Stress Changes Research Articles

Novel insights into antioxidant status, gene expression, and immunohistochemistry in an animal model infected with camel-derived Trypanosoma evansi and Theileria annulata

Abstract Background Hemoprotozoan diseases, especially trypanosomosis and theileriosis, adversely affect the productivity, growth, and performance of camels. Regular sampling and investigation of camels are challenging due to several factors. Consequently, there is a lack of knowledge on camel parasite genotyping, cytokine production, and oxidative stress parameters during infection. Methods The present study investigated two critical blood protozoa infecting camels in Egypt, Trypanosoma evansi and Theileria annulata, using molecular methods, specifically 18S rRNA gene analysis. Following molecular confirmation, experimental infections were induced in Swiss albino mice to assess the expression of immune response genes and oxidative stress parameters. The study further explored the correlation between histopathological alterations and inflammatory reactions in the kidney, spleen, and liver of infected mice, alongside the immunohistochemical expression of caspase-3, proliferating cell nuclear antigen (PCNA), and tumor necrosis factor (TNF). Results Trypanosoma evansi and T. annulata isolated from naturally infected camels were molecularly identified and deposited in GenBank under accession numbers OR116429 and OR103130, respectively. Infection with T. evansi and T. annulata caused significant adverse effects on the immune condition of infected mice, increasing the pathogenicity of the infection. This was evidenced by a significant increase in oxidative stress parameter levels in both naturally infected camels and experimentally infected mice compared to healthy controls. Furthermore, the expression of immune response genes was significantly elevated in infected mice. Immunohistochemistry analysis showed a pronounced upregulation of caspase-3, PCNA, and TNF in the infected groups relative to the control group. These findings are the first to be reported in Egypt. Conclusions This study successfully identified and genotyped two economically important blood protozoa, T. evansi and T. annulata, from camels in Egypt. Additionally, the experimental animal model provided valuable insights into the immune response, oxidative stress, and histopathological changes induced by these parasites, demonstrating comparable results to naturally infected camels. These findings highlight the potential of this model to study parasite–host interactions and immune responses, contributing to a better understanding of the pathogenic mechanisms of T. evansi and T. annulata infections. This model may be useful for future studies focused on disease control and therapeutic interventions. Graphical Abstract

Silymarin attenuates oxidative stress and pathological changes induced by salinomycin in adult male rabbits

AbstractFeed additives are used in animal husbandry to prevent diseases and enhance growth rates. Salinomycin sodium (SAL) is an approved feed additive for rabbit fattening diets, typically administered at a dosage of 20–25 mg/kg feed with a 5-day withdrawal period. However, the misuse or abuse of SAL can result in toxicity in rabbits. This study aimed to evaluate the adverse effects of SAL administration in different organs for the first time and the protective role of silymarin in rabbits. Seven groups of rabbits were randomly allocated. The control group received no additives. The second and third groups received rations with 20 mg SAL/kg and 40 mg SAL/kg, respectively. The fourth and fifth groups received the same SAL doses with silymarin at 6.5 mg/kg body weight (bw) and 13 mg/kg bw, respectively. The sixth and seventh groups were administered silymarin alone at 6.5 mg/kg bw and 13 mg/kg bw, respectively. Rabbits were euthanized and slaughtered on day 29 following the Halal method. SAL at 20 mg/kg ration caused mild to moderate pathological changes compared to the control group, while 40 mg SAL/kg ration induced severe pathological changes. However, silymarin supplementation, alone or with SAL, improved organs histology. Both silymarin doses (6.5 mg/kg bw and 13 mg/kg bw) mitigated SAL's harmful effects. In conclusion, this study highlights the potential detrimental effects of SAL toxicity on different organs in rabbits. The supplementation of silymarin reduced and prevented these hazardous effects. These findings emphasize the promising role of silymarin as a protective agent against SAL-induced toxicity in rabbits.

