Interleukin-1β (IL-1β) and the interleukin-1 receptor antagonist (IL-1Ra) share the β-trefoil fold, engage the same receptor (IL-1R), but produce opposite biological outcomes. IL-1β recruits the accessory protein IL-1RAcP to initiate inflammatory signaling while IL-1Ra occupies the receptor without supporting co-receptor recruitment. Seeking the origin of this divergence in properties not apparent from static structures, we used solution NMR relaxation to characterize fast internal motion in both proteins. Rigorous treatment of macromolecular tumbling shows both to be nearly maximally triaxial, which admits two near-degenerate axially symmetric solutions. This ambiguity was propagated throughout and found to have negligible impact. Complete replicate data sets from independently prepared IL-1β samples establish the experimental precision directly. Backbone amide and methyl-bearing side chain order parameters are indistinguishable between the two proteins, the latter averaging 0.484 ± 0.030 and 0.486 ± 0.033, indicating essentially equivalent residual conformational entropy. Their spatial distributions are uncorrelated when projected onto the shared fold. Importantly, the difference between the proteins is concentrated at the receptor interface, where methyl probes lying on the IL-1β footprint are considerably more mobile than those of IL-1Ra. It is therefore the agonist, not the antagonist, that presents an anomalously mobile binding surface. IL-1Ra also buries some 16% less surface while ostensibly binding IL-1R more tightly, the signature of an interface predisposed toward productive contact. Conformational entropy can thus distinguish protein function where structure and average flexibility are conserved, and the distinction resides not in how much entropy a protein has but in where it is kept.

Conventional techniques for repairing an irreparable posterosuperior massive rotator cuff tear (MRCT) typically fail[1,2]. The supraspinatus tendon reconstruction (STR) technique offers a systematic approach to achieve both anatomic restoration and functional recovery of the supraspinatus tendon[1]. The use of autografts for reconstruction is challenged by their limited availability, inadequate dimensions, and donor site morbidity. The Ligament Augmentation and Reconstruction System (LARS; MovMedix) is a synthetic ligament consisting of fibers made of polyethylene terephthalate that is used as an alternative to autograft; however, concerns remain regarding inadequate graft integration with bone[3]. In contrast, fascia lata autografts demonstrate enhanced interface healing with both the supraspinatus muscle and the bone at the footprint[4-6]. The present article describes a unique arthroscopic STR approach involving a hybrid LARS-fascia lata graft for irreparable posterosuperior MRCTs.

CRISPR-associated transposons (CASTs) enable programmable DNA integration, yet how the TnsC regulator forms processive filaments on DNA to coordinate RNA-guided transposition in type V-K CAST systems remains unknown. Here, we integrate large-scale molecular simulations, interpretable deep learning using graph attention networks (GATs), and causal inference analyses to define the molecular determinants of TnsC filament nucleation and elongation. We show that TnsC nucleates by inducing localized DNA deformation that propagates along extended filaments, with Granger causality revealing that TnsC motions precede and predict DNA deformation. Interpretable GAT models demonstrate that elongation is determined during early recognition between incoming and DNA-bound subunits, followed by structural reorganization that regenerates the recruitment interface and enables processive assembly. These results elucidate the molecular mechanism of processive TnsC filament assembly and explain why isolated TnsC filaments preferentially elongate in the 5' → 3' direction, while accessory transposition factors can reshape the interaction landscape and alter filament growth polarity. Together, these findings advance our understanding of CAST function and inform the engineering of programmable DNA integration platforms. Beyond CAST systems, this work introduces an interpretable GAT approach as a general and transferable deep learning strategy for uncovering molecular mechanisms in biological systems, while demonstrating the power of causal inference for dissecting directional relationships in molecular dynamics.

There is growing evidence that human-induced climate change and habitat loss are having negative impacts on insect populations. New technologies have a vital role in improving and expanding global biodiversity monitoring capacity to understand where change is happening and to support restoration. Monitoring of insects traditionally needs entomologists in the field, but insect camera traps powered by AI are emerging as a scalable approach to monitoring semi-autonomously. These systems attract, detect, and identify insects using a Raspberry Pi, camera and UV lights. AI algorithms are also being developed by a network of researchers across the world to help with identification, notably in Europe and North America. The first version of a system for monitoring nocturnal insects was developed by Bjerge et al. 2021. An Automated Light Trap to Monitor Moths (Lepidoptera) Using Computer Vision-Based Tracking and Deep Learning. Here we describe the second generation of the system as an open-source solution. This paper aims to enable anyone to build their own system, and to iterate and improve the design for their needs. This system captures images at set intervals or based on motion detection to monitor insects that are attracted to lights at night. The UKCEH Automated Monitoring of Insects system (UKCEH AMI-system) is an insect camera trap designed using a single board computer, USB camera and attractant lights as the primary components along with peripheral accessories to make an autonomous system capable of long-term deployment in the field. Nearly 200 UKCEH AMI-systems have been deployed to date in over 30 countries around the world.

The electric double layer (EDL) at the copper/polyethylene (Cu/PE) interface critically affects space charge injection and insulation performance of high-voltage cables and their accessories, yet its molecular-level regulation remains unclear. This study systematically investigates the effects of different EDL structures on the potential distribution and interfacial barrier at the Cu/PE interface using first-principles calculations. The results show that the EDL-induced built-in electric field significantly modulates the potential of the PE layer, while the Cu layer remains largely unaffected. When the Cu side is positively charged and PE negatively charged, the EDL increases the interfacial barrier, suppressing charge injection and restricting PE molecular diffusion. Conversely, an EDL with negatively charged Cu and positively charged PE lowers the barrier, promotes charge injection, and enhances the diffusion of PE molecules. Notably, Na-induced EDL enhances PE diffusivity, whereas F-induced EDL restricts molecular motion. This work elucidates the regulatory mechanisms of EDL on both electronic and kinetic properties at the Cu/PE interface, providing a theoretical foundation for improving high-voltage cable insulation.

