Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

Provenance and depositional setting of the Late MiocenePleistocene clastic sediments in the eastern Arabian Peninsula and western Iraq using rare earth elements geochemistry

The sandstones of the Late miocene–Pliocene Dibdibba Formation in the Najaf–Karbala Plateau and Basra were examined to determine their source rocks and origin. The rare earth elements(REE) and trace elements(Sc, Co, V, and Th) concentrations in these sandstones revealed that they likely derived from a single source. The steep light rare earth elements(LREE) and flat, heavy rare earth element(HREE) patterns, negative Eu anomaly, and high ΣREE contents in sandstones suggest its derivation from a suggests that a passive continental margin environment and originated from felsic source rocks. The average concentration of ΣREE is 93.5 ppm, which is lower than that of the average crustal compositions like Upper Continental Crust and Post Archean Australian Shale. The higher proportion of LREE compared to HREE implies that these sandstones were recycled and derived from a distal source. The Th/Co, Th/Sc, La/Sc, La/Co, Eu/Eu*and(La/Lu)cn elemental ratios indicated that these Late Miocene–Pliocene sandstones were derived from felsic rocks located in the marginal region of the Arabian Shield.

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.

Dendritic spine degeneration:a primary mechanism in the aging process

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

Debaryomyces hansenii supplementation in low fish meal diets promotes growth,modulates microbiota and enhances intestinal condition in juvenile marine fish

Background The development of a sustainable business model with social acceptance,makes necessary to develop new strategies to guarantee the growth,health,and well-being of farmed animals.Debaryomyces hansenii is a yeast species that can be used as a probiotic in aquaculture due to its capacity to i)promote cell proliferation and differen-tiation,ii)have immunostimulatory effects,iii)modulate gut microbiota,and/or iv)enhance the digestive function.To provide inside into the effects of D.hansenii on juveniles of gilthead seabream(Sparus aurata)condition,we inte-grated the evaluation of the main key performance indicators coupled with the integrative analysis of the intestine condition,through histological and microbiota state,and its transcriptomic profiling.Results After 70 days of a nutritional trial in which a diet with low levels of fishmeal(7%)was supplemented with 1.1%of D.hansenii(17.2×10^(5) CFU),an increase of ca.12%in somatic growth was observed together with an improve-ment in feed conversion in fish fed a yeast-supplemented diet.In terms of intestinal condition,this probiotic modu-lated gut microbiota without affecting the intestine cell organization,whereas an increase in the staining intensity of mucins rich in carboxylated and weakly sulphated glycoconjugates coupled with changes in the affinity for certain lectins were noted in goblet cells.Changes in microbiota were characterized by the reduction in abundance of several groups of Proteobacteria,especially those characterized as opportunistic groups.The microarrays-based transcrip-tomic analysis found 232 differential expressed genes in the anterior-mid intestine of S.aurata,that were mostly related to metabolic,antioxidant,immune,and symbiotic processes.Conclusions Dietary administration of D.hansenii enhanced somatic growth and improved feed efficiency param-eters,results that were coupled to an improvement of intestinal condition as histochemical and transcriptomic tools indicated.This probiotic yeast stimulated host-microbiota interactions without altering the intestinal cell organization nor generating dysbiosis,which demonstrated its safety as a feed additive.At the transcriptomic level,D.hansenii pro-moted metabolic pathways,mainly protein-related,sphingolipid,and thymidylate pathways,in addition to enhance antioxidant-related intestinal mechanisms,and to regulate sentinel immune processes,potentiating the defensive capacity meanwhile maintaining the homeostatic status of the intestine.

Artificial Intelligence-Driven FVM-ANNModel for Entropy Analysis ofMHD Natural Bioconvection in Nanofluid-Filled Porous Cavities

The research examines fluid behavior in a porous box-shaped enclosure.The fluid contains nanoscale particles and swimming microbes and is subject to magnetic forces at an angle.Natural circulation driven by biological factors is investigated.The analysis combines a traditional numerical approach with machine learning techniques.Mathematical equations describing the system are transformed into a dimensionless form and then solved using computational methods.The artificial neural network(ANN)model,trained with the Levenberg-Marquardt method,accurately predicts(Nu)values,showing high correlation(R=1),low mean squared error(MSE),and minimal error clustering.Parametric analysis reveals significant effects of parameters,length and location of source(B),(D),heat generation/absorption coefficient(Q),and porosity parameter(ε).Increasing the cooling area length(B)reduces streamline intensity and local Nusselt and Sherwood numbers,while decreasing isotherms,isoconcentrations,and micro-rotation.The Bejan number(Be+)decreases with increasing(B),whereas(Be+++),and global entropy(e+++)increase.Variations in(Q)slightly affect streamlines but reduce isotherm intensity and average Nusselt numbers.Higher(D)significantly impacts isotherms,iso-concentrations,andmicro-rotation,altering streamline contours and local Bejan number distribution.Increased(ε)enhances streamline strength and local Nusselt number profiles but has mixed effects on average Nusselt numbers.These findings highlight the complex interactions between cooling area length,fluid flow,and heat transfer properties.By combining finite volume method(FVM)with machine learning technique,this study provides valuable insights into the complex interactions between key parameters and heat transfer,contributing to the development of more efficient designs in applications such as cooling systems,energy storage,and bioengineering.

