Lifespan Research Articles

Design, Synthesis, Characterization, Molecular Docking Studies, In vitro and In vivo Cervical Cancer Activity of Novel N-Substituted Pyrazole Derivatives

The aim of this study is to design, synthesize, characterize few novel N-substituted pyrazole derivatives and evaluated for their anticancer capabilities; these compounds were selected based on their ability to inhibit the HPV E6 protein. The IR, 1H & 13C NMR, mass spectral and elemental analysis were used to determine the structural details of the newly synthesized substances. The molecular docking was performed using Auto Dock Vina, and the protein-ligand interaction was analyzed using Discovery Studio. The sulforhodamine B (SRB) assay was used to determine the in vitro anticancer activity against the HeLa cell line. Body weight analysis, mean survival time and % increase in life span approaches were used to assess in vivo anticancer effectiveness in Swiss albino mice bearing Dalton’s Lymphoma Ascites (DAL) tumor model. Synthesized compounds have excellent docking energies, according to docking experiments. Compounds I, II and III were selected for anticancer activity in vivo DAL-bearing mice based on the findings of their in vitro and SRB assays exhibiting the antiproliferative activity. Pyrazole derivatives, compounds I and III, demonstrated significant potential as anticancer agents.

Effects of agricultural carbon footprints and malnutrition on life expectancy in China.

This study explored the impact of carbon footprints and malnutrition on life expectancy in China over the periods of 2000 and 2021. Data from the World Bank Indicators database was utilized, and Dynamic Ordinary Least Squares (DOLS) was employed to analyse the extracted data. The results show that over the periods of 2000 and 2021, agricultural carbon footprints in China experienced a first sharp decline in 2015. In contrast, per capita food production in China rose from 88.29% in 2011 to over 108% in 2021. Within a space of a decade, the undernourished population in China was reduced by 78.8%. Moreover, per capita food production had a positive impact on life expectancy in China. Conversely, malnutrition exerted a negative and significant influence on life expectancy. Agricultural carbon footprints contributed a positive but insignificant impact on life expectancy, and GDP per capita growth increased life expectancy significantly in the country. We conclude that policymakers in China are should ensure that all citizens have access to food necessary to improve life span of the country`s population.

The Establishment of the Spiking Method to Evaluate the Rapid Diagnostic Test Antigen (Ag-RDT) Product for COVID-19 Detection

The quality control of the COVID-19 Rapid Diagnostic Test (Ag-RDT) product is regarded as one of the government’s responsibilities. The Indonesian government establishes rules for Ag-RDT post-market validation, where it should be performed by two designated laboratories, using the spiking technique. The usage of this technique raises concerns, especially if it does not represent the precise product quality, due to the sample dilution. In addition, the requisite of using fresh samples that should be prepared for less than 48 hours is considered costly and time-consuming. In response to this, we tested two samples from different age groups on the Ag-RDT brand recommended by the World Health Organization (WHO); Panbio™ Covid-19 Ag Rapid Test (Abbott) and standard Q Ag-RDT (SD Biosensor, Roche). In both Ag-RDT products, the samples observed in the cycle threshold (Ct) values≤25 groups exhibit >80%sensitivity and >97% specificity as in compliance with the WHO recommendation. Meanwhile, as observed in the Ct>25 groups, the sensitivity of the two Ag-RDT products was below 25%, which was not in compliance with the WHO recommendation. Overall, this study indicated that the Spiking technique is eligible to be used for evaluating the performance of Ag-RDT, especially at Ct≤25. Additionally, the samples’ life span of up to 2 weeks of storage at -80oC can be used for post-market validation of Ag-RDT. Furthermore, the quality control assay for longer sample storage is interesting to be carried out.

