Visualizing the fibre texture of satin spar using laboratory 2D X-ray diffraction.

The suitability of point focus X-ray beam and area detector techniques for the determination of the uniaxial symmetry axis (fibre texture) of the natural mineral satin spar is demonstrated. Among the various diffraction techniques used in this report, including powder diffraction, 2D pole figures, rocking curves looped on φ and 2D X-ray diffraction, a single simple symmetric 2D scan collecting the reciprocal plane perpendicular to the apparent fibre axis provided sufficient information to determine the crystallographic orientation of the fibre axis. A geometrical explanation of the 'wing' feature formed by diffraction spots from the fibre-textured satin spar in 2D scans is provided. The technique of wide-range reciprocal space mapping restores the 'wing' featured diffraction spots on the 2D detector back to reciprocal space layers, revealing the nature of the fibre-textured samples.

Examining the Corn Seedling Emergence-Temperature Relationship for Recent Hybrids: Insights from Experimental Studies.

Corn seedling emergence is a critical factor affecting crop yields. Accurately predicting emergence is crucial for precise crop growth and development simulation in process-based crop models. While various experimental studies have investigated the relationship between corn seedling emergence and temperature, there remains a scarcity of studies focused on newer corn hybrids. In the present study, statistical models (linear and quadratic functional relationships) are developed based on the seedling emergence of ten current corn hybrids, considering soil and air temperatures as influencing factors. The data used for model development are obtained from controlled soil plant atmospheric research chamber experiments focused on corn seedling emergence at five different temperatures. Upon evaluating the developed models, the quadratic model relating the air temperature with time to emergence was found more accurate for all corn hybrids (coefficient of determination (R2): 0.97, root mean square error (RMSE): 0.42 day) followed by the quadratic model based on soil temperature (R2: 0.96, RMSE: 1.42 days), linear model based on air (R2: 0.94, RMSE: 0.53 day) and soil temperature (R2: 0.94, RMSE: 0.70 day). A growing degree day (GDD)-based model was also developed for the newer hybrids. When comparing the developed GDD-based model with the existing GDD models (based on old hybrids), it was observed that the GDD required for emergence was 16% higher than the GDD used in the current models. This showed that the existing GDD-based models need to be revisited when adopted for newer hybrids and adapted to corn crop simulation models. The developed seedling emergence model, integrated into a process-based corn crop simulation model, can benefit farmers and researchers in corn crop management. It can aid in optimizing planting schedules, supporting management decisions, and predicting corn crop growth, development, and it yields more accurately.

Global employability skills in the 21st century workplace: A semi-systematic literature review.

This study conducts a semi-systematic literature review of research pertaining to employability to identify essential employability skills that employers seek in recent graduates. The comprehensive analysis of the existing literature review aims to present a set of global employability skills, identify similarities, variations, or changes in these skills across time, and explore the most relevant existing employability skills for the 21st-century workplace. The review includes 30 years of research articles and government reports published in English and considers 25 studies based on the Scientific Procedures and Rationales for Systematic Literature Reviews (SPAR-4-SLR). After removing duplicates, 87 unique skills were identified and listed under three distinct temporal themes (the 1990s, 2000s, and 2010s), with problem-solving, communication, teamwork, adaptability, and willingness to learn among the most commonly reported skills over time. The study found a mismatch between employers' expectations and graduates' possessed skills. Therefore, the list of employability skills identified in this study can serve as a valuable tool for addressing this mismatch. The study's findings can also help educators and employers to better align their efforts to prepare students for the modern workplace.

Nanolatex architectonics: Influence of cationic charge density and size on their adsorption onto surfaces with a 2D or 3D distribution of anionic groups.

