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Markov models have frequently been used in genetic sequence analysis. The number of parameters of a Markov model increases exponentially with model order, so it is often recommended that the order be chosen based on the size of data being modeled, lower orders for small and higher orders for large dataset sizes. Approaches based on model selection criterion have also been proposed. An important problem in microbiology and evolutionary biology is to decipher chimeric genomes of microbes, particularly, identify segments of distinct ancestries in genomes and reconstruct the plausible evolutionary scenarios that might have shaped the chimeric genomes in the microbial world. In this study, we assessed a Markov model-based segmentation method for its ability to detect compositionally disparate segments in chimeric sequence constructs as a function of model order, sequence length, and phylogenetic divergence. Our results show that the choice of Markov model order depends on both sequence size and composition. Higher order Markov models were found to be more effective in delineating sequence segments arising from closely related organisms in longer constructs; on the other hand, lower order Markov models were found to be more appropriate in delineating sequence segments arising from distantly related organisms in shorter constructs. These findings are important and timely, with broad implications in fields such as epidemiology that has to deal with the emergence of novel pathogenic chimeras that arise by foreign DNA acquisition, and ecology where chimeric structures may arise in various ecosystems, necessitating more robust approaches for their deconstruction and interpretation.

BackgroundCurrent models to study Alzheimer’s disease (AD) include cell cultures and animal models. Human diseases, however, are often poorly reproduced in animal models. Developing techniques to differentiate human brain cells from induced pluripotent stem cells (iPSCs) provides a novel approach to studying AD. Three-dimensional (3D) cultures to model AD are represented by organoids, neurospheroids, and scaffold-based cultures. Some AD-related phenotypes have been identified across 3D models [1]. However, to our knowledge, none of these studies could recapitulate several AD-related hallmarks in one single model and establish a temporal relation among them. Furthermore, to date, the transcriptomic features of these 3D models have not been compared with those of human AD brains. These data are, in our opinion, key to understanding the pertinency of these models for studying AD-related pathomechanisms over time.MethodsWe developed a 3D bioengineered model of iPSC-derived neural tissue that combines a porous scaffold composed of silk fibroin protein with an intercalated collagen hydrogel to support the growth of neurons and glial cells into complex and functional networks. This biomaterial scaffold, designed to match the mechanical properties of brain tissue, can support 3D neural cultures for an extended time without necrosis, a fundamental requisite for aging studies.We have optimized our protocol by seeding neural precursor cells (NPCs) into these scaffolds. NPC-derived cultures were generated from iPSC lines obtained from two subjects carrying the familial AD (FAD) APP London mutation, two well-studied control lines, and an isogenic control. Cultures were analyzed at 2 and 4.5 months.ResultsAn elevated Aβ42/40 ratio was detected in conditioned media from FAD cultures at both time points, as previously reported in 2D cultures derived from the same FAD lines. However, extracellular Aβ42 deposition and enhanced neuronal excitability were observed in FAD culture only at 4.5 months. The increased excitability of FAD cultures correlated with extracellular Aβ42 deposition but not with soluble Aβ42/40 ratio levels, as they were similar at both time points. These data suggest that extracellular Aβ deposition may trigger enhanced network activity. Notably, neuronal hyperexcitability has been described in AD patients early in the disease. Transcriptomic analysis revealed the deregulation of multiple gene sets in FAD samples. Notably, such alterations were similar to those observed in human AD brains in a large study that performed a co-expression meta-analysis of harmonized data from Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) across three independent cohorts.ConclusionsOur 3D tissue model supports the differentiation of healthy iPSC-derived cultures in a porous silk-collagen composite sponge with an optically clear central region. This design facilitates nutrient delivery to meet the metabolic demand of long-term cultures. These data provide evidence that our bioengineered model from patient-derived FAD iPSCs develops time-dependent AD-related phenotypes and establishes a temporal relation among them. Furthermore, FAD iPSC-derived neuronal tissue recapitulates transcriptomic features of AD patients. Thus, our bioengineered neural tissue represents a unique tool to model AD-related pathomechanisms over time, with several advantages compared to the existing models.