Molecular Detection of Human parvovirus B19 in Patients with Thalassemia in Wasit Province, Iraq

Background: Human B19 (PVB19) isssmall, non-envelope single strand DNA viruses from family of "Parvoviridae" it cause infections in human. In thalassemia are a heterogeneous grouping of genetic disorders that result from a decreased synthesis of alpha or beta chains of hemoglobin (Hb). Numerous factors contribute to functional abnormality found in βeta thalassemia patient like decrease red cells life span, rapidsiron turnover, and tissue deposition of excess iron B19 targets the erythroid progenitors in the bone marrow by binding to the glycosphingolipid. Materials and Methods: This case cross sectional study and the patients aged between (5-40) years , study has been carried outsin Al-Kut teaching hospitals in Al-Iraq-Wasit in a period between September 2023 and March 2024. This study followed the cross-sectional design. The populations of our study included 120 patients’ samples with thalassemia infected by Human Parvovirus B19 in blood transfusion patients 64 male and 56 female. Nested-PCR used to detect of B19V by using primers. PCR reaction was done by using special sets of primers mentioned previously and special components and specific program and procedure according to components of PCR reaction. Result: Human parvovirus 19 Positive case percentage using polymerase chain reaction indicated that the positive cases was reported according to polymerase chain reaction (PCR) as a percentage of case related to the main characteristic of patients, current study data has been indicated as following: in total of 120 patient sample with thalassemia has been included in this study, PCR positive case was 17 (14.2%), 6 (5%), 2 (1.7%) and 0 (0%) in the age groups (5-15), (16-25), (26-35) and (36-45) respectively. Male was more prevalent 17 (14.2%), than female 8 (6.7%), So as to records of major type in comparision to intermediate 19 (15.8%) and 6 (5%). All positive cases were 25 cases. Conclusion: Current data showed prevalence of Human parvovirus 19 in Iraqi patients. This prevalence should be alarming public health.

Variation in the Local Grey Mullet Populations (Mugil cephalus) on the Western Pacific Fringe

Background: Understanding population genetic structures is crucial for planning and implementing conservation programmes to preserve species’ adaptive and evolutionary potential and thus ensure their long-term persistence. The grey mullet (Mugil cephalus) is a globally distributed coastal fish. Its populations in waters surrounding Taiwan on the western Pacific fringe are divided into at least two stocks (migratory and residential), but questions remain regarding their genetic divergence and gene flow. Methods and Results: To cast more light on this, allozyme variations at 21 presumptive gene loci of 1217 adult grey mullets from 15 localities in Japan, Taiwan and mainland China, and four gene loci from 1470 juveniles from three localities in Taiwan were used to investigate patterns of genetic variation. The mean expected heterozygosity (He) was 0.128—ranging from 0.031 (Matsu) to 0.442 (Kaoping)—and the mean observed heterozygosity (Ho) was 0.086—ranging from 0.017 (Kaohsiung) to 0.215 (Kaoping). Both AMOVA and the high overall mean FST of 0.252 indicated enormous genetic differentiation among populations and the positive mean value of FIS was 0.328, indicating a deficiency of heterozygotes. PCoA indicated that the samples of M. cephalus could be split into three groups and STRUCTURE analysis showed that all individuals were grouped into three genetic clusters. The results of mutation-drift equilibrium tests did not suggest that the populations experienced any recent genetic bottleneck. The results from all localities in the present investigation showed significant change in the GPI-A genotype frequencies with latitudes—e.g., increases in GPI-A*135/135 homozygote frequencies and GPI-A*100/100 frequencies were highly correlated with latitudinal cline. All migratory populations with the GPI-A genotype were almost exclusively the GPI-A*100/100 homozygote. During the life history of M. cephalus, the GPI-A*100/135 heterozygote frequency significantly decreases with age. Conclusions: Based on these data, we suggest that each GPI-A genotype represents trait combinations of higher fitness in some portions of the environment. Furthermore, the genotypic frequencies change in accordance with life stages, suggesting that selection occurs throughout the life span.

