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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.
Efficient coupling of dual beam combined laser into micro water jet for deep processing
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 < .001) and accuracy (>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.
Prediction model establishment of prognosis factors for acute myeloid leukemia based on the SEER database
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.
Development and validation of a Malay version questionnaire for assessing risk perception of type 2 diabetes (RPDM)
Background The burden of type 2 diabetes is increasing globally. Risk perception of type 2 diabetes plays an important role in motivating adoption of healthy lifestyle and preventive health interventions. To address the increasing burden of type 2 diabetes in Malaysia, a better understanding on its risk perception is needed as a guide for preventive interventions. This study was aimed at developing and validating a Malay-language questionnaire to assess the risk perception of type 2 diabetes (RPDM) among Malaysians. Methods The questionnaire (RPDM) was developed based on the Health Belief Model and previous literature. A 59-item question pool was initially developed, reviewed by experts for content validity and pretested on five respondents. Different samples were used for pilot study (n = 100) and subsequent validation study (n = 158). Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) were used to evaluate construct validity and construct reliability of the questionnaire. Results The EFA yielded five-factors model, including 48 items with good factor loadings of > 0.40. CFA was carried out using item parceling. The final model shows acceptable model fit and had sufficient convergent and discriminant validity. The value of construct reliability ranged between 0.76 and 0.90. Conclusion This newly developed and validated Malay-language RPDM questionnaire is valid and reliable for measuring the five constructs (perceived self-efficacy, perceived severity, perceived benefit, perceived susceptibility and perceived barrier) of risk perception of type 2 diabetes among Malaysians. This Malay-language questionnaire may contribute to a better understanding of risk perception of type 2 diabetes among Malaysians, as well as enhancement of diabetes prevention communication between healthcare providers and their clients.
Mineral composition and ratios in aortic valves, serum, and epicardial fat among patients with aortic stenosis undergoing aortic valve replacement
Higher-order transient structures and the principle of dynamic connectivity in membrane signaling
We examine the role of higher-order transient structures (HOTS) in M2R regulation of GIRK channels. Electron microscopic membrane protein location maps show that both proteins form HOTS that exhibit a statistical bias to be near each other. Theoretical calculations and electrophysiological measurements suggest that channel activity is isolated near larger M2R HOTS. By invoking weak interactions that permit transient binding of M2R to M2R and GIRK to GIRK ( i-i interactions) and M2R to GIRK ( i-j interactions), the distribution patterns and electrophysiological properties of HL-1 cells are replicated in a reaction-diffusion simulation. We propose the principle of dynamic connectivity to explain communication between protein components of a membrane signaling pathway. Dynamic connectivity is mediated by weak, transient interactions between proteins. HOTS created by weak i-i interactions, and statistical biases created by weak i-j interactions promoted by the multivalence of HOTS, are the key elements of dynamic connectivity.
Research on boundary control of vehicle-mounted flexible manipulator based on partial differential equations
Vehicle-mounted flexible robotic arms (VFRAs) are crucial in enhancing operational capabilities in sectors where human intervention is limited due to accessibility or safety concerns, such as hazardous environments or precision surgery. This paper introduces the latest generation of VFRAs that utilize advanced soft materials and are designed with elongated structures to provide greater flexibility and control. We present a novel mathematical model, derived using Hamilton’s principle, which simplifies the analysis of the arm’s dynamic behaviors by employing partial differential equations (PDEs). This model allows us to understand how these arms behave over time and space, classifying them as distributed parameter systems. Furthermore, we enhance the practical utility of these robotic arms by implementing a proportional-derivative (PD) based boundary control law to achieve precise control of movement and suppression of vibrations, which are critical for operations requiring high accuracy. Our approach’s effectiveness and practical utility are evidenced by numerical simulations, which verify that our advanced control strategy greatly enhances the performance and dependability of VFRAs in actual applications. These advancements not only pave the way for more sophisticated robotic implementations but also have broad implications for the future of automated systems in various industries.
