Biology subjects

Khan, A.

Publications and source records attributed to Khan, A..

At least 127 records · Page 7Linked to original sources

bioRxiv2023

Carbohydrate distribution via SWEET17 is critical for Arabidopsis inflorescence branching under drought

Sugars Will Eventually be Exported Transporters (SWEETs) are the most recently discovered family of plant sugar transporters. Functioning as uniporters and thus facilitating the diffusion of sugars across cell membranes, SWEETs play an important role in various physiological processes such as abiotic stress adaptation. AtSWEET17, a vacuolar fructose facilitator, was shown to be involved in the modulation of the root system during drought. Moreover, overexpression of a homolog from apple results in increased drought tolerance of tomato plants. Therefore, SWEET17 appears to be essential for the plants drought response. Nevertheless, the role and function of SWEET17 in aboveground tissues under drought stress to date remains enigmatic. By combining gene expression analysis with analysis of the sugar profile of various aboveground tissues, we uncovered a putative role of SWEET17 in the carbohydrate supply, and thus cauline branch emergence and growth, particularly during periods of carbon limitation as occurs under drought stress. SWEET17 thereby being of critical importance for maintaining efficient reproduction under drought stress. HighlightThe fructose transporter SWEET17 supports shoot branching by increasing mobilization of carbohydrates from vacuoles to supply the newly forming inflorescence branch, thereby maintaining efficient reproduction under drought stress.

plant biology↗

bioRxiv2022

Inflammatory Synovial Fibroblast Culture in 3D Systems: A Comparative Transcriptomic and Functional Study.

Inflammation is essential for fighting infections and initiating tissue repair, but chronic unresolved inflammation underlies many conditions, like cancer and autoimmune disorders. While dysregulated immune responses drive chronic inflammation, non-immune stromal cells such as fibroblasts also play a critical role. Targeting fibroblasts could enable tissue-specific therapies while avoiding the systemic suppression caused by current drugs. However, traditional culture systems often induce artificial behaviours, limiting progress. Here, we demonstrate the importance of the mechanical properties of the 3D culture environments in fibroblast-mediated inflammation in the context of Rheumatoid Arthritis, a chronic disease that primarily affects joints but also impacts other organs. We isolated fibroblasts from healthy and arthritic mouse joints and expanded them on 2D tissue culture plastic, stiff fibronectin-coated scaffolds, or soft pegylated fibronectin-based hydrogels. Our results highlight the plasticity of fibroblasts, with microenvironmental cues driving inflammatory or regulatory phenotypes. The 3D environment offered by fibronectin-coated scaffolds restored inflammatory gene expression profiles that were lost in flat cultures, while the more physiologically relevant soft hydrogels shifted fibroblasts toward a resolving phenotype. These findings underscore the importance of the 3D environment in modulating fibroblast behaviour and establish a foundation for bioengineered systems that better model disease or guide therapeutic strategies.

bioengineering↗

bioRxiv2022

The vacuolar sugar transporter EARLY RESPONSE TO DEHYDRATION 6-LIKE4 regulates fructose signaling and plant growth

Regulation of intracellular sugar homeostasis is maintained by regulation of activities of sugar import and export proteins residing at the tonoplast. We show here that the EARLY RESPONSE TO DEHYDRATION6-LIKE4 protein, being the closest homolog to the proton/glucose symporter ERDL6, resides in the vacuolar membrane. Gene expression and subcellular fractionation studies indicated that ERDL4 was involved in fructose allocation across the tonoplast. Overexpression of ERDL4 increased total sugar levels in leaves, due to a concomitantly induced stimulation of TST2 expression, coding for the major vacuolar sugar loader. This conclusion is supported by the finding that tst1-2 knockout lines overexpressing ERDL4 lack increased cellular sugar levels. ERDL4 activity contributing to the coordination of cellular sugar homeostasis is also indicated by two further observations. Firstly, ERDL4 and TST genes exhibit an opposite regulation during a diurnal rhythm, and secondly, the ERDL4 gene is markedly expressed during cold acclimation representing a situation in which TST activity needs to be upregulated. Moreover, ERDL4-overexpressing plants show larger size of rosettes and roots, a delayed flowering time and increased total seed yield. Consistently, erdl4 knock-out plants show impaired cold acclimation and freezing tolerance along with reduced plant biomass. In summary, we show that modification of cytosolic fructose levels influences plant organ development and stress tolerance. One sentence summaryThe activity of the vacuolar sugar porter ERDL4 is important for balanced cytosolic monosaccharide homeostasis and influences plant growth and cold response in Arabidopsis The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors is: Benjamin Pommerrenig (pommerre@bio.uni-kl.de).