Transcriptomic analysis of the mammalian retinal pigment epithelium (RPE) aims to identify cellular networks that influence ocular development, maintenance, function, and disease. However, available evidence points to RPE cell heterogeneity in the native tissue, which adds complexity to transcriptomic analysis. Here, to assess cell heterogeneity, we performed single-cell RNA sequencing of RPE cells from two young adult male C57BL/6J mice. Following quality control to ensure robust transcript identification limited to cell singlets, we detected 13,858 transcripts among 2,667 and 2,846 RPE cells, respectively. Dimensional reduction by principal component analysis and uniform manifold approximation and projection revealed six distinct cell popu-lations. All clusters expressed transcripts typical of RPE cells; the smallest (C1, containing 1–2% of total cells) exhibited hallmarks of stem and/or progenitor cells. Placing C1–6 along a pseudotime axis suggested a relative decrease in melanogenesis and stem/progenitor gene expression, and a corresponding increase in visual cycle gene expression upon RPE maturation. K-means testing of all detected transcripts identified additional expression patterns that may advance understanding of RPE stem/pro-genitor cell maintenance and the evolution of cellular metabolic networks during development. This work provides new insights into the transcriptome of the mouse RPE and a baseline for identifying experimentally induced transcriptional changes in future studies of this tissue.

The application of a mixture of pesticides to the agricultural field may adversely affect the health of non-target organisms besides the target ones. In the present study, the antagonistic effect o...

Horizontal gene transfer (HGT) or lateral gene transfer (LGT), the exchange of genetic materials among organisms by means of other than parent-to-offspring (vertical) inheritance, plays a major role in prokaryotic genome evolution, facilitating adaptation of prokaryotes to changes in the environment. Phylogenetic methods have been frequently invoked to catalog horizontally acquired genes; however, these methods are often constrained by the paucity of sequenced genomes of close relatives (and even distant relatives) for a robust analysis and reliable inference. In this chapter, we describe a HGT quantification protocol that exploits the complementary strengths of the integrative segmentation and clustering method and the comparative genomics approach to identify foreign genes. Users can use this pipeline in combination with phylogenetic tree reconstruction to identify foreign genes that are supported by multiple lines of evidence, that is, atypical composition, atypical distribution in close relatives, and aberrant phylogenetic pattern.

Horizontal gene transfer (HGT) or lateral gene transfer (LGT), the exchange of genetic materials among organisms by means of other than parent-to-offspring (vertical) inheritance, plays a major role in prokaryotic genome evolution, facilitating adaptation of prokaryotes to changes in the environment. Phylogenetic methods have been frequently invoked to catalog horizontally acquired genes; however, these methods are often constrained by the paucity of sequenced genomes of close relatives (and even distant relatives) for a robust analysis and reliable inference. In this chapter, we describe a HGT quantification protocol that exploits the complementary strengths of the integrative segmentation and clustering method and the comparative genomics approach to identify foreign genes. Users can use this pipeline in combination with phylogenetic tree reconstruction to identify foreign genes that are supported by multiple lines of evidence, that is, atypical composition, atypical distribution in close relatives, and aberrant phylogenetic pattern.

