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Abstract Rab GTPases act as molecular switches to regulate organelle homeostasis and membrane trafficking. Rab6 plays a central role in regulating cargo flux through the Golgi and is activated via nucleotide exchange by the Ric1-Rgp1 protein complex. Ric1-Rgp1 is conserved throughout eukaryotes but the structural and mechanistic basis for its function has not been established. Here we report the cryoEM structure of a Ric1-Rgp1‐Rab6 complex representing a key intermediate of the nucleotide exchange reaction. Ric1-Rgp1 interacts with the nucleotide-binding domain of Rab6 using an uncharacterized helical domain, which we establish as a RabGEF domain by identifying residues required for Rab6 activation. Unexpectedly, the complex uses an arrestin fold to interact with the Rab6 hypervariable domain, indicating that interactions with the unstructured C-terminal regions of Rab GTPases may be a common binding mechanism used by their activators. Collectively, our findings provide a detailed mechanistic understanding of regulated Rab6 activation at the Golgi.

Eurya degeneri Kobuski (Pentaphylacaceae), a dioecious shrub endemic to Kaua‘i, is resurrected from synonymy with E. sandwicensis A. Gray. Eurya degeneri is distributed in montane mesic to wet forests in central and northwestern Kaua‘i. It can be distinguished from E. sandwicensis by its glabrous young stems, leaves and pedicels, linear-elliptic to ovate-elliptic leaves, longer pedicels (5–11 mm long), and shorter petals (4.5–7 mm long). A key to Hawaiian Eurya is provided. Two lectotypes are here assigned. Eurya degeneri is preliminarily designated as Critically Endangered according to the IUCN Red List guidelines.

Injectable biomaterials, such as thermosensitive chitosan (CH)-based hydrogels, present a highly translational potential in dentistry due to their minimally invasive application, adaptability to irregular defects/shapes, and ability to carry therapeutic drugs. This work explores the incorporation of azithromycin (AZI) into thermosensitive CH hydrogels for use as an intracanal medication in regenerative endodontic procedures (REPs). The morphological and chemical characteristics of the hydrogel were assessed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR). The thermosensitivity, gelation kinetics, compressive strength, cytocompatibility, and antibacterial efficacy were evaluated according to well-established protocols. An in vivo model of periapical disease and evoked bleeding in rats' immature permanent teeth was performed to determine disinfection, tissue repair, and root formation. AZI was successfully incorporated into interconnected porous CH hydrogels, which retained their thermosensitivity. The mechanical and rheological findings indicated that adding AZI did not adversely affect the hydrogels’ strength and injectability. Incorporating 3 % and 5 % AZI into the hydrogels led to minimal cytotoxic effects compared to higher concentrations while enhancing the antibacterial response against endodontic bacteria. AZI-laden hydrogel significantly decreased E. faecalis biofilm compared to the controls. Regarding tissue response, the 3 % AZI-laden hydrogel improved mineralized tissue formation and vascularization compared to untreated teeth and those treated with double antibiotic paste. Our findings demonstrate that adding 3 % AZI into CH hydrogels ablates infection and supports neotissue formation in vivo when applied to a clinically relevant model of regenerative endodontics.

Abstract Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we find the emergence of the cortical hierarchy revealed by the highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increases in a biphasic pattern featured by initial rapid and subsequently slower rate, and break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices are associated with enhanced language and motor skills, and frontoparietal association cortices with cognitive skills. The study discovers emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.

Abstract Single-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3′-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3′-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination.

Our understanding of how visual cortex neural processes mature during infancy and toddlerhood is limited. Using magnetoencephalography (MEG), the present study investigated the development of visual evoked responses (VERs) in cross-sectional and longitudinal samples of infants and toddlers 2 months to 3 years. Brain space analyses focused on N1m and P1m latency, as well as N1m-to-P1m amplitude. Associations between VER measures and developmental quotient (DQ) scores in the cognitive/visual and fine motor domains were also examined. Results showed a nonlinear decrease in N1m and P1m latency as a function of age, characterized by rapid changes followed by slower progression, with the N1m latency plateauing at 6–7 months and the P1m latency plateauing at 8–9 months. The N1m-to-P1m amplitude also exhibited a non-linear decrease, with strong responses observed in younger infants (∼2–3 months) and then a gradual decline. Associations between N1m and P1m latency and fine motor DQ scores were observed, suggesting that infants with faster visual processing may be better equipped to perform fine motor tasks. The present findings advance our understanding of the maturation of the infant visual system and highlight the relationship between the maturation of the visual system and fine motor skills.

Cognitive radio network (CRN) uses the available spectrum resources wisely. Spectrum sensing is the central element of a CRN. However, spectrum sensing is susceptible to multiple security breaches caused by malicious users (MUs). These attackers attempt to change the sensed result in order to decrease network performance. In our proposed approach, with the help of blockchain-based technology, the fusion center is able to detect and prevent such criminal activities. The method of our model makes use of blockchain-based MU detection with SHA-3 hashing and energy detection-based spectrum sensing. The detection strategy takes place in two stages: block updation phase and iron out phase. The simulation results of the proposed method demonstrate 3.125%, 6.5%, and 8.8% more detection probability at −5 dB signal-to-noise ratio (SNR) in the presence of MUs, when compared to other methods like equal gain combining (EGC), blockchain-based cooperative spectrum sensing (BCSS), and fault-tolerant cooperative spectrum sensing (FTCSS), respectively. Thus, the security of cognitive radio blockchain network is proved to be significantly improved.

Abstract Brain tumors, often referred to as intracranial tumors, are abnormal tissue masses that arise from rapidly multiplying cells. During medical imaging, it is essential to separate brain tumors from healthy tissue. The goal of this paper is to improve the accuracy of separating tumorous regions from healthy tissues in medical imaging, specifically for brain tumors in MRI images which is difficult in the field of medical image analysis. In our research work, we propose IC-Net (Inverted-C), a novel semantic segmentation architecture that combines elements from various models to provide effective and precise results. The architecture includes Multi-Attention (MA) blocks, Feature Concatenation Networks (FCN), Attention-blocks which performs crucial tasks in improving brain tumor segmentation. MA-block aggregates multi-attention features to adapt to different tumor sizes and shapes. Attention-block is focusing on key regions, resulting in more effective segmentation in complex images. FCN-block captures diverse features, making the model more robust to various characteristics of brain tumor images. Our proposed architecture is used to accelerate the training process and also to address the challenges posed by the diverse nature of brain tumor images, ultimately leads to potentially improved segmentation performance. IC-Net significantly outperforms the typical U-Net architecture and other contemporary effective segmentation techniques. On the BraTS 2020 dataset, our IC-Net design obtained notable outcomes in Accuracy, Loss, Specificity, Sensitivity as 99.65, 0.0159, 99.44, 99.86 and DSC (core, whole, and enhancing tumors as 0.998717, 0.888930, 0.866183) respectively.

