Interplay of chemotactic force, Péclet number, and dimensionality dictates the dynamics of auto-chemotactic chiral active droplets.

In living and synthetic active matter systems, the constituents can self-propel and interact with each other and with the environment through various physicochemical mechanisms. Among these mechanisms, chemotactic and auto-chemotactic effects are widely observed. The impact of (auto-)chemotactic effects on achiral active matter has been a recent research focus. However, the influence of these effects on chiral active matter remains elusive. Here, we develop a Brownian dynamics model coupled with a diffusion equation to examine the dynamics of auto-chemotactic chiral active droplets in both quasi-two-dimensional (2D) and three-dimensional (3D) systems. By quantifying the droplet trajectory as a function of the dimensionless Péclet number and chemotactic strength, our simulations well reproduce the curling and helical trajectories of nematic droplets in a surfactant-rich solution reported by Krüger et al. [Phys. Rev. Lett. 117, 048003 (2016)]. The modeled curling trajectory in 2D exhibits an emergent chirality, also consistent with the experiment. We further show that the geometry of the chiral droplet trajectories, characterized by the pitch and diameter, can be used to infer the velocities of the droplet. Interestingly, we find that, unlike the achiral case, the velocities of chiral active droplets show dimensionality dependence: its mean instantaneous velocity is higher in 3D than in 2D, whereas its mean migration velocity is lower in 3D than in 2D. Taken together, our particle-based simulations provide new insights into the dynamics of auto-chemotactic chiral active droplets, reveal the effects of dimensionality, and pave the way toward their applications, such as drug delivery, sensors, and micro-reactors.

Control of innate olfactory valence by segregated cortical amygdala circuits.

Animals perform innate behaviors that are stereotyped responses to specific evolutionarily relevant stimuli in the absence of prior learning or experience. These behaviors can be reduced to an axis of valence, whereby specific odors evoke approach or avoidance. The cortical amygdala (plCoA) mediates innate attraction and aversion to odor. However, little is known about how this brain area gives rise to behaviors of opposing motivational valence. Here, we sought to define the circuit features of plCoA that give rise to innate olfactory behaviors of valence. We characterized the physiology, gene expression, and projections of this structure, identifying a divergent, topographic organization that selectively controls innate attraction and avoidance to odor. First, we examined odor-evoked responses in these areas and found sparse encoding of odor identity, but not valence. We next considered a topographic organization and found that optogenetic stimulation of the anterior and posterior domains of plCoA elicits attraction and avoidance, respectively, suggesting a functional axis for valence. Using single cell and spatial RNA sequencing, we identified the molecular cell types in plCoA, revealing an anteroposterior gradient in cell types, whereby anterior glutamatergic neurons preferentially express Slc17a6 and posterior neurons express Slc17a7. Activation of these respective cell types recapitulates appetitive and aversive valence behaviors, and chemogenetic inhibition reveals partial necessity for valence responses to innate appetitive or aversive odors. Finally, we identified topographically organized circuits defined by projections, whereby anterior neurons preferentially project to medial amygdala, and posterior neurons preferentially project to nucleus accumbens, which are respectively sufficient and necessary for innate negative and positive olfactory valence. Together, these data advance our understanding of how the olfactory system generates stereotypic, hardwired attraction and avoidance, and supports a model whereby distinct, topographically distributed plCoA populations direct innate olfactory valence responses by signaling to divergent valence-specific targets, linking upstream olfactory identity to downstream valence behaviors, through a population code. This represents a novel circuit motif in which valence encoding is represented not by the firing properties of individual neurons, but by population level identity encoding that is routed through divergent targets to mediate distinct valence.

How far can air pollution affect tourism in China? Evidence from panel unconditional quantile regressions.

Previous studies provide empirical evidence for the connection between air pollution and tourism. However, many of them take the nexus as a linear one. It remains unexplored whether any thresholds are required for the nexus to materialize. This study systematically investigates whether PM2.5 concentrations-an essential indicator of air pollution-affect tourism in China at various tourism development levels. We analyze 284 Chinese cities from 2008 to 2018 using the Unconditional Quantile Regression method. Our statistical results reveal that air pollution positively influences tourism (regarding tourist visits and tourism revenue) in areas with low tourism development levels. However, a complex correlation between air pollution and tourism emerges when tourism development has reached a certain level. The correlation is initially negative, then positive, and finally disappears. But, the overall correlation remains negative. The effects of the interaction between air pollution and tourism resources on tourism are inverted U-shaped, implying that tourism resources can mitigate the negative effects of air pollution on tourism only when tourism development has reached a certain level. Based on the above findings, the associated policy implications are discussed.

Scanless two-photon voltage imaging.