Late-onset Alzheimer’s disease (AD; LOAD) is the most common human neurodegenerative disease, however, the availability and efficacy of disease-modifying interventions is severely lacking. Despite exceptional efforts to understand disease progression via legacy amyloidogenic transgene mouse models, focus on disease translation with innovative mouse strains that better model the complexity of human AD is required to accelerate the development of future treatment modalities. LOAD within the human population is a polygenic and environmentally influenced disease with many risk factors acting in concert to produce disease processes parallel to those often muted by the early and aggressive aggregate formation in popular mouse strains. In addition to extracellular deposits of amyloid plaques and inclusions of the microtubule-associated protein tau, AD is also defined by synaptic/neuronal loss, vascular deficits, and neuroinflammation. These underlying processes need to be better defined, how the disease progresses with age, and compared to human-relevant outcomes. To create more translatable mouse models, MODEL-AD (Model Organism Development and Evaluation for Late-onset AD) groups are identifying and integrating disease-relevant, humanized gene sequences from public databases beginning with APOEε4 and Trem2*R47H, two of the most powerful risk factors present in human LOAD populations. Mice expressing endogenous, humanized APOEε4 and Trem2*R47H gene sequences were extensively aged and assayed using a multi-disciplined phenotyping approach associated with and relative to human AD pathology. Robust analytical pipelines measured behavioral, transcriptomic, metabolic, and neuropathological phenotypes in cross-sectional cohorts for progression of disease hallmarks at all life stages. In vivo PET/MRI neuroimaging revealed regional alterations in glycolytic metabolism and vascular perfusion. Transcriptional profiling by RNA-Seq of brain hemispheres identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes. Similarly, age was the strongest determinant of behavioral change. In the absence of mouse amyloid plaque formation, many of the hallmarks of AD were not observed in this strain. However, as a sensitized baseline model with many additional alleles and environmental modifications already appended, the dataset from this initial MODEL-AD strain serves an important role in establishing the individual effects and interaction between two strong genetic risk factors for LOAD in a mouse host.

Late-onset Alzheimer’s disease (LOAD) is the most common human neurodegenerative disease. Legacy amyloidogenic mouse models have been useful for understanding disease progression, however in the face of failing human trials more focus on disease translation with new mouse strains that better model human Alzheimer’s disease (AD) is required. MODEL-AD (Model Organism Development and Evaluation for Late-onset AD) groups are identifying and integrating disease-relevant, humanized gene sequences from public databases to create more translatable mouse models for therapy development. Mice expressing strong genetic risk factors for LOAD, APOEe4 and Trem2*R47H, were extensively aged and assayed using a multi-disciplined phenotyping approach associated with and relative to human AD pathology. Behavioral, transcriptomic, metabolic, and neuropathological assays identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes in the absence of mouse amyloid plaque formation. These data provide an important, baseline understanding of the individual effects and interaction between two strong genetic risk factors for LOAD. These two alleles together form a sensitized, background strain (B6.APOE4.Trem2*R47H, which we have termed ‘LOAD1’) necessary to examine how important underlying risk factors interact with any subsequent genetic or environmental cues to drive pathology.

Industrial effluents reaching to the aquatic ecosystem is one of the major causes of environmental pollution. Heteropneustes fossilis, one of the most common edible fish if exposed to industrial effluents containing harmful substances may be a serious threat to human health. Therefore, the present study aimed to study the impact of fertilizer industry effluent on H. fossilis. Fish were exposed to treated and untreated fertilizer industry effluent (LC50 ​= ​2.35% v/v) for 96 ​h along with a proper control. The physico-chemical parameters such as turbidity, biological oxygen demand (BOD) and chemical oxygen demand (COD) of both treated and untreated fertilizer industry effluent were also analyzed as these parameters were not in range as per guidelines. Hematological parameters such as Red Blood cells (RBC), Haemoglobin (% Hb), Mean corpuscular volume (MCV), Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) showed significant decrease while there was sharp increase in differential leucocyte count (DLC) especially the neutrophil count. Distinct alteration in the architecture of gills, liver and kidney was observed besides significant increase in the level of lipid peroxidation (LPO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatases (ACP) and alkaline phosphatase (ALP) while the level of superoxide dismutase (SOD), catalase (CAT), glutathione s-transferase (GST) and reduced glutathione (GSH) activity decreased in metabolically active tissues like brain, liver, kidney, gills and muscles. The results indicate that industrial effluent has potent oxidative stress inducers on one hand and histoarchitectural and physiological altering contaminants on the other. This condition may adversely affect the health of aquatic organisms, the fish and ultimately the human beings.