HYPOTHESIS: It is theoretically predicted and hypothesized that the charge density and size of spherical nanoparticles are the key factors for their adsorption onto oppositely charged surfaces. It is also hypothesized that the morphology and charge of the surface are of great importance. In-plane 2D (silica) or a volumetric 3D (regenerated TEMPO-oxidized cellulose model surfaces) distribution of charged groups is expected to influence charge compensation and, thus, the adsorption behavior. EXPERIMENTS: In this work, self-stabilized nanolatexes with a range of cationic charge densities and sizes were synthesized through reversible addition - fragmentation chain-transfer (RAFT) polymerization coupled with polymerization-induced self-assembly (PISA). Their adsorption onto silica and anionic cellulose model surfaces was investigated using stagnation point adsorption reflectometry (SPAR) and quartz crystal microbalance with dissipation (QCM-D). FINDINGS: Experiments and theory agree and show that the size of the nanolatex and the difference in charge density compared to the substrate determine the charge compensation and, thus, the surface coverage. Highly charged or large nanolatexes overcompensate the surface charge of non-porous substrates leading to a significant repulsive zone where other particles cannot adsorb. For porous substrates like cellulose, the vertical distribution of charged groups in the 3D volume prevents overcompensation and thus increases the adsorption. This systematic study investigates the isolated effect of surface charge and size and paves the way for on-demand particles specifically designed for a surface with particular characteristics.

Brazilian Approach to Dorsum Preservation.

Brazil has always been a fertile place for plastic surgery techniques, especially cosmetic, and it was not different in rhinoplasty. In Brazil surgeons started using the dorsal preservation rhinoplasty in the 1970s. Techniques have changed, the problems and contraindications were challenged, and solutions proposed. As a result, indications were expanded to almost every kind of nose. Surface working executed with power tools, such as the piezoelectric device and the power drill, complemented the techniques and allowed for refinement in execution. Today the Brazilian preservation techniques are adopted and improved by many surgeons around the world.

Acute MPTP treatment decreases dendritic spine density of striatal medium spiny neurons via SNK-SPAR pathway in C57BL/6 mice.

Parkinson's disease (PD) is a well-known neurodegenerative disorder associated with a high risk in middle-aged and elderly individuals, severely impacting the patient's quality of life. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is frequently used to establish PD in animals. Dendritic spines are dendritic processes that form the foundation of learning and memory. Reportedly, dendritic spine density of striatal medium spiny neurons (MSNs) declines in PD, and this decline has been associated with PD progression; however, the underlying mechanism remains elusive. Herein, we used the MPTP animal model to examine whether serum-induced kinase (SNK) and spine-associated Rap guanosine triphosphatase (SPAR) contribute to decreased dendritic spine density in striatal MSNs. MPTP was used to establish the animal model, which exhibits motor function impairment and dopaminergic cell loss. To assess spine density, Golgi staining was performed to count striatal dendritic spines, which were reduced in the MPTP group when compared with those in the normal control group. Immunohistochemistry was performed to analyze changes in SNK and SPAR expression. MPTP treatment significantly increased the expression of SNK in striatal MSNs, whereas that of SPAR was significantly decreased when compared with the normal control group. These findings offer clues to further explore the mechanism of declining dendritic spine density in patients with PD and provide evidence for potential target identification in PD.

A Practical Risk-Based Model for Early Warning of Seafarer Errors Using Integrated Bayesian Network and SPAR-H.

Unsafe crew acts (UCAs) related to human errors are the main contributors to maritime accidents. The prediction of unsafe crew acts will provide an early warning for maritime accidents, which is significant to shipping companies. However, there exist gaps between the prediction models developed by researchers and those adopted by practitioners in human risk analysis (HRA) of the maritime industry. In addition, most research regarding human factors of maritime safety has concentrated on hazard identification or accident analysis, but not on early warning of UCAs. This paper proposes a Bayesian network (BN) version of the Standardized Plant Analysis Risk-Human Reliability Analysis (SPAR-H) method to predict the probability of seafarers' unsafe acts. After the identification of performance-shaping factors (PSFs) that influence seafarers' unsafe acts during navigation, the developed prediction model, which integrates the practicability of SPAR-H and the forward and backward inference functions of BN, is adopted to evaluate the probabilistic risk of unsafe acts and PSFs. The model can also be used when the available information is insufficient. Case studies demonstrate the practicability of the model in quantitatively predicting unsafe crew acts. The method allows evaluating whether a seafarer is capable of fulfilling their responsibility and providing an early warning for decision-makers, thereby avoiding human errors and sequentially preventing maritime accidents. The method can also be considered as a starting point for applying the efforts of HRA researchers to the real world for practitioners.

