Miracle-dz/UniFAR-FTUs huggingface dataset:
Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

Bone healing in tooth extraction sockets occurs in a complex environment containing saliva and many microorganisms and is affected by many factors. Endoplasmic reticulum (ER) stress affects bone metabolism, but the role of ER stress in bone healing after tooth extraction remains unclear. We utilized a rat tooth extraction model, in which we promoted wound healing by using salubrinal to regulate the ER stress response. Western blot analysis showed increased expression of p‐eIF2α/eIF2α, Runx2 and alkaline phosphatase (ALP) in bone tissue, and histological assays showed irregularly arranged and new bone with more collagen fibres 14 days after tooth extraction and after modulating the degree of ER stress. Micro‐CT showed that modulating ER stress to an appropriate degree increases bone filling in regards to the density in the bottom and the surrounding bone wall of the tooth extraction wounds. Transmission electron microscopy showed rough ER expansion and newly formed collagen fibrils in osteoblasts after modulating ER stress to an appropriate degree. We also used different concentrations of salubrinal to evaluate the resistance to tunicamycin‐induced ER stress in an osteogenic induction environment. Salubrinal restored the tunicamycin‐induced decrease in the viability of primary calvarial osteoblasts and increased the expression of Runx2 and ALP, and decreased p‐eIF2α/eIF2α in a dose‐dependent manner. Taken together, the results demonstrate that ER stress occurred after tooth extraction, and regulating the degree of ER stress can promote bone healing in tooth extraction sockets, providing clinical evidence for bone healing.
KrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice

Somatic KRAS mutations are highly prevalent in many cancers. In addition, a distinct spectrum of germline KRAS mutations causes developmental disorders called RASopathies. The mutant proteins encoded by these germline KRAS mutations are less biochemically and functionally activated than those in cancer. We generated mice harboring conditional KrasLSL-P34Rand KrasLSL-T58I knock-in alleles and characterized the consequences of each mutation in vivo. Embryonic expression of KrasT58I resulted in craniofacial abnormalities reminiscent of those seen in RASopathy disorders, and these mice exhibited hyperplastic growth of multiple organs, modest alterations in cardiac valvulogenesis, myocardial hypertrophy, and myeloproliferation. By contrast, embryonic KrasP34R expression resulted in early perinatal lethality from respiratory failure due to defective lung sacculation, which was associated with aberrant ERK activity in lung epithelial cells. Somatic Mx1-Cre–mediated activation in the hematopoietic compartment showed that KrasP34R and KrasT58I expression had distinct signaling effects, despite causing a similar spectrum of hematologic diseases. These potentially novel strains are robust models for investigating the consequences of expressing endogenous levels of hyperactive K-Ras in different developing and adult tissues, for comparing how oncogenic and germline K-Ras proteins perturb signaling networks and cell fate decisions, and for performing preclinical therapeutic trials.
Scale for maternity role perceptions

Abstract The purpose of this study was to develop and test the psychometric properties of the Maternal Role Perception Scale, a measure of motherhood, based on the perceptions of women. The 5-point Likert draft scale with 61 items was used. The data of 610 mothers were analyzed in the study. In the validity–reliability analysis of the scale, exploratory factor analysis and Cronbach’s alpha coefficients were used. As a result of the factor analysis, the scale consists of 28 items and two factors explaining 55.741% of the total variance. The internal consistency coefficient (Cronbach’s alpha) of the scale was calculated as 0.952. The Maternity Role Perception Scale (MRPS) is a reliable and valid scale developed for Turkish women. Maternal role is affected by physical, psychological, social status and the life of the woman. It is recommended to apply MRPS on different samples.
Exploring the Reversibility of Phase Transformations in Aluminum Anodes through Operando Light Microscopy and Stress Analysis.

