Browse Articles

Stochastic morphological swings in <i>Hydra</i> regeneration: A manifestation of noisy canalized morphogenesis

Animal morphogenesis, the development of an organism’s body form, is commonly perceived as a directed and almost deterministic process. However, noise and stochastic fluctuations are ubiquitous in biological systems. The questions on the role of fluctuations in morphogenesis and what ensures the robustness of this process under noisy conditions remain elusive. Here, we utilize Hydra regeneration, subjected to an external electric field, to provide unique insights into these questions. We found that during Hydra morphogenesis, a phase can be induced where fluctuations lead to stochastic morphological swings, back and forth, between a nearly spherical structure (the incipient tissue’s state) and an elongated cylindrical shape (the final body form of a mature Hydra ). Despite these prolonged swings, the tissue regenerates into a normal Hydra . The stochastic transitions between two well-defined shapes imply that morphological development occurs through an activation process. Indeed, by introducing a periodic perturbation through modulation of the electric field, we were able to demonstrate morphogenesis dynamics with characteristics of stochastic resonance —the tissue’s response to the perturbation displayed a resonance-like behavior as a function of the noise level. Our findings add a dynamic layer to the problem of morphogenesis and offer an unconventional physical framework based on an activation transition in a slowly varying double-well potential that ensures a canalized regeneration of the body form under fluctuations.

Vaccine hesitancy among health paraprofessionals: A mixed methods study

Background The World Health Organization (WHO) defines vaccine hesitancy as “a delay in acceptance or refusal of vaccines despite availability of vaccination services”. Vaccine hesitancy has also been declared a top threat to global health. Some employers imposed vaccine mandates during the Covid-19 pandemic resulting in health care employees resigning or being fired rather than receive a vaccine. Healthcare paraprofessionals such as certified nursing assistants, dietary and home health aides are among the most patient facing of all health care providers. Their beliefs and attitudes about vaccines are critical to how they communicate about vaccines with their patients. Objective The objective of this project was to survey health care paraprofessionals to explore their thoughts and opinions about vaccines in general, and Covid-19 vaccines specifically. Methods This was a 25 question, mixed methods, cross sectional email survey. Subjects were recruited from the mailing list of a non-profit organization in the Midwest. This organization is dedicated to bringing a face and a voice to healthcare paraprofessionals engaged in direct patient care. Results Most respondents were reasonably well informed about vaccines; had received one or more doses of indicated vaccines; used credible resources to learn about vaccines and believed physicians and pharmacists were the most trusted information sources. Qualitative results indicated that respondents expressed support for vaccines but that the support was often qualified in that a respondent may have had both pro and anti-vaccine opinions in the same response. They also expressed that communications about vaccines were often problematic. Additional vaccine-related continuing professional development for healthcare paraprofessionals appears to be indicated. Conclusions Although attitudes towards vaccines were generally positive, respondents had concerns about the quality of vaccine information. Additional vaccine-related continuing professional development for healthcare paraprofessionals appears to be indicated.

Daily briefing: Why did Europe’s first cities disappear? Uncovering the mysterious Cucuteni–Trypillia culture

Moiré magnetism and moiré excitons in twisted CrSBr bilayers

Moiré excitons and moiré magnetism are essential to semiconducting van der Waals magnets. In this work, we perform a comprehensive first-principles study to elucidate the interplay of electronic excitation and magnetism in twisted magnetic CrSBr bilayers. We predict a twist-induced quantum phase transition for interlayer magnetic coupling and estimate the critical twist angle below which moiré magnetism with mixed ferromagnetic and antiferromagnetic domains could emerge. Localized one-dimensional moiré excitons are stable if the interlayer coupling is ferromagnetic and become unstable if the coupling turns to antiferromagnetic. Exciton energy modulation by magnons is estimated and dependence of exciton oscillator strength on the twist angle and interlayer coupling is analyzed. An orthogonally twisted bilayer is revealed to exhibit layer-dependent, anisotropic optical transitions. Electric field is shown to induce net magnetic moments in moiré excitons, endowing them with exceedingly long lifetimes. Our work lays the foundation for using magnetic moiré bilayers in spintronic, optoelectronic, and quantum information applications.

