Tissue morphogenesis requires tight coordination between biochemical signaling and mechanical forces that sculpt cells and tissues. While actomyosin networks are well-established force generators, microtubule-based mechanics have recently emerged as crucial contributors to tissue remodeling. Yet, how dynamic microtubules, whose plus ends undergo compression-induced catastrophes that limit their load-bearing capacity, generate forces in vivo remains unclear. Here, we identify Orbit, the Drosophila cytoplasmic linker-associated protein (CLASP) homolog, as a key factor that stabilizes non-centrosomal microtubule plus ends in vivo, enabling them to sustain mechanical loads. In the pupal wing epithelium, these Orbit-stabilized, planar-polarized microtubules are consistent with a role in counteracting actomyosin contractility and promoting tissue elongation. Loss of Orbit increases catastrophe frequency and disrupts epithelial elongation, whereas Orbit overexpression enhances microtubule rescues by suppressing catastrophes, thereby promoting cell anisotropy and tissue extension. Moreover, Orbit-mediated stabilization is sufficient to induce microtubule-dependent, filopodia-like protrusions independent of actin. Together, these findings establish CLASP-dependent microtubule stabilization as a key mechanism linking polymerization dynamics to epithelial morphogenesis.
Machine learning is a powerful tool for modeling complex movements. However, the high cost of acquiring biomechanical data often limits observations and therefore the generalizability of machine learning models. Meanwhile, there is untapped utility in presently published musculoskeletal simulations for informing these predictions. This work evaluated whether a transfer learning model trained on both musculoskeletal simulation and recorded data outperforms a direct learning model trained on recorded experimental data alone. For the transfer learning model, we leveraged a simulation dataset with 6,594 lateral pinch simulations to train a long short-term memory neural network to predict three-component thumb-tip forces from muscle activations. We concatenated this pre-trained neural network with a feedforward architecture and used recorded data (n=12 subjects) to fine-tune the model. The feedforward architecture used the outputs of the long short-term memory neural network, as well as static subject-specific features (e.g., anthropometric measurements). We then trained a direct learning model with a similar architecture using just the recorded data. The transfer learning and direct learning models were parameterized via a random search and underwent five-fold cross-validation. To elucidate the impact of pre-training with simulations, we validated both neural networks and compared their test errors using a leave-out set (n=3 subjects). The transfer learning model outperformed the direct learning model, as suggested by statistically significant lower absolute errors (p = 0.04). Our results suggest the viability of using musculoskeletal simulations to bolster machine learning models that can expand the utility of simulated datasets and potentially improve predictions of real-world biomechanics.
Stokes flow studies are fundamental to advancing medical and industrial technologies, particularly in areas such as drug targeting, cell studies, the optimization of drug carrier vehicles, high viscosity flows, and magnetic particle imaging. While previous research has focused on the motion of obliquely falling cylindrical rods and magnetic particle chains, a broader analytical framework is required to understand more complex particle-fluid migrations. In this paper, we first generalize the two-dimensional motion of an obliquely falling rod in a gravitational field to the three-dimensional motion of an object possessing three mutually perpendicular planes of symmetry falling through a viscous fluid in the Stokes limit. We derive a general formula for the three components of velocity-including both downward and sideways components-for objects of arbitrary orientation and uniform density. These analytical solutions are defined in terms of the object's orientation, specified via Euler angles, and the velocity of the object falling along each of its three principal axes, or the drag coefficient along each of those axes. We give a variety of examples of objects that satisfy this general formula. In addition, we apply the formula to a cuboid for which those velocity components along each of its principal axes have been measured experimentally by other researchers, thus giving both the downward and sideways components for arbitrary orientation. We then analyze the motion in a gradient magnetic field of elongated magnetic particles, such as nanorods and nanoellipsoids, for which the induced magnetic moment is along the long axis of the particle. We discuss the similarities and differences with the gravitational case. By providing a unified framework for predicting the trajectories of these symmetric bodies, this work enhances the understanding of the motion of inertial and magnetic particles under the influence of gravitational and gradient magnetic fields, respectively.