Accessory meniscal tissue is a rare anatomical variant of the knee and may present with mechanical symptoms when it impinges between the femoral condyle and tibial plateau. We report a 23-year-old female with right knee pain, intermittent catching, and medial joint-line tenderness following a twisting injury of 2 months duration. Radiographs were unremarkable. Magnetic resonance imaging suggested a complex tear of the posterior horn/body of the medial meniscus with an additional curvilinear meniscal-like band. Arthroscopy confirmed a mobile accessory meniscal band overlying the posterior horn and body of the medial meniscus, associated with a complex medial meniscal tear. Arthroscopic partial meniscectomy with excision of the accessory band was performed while preserving a stable meniscal rim. The postoperative course was uneventful, pain improved by postoperative day 2, and at 6 weeks the patient was asymptomatic with full range of motion and no catching or locking. This case highlights the need to consider anomalous meniscal anatomy in young patients with persistent mechanical knee symptoms and atypical MRI findings. Arthroscopy remains both diagnostic and therapeutic, and targeted excision can provide rapid symptom relief while preserving meniscal tissue.

Recent advances in neural networks trained on natural language have revealed that category-selective regions encode complex semantics and contextual information of natural scenes in addition to object categories. However, the limited interpretability of embeddings derived from these models complicates the characterization of the aspects of natural scenes that contribute to such semantic representations. Here we addressed this question by developing an analysis of the relationship between object co-occurrence in large-scale natural scene captions and corresponding fMRI responses predicted by caption-based encoding models, inspired by the fact that the joint presence of multiple objects generally shapes the overall content of a scene. We performed this analysis on the extrastriate body area (EBA), which responds strongly to human body parts. We found that human bodies co-occurring with sports-related objects drive the strongest predicted responses in the EBA among all image categories, whereas those co-occurring with vehicles or accessories elicit strong but weaker predicted responses. The findings from the co-occurrence analysis helped identify three key body-related features that contribute to the semantic representation in the EBA and fusiform body area: human body motion speed implied in static images of natural scenes is a primary contributor, and the number of people and body size are secondary contributors. Our framework, integrating object co-occurrence with caption-based encoding models, offers an interpretable approach for understanding high-level visual representations underlying natural scene perception.

An embedded server layer of Experimental Physics and Industrial Control System (EPICS) for PowerPMAC motion controllers has been developed and deployed at two undulator beamlines of the National Institute of General Medical Sciences and the National Cancer Institute (GM/CA) Structural Biology Facility at the Advanced Photon Source (APS). This compact, open source solution makes the power and versatility of PowerPMAC motion controls directly accessible to distributed EPICS clients. At GM/CA the system controls about 200 servo and stepper motors - both encoded and unencoded - and multiple digital and analog I/O accessories. The server stack comprises two sublayers: a lower-level driver and database that communicates directly with PowerPMAC, and a facility-specific soft sublayer built on top. The paper describes installing EPICS on PowerPMAC, the implementation of both layers and client examples, including on-the-fly scanning.

Retinal direction selectivity is a vital component of many visual functions, including motion processing and gaze stabilization. Direction selectivity emerges from specialized retinal ganglion cells (RGCs) that encode motion along a single preferred direction. In the mouse retina, direction-selective (DS) RGC (DSGC) subtypes are quite diverse, but little is known about the genetic programs required to generate this diversity. Moreover, it is unclear whether transcription factors that specify distinct DS subtypes play additional roles in their maintenance or maturation. Here, we show that the transcription factor Gfi1 is a conserved regulator of two DSGC subtypes tuned to vertical motion: down ON-type DSGCs (D-oDSGCs) and F-mini ONs. We show that Gfi1 promotes early differentiation of both subtypes but has distinct roles later in their development. In D-oDSGCs, Gfi1 is required postnatally for directing dendritic elaboration, and loss of Gfi1 disrupts D-oDSGC-mediated downward motion-tracking behavior, whereas in F-mini ONs, Gfi1 is required for continued cell survival . These findings reveal shared and divergent temporally segregated functions of Gfi1 in the assembly of retinal DS circuits.

The optokinetic reflex (OKR) is an evolutionarily conserved reflexive behavior that ensures image stabilization on the retina during global motion. It consists of smooth eye tracking movements in the direction of the moving stimulus interspersed with rapid resetting saccades. This reflex is driven by retinal ON direction-selective ganglion cells (oDSGCs), which comprise distinct subtypes tuned either to vertical or horizontal motion. oDSGCs convey directional signals to the brain via precise axonal projections to specific accessory optic system (AOS) nuclei. However, the mechanisms that establish and maintain the specificity of these circuits remain poorly understood. Here, we identify a critical role for the mechanosensitive ion channel Piezo2 in refining AOS circuitry to ensure appropriate eye movement responses. Single-cell transcriptomic profiling revealed selective enrichment of Piezo2 in horizontally-tuned oDSGCs. We show that both loss and hyperactivation of Piezo2 in retinal neurons leads to cross-coupling of horizontal and vertical OKR responses, producing aberrant diagonal eye tracking movements during horizontal optokinetic stimulation. Mechanistically, Piezo2 regulates the developmental refinement of oDSGC axonal projections within the AOS, and disruption of this process results in persistent ectopic innervation that enables aberrant crosstalk between horizontal and vertical motion pathways. These findings reveal a channel activity-dependent mechanism that ensures the functional segregation of directional motion circuits underlying gaze stabilization.