Mobile Sleep Lab: Comparison of polysomnographic parameters with a conventional sleep laboratory

In remote areas, visiting a laboratory for sleep testing is inconvenient. We, therefore, developed a Mobile Sleep Lab in a bus powered by fuel cells with two sleep measurement chambers. As the environment in the bus could affect sleep, we examined whether sleep testing in the Mobile Sleep Lab was as feasible as in a conventional sleep laboratory (Human Sleep Lab). We tested 15 healthy adults for four nights using polysomnography (the first two nights at the Human Sleep Lab or Mobile Sleep Lab with a switch to the other facility for the next two nights). Sleep variables of the four measurements were used to assess the discrepancy of different places or different nights. No significant differences were found between the laboratories other than the percentage of total sleep time in stage N3. Next, we analyzed the intraclass correlation coefficient to evaluate the test-retest reliability. The intraclass correlation coefficient between these two measurements: the Human Sleep Lab and Mobile Sleep Lab showed similar reliability for the same sleep variables. The intraclass correlation coefficient revealed that several sleep indexes, such as total sleep time, sleep efficiency, wake after sleep onset, percentage of stage N1, and stage R latency, showed poor reliabilities (&lt;0.5) based on Koo and Li’s criteria. In contrast, the percentage of stage N3 showed moderate (0.5–0.75) or good (0.75–0.9) reliabilities. As almost all sleep variables showed no difference and same level of test-retest reliability between the Mobile Sleep Lab and Human Sleep Lab, the Mobile Sleep Lab might be suitable for conducting polysomnography as a conventional sleep laboratory. The reduction in N3 in the Mobile Sleep Lab should be scrutinized in the larger sample, including sleep disorders. Practical application of the Mobile Sleep Lab can transform sleep medicine in remote areas.

Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome

Spns1 mediates the rate-limiting efflux of lysophospholipids from the lysosome to the cytosol. Deficiency of Spns1 is associated with embryonic senescence, as well as liver and skeletal muscle atrophy in animal models. However, the mechanisms by which Spns1 transports lysophospholipid and proton sensing remain unclear. Here, we present a cryogenic electron microscopy structure of human Spns1 in lysophosphatidylcholine (LPC)-bound lumen-facing conformation. Notably, LPC snugly binds within the luminal-open cavity, where the molecular dynamics simulations reveal that LPC presents a propensity to enter between transmembrane-helices (TM) 5 and 8. Structural comparisons and cell-based transport assays uncover several pivotal residues at TM 5/8 that orchestrate the transport cycle, which are unique to Spns1. Furthermore, we identify a five-residue network that is crucial for proton-sensing by Spns1. Transference of these network residues to Spns2, a sphingosine-1-phosphate uniporter, causes the chimeric Spns2 to be low pH dependent. Our results reveal molecular insights into lysosomal LPC transport and the proton-sensing mechanism by Spns1.

Fault tolerance in distributed systems using deep learning approaches

Recently, distributed systems have become the backbone of technological development. It serves as the foundation for new trends technologies such as blockchain, the internet of things and others. A distributed system provides fault tolerance and decentralization, where a fault in any component does not result in a whole system failure. In addition, deep learning model enables processing data to find patterns, which helps in classification, regression, prediction, and clustering. This work employs deep learning to handle faults within distributed systems in three scenarios. Firstly, a faulty processor may not be able to produce the right output. Therefore, deep learning model uses the inputs and outputs of other processors to find patterns and produces the proper output of the faulty processor. Secondly, if a faulty possessor corrupts its inputs as well, then the deep learning model learns from the inputs and the outputs of successful processors and produces the proper output of the faulty processor, even with corrupted inputs. Thirdly, for unrelated data, in which the patterns of the input of the faulty processors differ from the patterns of the inputs of successful ones. In this case, the model is able to discover the new pattern and to be labeled as unknown. In the experiments, we use deep learning models like VGG16, VGG19, AlexNet LSTM and ResNet34, to investigate the performance of the deep learning in the three mentioned scenarios. For unstructured datasets, the accuracy of the models is affected by the size of the faulty data. The accuracy of all models lies between 60% when the size of the faulty data is 90%, and 96%, when the size of the faulty data is 90%. The structured datasets are not significantly affected by the portion of the faulty data and the accuracy reaches 99%.