Abstract Background The yeast Komagataella phaffii is widely used for manufacturing recombinant proteins, but secreted titers of recombinant proteins could be improved by genetic engineering. In this study, we hypothesized that cellular resources could be redirected from production of endogenous proteins to production of recombinant proteins by deleting unneeded endogenous proteins. In non-model microorganisms such as K. phaffii, however, genetic engineering is limited by lack gene annotation and knowledge of gene essentiality. Results We identified a set of endogenous secreted proteins in K. phaffii by mass spectrometry and signal peptide prediction. Our efforts to disrupt these genes were hindered by limited annotation of essential genes. To predict essential genes, therefore, we designed, transformed, and sequenced a pooled library of guide RNAs for CRISPR-Cas9-mediated knockout of all endogenous secreted proteins. We then used predicted gene essentiality to guide iterative disruptions of up to 11 non-essential genes. Engineered strains exhibited a ~20× increase in the production of human serum albumin and a twofold increase in the production of a monoclonal antibody. Conclusions We demonstrated that disruption of as few as six genes can increase production of recombinant proteins. Further reduction of the endogenous proteome of K. phaffii may further improve strain performance. The pooled library of secretome-targeted guides for CRISPR-Cas9 and knowledge of gene essentiality reported here will facilitate future efforts to engineer K. phaffii for production of other recombinant proteins and enzymes.

Abstract Integrated step‐selection analysis (ISSA) is frequently used to study habitat selection using animal movement data. Methods for incorporating random effects in ISSA have been developed, making it possible to quantify variability among animals in their space‐use patterns. Although it is possible to model variability in both habitat selection and movement parameters, applications to date have focused on the former despite the widely acknowledged and important role that movement plays in determining ecological processes from the individual to ecosystem level. One potential explanation for this omission is the absence of readily available software or examples demonstrating methods for estimating movement parameters in ISSA with random effects. We demonstrated methods for characterizing among‐individual variability in both movement and habitat‐selection parameters using a simulated data set and by fitting two models to an acoustic telemetry data set containing locations of 35 red snapper (Lutjanus campechanus). Movement kernels were assumed to depend on either the type of benthic reef habitat in which the fish was located (model 1) or the distance between the fish's current location and the nearest edge habitat (model 2). In both models, we also quantified habitat selection for different benthic habitat classes and distance to edge habitat, and we allowed for individual variability in movement and habitat‐selection parameters using random effects. The simulation example highlights the benefits of a mixed‐effects specification, namely, we can increase precision when estimating individual‐specific movement parameters by borrowing information across like individuals. In our applied example, we found substantial among‐individual variability in both habitat selection and movement parameters. Nonetheless, most red snapper selected for hardbottom habitat and for locations nearer to edge habitat. They also moved less when in hardbottom habitat. Turn angles were frequently near ± π but were more dispersed when fish were far away from edge habitat. We provide code templates and functions for quantifying variability in movement and habitat‐selection parameters when implementing ISSA with random effects. In doing so, we hope to encourage ecologists conducting ISSA to take full advantage of their ability to model among‐individual variability in both habitat‐selection and movement patterns.

Current methods for cancer risk assessment are resource-intensive and not feasible for most of the thousands of untested chemicals. In earlier studies, we developed a new approach methodology (NAM) to identify liver tumorigens using gene expression biomarkers and associated tumorigenic activation levels (TALs) after short-term exposures in rats. The biomarkers are used to predict the six most common rodent liver cancer molecular initiating events. In the present study, we wished to confirm that our approach could be used to identify liver tumorigens at only one time point/dose and if the approach could be applied to (targeted) RNA-Seq analyses. Male rats were exposed for 4 days by daily gavage to 15 chemicals at doses with known chronic outcomes and liver transcript profiles were generated using Affymetrix arrays. Our approach had 75% or 85% predictive accuracy using TALs derived from the TG-GATES or DrugMatrix studies, respectively. In a dataset generated from the livers of male rats exposed to 16 chemicals at up to 10 doses for 5 days, we found that our NAM coupled with targeted RNA-Seq (TempO-Seq) could be used to identify tumorigenic chemicals with predictive accuracies of up to 91%. Overall, these results demonstrate that our NAM can be applied to both microarray and (targeted) RNA-Seq data generated from short-term rat exposures to identify chemicals, their doses, and mode of action that would induce liver tumors, one of the most common endpoints in rodent bioassays.

There are well-documented gender differences in the risk and severity of sleep disorders and associated comorbidities. While fundamental sex differences in sleep regulatory mechanisms may contribute to gender disparities, biological responses to sleep loss and stress may underlie many of the risks for sleep disorders in women and men. Some of these sex differences appear to be dependent on sex chromosome complement (XX or XY) and the organizational effects of reproductive hormones. Reproductive development plays a critical role in the ability of sex chromosomes and reproductive hormones to produce sex differences in sleep and wakefulness. Rodent models reveal that reproductive hormones drive many but not all sex differences in sleep–wake architecture. The ability of reproductive hormones to alter sleep are often dependent on responses to sleep loss and stress. However, in the absence of reproductive hormones (in gonadectomized rodents) sex differences in sleep amount and the ability to recover from sleep loss persist. The suprachiasmatic nucleus (SCN) and the ventrolateral preoptic nucleus (VLPO) of the hypothalamus play crucial regulatory roles in mediating the effects of reproductive hormones on the sleep–wake cycle. Taken together, the work reviewed here reveals that the reproductive hormone environment and sex chromosome complement may underlie gender disparities in sleep patterns and the risk for sleep disorders.

Abstract Modern coexistence theory (MCT) offers a conceptually straightforward approach for connecting empirical observations with an elegant theoretical framework, gaining popularity rapidly over the past decade. However, beneath this surface‐level simplicity lie various assumptions and subjective choices made during data analysis. These can lead researchers to draw qualitatively different conclusions from the same set of experiments. As the predictions of MCT studies are often treated as outcomes, and many readers and reviewers may not be familiar with the framework's assumptions, there is a particular risk of ‘researcher degrees of freedom’ inflating the confidence in results, thereby affecting reproducibility and predictive power. To tackle these concerns, we introduce a checklist consisting of statistical best practices to promote more robust empirical applications of MCT. Our recommendations are organised into four categories: presentation and sharing of raw data, testing model assumptions and fits, managing uncertainty associated with model coefficients and incorporating this uncertainty into coexistence predictions. We surveyed empirical MCT studies published over the past 15 years and discovered a high degree of variation in the level of statistical rigour and adherence to best practices. We present case studies to illustrate the dependence of results on seemingly innocuous choices among competition model structure and error distributions, which in some cases reversed the predicted coexistence outcomes. These results demonstrate how different analytical approaches can profoundly alter the interpretation of experimental results, underscoring the importance of carefully considering and thoroughly justifying each step taken in the analysis pathway. Our checklist serves as a resource for authors and reviewers alike, providing guidance to strengthen the empirical foundation of empirical coexistence analyses. As the field of empirical MCT shifts from a descriptive, trailblazing phase to a stage of consolidation, we emphasise the need for caution when building upon the findings of earlier studies. To ensure that progress made in the field of ecological coexistence is based on robust and reliable evidence, it is crucial to subject our predictions, conclusions and generalisability to a more rigorous assessment than is currently the trend.