plant biology↗

bioRxiv2022

Completing the TRB family: newly characterized members show ancient evolutionary origins and distinct localization, yet similar interactions

Telomere repeat binding proteins (TRBs) belong to a family of proteins possessing a Myb-like domain which binds to telomeric repeats. Three members of this family (TRB1, TRB2, TRB3) from Arabidopsis thaliana have already been described as associated with terminal telomeric repeats (telomeres) or short interstitial telomeric repeats in gene promoters (telo-boxes). They are also known to interact with several protein complexes: telomerase, Polycomb repressive complex 2 (PRC2) E(z) subunits and the PEAT complex (PWOs-EPCRs-ARIDs-TRBs). Here we characterize two novel members of the TRB family (TRB4 and TRB5). Our wide phylogenetic analyses have shown that TRB proteins evolved in the plant kingdom after the transition to a terrestrial habitat in Streptophyta, and consequently TRBs diversified in seed plants. TRB4-5 share common TRB motifs while differing in several others and seem to have an earlier phylogenetic origin than TRB1-3. Their common Myb-like domains bind long arrays of telomeric repeats in vitro, and we have determined the minimal recognition motif of all TRBs as one telo-box. Our data indicate that despite the distinct localization patterns of TRB1-3 and TRB4-5 in situ, all members of TRB family mutually interact and also bind to telomerase/PRC2/PEAT complexes. Additionally, we have detected novel interactions between TRB4-5 and EMF2 and VRN2, which are Su(z)12 subunits of PRC2.

plant biology↗

bioRxiv2022

Cell-subtype specific effects of genetic variation in the aging and Alzheimer cortex

The relationship between genetic variation and gene expression in individual brain cell types and subtypes has remained elusive. Here, we generated single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of 424 individuals of advanced age; analyzing 1.5 million nuclear transcriptomes, we assessed the effect of genetic variants on RNA expression in cis (cis-eQTL) for 7 cell types and 81 cell subtypes. This effort identified 10,004 eGenes at the cell type level and 8,138 eGenes at the cell subtype level. Many eGenes are only detected within cell subtypes. A new variant influences APOE expression only in microglia and is associated with greater cerebral amyloid angiopathy but not Alzheimer pathology, accounting for the effect of APOE{varepsilon}4, providing mechanistic insights into both pathologies. While eQTLs are readily detected, only a TMEM106B variant robustly affects the proportion of cell subtypes. Integration of these results with GWAS highlighted the targeted cell type and likely causal gene within susceptibility loci for Alzheimers, Parkinsons, schizophrenia, and educational attainment.

genomics↗

bioRxiv2022

Possible Self-awareness in Wild Adelie Penguins Pygoscelis adeliae

This preliminary study, conducted in January-February 2020, investigates the potential presence of self-awareness in a population of wild Adelie penguins on the Dogs Neck Ice Shelf and on Svenner Island in East Antarctica. It is based on the responses and reactions of individual penguins to images, generated in mirrors during three experimental paradigms: a group-behaviour test; a modified mirror test and a hidden-head test. We believe that this set of experiments constitutes possibly the first investigations into the potential presence of self-awareness in any penguin species and is pioneering in conducting a set of cognitive experiments on free-ranging individuals of a nonhuman species in its natural environment, without any prior familiarisation, conditioning or acclimatisation to the experimental paradigms employed. Future studies, integrating the socioecology and cognitive ethology of penguins, may provide insights into whether our experimental paradigms could provide evidence to confirm the presence of self-awareness and even of self-recognition in this species and examine whether the observed social awareness may have evolved due to the social needs of individual penguins to engage in cooperative behaviour with conspecific individuals, while maintaining their independent decision-making capacities, throughout their communal lives.

animal behavior and cognition↗

bioRxiv2022

The multifaceted roles of R2R3 transcription factor HlMYB7 in the regulation of flavonoid and bitter acids pathways, development and biotic stress in hop (Humulus lupulus L.)