Spatial variations and social determinants of life expectancy in China, 2005-2020: A population-based spatial panel modelling study.

Background: Social determinants of health (SDOH) produce a broad range of life expectancy (LE) disparities. In China, limited literatures were found to report association between SDOH and LE at ecological level during a consecutive period of time from the spatial perspectives. This study aimed to determine the existence, quantify the magnitude, and interpret the association between SDOH and LE in China. Methods: Provincial-level LE were estimated from mortality records during 2005-2020 from National Mortality Surveillance System in China. A spatial panel Durbin model was used to investigate LE associated SDOH proxies. Spatial spillover effects were introduced to interpret direct and indirect effects caused by SDOH during long-term and short-term period on LE disparities. Findings: Nationwide, LE increased from 73.1 (95% confidence interval (CI): 71.3, 74.4) years to 77.7 (95%CI: 76.5, 78.7) years from 2005 to 2020. Unequally spatial distribution of LE with High-High clustering in coastal areas and Low-Low clustering in western regions were observed. Locally, it was estimated that SDOH proxies statistically significant related to an increase of LE, including GDP (coefficient: 0.02, 95%CI: 0.00, 0.03), Gini index (coefficient: 2.35, 95%CI: 1.82, 2.88), number of beds in health care institutions (coefficient: 0.02, 95%CI: 0.00, 0.05) and natural growth rate of resident population (coefficient: 0.02, 95%CI: 0.01, 0.02). Direct and indirect effects decomposition during long-term and short-term of LE associated SDOH proxies demonstrated that GDP, urbanization rate, unemployment rate, education attainment, Gini index, number of beds in health care institutions, sex ratio, gross dependence ratio and natural growth rate of resident population not only affected local LE, but also exerted spatial spillover effects towards geographical neighbors. Interpretation: Spatial variations of LE existed at provincial-level in China. SDOH regarding socioeconomic development and equity, healthcare resources, as well as population characteristics not only affected LE disparities at local scale but also among nearby provinces. Externalities of policy of those SDOH proxies should be took into consideration to promote health equity nationally. Comprehensive approaches on the basis of population strategy should be consolidated to optimize supportive socioeconomic environment and narrow the regional gap to reduce health disparities and increase LE. Funding: National Key Research & Development Program of China (Grant No.2018YFC1315301); Ministry of Education of China Humanities and Social Science General Program (Grant No.18YJC790138).

The patient as a prosumer of healthcare: insights from a bibliometric-interpretive review.

PURPOSE: Healthcare policies around the globe are aimed at achieving patient-centeredness. The patient is understood as a prosumer of healthcare, wherein healthcare service co-production and value co-creation take center stage. The article endeavors to unpack the state of the literature on the innovations promoting the transition toward patient-centeredness, informing policy and management interventions fostering the reconceptualization of the patient as a prosumer of healthcare services. DESIGN/METHODOLOGY/APPROACH: A hybrid review methodology consisting of a bibliometric-interpretive review following the Scientific Procedures and Rationales for Systematic Literature Reviews (SPAR-4-SLR) protocol is used. The bibliometric component enabled us to objectively map the extant scientific knowledge into research streams, whereas the interpretive component facilitated the critical analysis of research streams. FINDINGS: Patient-centeredness relies on a bundle of innovations that are enacted through a cycle of patients' activation, empowerment, involvement and engagement, wherein the omission of any steps arrests the transition toward service co-production and value co-creation. Institutional, organizational and cognitive barriers should be overcome to boost the transition of patients from consumers to prosumers in a patient-centered model of healthcare. ORIGINALITY/VALUE: The article delivers the state of the art of the scientific literature in the field of innovations aimed at sustaining the transition toward patient-centeredness and provides some food for thoughts to scholars and practitioners who wish to push forward service co-production and value co-creation in healthcare.

