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A growth cone is a highly motile tip of an extending axon that is crucial for neural network formation. Three‐dimensional‐structured illumination microscopy, a type of super‐resolution light microscopy with a resolution that overcomes the optical diffraction limitation (ca. 200 nm) of conventional light microscopy, is well suited for studying the molecular dynamics of intracellular events. Using this technique, we discovered a novel type of filopodia distributed along the z‐axis (“z‐filopodia”) within the growth cone. Z‐filopodia were typically oriented in the direction of axon growth, not attached to the substratum, protruded spontaneously without microtubule invasion, and had a lifetime that was considerably shorter than that of conventional filopodia. Z‐filopodia formation and dynamics were regulated by actin‐regulatory proteins, such as vasodilator‐stimulated phosphoprotein, fascin, and cofilin. Chromophore‐assisted laser inactivation of cofilin induced the rapid turnover of z‐filopodia. An axon guidance receptor, neuropilin‐1, was concentrated in z‐filopodia and was transported together with them, whereas its ligand, semaphorin‐3A, was selectively bound to them. Membrane domains associated with z‐filopodia were also specialized and resembled those of lipid rafts, and their behaviors were closely related to those of neuropilin‐1. The results suggest that z‐filopodia have unique turnover properties, and unlike xy‐filopodia, do not function as force‐generating structures for axon extension. [ABSTRACT FROM AUTHOR]

Bone age assessment (BAA) is crucial in various fields, including legal proceedings, athletic competitions, and clinical medicine. However, the use of X-ray methods for age estimation without medical indication is subject to ethical debate, especially in forensic and athletic fields. The application of magnetic resonance imaging (MRI) with non-ionizing radiation can overcome this limitation in BAA. This study aimed to compare the application value of several MRI modalities of proximal humeral in BAA. A total of 468 patients with shoulder MRIs were retrospectively collected from a Chinese Han population aged 12–30 years (259 males and 209 females) for training and testing, including T1 weighted MRI (T1WI), T2 weighted MRI (T2WI), and Proton density weighted MRI (PDWI). Optimal regression models were established for age estimation, yielding mean absolute error (MAE) values below 2.0 years. The MAE values of T1WI were the lowest, with 1.700 years in males and 1.798 years in females. The area under the curve (AUC) and accuracy values of different MRI modalities of 16-year and 18-year thresholds were all around 0.9. For the 18-year threshold, T1WI outperformed T2WI and PDWI. In conclusion, the three MRI modalities of the proximal humerus can serve as reliable indicators for age assessment, while the T1WI performed better in age assessment and classification. [ABSTRACT FROM AUTHOR]

Background: Radiological age assessment using reference studies is inherently limited in accuracy due to a finite number of assignable skeletal maturation stages. To overcome this limitation, we present a deep learning approach for continuous age assessment based on clavicle ossification in computed tomography (CT). Methods: Thoracic CT scans were retrospectively collected from the picture archiving and communication system. Individuals aged 15.0 to 30.0 years examined in routine clinical practice were included. All scans were automatically cropped around the medial clavicular epiphyseal cartilages. A deep learning model was trained to predict a person's chronological age based on these scans. Performance was evaluated using mean absolute error (MAE). Model performance was compared to an optimistic human reader performance estimate for an established reference study method. Results: The deep learning model was trained on 4,400 scans of 1,935 patients (training set: mean age = 24.2 years ± 4.0, 1132 female) and evaluated on 300 scans of 300 patients with a balanced age and sex distribution (test set: mean age = 22.5 years ± 4.4, 150 female). Model MAE was 1.65 years, and the highest absolute error was 6.40 years for females and 7.32 years for males. However, performance could be attributed to norm-variants or pathologic disorders. Human reader estimate MAE was 1.84 years and the highest absolute error was 3.40 years for females and 3.78 years for males. Conclusions: We present a deep learning approach for continuous age predictions using CT volumes highlighting the medial clavicular epiphyseal cartilage with performance comparable to the human reader estimate. [ABSTRACT FROM AUTHOR]

Skeletal dysplasias (SKDs) are a heterogeneous group of more than 750 genetic disorders characterized by abnormal development, growth, and maintenance of bones or cartilage in the human skeleton. SKDs are often caused by variants in early patterning genes and in many cases part of multiple malformation syndromes and occur in combination with non‐skeletal phenotypes. The aim of this study was to investigate the underlying genetic cause of congenital SKDs in highly consanguineous Pakistani families, as well as in sporadic and familial SKD cases from India using multigene panel sequencing analysis. Therefore, we performed panel sequencing of 386 bone‐related genes in 7 highly consanguineous families from Pakistan and 27 cases from India affected with SKDs. In the highly consanguineous families, we were able to identify the underlying genetic cause in five out of seven families, resulting in a diagnostic yield of 71%. Whereas, in the sporadic and familial SKD cases, we identified 12 causative variants, corresponding to a diagnostic yield of 44%. The genetic heterogeneity in our cohorts was very high and we were able to detect various types of variants, including missense, nonsense, and frameshift variants, across multiple genes known to cause different types of SKDs. In conclusion, panel sequencing proved to be a highly effective way to decipher the genetic basis of SKDs in highly consanguineous families as well as sporadic and or familial cases from South Asia. Furthermore, our findings expand the allelic spectrum of skeletal dysplasias. [ABSTRACT FROM AUTHOR]

Isoprenyl cysteine carboxyl methyltransferase (ICMT) catalyzes the last step of the prenylation pathway. Previously, we found that high ICMT levels enhance tumorigenesis in vivo and that its expression is repressed by the p53 tumor suppressor. Based on evidence suggesting that some ICMT substrates affect invasive traits, we wondered if this enzyme may promote metastasis. In this work, we found that ICMT overexpression enhanced lung metastasis in vivo. Accordingly, ICMT overexpression also promoted cellular functions associated with aggressive phenotypes such as migration and invasion in vitro. Considering that some ICMT substrates are involved in the regulation of actin cytoskeleton, we hypothesized that actin-rich structures, associated with invasion and metastasis, may be affected. Our findings revealed that ICMT enhanced the formation of invadopodia. Additionally, by analyzing cancer patient databases, we found that ICMT is overexpressed in several tumor types. Furthermore, the concurrent expression of ICMT and CTTN , which encodes a crucial component of invadopodia, showed a significant correlation with clinical outcome. In summary, our work identifies ICMT overexpression as a relevant alteration in human cancer that promotes the development of metastatic tumors. • ICMT overexpression promotes metastasis in vivo. • ICMT enhances migration, invasion and invadopodia formation in cancer cells. • The ICMT gene is overexpressed in several human cancers. • High expression of ICMT and CTTN correlate with por clinical outcome in lung cancer. [ABSTRACT FROM AUTHOR]