Two-photon voltage imaging has long been heralded as a transformative approach capable of answering many long-standing questions in modern neuroscience. However, exploiting its full potential requires the development of novel imaging approaches well suited to the photophysical properties of genetically encoded voltage indicators. We demonstrate that parallel excitation approaches developed for scanless two-photon photostimulation enable high-SNR two-photon voltage imaging. We use whole-cell patch-clamp electrophysiology to perform a thorough characterization of scanless two-photon voltage imaging using three parallel illumination approaches and lasers with different repetition rates and wavelengths. We demonstrate voltage recordings of high-frequency spike trains and sub-threshold depolarizations from neurons expressing the soma-targeted genetically encoded voltage indicator JEDI-2P-Kv. Using a low repetition-rate laser, we perform multi-cell recordings from up to fifteen targets simultaneously. We co-express JEDI-2P-Kv and the channelrhodopsin ChroME-ST and capitalize on their overlapping two-photon absorption spectra to simultaneously evoke and image action potentials using a single laser source. We also demonstrate in vivo scanless two-photon imaging of multiple cells simultaneously up to 250 µm deep in the barrel cortex of head-fixed, anaesthetised mice.

Clathrin mediates membrane fission and budding by constricting membrane pores.

Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles' pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles' pore closure and that clathrin around Ω-profiles' base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles' base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin's well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents' function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin's pivotal role in pore constriction/closure.

Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Radon concentration in seawater as a geochemical indicator of submarine fault activity in the Yatsushiro Sea, Japan.

This study examined the relationship between radon (222Rn) concentrations in seawater and crustal activity in the Yatsushiro Sea by investigating the submarine fault zone situated at the southern end of the Futagawa-Hinagu fault zone, activated by the 2016 Kumamoto earthquake (M7.3). We conducted an analysis of 222Rn concentration in samples of bottom water just above the seafloor and pore water in sediments, utilizing multiple and piston cores from the Hakuho Maru Expedition KH18-3. The findings revealed significantly elevated 222Rn concentrations in the central sites of the Yatsushiro Sea, coinciding with a high-stress field exhibiting dense active faults. Seismicity analysis revealed heightened moment release and a low b-value post the 2016 Kumamoto earthquake, indicative of increased seismic activity and the potential for substantial earthquakes in the Yatsushiro Sea vicinity. Our results indicate that heightened concentrations of 222Rn in seawater can serve as an effective tracer for identifying and estimating submarine fault activities. Moreover, our research highlights the utility of 222Rn concentrations in detecting active submarine faults and assessing their activity. It contributes to a comprehensive understanding of the potential for significant earthquakes in the Yatsushiro Sea in the future.

Menstrual Blood as a Diagnostic Specimen for Human Papillomavirus Genotyping and Genital Tract Infection Using Next-Generation Sequencing as a Novel Diagnostic Tool.

BACKGROUND: Menstrual blood (MB) is a convenient specimen type that can be self-collected easily and non-invasively by women. This study assessed the potential application of MB as a diagnostic specimen to detect genital tract infections (GTIs) and human papillomavirus (HPV) infections in women. METHOD: Genomic DNA was extracted from MB samples. Pacific Bioscience (Pacbio) 16S ribosomal DNA (rDNA) high-fidelity (HiFi) long-read sequencing and HPV PCR were performed. RESULTS: MB samples were collected from women with a pathological diagnosis of CIN1, CIN2, CIN3 or HPV infection. The sensitivity and positive predictive value (PPV) of high-risk HPV detection using MB were found to be 66.7%. A shift in vaginal flora and a significant depletion in Lactobacillus spp. in the vaginal microbiota communities were observed in the MB samples using 16S rDNA sequencing. CONCLUSIONS: In this study, we demonstrated that MB is a proper diagnostic specimen of consideration for non-invasive detection of HPV DNA and genotyping using PCR and the diagnosis of GTIs using metagenomic next-generation sequencing (mNGS). MB testing is suitable for all women who menstruate and this study has opened up the possibility of the use of MB as a diagnostic specimen to maintain women's health.

Game Theoretic Clustering for Finding Strong Communities.

We address the challenge of identifying meaningful communities by proposing a model based on convex game theory and a measure of community strength. Many existing community detection methods fail to provide unique solutions, and it remains unclear how the solutions depend on initial conditions. Our approach identifies strong communities with a hierarchical structure, visualizable as a dendrogram, and computable in polynomial time using submodular function minimization. This framework extends beyond graphs to hypergraphs or even polymatroids. In the case when the model is graphical, a more efficient algorithm based on the max-flow min-cut algorithm can be devised. Though not achieving near-linear time complexity, the pursuit of practical algorithms is an intriguing avenue for future research. Our work serves as the foundation, offering an analytical framework that yields unique solutions with clear operational meaning for the communities identified.

Development and Validation of a Quantitative Coronary CT Angiography Model for Diagnosis of Vessel-Specific Coronary Ischemia.