Industrial revolution is a good indicator of economic development of a country; however, it can be a threat to the flora and fauna if the untreated effluent of an industry is discharged. The present study is aimed to assess the comparative toxicological impacts of treated and untreated industrial effluents on acetylcholinesterase (AChE) activity in Heteropneustes fossilis and Labeo rohita, the most common edible fishes having diverse characters which include differences in morphology, habitat, food and feeding, etc. The physico-chemical parameters such as pH, electrical conductivity (EC), alkalinity, hardness, dissolved oxygen (DO), phosphate, sulphate, nitrate, free ammonia, chloride, zinc, iron, chromium and potassium of both untreated and treated effluent from the fertilizer industry were also analyzed as these parameters were not in range as per ISO guidelines. The LC50 value for untreated effluent was 2.34% (v/v) and 0.80% (v/v) for 96 h in H. fossilis and L. rohita, respectively, while no mortality was recorded in the treated effluent. The AChE activity in both fish species was found to decline in metabolically responsive organs like brain, muscle and gills through exposure to sub-lethal concentrations (1/15th, 1/10th and 1/5th of LC50 value) of the untreated effluent for 96 h. Further studies on biochemical and molecular aspects may reveal the mechanism of their action.

C-lignin is a linear polymer of caffeyl alcohol, found in the seed coats of several exotic plant species, with promising properties for generation of carbon fibers and high value chemicals. In the ornamental plant Cleome hassleriana, guaiacyl (G) lignin is deposited in the seed coat for the first 6-12 days after pollination, after which G-lignin deposition ceases and C-lignin accumulates, providing an excellent model system to study C-lignin biosynthesis. We performed RNA sequencing of seed coats harvested at 2-day intervals throughout development. Bioinformatic analysis identified a complete set of lignin biosynthesis genes for Cleome. Transcript analysis coupled with kinetic analysis of recombinant enzymes in Escherichia coli revealed that the switch to C-lignin formation was accompanied by down-regulation of transcripts encoding functional caffeoyl CoA- and caffeic acid 3-O-methyltransferases (CCoAOMT and COMT) and a form of cinnamyl alcohol dehydrogenase (ChCAD4) with preference for coniferaldehyde as substrate, and up-regulation of a form of CAD (ChCAD5) with preference for caffealdehyde. Based on these analyses, blockage of lignin monomer methylation by down-regulation of both O-methyltransferases (OMTs) and methionine synthase (for provision of C1 units) appears to be the major factor in diversion of flux to C-lignin in the Cleome seed coat, although the change in CAD specificity also contributes based on the reduction of C-lignin levels in transgenic Cleome with down-regulation of ChCAD5. Structure modeling and mutational analysis identified amino acid residues important for the preference of ChCAD5 for caffealdehyde.

The acute toxicity of three formula grade pesticides namely, triazophos (an organophosphate, OP), deltamethrin (a pyrethroid) and combined pesticide (triazophos + deltamethrin) was determined in ea...

Multiple chromosomes in bacteria are designated as a larger primary chromosome (CI) and smaller accessory chromosomes (CII and CIII). Although previous studies examined multiple chromosomes in several bacterial species, the evolutionary mechanisms for the origin of CIIs still remain unclear. In this study, the four following hypotheses were tested. 1) CIIs exhibit lower sequence conservation and sequence divergence compared to their corresponding CIs across species of Proteobacteria. 2) The differential sequence divergence of CI and CII depends on pathogenic and non-pathogenic lifestyles. 3) CIIs harbor a higher level of horizontal gene transfers (HGTs) than CIs. 4) Orthologs located on CIIs experience less purifying selection than their corresponding orthologs on CIs. Results reveal a higher level of sequence conservation of CIs than the sequence conservation of CIIs. There is no significant difference in HGT estimates between CIs and CIIs. A majority of orthologous genes of CIs and CIIs experience purifying selection; however, genes on CIIs were significantly less constrained than the corresponding ones on CIs. This finding is true for both pathogenic and non-pathogenic bacteria, but the selective constraints for non-pathogenic bacteria are relatively less constrained. It was concluded that the differential selective constraint is a potent driving force for the rapid evolution of CII. Therefore, gene expression analysis at the transcriptome and proteome levels may shed light on the gene regulation mechanisms that might affect the sequence divergence between CI and CII.