Overweight/Obesity in University Students from Mexico: Comparison Using Different Indices

The goal was to compare body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), and relative fat mas (RFM), to identify the best predictor of overweight and obesity in university students from Mexico. This is a cross-sectional survey with 697 university students from northern and central Mexico (448 women, and 249 men aged 18 - 19 years). Data was collected during 2018. Overweight and obesity were calculated from those indices and for both, female and male students, the order of correlation between a pair of indices were WHtR vs. RFM > WHtR vs. WC > RFM vs. WC > WHtR vs. BMI > BMI vs. WC > RFM vs. BMI. It is concluded to use the WHtR and the RFM to better predict overweight and obesity in young Mexican university students.

Principal Equatorial Null Geodesic Congruences in the Kerr Metric, and Their Quantum Propagators

Using the Raychaudhuri equation, we associate quantum probability amplitudes (propagators) to equatorial principal ingoing and outgoing null geodesic congruences in the Kerr metric. The expansion scalars diverge at the ring singularity;however, the propagators remain finite, which is an indication that at the quantum level singularities might disappear or, at least, become softened.

A Probabilistic Description of the Impact of Vaccine-Induced Immunity in the Dynamics of COVID-19 Transmission

The recent outbreak of COVID-19 has caused millions of deaths worldwide and a huge societal and economic impact in virtually all countries. A large variety of mathematical models to describe the dynamics of COVID-19 transmission have been reported. Among them, Bayesian probabilistic models of COVID-19 transmission dynamics have been very efficient in the interpretation of early data from the beginning of the pandemic, helping to estimate the impact of non-pharmacological measures in each country, and forecasting the evolution of the pandemic in different potential scenarios. These models use probability distribution curves to describe key dynamic aspects of the transmission, like the probability for every infected person of infecting other individuals, dying or recovering, with parameters obtained from experimental epidemiological data. However, the impact of vaccine-induced immunity, which has been key for controlling the public health emergency caused by the pandemic, has been more challenging to describe in these models, due to the complexity of experimental data. Here we report different probability distribution curves to model the acquisition and decay of immunity after vaccination. We discuss the mathematical background and how these models can be integrated in existing Bayesian probabilistic models to provide a good estimation of the dynamics of COVID-19 transmission during the entire pandemic period.

Growth phenology adjusts to seasonal changes in water availability in coexisting evergreen and deciduous mediterranean oaks

Different leaf(evergreen vs.deciduous habit)and xylem(diffuse-vs.ring-porous wood)traits represent contrasting strategies to face seasonal changes in water availability and temperature.However,how contrasting leaf and xylem habits of coexisting tree species affect stem wood formation and tree-ring development remains poorly understood.Here,we investigated the spatio-temporal patterns of wood formation in two deciduous oaks(Quercus faginea and Quercus petraea)and two evergreen oaks(Quercus ilex and Quercus suber)coexisting in seasonally dry Mediterranean forests along an aridity gradient in Spain.We hypothesized that growth responses to drought and intra-and inter-annual growth patterns would differ between functional groups.We simulated intra-and interannual growth using a modified version of the Vaganov-Shashkin(VS)process-based,growth model.The VS model simulations were used to estimate growth changes under a high emission scenario(RCP 8.5)for the current distribution of the study oak species and to forecast their future performance under warm(4.8℃)conditions in the Iberian Peninsula.Our simulations indicate that climate warming would induce a shortening of the ringgrowth season and a reduction of radial growth in evergreen and deciduous Mediterranean oaks,particularly in dry sites from southern and eastern Iberia currently occupied by Q.ilex and Q.faginea.Evergreen oaks may better recover after dry periods than deciduous oaks by resuming growth after the summer drought.Low soil water availability in spring would be more detrimental to growth of deciduous oaks.Process-based growth models should be refined and validated to better forecast changes in tree growth as a function of climate.