Hop (Humulus lupulus) biosynthesizes the highly economically valuable secondary metabolites, which include flavonoids, bitter acids, polyphenols and essential oils. These compounds have important pharmacological properties and are widely implicated in the brewing industry owing to bittering flavor, floral aroma and preservative activity. Our previous studies documented that ternary MYB-bHLH-WD40 (MBW) and binary WRKY1-WD40 (WW) protein complexes transcriptionally regulate the accumulation of bitter acid (BA) and prenylflavonoids (PF). In the present study, we investigated the regulatory functions of the R2R3-MYB repressor HlMYB7 transcription factor, which contains a conserved N-terminal domain along with the repressive motif EAR, in regulating the PF- and BA-biosynthetic pathway and their accumulation in hop. Constitutive expression of HlMYB7 resulted in transcriptional repression of structural genes involved in the terminal steps of biosynthesis of PF and BA, as well as stunted growth, delayed flowering, and reduced tolerance to viroid infection in hop. Furthermore, yeast two-hybrid and transient reporter assays revealed that HlMYB7 targets both PF and BA pathway genes and suppresses MBW and WW protein complexes. Heterologous expression of HlMYB7 leads to down-regulation of structural genes of flavonoid pathway in Arabidopsis thaliana, including a decrease in anthocyanin content in Nicotiana tabacum. The combined results from functional and transcriptomic analyses highlight the important role of HlMYB7 in fine-tuning and balancing the accumulation of secondary metabolites at the transcriptional level, thus offer a plausible target for metabolic engineering in hop.

plant biology↗

bioRxiv2022

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Genome-wide association studies (GWAS) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis associating serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) - a plasma membrane protein - and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells and in mice strongly impairs choline metabolism due to a block in choline import. Consistently, CRISPR-based genetic screens identified several components of the membrane phospholipid machinery as synthetic lethal with FLVCR1 loss. Finally, cells lacking FLVCR1 exhibit mitochondrial defects and upregulate the integrated stress response (ISR) through heme regulated inhibitors kinase (HRI). Altogether, these findings identify FLVCR1 as a universal mediator of choline transport in mammals and provide a platform to discover substrates for unknown metabolite transporters.

cell biology↗

bioRxiv2022

Unusual Morphological Changes of Rugositalea oryzae, A Novel Wrinkled Bacterium Isolated from The Rice Rhizosphere, Under Nutrient Stress

Bacterial cell morphology might result from natural selection to gain a competitive advantage under environmentally stressful conditions such as nutrient limitation. A bacterial strain YC6860T isolated from the rhizosphere of rice (Oryza sativa L.) showed pleomorphic behavior with smooth cell morphology and wrinkled surface rods depending upon nutritional conditions. Based on scanning and transmission electron microscopy studies, we hypothesized that the surface-to-volume ratio of cells increases with decreasing nutrient concentrations. The transition from smooth to wrinkled cell surface morphology could be one of the adaptation strategies by which YC6860T maximizes its ability to access available nutrients. To characterize the properties of the wrinkled strain, we performed taxonomic and phylogenetic analyses. 16S rRNA gene sequencing results showed that the strain represented a novel, deep-rooting lineage within the order Rhizobiales with the highest similarity of 94.2% to Pseudorhodoplanes sinuspersici RIPI 110T. Whole genome sequencing was also performed to characterize its genetic features. The strain YC6860T might belong to a new genus, named Rugositalea, and a new species, named Rugositalea oryzae, In addition, taxonomic analysis showed that YC6860T is Gram-negative, aerobic, and rod-shaped with large regular wrinkles resembling a delicate twist of fusilli, measuring 0.5-0.6 {micro}m in width and 1.5-1.6 {micro}m in length under nutrient-limiting conditions. This unique cell structure with regular rugosity could be the first finding that has not been reported in the existing bacterial morphology.

