Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

Sources of gene expression variation in a globally diverse human cohort.

Genetic variation influencing gene expression and splicing is a key source of phenotypic diversity. Though invaluable, studies investigating these links in humans have been strongly biased toward participants of European ancestries, diminishing generalizability and hindering evolutionary research. To address these limitations, we developed MAGE, an open-access RNA-seq data set of lymphoblastoid cell lines from 731 individuals from the 1000 Genomes Project spread across 5 continental groups and 26 populations. Most variation in gene expression (92%) and splicing (95%) was distributed within versus between populations, mirroring variation in DNA sequence. We mapped associations between genetic variants and expression and splicing of nearby genes (cis-eQTLs and cis-sQTLs, respective), identifying >15,000 putatively causal eQTLs and >16,000 putatively causal sQTLs that are enriched for relevant epigenomic signatures. These include 1310 eQTLs and 1657 sQTLs that are largely private to previously underrepresented populations. Our data further indicate that the magnitude and direction of causal eQTL effects are highly consistent across populations and that apparent "population-specific" effects observed in previous studies were largely driven by low resolution or additional independent eQTLs of the same genes that were not detected. Together, our study expands understanding of gene expression diversity across human populations and provides an inclusive resource for studying the evolution and function of human genomes.

Synthesis and Self-Assembling Properties of Carbohydrate- and Diarylethene-Based Photoswitchable Molecular Gelators.

Carbohydrate-based low-molecular-weight gelators are interesting new materials with many potential applications. These compounds can be designed to include multiple stimuli-responsive functional groups. In this study, we designed and synthesized several chemically responsive bola-glycolipids and dimeric carbohydrate- and diarylethene-based photoswitchable derivatives. The dimeric glycolipids formed stable gels in a variety of solvent systems. The best performing gelators in this series contained decanedioic and dithienylethene (DTE) spacers, which formed gels in eight and nine of the tested solvents, respectively. The two new DTE-containing esters possessed interesting photoswitching properties and DTE derivative 7 was found to have versatile gelation properties in many solvents, including DMSO solutions at low concentrations. The gels formed by these compounds were stable under acidic conditions and tended to hydrolyze under basic conditions. Several gels were used to absorb rhodamine B and Toluidine blue from aqueous solutions. In this study, we demonstrated the rational design of molecular gelators which incorporated photoresponsive and pH responsive functions, leading to the discovery of multiple effective stimuli-responsive gelators.

Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) - a protocol for two parallel, open-label, randomised controlled trials.

BACKGROUND: Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines. METHODS: The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety. DISCUSSION: These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood. TRIAL REGISTRATIONS: ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).

Thyrotoxic periodic paralysis: a rare cause of periodic paralysis - a case report.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by episodes of muscle weakness and hypokalemia. Patients may present with a sudden onset of muscle weakness. Though hyperthyroidism occurs more commonly in females, TPP typically occurs in young males in their third decade. Case Presentation: This is a case of a 32-year-old male who presented to the emergency room with a sudden onset of weakness in bilateral upper and lower limbs, which progressed to complete paralysis in an hour. A provisional diagnosis of hypokalemic periodic paralysis was made and admitted. Later, on further diagnostic workup, the final diagnosis of TPP was made. Discussion: Clinical features of hyperthyroidism in patients with TPP may be subtle. With immediate potassium supplementation, serious cardiopulmonary complications can be prevented and may hasten the recovery of muscle weakness. Nonselective ß-adrenergic blockers can lessen and prevent the recurrence of paralytic attacks. Conclusion: This case is reported with the objective of generating awareness regarding the clues to the diagnosis, appropriate management, and definitive treatment to a render euthyroid state in order to prevent future recurrence of similar episodes and prevent any complications, and eventually to raise the index of suspicion among treating physicians in cases that present with paralysis in clinical practice.

The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

The complex, dynamic SpliceOme of the small GTPase transcripts altered by technique, sex, genetics, tissue specificity, and RNA base editing.