SIPA1L1/SPAR1 Interacts with the Neurabin Family of Proteins and is Involved in GPCR Signaling.

Signal-induced proliferation-associated 1 (SIPA1)-like 1 (SIPA1L1; also known as SPAR1) has been proposed to regulate synaptic functions that are important in maintaining normal neuronal activities, such as regulating spine growth and synaptic scaling, as a component of the PSD-95/NMDA-R-complex. However, its physiological role remains poorly understood. Here, we performed expression analyses using super-resolution microscopy (SRM) in mouse brain and demonstrated that SIPA1L1 is mainly localized to general submembranous regions in neurons, but surprisingly, not to PSD. Our screening for physiological interactors of SIPA1L1 in mouse brain identified spinophilin and neurabin-1, regulators of G-protein-coupled receptor (GPCR) signaling, but rejected PSD-95/NMDA-R-complex components. Furthermore, Sipa1l1-/- mice showed normal spine size distribution and NMDA-R-dependent synaptic plasticity. Nevertheless, Sipa1l1-/- mice showed aberrant responses to α2-adrenergic receptor (a spinophilin target) or adenosine A1 receptor (a neurabin-1 target) agonist stimulation, and striking behavioral anomalies, such as hyperactivity, enhanced anxiety, learning impairments, social interaction deficits, and enhanced epileptic seizure susceptibility. Male mice were used for all experiments. Our findings revealed unexpected properties of SIPA1L1, suggesting a possible association of SIPA1L1 deficiency with neuropsychiatric disorders related to dysregulated GPCR signaling, such as epilepsy, attention deficit hyperactivity disorder (ADHD), autism, or fragile X syndrome (FXS).SIGNIFICANCE STATEMENT Signal-induced proliferation-associated 1 (SIPA1)-like 1 (SIPA1L1) is thought to regulate essential synaptic functions as a component of the PSD-95/NMDA-R-complex. In our screening for physiological SIPA1L1-interactors, we identified G-protein-coupled receptor (GPCR)-signaling regulators. Moreover, SIPA1L1 knock-out (KO) mice showed striking behavioral anomalies, which may be relevant to GPCR signaling. Our findings revealed an unexpected role of SIPA1L1, which may open new avenues for research on neuropsychiatric disorders that involve dysregulated GPCR signaling. Another important aspect of this paper is that we showed effective methods for checking PSD association and identifying native protein interactors that are difficult to solubilize. These results may serve as a caution for future claims about interacting proteins and PSD proteins, which could eventually save time and resources for researchers and avoid confusion in the field.

Genetic diversity and population structure assessment using molecular markers and SPAR approach in Illicium griffithii, a medicinally important endangered species of Northeast India.

BACKGROUND: Illicium griffithii is an aromatic medicinal tree species that has been listed in the IUCN Red List as an endangered species. Dried seed pods of I. griffithii have a good market potential in the spices and pharmaceutical industries. Fruits are the potential source of shikimic acid and used for the production of oseltamivir (a drug against bird flu). However, in recent years, unscientific harvesting and rampant exploitation of the species has caused a negative and adverse effect on its natural population. Proper knowledge of genetic diversity and population structure is crucial to understand the population dynamics, adaptation, and evolutionary pattern of a particular species for conservation. It was from this view point that the present study was undertaken so as to compare the various types of DNA-based molecular markers namely RAPD, ISSR, DAMD, and SCoT by their efficiency and SPAR approach to evaluate the genetic diversity of I. griffithii as well as to analyze population genetic structure for conservation purpose. RESULT: A total of 250 discernible bands were generated with 246 bands (98.40 %) being polymorphic in nature. All the primers in combination gave a mean polymorphic information content (PIC) of 0.81 and Rp value (resolving power) of 4.32. Nei's, Gst, and AMOVA analysis showed similar values of genetic differentiation among populations (Gst = 0.396, FST = 0.30, respectively), revealing a low level of genetic differentiation among the eight sampled populations. I. griffithii with an estimated gene flow value of Nm = 0.761 was significantly low among populations. Clustering pattern obtained with Bayesian structure and PCoA diagram revealed that intermixing of genetic material across populations is only possible when the populations lie close to each other. This is further validated with UPGMA clustering method where a positive correlation of genetic variability with geographical distance among closely related populations could be clearly seen. CONCLUSION: The result aids in the identification, collection, and preservation of diverse germplasm of I. griffithii from Arunachal Pradesh and Meghalaya of Northeast India. This would further help in understanding the population structure and genetic diversity among other Illicium species in order to formulate effective conservation strategies for the improvement of this endangered taxa.