Enhancing repeatability of follicle counting with deep learning reconstruction high-resolution MRI in PCOS patients
Abstract Follicle count, a pivotal metric in the adjunct diagnosis of polycystic ovary syndrome (PCOS), is often underestimated when assessed via transvaginal ultrasonography compared to MRI. Nevertheless, the repeatability of follicle counting using traditional MR images is still compromised by motion artifacts or inadequate spatial resolution. In this prospective study involving 22 PCOS patients, we employed periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and single-shot fast spin-echo (SSFSE) T2-weighted sequences to suppress motion artifacts in high-resolution ovarian MRI. Additionally, deep learning (DL) reconstruction was utilized to compensate noise in SSFSE imaging. We compared the performance of DL reconstruction SSFSE (SSFSE-DL) images with conventional reconstruction SSFSE (SSFSE-C) and PROPELLER images in follicle detection, employing qualitative indices (blurring artifacts, subjective noise, and conspicuity of follicles) and the repeatability of follicle number per ovary (FNPO) assessment. Despite similar subjective noise between SSFSE-DL and PROPELLER as assessed by one observer, SSFSE-DL images outperformed SSFSE-C and PROPELLER images across all three qualitative indices, resulting in enhanced repeatability in FNPO assessment. These results highlighted the potential of DL reconstruction high-resolution SSFSE imaging as a more dependable method for identifying polycystic ovary, thus facilitating more accurate diagnosis of PCOS in future clinical practices.
Conservation of symbiotic signaling since the most recent common ancestor of land plants
Plants have colonized lands 450 million years ago. This terrestrialization was facilitated by developmental and functional innovations. Recent evo-devo approaches have demonstrated that one of these innovations was the mutualistic arbuscular mycorrhizal symbiosis (AMS). The genetic pathways that have been involved in the establishment and functioning of AMS since its evolution remain poorly described. Here, we found that intracellular colonization by AM fungi induces a transcriptional reporter of the common symbiosis pathway, well-described in angiosperms, in the liverwort Marchantia paleacea . Mutants of either of the three main genes of this pathway, SYMRK , CCaMK, and CYCLOPS, disrupt the ability of M. paleacea to associate with AM fungi. Finally, overexpressing gain-of-function CCaMK or CYCLOPS leads to convergent transcriptomic signatures that partially overlap with AMS. Altogether, our data indicate that plants have maintained three genes of the common symbiotic pathway to support symbiotic interactions since their most recent common ancestor.
Using the Behaviour Change Wheel to develop an intervention to improve conversations about recovery on the stroke unit
Background Understanding recovery is important for patients with stroke and their families, including how much recovery is expected and how long it might take. These conversations can however be uncomfortable for stroke unit staff, particularly when they involve breaking bad news. This study aimed to begin development of a novel complex intervention to improve conversations about recovery on stroke units. Methods Informed by previously collected qualitative data, we used the Behaviour Change Wheel (BCW) approach to identify possible 1. barriers to communication about recovery on stroke units; 2. Intervention Functions; 3. Behaviour Change Techniques (BCTs) to incorporate in an intervention. We subsequently sought stroke professionals’ perspectives through an online survey. Respondents rated the importance of barriers for intervention inclusion and evaluated the usefulness and feasibility of the suggested BCTs. Results Our behavioural diagnosis identified a target behaviour of provision of information about recovery by stroke unit professionals to patients and carers. Twelve possible barriers to this behaviour were identified, with six potential Intervention Functions to address them, and 29 BCTs. Forty-eight multidisciplinary professionals responded to the survey. The six barriers rated as most important to address were: lack of confidence; perceptions of insufficient communication skills; lack of knowledge of the benefits; difficulties in deciding when and in what format to provide information; absence of private spaces for discussions; and lack of generic written information to support conversations. The developed intervention strategy comprised twelve clinically feasible and useful BCTs, encompassing the Intervention Functions of Training, Enablement, Persuasion, and Environmental restructuring. Conclusions The BCW approach was successfully used to begin development of an intervention to improve conversations about recovery on the stroke unit; our survey enabled incorporation of stakeholder perspectives. Further development work is required to design intervention materials and test whether the strategies are effective in improving staff and patient outcomes.