The significance of experimentally observed friction between orthodontic brackets and the connecting archwire for multibracket therapy is still debated. This publication is intended to provide detailed and validated information for the discussion of this issue during the initial alignment and levelling phase. Frictional forces were determined by using in vitro experiments of the simulated levelling of a malpositioned maxillary central incisor. For each experiment a straight archwire was placed in the slots of three aligned brackets. Levelling was simulated by bending the wire using a multistep displacement of the middle bracket. All force and moment components corresponding to each step were recorded at the central and lateral brackets. In vitro frictional forces and the corresponding friction coefficients were determined through direct comparison of experimental results and, additionally, using numerical methods. Different types of conventional orthodontic wires, made of stainless steel [SS] and titanium molybdenum alloy [TMA] were tested. Results indicated that calculated friction coefficients (SS ~0.1; TMA ~0.2) agreed with published reference data. The mesiodistal forces were proportionally more affected (~100% increase) by friction than the levelling forces (10%-20% reduction). Comparison with numerical models demonstrated that carefully dislodging and reinserting the wire is a viable strategy to remove frictional forces. The findings indicate that vertical tooth movement was only moderately influenced by friction when conventional SS or TMA wires were used. Clinically, the results suggest that an effective way to reduce friction may be re-opening wire ligatures or using passive self-ligating brackets. ZIELSETZUNG: Die Bedeutung der experimentell beobachteten Reibung zwischen kieferorthopädischen Brackets und dem verbindenden Bogendraht für die Multibracket-Therapie ist nach wie vor Gegenstand von Diskussionen. Diese Veröffentlichung soll detaillierte und validierte Informationen für die Erörterung dieser Frage während der anfänglichen Ausrichtungs- und Nivellierungsphase liefern. Die Reibungskräfte wurden anhand von In-vitro-Experimenten zur simulierten Nivellierung eines fehlgestellten oberen mittleren Schneidezahns ermittelt. Bei jedem Experiment wurde ein gerader Bogendraht in die Schlitze von drei nebeneinander angeordneten Brackets eingelegt. Die Nivellierung wurde durch Biegen des Drahtes mittels einer mehrstufigen Verschiebung des mittleren Brackets simuliert. Bei jedem Schritt wurden alle Kraft- und Momentkomponenten am mittleren und an den seitlichen Brackets aufgezeichnet. Die In-vitro-Reibungskräfte und die entsprechenden Reibungskoeffizienten wurden durch direkten Vergleich der Versuchsergebnisse sowie zusätzlich unter Verwendung numerischer Methoden ermittelt. Getestet wurden verschiedene Arten von konventionellen, kieferorthopädischen Drähten aus Edelstahl [SS] und Titan-Molybdän-Legierung [TMA]. Die Ergebnisse zeigten, dass die berechneten Reibungskoeffizienten (SS ~0,1; TMA ~0,2) mit veröffentlichten Referenzdaten übereinstimmten. Die mesiodistalen Kräfte wurden proportional stärker (~100% Anstieg) durch Reibung beeinflusst als die Nivellierungskräfte (10–20% Abnahme). Der Vergleich mit numerischen Modellen zeigte, dass das vorsichtige Lösen und erneute Einsetzen des Drahtes eine praktikable Strategie zur Beseitigung von Reibungskräften darstellt. Die Ergebnisse deuten darauf hin, dass die vertikale Zahnbewegung bei Verwendung herkömmlicher SS- oder TMA-Drähte nur mäßig durch Reibung beeinflusst wurde. Klinisch legen die Ergebnisse nahe, dass das erneute Öffnen von Drahtligaturen oder die Verwendung passiver, selbstligierender Brackets ein wirksames Mittel zur Verringerung der Reibung sein könnte.