Historical Subsurface Cooling in the Tropical Pacific and Its Dynamics

Abstract Understanding how the tropical Pacific responds to rising greenhouse gases in recent decades is of paramount importance given its central role in global climate systems. Extensive research has explored the long-term trends of tropical Pacific sea surface temperatures (SSTs) and the overlying atmosphere, yet the historical change in the upper ocean has received far less attention. Here, we present compelling evidence of a prominent subsurface cooling pattern along the thermocline in the central-to-eastern tropical Pacific since 1958. This subsurface cooling has been argued to be contributing to the observed cooling or lack of warming of the equatorial cold tongue SST. We further demonstrate that different mechanisms are responsible for different parts of the subsurface cooling. In the central-to-eastern equatorial Pacific and the southeastern off-equatorial Pacific, where zonal wind stress strengthens, a pronounced subsurface cooling trend emerges just above the thermocline that is closely tied to increased Ekman pumping. In the eastern equatorial Pacific where zonal wind stress weakens, the westward surface current and eastward Equatorial Undercurrent weaken as well, resulting in reduced vertical current shear and increased ocean stability, which suppresses vertical mixing and leads to local cooling. We conclude that the historical subsurface cooling is primarily linked to dynamical adjustments of ocean currents to tropical surface wind stress changes.

Exploring feasibility of fNIRS to assess delayed inhibition effect of prefrontal cortex for acute stress by acupuncture on GV20: a pilot study

IntroductionAcupuncture on the acupuncture point GV20 has been considered effective for managing psychoneurological disorders since ancient times, and GV20 is now regularly used to treat stress-related diseases (SRDs), including psychoneurological disorders. Although reports indicating that acupuncture stimulation of GV20 alone regulates cerebral blood flow (CBF) in brain regions associated with SRDs have been scattered, from the perspective of the need for earlier action, the effects on subjective stress as self-reported in the stress state of healthy individuals and CBF changes in related prefrontal cortex (PFC) subregions, which is based as underlying mechanism, remain unclear. Therefore, there is a need to explore effective methods for analyzing such effects.MethodsMultiple consecutive mental arithmetic tasks were performed to induce sufficient stress in healthy university students. Real acupuncture or sham acupuncture was performed on GV20, and subjective stress and CBF changes in PFC subregions were observed before and after acupuncture using functional near-infrared spectroscopy, which were analyzed based on the general linear model method and correlation analysis.ResultsSubjective stress was suppressed and recovered significantly faster in the true acupuncture group than in the sham acupuncture group. Furthermore, significant negative correlations were found between subjective stress and CBF in several PFC subregions during and after the tasks, with more correlated regions on the left side than on the right side of the PFC. Among them, the CBF of the left ventrolateral PFC (vl-PFC) was suggested to be maintained in the true acupuncture group under repeated tasks load, which was inferred to be correlated with delayed decreases in subjective stress after acupuncture.DiscussionThis pilot study showed that fNIRS is feasible for assessing delayed PFC inhibition in acute stress by acupuncture on GV20. Acupuncture treatment on GV20 resulted in early suppression of subjective stress and early recovery. The neuroscientific rationale for this finding may lie in its effect on maintaining CBF in the left vl-PFC related to delayed inhibition of subjective stress, and would make it reasonable to apply acupuncture to GV20 in healthy individuals. Larger studies are needed to corroborate these findings and obtain reliable conclusions.

The impact of varying sizes of silver nanoparticles on the induction of cellular damage in Klebsiella pneumoniae involving diverse mechanisms