Current self-supervised approaches for skeleton action representation learning often focus on constrained scenarios, where videos and skeleton data are recorded in laboratory settings. When dealing with estimated skeleton data in real-world videos, such methods perform poorly due to the large variations across subjects and camera viewpoints. To address this issue, we introduce ViA, a novel View-Invariant Autoencoder for self-supervised skeleton action representation learning. ViA leverages motion retargeting between different human performers as a pretext task, in order to disentangle the latent action-specific 'Motion' features on top of the visual representation of a 2D or 3D skeleton sequence. Such 'Motion' features are invariant to skeleton geometry and camera view and allow ViA to facilitate both, cross-subject and cross-view action classification tasks. We conduct a study focusing on transfer-learning for skeleton-based action recognition with self-supervised pre-training on real-world data (e.g., Posetics). Our results showcase that skeleton representations learned from ViA are generic enough to improve upon state-of-the-art action classification accuracy, not only on 3D laboratory datasets such as NTU-RGB+D 60 and NTU-RGB+D 120, but also on real-world datasets where only 2D data are accurately estimated, e.g., Toyota Smarthome, UAV-Human and Penn Action. Code and models will be publicly available at https://walker-a11y.github.io/ViA-project. [ABSTRACT FROM AUTHOR]

The Middle Jurassic was a critical time in pterosaur evolution, witnessing the appearance of major morphological innovations that underpinned successive radiations by rhamphorhynchids, basally branching monofenestratans, and pterodactyloids. Frustratingly, this interval is particularly sparsely sampled, with a record consisting almost exclusively of isolated fragmentary remains. Here, we describe new material from the Bathonian-aged Kilmaluag Formation of Skye, Scotland, which helps close this gap. Ceoptera evansae (gen. et sp. nov.) is based on a three-dimensionally preserved partial skeleton, which represents one of the only associated Middle Jurassic pterosaurs. Ceoptera is among the first pterosaurs to be fully digitally prepared, and µCT scanning reveals multiple elements of the skeleton that remain fully embedded within the matrix and otherwise inaccessible. It is diagnosed by unique features of the pectoral and pelvic girdle. The inclusion of this new Middle Jurassic pterosaur in a novel phylogenetic analysis of pterosaur interrelationships provides additional support for the existence of the controversial clade Darwinoptera, adding to our knowledge of pterosaur diversity and evolution. [ABSTRACT FROM AUTHOR]

Les glucocorticoïdes sont largement utilisés pour le traitement de diverses maladies et affections dans un certain nombre de spécialités. Les effets néfastes des glucocorticoïdes oraux sur la santé osseuse sont bien documentés et l'ostéoporose cortico-induite est la cause la plus répandue d'ostéoporose provoquée par des médicaments et de fractures. On ne sait toutefois pas avec certitude si, ni dans quelle mesure, les glucocorticoïdes administrés par d'autres voies ont des effets sur le squelette. Cette revue présente les résultats disponibles à propos des effets des glucocorticoïdes administrés par voie inhalée, épidurale, intra-articulaire et topique sur les paramètres osseux. Bien que les données probantes soient limitées et peu robustes, il semble qu'une petite proportion des glucocorticoïdes administrés puisse être absorbés, pénétrer dans la circulation systémique et avoir des effets néfastes sur le squelette. Les glucocorticoïdes puissants, les fortes doses et une longue durée de traitement pourraient entraîner un risque accru de perte osseuse et de fractures. On trouve peu de données, et celles qui sont disponibles concernent uniquement les glucocorticoïdes inhalés, sur l'efficacité des anti-ostéoporotiques chez les patients recevant une corticothérapie administrée par d'autres modes que la voie orale. Des études complémentaires sont nécessaires pour clarifier la relation entre les différentes voies d'administration des glucocorticoïdes et les paramètres osseux et contribuer à formuler des recommandations de prise en charge optimale de ces patients. Glucocorticoids (GCs) are widely used by several specialties for the treatment of a variety of diseases and conditions. The unfavorable effect of oral GCs on bone health is well-documented. The ensuing from their use glucocorticoid-induced osteoporosis (GIOP) is the most common cause of medication-induced osteoporosis and fractures. It is uncertain, however, if, and in what extent, GCs administered by other routes affect the skeleton. In the present review, we quote current evidence on the effect of inhaled GCs, epidural and intra-articular steroid injections, and topical GCs on bone outcomes. Although evidence is limited and weak, it seems that a small proportion of the administered GCs may be absorbed, enter the systemic circulation, and adversely affect the skeleton. Potent GCs, higher doses, and longer treatment duration seem to infer the greater risk for bone loss and fractures. There are scarce data, and only for inhaled GCs, regarding the efficacy of antiosteoporotic medications in patients receiving GCs through routes other than oral. Further studies are needed to clarify the relationship between GC administration through these routes and bone outcomes and to help establishing guidelines for the optimal management of such patients. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of asymmetry and lower extremity mobility restrictions on the effectiveness of a passive back-support exosuit in short-duration, static trunk flexion postures. Background: The effectiveness of trunk exoskeletons/suits for sagittally symmetric trunk posture maintenance has been investigated, but there has been limited study of the effects of asymmetric trunk postures or lower extremity motion restriction. Method: Sixteen participants held trunk flexion postures involving trunk flexion (20°, 40°, 60°), asymmetry (0°, 30°), and lower extremity mobility (Free, Restricted) for 3 s. Participants held these postures with and without an exosuit while erector spinae and abdominal muscle activities were collected. Results: There were no significant interactions between exosuit and asymmetry or exosuit and lower extremity motion restrictions, indicating no significant effects of these factors on the effectiveness of the exosuit at reducing trunk muscle activity. The exosuit was found to be effective at reducing erector spinae muscle activity regardless of asymmetry of posture or lower extremity restrictions (average 21%, from 11.2% MVC to 8.8% MVC). The magnitude of the erector spinae activity at 60° of trunk flexion with the exosuit was similar to that seen at 20° without the exosuit. Conclusion: The exosuit consistently provided biomechanical benefit through reduced activation of the erector spinae muscles and neither asymmetry of trunk posture nor lower extremity restriction influenced this effectiveness. Application: Trunk exoskeletons/suits can reduce trunk muscle activation and understanding how characteristics of the trunk postures assumed impact these responses may help target tasks wherein these devices may be effective. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: We report herein an unprecedented N‐heterocyclic carbene‐catalyzed formal [3 + 3] annulation of ynals with N‐Ts indolin‐3‐ones under the oxidation condition affording the functionalized pyrano[3,2‐b]indol‐2‐ones. The alkynyl acylazoliums via the combination of a carbene with ynals in the presence of oxidate proved to be the important intermediates for the success of this transformation. This method features a broad substrate scope and mild conditions, including axially chiral skeletons with suitable substitutions. [ABSTRACT FROM AUTHOR]