Abstract Non-fungible tokens (NFTs) are unique digital assets that exist on a blockchain and have provided new revenue streams for creators. This research investigates NFT market inefficiencies to identify claimed cyclic behavior and cryptocurrency influences on NFT prices. The research found that while linear models are not useful in modeling NFT price series, models that extract periodic behavior can provide explanations and predictions of price behavior. The investigation of autocycles in cryptocurrency and NFT markets did not support the existence of Elliott Wave behavior in any of these blockchain enabled assets. Rather NFT price behavior is strongly tied to the underlying asset and its community of fans. These fans commit to periodic bouts of idiosyncratic trading which cools for a while, and then restarts. The research found no evidence supporting whole market effects across the full price series of individual NFTs. The research strongly supports prior findings that the offsetting movements significantly influence NFT prices and trading volume in Bitcoin and Ether. The research found NFT markets exhibit characteristics resembling a social media platform rather than more traditional asset markets like stock exchanges. It found that traditional linear econometric models cannot predict or explain NFT price series, only that NFT price and volume were weakly correlated. Fractal models consistent with Elliott wave theory do explain some of NFT price behavior, but are not consistent or stable over time. This research confirmed prior research findings that Bitcoin and Ether price movements are correlated with general NFT price and volume series in periods of between 24 and 48 h, with significant numbers of trades into and out of cryptocurrencies at 2 and 8 h.

The bulk abundances of exoplanetesimals can be measured when they are accreted by white dwarfs. Recently, lithium from the accretion of exoplanetesimals was detected in relatively high levels in multiple white dwarfs. There are presently three proposed hypotheses to explain the detection of excess lithium in white dwarf photospheres: Big Bang and Galactic nucleosynthesis, continental crust, and an exomoon formed from spalled ring material. We present new observations of three previously known lithium-polluted white dwarfs (WD J1824+1213, WD J2317+1830, and LHS 2534), and one with metal pollution without lithium (SDSS J1636+1619). We also present atmospheric model fits to these white dwarfs. We then evaluate the abundances of these white dwarfs and two additional lithium-polluted white dwarfs that were previously fit using the same atmospheric models (WD J1644-0449 and SDSS J1330+6435) in the context of the three extant hypotheses for explaining lithium excesses in polluted white dwarfs. We find Big Bang and Galactic nucleosynthesis to be the most plausible explanation of the abundances in WD J1644-0449, WD J1824+1213, and WD J2317+1830. SDSS J1330+6435 will require stricter abundances to determine its planetesimal’s origins, and LHS 2534, as presently modeled, defies all three hypotheses. We find the accretion of an exomoon formed from spalled ring material to be highly unlikely to be the explanation of the lithium excess in any of these cases.

The Defense Mechanisms Rating Scales-Self Report-30 (DMRS-SR-30) was recently developed to add a self-report alternative to the assessment of defenses, reflecting their generally accepted hierarchical organization. In this study, we aimed to examine psychometric properties and factor structure of the Turkish language version of the DMRS-SR-30. The sample consisted of 1.002 participants who filled out a survey comprising the DMRS-SR-30, the Brief Symptom Inventory, and the Inventory of Personality Organization through Qualtrics. Confirmatory Factor Analysis indicated a three-factor structure (CFI = 0.89, RMSEA = 0.05) that confirms the DMRS theoretical frame with a relatively acceptable fit. Defensive categories and total scale scores showed good to excellent reliability (α values ranging from 0.64 to 0.89). Correlations between defenses, symptoms, and personality functioning demonstrated good convergent and discriminant validity. The individuals with clinically significant BSI scores (T-score ≥ 63) differed on the DMRS-SR-30 scores from the individuals in the non-clinical range. The Turkish version of the DMRS-SR-30 is a reliable and valid instrument to self-assess the hierarchy of defense mechanisms and overall defensive functioning. Moreover, the current study supports the validity of the tripartite model of defenses in a language and culture different from the origins of the DMRS and DMRS-SR-30.

In temperate climates, aquaponic producers must use artificial lighting; however, purchasing light-emitting diode (LED) grow lights can be cost-prohibitive. Two aquaponic trials evaluated low-cost LED lighting for the growth of bibb lettuce (Lactuca sativa var. capitata). In trial 1, seven low-cost LED lights were screened and compared with a high-end LED grow light. The three best-performing lights in terms of total plant biomass produced (grams) and total plant biomass per unit of electricity (grams per square meter per kilowatt-hour) were more intensively evaluated in trial 2. These lights included Spider Farmer SF-2000 [SPI ($300)], Fluence RAZRx [FLU ($364)], Designers Fountain 6-Light 5000 K LED High Bay Light [DES ($100)], and the control NeoSol DS [NEO ($1400)]. After 17 days, lettuce grown under NEO achieved higher (P ≤ 0.05) total biomass (939 g) than DES (812 g). There were no differences (P > 0.05) in the average individual plant weights in any treatment. Plant production efficiency (grams per square meter per kilowatt-hour) was higher in DES than NEO (P ≤ 0.05) but was not different from SPI and FLU (P > 0.05). Results indicate that low-cost LEDs are a viable option for producers looking to reduce investment costs while maintaining adequate plant growth. To further describe potential cost savings for producers, a partial budget analysis evaluated the net change in profits and benefit/cost ratio (BCR) of the experimental lights. All showed improved economic results compared with the control (NEO). These studies indicate that low-cost LED lights can support similar plant growth, at higher energy efficiencies, with better economic viability than more expensive grow lights.

Abstract Augmented Reality (AR) is applied in almost every field, and a few, but not limited, are engineering, medical, gaming and internet of things. The application of image tracking is inclusive in all these mentioned fields. AR uses image tracking to localize and register the position of the user/AR device for superimposing the virtual image into the real-world. In general terms, tracking the image enhance the users’ experience. However, in the image tracking application, establishing the interface between virtual realm and the physical world has many shortcomings. Many tracking systems are available, but it lacks in robustness and efficiency. The robustness of the tracking algorithm, is the challenging task of implementation. This study aims to enhance the users’ experience in AR by describing an image using Directional Intensified Features with Tertiary Filtering. This way of describing the features improve the robustness, which is desired in the image tracking. A feature descriptor is robust, in the sense that it does not compromise, when the image undergoes various transformations. This article, describes the features based on the Directional Intensification using Tertiary Filtering (DITF). The robustness of the algorithm is improved, because of the inherent design of Tri-ocular, Bi-ocular and Dia-ocular filters that can intensify the features in all required directions. The algorithm’s robustness is verified with respect to various image transformations. The oxford dataset is used for performance analysis and validation. DITF model is designed to achieve the repeatability score of illumination-variation , blur changes and view-point variation, as 100%, 100% and 99% respectively. The comparative analysis has been performed in terms of precision and re-call. DITF outperforms the state-of-the-art descriptors, namely, BEBLID, BOOST, HOG, LBP, BRISK and AKAZE. An Implementation of DITF source code is available in the following GitHub repository: github.com/Johnchristopherclement/Directional-Intensified-Feature-Descriptor.

