Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron disease.There is currently no cure and approximately 90% of cases are sporadic.ALS shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile dementia.ALS and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

Development and postnatal neurogenesis in the retina: a comparison between altricial and precocial bird species

The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller glia.The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very low.This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal neurons.Therefore,regenerative response after injury occurs with low efficiency in the precocial avian retina.In contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching.In particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer.Therefore,stem cell niches are very active in the retina of altricial birds.Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.

The dual role of necrostatin-1 in Parkinson’s disease models

Neuronal cell death is the main hallmark of Parkinson’s disease(PD).It is an irreversible process promoted by neurotoxins and/or genetic mutations.Different types of cell death have been associated with PD.The mechanisms by which neurons decide to specific type of cell death remain elusive.However,it is well known that cell death can be either programmed or not.Apoptosis is a programmed cell death that involves the release of cytochrome c from damaged mitochondria to cytosol and the activation of caspases leading to nuclear condensation.Necrosis is a caspase-independent cell death characterized by a gain in cell volume,rupture of plasma membrane and leak of cell contents,inflammation,and affects neighbouring cells.It was classified as a nonprogrammed cell death,but there are types of necrotic death triggered by a protein activation cascade,including necroptosis.

Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into osteoblasts.Interestingly,osteocalcin(associated to energy metabolism)was upregulated.Vascular endothelial growth factor an expression and low-density lipoprotein receptor related protein 5/6/dickkopf Wnt signaling pathway inhibitor 1(associated to Wnt/β-catenin pathway activation)increased in osteoblasts.Yet,they decreased in adipocytes after CH treatments,mainly with the longest hypoxia times.However,the same CH treatments increased the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio in both cell types.An increase in total bone mineral density was observed in elderly people exposed to CH,but not in specific regions.The percentage of fat did not vary between groups.CONCLUSION CH may have positive effects on bone health in the elderly,due to its possible inhibitory effect on bone resorption,by increasing the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio.

A Novel Ensemble Learning System for Cyberattack Classification

Nowadays,IT systems rely mainly on artificial intelligence(AI)algorithms to process data.AI is generally used to extract knowledge from stored information and,depending on the nature of data,it may be necessary to apply different AI algorithms.In this article,a novel perspective on the use of AI to ensure the cybersecurity through the study of network traffic is presented.This is done through the construction of a two-stage cyberattack classification ensemble model addressing class imbalance following a one-vs-rest(OvR)approach.With the growing trend of cyberattacks,it is essential to implement techniques that ensure legitimate access to information.To address this issue,this work proposes a network traffic classification system for different categories based on several AI techniques.In the first task,binary models are generated to clearly differentiate each type of traffic from the rest.With binary models generated,an ensemble model is developed in two phases,which allows the separation of legitimate and illegitimate traffic(phase 1)while also identifying the type of illegitimate traffic(phase 2).In this way,the proposed system allows a complete multiclass classification of network traffic.The estimation of global performance is done using a modern dataset(UNSW-NB15),evaluated using two approaches and compared with other state-of-art works.Our proposal,based on the construction of a two-step model,reaches an F1 of 0.912 for the first level of binary classification and 0.7754 for the multiclass classification.These results show that the proposed system outperforms other state-of-the-art approaches(+0.75%and+3.54%for binary and multiclass classification,respectively)in terms of F1,as demon-strated through comparison together with other relevant classification metrics.

Avian malaria,haematocrit,and body condition in invasive wetland passerines settled in southwestern Spain