A novel energy-efficiency framework for UAV-assisted networks using adaptive deep reinforcement learning

In the air-to-ground transmissions, the lifespan of the network is based on the “unmanned aerial vehicle's (UAV)” life span because of the limited battery capacity. Thus, the enhancement of energy efficiency and the outage of the ground candidate’s minimization are significant factors of the network functionality. UAV-aided transmission can highly enhance the spectrum efficacy and coverage. Because of their flexible deployment and the high maneuverability, the UAVs can be the best alternative for the situations where the “Internet of Things (IoT)” systems utilize more energy to attain the essential information rate, when they are far away from the terrestrial base station. Therefore, it is significant to win over the few troubles in the conventional UAV-aided efficiency approaches. Thus, this proposed work is aimed to design an innovative energy efficiency framework in the UAV-assisted network using a reinforcement learning mechanism. The energy efficiency optimization in the UAV offers better wireless coverage to the static and mobile ground user. Presently, reinforcement learning techniques effectively optimize the energy efficiency rate of the system by employing the 2D trajectory mechanism, which effectively removes the interference rate attained in the nearby UAV cells. The main objective of the recommended framework is to maximize the energy efficiency rate of the UAV network by performing the joint optimization using UAV 3D trajectory, with the energy utilized during interference accounting, and connected user counts. Hence, an efficient Adaptive Deep Reinforcement Learning with Novel Loss Function (ADRL-NLF) framework is designed to provide a better energy efficiency rate to the UAV network. Moreover, the parameter of ADRL is tuned using the Hybrid Energy Valley and Hermit Crab (HEVHC) algorithm. Various experimental observations are performed to observe the effectualness rate of the recommended energy efficiency model for UAV-based networks over the classical energy efficiency framework in UAV Networks.

The economic value of reducing avoidable mortality.

Living longer and healthier boosts individual and family welfare. As part of the World Bank's Healthy Longevity Initiative, we quantified the economic value of achieving the highest possible life span. We estimated the economic value of reducing avoidable mortality, defined as the difference between observed (or projected) mortality and lowest achieved (or projected) mortality, by world regions, sex, and age, between 2000 and 2021, with projection to 2050. In 2019, 69% of mortality, or 40 million deaths, was avoidable. The economic value of avoidable mortality globally was 23% of annual income, meaning that, globally, populations would be willing to give up about one-fifth of their current income in exchange for a year living at the lowest achieved mortality rate. This value ranges from 19% in China to 34% in sub-Saharan Africa. Under the rapid-progress scenario, in which countries experience fast but plausible mortality reductions from 2019 to 2050, we would expect globally the gap between projected and frontier life expectancy to be halved by 2050, and the economic value after achieving this scenario is equivalent to 14% of annual income. Our work provides supportive evidence on the high economic value placed on improving health.

Alternative Therapy for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Moving Cupping along Meridians.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition characterized by persistent and progressive airflow obstruction, resulting in chronic respiratory symptoms like dyspnea, cough, and sputum production, accompanied by wheezing, chest tightness, fatigue, and reduced physical activity. Under the influence of various factors, patients with COPD often experience acute exacerbations, which have a significant negative impact on the prognosis, quality of life, and life span of patients. As a branch of cupping therapy, moving cupping along meridians is an essential complementary therapy of the traditional Chinese medicine system. Cupping plays a unique role in treating and preventing many diseases by stimulating the local skin with negative pressure. This article elaborately describes the procedure of moving cupping along meridians therapy in the treatment of AECOPD. The effectiveness and feasibility of moving cupping along meridians therapy in relieving symptoms and enhancing the quality of life is demonstrated by comparing the changes in the 36-item Short-Form (SF-36) health survey questionnaire, the modified Medical Research Council dyspnea scale (mMRC), and the COPD Assessment Test (CAT) score before and after the treatment. As a cost-effective complementary treatment, the protocol for the moving cupping along meridians treatment described in this article is expected to provide a reference for non-pharmacological treatment options for AECOPD.