Recurrent application of chemical pesticides in the agricultural fields have adverse impact on flora and fauna of soil ecosystem. Earthworms immensely contribute in increasing the fertility of soil. They may act as a bioindicator for the ecotoxicological analysis of pesticide induced soil pollution. Earthworms, Eudrilus eugeniae were exposed to different concentrations of pesticides chlorpyrifos (OP), cypermethrin (a pyrethroid) and their combination for 48 h by paper contact toxicity method. The LC50 for commercial grade of chlorpyrifos, cypermethrin and combined pesticides were determined as 0.165, 0.066 and 0.020 μg/cm2, respectively. To assess the sub-lethal effect of these pesticides, E. eugeniae were exposed to 5% and 10% of LC50 of the pesticides for 48 h. Variation in morpho-behavioural changes such as coiling, clitellar swelling, mucus release, bleeding and body fragmentation in earthworms were observed after exposure of both pesticides and their combination. Various biochemical estimations such as specific activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione -S-transferase (GST); levels of lipid peroxidation (LPO) and reduced glutathione (GSH) were carried out in different body segments. Significant changes in these stress markers were observed at low and high sub-acute concentration of pesticides exposed earthworm, Eudrilus eugeniae. Such changes indicate potential health risk to E. eugeniae if exposed to the high concentrations of these pesticides accumulated in soil. Keywords: AChE activity, Stress markers, Chlorpyrifos, Cypermethrin, Chlorpyrifos + Cypermethrin, Eudrilus eugeniae

Background: Late-onset Alzheimer’s Disease (AD) (LOAD) is the most common neurodegenerative disease. Despite extensive efforts to understand disease progression there are currently no approved disease modifying interventions to delay or reverse neurodegeneration caused by AD. Repeated failures in human trials, despite promising preclinical results in amyloidogenic mouse models, highlight the need for animals that better model human AD. MODEL-AD (Model organism development and evaluation for late-onset AD) are identifying and integrating disease-relevant, humanized gene sequences identified from public AD data repositories to create more translatable mouse models relevant to AD.Methods: Strong risk factors for LOAD, APOEε4 and Trem2*R47H, were expressed alone or in combination on a congenic C57BL/6J (B6) background, in cohorts of mice established on multiple sites and aged to between 4-24 months. A deep phenotyping approach was employed to assess phenotypes relative to human AD. Results: The LOAD1 mouse strain, expressing humanized APOEε4 and Trem2*R47H alleles, was designed to elucidate the disease state of animals expressing the two strongest genetic risk factors of LOAD at endogenous levels. Robust analytical pipelines measured behavioral, transcriptomic, metabolic, and neuropathological phenotypes in cross-sectional cohorts for progression of disease hallmarks at all life stages. In vivo PET/MRI neuroimaging revealed regional alterations in glycolytic metabolism and vascular perfusion. Transcriptional profiling by RNA-Seq of brain hemispheres identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes. Similarly, age, but not genotype, was the strongest determinant of behavioral change. In the absence of mouse amyloid plaque formation, many of the hallmarks of AD were not observed in this strain. However, these two alleles together form a sensitized, background strain which will serve as a platform for the characterization of additional genetic and environmental LOAD risk factors. Conclusions: Comprehensive phenotyping provided key insights into genetic and environmental effects aimed at modeling human disease, critical to understand the complex intergenic interactions and subsequent molecular signaling cascades. The data provided by these assays are important for understanding the relative contributions of subsequent risk factors amended to LOAD1.