microbiology↗

bioRxiv2022

A phased, chromosome-scale genome of 'Honeycrisp' apple (Malus domestica)

Honeycrisp is one of the most valuable apple cultivars grown in the United States and a popular breeding parent due to its superior fruit quality traits, high levels of cold hardiness, and disease resistance. However, it suffers from a number of physiological disorders and is susceptible to production and postharvest issues. Although several apple genomes have been sequenced in the last decade, there is still a substantial knowledge gap in understanding the genetic mechanisms underlying cultivar-specific traits. Here we present a fully phased, chromosome-level genome of Honeycrisp apples, using PacBio HiFi, Omni-C, and Illumina sequencing platforms. Our genome assembly is by far the most contiguous among all the apple genomes. The sizes of the two assembled haplomes are 674 Mb and 660 Mb, with contig N50s of 32.8 Mb and 31.6 Mb, respectively. In total, 47,563 and 48,655 protein coding genes were annotated from each haplome, capturing 96.8-97.4% complete BUSCOs in the eudicot database, the most complete among all Malus annotations. A gene family analysis using seven Malus genomes shows that a vast majority of Honeycrisp genes are assigned into orthogroups shared with other genomes, but it also reveals 121 Honeycrisp-specific orthogroups. We provide a valuable resource for understanding the genetic basis of horticulturally important traits in apples and other related tree fruit species, including at-harvest and postharvest fruit quality, abiotic stress tolerance, and disease resistance, all of which can enhance breeding efforts in Rosaceae.

genomics↗

bioRxiv2022

Ultra high-throughput whole-genome methylation sequencing reveals trajectories in precancerous polyps to early colorectal adenocarcinoma

Aberrant shifts in DNA methylation have long been regarded as an early marker for cancer onset and progression. To chart DNA methylation changes that occur during the transformation from normal healthy colon tissue to malignant colorectal cancer (CRC), we collected over 50 samples from 15 familial adenomatous polyposis (FAP) and non-FAP colorectal cancer patients, and generated 30-70x whole-genome methylation sequencing (WGMS) runs via the novel Ultima Genomics ultra high-throughput sequencing platform. We observed changes in DNA methylation that occur early in the malignant transformation process, in gene promoters and in distal regulatory elements. Among these changes are events of hyper-methylation which are associated with a bivalent "poised" chromatin state at promoters and are CRC-specific. Distal enhancers show nonlinear dynamics, lose methylation in the progression from normal mucosa to dysplastic polyps but regain methylation in the adenocarcinoma state. Enhancers that gain chromatin accessibility in the adenocarcinoma state and are enriched with HOX transcription factor binding sites, a marker of developmental genes. This work demonstrates the feasibility of generating large high quality WGMS data using the Ultima Genomics platform and provides the first detailed view of methylation dynamics during CRC formation and progression in a model case.

genomics↗

bioRxiv2022

Near-chromosomal de novo assembly of Bengal tiger genome reveals genetic hallmarks of apex-predation

The tiger, a poster child for conservation, remains an endangered apex predator. Continued survival and recovery will require a comprehensive understanding of their genetic diversity and the use of such information for population management. A high-quality tiger genome assembly will be an important tool for conservation genetics, especially for the Indian tiger, the most abundant subspecies in the wild. Here, we present high-quality near-chromosomal genome assemblies of a female and a male wild Indian tiger (Panthera tigris tigris). Our assemblies had a scaffold N50 of >140{square}Mb, with 19{square}scaffolds, corresponding to the 19 numbered chromosomes, containing 95% of the genome. Our assemblies also enabled detection of longer stretches of runs of homozygosity compared to previous assemblies which will improve estimates of genomic inbreeding. Comprehensive genome annotation identified 26,068 protein-coding genes, including several gene families involved in key morphological features such as the teeth, claws, vision, olfaction, taste and body stripes. We also identified 301 microRNAs, 365 small nucleolar RNAs, 632 tRNAs and other noncoding RNA elements, several of which are predicted to regulate key biological pathways that likely contribute to tigers apex predatory traits. We identify signatures of positive selection in the tiger genome that are consistent with the Panthera lineage. Our high-quality genome will enable use of non-invasive samples for comprehensive assessment of genetic diversity, thus supporting effective conservation and management of wild tiger populations.