Aluminum is well-known to possess attractive properties for possible use as an anode material in Li-ion batteries (LIBs), but effort is still needed to understand how and why it degrades. Herein, we pursue investigations of the delithiation and the re-lithiation processes in Al thin films using an established operando light microscopic platform. Operando videos highlight that the extraction of Li from the β phase (LiAl) is accompanied by fracture and crack formation leading to the detachment of the α phase (Al) from the rest of the electrode. The evolution of mechanical stress in Al thin film electrodes is tracked and shows severe stress asymmetry as phase transformations progress. Combining with the observations from light and electron microscopy, the mechanical stress during dealloying can be explained by Li solubility with the β phase, formation of cracks and of a highly porous Al nanostructure. Although the results pave a difficult path for utilization of the Al/LiAl/Al (α/β/α) phase transformations in future LIBs, they also suggest excellent opportunities when structural changes can be prevented, which otherwise impact the stability of Al-based electrodes.
Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells

Podoplanin and CD44 are transmembrane glycoproteins involved in inflammation and cancer. In this paper, we report that podoplanin is coordinately expressed with the CD44 standard (CD44s) and variant (CD44v) isoforms in vivo—in hyperplastic skin after a pro-inflammatory stimulus with 12-O-tetradecanoylphorbol-13-acetate (TPA)—and in vitro—in cell lines representative of different stages of mouse-skin chemical carcinogenesis, as well as in human squamous carcinoma cell (SCC) lines. Moreover, we identify CD44v10 in the mouse-skin carcinogenesis model as the only CD44 variant isoform expressed in highly aggressive spindle carcinoma cell lines together with CD44s and podoplanin. We also characterized CD44v3-10, CD44v6-10 and CD44v8-10 as the major variant isoforms co-expressed with CD44s and podoplanin in human SCC cell lines. Immunofluorescence confocal microscopy experiments show that these CD44v isoforms colocalize with podoplanin at plasma membrane protrusions and cell–cell contacts of SCC cells, as previously reported for CD44s. Furthermore, CD44v isoforms colocalize with podoplanin in chemically induced mouse-skin SCCs in vivo. Co-immunoprecipitation experiments indicate that podoplanin physically binds to CD44v3-10, CD44v6-10 and CD44v8-10 isoforms, as well as to CD44s. Podoplanin–CD44 interaction is mediated by the transmembrane and cytosolic regions and is negatively modulated by glycosylation of the extracellular domain. These results point to a functional interplay of podoplanin with both CD44v and CD44s isoforms in SCCs and give insight into the regulation of the podoplanin–CD44 association.
Minoxidil Cannot Be Used To Target Lysyl Hydroxylases during Postnatal Mouse Lung Development: A Cautionary Note

The lysyl hydroxylases (procollagen-lysine 5-dioxygenases) PLOD1, PLOD2, and PLOD3 have been proposed as pathogenic mediators of stunted lung development in bronchopulmonary dysplasia (BPD), a common complication of preterm birth. In affected infants, pulmonary oxygen toxicity stunts lung development. Mice lacking Plod1 exhibit 15% mortality, and mice lacking Plod2 or Plod3 exhibit embryonic lethality. Therefore, to address any pathogenic role of lysyl hydroxylases in stunted lung development associated with BPD, minoxidil was administered to newborn mice in an oxygen toxicity–based BPD animal model. Minoxidil, which has attracted much interest in the management of systemic hypertension and androgenetic alopecia, can also be used to reduce lysyl hydroxylase activity in cultured cells. An in vivo pilot dosing study established 50 mg⋅kg−1⋅day−1 as the maximum possible minoxidil dose for intraperitoneal administration in newborn mouse pups. When administered at 50 mg⋅kg−1⋅day−1 to newborn mouse pups, minoxidil was detected in the lungs but did not impact lysine hydroxylation, collagen crosslinking, or lysyl hydroxylase expression in the lungs. Consistent with no impact on mouse lung extracellular matrix structures, minoxidil administration did not alter the course of normal or stunted lung development in newborn mice. At doses of up to 50 mg⋅kg⋅day−1, pharmacologically active concentrations of minoxidil were not achieved in neonatal mouse lung tissue; thus, minoxidil cannot be used to attenuate lysyl hydroxylase expression or activity during mouse lung development. These data also highlight the need for new and specific lysyl hydroxylase inhibitors. SIGNIFICANCE STATEMENT Extracellular matrix crosslinking is mediated by lysyl hydroxylases, which generate hydroxylated lysyl residues in procollagen peptides. Deregulated collagen crosslinking is a pathogenic component of a spectrum of diseases, and thus, there is interest in validating lysyl hydroxylases as pathogenic mediators of disease and potential “druggable” targets. Minoxidil, administered at the maximum possible dose, did not inhibit lysyl hydroxylation in newborn mouse lungs, suggesting that minoxidil was unlikely to be of use in studies that pharmacologically target lysyl hydroxylation in vivo.
Finite element simulation of head impacts in mixed martial arts

