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Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing
The pituitary adenylate cyclase-activating polypeptide (PACAP) 1 receptor (PAC1R) is a class B1 G protein–coupled receptor activated by the endogenous peptide agonists PACAP and vasoactive intestinal peptide (VIP). Alternate splicing within the receptor extracellular domain (ECD) generates the PAC1R short variant (PAC1sR) that has selectively enhanced VIP function compared to the full-length, PAC1R null variant (PAC1nR). However, to date, a comprehensive pharmacological assessment of the downstream signaling outcomes of PAC1sR activation compared to PAC1nR has not been performed, and little information is available to mechanistically understand how ECD splicing may alter ligand engagement. Here, we demonstrated that VIP, but not PACAP, has globally enhanced activity across a broad range of functional endpoints at PAC1sR compared to PAC1nR. Cryo-EM structures of VIP-bound, stimulatory G protein (G s )-coupled PAC1sR and PAC1nR, supported by molecular dynamics (MD) simulations, demonstrate transient engagement of the null loop in PAC1nR, which is absent in PAC1sR, with residues in extracellular loop 2 (ECL2) and the N-terminal helix of the ECD. These interactions result in differential engagement of VIP with these domains and the top of TM2/ECL1 with PAC1sR and PAC1nR. Moreover, MD simulations predicted differential interactions of the G s protein with the two PAC1R variants when bound by VIP that correlate with a greater allosteric influence of the G s protein on VIP affinity at the PAC1sR, relative to PAC1nR. Our study provides insights into the structural basis and functional consequences of PAC1R ECD splicing, increasing understanding of PAC1R ligand selectivity and signaling.
Intelligent single-shot full-field characterization over femtosecond pulses
Abstract Conventional approaches to femtosecond (fs) pulse characterization depend on nonlinearities without exception, thereby impeding their utilization in measuring weak fs pulses. Their reliance on iterative phase retrieval or spectrometer-based readout further prevents single-shot full-field characterization over high-repetition-rate fs pulse trains. Here, we present linear spectral shearing interferometry (LSSI) based intelligent single-shot full-field characterization (ISFC) towards high-repetition-rate fs pulse trains, where both intensity and phase of fs pulses are reconstructed in single shot from temporal interferograms through a well-trained fully-connected neural network. The spectral shear in LSSI is created completely by linear effects enabling measurement of weak fs pulses. We validate the proposed method on a megahertz fs pulse train with picojoule-level energy. Moreover, the switching dynamics of a programmable spectral filter are successfully resolved with the proposed method at a megahertz frame rate. We anticipate LSSI-based ISFC to be a particularly powerful tool for characterizing weak ultraviolet fs pulses, and even attosecond pulses with high repetition rates.
Quercetin hybrid-hydrogel microparticles modulate gut microbiota and improve memory in an antibiotic-induced dysbiosis rat model
Abstract Gut microbiota plays a pivotal role in maintaining human health and well-being. Antibiotic-induced dysbiosis disrupts microbial balance and diversity leading to compromised physiological functions and adverse health outcomes. The present study investigates the functional potential of a dietary fiber-based hybrid-hydrogel microparticles formulation of the naturally occurring dietary flavonoid, quercetin (FQ-35), as a prebiotic intervention to restore gut and brain health through modulation of microbiome-gut-brain axis. An antibiotic cocktail was administered to induce gut microbial imbalance, and subsequently assessed the effects of supplementation of FQ-35 (100 mg/kg b.wt, for 14 days) on cognitive performance, gut microbiota, markers of gut and brain integrity, along with histopathological changes. FQ-35 effectively restored gut microbial diversity, demonstrated by a significant enrichment of beneficial taxa such as Lactobacillus and Bacteroides , alongside the normalization of key gut integrity markers, including ZO-1 and Occludin. Behavioural studies further demonstrated the improvement in memory and restoration of acetylcholinesterase activity, which were impaired by antibiotic cocktail. The intervention also led to the downregulation of pro-inflammatory mediators such as TLR4, TNF-α, and IL-1β. These findings highlight the therapeutic/functional potential of FQ-35 in restoring homeostasis via. the gut-brain axis, indicating its plausible role in the mitigation of dysbiosis.