Carbon gain in upper but loss in deeper cropland soils across China over the last four decades

Increasing soil organic carbon (SOC) in agricultural systems is a primary nature-based option for mitigating climate change, improving soil fertility, and ensuring food security. However, the consequences of global warming and increases in carbon inputs on cropland SOC stocks over the last few decades remain largely unknown, particularly in deeper soil layers. Here, by using repeated measurements, we reassess variations in SOC stocks across a 0 to 100 cm soil profile at the same locations in China’s upland croplands in 1980 and 2023. We observe an overall net accumulation of 0.74 Pg SOC (7%) with a mean sequestration rate of 13.7 g SOC m −2 y −1 . This accumulation results from 0.86 Pg SOC gains at upper soil depths (0 to 60 cm) induced by carbon inputs, alongside 0.12 Pg SOC losses at deeper soil layers (60 to 100 cm) prompted by warming-enhanced decomposition. While our findings indicate a successful, though lower than expected, increase in overall net SOC stocks, the loss of more recalcitrant deeper SOC warrants further consideration of its effects on enhancing cropland SOC accumulation to achieve carbon neutrality over the long term.

Accurate multi-behavior sequence-aware recommendation via graph convolution networks

How can we recommend items to users utilizing multiple types of user behavior data? Multi-behavior recommender systems leverage various types of user behavior data to enhance recommendation performance for the target behavior. These systems aim to provide personalized recommendations, thereby improving user experience, engagement, and satisfaction across different applications such as e-commerce platforms, streaming services, news websites, and content platforms. While previous approaches in multi-behavior recommendation have focused on incorporating behavioral order and dependencies into embedding learning, they often overlook the nuanced importance of individual behaviors in shaping user preferences during model training. We propose MBA (Multi-Behavior sequence-Aware recommendation via graph convolution networks), an accurate framework for multi-behavior recommendations. MBA adopts a novel approach by learning embeddings that capture both the dependencies between behaviors and their relative importance in influencing user preferences. Additionally, MBA employs sophisticated sampling strategies that consider the sequential nature of behaviors during model training, ensuring that the model effectively learns from the entire behavioral sequence. Through extensive experiments on real-world datasets, we demonstrate the superior performance of MBA compared to existing methods. MBA outperforms the best competitor, achieving improvements of up to 11.2% and 11.4% in terms of HR@10 and nDCG@10, respectively. These findings underscore the effectiveness of MBA in providing accurate and personalized recommendations tailored to individual user preferences.

Memory control deficits in the sleep-deprived human brain

Sleep disturbances are associated with intrusive memories, but the neurocognitive mechanisms underpinning this relationship are poorly understood. Here, we show that sleep deprivation disrupts prefrontal inhibition of memory retrieval, and that the overnight restoration of this inhibitory mechanism is associated with time spent in rapid eye movement (REM) sleep. The functional impairments arising from sleep deprivation are linked to a behavioral deficit in the ability to downregulate unwanted memories, and coincide with a deterioration of deliberate patterns of self-generated thought. We conclude that sleep deprivation gives rise to intrusive memories via the disruption of neural circuits governing mnemonic inhibitory control, which may rely on REM sleep.

Label-free determination of diffusion coefficients at the nanoscale through modelling of the Surface Plasmon Resonance signal

Surface plasmon resonance (SPR) is normally used to measure the kinetic parameters of biomolecular interactions between a molecule immobilized on a gold surface and another one flowing in a microfluidic channel above the surface. During the SPR measurements, convection-diffusion phenomena occur inside the microfluidic channels, but they are generally minimized by appropriate experimental setup in order to obtain diffusion free kinetic parameters of the molecular interactions. In this work, for the first time, a commercial SPR apparatus has been used to obtain non canonical scientific parameters. Indeed, a specifically designed SPR experimental setup is described for carrying out measurements of the diffusion coefficient (D) of molecules in solutions. The high precision and reproducibility of the approach, as well as the wide applicability of the newly proposed SPR based method for the measurement of D of many different molecules and biomolecules, are here demonstrated and illustrated in detail.