Avian malaria and related haemosporidian parasites can negatively impact fitness in many songbirds.Research on the malaria infection and its physiological costs on their avian hosts is heavily skewed toward native passerines,with exotic species underrepresented.However,introduced species may carry on and spread new pathogens to native species,and play a role on parasite transmission cycle in invaded bird communities as pathogen reservoir.Here,we molecularly assess the prevalence and diversity of haemosporidian parasites in three introduced wetland passerines(the Red Avadavat Amandava amandava,the Yellow-crowned Bishop Euplectes afer,and the Common Waxbill Estrilda astrild)captured during the same season in southwestern Spain.We also explored the relation between parasite infection,body condition,haematocrit,and uropygial gland volume.We detected an overall parasite prevalence of 3.55%,where Common Waxbills showed higher prevalence(6.94%)than Red Avadavats(1.51%).None Yellow-crowned Bishops were infected with haemosporidians.Almost 60%of infections were caused by Leucocytozoon,and about 40%by Plasmodium.We identified four unique lineages of Plasmodium and three of Leucocytozoon.Moreover,91%of the identified host-parasite interactions represented new host records for these haemosporidian parasites.Parasite infection was not related to body condition,haematocrit,and uropygial gland volume of the wetland passerines.Haematocrit values varied seasonally among bird species.Additionally,haematocrit was positively related to body condition in the Yellow-crowned Bishops,but not in the other species.Red Avadavats had higher haematocrit levels than Yellow-crowned Bishops,whereas Common Waxbills showed the lower haematocrit values.The uropygial gland volume was positively correlated with body condition in all bird species.Common Waxbills showed higher uropygial gland volumes related to their body size than birds from other two species.These outcomes highlight the importance of exotic invasive species in the transmission dynamics of haemosporidian parasites.

三维打印β-TCP颌骨修复支架的生物学评价

目的:探讨三维打印β-磷酸三钙(β-Tricalcium Phosphate,β-TCP)颌骨修复支架的生物学特性及体内成骨作用。方法:采用自动注浆技术制作β-TCP支架,将前成骨细胞(MC35T3-E1)接种在支架上,扫描电镜(SEM)观察材料结构与细胞黏附,CCK-8法检测细胞增殖,ALP法检测碱性磷酸酶活性。将2种支架复合重组人骨形成蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)后植入大鼠体内,发泡法制作的β-TCP支架为对照组,6周后取材行组织学观察。结果:三维打印支架具有规则多孔的立体结构,适合细胞黏附,且增殖及分化能力均高于对照组(P<0.05)。组织学显示复合rhBMP-2后三维打印支架新骨生成量高于发泡法制作的β-TCP支架(P<0.05)。结论:三维打印TCP支架生物相容性良好,复合rhBMP-2后可异位成骨。

The paradigm of protein acetylation in Parkinson's disease

Acetylation is a post-translational modification that is regulated by two antagonistic enzymes,histone acetyltransferases(HATs)and histone deacetylases(HDACs).HATs transfer the acetyl group from acetyl-CoA to lysine residues of proteins while HDACs remove it(Yakhine-Diop et al.,2018b).The impairment of HAT or HDAC activity elicits changes in the protein acetylation status which disturb several cellular processes,among others,gene expression,autophagy etc.,leading finally to cell death.Both enzymes are associated with Parkinson’s disease(PD)pathogenesis.In dopaminergic cells,neurotoxins provoke apoptotic cell death by increasing histone acetylation levels.While paraquat(Song et al.,2011)and rotenone(Feng et al.,2015)reduce HDAC activity,dieldrin(Song et al.,2010)enhances HAT activity.However in vivo,paraquat-induced upregulation ofα-synuclein triggers histone hypoacetylation.

The role of Islet-1 in cell specification,differentiation,and maintenance of phenotypes in the vertebrate neural retina

Many blinding diseases,such as retinitis pigmentosa,age-related macular degeneration,and glaucoma involve the permanent loss of retinal neurons,especially photoreceptors or the centrally projecting retinal ganglion cells.Stem cells have been proposed as a potential source of cells for neuronal transplantation.

The first meteorological observations at a tropical high elevation site:Antisana,1846

Antisana is a stratovolcano with an associated glacier located in the Ecuadorian Andes. Dr Aguirre made meteorological readings every day, at every hour from sunrise to sunset, from December 1845 to December 1846, at Antisana using a meteorological station at 4060 mamsl （meters above mean sea level）. Unfortunately, only the monthly average data have been preserved. These meteorological data are here studied and compared with the closest modern stations for monthly values of temperature, rainfall, and pressure. According to these comparisons, the year 1846 was rainy and cold in comparison with the current climate. Moreover, these observations have been useful to help resolve a debate about a possible E1Nifio event in 1846 with the high precipitation in Antisana and Quito in 1846 discarding the occurrence of an E1 Nifio event. The probable occurrence of a La Nifia event is discussed. These data are the earliest known systematic instrumental meteorological observations taken at above 4000 mamsl.