Abstract Cognitive radio network is a promising technology to enhance the spectrum utilization and to resolve the spectrum scarcity issues. But the malicious users play havoc with the network during spectrum sensing and demean the network performance. It is mandatory to identify such malicious attacks and address it. There have been many traditional methods to mitigate the cognitive radio network attacks. In this paper, we have surveyed advanced attack mitigation techniques like machine learning, deep learning and blockchain. Thus, by detecting and addressing the malicious activities, the throughput and overall network performance can be improved.

Abstract Background Well-designed public health interventions ideally aspire to reduce health disparities between racial and ethnic groups. Yet, there remains virtually no research examining racial/ethnic disparities in interventions for marginalized perinatal populations with substance use disorders (SUD). We sought to examine whether there were racial/ethnic differences at intake, in retention, and in program outcomes among pregnant or postpartum women with prenatal substance use enrolled in a three-year intensive case management intervention. We hypothesized that: (1) at baseline, numerous racial/ethnic disparities in well-being, health, and health care would be observed, and (2) after the three-year intervention few racial/ethnic disparities in maternal and child health and welfare would be found. Methods We used self-reported data from 3,165 women aged 18 to 45 years enrolled in the Parent-Child Assistance Program in Washington State between May 10, 2006, and September 21, 2017. We used Fisher-Freeman-Halton Exact Tests and t-tests to compare racial/ethnic groups at program enrollment and exit and logistic regression to examine likelihood of completing the intervention by group, controlling for other factors. Results Despite numerous racial/ethnic differences at enrollment, there were no such differences in outcomes among those who finished the program and completed an exit interview. Different racial/ethnic groups received comparable case manager time. American Indians/Alaska Natives were less likely to finish the program (Adjusted Odds = 0.66). Conclusions Participants who finished the program achieved comparable outcomes regardless of race/ethnicity. More work is needed to understand why American Indian/Alaska Native women were less likely than the others to finish the program and to close this service gap.

Artificial reefs can play an important role in marine fisheries management by supplementing or enhancing natural habitats. Despite their increased use in recent years, the choice of structures used at artificial reefs remains largely haphazard due to the lack of information on reef structure performance. Few studies have examined the use of different artificial reef structures by individual fish. From 2021-2022, we acoustically tagged 72 black sea bass (Centropristis striata), 34 gag (Mycteroperca mircrolepis), 27 greater amberjack (Seriola dumerili), nine almaco jack (S. rivoliana), and eight red snapper (Lutjanus campechanus) on four artificial reef complexes near Cape Lookout, North Carolina, U.S. Available artificial reef structures consisted of materials of various sizes and heights made of concrete and metal. We tracked tagged fish using a fine-scale positioning system for ~100 days. Black sea bass exhibited high site fidelity to the artificial structure where we caught them, rarely moving away from that structure. The limited movement resulted in low transition probabilities; we conclude that black sea bass do not select for particular artificial structures. Gag and red snapper moved greater distances away from artificial structures and routinely moved between them. Greater amberjack and almaco jack moved the most within the complexes displaying circling behavior around individual structures and were the only species that regularly moved off the artificial reef complexes. Greater amberjack movements away from artificial sites were most commonly directed to surrounding shipwrecks. Whereas gag, red snapper, almaco jack, and greater amberjack used all available structures, they consistently selected for high relief structures, such as vessels, more than other structures. These results will be useful to managers charged with decisions on what types of structures to place at artificial reef complexes to supplement or enhance habitat for economically important fishes.

Repairing alliance ruptures has the potential to serve as a powerful mechanism of change in psychotherapy. In this article, a transtheoretical individual-specific framework for repairing alliance ruptures is proposed. According to the proposed framework, at the intake session, the therapist evaluates the trait-like tendencies of individual patients to face ruptures in interpersonal relationships. We propose a typology based on which patients are assigned to one of the following therapeutic strategies: (a) a treatment where alliance rupture and repair is the main mechanism of change (Type A), (b) an added module that augments another treatment, focusing on rupture and repair (Type B), or (c) treatment where no rupture resolution work is carried out (Type C). The proposed framework is based on cumulative clinical knowledge, and its validity and utility need to be assessed in future research.

Abstract Figurative depictions in art first occur ca. 50,000 years ago in Europe, Africa, and Southeast Asia. Considered by most as an advanced form of symbolic behavior, they are restricted to our species. Here, we report a piece of ornament interpreted as a phallus-like representation. It was found in a 42,000 ca.-year-old Upper Paleolithic archaeological layer at the open-air archaeological site of Tolbor-21, in Mongolia. Mineralogical, microscopic, and rugosimetric analyses points toward the allochthonous origin of the pendant and a complex functional history. Three-dimensional phallic pendants are unknown in the Paleolithic record, and this discovery predates the earliest known sexed anthropomorphic representation. It attests that hunter-gatherer communities used sex anatomical attributes as symbols at a very early stage of their dispersal in the region. The pendant was produced during a period that overlaps with age estimates for early introgression events between Homo sapiens and Denisovans, and in a region where such encounters are plausible.

Defense mechanisms are adaptative processes that are related to mental health and psychological functioning and may play an important role in adaptation to distress, as well as in mental health interventions. The present study aimed to compare the use of defense mechanisms and their relationship to mental health symptoms across six countries. In a large-scale descriptive study, we collected data from community- based individuals (N=19,860) in the United States, Australia, Canada, Germany, Italy, and the United Kingdom about the use of defense mechanisms and experienced mental health symptoms during the early phase of the pandemic. We found that the use of defense mechanism categories was similar across countries. Moreover, lower defensive functioning, specifically, neurotic and immature defenses were related to experiencing higher distress across countries, whereas mature defenses were generally inversely related to symptoms. Furthermore, these findings were relatively similar across the six countries. Cross-cultural research on defense mechanisms and mental health has important clinical implications. Our results are consistent with the goal of promoting more adaptive defensive functioning to increase psychological well-being and mitigate the detrimental impact of situational stress

After over three decades of unsuccessful attempts, we report the first detection of molecular gas emission in Malin 1, the largest spiral galaxy observed to date, and one of the most iconic giant low surface brightness galaxies. Using Atacama Large Millimeter/submillimeter Array, we detect significant ^12 CO ( J = 1–0) emission in the galaxy’s central region and tentatively identify CO emission across three regions on the disk. These observations allow for a better estimate of the H _2 mass and molecular gas mass surface density, both of which are remarkably low given the galaxy’s scale. By integrating data on its H i mass, we derive a very low molecular-to-atomic gas mass ratio. Overall, our results highlight the minimal presence of molecular gas in Malin 1, contrasting sharply with its extensive, homogeneous atomic gas reservoir. For the first time, we position Malin 1 on the Kennicutt–Schmidt diagram, where it falls below the main sequence for normal spirals, consistent with previous upper limits but now with more accurate figures. These findings are crucial for constraining our understanding of star formation processes in environments characterized by extremely low molecular gas densities and for refining models of galaxy formation, thereby improving predictions concerning the formation, evolution, and distribution of these giant, elusive galaxies.