The unexplored potential of exosomes in the muscle–brain axis

Mobile clinics routing and scheduling in the Witzenberg region of South Africa

Despite much literature on operations research applied to various healthcare problems, impactful implementation in public healthcare is limited, which often results in allocative inefficiency. This article uses a mobile clinic routing and scheduling problem in the Witzenberg region of South Africa as a case study to demonstrate the improvement of implementation success through cross-disciplinary collaboration, and also to propose a new three-stage approach for modelling a mobile clinic problem that incorporates continuity of care, fairness, and minimisation of distance travelled. Mobile clinics are used in many countries to improve access to healthcare for rural communities. Decision makers must assign farms or villages to mobile clinics, and determine their monthly visit schedules. To improve implementation success, we follow a collaborative three-phased mixed-methods approach with healthcare professionals to improve workload balance, fairness, and transportation cost. During phase 1, qualitative and quantitative data are gathered through qualitative research methods. In phase 2, fairly distributed optimal routes and schedules are designed using a three-stage model that incorporates a multi-vehicle routing problem to determine daily routes, a knapsack problem to establish a fair allocation of these daily routes between different clinics, and another variation on the vehicle routing problem to determine the monthly visit schedule that minimises the distance between the last farm visited on each consecutive day in the case of having to return to a farm the next day. Different input parameter estimations result in different routes and schedules. In phase 3, AHP is performed with main decision makers to determine their preferred solution. Final routes and schedules are designed based on model results, AHP results, and contextual input from decision makers. In our case study, an improved workload balance, a 23% reduction in total distance travelled, and buy-in to implement the changes, were obtained.

Molecular mechanism governing the plasticity of use-dependent spike broadening in dorsal root ganglion neurons

Use-dependent spike broadening (UDSB) results from inactivation of the voltage-gated K + (Kv) channels that regulate the repolarization of the action potential. However, the specific signaling and molecular processes that modulate UDSB have remained elusive. Here, we applied an adeno-associated viral vector approach and dynamic clamping to conclusively demonstrate how multisite phosphorylation of the N-terminal inactivation domain (NTID) of the Kv3.4 channel modulates UDSB in rat dorsal root ganglion (DRG) neurons. The Kv3.4 phosphonull variant promotes slow recovery from inactivation, cumulative inactivation, and UDSB. In contrast, the Kv3.4 phosphomimic variant promotes fast recovery from inactivation and robust resistance to cumulative inactivation and UDSB. Furthermore, knocking down Kv3.4 maximizes AP width and eliminates UDSB modulation. Together with the evidence from previous work, the results concretely suggest how dynamic UDSB modulation governed by multisite phosphorylation of the NTID of Kv3.4 in DRG neurons may play a significant role in mechanosensory transduction and pain modulation.

ChatGPT-4o can serve as the second rater for data extraction in systematic reviews

Background Systematic reviews provide clarity of a bulk of evidence and support the transfer of knowledge from clinical trials to guidelines. Yet, they are time-consuming. Artificial intelligence (AI), like ChatGPT-4o, may streamline processes of data extraction, but its efficacy requires validation. Objective This study aims to (1) evaluate the validity of ChatGPT-4o for data extraction compared to human reviewers, and (2) test the reproducibility of ChatGPT-4o’s data extraction. Methods We conducted a comparative study using papers from an ongoing systematic review on exercise to reduce fall risk. Data extracted by ChatGPT-4o were compared to a reference standard: data extracted by two independent human reviewers. The validity was assessed by categorizing the extracted data into five categories ranging from completely correct to false data. Reproducibility was evaluated by comparing data extracted in two separate sessions using different ChatGPT-4o accounts. Results ChatGPT-4o extracted a total of 484 data points across 11 papers. The AI’s data extraction was 92.4% accurate (95% CI: 89.5% to 94.5%) and produced false data in 5.2% of cases (95% CI: 3.4% to 7.4%). The reproducibility between the two sessions was high, with an overall agreement of 94.1%. Reproducibility decreased when information was not reported in the papers, with an agreement of 77.2%. Conclusion Validity and reproducibility of ChatGPT-4o was high for data extraction for systematic reviews. ChatGPT-4o was qualified as a second reviewer for systematic reviews and showed potential for future advancements when summarizing data.