Labiaplasty has expanded worldwide, provoking debate over whether it reflects women's liberation, reinforces objectifying beauty norms, or medicalizes normal vulvar variation. Clinicians lack integrative guidance linking outcomes with feminist ethical analysis. To synthesize evidence on labiaplasty through feminist frameworks of liberation, objectification, and medicalization; evaluate functional, sexual, and psychological outcomes; and propose a clinical framework centered on relational autonomy and non-pathologizing education. A narrative review of peer-reviewed literature (2002-2025) was conducted using PubMed and Google Scholar, with screening of relevance based on predefined thematic domains including motivations, outcomes, sociocultural influences, and ethics. Empirical studies on motivations, outcomes, and educational interventions were included as clinical evidence, while feminist theoretical and ethical analyses were used for interpretive synthesis. Data were synthesized thematically along three axes: Liberation/autonomy, objectification/sociocultural pressure, and medicalization of normal anatomy. Utilization of labiaplasty has increased markedly, including in adolescents, although population-level rates remain underreported. Patients commonly endorse overlapping functional, aesthetic, and psychosexual motivations; many have labial dimensions within published normative ranges. Prospective cohorts and meta-analyses show high satisfaction and improvement in pain, functional symptoms, genital self-image, and sexual function, with low rates of major complications or long-term sensory loss when nerve-sparing techniques are used. However, elevated body-image distress and clinically significant body dysmorphic disorder (BDD) occur in a substantial subset. Media, pornography, and clinical marketing narrow perceptions of "normality," while language and diagnostic labels can pathologize benign variation. Labiaplasty sits at the intersection of liberation, objectification, and medicalization: Many patients experience benefit, yet decisions are shaped by sociocultural forces that constrain autonomy and recast normal anatomy as abnormal. The proposed L.A.B.I.A. framework (legal safeguards, autonomy assessment, body-image/BDD screening, informed consent and non-pathologizing education, and aftercare) offers clinicians an ethically grounded approach to counseling, patient selection, and follow-up while underscoring the need for education and policy that normalize vulvar diversity.
Nanofiltration (NF) is an effective barrier for removing nanoplastics (NPs) from water. However, NPs can deposit on the membrane surface and remain even after backwash, altering surface properties and reducing filtration performance. In this study, laser-induced breakdown detection (LIBD) is coupled in-line with a bench-scale NF system to quantify the deposition and release of polystyrene (PS) particles and weathered NPs at environmentally relevant concentrations (1-500 µg/L; 107-109 particles/mL). Particle deposition during filtration and release during backwash were successfully determined in all experiments, supported by theoretical analysis of the interplay between hydrodynamic and intermolecular forces. At permeate fluxes higher than 100 L/m2.h, 50-100% of PS particles were deposited by the end of filtration experiments, forming cake layers up to 9 particle diameters thick. In contrast, weak permeate drag forces corresponding to fluxes below 50 L/m2.h (i.e., just beyond the critical flux) resulted in insignificant deposition. Backwash fluxes from 15 to 57 L/m2.h exhibited negligible differences in the release of deposited particles owing to only a little increase in backwash drag force. Two mechanisms were observed for the release of NPs during backwash: i) complete release in small circular areas (diameter ≤2 µm) for thin deposits and ii) fracturing of the cake layer for thick deposits. For weathered NPs, irreversible deposition on the membrane surface was observed, although potential particle aggregation and polydispersity must be accounted for to obtain truly quantitative results. The successful quantification of particle deposition and release showcases LIBD as an effective method for fundamental investigations on NP transport during membrane filtration.
Subterranean ecosystems play a pivotal role in shaping diversification processes, particularly among invertebrates, which frequently exhibit convergent troglomorphic traits such as ocular reduction and elongation of appendages. Among crustaceans, amphipods demonstrate exceptional adaptive potential for colonizing hypogean habitats, revealing an often underappreciated reservoir of subterranean biodiversity. In the semiarid Caatinga of northeastern Brazil, the Jandaíra Formation constitutes an extensive Cretaceous limestone system, harboring more than 1,400 documented caves and representing a critical hotspot for stygobiotic taxa. Building on this insight, we expand the known range of Seborgia within the Jandaíra Formation and describe a single new troglobitic species from a spatially isolated cave system. This species is readily diagnosable by distinct morphological characters of the gnathopods, uropods, and telson, and its occurrence in strict allopatry is consistent with diversification driven by subterranean vicariance. Its highly restricted distribution highlights the role of hydrogeological isolation and habitat fragmentation as key evolutionary forces shaping subterranean diversity in this region. Notably, the newly described species occurs in a cave in the Furna Feia National Park, highlighting the importance of protected areas for the conservation of subterranean ecosystems and their unique biodiversity.