Investigation of the Fitness for Service (FFS) of Cracks in API 5L X70 Pipeline Steel using Failure Assessment Diagram (FAD)

In this study, the fitness for service of crack propagation in API 5L X-70 stee1 was investigated using a model called Failure Assessment Diagram (FAD) to determine how fit a crack can be under certain operational pressure. It is a known fact that during the production of pipes, there are tendencies for flaws such as inclusions and cracks to occur in the pipes. When these flaws are subjected to stresses, there are tendencies for failures to occur starting from where the cracks or flaws are located. The failure due to the propagation of the cracks leads to oil spillage causing pollution to the environment which had negatively impacted livelihood of the host communities and aquatic lives. This had resulted in Government spending huge amount of money maintaining the pipelines and remediation. The purpose of this paper is to investigate the fitness for service of crack lengths 12 mm, 17 mm, 22 mm and 27 mm using the Failure Assessment Diagram (FAD) mode1. The material used in this paper is API 5L X 70 steel in the form of a Compact Tension (CT) specimen machined according to ASTM E1820 – 13. API 5L X-70 stee1 is a low-carbon stee1 with a carbon content of as low as 0.04 %. It is used in the production of pipelines for conveying crude oil and natural gas from the place of production to the place of refining or export. In the investigation of the fitness for service of the cracks, a charpy V-notch impact test was carried out to determine the energy required to fracture the steel, which was later inputted numerically into a critical stress intensity factor formula in accordance with BS 7910 – 13 standards to obtain the critical stress intensity factor (KIC or KQ). The stress intensity factor (KI) was obtained from formula also according to BS 7910 – 13 standards. The ratio of KI to KQ was used in the FAD analysis. Subsequently, a monotonic tensile test was conducted to obtain the yield stress ( ys) and the reference stress ( ref) was obtained numerically according to BS 7910 – 13. The ratio of ref) to ys) was also used in the FAD analysis. The FAD analysis was used to determine the fitness for services and fracture behaviour of each crack. Scanning electron microscopy (SEM) was used to confirm the fracture behaviour obtained from the FAD. The results obtained show that the energy from the charpy V-notch impact test was 302.9 J and the critical stress intensity factor (KQ) correlated numerically according to BS 7910 – 13 was determine as 246.73 MPa . The yield stresses obtained from the monotonic test for crack lengths of 12 mm, 17 mm, 22 mm and 27 mm were 132.51 MPa, 109.10 MPa, 114.36 MPa and 118.21 MPa, respectively. In the FAD analysis, it was observed that the safe operational stress to ensure fitness for service decreases with an increase in crack length. The fracture behaviour shows a ductile fracture behaviour since the FAD lies within the plastic collapse region. This fracture behaviour was confirmed by the image obtained from the scanning electron microscopy (SEM), which showed a cup and cone image suggesting ductile fracture behaviour. This FAD method will ensure that safe operational stresses are maintained for various crack length to prolong the life span of the pipeline. It is a novel method that can also be used to properly schedule the rate of inspection in pipelines alongside Ultrasonic sound, Liquid penetrant, Magnetic particle and radiographic methods of inspection.

H3PO4-Impregnated Covalent Organic Framework Membrane on Separators to Prevent Lithium Metal Anode Dendrite Growth.

Inhibiting the growth of lithium dendrites is crucial for battery safety. For separators, their favorable electrolyte wettability, uniform current density, and high ionic conductivity are beneficial for avoiding Li dendrite growth. In this work, we propose a separator (PA@COF/PP) by modifying a polypropylene separator with H3PO4-functionalized covalent organic frameworks. The uniform channels of the covalent organic frameworks and H3PO4 can homogenize the current and act as ionic conductors for efficient Li+ migration. The synthesized separator effectively suppresses the growth of lithium dendrites and improves the stability of the batteries. A symmetric cell with the PA@COF/PP separator exhibits a stable life span over 4000 hours at a high current density of 5 mA cm-2, compared to the commercial PP separator, which lasts only 159 hours. This work provides an efficient method and novel inspiration for the construction of dendrite-free lithium metal batteries.