Mapping the Genetic Diversity of Castanea sativa: Exploiting Spatial Analysis for Biogeography and Conservation Studies

The current distribution of forest tree species is a result of natural or human mediated historical and contemporary processes. Knowledge of the spatial distribution of the diversity and divergence of populations is crucial for managing and conserving genetic resources in forest tree species. By combining tools from population genetics, landscape ecology and spatial statistics, landscape genetics thus represents a powerful method for evaluating the geographic patterns of genetic resources at the population level. In this study, we explore the possibility of combining genetic diversity data, spatial statistic tools and GIS technologies to map the genetic divergence and diversity of 31 Castanea sativa populations collected in Spain, Italy, Greece, and Turkey. The IDW technique was used to interpolate the diversity values and divergence indices as expected hetereozygosity (He), allelic richness (Rs), private allelic richness (PRs), and membership values (Q) of each population to different clusters. Genetic diversity maps and a synthetic map of the spatial genetic structure of European chestnut populations were produced. Spatial coincidences between landscape elements and statistically significant genetic discontinuities between populations were investigated. Evidence is provided of the significance of cartographic outputs produced in the study and on their usefulness in managing genetic resources.

Low-cost disordered carbons for Li/S batteries： A high- performance carbon with dual porosity derived from cherry pits

A micro- and mesoporous carbon obtained from cherry pit waste and activated with HBPO4 acid has been studied as the sulfur host for Li/S batteries. The carbon has a high specific surface area of 1,662 m2·g-1 （SBET） and micropore and mesopore volumes of 0.57 and 0.40 cm3·g-1, respectively. The S/C composite, with a sulfur content of 57% deposited by the disproportionate reaction of a SaO2- solution in an acid medium without an additional heating step above the S melting point, delivers an initial specific capacity of 1,148 mah·g-1 at a current of C/16. It also has a high capacity retention of 915 mAh·g-1 after 100 cycles and a Coulombic efficiency close to 100%. The good performance of the composite was also observed under higher current rates and long-term cycling tests. The capacities delivered by the cell after 200 cycles were 707 and 410 mAh·g-1 at C/2 and 1C （1C = 1,675 mA·g-1）, respectively, maintaining the high Coulombic efficiency. The overall electrochemical response of this carbon as the sulfur matrix is among the best reported so far among the other biomass-derived carbons, probably because of the micro- and mesopore system formed upon activation.

Evidence on antimicrobial activity of essential oils and herbal extracts against Yersinia enterocolitica - A review

Yersinia enterocolitica is a very common food-borne pathogen which causes gastrointestinal infections (yersiniosis) in humans and a wide array of animals (e.g.cattle,deer,pigs,and birds).Due to the increasing interest in innovative plant-based substances as common food preservatives,several essential oils and herbal extracts have been investigated deeply that resulted in the emergence of novel anti-Yersinia additives.We reviewed relevant work done by 53 researchers covering literature from the year 2002 to till date.Some species such as Origanum vulgare ,Rosmarinus officinalis ,Thymus vulgaris ,Ocimum basilicum have been extensively investigated and identified that 1,8-cineole,linalool and γ-terpinene as compounds found in the essential oils of these plants have anti-Yersinia activity active food packaging agents.In the same direction,some promising results have been mentioned about the herbal extracts of Murrya koenigii ,Tanacetum vulgare and Tanacetum balsamita,but further investigations are needed for their sustainable implications.According to hierarchical cluster analysis,we found that Lamiaceae and Lauracea as the most significant families with anti-Yersinia activity.Towards the end,we proposed new research trends in order to enhance a global knowledge about the use of natural products against Y.enterocolitica .

Resource manipulation reveals flexible allocation rules to growth and reproduction in a Mediterranean evergreen oak