Polychlorinated Biphenyls (PCBs) are persistent organic pollutants in the environment. With high lipophilicity, PCBs are easily accumulated in the brain, finally leading to neurotoxicity. The underlying neurotoxicity mechanism of PCBs remains poorly understood and requires urgent investigation. The neurotransmitter system has been identified as a potential target of PCB-involved neurotoxicity. Current research on the neurotoxicity mechanism of PCBs predominantly focuses on single target. Due to the high complexity of the brain, the disorder of synaptic transmission triggered by environmental pollutants is highly complicated, and the corresponding mechanisms are likely to involve multi-targets. Here, we focused on two highly correlated components of the dopaminergic system-the dopamine transporter (DAT) and dopamine receptor (DR), to investigate whether there is a synergetic effect between them. By combining multiple computational methods and experimental assays, this study elucidated that DAT was a potential target of neurotoxicity for PCBs in the dopaminergic system, whereas it was highly unlikely for DR to bind PCBs. The computational results indicated that the affinity of the pentachloro biphenyl was higher than the tetrachloro biphenyl. The Van der Waals and π-π interactions were the main driving forces for PCBs binding to DAT. The decomposition energy confirmed that the key residues involved in the ligand binding were converged to Val120, Tyr124, and Phe325 for most of the tested PCBs. Our findings not only provide a detailed and plausible molecular mechanism of PCBs' neurotoxicity, but also are useful for the rational drug design to fight diverse CNS disorders and other diseases involving DAT.
This study explored the impact of varying cassava starch (CS) levels on the rheological and textural attributes and printability of sodium caseinate-cassava starch (NaCas-CS) composite emulsion gels. Increasing the CS content led to higher apparent viscosity and gel hardness, reduced fluidity, and promoted the formation of a tighter network. The composite containing 12% CS exhibited the best printing performance and dimensional accuracy, suggesting that an optimal balance of viscosity, hardness, and flow behavior is essential for successful 3D printing. Furthermore, increasing CS caused a leftward shift in relaxation time, indicating restricted water mobility and enhanced water-binding capacity. Microstructural analysis confirmed that elevated CS contents facilitated the development of a denser network. FT-IR analysis supported that the enhanced emulsion gel properties were driven by strengthened intermolecular interactions between CS and NaCas, including hydrogen bonding and electrostatic forces. These findings guide starch-enhanced 3D printability of protein gels and support starch-protein composites in food applications.
Focal adhesions are central structures that allow cells to sense and respond to extracellular mechanical cues, yet traditional interaction-based models cannot fully explain their efficient protein enrichment, rapid turnover, and strong mechanical sensitivity. Recent studies highlight liquid-liquid phase separation (LLPS) as a novel physicochemical mechanism that reshapes our understanding of focal adhesion organization and function. This review summarizes current mechanisms of focal adhesion-mediated mechanosensing, with a focus on the emerging role of phase separation. Several core focal adhesion proteins, such as talin and paxillin, can form biomolecular condensates whose assembly is regulated by mechanical forces and post-translational modifications. These condensates offer a mechanism for converting mechanical inputs into biochemical signals. We highlight how phase separation contributes to focal adhesion assembly, maturation, cytoskeletal regulation, and dynamic turnover. The concept of LLPS provides a unified framework for understanding focal adhesion behavior and advances our understanding of cellular mechanosensing.
Engineering organized microvascular networks remains a critical challenge in tissue engineering and regenerative medicine. While biochemical approaches for patterning angiogenesis via growth factor delivery have shown promise, their inability to pattern sustained growth factors with spatiotemporal control limits effectiveness. Here, we demonstrate that dynamically patterned mechanical forces enable precise spatiotemporal control over angiogenic sprouting. We developed a magnetically actuated human vessel-on-a-chip platform that integrates a perfusable endothelialized microchannel within a collagen matrix and allows noninvasive and tunable mechanical stimulation across three spatial dimensions and time (4D). Using an automated 3-axis actuator, we systematically investigated how strain magnitude, frequency, and direction modulate endothelial cell behavior and vessel morphogenesis. Dynamic mechanical stimulation at physiological strain magnitudes (5 to 15%) enhanced endothelial alignment and barrier function while promoting angiogenesis in a strain magnitude-dependent manner: lower dynamic strain (5%) maximized sprout initiation, whereas higher dynamic strain (15%) promoted elongation of sprouts. Sequential reorientation of strain direction reprogrammed sprouting trajectories along X, Y, and Z directions, generating complex sprout geometries such as L-shaped branches. RNA sequencing revealed mechanically induced transcriptional profiles distinct from unstimulated controls, characterized by upregulation of genes associated with angiogenesis, mechanotransduction, and extracellular matrix remodeling. Functional perturbation of PIEZO1 reduced strain-induced sprouting without altering barrier function, indicating that dynamic mechanical stimulation engages multiple mechanotransduction pathways to regulate angiogenesis. Collectively, these findings establish a strategy for spatiotemporally controlled angiogenesis through 4D force patterning to program vascular morphogenesis while preserving function. This approach provides a foundation for engineering hierarchically organized vascular networks for tissue regeneration.