Functional Lignin Nanoparticles with Tunable Size and Surface Properties: Fabrication, Characterization, and Use in Layer-by-Layer Assembly.

Lignin is the richest source of renewable aromatics and has immense potential for replacing synthetic chemicals. The limited functionality of lignin is, however, challenging for its potential use, which motivates research for creating advanced functional lignin-derived materials. Here, we present an aqueous-based acid precipitation method for preparing functional lignin nanoparticles (LNPs) from carboxymethylated or carboxypentylated lignin. We observe that the longer grafted side chains of carboxypentylated lignin allow for the formation of larger LNPs. The functional nanoparticles have high tolerance against salt and aging time and well-controlled size distribution with Rh ≤ 60 nm over a pH range of 5-11. We further investigate the layer-by-layer (LbL) assembly of the LNPs and poly(allylamine hydrochloride) (PAH) using a stagnation point adsorption reflectometry (SPAR) and quartz crystal microbalance with dissipation (QCM-D). Results demonstrate that LNPs made of carboxypentylated lignin (i.e., PLNPs with the adsorbed mass of 3.02 mg/m2) form a more packed and thicker adlayer onto the PAH surface compared to those made of carboxymethylated lignin (i.e., CLNPs with the adsorbed mass of 2.51 mg/m2). The theoretical flux, J, and initial rate of adsorption, (dΓ/dt)0, analyses confirm that 22% of PLNPs and 20% of CLNPs arriving at the PAH surface are adsorbed. The present study provides a feasible platform for engineering LNPs with a tunable size and adsorption behavior, which can be adapted in bionanomaterial production.

Design and Performance Evaluation of a "Fixed-Point" Spar Buoy Equipped with a Piezoelectric Energy Harvesting Unit for Floating Near-Shore Applications.

In the present work, a spar-buoy scaled model was designed and built through a "Lab-on-Sea" unit, equipped with an energy harvesting system. Such a system is based on deformable bands, which are loyal to the unit, to convert wave motion energy into electricity by means of piezo patch transducers. In a preliminary stage, the scaled model, suitable for tests in a controlled ripples-type wave motion channel, was tested in order to verify the "fixed-point" assumption in pitch and roll motions and, consequently, to optimize energy harvesting. A special type of structure was designed, numerically simulated, and experimentally verified. The proposed solution represents an advantageous compromise between the lightness of the used materials and the amount of recoverable energy. The energy, which was obtained from the piezo patch transducers during the simulations in the laboratory, was found to be enough to self-sustain the feasible on-board sensors and the remote data transmission system.

Numerical investigation of parametric resonance due to hydrodynamic coupling in a realistic wave energy converter.

Representative models of the nonlinear behavior of floating platforms are essential for their successful design, especially in the emerging field of wave energy conversion where nonlinear dynamics can have substantially detrimental effects on the converter efficiency. The spar buoy, commonly used for deep-water drilling, oil and natural gas extraction and storage, as well as offshore wind and wave energy generation, is known to be prone to experience parametric resonance. In the vast majority of cases, parametric resonance is studied by means of simplified analytical models, considering only two degrees of freedom (DoFs) of archetypical geometries, while neglecting collateral complexity of ancillary systems. On the contrary, this paper implements a representative 7-DoF nonlinear hydrodynamic model of the full complexity of a realistic spar buoy wave energy converter, which is used to verify the likelihood of parametric instability, quantify the severity of the parametrically excited response and evaluate its consequences on power conversion efficiency. It is found that the numerical model agrees with expected conditions for parametric instability from simplified analytical models. The model is then used as a design tool to determine the best ballast configuration, limiting detrimental effects of parametric resonance while maximizing power conversion efficiency.