The small GTPase family is well-studied in cancer and cellular physiology. With 162 annotated human genes, the family has a broad expression throughout cells of the body. Members of the family have multiple exons that require splicing. Yet, the role of splicing within the family has been underexplored. We have studied the splicing dynamics of small GTPases throughout 41,671 samples by integrating Nanopore and Illumina sequencing techniques. Within this work, we have made several discoveries. 1). Using the GTEx long read data of 92 samples, each small GTPase gene averages two transcripts, with 83 genes (51%) expressing two or more isoforms. 2). Cross-tissue analysis of GTEx from 17,382 samples shows 41 genes (25%) expressing two or more protein-coding isoforms. These include protein-changing transcripts in genes such as RHOA, RAB37, RAB40C, RAB4B, RAB5C, RHOC, RAB1A, RAN, RHEB, RAC1, and KRAS. 3). The isolation and library technique of the RNAseq influences the abundance of non-sense-mediated decay and retained intron transcripts of small GTPases, which are observed more often in genes than appreciated. 4). Analysis of 16,243 samples of "Blood PAXgene" identified seven genes (3.7%; RHOA, RAB40C, RAB4B, RAB37, RAB5B, RAB5C, RHOC) with two or more transcripts expressed as the major isoform (75% of the total gene), suggesting a role of genetics in altering splicing. 5). Rare (ARL6, RAB23, ARL13B, HRAS, NRAS) and common variants (GEM, RHOC, MRAS, RAB5B, RERG, ARL16) can influence splicing and have an impact on phenotypes and diseases. 6). Multiple genes (RAB9A, RAP2C, ARL4A, RAB3A, RAB26, RAB3C, RASL10A, RAB40B, and HRAS) have sex differences in transcript expression. 7). Several exons are included or excluded for small GTPase genes (RASEF, KRAS, RAC1, RHEB, ARL4A, RHOA, RAB30, RHOBTB1, ARL16, RAP1A) in one or more forms of cancer. 8). Ten transcripts are altered in hypoxia (SAR1B, IFT27, ARL14, RAB11A, RAB10, RAB38, RAN, RIT1, RAB9A) with RHOA identified to have a transient 3'UTR RNA base editing at a conserved site found in all of its transcripts. Overall, we show a remarkable and dynamic role of splicing within the small GTPase family that requires future explorations.

Unique Features of Alarmone Metabolism in Clostridioides difficile.

The "magic spot" alarmones (pp)pGpp, previously implicated in Clostridioides difficile antibiotic survival, are synthesized by the RelA-SpoT homolog (RSH) of C. difficile (RSHCd) and RelQCd. These enzymes are transcriptionally activated by diverse environmental stresses. RSHCd has previously been reported to synthesize ppGpp, but in this study, we found that both clostridial enzymes exclusively synthesize pGpp. While direct synthesis of pGpp from a GMP substrate, and (p)ppGpp hydrolysis into pGpp by NUDIX hydrolases, have previously been reported, there is no precedent for a bacterium synthesizing pGpp exclusively. Hydrolysis of the 5' phosphate or pyrophosphate from GDP or GTP substrates is necessary for activity by the clostridial enzymes, neither of which can utilize GMP as a substrate. Both enzymes are remarkably insensitive to the size of their metal ion cofactor, tolerating a broad array of metals that do not allow activity in (pp)pGpp synthetases from other organisms. It is clear that while C. difficile utilizes alarmone signaling, its mechanisms of alarmone synthesis are not directly homologous to those in more completely characterized organisms. IMPORTANCE Despite the role of the stringent response in antibiotic survival and recurrent infections, it has been a challenging target for antibacterial therapies because it is so ubiquitous. This is an especially relevant consideration for the treatment of Clostridioides difficile infection (CDI), as exposure to broad-spectrum antibiotics that harm commensal microbes is a major risk factor for CDI. Here, we report that both of the alarmone synthetase enzymes that mediate the stringent response in this organism employ a unique mechanism that requires the hydrolysis of two phosphate bonds and synthesize the triphosphate alarmone pGpp exclusively. Inhibitors targeted against these noncanonical synthetases have the potential to be highly specific and minimize detrimental effects to stringent response pathways in commensal microbes.

A cross-sectional study on health-seeking behavior in relation to reproductive tract infection among ever-married rural women in Kancheepuram district, Tamil Nadu.

INTRODUCTION: Reproductive tract infection (RTI) is the infection of the reproductive tract. Due to the hesitation in reporting the symptoms and receiving the treatment from the health centers, there is a significant dropout. The health care-seeking actions of the women reflects the attentiveness of the disease in that community and the inadequacy of the health care facility. Since the women from the rural area belongs to high-risk group for RTI, this study was conducted with the objective to assess the health care-seeking behavior about reproductive tract infection among rural women in the reproductive age group in Kancheepuram district, Tamil Nadu. Primary care physicians play a vital role in improving health care system, assessing the health-seeking practice helps in improvement and decision making and implementing. METHODS AND MATERIAL: A community-based cross-sectional study was conducted in the rural field practice area of Chettinad hospital. A sample size of 330 was arrived by multi-stage random sampling and population proportion to size method. Data was collected using a standardized questionnaire of DLHS- 4 on RTI/STI. Data entered in MS-EXCEL and analyzed using SPSS version 21 and results interpreted. RESULTS: The prevalence of RTI was found to be 50.3%. 60.8% of the affected females received treatment with majority of them in the group following home remedies. Significant association was noted between treatment seeking behavior, age, and the socioeconomic status (P- < 0.05). CONCLUSIONS: The women in the reproductive age group in the rural areas should be provided with regular health education regarding the symptoms of the RTI and also motivate them to seek appropriate treatment.