Abstract Silver nanoparticles (AgNPs) are extensively studied as potent antibacterial agents targeting antibiotic-resistant pathogens. Cellular damage induced through various mechanisms that can affect multiple cell components like the outer membrane, enzymes, and proteins is closely linked to their chemical and morphological characteristics. We investigated the impact of AgNPs’ size on their antibacterial effectiveness using two differently sized nanoparticles: silver nanoparticle-Citrus limon (AgCL) with an average size of 21 nm and silver nanoparticle-Citrus sinensis (AgCS) with an average size of 13 nm, derived from C. limon and C. sinensis through environmentally friendly methods. The study evaluated their antibacterial effects by assessing morphology changes via scanning electron microscopy, metabolic alterations using Fourier transform infrared (FT-IR) spectroscopy, and oxidative stress responses through biochemical markers in Klebsiella pneumoniae cells exposed to AgNPs. The results showed that both AgCL and AgCS exhibited remarkable antibacterial activity, evidenced by inhibition zones of 14 ± 1.5 and 16 ± 1.0 mm, respectively. Morphological changes in K. pneumoniae cells treated with AgNPs were size dependent, with notable alterations noted. FT-IR spectroscopy revealed size and concentration-dependent biochemical changes, particularly in shifts in functional groups involved in the fluidity of cell wall lipid, and protein structure. Exposure to AgNPs led to increased oxidative stress markers like lipid peroxides and reduced levels of enzymatic and non-enzymatic antioxidants, more prominently observed with smaller AgCS nanoparticles (13 nm). AgNPs induce oxidative stress and morphological changes in K. pneumoniae strains, with smaller nanoparticles demonstrating greater efficacy. These findings underscore the importance of nanoparticle size in optimizing the antibacterial properties against pathogens.

Co- and post-seismic deformation of the 2022 Menyuan Mw6.6 earthquake from InSAR and GPS observations

Summary This study combines InSAR and GPS data to examine the co-seismic slip and post-seismic deformation of the 2022 Menyuan Mw6.6 earthquake, shedding light on the fault structure, slip distribution, and rheology of the northeastern Tibetan Plateau. InSAR co-seismic deformation revealed fault dip angle of 82° for the Lenglongling fault and 84° for the Tuolaishan fault. The optimal co-seismic slip model, derived from InSAR, GPS, and near-field pixel-offset data, indicates a maximum slip of 3.3 m, concentrated in the upper 3 km of the fault. We propose a three-step procedure to comprehensively invert the post-seismic deformation, accounting for both afterslip and viscoelastic relaxation, constrained by the InSAR and GPS observations. The optimal afterslip model indicates a cumulative afterslip of 9 cm over two years, primarily concentrated in the deeper sections of the co-seismic slip zone. Incorporating viscoelastic relaxation improved the spatial distribution of the afterslip on the Tuolaishan fault. The afterslip released a seismic moment of 1.96 × 10¹⁸ Nm, accounting for approximately 15 per cent of the co-seismic moment release. The viscosity of the lower crust in the region was estimated to range from 1.5 to 5 × 1018 Pa·s, with an optimal value of 2 × 10¹⁸ Pa·s. As the distance from the epicenter increased, viscoelastic relaxation became the dominant post-seismic mechanism, contributing up to 80 per cent of the deformation observed at the QHGC and GSMI stations. Additionally, the earthquake increased Coulomb stress on the ‘Tianzhu Seismic Gap’ and nearby faults, raising seismic hazard in the region. These findings highlight the importance of simultaneously considering both afterslip and viscoelastic relaxation mechanisms in post-seismic deformation analysis, and accounting for post-seismic effects when evaluating seismic stress changes.

The Impact of the COVID-19 Pandemic: A Longitudinal Analysis of Body Weight Variations and Their Implications for Daily Habits

Assessing changes in lifestyle, dietary habits, eating behaviors, and stress during the pandemic and their impact on weight is crucial for developing effective interventions. This study investigated weight variations among Brazilians and associated habit changes over nine months during the COVID-19 pandemic. An online questionnaire was applied (T0/T1, T2). Weight variation classifications were determined from T0 to T1 and evaluated longitudinally for changes in lifestyle, dietary habits, food consumption, eating behavior, and perceived stress using generalized estimating equations (p < 0.05). Out of 453 participants, 23.6% lost weight, 18.1% maintained their weight, 26.0% gained up to 2.4 kg, and 32.2% gained ≥2.5 kg. Weight loss was associated with decreased food consumption and increased stress at T2. The group that gained up to 2.4 kg reported reduced food intake, snacking, meal preparation, and candy consumption but increased stress at T2. Those gaining ≥2.5 kg initially increased food consumption, snacking, meal preparation, hamburgers/canned products, sugary drinks, instant meals/snacks, candies, and fast food consumption at T1, all of which were reduced at T2, along with a decrease in uncontrolled and emotional eating. Although the pandemic initially affected daily habits differently based on weight changes, participants—especially those who gained more weight—tended to revert to pre-pandemic habits.

