, XVe-XVIe siècles)

Prolongeant le fameux dilemme augustinien qui reconnaissait dans le chant liturgique la source d’une jouissance suspecte autant qu’un accès à l’intelligence du verbe –, les traditions régulières ont souvent oscillé entre la prohibition et la tolérance des pratiques musicales conventuelles. Tandis que la seconde option a, logiquement, largement retenu l’attention des musicologues, la première n’a été observée que marginalement, essentiellement sous l’angle du conservatisme culturel ou de l’iconoclasme sonore. Pourtant, la prohibition musicale en contexte religieux est un phénomène dont les enjeux dépassent de loin les seules questions morales et esthétiques. Tandis que les motivations réglementaires sont habituellement occultées par des structures conventuelles monolithiques et strictement verticales, il est possible d’en déceler la trace dans des ordres dont le régime de gouvernance implique une certaine diversification des acteurs. Fondée à l’aube du XVe siècle au paroxysme des remous schismatiques, la congrégation des chanoines réguliers de San Salvatore est à cet égard exemplaire. De fait, répondant à la nécessité de forger un clergé fidèle à une obédience romaine alors défaillante, celle-ci se distingue par un régime conçu pour éviter toute prise de pouvoir individuel. Inspiré du modèle athénien (ou florentin), il implique ainsi la suppression des vœux de stabilité, la rotation des charges et une gouvernance combinant élection aristocratique et tirage au sort démocratique. En exploitant les interstices ouverts par l’hétérogénéité des individus impliqués dans ce système – réglementations contradictoires ou abandonnées, groupes cléricaux hiérarchisés, etc. –, cette communication tâchera d’interpréter la portée des décisions capitulaires concernant les prohibitions et régulations musicales

Unique transcriptomic responses of rat and human alveolar macrophages in an in vitro model of overload with TiO and carbon black.

Chronic inhalation of titanium dioxide or carbon black can lead, at high exposure, to lung overload, and can induce chronic inflammation and lung cancer in rats. Whether this rat adverse response is predictive for humans has been questioned for more than 40 years. Currently, these particles are conservatively considered as possible human carcinogens. To clarify the mechanisms of the adverse rat response to lung overload and its human relevance. Primary rat and human alveolar macrophages were exposed in vitro to control, non-overload or overload doses of titanium dioxide (P25) or carbon black (Printex 90) particles, and their activation profile was examined by untargeted transcriptomics. Rat macrophages were largely the most responsive to particle overload. In particular, eighteen genes were identified as robust markers of P25 and Printex 90 overload in rat cells. The known functions of these genes can be related to the potential mechanisms of the adverse outcomes recorded in rats in vivo. Most of these 18 genes were similarly modulated in human macrophages, but with a markedly lower magnitude. In addition, a 16 gene signature was observed upon overload in human macrophages, but not in rat macrophages. These findings provide insights into the mechanisms of lung overload and inflammation in rats, and highlight similarities and differences in transcriptomic responses of rat and human alveolar macrophages

preliminary investigations of a design framework for low-to-midrise buildings with robotically shaped whole timber structural elements with low-to-no steel joints

Following an exhaustive evaluation of the limitations of whole-timber carpentry connections in low-to­midrise buildings, recommendations therein have been extrapolated and applied to a small preliminary study of four beam-to-column connection details. These connections included two steel-free and two steel-minimised connections, each with compressive reinforcement. To understand the potential of each connection, fabrication trials and observational assembly tests were conducted. The complications of fabrication were workshopped across all stakeholders, and preliminary moment-rotation, pull-out, and gravity load observations were conducted to better understand how the fabrication frameworks and joint designs could be improved. The observations highlighted key successes as well as weaknesses in the design, fabrication, and construction methodologies, which were rectified. One connection that resulted from this revision is based on traditional interlocking dovetail mortise-tenon carpentry designs and the second is a blend of traditional mortise-tenon and contemporary connections with internal steel fasteners. The preliminary design and fabrications methods, as well as consequential changes, are discussed to provide a better understanding of the applications and limitations of natural-form structural elements and low-to-no steel beam-to-column joints in practice. The final connection designs and preliminary design framework is presented and upcoming sequential research is summarised