genomics↗

bioRxiv2022

Anaerobic degradation of acid red 73 by obligately aerobic Aspergillus tabacinus LZ-M though a self-redox mechanism

Fungi are potential biological resources for refractory organics degradation, but their anaerobic degradation of azo dyes are rarely reported. In this study, a fungus Aspergillus tabacinus LZ-M was isolated grown aerobically and degraded acid red 73 (AR73) with a decolorization rate of 90.28% in 5 days at 400 mg/L of concentration anaerobically. Metabolic pathway showed that AR73 was reduced into 2-hydroxynaphthalene and aniline then mineralized into CO2. The anaerobic self-redox process revealed electrons generated in carbon oxidation and transferred to -C-N= and -N=N, resulting in complete mineralization of AR73 in strain LZ-M. Data of transcriptome analysis showed that the benzene compounds produced from AR73 by declorizing reductase entered the catechol pathway and glycolysis process to mineralize. Enzymes involved in aromatics degradation, glycolysis processes, cytochrome C and quinone oxidoreductases were up-regulate, but the key reductase responsible to cleave AR73 to phenylhydrazine was not found. A novel enzyme Ord95 containing a glutamate S-transferase domain was identified in the unknown genes as a reductase which cleaving -C-N= in AR73 using NADH as electron donor, and three arginines key active sites. These observations reveal a new degradation mechanism of AR73 in strain LZ-M which would be potential candidate for treatment of azo dyes wastewater. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2022

Extended DNA binding interface beyond the canonical SAP domain contributes to SDE2 function at DNA replication forks

Elevated DNA replication stress causes instability of the DNA replication fork and DNA mutations, which underlies tumorigenesis. The DNA replication stress regulator SDE2 binds to TIMELESS (TIM) of the fork protection complex (FPC) and enhances its stability, thereby supporting replisome activity at DNA replication forks. Here, we structurally and functionally characterize a new conserved DNA binding motif related to SAP (SAF-A/B, Acinus, PIAS) in human SDE2 and establish its preference for single-stranded DNA (ssDNA). The nuclear magnetic resonance solution structure of SDE2SAP reveals a helix-extended loop-helix core aligned parallel to each other, consistent with known canonical SAP folds. Notably, its DNA interaction extends beyond the core SAP domain and is augmented by two lysine residues in the C-terminal tail, which is uniquely positioned adjacent to SAP and conserved in the pre-mRNA splicing factor SF3A3. Mutation in the SAP domain with extended C-terminus not only disrupts ssDNA binding but also impairs TIM localization at replication forks, thus inhibiting efficient fork progression. Together, our study establishes SDE2SAP as an essential element for SDE2 to exert its role in preserving replication fork integrity via FPC regulation and highlights the structural diversity of the DNA-protein interactions achieved by a specialized DNA binding motif.

biochemistry↗

bioRxiv2022

Exploring the mobilome and resistome of Enterococcus faecium in a One Health context across two continents

Enterococcus faecium is a ubiquitous opportunistic pathogen that is exhibiting increasing levels of antimicrobial resistance (AMR). Many of the genes that confer resistance and pathogenic functions are localized on mobile genetic elements (MGEs), which facilitate their transfer between lineages. Here, features including resistance determinants, virulence factors, and MGEs were profiled in a set of 1273 E. faecium genomes from two disparate geographic locations (in the UK and Canada) from a range of agricultural, clinical, and associated habitats. Neither lineages of E. faecium nor MGEs are constrained by geographic proximity, but our results show evidence of a strong association of many profiled genes and MGEs with habitat. Many features were associated with a group of clinical and municipal wastewater genomes that are likely forming a new human-associated ecotype. The evolutionary dynamics of E. faecium make it a highly versatile emerging pathogen, and its ability to acquire, transmit, and lose features presents a high risk for the emergence of new pathogenic variants and novel resistance combinations. This study provides a workflow for MGE-centric surveillance of AMR in Enterococcus that can be adapted to other pathogens.