Melatonin-loaded PLA nanoparticles are nowadays important in biological system for its biodegradable nature for targeted drug delivery. Hence, aim of the study is to note applicability and toxicity of Mel-PLA nanoparticles in osteoporosis. Different concentrations of melatonin and PLA were prepared by dissolving in dichloromethane (DCM). The final dried nanoparticles were used for structural analysis by SEM, TEM, and FTIR. Toxicity and immunological impact of nanoparticles were evaluated on rats: control and nanoparticle treated (n = 5/group) for 7 days. Afterward animals were sacrificed and blood, liver, and kidney were collected. A fraction of blood was processed for TLC, DLC, and %LC, and the remaining was centrifuged at 3000x g at 4 °C for 30 min. Separated plasma was used for measurements of IL-2, IL-6, TNF-α, IFN-γ, IL-1β, urea, creatinine, and BUN. Both plasma and tissue homogenates were used for AST, ALT, ACP, and ALP estimations. We noted significantly high (p 0.05) or unaffected (IFN-γ, ACP, and ALP). From our preliminary study, we may conclude that we have synthesized Mel-PLA nanoparticles and their effects were nontoxic to animals.

Graphical abstract, Highlights • The pesticides have adverse effect on the health of aquatic biota including fishes. • Comparative acute toxicity of both pesticides was determined in the present study. • Both pesticides have affected the behavioural activities of C. punctatus. • Alteration of behavioural patterns may be due to strong inhibition of AChE activity. • Triazophos (organophosphate) is more neurotoxic than deltamethrin (pyrethroid)., Pesticides are applied to control the pests indoor and outdoor; however, their remarkable amount reaches to the aquatic system through various routes like run-off, leaching, spray-drift, effluent from factories. These are reported to have negative metabolic impact on different non-target aquatic organisms like fishes. Thus, present study is aimed to evaluate the acute toxicity of two groups of pesticides, organophosphate and pyrethroid, namely triazophos and deltamethrin, respectively. The test was conducted for 96 h period in a freshwater teleost, Channa punctatus. The LC50 values for triazophos and deltamethrin after 96 h treatment was found to be 0.069 mg/L and 7.33 μg/L. The deltamethrin was found to be about ten times more toxic than triazophos to the fish. In treated fish, alterations in various behavioural patterns were observed with increasing concentrations of both the pesticides as compared to control. Further, tissue specific as well as dose dependent inhibition in the acetylcholinesterase (AChE, EC 3.1.1.7) activity was found in brain, muscle and gills in Channa punctatus exposed to both the insecticides. However, the effect was more pronounced in triazophos treated fishes than the deltamethrin. A futuristic approach on biochemical and molecular studies may throw light on the mechanism of action of these pesticides.

In the present study, the acute toxicity of chlorpyrifos (an organophosphate, OP) and cypermethrin (a pyrethroid) pesticides was estimated for 96 h in Heteropneustes fossilis. The LC50 for ...

In the present study, the crude ethanol extracts of leaves of Calotropis procera and Annona squamosa have been screened for their insecticidal activities against Musca domestica (a housefly). The third instar larvae of housefly were exposed with two different concentrations of both the extracts for 48 h by dipping method. The effect of extract exposure was studied on the activities of alkaline phosphatase, acid phosphatase, glutamate oxaloacetate transaminases and glutamate pyruvate transaminase. The enzyme inhibitory effect of leaf extract of C. procera was more pronounced than that of A. squamosa. The data indicate that these extracts may be used as the probable candidates for the development of bioinsecticides as safer and economic alternatives to the synthetic insecticides to control the M. domestica population.