The complex morphology of neurons requires precise control of their microtubule cytoskeleton. This is achieved by microtubule-associated proteins (MAPs) that regulate the assembly and stability of microtubules, and transport of molecules and vesicles along them. While many of these MAPs function in all cells, some are specifically or predominantly involved in regulating microtubules in neurons. Here we use the sea anemone Nematostella vectensis as a model organism to provide new insights into the early evolution of neural microtubule regulation. As a cnidarian, Nematostella belongs to an outgroup to all bilaterians and thus occupies an informative phylogenetic position for reconstructing the evolution of nervous system development. We identified an ortholog of the microtubule-binding protein doublecortin-like kinase (NvDclk1) as a gene that is predominantly expressed in neurons and cnidocytes (stinging cells), two classes of cells belonging to the neural lineage in cnidarians. A transgenic NvDclk1 reporter line revealed an elaborate network of neurite-like processes emerging from cnidocytes in the tentacles and the body column. A transgene expressing NvDclk1 under the control of the NvDclk1 promoter suggests that NvDclk1 localizes to microtubules and therefore likely functions as a microtubule-binding protein. Further, we generated a mutant for NvDclk1 using CRISPR/Cas9 and show that the mutants fail to generate mature cnidocytes. Our results support the hypothesis that the elaboration of programs for microtubule regulation occurred early in the evolution of nervous systems. [ABSTRACT FROM AUTHOR]

The development of electronic skin with dual stealth functionality is crucial for enabling devices to operate effectively in dynamic electromagnetic environments, thereby facilitating intelligent electromagnetic protection for autonomous perception. However, achieving compatibility between terahertz (THz) and infrared (IR) stealth technologies remains largely unexplored due to their inherent contradictions. Herein, inspired by natural corals, a novel coral‐like multi‐scale composite foam (CMSF) was proposed that ingeniously reconciles these contradictions. The design capitalizes on the conductive network and heat insulation properties of the foam skeleton, the loss effects and low infrared emission of metal particles, and the infrared transparency of magneto‐optical materials. This approach leads to the realization of a THz‐IR bi‐stealth electronic skin concept. The CMSF exhibits a maximum reflection loss of 84.8 dB in the terahertz band, while its infrared stealth capability ensures environmental adaptability under varying temperatures. Furthermore, the electronic skin exhibits exceptional sensitivity and reliability as a wearable device for perceiving environmental changes. This advanced material, combining multispectral stealth with sensing capabilities, holds immense potential for applications ranging from camouflage technology to smart wearables. [ABSTRACT FROM AUTHOR]

The development of electronic skin with dual stealth functionality is crucial for enabling devices to operate effectively in dynamic electromagnetic environments, thereby facilitating intelligent electromagnetic protection for autonomous perception. However, achieving compatibility between terahertz (THz) and infrared (IR) stealth technologies remains largely unexplored due to their inherent contradictions. Herein, inspired by natural corals, a novel coral‐like multi‐scale composite foam (CMSF) was proposed that ingeniously reconciles these contradictions. The design capitalizes on the conductive network and heat insulation properties of the foam skeleton, the loss effects and low infrared emission of metal particles, and the infrared transparency of magneto‐optical materials. This approach leads to the realization of a THz‐IR bi‐stealth electronic skin concept. The CMSF exhibits a maximum reflection loss of 84.8 dB in the terahertz band, while its infrared stealth capability ensures environmental adaptability under varying temperatures. Furthermore, the electronic skin exhibits exceptional sensitivity and reliability as a wearable device for perceiving environmental changes. This advanced material, combining multispectral stealth with sensing capabilities, holds immense potential for applications ranging from camouflage technology to smart wearables. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton. Methods: Pregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology. Results: Osteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤ 30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals. Conclusions: Evidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD. Plain English summary: Prenatal alcohol exposure (PAE) can lead to a set of lifelong cognitive, behavioural, and physical disabilities known as foetal alcohol spectrum disorder (FASD). FASD is a significant burden on healthcare, justice and education systems, which is set to worsen with rising alcohol consumption rates. FASD children have an increased risk of long bone fracture and adolescents are smaller in stature. However, sex differences and the long-term effects of PAE on the skeleton have not been investigated and was the aim of this study. Using a mouse model of PAE, we examined the function and gene expression of bone-forming cells (osteoblasts). We then analysed the skeletons of male and female mice at 12-weeks-old (adult) and 4-weeks-old (juvenile). PAE reduced osteoblast bone formation in both sexes, compared to control. Differential gene expression was predominantly observed in PAE males and largely involved genes related to blood vessel formation. High resolution x-ray imaging (micro-CT) revealed PAE had a detrimental effect on the inner trabecular bone component in 12-week-old male mice only. Analysis of the outer cortical bone revealed that whilst both male and female PAE mice were negatively affected, anatomical variations were observed. Mechanical testing also revealed differences in bone strength in PAE mice, compared to control. Interestingly, 4-week-old mice did not possess these sex differences observed in our PAE model at 12 weeks of age. Our data suggest PAE has detrimental and yet sex-dependent effects on the skeleton. Establishing these sex differences will support future policies and clinical management of FASD. Highlights: Primary calvarial osteoblasts isolated from male and female PAE mice displayed reduced mineralised bone nodule formation and differential gene expression compared to control. PAE had a detrimental effect on trabecular bone parameters in 12-week-old male mice only. PAE leads to spatial variation in cortical bone parameters and geometry, with male mice negatively affected along the tibial length and female mice only affected at the distal end. Mechanical testing revealed PAE male mice had significantly reduced bone stiffness compared to controls; PAE in both sexes reduced maximum load and yield. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals. [ABSTRACT FROM AUTHOR]

We reported a chiral oxamide‐phosphine ligand (COAP−Ph)‐Pd‐catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3‐indanedione and 2‐vinylcyclopropane‐1,1‐dicarboxylates with cyclic sulfonyl 1‐azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane‐indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo‐ and enantioselectivity. The COAP−Pd complex serves not only to promote generation of chiral π‐allyl‐palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction. [ABSTRACT FROM AUTHOR]

Summary: Calcium ion (Ca2+) serves as a versatile and conserved second messenger in orchestrating immune responses. In plants, plasma membrane‐localized Ca2+‐permeable channels can be activated to induce Ca2+ influx from extracellular space to cytosol upon pathogen infection. Notably, different immune elicitors can induce dynamic Ca2+ signatures in the cytosol. During pattern‐triggered immunity, there is a rapid and transient increase in cytosolic Ca2+, whereas in effector‐triggered immunity, the elevation of cytosolic Ca2+ is strong and sustained. Numerous Ca2+ sensors are localized in the cytosol or different intracellular organelles, which are responsible for detecting and converting Ca2+ signals. In fact, Ca2+ signaling coordinated by cytosol and subcellular compartments plays a crucial role in activating plant immune responses. However, the complete Ca2+ signaling network in plant cells is still largely ambiguous. This review offers a comprehensive insight into the collaborative role of intracellular Ca2+ stores in shaping the Ca2+ signaling network during plant immunity, and several intriguing questions for future research are highlighted. [ABSTRACT FROM AUTHOR]