Abstract Thirteen MMA athletes were fitted with the MiG2.0 Stanford instrumented mouthguard. 451 video confirmed impacts were recoded during sparring sessions and competitive events. The competitive events resulted in five concussions. The impact with the highest angular acceleration from each event was simulated using the GHBMC head model. Average strain in the corpus callosum of concussed fighters was 0.27, which was 87.9% higher than uninjured fighters and was the best strain indicator of concussion. The best overall predictor of concussion found in this study was shear stress in the corpus callosum which differed by 111.4% between concussed and uninjured athletes.
Neurturin regulates the lung-resident macrophage inflammatory response to viral infection

The neurotrophic factor RET is induced in lung macrophages by viral triggers and activation via its ligand neurturin regulates matrix proteins and cytokines that shape the inflammatory response. Lung-resident macrophages are crucial to the maintenance of health and in the defence against lower respiratory tract infections. Macrophages adapt to local environmental cues that drive their appropriate function; however, this is often dysregulated in many inflammatory lung pathologies. In mucosal tissues, neuro-immune interactions enable quick and efficient inflammatory responses to pathogenic threats. Although a number of factors that influence the antimicrobial response of lung macrophages are known, the role of neuronal factors is less well understood. Here, we show an intricate circuit involving the neurotrophic factor, neurturin (NRTN) on human lung macrophages that dampens pro-inflammatory cytokine release and modulates the type of matrix metalloproteinases produced in response to viral stimuli. This circuit involves type 1 interferon–induced up-regulation of RET that when combined with the glial cell line-derived neurotrophic factor (GDNF) receptor α2 (GFRα2) allows binding to epithelial-derived NRTN. Our research highlights a non-neuronal immunomodulatory role for NRTN and a novel process leading to a specific antimicrobial immune response by human lung-resident macrophages.
Resilient H∞ State Estimation for Discrete-Time Stochastic Delayed Memristive Neural Networks: A Dynamic Event-Triggered Mechanism

In this article, a resilient <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> approach is put forward to deal with the state estimation problem for a type of discrete-time delayed memristive neural networks (MNNs) subject to stochastic disturbances (SDs) and dynamic event-triggered mechanism (ETM). The dynamic ETM is utilized to mitigate unnecessary resource consumption occurring in the sensor-to-estimator communication channel. To guarantee resilience against possible realization errors, the estimator gain is permitted to undergo some norm-bounded parameter drifts. For the delayed MNNs, our aim is to devise an event-based resilient <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> estimator that not only resists gain variations and SDs but also ensures the exponential mean-square stability of the resulting estimation error system with a guaranteed disturbance attenuation level. By resorting to the stochastic analysis technique, sufficient conditions are acquired for the expected estimator and, subsequently, estimator gains are obtained via figuring out a convex optimization problem. The validity of the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> estimator is finally shown via a numerical example.
Small Fibre Involvement in Multifocal Motor Neuropathy Explored with Sudoscan: A Single-Centre Experience

Objective: Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy, clinically characterized by exclusive motor involvement. We wished to evaluate the possible presence of sensory dysfunction, including the evaluation of small fibres, after a long-term disease course. Patients and methods: seven MMN patients, regularly followed in our Neurology Department, underwent clinical evaluation, neurophysiological examination by nerve conduction studies (NCSs), and Sudoscan. We compared neurophysiological data with a group of patients with other disorders of the peripheral nervous system. Results: NCSs showed a reduction of sensory nerve action potential amplitude in 2/7 MMN patients. Sudoscan showed borderline electrochemical skin conductance (ESC) values in 3/7 MMN patients (two of them with abnormal sensory NCSs). Conclusions: Our results confirm that sensory involvement may be found in some MMN after a long-term disease course, and it could also involve the small fibres.
Advances in Multimodal Emotion Recognition Based on Brain–Computer Interfaces

