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Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicate in IGROV-1 but no longer in Vero E6 and are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals are markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhances NAb responses against both XBB and BA.2.86 variants. JN.1 displays lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.

In the energy production and transportation industries, numerous metallic structures may be subjected to at least several billions of cycles, i.e. loaded in the very high cycle fatigue domain (VHCF). Therefore, to design structures in the VHCF domain, a reliable methodology is necessary. One useful quantity to characterize plastic activity at the microscopic scale and fatigue damage evolution is the mechanical work supplied to a material. However, the estimation of this mechanical work in a metal during ultrasonic fatigue tests remains challenging. This paper aims to present an innovative methodology to quantify this. An experimental procedure was developed to estimate the mechanical work from stress and total strain evolution measurements during one loading cycle with a time accuracy of about 50 ns. This was achieved by conducting time-resolved X-ray diffraction coupled to strain gauge measurements at a synchrotron facility working in pulsed mode (single-bunch mode).

In the presence of molecular oxygen, edible oils can be oxidized to form a multitude of α,β-unsaturated carbonyl products collectively called 'lipid-derived electrophiles'. These molecules affect the taste of fat-containing foods but also act as electrophiles by covalently binding to protein amines/thiols and DNA nucleotides. The chemical modification of proteins by lipid-derived electrophiles appears to play an important role in human health, but the quantification of this diverse class of compounds remains a challenge. In this study, we describe a method capable of measuring the relative content of α,β-unsaturated carbonyls in food containing edible oils by using a "turn-on" fluorescent probe. The detection of electrophiles is based on a pre-fluorescent probe, 7-mercapto-4-methyl-coumarin (C-SH). The fluorescence of C-SH increases after nucleophilic addition to electrophilic lipid oxidation products. Since different lipid-derived electrophiles will react at a different rate with our fluorescent probe, we expressed the probe's response against a standard electrophile: trans-2-nonenal. In this assay, electrophiles which react more quickly will have a more dominant weight in the measurements carried out. Using this analytical technique, we can compare electrophilic content in French fries from several restaurants, and find they have lower amounts of lipid-derived electrophiles versus frozen fries baked at home. We also demonstrate that potato chips sealed in a reduced oxygen atmosphere will have a low 'electrophilic content' that increases over time, whereas chips in oxygen-permeable packaging initially have a higher 'electrophilic content' that does not increase as much over time. The relative ease of fluorescence measurements using microplate readers coupled with a simple oil extraction protocol should allow this method to quantify 'electrophilic content' in several food sources. [ABSTRACT FROM AUTHOR]

Summary: Hearing depends on fast and sustained calcium-dependent synaptic vesicle fusion at the ribbon synapses of cochlear inner hair cells (IHCs). The implication of the canonical neuronal SNARE complex in this exocytotic process has so far remained controversial. We investigated the role of SNAP-25, a key component of this complex, in hearing, by generating and analyzing a conditional knockout mouse model allowing a targeted postnatal deletion of Snap-25 in IHCs. Mice subjected to IHC Snap-25 inactivation after hearing onset developed severe to profound deafness because of defective IHC exocytosis followed by ribbon degeneration and IHC loss. Viral transfer of Snap-25 in these mutant mice rescued their hearing function by restoring IHC exocytosis and preventing synapses and hair cells from degeneration. These results demonstrate that SNAP-25 is essential for normal hearing function, most likely by ensuring IHC exocytosis and ribbon synapse maintenance.

SARS-CoV-2 infection damages the airways. Here the authors show that SARS-CoV-2 infection induces the rapid loss of airway motile cilia, resulting in altered cilia clearance function. Cilia loss is preceded by reduced expression of the ciliogenesis regulator Foxj1.

A key problem in the modeling of polyurethane (PU) foaming is the determination of relevant physical parameters for the viscosity, the gas expansion, and the curing rate. Indeed, it is difficult to measure the chemical kinetics parameters as well as the viscosity of industrial PU formulations (polyol-isocyanatewater mixture) because the time scales of gas production and PU crosslinking are very short and hardly compatible with the installation of the sample in characterization devices such as differential scanning calorimetry and parallel plates rheometer. A FOAMAT[R] system has been developed to get these experimental data but the relationship between measurements and the rheo-chemical parameters has not been clearly established. In this paper, an analytical model of the foaming process is developed in the cylindrical FOAMAT geometry, which allows identifying the parameters of the curing and gas production kinetics equations, as well as the viscosity. This analytical model is based on a set of simplifying hypotheses which validity is checked using the finite element computation software REM3D dedicated to foaming modeling and applicable for injection-molding processing. KEYWORDS foam, FOAMAT experiments, foaming and curing kinetics, modeling, polyurethane, rheology, 1 | INTRODUCTION Polyurethane (PU) foams are produced by mixing polyol, isocyanate, and a blowing agent such as water. Two main chemical reactions are in competition: isocyanate and water produce [...]

Introduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation, coordination of hair cell orientation with neighboring hair cells, and orientation around the striola in otolithic organs. Celsr1 is a PCP protein and a Celsr1 KO mouse model showed hair cell disorganization in all vestibular organs, especially in the canalar ampullae. The objective of this work was to assess to what extent the different vestibulo-ocular reflexes were impaired in Celsr1 KO mice.Methods: Vestibular function was analyzed using non-invasive video-oculography. Semicircular canal function was assessed during sinusoidal rotation and during angular velocity steps. Otolithic function (mainly utricular) was assessed during off-vertical axis rotation (OVAR) and during static and dynamic head tilts.Results: The vestibulo-ocular reflex of 10 Celsr1 KO and 10 control littermates was analyzed. All KO mice presented with spontaneous nystagmus or gaze instability in dark. Canalar function was reduced almost by half in KO mice. Compared to control mice, KO mice had reduced angular VOR gain in all tested frequencies (0.2–1.5 Hz), and abnormal phase at 0.2 and 0.5 Hz. Concerning horizontal steps, KO mice had reduced responses. Otolithic function was reduced by about a third in KO mice. Static ocular-counter roll gain and OVAR bias were both significantly reduced. These results demonstrate that canal- and otolith-dependent vestibulo-ocular reflexes are impaired in KO mice.Conclusion: The major ampullar disorganization led to an important reduction but not to a complete loss of angular coding capacities. Mildly disorganized otolithic hair cells were associated with a significant loss of otolith-dependent function. These results suggest that the highly organized polarization of otolithic hair cells is a critical factor for the accurate encoding of the head movement and that the loss of a small fraction of the otolithic hair cells in pathological conditions is likely to have major functional consequences. Altogether, these results shed light on how partial loss of vestibular information encoding, as often encountered in pathological situations, translates into functional deficits.

Background: The clinical presentation of SARS-CoV-2 infection was initially dominated by respiratory symptoms. However the clinical spectrum is wide and neuropsychiatric syndromes are also a source of medical concern. Our aims are to present an atypical clinical presentation of SARS-CoV-2 infection characterized by auditory hallucinations and unusual behavior and to emphasize the diversity of clinical manifestations of SARS-CoV-2 infection. Case Presentation: A 33-year-old woman was admitted to the emergency department (ED) with a one-day history of auditory hallucinations, unusual behavior, changes in her sleeping habits and incoherent speech. No other symptoms were reported. Blood examinations confirmed high elevated white cell count and C-reactive protein. The head CT scan was normal but the chest scan showed right ground-glass opacities in the lower zones. The oropharyngeal swab was positive for SARS-CoV-2. Based on these results, the diagnosis of SARS-CoV-2 infection was retained. The patient received no specific treatment for SARS-CoV-2 infection and only needed oxygen therapy support for 7 days. Additional dose of Olanzapine 10 mg daily was initially prescribed but the patient was back to her usual self on day 14 of hospital admission leading to its discontinuation. This clinical course was consistent with a first episode of psychosis triggered by SARS-CoV-2 infection. Conclusions: Neuroinflammation owing to SARS-CoV-2 infection could be responsible for a wide and unknown spectrum of neuropsychiatric manifestations. During this pandemic, special attention should be given to patients with no previous history of psychiatric disorders presenting to ED with neuropsychiatric syndromes of unknown etiology.

Abstract Defects of CIB2, calcium‐ and integrin‐binding protein 2, have been reported to cause isolated deafness, DFNB48 and Usher syndrome type‐IJ, characterized by congenital profound deafness, balance defects and blindness. We report here two new nonsense mutations (pGln12* and pTyr110*) in CIB2 patients displaying nonsyndromic profound hearing loss, with no evidence of vestibular or retinal dysfunction. Also, the generated CIB2−/− mice display an early onset profound deafness and have normal balance and retinal functions. In these mice, the mechanoelectrical transduction currents are totally abolished in the auditory hair cells, whilst they remain unchanged in the vestibular hair cells. The hair bundle morphological abnormalities of CIB2−/− mice, unlike those of mice defective for the other five known USH1 proteins, begin only after birth and lead to regression of the stereocilia and rapid hair‐cell death. This essential role of CIB2 in mechanotransduction and cell survival that, we show, is restricted to the cochlea, probably accounts for the presence in CIB2−/− mice and CIB2 patients, unlike in Usher syndrome, of isolated hearing loss without balance and vision deficits.