Summary: Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell activity in participants with severe infection, whereas asymptomatic donors had higher expression of genes associated with anti-inflammatory CD16+ monocytes. Therefore, we demonstrated the potential of systems immunology using multiple cell-type and cell-state-specific analyses to identify correlates of infection severity and host cellular activity contributing to an effective anti-viral response.

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear. Methods: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. Mouse models of hepatic steatosis were used to investigate observations made from human liver tissue. Results: We observed variable degrees of liver steatosis with minimal fibrosis in our participants. Single-cell RNA sequencing revealed four macrophage clusters that exist in the human fatty liver encompassing Kupffer cells and monocyte-derived macrophages (MdMs). The genes expressed in these macrophage subsets were similar to those observed in mouse models of MAFLD. Hepatic CD14+ monocyte/macrophage number correlated with the degree of steatosis. Using mouse models of early liver steatosis, we demonstrate that recruitment of MdMs precedes Kupffer cell loss and liver damage. Electron microscopy of isolated macrophages revealed increased lipid accumulation in MdMs, and ex vivo lipid transfer experiments suggested that MdMs may serve a distinct role in lipid uptake during MAFLD. Conclusions: The human liver in MAFLD contains macrophage subsets that align well with those that appear in mouse models of fatty liver disease. Recruited myeloid cells correlate well with the degree of liver steatosis in humans. MdMs appear to participate in lipid uptake during early stages of MALFD. Impact and implications: Metabolic dysfunction associated fatty liver disease (MAFLD) is extremely common; however, the early inflammatory responses that occur in human disease are not well understood. In this study, we investigated macrophage heterogeneity in human livers during early MAFLD and demonstrated that similar shifts in macrophage subsets occur in human disease that are similar to those seen in preclinical models. These findings are important as they establish a translational link between mouse and human models of disease, which is important for the development and testing of new therapeutic approaches for MAFLD.

Abstract Background Droplets and aerosols produced during dental procedures are a risk factor for microbial and viral transmission. Unlike sodium hypochlorite, hypochlorous acid (HOCl) is nontoxic to tissues but still exhibits broad microbicidal effect. HOCl solution may be applicable as a supplement to water and/or mouthwash. This study aims to evaluate the effectiveness of HOCl solution on common human oral pathogens and a SARS-CoV-2 surrogate MHV A59 virus, considering the dental practice environment. Methods HOCl was generated by electrolysis of 3% hydrochloric acid. The effect of HOCl on human oral pathogens, Fusobacterium nucleatum, Prevotella intermedia, Streptococcus intermedius, Parvimonas micra, and MHV A59 virus was studied from four perspectives: concentration; volume; presence of saliva; and storage. HOCl solution in different conditions was utilized in bactericidal and virucidal assays, and the minimum inhibitory volume ratio that is required to completely inhibit the pathogens was determined. Results In the absence of saliva, the minimum inhibitory volume ratio of freshly prepared HOCl solution (45–60 ppm) was 4:1 for bacterial suspensions and 6:1 for viral suspensions. The presence of saliva increased the minimum inhibitory volume ratio to 8:1 and 7:1 for bacteria and viruses, respectively. Applying a higher concentration of HOCl solution (220 or 330 ppm) did not lead to a significant decrease in the minimum inhibitory volume ratio against S. intermedius and P. micra. The minimum inhibitory volume ratio increases in applications of HOCl solution via the dental unit water line. One week of storage of HOCl solution degraded HOCl and increased the minimum growth inhibition volume ratio. Conclusions HOCl solution (45–60 ppm) is still effective against oral pathogens and SAR-CoV-2 surrogate viruses even in the presence of saliva and after passing through the dental unit water line. This study indicates that the HOCl solution can be used as therapeutic water or mouthwash and may ultimately reduce the risk of airborne infection in dental practice.

Installations of artificial structures in coastal oceans create de facto habitat for marine life. These structures encompass wide varieties of physical characteristics, reflecting their multiple, diverse purposes and creating a need to understand which characteristics maximize fish habitat. Here, we test how physical characteristics – horizontal area, vertical relief, and spatial isolation – relate to fish density from echosounder surveys over artificial structures like concrete pipes, train boxcars, and ships purposely sunk to function as reefs. Echosounder mapping of 31 artificial reef structures and associated fish across a 200 km linear length of the continental shelf of North Carolina, USA, revealed that structures with greater horizontal area and vertical relief host higher fish densities than smaller, shorter structures. Artificial structure spatial arrangement also relates to fish density, as isolated structures are generally associated with greater localized fish densities than structures closer to one another. Patterns in the relationships between fish density and reef characteristics differed for schooling fish, as there was some evidence that reefs of intermediate area exhibited higher schooling fish density. These results suggest that intentional design and spatial arrangement of marine built structures like artificial reefs relates to and can be deliberately incorporated into siting and deployment decisions to enhance their role as fish habitat.

Epiphytic microalgae are important contributors to the carbon and nutrient cycles yet are often overlooked during ecological surveys. In reef habitats, epiphytes are often found living on host organisms, including seaweeds or corals, and can influence community composition of higher trophic level taxa. Hence, understanding how epiphytes respond to different reef substrate materials can help inform designs of substrates intentionally deployed to form artificial reefs which can encourage high biodiversity and ecological functioning. One such epiphyte, Gambierdiscus spp., is a harmful benthic dinoflagellate which produces toxins that bioaccumulate and cause ciguatera fish poisoning (CFP) when contaminated fish is consumed by humans. CFP is one of the most frequently reported seafood-associated illnesses around the world, occurring most often near tropical reefs. We surveyed the epiphytes amongst 13 natural and artificial reef sites located off the coast of North Carolina to determine the role of the reefs’ foundational substrate (e.g., natural marl, steel or concrete) on structuring the epiphyte community with an emphasis on Gambierdiscus spp. abundance. No Gambierdiscus spp. were detected among the sampled reefs, likely due to suboptimal water temperatures. An ex-situ substrate preference experiment for Gambierdiscus spp. was performed using marl to represent natural rocky reefs, and steel and concrete to represent artificial reefs. Experimental results indicated that Gambierdiscus spp. grew fastest in the presence of marl and density decreased significantly when exposed to steel. However, steel artificial reefs had the highest average epiphyte biomass and species richness amongst the sampled reefs. 18s rRNA gene sequence analysis revealed that natural reefs were more likely to be dominated by dinoflagellates, whereas steel and concrete reefs were dominated by diatoms. We found that epiphyte composition was related to material at a phylum level, but seaweed hosts played a more significant role at the species level. These findings suggest that CFP risk is relatively low on the reefs studied but natural reefs would likely be preferentially colonized by Gambierdiscus spp. should ambient conditions become appropriate.