Three new studies show that a single receptor-ligand pair, Teneurin-3 and Latrophilin-2, directs long-range circuit assembly across diverse brain regions through opposing forces of attraction and repulsion. The same two molecules, reused again and again, wire the brain.
In this study, the polygonatum sibiricum polysaccharide (PSP) was extracted using the deep eutectic solvent (DES) and added into soybean protein isolate (SPI) to prepare the SPI - PSP gel. Afterwards, the SPI - PSP gel properties were analyzed to explore how the PSP affected the gel properties and the gelation mechanism. When the PSP addition was from 0% to 2.5% (w/v, g/100 mL), the gel hardness increased from (18.70 ± 2.10) g to (36.10 ± 3.22) g. The gel consistency was enhanced, but the gel flow behavior was inhibited. Besides, the gel water-holding capacity rose from (83.56 ± 1.13) % to (89.80 ± 1.28) %, and the gel thermal stability was enhanced due to the PSP addition. The free sulfhydryl group, the protein structure changes and the intermolecular forces in the SPI - PSP gels were evaluated for exploring the gel formation mechanisms. It was found that the free sulfhydryl group content increased from (2.77 ± 0.01) to (3.40 ± 0.00) μmol/100 mg. The PSP significantly diminished α-helix and β-turn contents and elevated β-sheet content of the SPI secondary structure. So, more hydrogen bonding was formed to improve the SPI - PSP gel formation due to the changes of the SPI secondary structure. It was provided a basic to adjusting the gel properties according the polysaccharide addition.
Preclinical assessment of patient-specific mandibular reconstruction plates relies on bench testing and computational modeling, yet existing setups are typically designed on practical grounds without a structured method to ensure their mechanical relevance to the intended clinical context of use (COU). This study proposes and demonstrates a methodology for constructing and assessing a validation domain with experimental and computational components for patient-specific fibula free flap mandibular reconstruction. A clinical reference finite element model (M-COU) representing the reconstructed mandible under physiological clenching conditions was used as an active design tool to derive the validation setup. Parameters were identified through analytical calibration of M-COU reaction forces and refined via a design-of-experiments procedure. The resulting setup was implemented as two coordinated components: a physical validation platform (R-VAL) enabling bench testing of the actual reconstruction plate, and a validation computational model (M-VAL) reproducing the same setting numerically. The resulting setup preserved the dominant mechanical features of the clinical scenario. In consistency analysis against M-COU, M-VAL achieved R2 = 0.75, substantially exceeding literature-based benchmark configurations (R2 = 0.27 and 0.40), and was the only configuration to preserve the clinically relevant stress distribution at the mandibular angle. Comparison between M-VAL and R-VAL showed close agreement in initial structural stiffness (0.6% difference) and local strain distribution (R2 = 0.93; RMSE = 10.9%). The proposed methodology provides a transferable framework for constructing validation domains that are simultaneously experimentally feasible, mechanically interpretable, and grounded in a defined clinical COU.