Aims To compare the long-term outcomes of deep anterior lamellar keratoplasty (DALK) with penetrating keratoplasty (PK) in keratoconus. Methods Retrospective comparative case series (228 DALKs and 274 PKs). A biphasic linear model was used to describe the postoperative outcome of the endothelial cell density (ECD). Visual acuity, specular microscopy, corneal topography and optical coherence tomography findings were recorded. Results Graft survival of the 502 keratoconus eyes was 96.7 at 10 years and 95.6% at 20 years. Visual acuity improved from 20/378±5.1 lines preoperatively to 20/32±2.1 lines at 30 months. The corneal ECD decreased from 2494±382 cells/mm2 to 1521±659 cells/mm2 at 10 years. The mean simulated keratometry increased from 44.88±2.54 D at 1 year to 46.60±3.0 D at 3 years. The mean follow-up was 103.4 months for DALKs and 106.1 months for PKs. The cumulated incidence of postoperative ocular hypertension requiring treatment was significantly higher in PKs than in DALKs. The early- and late-phase rates of ECD loss were significantly lower in DALKs than in PKs. These figures in DALKs were 50% of those observed in PKs. The simulated mean keratometry was significantly higher in DALKs than in PKs in the mid but not in the long term. No significant differences in visual acuity were observed between both groups. Manual dissection-DALK featured slower visual recovery than PK and big bubble-DALK, whereas big bubble-DALK and PK featured similar visual recovery. Conclusions DALK featuring higher endothelial survival and lower risk of postoperative ocular hypertension may be superior to PK when indicated for keratoconus. [ABSTRACT FROM AUTHOR]

Sound analysis by the cochlea relies on frequency tuning of mechanosensory hair cells along a tonotopic axis. To clarify the underlying biophysical mechanism, we have investigated the micromechanical properties of the hair cell’s mechanoreceptive hair bundle within the apical half of the rat cochlea. We studied both inner and outer hair cells, which send nervous signals to the brain and amplify cochlear vibrations, respectively. We find that tonotopy is associated with gradients of stiffness and resting mechanical tension, with steeper gradients for outer hair cells, emphasizing the division of labor between the two hair-cell types. We demonstrate that tension in the tip links that convey force to the mechano-electrical transduction channels increases at reduced Ca2+. Finally, we reveal gradients in stiffness and tension at the level of a single tip link. We conclude that mechanical gradients of the tip-link complex may help specify the characteristic frequency of the hair cell.

The microstructures induced by the laser-powder bed fusion (L-PBF) process have been widely investigated over the last decade, especially on austenitic stainless steels (AISI 316L) and nickel-based superalloys (Inconel 718, Inconel 625). However, the conditions required to initiate recrystallization of L-PBF samples at high temperatures require further investigation, especially regarding the physical origins of substructures (dislocation densities) induced by the L-PBF process. Indeed, the recrystallization widely depends on the specimen substructure, and in the case of the L-PBF process, the substructure is obtained during rapid solidification. In this paper, a comparison is presented between Inconel 625 specimens obtained with different laser-powder bed fusion (L-PBF) conditions. The effects of the energy density (VED) values on as-built and heat-under microstructures are also investigated. It is first shown that L-PBF specimens created with high-energy conditions recrystallize earlier due to a larger density of geometrically necessary dislocations. Moreover, it is shown that lower energy densities offers better tensile properties for as-built specimens. However, an appropriate heat treatment makes it possible to homogenize the tensile properties.

Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

Objectives Develop and validate a thorough exposure questionnaire to comprehensively explore crystalline silica (SiO2) exposure in the general population (gender-specific, occupational and non-occupational) and in patients with autoimmune diseases (rheumatoid arthritis (RA), systemic sclerosis (SSc)). Methods Lifetime exposures to SiO2 in occupational and non-occupational settings were assessed using a thorough exposure questionnaire. The questionnaire was applied to a general population panel (n  = 2911) sampled from the French rolling census, and to unselected patients with SSc (n  = 100) and RA (n  = 97). Global (GES), occupational (OES) and non-occupational (NOES) exposure scores were assessed in SSc and RA patients, and compared with up to four controls from the general population, matched by age group, sex and tobacco consumption. Results Patients had higher GES than their matched controls (SSc: P  = 0.001; RA: P  < 0.0001) due to higher OES (P  < 0.0001 for SSc and RA). Men had higher GES than women (SSc: P  < 0.0001; RA: P  = 0.002) due to higher OES (P  < 0.0001 for SSc and RA). The NOES did not differ between men and women. In SSc patients: Men had higher GES than controls (P  < 0.0001). Men and women with SSc had higher OES than controls (P  < 0.0001). In RA patients: GES and OES were higher in both men (P  = 0.00521; P  < 0.0001) and women (P  < 0.0001; P  < 0.0001) than in their respective controls. Women had higher NOES than controls (P  = 0.045). Conclusion The lifetime SiO2 exposure gap between RA and SSc patients and controls was substantially due to occupational exposure. In both diseases, men had higher exposure scores than women. [ABSTRACT FROM AUTHOR]