GBT1118, a Voxelotor Analog, Ameliorates Hepatopathy in Sickle Cell Disease.

Background and Objectives: In sickle cell disease (SCD), hepatopathy is a cumulative consequence of ischemia/reperfusion (I/R) injury from a vaso-occlusive crisis, tissue inflammation, and iron overload due to blood transfusion. Hepatopathy is a major contributing factor of shortened life span in SCD patients. We hypothesized that the voxelotor, a hemoglobin allosteric modifier, ameliorates sickle hepatopathy. Materials and Methods: Townes SCD mice and their controls were treated with either chow containing GBT1118, a voxelotor analog, or normal chow. We evaluated inflammation, fibrosis, apoptosis and ferroptosis in their livers using qPCR, ELISA, histology, and immunohistochemistry. Results: GBT1118 treatment resulted in reduced hemolysis, iron overload and inflammation in the liver of SCD mice. There were significant reductions in the liver enzyme levels and bile acids. Furthermore, GBT1118-treated mice exhibited reduced apoptosis, necrosis, and fibrosis. Increased ferroptosis as evident from elevated 4-hydroxynonenal (4-HNE) staining, malondialdehyde (MDA) levels, and expression of Ptgs2 and Slc7a11 mRNAs, were also significantly reduced after GBT1118 treatment. To explain the increased ferroptosis, we evaluated iron homeostasis markers in livers. SCD mice showed decreased expression of heme oxygenase-1, ferritin, hepcidin, and ferroportin mRNA levels. GBT1118 treatment significantly increased expressions of these genes. Conclusions: Our results suggest GBT1118 treatment in SCD confers the amelioration of sickle hepatopathy by reducing inflammation, fibrosis, apoptosis, iron overload and ferroptosis.

Analysis of Girder Deflection in a Simulated Bridge Using SAP 2000: Study Case of Nongsa Pura Bridge

Within structural engineering, bridges demonstrate how the practical import of scientific hypotheses becomes clear to humanity. Engineers use computer simulations and models to anticipate how the bridge will react under various stresses and what its response is likely given all sorts of environments over its life span. The construction of the Nongsa Pura Bridge in Batam, which showcases cutting-edge civil engineering accomplishments customized to local requirements, represents a critical turning point in the region's infrastructure improvement. This paper aims to analyze the deflection of a Nongsa Pura Planning Simulation using SAP2000 software. This research uses secondary data and the author's assumptions as necessary data to design a bridge. The results of this research are deflection values for the main girder, transverse girder, and longitudinal girder. In the main girder, the most considerable deflection value is 0,0778724 m. In contrast, in the transverse girder, the most considerable deflection value is 0,034118 m, and the longitudinal beam has the most considerable deflection value of 0,077809 m.

Synergistic enhancement of the photocatalytic activity of g-C3N4 via in-situ surface alkalization and CQDs loading strategies

The CQDs/alkaline carbon nitride heterojunction photocatalysts were synthesized employing dicyandiamide as the nitrogen material, Citric acid was used as the carbon source, while KCl and NH4Cl were as alkaline reagents. The study investigated the influence of CQDs on the adsorption performance, photocatalytic activity, and band structure of alkalized carbon nitride. The dark adsorption results revealed that CNK/CQDs1: 12 exhibited outstanding adsorption performance, capable of degrading adsorbed pollutants in a relatively short period. The photocatalytic degradation study demonstrates that CNK/CQDs1:12 exhibits significantly higher degradation efficiencies compared to the pristine CN and alkalinized CNK samples, with degradation efficiencies of 94.4 % for Methylene Blue (MB) and 71.68 % for tetracycline hydrochloride (TC-HCl) within 60 min. This is due to the synergistic effects of alkalization of the g-C3N4 surface and CQDs loading, which modified the heterojunction interfacial charge transfer efficiency, suppressing the recombination of photoelectron-hole pair, extending the life span of transient photogenerated carriers, thereby improving photocatalytic activity. Free radical trapping experiment indicated that h+ and ·O2− are the primary active species during the photocatalytic degradation process of CNK/CQDs1:12.