Virtual communities of practice: nurturing teacher-coordinators’ well-being amidst stress and crisis

PurposeThis longitudinal study investigated the ways in which virtual communities of practice (VCoPs) can support the well-being of teachers in managerial roles during stressful changes and crises. Specifically, it examined the experiences of these educators to better understand how VCoPs contribute to sustaining well-being in the face of challenges.Design/methodology/approachA qualitative study methodology was utilized, consisting of three rounds of interviews with seven teacher-coordinators, coupled with content analysis to discern patterns and insights. A multidimensional model was then applied to pinpoint the associations between the community’s characteristics and the different approaches implemented by these teacher-coordinators to address stress and crises.FindingsThe analysis revealed a range of coping strategies within the VCoPs for handling stress and crises. Participation in virtual spaces was shown to foster in-depth, rich discussions. The multidimensional model captures how social, emotional and cognitive factors can help teacher coordinators navigate challenges.Originality/valueThis study contributes to a broader understanding of the well-being of educational staff, especially in managerial roles, by exploring the subtle dynamics of a VCoP. The findings highlight the impact of the community on teacher-coordinators' well-being in routine, stressful and crisis situations. These insights can provide valuable guidance for educational practitioners and policymakers to enhance the resilience of the education system to diverse challenges.

On a contact problem for a homogeneous plane with a finite crack under friction

An exact solution to the contact problem of indentation of an absolutely rigid punch with a straight base, taking into account friction, into one of the edges of a finite crack located in a homogeneous elastic plane was derived. It is assumed that shear contact stresses are directly proportional to normal contact pressure. In this case, it is assumed that the friction coefficient is directly proportional to the coordinates of the contacting points of the contacting surfaces. The governing system of equations for the problem was derived in the form of the heterogeneous Riemann problem for two functions with variable coefficients and its closed solution is constructed in quadratures. Simple formulas for contact stresses and the normal dislocation component of displacements of crack edge points were obtained. The patterns of changes in contact stresses and crack opening depending on the maximum value of the friction coefficient have been studied.

MiR-204-5p regulates SIRT1 to promote the endoplasmic reticulum stress-induced apoptosis of inner ear cells in C57BL/6 mice with hearing loss.

This study investigated the effect of miR-204-5p-mediated silencing of SIRT1 on the development of deafness in C57BL/6 mice and the roles of miR-204-5p and SIRT1 in deafness. Auditory brainstem response recordings, H&E staining, and immunohistochemistry were used to observe changes in hearing function and cochlear tissue morphology in 2-month-old and 15-month-old C57BL/6 mice. A senescence model was induced using H2O2 in inner ear cells (HEI-OC1). Changes in HEI-OC1 cell proliferation were detected using the CCK-8 assay, whereas flow cytometry was used to detect changes in apoptosis. MiR-204-5p expression was measured via RT‒qPCR. The SIRT1 agonist RSV and a miR-204-5p inhibitor were used to study changes in ER stress (ERS), proliferation, and apoptosis in HEI-OC1 cells. Western blotting was performed to detect changes in ATF4, CHOP, SIRT1, PERK, p-PERK, Bax, and Bcl-2 protein levels. A dual-luciferase reporter gene assay was carried out to assess the ability of miR-204-5p to target SIRT1. Relative miR-204-5p expression levels in the cochleae of aged C57BL/6 mice increased, whereas SIRT1 expression levels decreased, and miR-204-5p and SIRT1 expression levels were negatively correlated. ERS and increased 8-OHDG levels were observed in aged C57BL/6 mice. In a model of inner ear cell aging, H2O2 treatment induced increases in miR-204-5p expression and ERS-mediated apoptosis. MiR-204-5p was found to target SIRT1 and inhibit its expression. SIRT1 activation and a miR-204-5p inhibitor promoted HEI-OC1 cell proliferation and reduced apoptosis. The miR-204-5p inhibitor regulated expression of the ERS proteins PERK, ATF4, and CHOP to upregulate Bcl-2 and downregulate Bax. This study identified the roles of miR-204-5p and SIRT1 in deafness in C57BL/6 mice and investigated the loss of cochlear outer hair cells and the involvement of apoptosis and ERS in deafness.