Abstract Background Komagataella phaffii is a commonly used alternative host for manufacturing therapeutic proteins, in part because of its ability to secrete recombinant proteins into the extracellular space. Incorrect processing of secreted proteins by cells can, however, cause non-functional product-related variants, which are expensive to remove in purification and lower overall process yields. The secretion signal peptide, attached to the N-terminus of the recombinant protein, is a major determinant of the quality of the protein sequence and yield. In K. phaffii, the signal peptide from the Saccharomyces cerevisiae alpha mating factor often yields the highest secreted titer of recombinant proteins, but the quality of secreted protein can vary highly. Results We determined that an aggregated product-related variant of the SARS-CoV-2 receptor binding domain is caused by N-terminal extension from incomplete cleavage of the signal peptide. We eliminated this variant and improved secreted protein titer up to 76% by extension of the N-terminus with a short, functional peptide moiety or with the EAEA residues from the native signal peptide. We then applied this strategy to three other recombinant subunit vaccine antigens and observed consistent elimination of the same aggregated product-related variant. Finally, we demonstrated that this benefit in quality and secreted titer can be achieved with addition of a single amino acid to the N-terminus of the recombinant protein. Conclusions Our observations suggest that steric hindrance of proteases in the Golgi that cleave the signal peptide can cause unwanted N-terminal extension and related product variants. We demonstrated that this phenomenon occurs for multiple recombinant proteins, and can be addressed by minimal modification of the N-terminus to improve steric accessibility. This strategy may enable consistent secretion of a broad range of recombinant proteins with the highly productive alpha mating factor secretion signal peptide.

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left–right hemisphere P2m maturation is associated with language performance.

Background The effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on β cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.Methods BCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, 16%) of WL induced by a low-calorie diet (LCD) in people with obesity without diabetes, (b) ~20% WL after RYGB surgery or laparoscopic adjustable gastric banding (LAGB) in people with obesity without diabetes, and (c) ~20% WL after RYGB surgery or LCD alone in people with obesity and diabetes.Results Diet-induced progressive WL in people without diabetes progressively decreased BCF. Marked WL after LAGB or RYGB in people without diabetes did not alter BCF. Marked WL after LCD or RYGB in people with diabetes markedly increased BCF, without a difference between groups.Conclusion Marked WL increases BCF in people with obesity and diabetes but not in people with obesity without diabetes. The effect of RYGB-induced WL on BCF is not different from the effect of matched WL after LAGB or LCD alone.trial registration NCT00981500, NCT02207777, NCT01299519.Funding NIH grants R01 DK037948, P30 DK056341, P30 DK020579, UL1 TR002345.

BACKGROUND There is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODS We evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as “Responders” (n = 11) or “Non-responders” (n = 11), defined as the top (>75% increase) and bottom (

Chronic inorganic arsenic (iAs) exposure in drinking water is a global issue affecting >225 million people. Skin is a major target organ for iAs. miRNA dysregulation and chromosomal instability (CIN) are proposed mechanisms of iAs-induced carcinogenesis. CIN is a cancer hallmark and tetraploid cells can better tolerate increase in chromosome number and aberration, contributing to the evolution of CIN. miR-186 is overexpressed in iAs-induced squamous cell carcinoma relative to iAs-induced hyperkeratosis. Bioinformatic analysis indicated that miR-186 targets mRNAs of important cell cycle regulators including mitotic checkpoint serine/threonine kinase B (BUB1) and cell division cycle 27 (CDC27). We hypothesized that miR-186 overexpression contributes to iAs-induced transformation of keratinocytes by targeting mitotic regulators leading to induction of CIN. Ker-CT cells, a near diploid human keratinocyte cell line, were transduced with miR-186 overexpressing or scrambled control lentivirus. Stable clones were isolated after puromycin selection. Clones transduced with lentivirus expressing either a scrambled control miRNA or miR-186 were maintained with 0 or 100 nM iAs for 4 weeks. Unexposed scrambled control clones were considered as passage matched controls. Chronic iAs exposure increased miR-186 expression in miR-186 clones. miR-186 overexpression significantly reduced CDC27 levels irrespective of iAs exposure. The percentage of tetraploid or aneuploid cells was increased in iAs exposed miR-186 clones. Aneuploidy can arise from a tetraploid intermediate. Suppression of CDC27 by miR-186 may lead to impairment of mitotic checkpoint complex formation and its ability to maintain cell cycle arrest leading to chromosome misalignment. As a result, cells overexpressing miR-186 and chronically exposed to iAs may have incorrect chromosome segregation and CIN. These data suggest that dysregulation of miRNA by iAs mediates tetraploidy, aneuploidy and chromosomal instability contributing to iAs-induced carcinogenesis.

IntroductionThe M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed).MethodsThe goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome.ResultsNon-linear TD support vector regression modeling methods accounted for considerably more M50 latency variance than linear models, likely due to the non-linear dependence on neuroimaging factors such as GABA MRS. While SVR models accounted for ~80% of the M50 latency variance in TD and the genetically homogenous XYY syndrome, a similar approach only accounted for ~20% of the M50 latency variance in ASD, implicating the insufficiency of diffusion MR, GABA MRS, and age factors alone. Biologically based stratification of ASD was performed by assessing the conformance of the ASD population to the TD SVR model and identifying a sub-population of children with unexpectedly long M50 latency.DiscussionMultimodal integration of neuroimaging data can help build a mechanistic understanding of brain connectivity. The unexplained M50 latency variance in ASD motivates future hypothesis generation and testing of other contributing biological factors.