Microbial-metabolic axis drives meat quality deterioration and shelf-life changes along commercial supply chains. This study tracked pork quality and freshness from postmortem processing to retail sale by integrating untargeted metabolomic and metagenomic analyses. Over the first 1700 min postmortem, pork showed a decline in pH and increases in L*, a* and b* values, cooking loss, shear force, total volatile basic nitrogen and total viable counts. At the point of sale, the meat remained in rigor mortis and retained acceptable freshness. Metabolic profiles remained dynamic after warehousing and were further modified by ambient exposure during transport and retail sale. Results revealed that differential metabolites were predominantly enriched in purine metabolism, nucleotide metabolism, lysosome pathway, as well as alanine, aspartate and glutamate metabolism. Likewise, several genera potentially associated with spoilage or contamination-associated bacteria were influenced by commercial condition along the supply chain, with increased abundance of Acinetobacter, Bacillus, Listeria, Psychrobacter, Salmonella andEnterobacter during transport and retail sale, while Listeria, Salmonella andEnterobacter may originate from environmental or processing-associated sources. These findings identify stage-specific metabolic and microbial signatures shaped by commercial handling, such as temperature, relative humidity and provide insights for improving pork quality and safety management during the early postmortem period.
This study aimed to clarify the age-related adaptations in propulsive and braking mechanisms during gait acceleration and deceleration. Spatiotemporal gait parameters; the anteroposterior (AP), mediolateral (ML), and vertical (V) components of the ground reaction force (GRF); and the center of mass external moment (COM Mext) were analyzed and compared between younger and older adults. Thirty younger and thirty older healthy participants were enrolled. The participants performed walking trials under normal, maximum, acceleration, and deceleration conditions; kinematic and kinetic data were collected using a three-dimensional motion capture system and force plates. The spatiotemporal gait parameters, GRF AP, GRF V, and COM Mext were analyzed. Differences between younger and older adults were examined across gait conditions. During acceleration, older participants exhibited significantly smaller anterior GRF AP in the second half of the stance phase and slower gait speed compared with younger participants. During deceleration, older participants exhibited significantly smaller posterior GRF AP in the first half of the stance phase and higher cadence compared with younger adults. Older participants also exhibited greater GRF V in the first half of the stance phase during acceleration and deceleration, and lower values in the second half of the stance phase during acceleration compared with younger adults. Older participants exhibited reduced anterior GRF AP during the second half of the stance phase under acceleration, limiting their ability to increase gait speed from the initial step. During deceleration, insufficient braking force within a single step necessitated an increased number of steps to reduce speed.
We review and discuss all named United States and Mexico species of Ammopelmatus Tinkham Jerusalem crickets, even if synonymized in earlier literature. We recognize as valid 12 previously named taxa: A. cahuilaensis (Tinkham), A. comanchus (Saussure & Pictet), A. davewerneri (Tinkham), A. fuscus (Haldeman), A. intermedius (David & Smith), A. kelsoensis Tinkham, A. longispinus (Brunner von Wattenwyl), A. mescaleroensis (Tinkham), A. muwu Rentz & Weissman, A. navajo (Rentz), A. nigrocapitatus (Tinkham & Rentz), and A. pictus (Scudder). We confirm A. californicus (Brunner von Wattenwyl) as a junior synonym of A. longispinus. We synonymize A. monahansensis (Stidham & Stidham) under A. mescaleroensis. We designate neotypes for A. fuscus and A. mescaleroensis. We declare the following 6 names to be nomen dubium: A. cephalotes (Walker), A. fasciatus (Thomas), A. hydrocephalus (Brunner von Wattenwyl), A. irregularis (Brunner von Wattenwyl), A. oculatus (Scudder), and A. terrenus (Rehn). We recognize 11 major clades, and 26 Groups within those 11 clades, delimited by DNA, morphology, karyotype, ecology, and