Relationship between tooth macrowear and jaw morphofunctional traits in representative hypercarnivores.

The mammalian adult dentition is a non-renewable resource. Tooth attrition and disease must be accommodated by individuals using behavioral, physiological, and/or musculoskeletal shifts to minimize impact on masticatory performance. From a biomechanical perspective, the musculoskeletal system becomes less efficient at producing bite force for a given amount of muscle input force over an individual's life, because tooth-food contact area increases as cusps wear. In this study we ask the question: does mandibular biomechanical performance show evidence of compensation with increasing tooth wear? We use representative taxa of three carnivoran ecomorphologies (meat specialist, scavenger, bone cracker) as a study system to compare morphofunctional data on tooth macrowear, jaw depth, bite mechanical efficiency, and jaw stress during biting. No significant shifts in adult mandibular corpus dimensions occurs in the sampled taxa as canine and carnassial teeth wear. In bone cracking spotted hyenas carnassial biting mechanical efficiency increases significantly with increasing tooth wear, with no significant change in mandibular stress. Analyses of the fossil carnivore Hyaenodon suggests an increase in canine biting efficiency with increased tooth wear, but this may reflect interspecific variation or phylogenetic contingency rather than a life history shift. Overall, these findings indicate that scavenging hyaenids and felid meat specialists do not exhibit morphofunctional compensation for the decreased mechanical capability of worn and dull teeth. Behavioral modifications, rather than musculoskeletal adjustments, may instead play a major role in maintaining food acquisition and processing capabilities for individuals surviving into advanced ontogenetic age and tooth wear. These observations highlight the mammalian masticatory system as having a dynamic performance profile through its useful lifespan, and encourage a more nuanced understanding of past and present carnivore guilds by considering wear-dependent performance changes as a possible source of selection.

Real-time experiences of racism and stress in association with postpartum weight retention: A longitudinal ecological momentary assessment study.

Racial inequities in postpartum weight have been documented with limited studies on the influences of racism and other forms of discrimination. In a prospective longitudinal study applying ecological momentary assessment (EMA) and ambulatory assessment of weight, we measured the association between discrimination, stress and postpartum weight change. The Postpartum Mothers Mobile Study (PMOMS) is a cohort of 313 pregnant and birthing individuals who were followed during their second and third trimester through 1 year postpartum. They were recruited in clinical settings between 2017-2020 in a major city center in Pennsylvania. Measures of racism and gender-based discrimination were collected via random EMA surveys throughout pregnancy and postpartum; and weight was collected via blue-tooth enabled scales at least weekly. Among Black participants, a 10% increase in the number of days a participant experienced racial discrimination in the past month was associated with retaining 0.3 more pounds; 10% increase in EMA gender discrimination was associated with retaining 0.4 more pounds; and EMA stress reported in the past month was associated with decreased weight retention. Chronic experiences of racial and gender discrimination may contribute to weight retention immediately after pregnancy and beyond.

Investigation of co-seismic stress and aftershock distribution along the Sumatra–Andaman subduction zone