Strength prediction of ECC-CES columns under eccentric compression using adaptive sampling and ML techniques
AbstractA novel type of concrete-encased steel (CES) composite column implementing Engineered Cementitious Composites (ECC) confinement (ECC-CES) has recently been introduced, offering significantly enhanced failure behavior, ductility, and toughness when compared to conventional CES columns. This study presents an innovative method for predicting the eccentric compressive capacity of ECC-CES columns, utilizing adaptive sampling and machine learning (ML) techniques. Initially, the research introduces a finite element (FE) model for ECC-CES columns, incorporating material and geometric nonlinearities to capture the inelastic behavior of both ECC and steel through appropriate constitutive material laws. The FE model was validated against experimental data, demonstrating strong predictive accuracy. An adaptive sampling process was employed to efficiently explore the design space, resulting in a database of 2,908 FE models. Subsequently, six machine learning models were used to predict the eccentric compressive capacity based on the generated FE database. These models were thoroughly evaluated and demonstrated superior prediction accuracy compared to established design standards like EC4 and AISC360. Based on evaluation metrics, the Gaussian Process Regression (GPR), CatBoost (CATB), and LightGBM (LGBM) models emerged as the most accurate and reliable, with over 97% of the finite element (FE) samples falling within a 10% error range. While the ML models demonstrate impressive performance, their black-box nature restricts their practical use in design applications. Consequently, this study introduces a proposed design that offers competitive performance metrics. The novelty of this work lies in integrating adaptive sampling through Bayesian Optimization (BO) with the power of machine learning (ML) to generate training data that effectively covers a large input space while minimizing error. SVR, CatBoost, and GPR models demonstrated mean μ, R2, and a20-index values near 1.0, with CoV and MAPE% values consistently low, indicating highly accurate predictions across testing subsets.
The carnivorous plant <i>Genlisea</i> harnesses active particle dynamics to prey on microfauna
Carnivory in plants is an unusual trait that has arisen multiple times, independently, throughout evolutionary history. Plants in the genus Genlisea are carnivorous and feed on microorganisms that live in soil using modified subterranean leaf structures (rhizophylls). A surprisingly broad array of microfauna has been observed in the plants’ digestive chambers, including ciliates, amoebae, and soil mites. Here, we show, through experiments and simulations, that Genlisea exploit active matter physics to “rectify” bacterial swimming and establish a local flux of bacteria through the structured environment of the rhizophyll toward the plant’s digestion vesicle. In contrast, macromolecular digestion products are free to diffuse away from the digestion vesicle and establish a concentration gradient of carbon sources to draw larger microorganisms further inside the plant. Our experiments and simulations show that this mechanism is likely to be a localized one and that no large-scale efflux of digested matter is present.
Parental effects provide an opportunity for coral resilience following major bleaching events
Identifying processes that promote coral reef recovery and resilience is crucial as ocean warming becomes more frequent and severe. Sexual reproduction is essential for the replenishment of coral populations and maintenance of genetic diversity; however, the ability for corals to reproduce may be impaired by marine heatwaves that cause coral bleaching. In 2014 and 2015, the Hawaiian Islands experienced coral bleaching with differential bleaching susceptibility in the species Montipora capitata, a dominant reef-building coral in the region. We tested the hypothesis that coral bleaching resistance enhances reproductive capacity and offspring performance by examining the reproductive biology of colonies that bleached and recovered (B) and colonies that did not bleach (NB) in 2015 in the subsequent spawning seasons. The proportion of colonies that spawned was higher in 2016 than in 2017. Regardless of parental bleaching history, we found eggs with higher abnormality and bundles with fewer eggs in 2016 than 2017. While reproductive output was similar between B and NB colonies in 2016, survivorship of offspring that year were significantly influenced by the parental bleaching history (egg donor × sperm donor: B × B, B × NB, NB × B, and NB × NB). Offspring produced by NB egg donors had the highest survivorship, while offspring from previously bleached colonies had the lowest survivorship, highlighting the negative effects of bleaching on parental investment and offspring performance. While sexual reproduction continues in M. capitata post-bleaching, gametes are differentially impacted by recovery time following a bleaching event and by parental bleaching resistance. Our results demonstrate the importance of identifying bleaching resistant individuals during and after heating events. This study further highlights the significance of maternal effects through potential egg provisioning for offspring survivorship and provides a baseline for human-assisted intervention (i.e., selective breeding) to mitigate the effects of climate change on coral reefs.