genomics↗

bioRxiv2022

Experimental evolution in TP53 deficient gastric organoids recapitulates tumorigenesis

The earliest events during human tumor initiation, while poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult pre-neoplasia by bi-allelically inactivating TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over two years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single cell sequencing of TP53 deficient gastric organoids similarly indicates progression towards malignant transcriptional programs. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programs repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference, and a striking degree of phenotypic convergence in pre-malignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and reveal evolutionary constraints and barriers to malignant transformation with implications for earlier detection and interception of aggressive, genome instable tumors.

cancer biology↗

bioRxiv2022

Small molecules from Bacopa monneiri as potent inhibitors against Neurodegenerative disorders

Alzheimers is characterized by the formation of senile plaques and fibril tangles. Several methodologies have been employed to treat the disease. Albeit engineered medications which are accessible for the treatment of Alzheimers, due to their numerous side-effects, it becomes imperative to formulate and synthesize novel drug candidates. Plants could be utilized as an alternative for these manufactured medications because of their low incidental effects in contrast with the engineered drugs. Bacopa monneiri (BM) is a therapeutic plant which is accounted for to be utilized to treat NDs. Therefore, in current study an in-silico approach was carried out to evaluate the pharmacological effect of BM. Molecular Docking was carried out to screen the active phytochemicals of BM which can act as potential drug candidates against amyloid-{beta} plaques. A total of 8 biologically active phytochemicals from BM were docked against p75NTR receptor. Based on molecular docking study it was observed that the phytocompounds Bacopasaponin D and Bacopasaponin G of BM significantly fits to the active site of p75NTR. Further Molecular Dynamics simulation study was performed to examine the stability of the binding of these phytochemicals with the selected targets. Our findings suggested that the phytocompounds Bacopasaponin D and Bacopasaponin G significantly binds with p75NTR and thus might have a potential to inhibit the natural binding activity of amyloid-b plaques and act as a potential anti-neurodegenerative drug.

bioinformatics↗

bioRxiv2022

In silico analysis of Bacopa monnieri (L.) Wettst. compounds for drug development against Neurodegenerative Disorders

Neurotrophins play a crucial role in the development and regulation of neurons. Alterations in the functioning of these Neurotrophins leads to several Neurodegenerative Disorders. Albeit engineered medications which are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side-effects, it becomes imperative to formulate and synthesize novel drug candidates. Plants could be utilized as an alternative for these manufactured medications because of their low incidental effects in contrast with the engineered drugs. Bacopa monnieri has been traditionally known to be utilized to treat Neurodegenerative Disorders. Therefore, in current study an in-silico based study was carried out to evaluate the pharmacological effect of Bacopa monnieri. Molecular Docking was carried out to screen the active phytochemicals of Bacopa monnieri which can act as potential drug candidates against the causative proteins of Neurodegenerative Disorders. A total of 105 biologically active phytochemicals from Bacopa monnieri were docked against the receptors of brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, and nerve growth factor. Based on molecular docking study it was observed that the phytocompounds Vitamin E, Benzene propanoic acid, 3,5-bis(1,1dimethylethyl)4-hydroxy-, methyl ester (BPA), Stigmasterol, and Nonacosane of Bacopa monnieri significantly fits to the active residues of the four selected drug targets. Further Molecular Dynamics simulation study was performed to examine the stability of the binding of these phytochemicals with the selected targets. Drug likeness properties as well as related physico-chemical properties were analyzed through ADMETox study. Our findings suggested that the phytocompounds Vitamin E, BPA, Stigmasterol and Nonacosane significantly bind against brain-derived neurotrophic factor, neurotrophin-3, neurotrophin4, and nerve growth factor, respectively which may be the potential drug candidates for the treatment of neurodegenerative disorders. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/486025v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@2c39aforg.highwire.dtl.DTLVardef@17f4fd9org.highwire.dtl.DTLVardef@1534e13org.highwire.dtl.DTLVardef@2ad383_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