AbstractThis study aimed to investigate co-seismic stress and aftershock distribution along the Sumatra–Andaman subduction zone (SASZ). The fault parameters of six major earthquakes with an M ≥ 7 that occurred during 2010–2022 along the SASZ, were utilized to determine the Coulomb stress change using numerical modeling techniques calculated on the receiver faults with similar focal mechanisms of the mainshock, strike-slip, thrust, and normal faulting, respectively. The earthquake events were then classified to analyze the aftershocks of major earthquakes in the area. These aftershocks were mapped in order to determine the relationship between the aftershock distribution and the areas of increased or decreased stress. The relationship between the co-seismic stress and distribution of aftershocks in the SASZ was found to mainly depend on the focal mechanism of major earthquakes and the type of receiver fault used for calculation. After a major earthquake in the SASZ, there are two possible patterns that most aftershocks will be generated from in the areas of increased stress. First, a major earthquake is a type of thrust fault calculated on the receiver fault using the focal mechanism of the mainshock. Second, a major earthquake is a type of strike-slip fault calculated on the receiver fault with an optimum-oriented strike-slip fault. This relationship is likely to represent the specific pattern of the seismotectonic stress in the SASZ that can be used to evaluate the risk areas of aftershocks after a major earthquake has occurred. Furthermore, two earthquake events with large magnitudes were generated following the respective major earthquake in the SASZ that were located around the areas of increased stress, indicating that these two earthquake events were likely triggered in areas of increased stress following the respective major earthquake. Therefore, this study concluded that after a major earthquake occurrence in the SASZ, the areas of increased stress have a higher risk of generating both a large number of aftershocks and a new large-magnitude mainshock event. The investigation of co-seismic stress is very important to estimate areas of increased stress after a major earthquake, as this can be useful for monitoring both earthquake and tsunami hazards in the area.

Addressing Mental Health Symptoms Among COVID-19 Healthcare Workers: A Heart Rate Variability Biofeedback Pilot Study.

Psychological stress among frontline healthcare workers (HCWs) increased during the COVID-19 pandemic, elevating mental health risks. Heart rate variability biofeedback (HRV-BF) is an evidence-based intervention with potential to reduce psychological burden on frontline HCWs; however, no studies have examined its use among this population since the pandemic began. We designed a trial to assess the effects of a brief HRV-BF intervention delivered via telemedicine on measures of anxiety, depression and stress, and heart rate variability, compared to an in-person intervention. We hypothesised that the telemedicine intervention would be non-inferior to the in-person intervention. Using a randomized comparison trial design, we tested a 10-day brief heart rate variability biofeedback intervention among frontline HCWs during the COVID-19 pandemic. They received remote, 30-min guided sessions every other day and were taught methods of heart rate variability biofeedback. Depression, anxiety and stress were assessed at baseline, 10days, and 40days with additional measures of anxiety measured before and after each session. HRV scores were collected at baseline, as well as during the course of the 10days. Multilevel modelling was used to examine the change in depression, anxiety, stress and HRV scores across multiple time points and session types (telemedicine vs. in-person). There was no significant differences between telemedicine (n=32) and in-person (n=15) interventions on the main outcomes. Both session types showed a significant decrease in depression, anxiety and stress scores across the entire intervention, and HRV scores significantly increased across both groups. Anxiety levels also significantly decreased after each session. The non-inferiority of the telemedicine intervention to a comparable in-person intervention affirms its promise for decreasing anxiety, depression and stress among frontline HCWs and may offer a cost-effective and feasible tool to use in crises situations.

Glacial Hydro-Isostatic Adjustment at Mid-Ocean Ridges

Summary Recent studies have suggested a link between ice age sea level fluctuations and variations in magma production and crustal faulting along mid-ocean ridges based on the detection of Milankovitch cycle frequencies in topography off several ridges. These fluctuations have also been connected to variability in hydrothermal metal fluxes near ridges. Ice age sea level calculations have shown that the sea level change across glacial cycles will be characterized by significant geographic variability, that is, departures from eustasy, due to the gravitational, deformation and rotational effects of the glacial isostatic adjustment (GIA) process. Using a state-of-the-art GIA simulation that incorporates 3-D variations in Earth viscoelastic structure, including plate boundaries, and updated constraints on the magnitude and geometry of ice mass fluctuations, we predict global sea level changes from Last Glacial Maximum (LGM, 26 ka) to present and from the Penultimate Glacial Maximum (PGM, 143 ka) to the Last Interglacial (LIG, 128 ka). We focus on the results along three ridges: the Mid-Atlantic Ridge, Juan de Fuca Ridge and East Pacific Rise, which are examples of slow, intermediate and fast spreading ridges, respectively. Sea level change across the Mid-Atlantic Ridge shows the greatest variability, ranging from a sea level fall greater than 200 m in Iceland to a maximum rise of ∼150 m in the South Atlantic, with significant non-monotonicity north of the Equator as the ridge weaves across the field of sea level changes. We also calculate changes in crustal normal stress from LGM to present-day across the Mid-Atlantic and Juan de Fuca Ridges and the East Pacific Rise. These results indicate that the contribution from ice mass changes to the crustal stress field can be significant well away from the location of ancient ice complexes. We conclude that any exploration of the hypothesized links to magma production and crustal faulting must consider both ocean and ice loading effects and, more generally, the profound geographic variability of the GIA process.

Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.

Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. The evolution of an extensive corticomotoneuronal system appears restricted to the human species, with ALS representing a uniquely human disease. While some, very select non-human primates have limited corticomotoneuronal projections, these tend to be absent in all other animals. From a general perspective, the early clinical features of ALS may be considered to reflect failure of the corticomotoneuronal system. The characteristic loss of skilled motor dexterity involving the limbs, and speech impairment through progressive bulbar dysfunction specifically involve those motor units having the strongest corticomotoneuronal projections. A similar explanation likely underlies the unique "split phenotypes" that have now been well characterized in ALS. Large Betz cells and other pyramidal corticomotoneuronal projecting neurons, with their extensive dendritic arborization, are particularly vulnerable to the elements of the ALS exposome such as aging, environmental stress and lifestyle changes. Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons. Betz cell failure is further accentuated through dysfunction of its profuse dendritic arborizations. Clarification of system specific genomes and neural networks will likely promote the initiation of precision medicine approaches directed to support the key structure that underlies the neurological manifestations of ALS, the corticomotoneuronal system.

Infinitely rugged intra-cage potential energy landscape in metallic glasses caused by many-body interaction

The absence of translational symmetry in glassy materials poses a significant challenge in establishing effective structure-property relationships in real space. Consequently, the potential energy landscape (PEL) in phase space is widely utilized to comprehend the complex phenomena in glasses. The classical PEL features a two-scale profile comprising mega-basins and sub-basins, corresponding to α-relaxations (e.g. glass transition) and β-relaxations (e.g. local cage-breaking atomic rearrangements), respectively. Recent studies, however, reveal that sub-basins are not smooth and contain finer structures, the origins of which remain elusive. Here we probe the smoothness of sub-basin bottoms in glasses' PEL by introducing small intra-cage cyclic loading and then measuring the net changes in atomic-level stresses. Compared to glasses with pair interaction, glasses with many-body interaction exhibit orders-of-magnitude larger and loading-dependent stress changes even before the first cage-breaking event takes place, which reflect much more feature-rich sub-basins. We further demonstrate this stark contrast stems from the spatial distribution of individual atom's constraining force field. Specifically, at vanishing perturbations, many-body interactions disrupt the positive-definite synchrony in energy variations of the perturbed atom and the whole system, causing inherently less confined atomic responses and infinitely rugged sub-basins. The implications of these findings for the selective addition or removal of fine structures in the PEL and the subsequent tuning of glassy materials' responses to external stimuli are also explored.

Time-Dependent Stress Drop Variations After Large Earthquakes Along the North Chilean Megathrust