Molecular analyses of genetic variability in the populations of Bergenia ciliata in Indian Himalayan Region (IHR).

Bergenia ciliata is an important medicinal plant species of Indian Himalayan Region (IHR). Genetic variability and population genetic structure of B. ciliata sampled from IHR was studied using two single primer amplification reaction (SPAR) methods (DAMD: Directed Amplification of Minisatellite region DNA; ISSR: Inter Simple Sequence Repeats). To provide a reasonable scientific basis for management and conservation of B. ciliata populations in IHR, genetic diversity analysis of 11 populations with 24 SPAR markers (15 ISSR and 9 DAMD) revealed significantly high level of (90.03%) polymorphism at species level. However, genetic variability was low at population level and KUL and BWS populations showed maximum while SHM population revealed least genetic diversity among the 11 populations. Analysis of molecular variance revealed highest percentage of variation (73%) within populations, followed by 17% among populations and least (10%) among the Himalayan regions. Clustering pattern obtained from UPGMA dendrogram was supported by STRUCTURE and principal coordinate analysis, segregating all the 11 natural populations of B. ciliata into two genetic clusters: Eastern and Western Himalayan populations. The clustering patterns of all the three statistical methods indicated that populations of B. ciliata have structured in response to the local micro-climates of the habitats in IHR, and therefore, it can be concluded that genetic variability is in congruence with the geographical diversity.

Reliability and lifetime assessment of glider wing's composite spar through accelerated fatigue life testing.

The evaluation of the reliability and the lifetime of aerospace components has become an important segment of the design stage. The aeronautical components are subjected to complex, rigorous tests and have a long test life. The main goal in the field of aviation is to have components with high reliability and quality and to meet the mandatory requirements and regulations. The spars are stiffening components positioned along the wing and which take up most of the load and are tested for fatigue over a long period of time. The spar which was analysed in this study has a sandwich structure with GFRP (glass fiber reinforced plastic) skin and foam core. In this paper, the performances in the static and dynamic conditions of the GFRP-foam sandwich structures cut out of the composite spar of a glider were analysed. Additionally, using accelerated techniques based on the three-point fatigue bending test, the main reliability indicators of the GFRP-foam sandwich structures were determined. Using the statistical processing of the experimental data and the Inverse Power Law-Weibull acceleration model, the mean number of cycles to failure, in normal testing conditions of the GFRP-foam specimens was determined, with a value of 102,814. Using the accelerated testing techniques of the GFRP-foam sandwich structures an important decrease of the test time (8.43 times) was obtained.

Iceland spar calcite: Humidity and time effects on surface properties and their reversibility.

Understanding the complex and dynamic nature of calcite surfaces under ambient conditions is important for optimizing industrial applications. It is essential to identify processes, their reversibility, and the relevant properties of CaCO3 solid-liquid and solid-gas interfaces under different environmental conditions, such as at increased relative humidity (RH). This work elucidates changes in surface properties on freshly cleaved calcite (topography, wettability and surface forces) as a function of time (≤28 h) at controlled humidity (≤3-95 %RH) and temperature (25.5 °C), evaluated with atomic force microscopy (AFM) and contact angle techniques. In the presence of humidity, the wettability decreased, liquid water capillary forces dominated over van der Waals forces, and surface domains, such as hillocks, height about 7.0 Å, and trenches, depth about -3.5 Å, appeared and grew primarily in lateral dimensions. Hillocks demonstrated lower adhesion and higher deformation in AFM experiments. We propose that the growing surface domains were formed by ion dissolution and diffusion followed by formation of hydrated salt of CaCO3. Upon drying, the height of the hillocks decreased by about 50% suggesting their alteration into dehydrated or less hydrated CaCO3. However, the process was not entirely reversible and crystallization of new domains continued at a reduced rate.

Lead, cadmium, arsenic, and mercury combined exposure disrupted synaptic homeostasis through activating the Snk-SPAR pathway.

Lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) are among the leading toxic agents detected in the environment, and they have also been detected simultaneously in blood, serum, and urine samples of the general population. Meanwhile early neurologic effects and multiple interactions of Pb, Cd, As, and Hg had been found in children from environmentally polluted area. However, the current studies of these four metals were mostly limited to the interactions between any two metals, whereas the interaction characteristics between any three and four metals were rarely studied. In our study, we firstly explored the characteristics of the neurotoxic interactions among these four elements in nerve cells with factorial designs. The results showed that Pb+Cd+As+Hg co-exposure had a synergistic neurotoxic effect that was more severe than that induced by any two or three metals, when their individual metals were at human environmental exposure (in the blood of U.S. population) relevant levels and below no observed adverse effect levels (NOAELs). Therefore, Pb+Cd+As+Hg co-exposure at human environmental exposure relevant levels were further selected to examine synaptic homeostasis as the cellular and molecular foundation of learning and memory. We reported for the first time that Pb+Cd+As+Hg co-exposure induced dose-dependent decreases of the dendritic lengths and branching, as well as spine density and mature phenotype in primary hippocampal neurons, and the stimulated neurite outgrowths in NGF-differentiated PC12 cells. And the above synaptic homeostasis disruption was associated with serum induced kinase (Snk)-spine associated Rap GTPase activating protein (SPAR) pathway. Our study suggests that human environmental Pb, Cd, As, and Hg co-exposure has the potential to evoke synergistic neurotoxicity even if their individual metals are below NOAELs, which reinforces the need to control and regulate potential sources of metal contamination.

Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the Brain.

Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of cytoskeletal remodeling in the brain. Cdk5 is essential for brain development during embryogenesis. After birth, it is essential for numerous neuronal processes such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity is deregulated in various brain disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton, loss of synapses, and ultimately neurodegeneration. This review focuses on the "good and bad" Cdk5 in the brain and its pleiotropic contribution in regulating neuronal actin cytoskeletal remodeling. A vast majority of physiological and pathological Cdk5 substrates are associated with the actin cytoskeleton. Thus, our special emphasis is on the numerous Cdk5 substrates identified in the past two decades such as ephexin1, p27, Mst3, CaMKv, kalirin-7, RasGRF2, Pak1, WAVE1, neurabin-1, TrkB, 5-HT6R, talin, drebrin, synapsin I, synapsin III, CRMP1, GKAP, SPAR, PSD-95, and LRRK2. These substrates have unraveled the molecular mechanisms by which Cdk5 plays divergent roles in regulating neuronal actin cytoskeletal dynamics both in healthy and diseased states.

Inhibition of SNK-SPAR signaling pathway promotes the restoration of motor function in a rat model of ischemic stroke.

This study aimed to investigate the effects of SPAR signaling pathway on the restoration of motor function in ischemic stroke (IS). Sprague-Dawley male rats were separated into the control and sham groups, as well as the group for middle cerebral artery occlusion (MCAO) model establishment. Successfully established rat ischemic models were randomly divided into model, SNKMCAO-del and pcDNA3.1-SNK groups. The evaluation of motor function among the rats in each group was assessed using a balance beam, a screen test and the Garcia scoring method. CatWalk gait analysis was employed to evaluate the effect of the SNK signaling pathway on rat motor function. Triphenyltetrazolium chloride (TTC) and TUNEL staining were techniques were utilized for cerebral infarction (CI) area as well for hippocampal neuron apoptosis. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting methods were performed to detect mRNA and protein expressions of SNK and SPAR. When compared with the model group, the SNKMCAO-del group displayed decreased motor function score and CI area, while contrasting results were observed in the pcDNA3.1-SNK group. According to the results obtained from the CatWalk gait analysis, the SNKMCAO-del group showed a clear improvement compared to the model group whereas the pcDNA3.1-SNK group exhibited poorer results than the model group in the objective parameters of the study, such as movement, speed, running duration, print area, maximal contact area, maximal, mean intensity, and stride length. These findings suggested that SNK gene silencing promotes motor function by inhibiting the SNK-SPAR signaling pathway in rats with ischemic stroke.