Industrijska revolucija je dobar pokazatelj gospodarskog razvoja države, međutim, može biti i prijetnja za floru i faunu ako se u prirodu ispuštaju nepročišćene otpadne vode industrije. Cilj ovog istraživanja je procijeniti toksikološke učinke pročišćenih i nepročišćenih industrijskih otpadnih voda na aktivnost acetilkolinesteraze (AChE) kod Heteropneustes fossilis i Labeo rohita, jestivih riba različitih karakteristika poput razlika u morfologiji, staništu, ishrani, itd. Analizirani su fizikalno-kemijski parametri otpadnih voda kao što su: pH, električna vodljivost (EC), alkalitet, tvrdoća, otopljeni kisik (DO), fosfati, sulfati, nitrati, slobodni amonijak, kloridi, cink, željezo, krom i kalij jer ti parametri nisu bili u rasponu prema ISO smjernicama. Vrijednost LC50 za nepročišćene vode iznosila je 2,34% (v/v) i 0,80% (v/v) tijekom 96 h kod H. fossilis i L. rohita. Smrtnost riba u obrađenim otpadnim vodama nije zabilježena. Tijekom izlaganja subletalnim koncentracijama (1/15, 1/(10 ), 1/5 LC50) kod obje vrste riba aktivnost AChE u metabolički osjetljivim organima (mozak, mišići, škrge) je bila smanjena. Daljnja istraživanja biokemijskih i molekularnih pokazatelja mogla bi približiti mehanizam njihovog djelovanja., Industrial revolution is a good indicator of economic development of a country; however, it can be a threat to the flora and fauna if the untreated effluent of an industry is discharged. The present study is aimed to assess the comparative toxicological impacts of treated and untreated industrial effluents on acetylcholinesterase (AChE) activity in Heteropneustes fossilisand Labeo rohita, the most common edible fishes having diverse characters which include differences in morphology, habitat, food and feeding, etc. The physico-chemical parameters such as pH, electrical conductivity (EC), alkalinity, hardness, dissolved oxygen (DO), phosphate, sulphate, nitrate, free ammonia, chloride, zinc, iron, chromium and potassium of both untreated and treated effluent from the fertilizer industry were also analyzed as these parameters were not in range as per ISO guidelines. The LC50 value for untreated effluent was 2.34% (v/v) and 0.80% (v/v) for 96 h in H. fossilis and L. rohita, respectively, while no mortality was recorded in the treated effluent. The AChE activity in both fish species was found to decline in metabolically responsive organs like brain, muscle and gills through exposure to sub-lethal concentrations (1/15th, 1/10th and 1/5th of LC50 value) of the untreated effluent for 96 h. Further studies on biochemical and molecular aspects may reveal the mechanism of their action.

Graphical abstract, Highlights • In the present study, co-exposed administered pesticides induced a higher level of toxicity to Eudrilus eugeniae. • Statistically significant changes were observed after 48 h exposure of CPF, cypermethrin and combination of the two, reflects the synergistic cumulative impact on the AChE and oxidative stress parameters in dose- dependent manner. • Significant changes were observed in different body segments (Pre-Clitellar, Clitellar and Post-Clitellar) of earthworm in tissue specific pattern., Recurrent application of chemical pesticides in the agricultural fields have adverse impact on flora and fauna of soil ecosystem. Earthworms immensely contribute in increasing the fertility of soil. They may act as a bioindicator for the ecotoxicological analysis of pesticide induced soil pollution. Earthworms, Eudrilus eugeniae were exposed to different concentrations of pesticides chlorpyrifos (OP), cypermethrin (a pyrethroid) and their combination for 48 h by paper contact toxicity method. The LC50 for commercial grade of chlorpyrifos, cypermethrin and combined pesticides were determined as 0.165, 0.066 and 0.020 μg/cm2, respectively. To assess the sub-lethal effect of these pesticides, E. eugeniae were exposed to 5% and 10% of LC50 of the pesticides for 48 h. Variation in morpho-behavioural changes such as coiling, clitellar swelling, mucus release, bleeding and body fragmentation in earthworms were observed after exposure of both pesticides and their combination. Various biochemical estimations such as specific activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione -S-transferase (GST); levels of lipid peroxidation (LPO) and reduced glutathione (GSH) were carried out in different body segments. Significant changes in these stress markers were observed at low and high sub-acute concentration of pesticides exposed earthworm, Eudrilus eugeniae. Such changes indicate potential health risk to E. eugeniae if exposed to the high concentrations of these pesticides accumulated in soil.