BACKGROUND: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs. OBJECTIVES: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCTISCHEMIA) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE). METHODS: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed. In both studies, symptomatic patients with suspected stable coronary artery disease had prospectively undergone coronary computed tomography angiography (CTA), myocardial perfusion imaging (MPI), SPECT, or PET, fractional flow reserve by CT (FFRCT), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCTISCHEMIA model was developed in the derivation cohort of the CREDENCE study, and its diagnostic performance for coronary ischemia (FFR ≤0.80) was evaluated in the CREDENCE validation cohort and PACIFIC-1. Its prognostic value was investigated in PACIFIC-1. RESULTS: In CREDENCE validation (n = 305, age 64.4 ± 9.8 years, 210 [69%] male), the diagnostic performance by area under the receiver-operating characteristics curve (AUC) on per-patient level was 0.80 (95% CI: 0.75-0.85) for AI-QCTISCHEMIA, 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFRCT, and 0.65 (95% CI: 0.59-0.71; P < 0.001) for MPI. In PACIFIC-1 (n = 208, age 58.1 ± 8.7 years, 132 [63%] male), the AUCs were 0.85 (95% CI: 0.79-0.91) for AI-QCTISCHEMIA, 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFRCT, 0.89 (95% CI: 0.84-0.93; P = 0.262) for PET, and 0.72 (95% CI: 0.67-0.78; P < 0.001) for SPECT. Adjusted for clinical risk factors and coronary CTA-determined obstructive stenosis, a positive AI-QCTISCHEMIA test was associated with aHR: 7.6 (95% CI: 1.2-47.0; P = 0.030) for MACE. CONCLUSIONS: This newly developed coronary CTA-based ischemia model using coronary atherosclerosis and vascular morphology characteristics accurately diagnoses coronary ischemia by invasive FFR and provides robust prognostic utility for MACE beyond presence of stenosis.

Chiral active particles are sensitive reporters to environmental geometry.

Chiral active particles (CAPs) are self-propelling particles that break time-reversal symmetry by orbiting or spinning, leading to intriguing behaviors. Here, we examined the dynamics of CAPs moving in 2D lattices of disk obstacles through active Brownian dynamics simulations and granular experiments with grass seeds. We find that the effective diffusivity of the CAPs is sensitive to the structure of the obstacle lattice, a feature absent in achiral active particles. We further studied the transport of CAPs in obstacle arrays under an external field and found a reentrant directional locking effect, which can be used to sort CAPs with different activities. Finally, we demonstrated that parallelogram lattices of obstacles without mirror symmetry can separate clockwise and counter-clockwise CAPs. The mechanisms of the above three novel phenomena are qualitatively explained. As such, our work provides a basis for designing chirality-based tools for single-cell diagnosis and separation, and active particle-based environmental sensors.

Bilobed Flap Coverage for the Reconstruction of Dorsal Soft Tissue Defect Over the Proximal Phalanx: A Case Report.

Soft tissue defects over the dorsal finger are common and may result from trauma, burns, or surgical management of infections and tumors. We present a case where a bilobed flap was used for the reconstruction of a soft tissue defect dorsal to the proximal phalanx of the ring finger and discuss the design of this flap. The defect was secondary to a collar button abscess of the right third webspace and the surgical debridement required to control the infection. The exposed extensor tendon over the proximal phalanx required coverage. The bilobed flap was designed with the first lobe over the right middle finger proximal phalanx and the second lobe over the right second webspace and index finger. The flap healed uneventfully and the patient had good functional recovery. This design for a bilobed flap is suitable for soft tissue reconstruction of defects over the dorsum of the proximal phalanx. It is a simple, reliable, single-staged procedure that provides like-for-like reconstruction and has minimal donor site morbidity.

Membrane transformations of fusion and budding.

Membrane fusion and budding mediate fundamental processes like intracellular trafficking, exocytosis, and endocytosis. Fusion is thought to open a nanometer-range pore that may subsequently close or dilate irreversibly, whereas budding transforms flat membranes into vesicles. Reviewing recent breakthroughs in real-time visualization of membrane transformations well exceeding this classical view, we synthesize a new model and describe its underlying mechanistic principles and functions. Fusion involves hemi-to-full fusion, pore expansion, constriction and/or closure while fusing vesicles may shrink, enlarge, or receive another vesicle fusion; endocytosis follows exocytosis primarily by closing Ω-shaped profiles pre-formed through the flat-to-Λ-to-Ω-shape transition or formed via fusion. Calcium/SNARE-dependent fusion machinery, cytoskeleton-dependent membrane tension, osmotic pressure, calcium/dynamin-dependent fission machinery, and actin/dynamin-dependent force machinery work together to generate fusion and budding modes differing in pore status, vesicle size, speed and quantity, controls release probability, synchronization and content release rates/amounts, and underlies exo-endocytosis coupling to maintain membrane homeostasis. These transformations, underlying mechanisms, and functions may be conserved for fusion and budding in general.