Assessing computational reproducibility in Behavior Research Methods

Psychological science has thrived thanks to new methods and innovative practices. Journals, including Behavior Research Methods (BRM), continue to support the dissemination and evaluation of research assets including data, software/hardware, statistical code, and databases of stimuli. However, such research assets rarely allow for computational reproducibility, meaning they are difficult to reuse. Therefore, in this preregistered report, we explore how BRM’s authors and BRM structures shape the landscape of functional research assets. Our broad research questions concern: (1) How quickly methods and analytical techniques reported in BRM can be used and developed further by other scientists; (2) Whether functionality has improved following changes to BRM journal policy in support of computational reproducibility; (3) Whether we can disentangle such policy changes from changes in reproducibility over time. We randomly sampled equal numbers of papers (N = 204) published in BRM before and after the implementation of policy changes. Pairs of researchers recorded how long it took to ensure assets (data, software/hardware, statistical code, and materials) were fully operational. They also coded the completeness and reusability of the assets. While improvements were observed in all measures, only changes to completeness were altered significantly following the policy changes (d = .37). The effects varied between different types of research assets, with data sets from surveys/experiments showing the largest improvements in completeness and reusability. Perhaps more importantly, changes to policy do appear to have improved the life span of research products by reducing natural decline. We conclude with a discussion of how, in the future, research and policy might better support computational reproducibility within and beyond psychological science.

A new approach to monitor the life cycle of urban street tree canopies

One common measure to mitigate the impacts of rising temperatures within cities is increasing the amount of vegetation, especially urban trees and their canopies. To maximize the associated benefits of urban trees in a given city or neighborhood, it is important that the canopy of newly planted trees matches or exceeds the canopy of the trees that are lost. However, cities often use cross-sectional data to make decisions about the number of trees that should be planted without considering an individual tree’s growth and life span. In this study, individual tree growth and longevity data were used to portray the current and future conditions of street trees in six neighborhoods near Downtown Los Angeles and to identify locations in those neighborhoods that are in urgent need of interventions for tree planting. The results of this study indicate that, under the typical tree mortality scenario, near half of the current tree canopy will disappear by 2050, and on average, approximately one percent of the existing street trees will be lost due to aging each year. The approach used in this study shows how cities can monitor the age and mortality rate of the urban tree canopy over time. This approach informs tree planting campaigns that will preserve the long-term vitality and size of urban tree canopies and contribute to the resiliency of cities in a warmer future climate.

Class experiences and the long-term evolution of economic values

Abstract While there is a strong cross-sectional association between social class and political attitudes, recent research—based on longitudinal data—finds that changes in class are, at most, weakly related to changes in such attitudes. One common explanation for this finding is that early life socialization affects both social class and political attitudes and that class has little, if any, direct effect on them. In this manuscript, we explore an alternative explanation that centers on the importance of cumulative class experiences for the long-term evolution of attitudes. To evaluate this perspective, we leverage data from the British Household Panel Survey, which contains measures of economic values that span up to 16 years, as well as complete work-life histories of respondents that allow us to track individual class experiences over people’s life span. Our findings show that cumulative class experiences are strongly associated with the development of economic values.

The resistance of domestic canine skin-derived fibroblasts to oxidative and non-oxidative chemical injury: implications of breed and body size.