Functional diversity in an Andean subparamo affected by wildfire in Colombia

Recently,the Andean subparamo in Colombia has experienced severe wildfires,but little is known about the functional composition of recovering or not after a wildfire.Therefore,we examined the functional community composition subparamo affected byfire in 2016.We documented how functional traits changed 31 months after the disturbance and compared them with an unburned site.We sampled from one to two years after the fire every four months,then registered all recruits in 1655m plots.New individuals were classified into strategy functional groups based on the traits of persistence and dispersal.The first group was stem type and regeneration mechanism(seedling and resprout),and the second was fruit type and dispersal mode.We investigated the degree to which functional diversity changes plant communities over time(woody and non-woody),and we compared it with an unburned site.The most relevant results showed that resprouts and seed regenerated increased post-fire time and significant differences between sampling periods.The anemochory is the most relevant dispersal mode that indicates the community capacity to colonize the new gaps opened by the fire rapidly.We discuss how wildfire appears to be a triggering factor for persistence and dispersal strategy groups in subparamo burned given their characteristics of tolerance to stress.For this reason,a greater functional divergence between the ecosystems studied post-fire recovery has been related to higher levels of biodiversity at the landscape scale due to the high degree of endemism and significant differences in species composition between paramos.

TIME PERIODIC SOLUTIONS TO THE EVOLUTIONARY OSEEN MODEL FOR A GENERALIZED NEWTONIAN INCOMPRESSIBLE FLUID

In this paper we study a nonstationary Oseen model for a generalized Newtonian incompressible fluid with a time periodic condition and a multivalued,nonmonotone friction law.First,a variational formulation of the model is obtained;that is a nonlinear boundary hemivariational inequality of parabolic type for the velocity field.Then,an abstract first-order evolutionary hemivariational inequality in the framework of an evolution triple of spaces is investigated.Under mild assumptions,the nonemptiness and weak compactness of the set of periodic solutions to the abstract inequality are proven.Furthermore,a uniqueness theorem for the abstract inequality is established by using a monotonicity argument.Finally,we employ the theoretical results to examine the nonstationary Oseen model.

Impact of glacier changes and permafrost distribution on debris flows in Badswat and Shishkat catchments,Northern Pakistan

Knowledge of glacier changes and associated hazards is of great importance for the safety consideration of the population and infrastructure in the mountainous regions of Upper Indus Basin(UIB).In this study,we assessed the variations in glacier velocity,glacier surface elevation change,meteorological conditions,and permafrost distribution in Badswat and Shishkat catchments located in UIB to access the potential impact on the occurrence of debris flow in both catchments.We find that the glacier surface velocity increased during the debris flow event in the Badswat catchment and the mean daily temperature was 3.7℃to 3.9℃higher in most of the locations.The enhanced glacier surface elevation lowering period coincide with the rise in temperature during spring and autumn months between 2015 to 2019 in Badswat catchment.The source region of debris flow falls within the lower boundary of permafrost occurrence zone and lies below the 0℃isotherm during late spring and summer months.In Shishkat catchment the 0℃isotherm reaches above the debris flow source area during August and the glacier do not show any significant variations in velocity and surface elevation change.The debris flow source area is adjacent to the slow-moving rock glacier in Shishkat catchment while in Badswat catchment the debris flow initiated from the former glacier moraine.Both catchments are largely glacierized and thus sensitive to changes in climatic conditions and changes in the cryosphere response possess significant threats to the population downstream.Continuous monitoring of cryosphere-climate change in the region can contribute toward the improvement of disaster risk reduction and mitigation policies.

Cannabidiol-Mediated Sequestration of Alzheimer’s Amyloid-β Peptides in ADDL Oligomers

Cannabidiol (CBD), one of the most studied phytocannabinoids, is non-psychotropic and can induce protective effects on the central nervous system against acute and chronic brain injury. Interestingly, CBD inhibits processes relating to amyloid beta (Aβ)-induced neurotoxicity in mouse models of Alzheimer’s disease, though the detailed molecular mechanism underlying the CBD neurotoxicity modulation is not fully understood. In this study, using atomic force microscopy, we find that CBD promotes the aggregation of Aβ peptides, enhancing the formation of Aβ oligomers, also known as Aβ-derived diffusible ligands (ADDLs). The CBD-mediated sequestration of Aβ monomers in soluble ADDLs could reduce neurotoxicity. This study highlights a possible role of CBD in modulating the formation of ADDL aggregates and provides insight into potentially neuroprotective properties of CBD in Alzheimer’s disease.