Here we report B(C6F5)3/CPA‐catalyzed enantioselective aza‐Diels–Alder reaction of 3,3‐difluoro‐2‐Aryl‐3H‐indoles with unactivated dienes to access chiral 10,10‐difluoro‐tetrahydropyrido[1,2‐a]indoles. This protocol allows the formation of pyrazole‐based C2‐quaternary indolin‐3‐ones with high enantioselectivities and regioselectivities. Moreover, gram‐scale synthesis of the 10,10‐difluoro‐tetrahydropyrido[1,2‐a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

SUMMARY: Melon (Cucumis melo L.), being under intensive domestication and selective breeding, displays an abundant phenotypic diversity. Wild germplasm with tolerance to stress represents an untapped genetic resource for discovery of disease‐resistance genes. To comprehensively characterize resistance genes in melon, we generate a telomere‐to‐telomere (T2T) and gap‐free genome of wild melon accession PI511890 (C. melo var. chito) with a total length of 375.0 Mb and a contig N50 of 31.24 Mb. The complete genome allows us to dissect genome architecture and identify resistance gene analogs. We construct a pan‐NLRome using seven melon genomes, which include 208 variable and 18 core nucleotide‐binding leucine‐rich repeat receptors (NLRs). Multiple disease‐related transcriptome analyses indicate that most up‐regulated NLRs induced by pathogens are shell or cloud NLRs. The T2T gap‐free assembly and the pan‐NLRome not only serve as essential resources for genomic studies and molecular breeding of melon but also provide insights into the genome architecture and NLR diversity. Significance Statement: We report a complete genome of wild melon accession PI 511809 (Cucumis melo var. chito) and comprehensively dissect its genome architecture, and further accurately re‐annotate the NLR genes in PI 511890 and the other six published melon genomes and construct a pan‐NLRome for melon. [ABSTRACT FROM AUTHOR]

Members of the myosin superfamily of molecular motors are large mechanochemical ATPases that are implicated in an ever-expanding array of cellular functions. This review focuses on mammalian nonmuscle myosin-2 (NM2) paralogs, ubiquitous members of the myosin-2 family of filament-forming motors. Through the conversion of chemical energy into mechanical work, NM2 paralogs remodel and shape cells and tissues. This process is tightly controlled in time and space by numerous synergetic regulation mechanisms to meet cellular demands. We review how recent advances in structural biology together with elegant biophysical and cell biological approaches have contributed to our understanding of the shared and unique mechanisms of NM2 paralogs as they relate to their kinetics, regulation, assembly, and cellular function. [ABSTRACT FROM AUTHOR]

A new species (Marcopoloichthys mirigioliensis) of the stem teleosteomorph genus Marcopoloichthys is described from the lower Besano Formation (late Anisian at Monte San Giorgio, southern Switzerland), making this new species distinct from Marcopoloichthys furreri from the Prosanto Formation (early Ladinian at Ducanfurgga, southeastern Switzerland). Marcopoloichthys mirigioliensis n. sp. is smaller (ca. 32 mm standard length) than M. furreri (ca. 40 mm standard length), and in addition, the two species have some important differences in the caudal endoskeleton and fin, e.g., number of epaxial and hypaxial basal fulcra, uroneural structure, size of hypurals, and presence versus absence of urodermals. Marcopoloichthys mirigioliensis n. sp. is the smallest member of Marcopoloichthyidae which is currently known from at least five species living in the Triassic of China (one species), Italy (two and others that remain undescribed), and Switzerland and according to current information, with its ca. 32 mm standard length is candidate to be considered a miniature fish. Additionally, this size makes it the smallest known stem teleost. As in other marcopoloichthyids, the buccal and suspensorium anatomy of M. mirigiolensis n. sp. corresponds to that of suction-feeder fishes. [ABSTRACT FROM AUTHOR]

Background: Tubulins play crucial roles in numerous fundamental processes of plant development. In flowering plants, tubulins are grouped into α-, β- and γ-subfamilies, while α- and β-tubulins possess a large isotype diversity and gene number variations among different species. This circumstance leads to insufficient recognition of orthologous isotypes and significantly complicates extrapolation of obtained experimental results, and brings difficulties for the identification of particular tubulin isotype function. The aim of this research is to identify and characterize tubulins of an emerging biofuel crop Camelina sativa. Results: We report comprehensive identification and characterization of tubulin gene family in C. sativa, including analyses of exon-intron organization, duplicated genes comparison, proper isotype designation, phylogenetic analysis, and expression patterns in different tissues. 17 α-, 34 β- and 6 γ-tubulin genes were identified and assigned to a particular isotype. Recognition of orthologous tubulin isotypes was cross-referred, involving data of phylogeny, synteny analyses and genes allocation on reconstructed genomic blocks of Ancestral Crucifer Karyotype. An investigation of expression patterns of tubulin homeologs revealed the predominant role of N6 (A) and N7 (B) subgenomes in tubulin expression at various developmental stages, contrarily to general the dominance of transcripts of H7 (C) subgenome. Conclusions: For the first time a complete set of tubulin gene family members was identified and characterized for allohexaploid C. sativa species. The study demonstrates the comprehensive approach of precise inferring gene orthology. The applied technique allowed not only identifying C. sativa tubulin orthologs in model Arabidopsis species and tracking tubulin gene evolution, but also uncovered that A. thaliana is missing orthologs for several particular isotypes of α- and β-tubulins. [ABSTRACT FROM AUTHOR]

Many viral, protozoal, and fungal pathogens represent major human and animal health problems due to their great potential of causing infectious diseases. Research on these pathogens has contributed substantially to our current understanding of both microbial virulence determinants and host key factors during infection. Countless studies have also shed light on the molecular mechanisms of host–pathogen interactions that are employed by these microbes. For example, actin cytoskeletal dynamics play critical roles in effective adhesion, host cell entry, and intracellular movements of intruding pathogens. Cortactin is an eminent host cell protein that stimulates actin polymerization and signal transduction, and recently emerged as fundamental player during host–pathogen crosstalk. Here we review the important role of cortactin as major target for various prominent viral, protozoal and fungal pathogens in humans, and its role in human disease development and cancer progression. Most if not all of these important classes of pathogens have been reported to hijack cortactin during infection through mediating up‐ or downregulation of cortactin mRNA and protein expression as well as signaling. In particular, pathogen‐induced changes in tyrosine and serine phosphorylation status of cortactin at its major phospho‐sites (Y‐421, Y‐470, Y‐486, S‐113, S‐298, S‐405, and S‐418) are addressed. As has been reported for various Gram‐negative and Gram‐positive bacteria, many pathogenic viruses, protozoa, and fungi also control these regulatory phospho‐sites, for example, by activating kinases such as Src, PAK, ERK1/2, and PKD, which are known to phosphorylate cortactin. In addition, the recruitment of cortactin and its interaction partners, like the Arp2/3 complex and F‐actin, to the contact sites between pathogens and host cells is highlighted, as this plays an important role in the infection process and internalization of several pathogens. However, there are also other ways in which the pathogens can exploit the function of cortactin for their needs, as the cortactin‐mediated regulation of cellular processes is complex and involves numerous different interaction partners. Here, the current state of knowledge is summarized. [ABSTRACT FROM AUTHOR]