We use Hubble Space Telescope imaging to study the globular cluster system of the Virgo Cluster ultradiffuse galaxy (UDG) VCC 615. We select globular cluster candidates through a combination of size and color, while simultaneously rejecting contamination from background galaxies that would be unresolved in ground-based imaging. Our sample of globular cluster candidates is essentially complete down to a limiting magnitude of F814W = 24.0, ≈90% down the globular cluster luminosity function (GCLF). We estimate a total globular cluster population for VCC 615 of ${N}_{{\rm{GC}}}=25.{1}_{-5.4}^{+6.5}$ , resulting in a specific frequency of ${S}_{N}=55.{5}_{-12.0}^{+14.5}$ , quite high compared to normal galaxies of similar luminosity, but consistent with the large specific frequencies found in some other UDGs. The abundant cluster population suggests the galaxy is enshrouded by a massive dark halo, consistent with previous dynamical mass estimates using globular cluster kinematics. While the peak of the GCLF appears slightly brighter than expected (by ≈0.3–0.5 mag), this difference is comparable to the 0.3 mag uncertainty in the measurement, and we see no sign of an extremely luminous population of clusters similar to those detected in the UDGs NGC1054-DF2 and -DF4. However, we do find a relatively high fraction ( $3{2}_{-4}^{+5}$ %) of large clusters with half-light radii R _h > 9 pc. The galaxy's offset nucleus appears photometrically distinct from the globular clusters, and is more akin to ultracompact dwarfs (UCDs) in Virgo. Over time, VCC615’s already diffuse stellar body may be further stripped by cluster tides, leaving the nucleus intact to form a new Virgo UCD.

Using deep, narrowband imaging of the nearby spiral galaxy M101, we present stellar age information across the full extent of the disk of M101. Our narrowband filters measure age-sensitive absorption features such as the Balmer lines and the slope of the continuum between the Balmer break and 4000 Å break. We interpret these features in the context of inside-out galaxy formation theories and dynamical models of spiral structure. We confirm the galaxy’s radial age gradient, with the mean stellar age decreasing with radius. In the relatively undisturbed main disk, we find that stellar ages get progressively older with distance across a spiral arm, consistent with the large-scale shock scenario in a quasi-steady spiral wave pattern. Unexpectedly, we find the same pattern across spiral arms in the outer disk as well, beyond the corotation radius of the main spiral pattern. We suggest that M101 has a dynamic, or transient, spiral pattern with multiple pattern speeds joined together via mode coupling to form coherent spiral structure. This scenario connects the radial age gradient inherent to inside-out galaxy formation with the across-arm age gradients predicted by dynamic spiral arm theories across the full radial extent of the galaxy.

We use deep Hubble Space Telescope imaging to study the resolved stellar populations in BST1047+1156, a gas-rich, ultradiffuse dwarf galaxy found in the intragroup environment of the Leo I galaxy group. While our imaging reaches approximately two magnitudes below the tip of the red giant branch at the Leo I distance of 11 Mpc, we find no evidence for an old red giant sequence that would signal an extended star formation history for the object. Instead, we clearly detect the red and blue helium-burning sequences of its stellar populations, as well as the fainter blue main sequence, all indicative of a recent burst of star formation having taken place over the past 50–250 Myr. Comparing to isochrones for young metal-poor stellar populations, we infer this post-starburst population to be moderately metal-poor, with metallicity [ M/H ] in the range −1 to −1.5. The combination of a young, moderately metal-poor post starburst population and no old stars motivates a scenario in which BST1047 was recently formed during a weak burst of star formation in gas that was tidally stripped from the outskirts of the neighboring massive spiral M96. BST1047's extremely diffuse nature, lack of ongoing star formation, and disturbed H i morphology all argue that it is a transitory object, a “failing tidal dwarf” in the process of being disrupted by interactions within the Leo I group. Finally, in the environment surrounding BST1047, our imaging also reveals the old, metal-poor ([ M/H ] = − 1.3 ± 0.2) stellar halo of M96 at a projected radius of 50 kpc.

Species-rich Lotka-Volterra competition models of ecosystem dynamics transition with increasing species pool size from a phase with well-defined stable equilibrium to a dynamic phase that remains incompletely understood. We analytically describe the statistical mechanics of the steady state deep inside this dynamic phase, characterized by incessant turnover in species composition, and extract the distribution of invasion fitness of random invaders. We find that steady state invasion probability universally equals 1/2. This striking result agrees well with observations in plants and animals.

We study the size and structure of globular cluster (GC) systems of 118 early-type galaxies from the NGVS, MATLAS, and ACSVCS surveys. Fitting Sérsic profiles, we investigate the relationship between effective radii of GC systems ( R _e _,gc ) and galaxy properties. GC systems are 2–4 times more extended than host galaxies across the entire stellar mass range of our sample (10 ^8.3 M _⊙ < M _* < 10 ^11.6 M _⊙ ). The relationship between R _e _,gc and galaxy stellar mass exhibits a characteristic “knee” at a stellar mass of M _p ≃ 10 ^10.8 , similar to the galaxy R _e –stellar mass relationship. We present a new characterization of the traditional blue and red GC color subpopulations, describing them with respect to host galaxy $(g^{\prime} -i^{\prime} )$ color (Δ _gi ): GCs with similar colors to their hosts have a “red” Δ _gi , and those significantly bluer GCs have a “blue” Δ _gi . The GC populations with red Δ _gi , even in dwarf galaxies, are twice as extended as the stars, suggesting that formation or survival mechanisms favor the outer regions. We find a tight correlation between R _e _,gc and the total number of GCs, with intrinsic scatter ≲0.1 dex spanning two and three orders of magnitude in size and number, respectively. This holds for both red and blue subpopulations, albeit with different slopes. Assuming that N _GC,Total correlates with M _200 , we find that the red GC systems have effective radii of roughly 1%–5% R _200 , while the blue GC systems in massive galaxies can have sizes as large as ∼10% R _200 . Environmental dependence on R _e _,gc is also found, with lower-density environments exhibiting more extended GC systems at fixed mass.

We analyze the O vi content and kinematics for 126 H i -selected absorbers at 0.14 ≲ z ≲ 0.73 for which the metallicities of their cool photoionized phase have been determined. We separate the absorbers into 100 strong Ly α forest systems (SLFSs with 15 ≲ log N (H i ) < 16.2) and 26 partial Lyman Limit systems (pLLSs with 16.2 ≤ log N (H i ) ≤ 17.2). The sample is drawn from the COS CGM Compendium (CCC) and has O vi coverage in signal-to-noise ratio ≥ 8 Hubble Space Telescope/COS G130M/G160M QSO spectra, yielding a 2 σ completeness level of $\mathrm{log}N$ (O vi ) ≥ 13.6. The O vi detection rates differ substantially between low-metallicity (LM; [X/H] ≤ −1.4) and high-metallicity (HM; [X/H] > −1.4) SLFSs, with 20% and 60% detection rates, respectively. The O vi detection frequency for the HM and LM pLLSs is, however, similar at ∼60%. The SLFSs and pLLSs without detected O vi are consistent with the absorbing gas being in a single phase, while those with O vi trace multiphase gas. We show that the O vi velocity widths and column densities have different distributions in LM and HM gas. We find a strong correlation between O vi column density and metallicity. The strongest ( $\mathrm{log}N$ (O vi ) ≳ 14) and broadest O vi absorbers are nearly always associated with HM absorbers, while weaker O vi absorbers are found in both LM and HM absorbers. From comparisons with galaxy-selected and blind O vi surveys, we conclude absorbers with $\mathrm{log}N$ (O vi ) ≳ 14 most likely arise in the CGM of star-forming galaxies. Absorbers with weak O vi likely trace the extended CGM or intergalactic medium, while those without O vi likely originate in the intergalactic medium.