Aims In plants,resource allocation to growth and reproduction may depart from trade-off expectations if(i)investment in growth and reproduction relies on different resource pools,(ii)allocation to reproduction is dependent upon reaching some growth threshold or(iii)reproduction is developmentally linked to growth,both functions relying on the same resource pool.We examined the effects of enhanced resource level on patterns of resource allocation to growth and reproduction in holm oak(Quercus ilex sbsp.ballota),a Mediterranean evergreen tree.Methods In the experimental year(2003),we manipulated the amount of soil nutrients in autumn(to increase nutrient uptake during shoot elongation in the following spring)and soil water in summer(to increase water uptake during acorn growth).Indicators of growth and male and female reproduction were estimated in the preexperimental(2002),experimental(2003)and post-experimental(2004)years.Important Findings Fertilized trees produced significantly longer shoots,but the number of female flowers per shoot was not affected by treatments.The production of male catkins was also enhanced by fertilization.Irrigation did not affect the production of female flowers or abortion rates.Growth and female reproduction showed no consistent relationship in untreated trees,but resource addition elicited a growth-female reproduction trade-off in the experimental year.The sign of this significant relationship changed in the post-experimental year,indicating the existence of lagged effects of resource manipulation on acorn production.Overall,patterns of allocation to growth and reproduction varied as a function of sex,resource availability and year,a result consistent with extreme allocational plasticity in holm oak.

Classification of Some Nilpotent Class of Leibniz Superalgebras

The aim of this work is to present the description of Leibniz superalgebras up to isomorphism with characteristic sequence （n｜m - 1, 1） and nilindex n ＋ m.

A Characterization of Linearly Semisimple Groups

Let G -- Spec A be an affine K-group scheme and A = （w ∈ A＊ ： dimK A＊-w 〈 ∞, dimK w. A＊ 〈 ∞}. Let （-, -） ： A＊ × A → K, （w, w） ：= tr（ww）, be the trace form. We prove that G is linearly reductive if and only if the trace form is non-degenerate on A＊.

Mechanisms oftoothdamageand Paranthropus dietary reconstruction

According to the current fossil record,the extinct hominin genus Paranthropus and the genus Homo both first appeared~2.7 million years ago.Despite this similarity in geological age,Paranthropus evolved enormous postcanine teeth with very thick enamel while Homo evolved smaller teeth.Results from contact mechanics mode ls derived from mu ltiple scales of tooth damage(microwear,macrowear,and fracture)are reviewed to examine this evolutionary divergence and the role that diet may have played in it.Each scale of investigation reveals different kinds of evide nce that can be combined into a more complete picture of hominin diet and feeding beh aviour.Micr owear reveals information about recent feeding events,while macrowear and fr acture record longer-term trends.The synthesis of all three levels of evidence exposes significant dietary diversity,not only between these two hominin genera but within them as well.Within Paranthropus,the eastern and southern African species(P.boisei and P.robustus,respectively)were morphologically similar but appear to have been functionally different.Whereas P.boisei apparently used its teeth to consume large quantities of low qua lity vegetation,P.robustus had a more varied diet that included harder objects,possibly items such as seeds,nuts,or underground storage organs.

Diversity and host assemblage of avian haemosporidians in different terrestrial ecoregions of Peru

Characterizing the diversity and structure of host–parasite communities is crucial to understandingtheir eco-evolutionary dynamics.Malaria and related haemosporidian parasites are responsible forfitness loss and mortality in bird species worldwide.However,despite exhibiting the greatest ornithologicalbiodiversity,avian haemosporidians from Neotropical regions are quite unexplored.Here,we analyze the genetic diversity of bird haemosporidian parasites(Plasmodium andHaemoproteus)in 1,336 individuals belonging to 206 bird species to explore for differences in diversityof parasite lineages and bird species across 5 well-differentiated Peruvian ecoregions.Wedetected 70 different haemosporidian lineages infecting 74 bird species.We showed that 25 out ofthe 70 haplotypes had not been previously recorded.Moreover,we also identified 81 new host–parasite interactions representing new host records for these haemosporidian parasites.Our outcomesrevealed that the effective diversity(as well as the richness,abundance,and Shannon–Weaver index)for both birds and parasite lineages was higher in Amazon basin ecoregions.Furthermore,we also showed that ecoregions with greater diversity of bird species also had highparasite richness,hence suggesting that host community is crucial in explaining parasite richness.Generalist parasites were found in ecoregions with lower bird diversity,implying that the abundanceand richness of hosts may shape the exploitation strategy followed by haemosporidian parasites.These outcomes reveal that Neotropical region is a major reservoir of unidentified haemosporidianlineages.Further studies analyzing host distribution and specificity of these parasites inthe tropics will provide important knowledge about phylogenetic relationships,phylogeography,and patterns of evolution and distribution of haemosporidian parasites.