ABSTRACT We observe a time dependence of the median stress drop in spatiotemporal proximity of large earthquakes. The median stress drop of the early aftershock seismicity is elevated for only a few days after the mainshocks and then rapidly falls back to the long-term average. This short-term variation has remained largely unnoticed by previous studies, presumably due to their usually low temporal resolution. Our study uses a recent extensive stress drop catalog, which contains more than 51,000 events from northern Chile. It includes observations from three Mw>7 megathrust earthquakes, namely the 2007 Mw 7.7 Tocopilla earthquake, the 2014 Mw 8.1 Iquique earthquake, and its largest Mw 7.6 aftershock, as well as another eleven Mw>6 earthquakes. A detailed analysis reveals that the elevated stress drop is not primarily linked to an increase of seismic moment during the early aftershock phase but is rather attributable to higher measured corner frequencies in the corresponding time interval. We propose two possible explanations: (1) The high stress changes induced by the mainshock allow failure of strong structures at or adjacent to the main rupture area, which produces higher stress drop events. After a few days, afterslip activity has reduced the in situ stresses and thereby the failure potential of the stronger regions. (2) The mainshock disturbs the fluid-sealing plate interface, allowing overpressured fluids to escape, exhibiting the so-called fault-valve behavior. The effect appears to persist only for several days until the sealing effect is restored and average stress drop levels are recovered.

Exploring the role of nanoparticle additives in reducing emissions in compression ignition engine

The paper discusses the growing environmental issues caused by vehicle emissions, leading many countries to tighten their emission standards to reduce the harmful gases released by motor vehicles. This is especially important as urbanization has increased, leading to more consumption of petroleum products. As a result, there is a growing need for cleaner, more sustainable fuel alternatives. Biodiesel has been recognized as a potential solution since it is renewable, non-toxic, and less environmentally harmful than traditional diesel. The study in question explores how adding biodiesel and nanoparticles affects diesel engine performance, particularly in terms of noise and particulate matter emissions (small particles of pollution). The research was carried out using a compression ignition engine (like those found in diesel vehicles) under constant RPM (revolutions per minute) and variable loads (changes in engine stress or power requirements). The results showed that when biodiesel was blended with nanoparticles and used as fuel, there was a noticeable reduction in noise levels, carbon dioxide (CO2), and particulate matter emissions compared to regular diesel. This suggests that biodiesel, especially when enhanced with nanoparticles, can effectively lower the harmful effects of diesel engines on the environment, offering a greener and quieter alternative.

Amyloid beta-induced signalling in leptomeningeal cells and its impact on astrocyte response.

The pathological signature of Alzheimer's disease (AD) includes the accumulation of toxic protein aggregates, mainly consisting of amyloid beta (Aβ). Recent strides in fundamental research underscore the pivotal role of waste clearance mechanisms in the brain suggesting it may be an early indication of early onset AD. This study delves into the involvement of leptomeningeal cells (LMCs), crucial components forming integral barriers within the clearance system, in the context of AD. We examined the inflammatory cytokine responses of LMCs in the presence of Aβ, alongside assessments of LMC growth response, viability, oxidative stress, and changes in vimentin expression. The LMCs showed no changes in growth, viability, oxidative stress, or vimentin expression in the presence of Aβ, indicating that LMCs are less susceptible to Aβ damage compared to other CNS cells. However, LMCs exhibited a unique pro-inflammatory response to Aβ when compared to an LPS inflammatory control, showing an mRNA expression of pro-inflammatory cytokines such IL-6, IL-10 and IL-33 but no changes in IL-1α and IL-1β. Furthermore, LMCs influenced the astrocyte response to Aβ, as conditioned media from Aβ-treated LMCs was observed to downregulate somatic S100β in astrocytes. We also investigated whether the JAK/STAT3 pathway was involved in the Aβ response of the LMCs, as this pathway has been shown to be activated in astrocytes and neurons in the presence of Aβ. JAK/STAT3 activation was assessed through phosphorylated STAT3, revealing that JAK/STAT3 was not active in the cells when in the presence of Aβ. However, when JAK1 and JAK2 were inhibited, cytokine protein levels of IL7, IL10, IL15 and IL33 levels, which had shown alteration when LMCs were treated with Aβ, returned to base levels. This indicates that although JAK1/STAT3 and JAK2/STAT3 are not the direct pathway for Aβ response in LMCs, JAK1 and JAK2 may still play a role in regulating cytokine levels, potentially through indirect means or crosstalk. Overall, our findings reveal that LMCs are resilient to Aβ toxicity and suggest that JAK1/STAT3 and JAK2/STAT3 does not play a central role in the inflammatory response, providing new insights into the cellular mechanisms underlying AD.