calling drum pattern. In their phylogenetic tree order, we recognize (1) the Winchester Group, with 11 (possibly 12) species; (2) the Big Sur Group, with 1 species; (3) the Longispinus Group, with 12 species; (4) the Portal Group, with 2 species; (5) the Argus Group, with 5 species; (6) the Mojave Desert Group, with 8 species, 1 which is tentative; (7) the Springville Group, with 1 species; (8) the Lightfooti Group, with 10 species; (9) the Smithi Group, with 3 species; (10) the Grayi Group, with 1 species; (11) the Southern California Group #1, with 4 species; (12) the Southern California Group #2, with 4 species; (13) the Southern California/Baja California Group #3, with 9 species; (14) the Lincoln County Group, with 1 species; (15) the Utah Group, with 3 species; (16) the Fuscus Group, with 5 species, 2 of which are tentative; (17) the Mono Lake Group, with 7 species; (18) the Muwu Group, with 1 species; (19) the Pratti Group, with 1 species; (20) the Fast Drumming Group, with 13 species; (21) the Vandenberg Air Force Base Group, with 2 species; (22) the San Gabriel/ Pelona Mts Group, with 2 species; (23) the Islander Group, with 2 species; (24) the Southern California Group #4, with 3 species; (25) the Southern California Group #5, with 2 species; and (26) the Monica Mts Group, with 2 species; We describe the following 105 taxa as new: A. abelai Weissman, A. acton Weissman, A. angelusoaks Weissman, A. anzaborrego Weissman, A. argus Weissman, A. ashleighi Weissman, A. bajasur Weissman, A. bakersfield Weissman, A. ballmeri Weissman, A. ballonadark Weissman, A. bartonflats Weissman, A. bigsur Weissman, A. brachysocius Weissman, A. briani Weissman, A. brockovichi Weissman, A. bruneaudunes Weissman, A. calimesa Weissman, A. carsoncity Weissman, A. castaneus Weissman, A. catalinae Weissman, A. cathedralgorge Weissman, A. cedarview Weissman, A. chimineas Weissman, A. chinalake Weissman, A. christmasvalleydunes Weissman, A. clarki Weissman, A. coralpink Weissman, A. coyflat Weissman, A. crypticus Weissman, A. danieli Weissman, A. descansodunes Weissman, A. dogtown Weissman, A. eatoncanyon Weissman, A. ensenada Weissman, A. etiwanda Weissman, A. evansi Weissman, A. finnon Weissman, A. fisheri Weissman, A. fremontpeak Weissman, A. glacierlodge Weissman, A. glennville Weissman, A. gomezfarias Weissman, A. grahami Weissman, A. grapevine Weissman, A. grayi Weissman, A. hovorei Weissman, A. icenoglei Weissman, A. idaho Weissman, A. intermedioides Weissman, A. islander Weissman, A. joshuatree Weissman, A. juniperdunes Weissman, A. kennedymeadows Weissman, A. kennedymeadowsdos Weissman, A. kirai Weissman, A. knighti Weissman, A. kokoweef Weissman, A. lagunahanson Weissman, A. lakecachuma Weissman, A. lakesherwood Weissman, A. larumorosa Weissman, A. leei Weissman, A. lightfooti Weissman, A. lincolncounty Weissman, A. longispinoides Weissman, A. mahogani Weissman, A. monolake Weissman, A. mtpinos Weissman, A. mtshasta Weissman, A. oneillpark Weissman, A. owensvalley Weissman, A. pinnacles Weissman, A. pinyonpines Weissman, A. piute Weissman, A. portal Weissman, A. pratti Weissman, A. reno Weissman, A. rentzi Weissman, A. rusti Weissman, A. sakai Weissman, A. sandiego Weissman, A. sanfrancisco Weissman, A. sangabriel Weissman, A. sanjacinto Weissman, A. sanmartinensis Weissman, A. sanpedromartir Weissman, A. santarosaplateau Weissman, A. sierrapelona Weissman, A. skinner Weissman, A. smithi Weissman, A. sonoraensis Weissman, A. springville Weissman, A. stringfellow Weissman, A. tarcanyon Weissman, A. tehachapi Weissman, A. temblor Weissman, A. tomsplace Weissman, A. vandenberg Weissman, A. warnermts Weissman, A. westgardpass Weissman, A. whitewater Weissman, A. winnemucca Weissman, A. wrightwoodi Weissman, A. yubalake Weissman, and A. zayante Weissman. Ammopelmatus has its highest species' diversity in Southern and Central California, with most taxa having limited distributions; and with most species nearest genetic relative usually being geographically close. Six newly described taxa rank as the six heaviest insect species in California, with some adults exceeding 12 grams. Where two Ammopelmatus species are sympatric, we present data that indirectly suggest that calling song drums may act as a premating barrier; and that diploid chromosome number may act as a post mating barrier.