New fruit waste-derived activated carbons of high adsorption performance towards metal, metalloid, and polymer species in multicomponent systems
Abstract The main aim of the study was to develop new fruit waste-derived activated carbons of high adsorption performance towards metals, metalloids, and polymers by the use of carbon dioxide (CO 2 )-consuming, microwave-assisted activation. The authors compared morphology, surface chemistry, textural parameters, and elemental composition of precursors (chokeberry seeds, black currant seeds, orange peels), as well as biochars (BCs) and activated carbons (ACs) obtained from them. The adsorption mechanisms of metals (copper, cadmium), metalloids (arsenic, selenium), and macromolecular compounds (bacterial exopolysaccharide, ionic polyacrylamides) on the surface of selected materials were investigated in one- and two-component systems. Consequently, the capacities of BCs and ACs prepared through direct/indirect physical activation, using conventional/microwave heating were determined. It was noted that microwave heating favoured surface development and thus enhanced adsorbent ability to bind ions or macromolecules. Direct biomass activation led to higher microporosity compared to indirect (two-stage) one, whilst CO 2 -consuming activation increased aromaticity and hydrophobicity of the solids. In the two-component systems, polymers could favour metal/metalloid adsorption based on complexation phenomena. However, the most efficient and environmentally safe activated carbon turned out to be the one obtained from orange peels by microwave-assisted, direct activation at 800 °C in the CO 2 atmosphere.
Evolution takes multiple paths to evolvability when facing environmental change
Life at all scales is surprisingly effective at exploiting new opportunities, as demonstrated by the rapid emergence of antimicrobial resistance and novel pathogens. How populations acquire this level of evolvability and the various ways it aids survival are major open questions with direct implications for human health. Here, we use digital evolution to show that changing environments facilitate the simultaneous evolution of high mutation rates and a distribution of mutational effects skewed toward beneficial phenotypes. The evolved mutational neighborhoods allow rapid adaptation to previously encountered environments, whereas higher mutation rates aid adaptation to completely new environmental conditions. By precisely tracking evolving lineages and the phenotypes of their mutants, we show that evolving populations localize on phenotypic boundaries between distinct regions of genotype space. Our results demonstrate how evolution shapes multiple determinants of evolvability concurrently, fine-tuning a population’s adaptive responses to unpredictable or recurrent environmental shifts.
Negligible contribution of body density to in-water vertical jump performance in elite male water polo players
The aim of this study was to investigate the associations among in-water vertical jump and various dry-land physical measures by taking the law of Archimedes into consideration, and by normalizing the dry-land measures both to body density and body mass. Seventeen elite water polo players from Hungarian first league were tested for dry-land counter movement and squat jump mechanical impulse, isometric squat force, and in-water vertical jump height. Body density was estimated by anthropometric measurements. Body density alone did not influence in-water vertical jump height. Both the impulse of counter movement jump normalized to body mass (9.42±0.86 N·s/kg) and impulse of counter movement jump normalized to body density (773.92±109.68 N·s/kg/g/cm3) correlated with the in water vertical jump height (69.37±6.12 cm) (p≤0.05), but the magnitudes of the correlation coefficients 0.49 vs. 0.50 were not statistically different (p = 0.480, z = 0.04). Neither the impulse of squat jump normalized to body mass (7.07±0.59 N·s/kg) nor impulse of squat jump normalized to body density (577.87±89.16 N·s/kg/g/cm3) correlated with the in water vertical jump height (both p>0.05). The correlation between the force of the maximum voluntary isometric contraction normalized to body density (1052.13±244.65 N/kg/g/cm3) and the in water vertical jump height only approached the level of significance (p = 0.077). We concluded that dry-land reactive strength determines the ability to jump out of water, but players’ body density does not seem to contribute to jump height.