Performance measurement of high gain Landsman converter with ANFIS based MPPT and cascaded H-bridge thirty-one multilevel inverter in a single-phase grid-connected PV system
Measuring eye vergence angle in extended reality
Recently, extended reality (XR) displays, including augmented reality (AR) and virtual reality (VR), have integrated eye tracking capabilities, which could enable novel ways of interacting with XR content. In natural settings, eye vergence angle (EVA) changes constantly, based on the distance of fixated objects. Here, we measured EVA for eye fixations on real and virtual target objects in three different environments: real objects in the real world (real), virtual objects in the real world (AR), and virtual objects in a virtual world (VR). In a repeated measures design with 13 participants, EVA was measured while participants fixated on targets at varying distances. As expected, the results showed a significant main effect of target depth such that increasing EVA was associated with closer targets. However, there were consistent individual differences in baseline EVA. There was also a smaller but statistically significant main effect of environment (real, AR, VR) on EVA. Importantly, EVA was stable with respect to the starting depth of previously fixated targets and invariant to the direction (convergence vs. divergence) of vergence changes. In addition, EVA proved to be a more veridical depth estimate than verbal subjective depth judgments.
Prevalence and Patterns of Iatrogenic Damage to Adjacent Teeth during Fixed Prosthodontic Preparation
ATP-dependent actin barbed-end fluctuations at steady state
Actin networks in cells are dynamic and constantly turning over as actin subunits exchange between monomer and polymer pools. Understanding these dynamics in vivo requires a detailed understanding of pure actin behavior in vitro. The prevailing model is treadmilling, which predicts continuous growth of filament barbed ends balanced by continuous shrinkage of pointed ends, while filament length remains roughly constant. While treadmilling has been observed directly at the level of single filaments, length fluctuations—expressed as “length diffusivity”—are much greater than expected, and the origin of these high diffusivity values could not be identified experimentally. By imaging single filaments tethered to glass via α-actinin, we observed frequent, low-amplitude barbed-end fluctuations of ±2–6 subunits per event and rarer, high-amplitude fluctuations of ±50–150 subunits per event. Barbed-end fluctuations depended on adenosine triphosphate (ATP) hydrolysis and release of inorganic phosphate (Pi) and were blocked by phalloidin and barbed-end capping agents. Barbed-end fluctuations consumed an estimated one-third of the ATP at steady state, while two-thirds is still consumed by treadmilling. Fluctuations result in diffusive spreading of filament lengths that exceeds predictions from pure treadmilling yet is lower than previously reported values, suggesting that earlier measurements captured additional sources of variability. Our results provide direct experimental evidence for kinetic models that proposed a dampened form of dynamic instability in pure actin where transient loss of the ATP/ADP•Pi barbed-end cap leads to rare, large excursions superimposed on more frequent, small fluctuations.