A mechanosensitive circuit of FAK, ROCK, and ERK controls biomineral growth and morphology in the sea urchin embryo

Biomineralization is the utilization of different minerals by a vast array of organisms to form hard tissues and shape them in various forms. Within this diversity, a common feature of all mineralized tissues is their high stiffness, implying that mechanosensing could be commonly used in biomineralization. Yet, the role of mechanosensing in biomineralization is far from clear. Here, we use the sea urchin larval skeletogenesis to investigate the role of substrate stiffness and focal adhesion kinase (FAK) in biomineralization. We demonstrate that substrate stiffness alters spicule morphology and growth, indicating a mechanosensitive response during skeletogenesis. We show that active FAK, F-actin, and vinculin are enriched around the spicules, indicating the formation of focal adhesion complexes and suggesting that the cells sense the mechanical properties of the biomineral. Furthermore, we find that FAK activity is regulated by Rho-associated protein kinase (ROCK) and is crucial for skeletal growth and normal branching. FAK and ROCK activate extracellular signal-regulated kinase (ERK), which regulates skeletogenic gene expression at the tips of the spicules. Thus, the FAK-ROCK-ERK circuit seems to provide essential mechanical feedback on spicule elongation to the skeletogenic gene regulatory network, enabling skeletal growth. Remarkably, the same factors govern mammalian osteoblast differentiation in vitro and pathological calcification in vivo. Thus, this study highlights a common mechanotransduction pathway in biomineralization that was probably independently co-opted across different organisms to shape mineralized structures in metazoans.

Comparison of cellular-based therapies following a long-segmental peripheral nerve defect in a rat model

Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity, often leading to limited functional recovery and pain. Many PNIs are not amenable to repair with traditional techniques; however, cell therapies, particularly Schwann cells (SCs), offer the promise of neural tissue replacement and functional improvement. Exosomes, which carry cellular signaling molecules, can be secreted by SCs and have shown promise in PNI. Our laboratory has had success using SCs in preclinical and clinical treatment settings. Transplanted cells have several known limitations, which exosomes mitigate. To that end, the current study investigated if implanted SC-derived exosomes in conduits, conduits with SCs, reverse autograft, or empty conduits comparably improve axonal regeneration and pain outcomes 16-weeks after repair of a long gap PNI in adult rats. Results show that there were no differences between groups in the von Frey filament testing or in the Hargreaves test. Electrophysiological testing showed a significant difference between the injured (ipsilateral) and uninjured (contralateral) limbs while histological assessment showed a significant difference between axonal counts in different areas of the conduit. Based on the results of the current study, more research is needed to understand the therapeutic role of exosomes in PNI.

In situ architecture of a nucleoid-associated biomolecular co-condensate that regulates bacterial cell division