With the continuous development of portable noninvasive human sensor technologies such as brain–computer interfaces (BCI), multimodal emotion recognition has attracted increasing attention in the area of affective computing. This paper primarily discusses the progress of research into multimodal emotion recognition based on BCI and reviews three types of multimodal affective BCI (aBCI): aBCI based on a combination of behavior and brain signals, aBCI based on various hybrid neurophysiology modalities and aBCI based on heterogeneous sensory stimuli. For each type of aBCI, we further review several representative multimodal aBCI systems, including their design principles, paradigms, algorithms, experimental results and corresponding advantages. Finally, we identify several important issues and research directions for multimodal emotion recognition based on BCI.
Shear Wave Generation by Remotely Stimulating Aluminum Patches With a Transient Magnetic Field and Its Preliminary Application in Elastography

<italic>Objective:</italic> This article presents shear wave generation by remotely stimulating aluminum patches through a transient magnetic field, and its preliminary application in the cross-correlation approach based ultrasound elastography. <italic>Methods:</italic> A transient magnetic field is employed to remotely vibrate the patch actuators through the Lorentz force. The origin, and the characteristics of the Lorentz force are confirmed using an interferometric laser probe. The shear wave displacement fields generated in the soft medium are studied through the ultrafast ultrasound imaging. The potential of the shear wave fields generated through the patch actuators for the cross-correlation approach based elastography is confirmed through experiments on an agar phantom sample. <italic>Results:</italic> Under a transient magnetic field of changing rate of 10.44 kT/s, the patch actuator generates a shear wave source of amplitude of 100 <inline-formula><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>m in a polyvinyl alcohol (PVA) phantom sample. The shear wave fields created by experiments agree qualitatively well with those by theory. From the shear wave velocity map computed from 100 frames of shear wave fields, the boundaries of cylindrical regions of different stiffness can be clearly recognized, which are completely concealed in the ultrasound image. <italic>Conclusion:</italic> Shear wave fields in the level of 100 <inline-formula><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>m can be remotely generated in soft medium through stimulating aluminum patches with a transient magnetic field, and qualitative shear wave velocity maps can be reconstructed from the shear wave fields generated. <italic>Significance:</italic> The proposed method allows potential application of the cross-correlation approach based elastography in intravascular-based or catheter-based cardiology.
ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping

The ProAlanase protease cleaves after proline and alanine residues in highly acidic conditions and provides efficient digestion of proline-rich proteins allowing for accurate phosphorylation site profiling. Because of its activity at low pH, it facilitates efficient disulfide bond mapping in monoclonal antibodies and is highly suitable for analysis of histone family members and their PTMs. The protease is complementary to trypsin and allows for increased protein sequence coverage and nearly complete de novo sequencing of exogenously expressed proteins when combined with trypsin. Graphical Abstract Highlights ProAlanase is a powerful protease for efficient low pH disulfide bond mapping. High suitability for analysis of histone family members and their PTMs. Accurate phosphorylation profiling in proline-rich proteins. Sequence coverage increase and full de novo sequencing in combination with trypsin. Trypsin is the protease of choice in bottom-up proteomics. However, its application can be limited by the amino acid composition of target proteins and the pH of the digestion solution. In this study we characterize ProAlanase, a protease from the fungus Aspergillus niger that cleaves primarily on the C-terminal side of proline and alanine residues. ProAlanase achieves high proteolytic activity and specificity when digestion is carried out at acidic pH (1.5) for relatively short (2 h) time periods. To elucidate the potential of ProAlanase in proteomics applications, we conducted a series of investigations comprising comparative multi-enzymatic profiling of a human cell line proteome, histone PTM analysis, ancient bone protein identification, phosphosite mapping and de novo sequencing of a proline-rich protein and disulfide bond mapping in mAb. The results demonstrate that ProAlanase is highly suitable for proteomics analysis of the arginine- and lysine-rich histones, enabling high sequence coverage of multiple histone family members. It also facilitates an efficient digestion of bone collagen thanks to the cleavage at the C terminus of hydroxyproline which is highly prevalent in collagen. This allows to identify complementary proteins in ProAlanase- and trypsin-digested ancient bone samples, as well as to increase sequence coverage of noncollagenous proteins. Moreover, digestion with ProAlanase improves protein sequence coverage and phosphosite localization for the proline-rich protein Notch3 intracellular domain (N3ICD). Furthermore, we achieve a nearly complete coverage of N3ICD protein by de novo sequencing using the combination of ProAlanase and tryptic peptides. Finally, we demonstrate that ProAlanase is efficient in disulfide bond mapping, showing high coverage of disulfide-containing regions in a nonreduced mAb.
Intramolecular Spodium Bonds in Zn(II) Complexes: Insights from Theory and Experiment