An array of cyanopyridazine derivatives have been developed through a sequence of (3+3) cycloaddition/oxidative aromatization/derivatization steps. Investigation of the physicochemical properties of these compounds shows that four have interesting fluorescence properties and have the potential to be developed into bimodal photoredox catalysts. One has been confirmed to be an photoredox catalyst in the reactions of N‐aryl‐ tetrahydroisoquinolines with phosphite, nitromethane, malonitrile and sodium thiocyanate, led to 22%–95% yields. The catalyst capabilities remain with recyclable using under the reaction conditions. [ABSTRACT FROM AUTHOR]

Robotically assisted proteomics provides insights into the regulation of multiple proteins achieving excellent spatial resolution. However, developing an effective method for spatially resolved quantitative proteomics of formalin fixed paraffin embedded tissue (FFPE) in an accessible and economical manner remains challenging. We introduce non-robotic In-insert FFPE proteomics approach, combining glass insert FFPE tissue processing with spatial quantitative data-independent mass spectrometry (DIA). In-insert approach identifies 450 proteins from a 5 µm thick breast FFPE tissue voxel with 50 µm lateral dimensions covering several tens of cells. Furthermore, In-insert approach associated a keratin series and moesin (MOES) with prolactin-induced protein (PIP) indicating their prolactin and/or estrogen regulation. Our data suggest that PIP is a spatial biomarker for hormonally triggered cytoskeletal remodeling, potentially useful for screening hormonally affected hotspots in breast tissue. In-insert proteomics represents an alternative FFPE processing method, requiring minimal laboratory equipment and skills to generate spatial proteotype repositories from FFPE tissue. In-insert protocol offers cost-effective, versatile, and low loss spatial quantitative proteomic analysis of FFPE tissue, identifying prolactin-induced protein as a hormonal cytoskeleton reorganization spatial biomarker in mammary tissue. [ABSTRACT FROM AUTHOR]

Background: Although sorafenib has been consistently used as a first-line treatment for advanced hepatocellular carcinoma (HCC), most patients will develop resistance, and the mechanism of resistance to sorafenib needs further study. Methods: Using KAS-seq technology, we obtained the ssDNA profiles within the whole genome range of SMMC-7721 cells treated with sorafenib for differential analysis. We then intersected the differential genes obtained from the analysis of hepatocellular carcinoma patients in GSE109211 who were ineffective and effective with sorafenib treatment, constructed a PPI network, and obtained hub genes. We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients. Results: In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton. Conclusions: The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. Using KAS-seq to analyze the early changes in tumor cells treated with drugs is feasible for studying the drug resistance of tumors, which provides reference significance for future research. [ABSTRACT FROM AUTHOR]

The eukaryotic cytoskeleton is a complex scaffold consisting of actin filaments, intermediate filaments, and microtubules. Although fungi and plants lack intermediate filaments, their dynamic structural network of actin filaments and microtubules regulates cell shape, division, polarity, and vesicular trafficking. However, the specialized functions of the cytoskeleton during plant–fungus interactions remain elusive. Recent reports demonstrate that the plant cytoskeleton responds to signal cues and pathogen invasion through remodeling, thereby coordinating immune receptor trafficking, membrane microdomain formation, aggregation of organelles, and transport of defense compounds. Emerging evidence also suggests that cytoskeleton remodeling further regulates host immunity by triggering salicylic acid signaling, reactive oxygen species generation, and pathogenesis-related gene expression. During host invasion, fungi undergo systematic cytoskeleton remodeling, which is crucial for successful host penetration and colonization. Furthermore, phytohormones act as an essential regulator of plant cytoskeleton dynamics and are frequently targeted by fungal effectors to disrupt the host's growth–defense balance. This review discusses recent advances in the understanding of cytoskeleton dynamics during plant–fungus interactions and provides novel insights into the relationship between phytohormones and cytoskeleton remodeling upon pathogen attack. We also highlight the importance of fungal cytoskeleton rearrangements during host colonization and suggest directions for future investigations in this field. [ABSTRACT FROM AUTHOR]

Aim Location Time period Major taxa studied Methods Results Main conclusions Quantify the contribution of environmental factors (water temperature, salinity and depth) and evolutionary history to varied skeletal mineralogy in calcifying marine organisms.Global Ocean.Present.Order: Cheilostomatida; Phylum: Bryozoa.We employed X‐ray diffraction (XRD) to analyse the skeletal mineral composition of 872 individual colonies, representing 437 bryozoan species, in terms of calcite/aragonite ratios. We integrated these data with equivalent published data, thus reaching 981 species, and applied linear models (LMs), generalized linear models (GLMs) and phylogenetic generalized least squares models (PGLSs) to investigate the influences of temperature, salinity, depth and phylogenetic history on the mineralogy of nearly 1000 cheilostome bryozoan species.Cheilostome bryozoans vary considerably in their skeletal mineral composition: in our dataset 65% of the species possess purely calcite skeletons, 15% exclusively employ aragonite and 20% exhibit mixed (i.e. calcite and aragonite) mineralogies. Temperature is the predominant measured environmental factor influencing bryozoan skeletal mineralogy, accounting for 20% of its variability across species, when phylogenetic relatedness is unaccounted for. Bryozoans in lower latitudes, characterized by higher seawater temperatures, have higher aragonite concentrations. By accounting for phylogenetic structure using a subset of 87 species for which we have topological information, 40% of the observed mineralogical variability could be attributed to present‐day temperature. In contrast, depth and salinity played minor roles, explaining less than 1% of the mineralogical variation each.This study emphasizes the influence of evolutionary history on the mineralogical variability of calcifying organisms, even when it can be shown that a single environmental factor (temperature) explains a substantial amount of this variability. When confronted with changing temperature, calcifiers such as bryozoans are likely to respond in diverse ways, depending on the species, given their phylogenetic relatedness and the external conditions they meet. [ABSTRACT FROM AUTHOR]

Contractile actomyosin bundles play crucial roles in various physiological processes, including cell migration, morphogenesis, and muscle contraction. The intricate assembly of actomyosin bundles involves the precise alignment and fusion of myosin II filaments, yet the underlying mechanisms and factors involved in these processes remain elusive. Our study reveals that LUZP1 plays a central role in orchestrating the maturation of thick actomyosin bundles. Loss of LUZP1 caused abnormal cell morphogenesis, migration, and the ability to exert forces on the environment. Importantly, knockout of LUZP1 results in significant defects in the concatenation and persistent association of myosin II filaments, severely impairing the assembly of myosin II stacks. The disruption of these processes in LUZP1 knockout cells provides mechanistic insights into the defective assembly of thick ventral stress fibers and the associated cellular contractility abnormalities. Overall, these results significantly contribute to our understanding of the molecular mechanism involved in actomyosin bundle formation and highlight the essential role of LUZP1 in this process. [ABSTRACT FROM AUTHOR]