Keeping sodium hypochlorite (NaOCl) within the root canal is challenging in regenerative endodontics. In this study, we developed a drug delivery system using a gelatin methacryloyl (GelMA) hydrogel incorporated with aluminosilicate clay nanotubes (HNTs) loaded with NaOCl. Pure GelMA, pure HNTs, and NaOCl-loaded HNTs carrying varying concentrations were assessed for chemo-mechanical properties, degradability, swelling capacity, cytocompatibility, antimicrobial and antibiofilm activities, and in vivo for inflammatory response and degradation. SEM images revealed consistent pore sizes of 70–80 µm for all samples, irrespective of the HNT and NaOCl concentration, while HNT-loaded hydrogels exhibited rougher surfaces. The hydrogel’s compressive modulus remained between 100 and 200 kPa, with no significant variations. All hydrogels demonstrated a 6–7-fold mass increase and complete degradation by the seventh day. Despite an initial decrease in cell viability, all groups recovered to 65–80% compared to the control. Regarding antibacterial and antibiofilm properties, 12.5 HNT(Double) showed the highest inhibition zone on agar plates and the most significant reduction in biofilm compared to other groups. In vivo, the 12.5 HNT(Double) group displayed partial degradation after 21 days, with mild localized inflammatory responses but no tissue necrosis. In conclusion, the HNT-NaOCl-loaded GelMA hydrogel retains the disinfectant properties, providing a safer option for endodontic procedures without harmful potential.

Per- and poly-fluoroalkyl substances (PFAS) are a large class of fluorinated carbon chains that include legacy PFAS, such as perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). These compounds induce adverse health effects, including hepatotoxicity. Potential alternatives to the legacy PFAS (HFPO-DA (GenX), HFPO4, HFPO-TA, F-53B, 6:2 FTSA, and 6:2 FTCA), as well as a byproduct of PFAS manufacturing (Nafion BP2), are increasingly being found in the environment. The potential hazards of these new alternatives are less well known. To better understand the diversity of molecular targets of the PFAS, we performed a comparative toxicogenomics analysis of the gene expression changes in the livers of mice exposed to these PFAS, and compared these to five activators of PPARα, a common target of many PFAS. Using hierarchical clustering, pathway analysis, and predictive biomarkers, we found that most of the alternative PFAS modulate molecular targets that overlap with legacy PFAS. Only three of the 11 PFAS tested did not appreciably activate PPARα (Nafion BP2, 6:2 FTSA, and 6:2 FTCA). Predictive biomarkers showed that most PFAS (PFHxS, PFOA, PFOS, PFNA, HFPO-TA, F-53B, HFPO4, Nafion BP2) activated CAR. PFNA, PFHxS, PFOA, PFOS, HFPO4, HFPO-TA, F-53B, Nafion BP2, and 6:2 FTSA suppressed STAT5b, activated NRF2, and activated SREBP. There was no apparent relationship between the length of the carbon chain, type of head group, or number of ether linkages and the transcriptomic changes. This work highlights the similarities in molecular targets between the legacy and alternative PFAS.

Abstract Background Impaired cognitive reappraisal, associated with the social functioning and well-being of patients affected by mood or anxiety disorders, is characterized by distinct neural activation patterns across clinical populations. To date, studies dedicated to identifying common and distinct neural activation profiles need to be clarified. The aim of the present study was to investigate transdiagnostic differences and commonalities in brain activation patterns during reappraisal-mediated downregulation of emotions. Methods Cognitive reappraisal of negative images was contrasted with maintaining emotions during a control viewing condition. Brain activation in 35 patients with major depressive disorder (MDD), 20 patients with post-traumatic stress disorder (PTSD), and 34 healthy controls (HC) during cognitive reappraisal was compared. Moreover, the neural circuitry of emotion regulation in these clinical populations was examined using seed-to-voxel and voxel-to-voxel functional connectivity analyses. Results Whole-brain fMRI analyses showed less right-lateralized activation of the inferior, middle, and superior frontal gyrus during cognitive reappraisal compared to viewing of negative images in MDD and PTSD patients compared to HCs. Right IFG activation was negatively correlated with the severity of anxiety and depressive symptomatology. In addition, increased seed-to-voxel connectivity of the right IFG as well as increased voxel-to-voxel connectivity was observed in PTSD patients compared to HCs and MDD patients. Conclusions FMRI results therefore suggested a common deficit of depression and anxiety symptomatology reflected by reduced activation in right IFG during cognitive reappraisal as well as diagnosis specific effects in patients with PTSD based on seed-to-voxel and voxel-to-voxel connectivity showing an overactive and hyperconnected salience network. Findings highlight the role of transdiagnostic research to identify disorder specific brain patterns as well as patterns common across disorders.

Abstract Background Tuberous sclerosis complex (TSC)–associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. Methods The study was conducted in accordance with stages outlined within the Arksey and O’Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. Results Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low–middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder–like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). Conclusions Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified.

Coastal fish communities are under increasing levels of stress associated with climate variation and anthropogenic activities. However, the high degree of behavioral plasticity of many species within these communities allow them to cope with altered environmental conditions to some extent. Here, we combine meteorological information, data from hydroacoustic surveys, and recordings of goliath grouper sound production to examine the response of coastal fish communities to heavy rainfall events in South Florida, USA, that resulted in the release of excess storm water into surrounding estuaries and coastal waters. We observed a nearly 12,000% increase in water column acoustic backscatter following a heavy rainfall event of September 16th, 2015. Interestingly, estimates of school backscatter, a proxy for biomass, increased by 172% with the onset of the perturbation. Schooling fish density also increased by 182%, as did acoustically derived estimates of mean schooling fish length (21%). Following the perturbed period, school backscatter decreased by 406%, along with schooling density (272%), and mean schooling fish length (35%). Hydrophone and hydroacoustic data also revealed that goliath grouper (Epinephelus itajara) spawning aggregations were persistent in the region throughout the duration of the study and continued to exhibit courtship behavior during the perturbed period. Our observations demonstrate the high level of resistance common in coastal species but raises new questions regarding the threshold at which fish communities and reproductive activities are disrupted. As coastal land use continues to increase, and the effects of global climate change become more pronounced, more Before-After Control Impact (BACI) studies will provide improved insight into the overall response of nearshore communities to future perturbations and the cumulative effect of repeated perturbations over extended periods.