Small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. Underlying this observed physiological difference across domestic dogs, there must also be differences at other levels of organization that could lead to elucidating what accounts for the disparity in aging rates and life span within this species. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated. Here, we cultured dermal fibroblasts from large and small breed dogs from both young and old age categories and examined the degree of resistance to multiple sources of cytotoxic stress. This included heat (42°C), paraquat, cadmium, and hydrogen peroxide for increasing amounts of time (heat) or increasing concentrations (chemical stressors). We hypothesized that small breed dogs, with longer lifespans, would have greater cellular resistance to stress compared with large breed dogs. Final sample sizes include small puppies (N = 18), large puppy (N = 32), small old (N = 11), and large old (N = 23) dogs. Using a 2 (donor size) by 2 (donor age) between-subjects multivariate analysis of variance, we found that the values for the dose that killed 50% of the cells (LD50) were not significantly different based on donor size (p = 0.45) or donor age (p = 0.20). The interaction was also not significant (p = 0.47). Interestingly, we did find that the degree of resistance to cadmium toxicity was significantly correlated with the degree of resistance to both heat and hydrogen peroxide, but not paraquat (p < 0.01 for both). These data suggest that cellular stress resistance does not differ among domestic dogs as a function of size or age, pointing to other cellular pathways as the mechanistic basis for the observed differences in lifespan.

Kinetics and Thermodynamic Study of Cellulase Embedded Metal Organic Frameworks

Cellulase is an important enzyme used for many purposes in different industrial sectors. Even though cellulase has so many applications, it easily denatures with a little change in pH and temperature, which causes low stability, usability, and activity. To enhance its activity and stability, immobilization of porous materials is the best way to enhance its activity, stability, and life span. For immobilization, a Metal-organic framework (MOF) is considered as a potential candidate. Cellulase@Zn- benzene 1-4 di-carboxylic acid (BDC) by hydrothermal method and Zn-cellulase-benzene 1-4 dicarboxylic acid (BDC) by de novo approach were prepared, and their activities were analyzed. Zn-cellulase-benzene 1-4 dicarboxylic acid (BDC) produced by the de novo approach, shows higher activity, stability, catalytic performance, and life span than the free enzyme, and cellulase@Zn- benzene 1-4 di-carboxylic acid (BDC) produced by the hydrothermal method.

Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.

Neurodegenerative diseases are the leading cause of human disability and immensely reduce patients' life span and quality. The diseases are characterized by the functional loss of neuronal cells and share several common pathogenic mechanisms involving the malfunction, structural distortion, or aggregation of multiple key regulatory proteins. Cellular phase separation is the formation of biomolecular condensates that regulate numerous biological processes, including neuronal development and synaptic signaling transduction. Aberrant phase separation may cause protein aggregation that is a general phenomenon in the neuronal cells of patients suffering neurodegenerative diseases. In this review, we summarize the pathological causes of common neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. We discuss the regulation of key amyloidogenic proteins with an emphasis of their aberrant phase separation and aggregation. We also introduce the approaches as potential therapeutic strategies to ameliorate neurodegenerative diseases through intervening protein aggregation. Overall, this review consolidates the research findings of phase separation and aggregation caused by misfolded proteins in a context of neurodegenerative diseases.

Wear Mechanics of the Female Locust Digging Valves: The “Good Enough” Principle

AbstractAdult female desert locusts (Schistocerca gregaria) dig underground to lay their eggs, ensuring optimal conditions for successful hatching. Digging is performed using the two pairs of oviposition valves at the tip of the female's abdomen. These valves are subjected to considerable shear forces during the repeated digging cycles, potentially leading to wear over time. The resilience of the valves is investigated by analyzing the relationship between digging experience and valve damage and wear throughout the female locust's life. The findings reveal the ability of the valves to withstand the significant shear forces encountered during digging. Despite this resilience, however, perceptible limitations in the valves’ mechanical durability against wear are observed. Toward the end of the female locust's life, the valves show substantial signs of wear, indicating effective performance but with limited longevity, i.e., a designated life span that enables successful oviposition for ca. four oviposition cycles. A comparison of the valve material with that of the animals’ mandibles, which are used continuously throughout their life and show remarkable wear‐resistance, further highlights the evolutionary adaptation of the valve materials to their specific function, suggesting a trade‐off between energetic investment and the sufficient, or “good‐enough”, performance that is required for survival.