During mammalian terrestrial locomotion, body flexibility facilitated by the vertebral column is expected to be correlated with observed modes of locomotion, known as gait (e.g., sprawl, trot, hop, bound, gallop). In small‐ to medium‐sized mammals (average weight up to 5 kg), the relationship between locomotive mode and vertebral morphology is largely unexplored. Here we studied the vertebral column from 46 small‐ to medium‐sized mammals. Nine vertebrae across cervical, thoracic, and lumbar regions were chosen to represent the whole vertebral column. Vertebra shape was analysed using three‐dimensional geometric morphometrics with the phylogenetic comparative method. We also applied the multi‐block method, which can consider all vertebrae as a single structure for analysis. We calculated morphological disparity, phylogenetic signal, and evaluated the effects of allometry and gait on vertebral shape. We also investigated the pattern of integration in the column. We found the cervical vertebrae show the highest degree of morphological disparity, and the first thoracic vertebra shows the highest phylogenetic signal. A significant effect of gait type on vertebrae shape was found, with the lumbar vertebrae having the strongest correlation; but this effect was not significant after taking phylogeny into account. On the other hand, allometry has a significant effect on all vertebrae regardless of the contribution from phylogeny. The regions showed differing degrees of integration, with cervical vertebrae most strongly correlated. With these results, we have revealed novel information that cannot be captured from study of a single vertebra alone: although the lumbar vertebrae are the most correlated with gait, the cervical vertebrae are more morphologically diverse and drive the diversity among species when considering whole column shape. [ABSTRACT FROM AUTHOR]

Phytosaurs are a group of Upper Triassic semi‐aquatic archosauriform reptiles. Their variable skull morphology forms the foundation of our understanding of their relationships and paleoecology, while only a few studies have focused on demonstrating the existence of postcranial variation. The numbers of vertebrae in the sacrum are thought to vary from two, the plesiomorphic condition for archosauriforms, to three, with the addition of a sacralized dorsal (i.e., dorsosacral) vertebra. In this study, we demonstrate the presence of a sacralized first caudal (i.e., caudosacral) vertebra in a sacrum belonging to Machaeroprosopus mccauleyi. We rule out taphonomic distortion or pathology as explanations for the inclusion of this element in the sacrum, suggesting instead that it occurred through modifications of the same developmental processes that likely produced dorsosacral vertebrae in phytosaurs. Additionally, we show that a dorsosacral vertebra is common in phytosaur specimens from the Chinle Formation and Dockum Group of the southwestern United States and suggest that it may be widespread among phytosaurs. The addition of sacral vertebrae potentially aided adaptation to larger body sizes or more terrestrial lifestyles in certain taxa. [ABSTRACT FROM AUTHOR]

Inference using skeleton to steer RGB videos is applicable to fine‐grained activities in indoor human action recognition (IHAR). However, existing methods that explore only spatial alignment are prone to bias, resulting in limited performance. The authors propose a Three‐stage Guidance (3sG) framework, leveraging skeleton knowledge to promote RGB in three stages. First, a soft shading image is proposed for alleviating background noise in videos, allowing the network to directly focus more on the motion region. Second, the authors propose to extract RGB frames of interest to reduce the computational effort. Furthermore, to explore more fully the complementary information between skeletons and RGB, the skeleton is coupled to the frame representation in a different spatial–temporal sharing pattern. Third, the global skeleton and skeleton‐guided RGB features are fed into the shared classifiers, which approximate the logit distributions of the two to enhance the performance in RGB unimodal. Finally, a fusion strategy that utilizes two learnable parameters to adaptively integrate the skeleton with the RGB is proposed. 3sG outperforms the state‐of‐the‐art results on the Toyota Smarthome dataset while it is more efficient than similar methods on the NTU RGB+D dataset. [ABSTRACT FROM AUTHOR]

In recent years, there has been increasing attention focused on various products belonging to the imidazopyridine family; this class of heterocyclic compounds shows unique chemical structure, versatile optical properties, and diverse biological attributes. The broad family of imidazopyridines encompasses different heterocycles, each with its own specific properties and distinct characteristics, making all of them promising for various application fields. In general, this useful category of aromatic heterocycles holds significant promise across various research domains, spanning from material science to pharmaceuticals. The various cores belonging to the imidazopyridine family exhibit unique properties, such as serving as emitters in imaging, ligands for transition metals, showing reversible electrochemical properties, and demonstrating biological activity. Recently, numerous noteworthy advancements have emerged in different technological fields, including optoelectronic devices, sensors, energy conversion, medical applications, and shining emitters for imaging and microscopy. This review intends to provide a state-of-the-art overview of this framework from 1955 to the present day, unveiling different aspects of various applications. This extensive literature survey may guide chemists and researchers in the quest for novel imidazopyridine compounds with enhanced properties and efficiency in different uses. [ABSTRACT FROM AUTHOR]

Kallopterolides A–I (1–9), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume Antillogorgia kallos. The structures and relative configurations of 1–9 were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents. [ABSTRACT FROM AUTHOR]

cis-1-amino-2-indanol is an important building block in many areas of chemistry. Indeed, this molecule is currently used as skeleton in many ligands (BOX, PyBOX...), catalysts and chiral auxiliaries. Moreover, it has been incorporated in numerous bioactive structures. The major issues during its synthesis are the control of cis-selectivity, for which various strategies have been devised, and the enantioselectivity of the reaction. This review highlights the various methodologies implemented over the last few decades to access cis-1-amino-2-indanol in racemic and enantioselective manners. In addition, the various substitution patterns on the aromatic ring and their preparations are listed. [ABSTRACT FROM AUTHOR]

Simple Summary: Archaeozoological investigation of the horse remains discovered in Alba Iulia-CX 143 complex of the La Tène period reveals the existence of a small-sized male horse (Equus caballus) of 1200–1300 mm in height with slender extremities that died at the age of 7–8 years with no evident paleopathological changes characteristic to horseback riding but showing distinctive elements of bit wear. The present paper deals with the archaeozoological investigation carried out on a horse skeleton discovered in a Late Iron Age La Tène tomb (coded CX 143) in Alba Iulia, Romania. The paper presents all the results of the investigation, with a description of finds, adding a detailed assessment of the dentition with some interesting conclusions on the usage of a horse bit and the possible consequences of this use. The morphological features of the horse indicate a 7–8-year-old male individual, with a recalculated height of 1200–1300 mm. What is also stressed in the investigated sample is the lack of the characteristic pathological lesions typical for horseback riding but showing distinctive elements of bit wear. A comparative perspective over the few findings from the same period is provided to ensure the framing of the identified individual into the much larger historical context. [ABSTRACT FROM AUTHOR]