Possible Relevance of the Allende Meteorite Conditions in Prebiotic Chemistry: An Insight into the Chondrules and Organic Compounds

The study of the mineral and organic content of the Allende meteorite is important for our understanding of the molecular evolution of the universe as well as the ancient Earth. Previous studies have characterized the magnetic minerals present in ordinary and carbonaceous chondrites, providing information on the evolution of magnetic fields. The interaction of organic compounds with magnetic minerals is a possible source of chemical diversity, which is crucial for molecular evolution. Carbon compounds in meteorites are of great scientific interest for a variety of reasons, such as their relevance to the origins of chirality in living organisms. This study presents the characterization of organic and mineral compounds in the Allende meteorite. The structural and physicochemical characterization of the Allende meteorite was accomplished through light microscopy, powder X-ray diffraction with complementary Rietveld refinement, Raman and infrared spectroscopy, mass spectrometry, scanning electron microscopy, and atomic force microscopy using magnetic signal methods to determine the complex structure and the interaction of organic compounds with magnetic Ni-Fe minerals. The presence of Liesegang-like patterns of chondrules in fragments of the Allende structure may also be relevant to understanding how the meteorite was formed. Other observations include the presence of magnetic materials and nanorod-like solids with relatively similar sizes as well as the heterogeneous distribution of carbon in chondrules. Signals observed in the Raman and infrared spectra resemble organic compounds such as carbon nanotubes and peptide-like molecules that have been previously reported in other meteorites, making the Mexican Allende meteorite a feasible sample for the study of the early Earth and exoplanetary bodies.

A Class of Potentials for Hyperbolic Transcendental Entire Maps

We identify a class of transcendental entire maps of finite order, of disjoint-type, satisfying the rapid derivative growth condition. Within this class, we show that there exist hyperbolic transcendental entire maps that generate a large class of potentials which intersect the so-called tame potentials and form a distinct class of potentials. The methods and techniques derived from the thermodynamic formalism are applied to these potentials for transcendental entire maps acting on some subset of the Julia set which is conjugated to the shift map over a code space with a countable alphabet endowed with the euclidean induced metric on the complex plane.

Two-Dimensional Continuous Model in Bimolecular Reactive Transport

In this work, a continuum 2D model is proposed to study the interaction at the interface of reactive transport processes in porous media. The analysis of the segregation produced by poor reactant homogenization at the poral scale is addressed by a parametric heuristic model that considers the relative gradient of the reacting species involved in the process. The micro inhomogeneities are incorporated by means of longitudinal and transversal mechanical dispersion coefficients. A two-dimensional continuous model for the bimolecular reactive transport is considered where modelling parameters are estimated numerically from experimental data. A competitive effect between segregation and dispersion is observed that is analyzed by means of numerical experiments. The two-dimensional model reproduces properly both the total mass of the product as well as its increase with the velocity of flow and the inhomogeneity of the advanced front. The methodology used is simple and fast, and the numerical results presented here indicate its effectiveness.

Determination of the Sound Absorption Capacity of Hydraulic Concrete Mixtures Added with Waste Tire Rubber

There are different types of pollutants that are harmful to the environment, including smog, chemicals that are dumped into rivers, scrap tires, etc. The latter have the particularity that it is not possible to recycle them to manufacture new tires. In the present work, hydraulic concrete plates added with waste tire rubber were manufactured to modify their sound absorption capacity. It was found that the rubber additions produce changes in the density of the material and in the sound absorption capacity. When the material is exposed to high-frequency sounds that correspond to high-pitched sounds, its absorption capacity increases. On the contrary, when the test frequency is low, that is, bass sounds, the sound absorption capacity decreases. The results obtained in this work suggest that the proposed mixtures are suitable for the possible manufacture of acoustic insulating shields.

Hidden Quantum Effect in General Relativity

If the Planck length is chosen as the natural length scale of the Universe, the Penrose-Carter diagram associated with the classical gravitational collapse of a thin spherical shell of massless matter reveals, beyond and in agreement with the claimed non locality of the horizon, a quantum nature of the whole process.

Words apart:Standardizing forestry terms and definitions across European biodiversity studies

Forest biodiversity studies conducted across Europe use a multitude of forestry terms,often inconsistently.This hinders the comparability across studies and makes the assessment of the impacts of forest management on biodiversity highly context-dependent.Recent attempts to standardize forestry and stand description terminology mostly used a top-down approach that did not account for the perspectives and approaches of forest biodiversity experts.This work aims to establish common standards for silvicultural and vegetation definitions,creating a shared conceptual framework for a consistent study on the effects of forest management on biodiversity.We have identified both strengths and weaknesses of the silvicultural and vegetation information provided in forest biodiversity studies.While quantitative data on forest biomass and dominant tree species are frequently included,information on silvicultural activities and vegetation composition is often lacking,shallow,or based on broad and heterogeneous classifications.We discuss the existing classifications and their use in European forest biodiversity studies through a novel bottom-up and top-driven review process,and ultimately propose a common framework.This will enhance the comparability of forest biodiversity studies in Europe,and puts the basis for effective implementation and monitoring of sustainable forest management policies.The standards here proposed are potentially adaptable and applicable to other geographical areas and could be extended to other forest interventions.