Magnetic and pneumatic actuation of polymeric microneedles for plasmonic hot-spot engineering and molecular sensing
Multi-objective trajectory optimization method for industrial robots based on improved TD3 algorithm
Association of SARC-F with muscle mass, strength, and quality derived from bioelectrical impedance spectroscopy for sarcopenia assessment
Abstract The SARC-F is a 5-item questionnaire screening for patients at risk of sarcopenia. The electrical properties of tissues derived from bioelectrical impedance spectroscopy (BIS), including phase angle (PhA) and intracellular-extracellular water ratio (ICW/ECW) indices, are biomarkers of age-related loss of skeletal muscle quantity and quality. The purpose of the current study was to examine the association between SARC-F and muscle mass, strength, muscle-specific strength, and muscle quality as assessed by BIS and hand grip strength (HGS). Sarcopenia risk was assessed using the SARC-F questionnaire. BIS was used to obtain skeletal muscle mass (SMM) and skeletal muscle mass index (SMI), PhA, ICW/ECW index, membrane capacitance (Cm) and characteristic frequency (fc) for assessing muscle quantity and quality. HGS was evaluated, and muscle-specific strength (HGS/SMM) was calculated. The Pearson correlation coefficient was used to examine the associations between SARC-F scores and each muscle parameter. A total of 205 older adults aged 65–99 years were included in the current cross-sectional analysis. Of those, 142 were community-dwelling healthy older adults (110 women and32 men) and 63 were the older adults living in special nursing homes for the older adults (45 women and 18 men). SARC-F was significantly correlated with SMM, SMI, HGS, and HGS/SMM in both men and women ( p < 0.05). SARC-F was also correlated with PhA, ICW/ECW index, Cm, and fc in both men and women ( p < 0.001). The SARC-F score was associated with SMM, HGS, HGS/SMM, PhA, ICW/ECW index, Cm, and fc independently of age, sex, height, and BMI. SARC-F is a subjective yet simple assessment tool for muscle mass, strength, and quality relevant to sarcopenia.
The effects of narrative framing of own broken love on understanding the past and imagining the future in close relationships
The project aimed to assess the effects of narrative framing applied to one’s past romantic relationship. It was expected that the activation of self-story on broken love would lead to more beneficial thinking about the personal past and possible future in close relationships. Women after the romantic relationship breakup (N = 422, 18–30 years old) took part in a two-stage naturalistic experiment in which they were randomly assigned to two sets. The narrative set participants wrote a story of broken love, while the control set participants answered questions about the past relationship. After seven days, participants declared their current thoughts and breakup understanding and provided open responses on the breakup reasons and thoughts about the future in close relationships. Self-story activation led to higher reflection elaboration and greater focus on causal connections, actions, and appropriate time perspectives. Women with activated self-stories provided more coherent descriptions of breakup reasons, declared a higher understanding of breakup, and experienced more future-oriented thoughts. The presence of the reported effects differed with the mode of exploration of the self-story activation level, and most of them were positively related to the level of narrative organization (plot structuring) of the narrative set participants’ self-stories. These results underscore the impact of narrative thinking on cognition, and suggest that self-story writing interventions could help manage challenging interpersonal experiences.
Assessment of Fatigue Resistance in Heat-treated Nickel-titanium Rotary Instruments with Single Canal Curvatures: An In Vitro Evaluation
Students’ motives for restricting academic freedom: Viewpoint discrimination and prosocial concerns
We advance the understanding of so-called “cancel culture” at the university by presenting the results of three survey experiments among university students. Designed in an “adversarial collaboration” among researchers with competing perspectives, these experiments disentangle whether students’ preferences for curtailing academic freedom are based on viewpoint discrimination, professional academic standards, or prosocial concerns. Our findings show that a substantive share of university students support viewpoint-based restrictions on academic discourse. While they also apply academic and prosocial criteria, they apply them more strongly to conservative viewpoints. The results further show that conservative statements are perceived as causing more social harm. However, prosocial concerns do not fully explain the higher demand for ideological viewpoint discrimination. These results are important because they can inform the debate about universities as ideological spaces—a view often invoked in recent government-led attacks on academic freedom.