Radiation-induced pulmonary fibrosis (RIPF) is a severe complication lacking effective treatment after thoracic radiotherapy. Cellular senescence and the senescence-associated secretory phenotype (SASP) are central drivers of this condition. Granzyme K (GZMK) is an inflammatory amplifier, yet its role in promoting RIPF by regulating cellular senescence remains unknown. A time-course mouse model of radiation-induced lung injury was established using single-dose 15 Gy thoracic irradiation. Histopathology and molecular analyses were performed to assess injury and GZMK expression. Cellular origins of GZMK were identified via publicly available single-cell data and multiplex immunofluorescence. In vitro, mouse lung epithelial (MLE12) and alveolar macrophage (MH-S) cell lines were treated with recombinant GZMK. Senescence was evaluated by SA-β-gal staining, EdU assay, and expression of p53/p21/p16 and SASP factors via WB and RT-qPCR. From week 12 post-irradiation, the GZMK inhibitor PPACK was administered to evaluate its therapeutic effects. GZMK was significantly upregulated during the fibrotic phase and localized predominantly to infiltrating CD8+ T cells. In vitro, GZMK directly induced cellular senescence and activated the p53/p21/p16 pathway along with SASP factor expression. In vivo inhibition of GZMK markedly attenuated lung collagen deposition, myofibroblast activation, senescent cell burden, and levels of SASP factors (IL-6, TNF-α, TGF-β). This study demonstrates that CD8+ T cell-derived GZMK drives RIPF by promoting cellular senescence and SASP. Targeting GZMK alleviated fibrosis, highlighting its potential as a therapeutic target for radiation-induced lung injury.
Excessive adiposity may alter dynamic postural control during functional tasks, but its influence on direction-specific acceleration during unilateral sit-to-stand transitions remains insufficiently understood. This study aims to examine the association between percent body fat and smartphone-derived direction-specific acceleration variables during the single-leg sit-to-stand test (SLSTST) in young adult females. Sixty young adult females, categorized by percent body fat as normal fat, overfat, and severe fat groups (n = 20 per group), performed the five-times SLSTST using the dominant leg. A smartphone positioned at the S2 level recorded linear acceleration in the mediolateral (ML), vertical (VT), and anteroposterior (AP) directions. Smartphone-derived acceleration variables were reported in cm/s², and task completion time was reported in seconds. Group differences were examined using one-way ANOVA with Bonferroni-adjusted post-hoc comparisons. The severe fat group exhibited greater direction-specific acceleration than the normal fat group, including posterior AP acceleration (-20.93 vs. -11.31 cm/s²), ML acceleration (5.85 vs. 1.38 cm/s²), and downward VT acceleration (-13.09 vs. -6.15 cm/s²). Task completion time was also longer in the severe fat group than in the normal fat group (18.21 vs. 11.72 s; p < 0.001). Total acceleration did not differ significantly among groups (p = 0.096). Severe adiposity was associated with altered direction-specific acceleration behavior and slower SLSTST performance. These findings suggest increased mechanical demand for dynamic postural control during unilateral functional transitions. Smartphone-based accelerometry may provide a feasible approach for detecting movement-control alterations, although future studies incorporating force plates, motion capture, electromyography, and segmental body composition assessment are required to confirm the underlying mechanisms.
Uterine fibroids (UFs) are the most important benign neoplastic threat to women's health worldwide, with no long-term noninvasive treatment options currently available. Among known UF driver alterations, somatic mutations in Mediator subunit MED12 are by the far the most prevalent, accounting for up to 80% of these clinically significant lesions. Although it is presently unclear how MED12 mutations trigger neoplastic transformation, MED12-mutant UFs are nonetheless characterized by significant chromosomal loss and rearrangement, suggesting genomic instability as a driving force in tumor development. However, the basis by which MED12 mutations drive genomic instability is not known. Herein, we show that R-loop-driven replication stress in MED12-mutant UFs leads to DNA under-replication and mitotic segregation errors that drive chromosomal instability. Notably, we find that vitamin D3 (VD3), a modifiable risk factor in UF development, suppresses pathogenic R-loop accrual and ameliorates replication stress-driven chromosomal instability, contributing to growth inhibition of patient-derived MED12-mutant UF xenografts in vivo. Altogether these findings uncover a molecular basis by which the predominant UF driver converges with a known risk factor at the interface of genomic instability, with significant translational implications for personalized UF prevention and treatment.