Alzheimer’s Disease (AD) is characterized by multiple clinical phenotypes and molecular signatures at different stages of the disease and aging is the major risk factor for sporadic AD. Aging and AD are linked at molecular, cellular and systems level with commonalities in inflammation and associated immune response in the brain. Mouse models of AD were developed that mimic various aspects of aging-associated neurodegeneration and inflammation. Research in mouse models of AD showed that drugs and treatments designed for AD can decelerate aging phenotypes suggesting efficient utilization of these models in aging research. We analyzed RNA-Seq transcriptomic data from transgenic mouse models of familial AD (APP/PS1 and 5XFAD) and knock-in mouse models of late-onset AD (APOE and TREM2) at the ages between 4-months and 24-months. The number of differentially expressed genes between transgenic/knock-in and WT mice increased by age in all mouse models. Gene set enrichment analysis identified metabolic pathways, including oxidative phosphorylation, altered in an age and genotype related manner in the brain of APP/PS1 and 5XFAD mice that recapitulate major features of amyloid pathology. Immunity related pathways were enriched in APOE4 model carrying Trem2*R47H mutation at >12 months-old. We also mapped the transcriptional signatures to co-expression gene modules of human LOAD from the AMP-AD consortium and observed correlations specific to each mouse model. Our study provides a detailed view of how the aging interacts with AD-relevant pathologies at the transcriptome level and demonstrates potential translational relevance of the AD mouse models in the context of human aging.

Identification of horizontal gene transfers (HGTs) has primarily relied on phylogenetic tree based methods, which require a rich sampling of sequenced genomes to ensure a reliable inference. Because the success of phylogenetic approaches depends on the breadth and depth of the database, researchers usually apply stringent filters to detect only the most likely gene transfers in the genomes of interest. One such study focused on a highly conservative estimate of trans-domain gene transfers in the extremophile eukaryote, Galdieria sulphuraria (Galdieri) Merola (Rhodophyta), by applying multiple filters in their phylogenetic pipeline. This led to the identification of 75 inter-domain acquisitions from Bacteria or Archaea. Because of the evolutionary, ecological, and potential biotechnological significance of foreign genes in algae, alternative approaches and pipelines complementing phylogenetics are needed for a more comprehensive assessment of HGT. We present here a novel pipeline that uncovered 17 novel foreign genes of prokaryotic origin in G. sulphuraria, results that are supported by multiple lines of evidence including composition-based, comparative data, and phylogenetics. These genes encode a variety of potentially adaptive functions, from metabolite transport to DNA repair.

The importance of the earthworms in the agricultural practices is well known. The increasing applications of pesticides and chemicals in the agricultural farms have adversely influenced the flora and fauna of the soil. Earthworms which immensely contribute in increasing the quality and fertility of agricultural soil are reported be worst hit organisms under such conditions. Recent reports have indicated growing interests among researchers to explore biochemical and molecular markers as indicators of accumulation of pollutants in the soil in general and pesticides in particular. The varying levels of several biomolecules in different parts of the earthworm have been reported which are indicative of sensitivity of the organisms to different xenobiotics. However, the existing information lacks the literature displaying stock of information regarding the impact of pesticides on the levels of some key enzymes regulating many crucial functions in the earthworm at one place. Keeping in view this issue, it was envisaged to bring out a mini review which illustrates updated information available on the impact of pesticides on the activities of certain key enzymes reported to be responsible for catalysing metabolic pathways concerning the neurotransmission system, energy metabolism, oxidative stress and amino acids metabolism in different body parts of the earthworms, a prospective bioindicators of pesticides contamination in the soil.