The synthesis of biphenylmethoxydibenzo[b,f]oxepine or photoswitchable fluorinated dibenzo[b,f]oxepine derivatives with one or three azo bonds, potential microtubule inhibitors, is described. Our studies provide a concise method for constructing derivatives containing the dibenzo[b,f]oxepine skeleton. An analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light. [ABSTRACT FROM AUTHOR]

Estrogen (17β-estradiol) deficiency post-menopause alters bone homeostasis whereby bone resorption by osteoclasts exceeds bone formation by osteoblasts, leading to osteoporosis in females. We established an in vitro model to examine the consequences of estrogen withdrawal (E2-WD) on osteoclasts derived from the mouse macrophage RAW 264.7 cell line and utilized it to investigate the mechanism behind the enhanced osteoclast activity post-menopause. We found that a greater population of osteoclasts that underwent E2-WD contained a podosome belt necessary for osteoclasts to adhere and resorb bone and possessed elevated resorptive activity compared to osteoclasts exposed to estrogen (E2) continuously. Our results show that compared to osteoclasts that received E2 continuously, those that underwent E2-WD had a faster rate of microtubule (MT) growth, reduced RhoA activation, and shorter podosome lifespan. Thus, altered podosome and MT dynamics induced by the withdrawal of estrogen supports podosome belt assembly/stability in osteoclasts, which may explain their enhanced bone resorption activity. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs), pivotal for tissue repair, utilize collagen to restore structural integrity in damaged tissue, preserving its organization through concomitant remodeling. The non-enzymatic glycation of collagen potentially compromises MSC communication, particularly upon advancing the process, underlying various pathologies such as late-stage diabetic complications and aging. However, an understanding of the impact of early-stage collagen glycation on MSC interaction is lacking. This study examines the fate of in vitro glycated rat tail collagen (RTC) upon exposure to glucose for 1 or 5 days in contact with MSCs. Utilizing human adipose tissue-derived MSCs (ADMSCs), we demonstrate their significantly altered interaction with glycated collagen, characterized morphologically by reduced cell spreading, diminished focal adhesions formation, and attenuated development of the actin cytoskeleton. The morphological findings were confirmed by ImageJ 1.54g morphometric analysis with the most significant drop in the cell spreading area (CSA), from 246.8 μm2 for the native collagen to 216.8 μm2 and 163.7 μm2 for glycated ones, for 1 day and 5 days, respectively, and a similar trend was observed for cell perimeter 112.9 μm vs. 95.1 μm and 86.2 μm, respectively. These data suggest impaired recognition of early glycated collagen by integrin receptors. Moreover, they coincide with the reduced fibril-like reorganization of adsorbed FITC-collagen (indicating impaired remodeling) and a presumed decreased sensitivity to proteases. Indeed, confirmatory assays reveal diminished FITC-collagen degradation for glycated samples at 1 day and 5 days by attached cells (22.8 and 30.4%) and reduced proteolysis upon exogenous collagenase addition (24.5 and 40.4%) in a cell-free system, respectively. The mechanisms behind these effects remain uncertain, although differential scanning calorimetry confirms subtle structural/thermodynamic changes in glycated collagen. [ABSTRACT FROM AUTHOR]

The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers. [ABSTRACT FROM AUTHOR]

This article discusses the use of X-ray fluorescence analysis (RFA) and gamma spectroscopy as analytical techniques in chemistry education. The experiments described in the article focus on exploring atomic models and characterizing different materials. RFA is used to determine the composition of compounds and metals, while gamma spectroscopy can detect gamma radiation emitted by isotopes. The article provides examples of using these techniques to analyze specific materials, such as coins and white pigments. The authors suggest that the benefits of these techniques justify the cost of acquiring the necessary equipment. [Extracted from the article]

SUMMARY: Over the past decade, the history of tobacco's introduction to Europe and its societal impact has been extensively studied, resulting in prevailing narratives about its adoption and consumption. In the Netherlands, historical records generally concur that: (I) tobacco rose in popularity among all socioeconomic classes between 1590 and 1630 CE; and (II) it spread throughout the Country as a male habit. However, the presence and consumption of tobacco have exhibited profound variations across diverse societies throughout history, manifesting dissimilar patterns of employment and significance over varying temporal and spatial dimensions. By analysing a sample of 351 human skeletons dating from 1300 to 1829 CE, the present study challenges the limited historical narratives presented above and emphasizes the diverse contextual factors that influenced tobacco's prevalence in two different Dutch centres. Our results suggest that in certain areas of the Netherlands tobacco was likely present and widely consumed well before 1630 CE, while also highlighting overall substantial female participation in the practice. Furthermore, our analysis hints at the possibility of divergent methods of tobacco consumption between sexes, suggesting that the historical narrative of tobacco as solely a male habit may warrant reconsideration. Overall, our study contributes to a deeper understanding of the complex history of tobacco in the Netherlands, shedding light on historical trends and cultural practices. [ABSTRACT FROM AUTHOR]

While cytoskeletal proteins have long been considered to be present only in eukaryotes, but not in prokaryotes, homologs of the major cytoskeletal proteins, including tubulin, have been discovered in bacteria and archaea in the last 30 years. The properties of tubulin homologs, as well as of the cytoskeleton-like structures they form in prokaryotic cells, vary and differ significantly from the relevant properties of eukaryotic tubulins. The comparison of prokaryotic tubulin homologs with each other seems therefore to be an interesting task and thus is the goal of the current review. We consider such tubulin homologs found in bacteria and archaea as FtsZ, TubZ, PhuZ, BtubA/BtubB, CetZ, etc. The ability of various tubulin homologs to act as targets for pharmaceuticals, similar to the FtsZ protein, which is already a target for promising antibiotics, is also discussed. [ABSTRACT FROM AUTHOR]

Neutrophil granulocytes play a crucial role in host defense against invading pathogens and in inflammatory diseases. The aim of this study was to elucidate membrane potential dynamics during the initial phase of neutrophil activation and its relation to migration and production of reactive oxygen species (ROS). We performed ROS production measurements of neutrophils from healthy C57BL/6J mice after TNFα-priming and/or C5a stimulation. The actin cytoskeleton was visualized with fluorescence microscopy. Furthermore, we combined migration assays and measurements of membrane potential dynamics after stimulating unprimed and/or TNFα-primed neutrophils with C5a. We show that C5a has a concentration-dependent effect on ROS production and chemokinetic migration. Chemokinetic migration and chemotaxis are impaired at C5a concentrations that induce ROS production. The actin cytoskeleton of unstimulated and of ROS-producing neutrophils is not distributed in a polarized way. Inhibition of the phagocytic NADPH oxidase NOX2 with diphenyleneiodonium (DPI) leads to a polarized distribution of the actin cytoskeleton and rescues chemokinetic migration of primed and C5a-stimulated neutrophils. Moreover, C5a evokes a pronounced depolarization of the cell membrane potential by 86.6 ± 4.2 mV starting from a resting membrane potential of -74.3 ± 0.7 mV. The C5a-induced depolarization occurs almost instantaneously (within less than one minute) in contrast to the more gradually developing depolarization induced by PMA (lag time of 3—4 min). This initial depolarization is accompanied by a decrease of the migration velocity. Collectively, our results show that stimulation with C5a evokes parallel changes in membrane potential dynamics, neutrophil ROS production and motility. Notably, the amplitude of membrane potential dynamics is comparable to that of excitable cells. [ABSTRACT FROM AUTHOR]