In most bacteria, cell division depends on the tubulin-homolog FtsZ that polymerizes in a GTP-dependent manner to form the cytokinetic Z-ring at the future division site. Subsequently, the Z-ring recruits, directly or indirectly, all other proteins of the divisome complex that executes cytokinesis. A critical step in this process is the precise positioning of the Z-ring at the future division site. While the divisome proteins are generally conserved, the regulatory systems that position the Z-ring are more diverse. However, these systems have in common that they modulate FtsZ polymerization. In Myxococcus, PomX, PomY, and PomZ form precisely one MDa-sized, nonstoichiometric, nucleoid-associated assembly that spatiotemporally guides Z-ring formation. Here, using cryo-correlative light and electron microscopy together with in situ cryoelectron tomography, we determine the PomXYZ assembly’s architecture at close-to-live conditions. PomX forms a porous meshwork of randomly intertwined filaments. Templated by this meshwork, the phase-separating PomY protein forms a biomolecular condensate that compacts and bends the PomX filaments, resulting in the formation of a selective PomXYZ co-condensate that is associated to the nucleoid by PomZ. These studies reveal a hitherto undescribed supramolecular structure and provide a framework for understanding how a nonstoichiometric co-condensate forms, maintains number control, and nucleates GTP-dependent FtsZ polymerization to precisely regulate cell division.

Multivariate description of gait changes in a mouse model of peripheral nerve injury and trauma

Objective Animal models of nerve injury are important for studying nerve injury and repair, particularly for interventions that cannot be studied in humans. However, the vast majority of gait analysis in animals has been limited to univariate analysis even though gait data is highly multi-dimensional. As a result, little is known about how various spatiotemporal components of the gait relate to each other in the context of peripheral nerve injury and trauma. We hypothesize that a multivariate characterization of gait will reveal relationships among spatiotemporal components of gait with biological relevance to peripheral nerve injury and trauma. We further hypothesize that legitimate relationships among said components will allow for more accurate classification among distinct gait phenotypes than if attempted with univariate analysis alone. Methods DigiGait data was collected of mice across groups representing increasing degrees of damage to the neuromusculoskeletal sequence of gait; that is (a) healthy controls, (b) nerve damage only via total nerve transection + reconnection of the femoral and sciatic nerves, and (c) nerve, muscle, and bone damage via total hind-limb transplantation. Multivariate relationships among the 30+ spatiotemporal measures were evaluated using exploratory factor analysis and forward feature selection to identify the features and latent factors that best described gait phenotypes. The identified features were then used to train classifier models and compared to a model trained with features identified using only univariate analysis. Results 10–15 features relevant to describing gait in the context of increasing degrees of traumatic peripheral nerve injury were identified. Factor analysis uncovered relationships among the identified features and enabled the extrapolation of a set of latent factors that further described the distinct gait phenotypes. The latent factors tied to biological differences among the groups (e.g. alterations to the anatomical configuration of the limb due to transplantation or aberrant fine motor function due to peripheral nerve injury). Models trained using the identified features generated values that could be used to distinguish among pathophysiological states with high statistical significance (p &lt; .001) and accuracy (&gt;80%) as compared to univariate analysis alone. Conclusion This is the first performance evaluation of a multivariate approach to gait analysis and the first demonstration of superior performance as compared to univariate gait analysis in animals. It is also the first study to use multivariate statistics to characterize and distinguish among different gradations of gait deficit in animals. This study contributes a comprehensive, multivariate characterization pipeline for application in the study of any pathologies in which gait is a quantitative translational outcome metric.

X*Y females exhibit steeper reproductive senescence in the African pygmy mouse

A wave of studies has recently emphasized the influence of sex chromosomes on both lifespan and actuarial senescence patterns across vertebrates and invertebrates. Basically, the heterogametic sex (XY males in XX/XY systems or ZW females in ZW/ZZ systems) typically displays a lower lifespan and a steeper rate of actuarial senescence than the homogametic sex. However, whether these effects extend to the senescence patterns of other phenotypic traits or physiological functions is yet to be determined. Here, we investigated whether sex chromosomes modulate reproductive senescence using females from the African pygmy mouse ( Mus minutoides ). This biological model exhibits an odd sex determining system with a third, feminizing sex chromosome, X*, resulting in three distinct female genotypes (XX, X*X, or X*Y) that coexist in natural populations. We found that the rate of senescence in litter size at birth is much more pronounced in heterogametic X*Y females than in homogametic XX or X*X females that may support the unguarded X or toxic Y hypotheses and can be directly linked to the complex and unique X*Y phenotype. A decrease in neonatal survival with mother’s age has also been found, but this decline is not different between the three female genotypes.