Multi-omic analysis reveals lipid dysregulation associated with mitochondrial dysfunction in parkinson’s disease brain
Abstract Parkinson’s disease (PD) is an increasingly prevalent neurodegenerative disorder, largely sporadic in origin, with limited understanding of age- and region-specific lipid alterations in the human brain. Dysregulation of glycosphingolipid catabolism has been implicated in PD, yet comprehensive spatiotemporal profiling remains sparse. Here, we performed targeted lipidomics across eight anatomically distinct brain regions in post-mortem controls, mid-stage, and late-stage PD cases using high-precision tissue dissection. Each region displayed distinct lipid signatures, with several age-associated alterations—most notably in hexosylceramides, including glucosylceramide. In PD, glycosphingolipids were reduced in subcortical regions but elevated in cortical regions, particularly gangliosides, HexCer, and Hex2Cer, accompanied by increased sphingolipids and decreased phospholipids. The most pronounced mid-stage changes occurred in the putamen, where very long chain ceramide species and plasmalogen PE decreased, then normalising in late-stage disease. Lyso-phosphatidylcholine increased progressively throughout PD progression. Integrating proteomic data, we observed sphingomyelin levels associated with PD-related proteins, while dysregulated mitochondrial function correlated with antioxidant plasmalogens, long-chain ceramides, lyso-phosphatidylcholine, and HexCer in the putamen. These findings highlight region- and stage-specific lipid alterations in PD and their potential convergence with mitochondrial dysfunction.
Earphone use habits and their association with auditory and dermatologic complications
A hybrid ANN-PSO approach for self-tuning parameters of polycrystalline photovoltaic arrays
The influence of publication ranking specifications on publication strategy and academic careers in business administration
This study examines the impact of methodological variations in publication-based rankings on the evaluation of individual research performance in business administration. Drawing on a unique dataset comprising complete personal publication lists of 233 professors from Austrian public universities (2009–2018), we apply ten distinct ranking variants that differ in their treatment of data sources, co-authorship, publication languages, article lengths, and journal qualities. These variants are categorized into purely quantity-focused and predominantly quality-focused rankings. Our results demonstrate that researcher rankings are susceptible to specification choices. While quantity-focused rankings produce relatively small performance differentials and high variability, quality-focused variants consistently identify a stable group of leading researchers. These scholars publish more frequently in English, in journals indexed by Web of Science (WoS), and in top-tier outlets according to the JOURQUAL ranking. Notably, leading researchers publish over twice as many articles in high-ranking journals as their peers. The findings underscore the significant implications of ranking design for career advancement and research strategy. For early-career researchers, aligning publication efforts with the logic of quality-focused rankings—favoring English-language publications in highly ranked, peer-reviewed journals—is crucial for enhancing academic visibility and competitiveness. Moreover, our study offers a methodological stress test for ranking systems, revealing the extent to which technical design influences outcomes. By leveraging comprehensive and multilingual publication data and systematically comparing multiple ranking methodologies, this study contributes to both the academic evaluation literature and practical guidance for researchers navigating the demands of a metric-driven academic environment.
Evaluation of the Preventive Effect of Casein Phosphopeptide–Amorphous Calcium Phosphate (CPP–ACP) on White Spot Lesions during Fixed Orthodontic Treatment Using Scanning Electron Microscopy
Defects at play: Shaping the photophysics and photochemistry of ice
The mechanisms by which light interacts with ice and the impact of photoinduced reactions are central to our understanding of environmental, atmospheric, and astrophysical processes. However, a microscopic description of the photoproducts originating from ultraviolet (UV) absorption and emission processes has remained elusive. Here, we explore the photochemistry of ice using time-dependent hybrid density functional theory on various models of pristine and defective ice Ih. Our investigation of the excited state potential energy surface of the crystal shows that UV absorption can lead to the formation of hydronium ions, hydroxyl radicals, and excess electrons. One of the dominant mechanisms of decay from the excited to the ground-state involves the recombination of the electron with the hydroxyl radical yielding hydronium-hydroxide ion-pairs. We find that the details of this charge recombination process sensitively depend on the presence of defects in the lattice, such as vacancies and preexisting photoproducts. We also observe the formation of Bjerrum defects following UV absorption; we suggest that, together with hydroxide anions, they are likely responsible for prominent features experimentally detected in long UV exposure absorption spectra, remarkably red-shifted relative to short exposure spectra. Our results highlight the key role of defects in determining the onset of absorption and emission processes in ice.