Two new dinuclear zinc(II) complexes, [Zn2(µ1,3-OAc)(L1)2]I·MeOH (1) and [Zn2(µ1,3-OAc)(L2)(NCS)] (2), (where HL1 = 2-(((3-(dimethylamino)propyl)amino)methyl)-6-methoxy-phenol and H2L2 = 2,2′-[(1-Methyl-1,2-ethanediyl)bis(iminomethylene)]bis[6-ethoxyphenol]) have been synthesized and characterized by elemental and spectral analysis. Their X-ray solid state structures have been determined, revealing the existence of intramolecular Zn···O spodium bonds in both complexes due to the presence of methoxy (1) or ethoxy (2) substituents adjacent to the coordinated phenolic O-atom. These noncovalent interactions have been studied using density functional theory (DFT) calculations, the quantum theory of “atoms-in-molecules” and the noncovalent interaction plot. Moreover, a search in the Cambridge structure database (CSD) has been conducted in order to investigate the prevalence of intramolecular spodium bonds in Zn complexes. To our knowledge this is the first investigation dealing with intramolecular spodium bonds.
A HY5-COL3-COL13 regulatory chain for controlling hypocotyl elongation in Arabidopsis.

CONSTANS-LIKE (COL) family members are commonly implicated in light signal transduction during early photomorphogenesis. However, some of their functions remain unclear. Here, we propose a role for COL13 in hypocotyl elongation in Arabidopsis thaliana. We found that COL13 RNA accumulates at high levels in hypocotyls and that a disruption in the COL13 function via a T-DNA insertion or RNAi led to the formation of longer hypocotyls of Arabidopsis seedlings under red light. On the contrary, overexpression of COL13 resulted in the formation of shorter hypocotyls. Using various genetic, genomic, and biochemical assays, we proved that another COL protein, COL3, directly binds to the promoter of COL13, and the promoter region of COL3 was targeted by the transcription factor LONG HYPOCOTYL 5 (HY5), to form an HY5-COL3-COL13 regulatory chain for regulating hypocotyl elongation under red light. Additionally, further study demonstrated that COL13 interacts with COL3, and COL13 promotes the interaction between COL3 and CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), suggesting a possible COP1-dependent COL3-COL13 feedback pathway. Our results provide new information regarding the gene network in mediating hypocotyl elongation. This article is protected by copyright. All rights reserved.
The impact of extreme skull morphology in domestic dogs on cribriform plate shape

Dog owners are often impressed by their dog's sense of smell. Many of these dogs, however, have skulls that are quite altered from those of their closest canid relatives. Housed within these skulls are essential olfactory structures like the cribriform plate that play a role in olfaction and the transmission of olfactory nerve impulses to the olfactory bulb of the brain. With improvements in CT technology and accessibility, we are now able to digitally reconstruct in 3D cribriform plate morphology and study its variation within and among species. In this study, we CT scanned the skulls of 95 dog specimens from 45 different domestic dog breeds and 12 species of wild canid and compared the shape of the cribriform plate among three main groups: domestic dog breeds, wolf‐like canids, and fox‐like canids. Despite only recent selective pressure for extreme skull morphology, domestic dogs display much more variation in cribriform plate shape than wild canids, indicating that cribriform plate shape is plastic and linked to skull shape. Intense artificial selection on domestic dog skull phenotype in the last 200 years has clear effects on secondary features of the domestic dog skull, implying that selection for overt phenotypes also can impact other anatomical features associated with the skull, like the cribriform plate.