Objectives: Ecogeographic variation in human nasal anatomy has historically been analyzed on skeletal morphology and interpreted in the context of climatic adaptations to respiratory air‐conditioning. Only a few studies have analyzed nasal soft tissue morphology, actively involved in air‐conditioning physiology. Materials and Methods: We used in vivo computer tomographic scans of (N = 146) adult individuals from Cambodia, Chile, Russia, and Spain. We conducted (N = 438) airflow simulations during inspiration using computational fluid dynamics to analyze the air‐conditioning capacities of the nasal soft tissue in the inflow, functional, and outflow tract, under three different environmental conditions: cold–dry; hot–dry; and hot–humid. We performed statistical comparisons between populations and sexes. Results: Subjects from hot–humid regions showed significantly lower air‐conditioning capacities than subjects from colder regions in all the three conditions, specifically within the isthmus region in the inflow tract, and the anterior part of the internal functional tract. Posterior to the functional tract, no differences were detected. No differences between sexes were found in any of the tracts and under any of the conditions. Discussion: Our statistical analyses support models of climatic adaptations of anterior nasal soft tissue morphology that fit with, and complement, previous research on dry skulls. However, our results challenge a morpho‐functional model that attributes air‐conditioning capacities exclusively to the functional tract located within the nasal cavity. Instead, our findings support studies that have suggested that both, the external nose and the intra‐facial soft tissue airways contribute to efficiently warming and humidifying air during inspiration. This supports functional interpretations in modern midfacial variation and evolution. [ABSTRACT FROM AUTHOR]

Objectives: Dental anthropological investigations into sexual dimorphism have conventionally concentrated on evaluating the dimensions and configuration of the enamel cap of canines. However, the morphology of the crown dentine surface can be closely linked to that of the enamel surface. This link can facilitate examination of crown morphology even when the enamel surface is slightly worn. Here, we determine if the morphology of the enamel‐dentine junction (EDJ) differs within (maxillary vs. mandibular) and between a sample of male (n = 26) and female (n = 21) contemporary human permanent canines from Europe. Methods: The morphological data of the EDJ were gathered employing a template comprising 96 landmarks and sliding semilandmarks. Subsequently, the data underwent analysis through form space principal component analysis following Procrustes registration, utilizing standard 3D geometric morphometric techniques. Results: Significant differences in the morphology of the EDJ were observed between the sexes, particularly concerning the overall shape of the crown, the symmetry of the mesial and distal edges, and the development of the distal accessory ridge. Conclusions: Sex differences in the morphology of the EDJ could relate in part to retention of the canine‐premolar honing complex in males. Our results indicate that analyses of the permanent canine EDJ may potentially provide a novel method for estimating the sex of adult and nonadult skeletons. [ABSTRACT FROM AUTHOR]

Objectives: Over the past few years, several methods have been proposed to improve the accuracy of age estimation in infants with a focus on dental development as a reliable marker. However, traditional approaches have limitations in efficiently combining information from different teeth and features. In order to address these challenges, this article presents a study on age estimation in infants with Machine Learning (ML) techniques, using deciduous teeth. Materials and Methods: The involved dataset comprises 114 infant skeletons from the Granada osteological collection of identified infants, aged between 5 months of gestation and 3 years of age. The samples consist of features such as the maximum length and mineralization and alveolar stages of teeth. For the purpose of designing a method capable of combining all the information available from each individual, a Multilayer Perceptron model is proposed, one of the most popular artificial neural networks. This model has been validated using the leave‐one‐out experimental validation protocol. Through different groups of experiments, the study examines the informativeness of the aforementioned features, individually and in combination. Results: The results indicate that the fusion of different variables allows for more accurate age estimates (RMSE = 66 days) than when variables are analyzed separately (RMSE = 101 days). Additionally, the study demonstrates the benefits of involving multiple teeth, which significantly reduces the RMSE compared to a single tooth. Discussion: This article underlines the clear advantages of ML‐based methods, emphasizing their potential to improve the accuracy and robustness when estimating the age of infants. [ABSTRACT FROM AUTHOR]

Endothelial cell monolayers line the inner surfaces of blood and lymphatic vessels. They are continuously exposed to different mechanical loads, which may trigger mechanobiological signals and hence play a role in both physiological and pathological processes. Computer-based mechanical models of cells contribute to a better understanding of the relation between cell-scale loads and cues and the mechanical state of the hosting tissue. However, the confluency of the endothelial monolayer complicates these approaches since the intercellular cross-talk needs to be accounted for in addition to the cytoskeletal mechanics of the individual cells themselves. As a consequence, the computational approach must be able to efficiently model a large number of cells and their interaction. Here, we simulate cytoskeletal mechanics by means of molecular dynamics software, generally suitable to deal with large, locally interacting systems. Methods were developed to generate models of single cells and large monolayers with hundreds of cells. The single-cell model was considered for a comparison with experimental data. To this end, we simulated cell interactions with a continuous, deformable substrate, and computationally replicated multistep traction force microscopy experiments on endothelial cells. The results indicate that cell discrete network models are able to capture relevant features of the mechanical behaviour and are thus well-suited to investigate the mechanics of the large cytoskeletal network of individual cells and cell monolayers. [ABSTRACT FROM AUTHOR]

Stress granules and P-bodies are conserved cytoplasmic biomolecular condensates whose assembly and composition are well documented, but whose clearance mechanisms remain controversial or poorly described. Such understanding could provide new insight into how cells regulate biomolecular condensate formation and function, and identify therapeutic strategies in disease states where aberrant persistence of stress granules in particular is implicated. Here, I review and compare the contributions of chaperones, the cytoskeleton, post-translational modifications, RNA helicases, granulophagy and the proteasome to stress granule and P-body clearance. Additionally, I highlight the potentially vital role of RNA regulation, cellular energy, and changes in the interaction networks of stress granules and P-bodies as means of eliciting clearance. Finally, I discuss evidence for interplay of distinct clearance mechanisms, suggest future experimental directions, and suggest a simple working model of stress granule clearance. [ABSTRACT FROM AUTHOR]