Knowledge of Adverse Drug Reactions Reporting among Doctors and Nurses in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Doctors and nurses have a significant role in the detection of serious and unusual drug reactions. Effective implementation of an adverse drug reaction reporting system is required to ensure patient safety and quality care. This study's objective was to find the prevalence of good knowledge of adverse drug reaction reporting among the Doctors and nurses working in a tertiary care hospital. METHODS: A descriptive cross-sectional study was conducted among doctors and nurses from 15 February 2020 to 15 July 2020 at Birat Medical College and Teaching Hospital. The convenience sampling method was used to select 192 study participants. A semi-structured questionnaire was used to know the knowledge concept of adverse drug reaction reporting. Ethical clearance was taken from IRC (PA-047/2076-77) of Birat Medical College and Teaching Hospital. Written informed consent was taken from each study participant. Collected data were entered in Microsoft Excel 2010 and analyzed by Statistical Package for the Social Sciences v23. RESULTS: In total, 192 doctors and nurses, the questionnaires were distributed to 52 (27.1%) doctors and 140 (72.9%) nurses. The mean age of study participants was 28.14 years (SD±4.5). To know the prevalence of knowledge, 15 knowledge related questions of adverse drug reaction had asked. The majority of doctors and nurses had good knowledge about adverse drug reaction reporting, 75% and 64%, respectively. CONCLUSIONS: Overall, doctors and nurses have had good knowledge of adverse drug reaction reporting. Data shows there is still more gap in training and experience on adverse drug reaction reporting systems.

Synthesis of Carbohydrate Based Macrolactones and Their Applications as Receptors for Ion Recognition and Catalysis.

Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone moieties have been designed and synthesized. The synthesis features an intramolecular nucleophilic substitution reaction for the macrocyclization step. In this article, the effect of some common sulfonate leaving groups is evaluated for macrolactonization. Using tosylate gave good selectivity for monolactonization products with good yields. Fourteen different macrocycles have been synthesized and characterized, of which eleven macrocycles are from cyclization of the C1 to C6 positions of N-acetyl D-glucosamine derivatives and three others from C2 to C6 cyclization of functionalized D-glucosamine derivatives. These novel macrolactones have unique structures and demonstrate interesting anion binding properties, especially for chloride. The macrocycles containing two triazoles form complexes with copper sulfate, and they are effective ligands for copper sulfate mediated azide-alkyne cycloaddition reactions (CuAAC). In addition, several macrocycles show some selectivity for different alkynes.

May Measurement Month 2019: an analysis of blood pressure screening results from Nepal.

May Measurement Month (MMM) is a global initiative to screen high blood pressure (BP) in the community and increase awareness at the population level. High BP is the leading risk factor for mortality worldwide and in Nepal. This study presents the results of the 2019 MMM in Nepal. Opportunistic BP screening was conducted in 30 out of 77 districts across Nepal and aged ≥18 years at the community and public places. BP was measured three times in a seated position. A total of 74 205 individuals participated in the study, mean age 39.9 years, and 58% were male. BP measurements for the second and third readings were available for 69 292 (93.3%) individuals. The proportion of the population that were hypertensive was 27.5% (n = 20 429). Among those hypertensives, 46.3% were aware of their hypertensive status and of these, 37.5% were on antihypertensive medication. Only 54.3% of those on antihypertensive medication had their BP controlled. Of the community screened, those self reporting to have diabetes, current tobacco users, and current alcohol drinkers were 6.7%, 23.6%, and 31.9%, respectively; 20.6% of the participants were overweight, and 6.5% were obese. Since the first BP screening campaign, MMM 2017 in Nepal, the number of participants screened has largely increased over the years. MMM's success in Nepal is through a coordinated mobilization of trained health science students and volunteers in the communities. The Nepal MMM data demonstrates that large community-based BP screening campaigns are possible in low resource settings.

sn-spMF: matrix factorization informs tissue-specific genetic regulation of gene expression.

Genetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), exhibits complex patterns of tissue-specific effects. Characterization of these patterns may allow us to better understand mechanisms of gene regulation and disease etiology. We develop a constrained matrix factorization model, sn-spMF, to learn patterns of tissue-sharing and apply it to 49 human tissues from the Genotype-Tissue Expression (GTEx) project. The learned factors reflect tissues with known biological similarity and identify transcription factors that may mediate tissue-specific effects. sn-spMF, available at https://github.com/heyuan7676/ts_eQTLs , can be applied to learn biologically interpretable patterns of eQTL tissue-specificity and generate testable mechanistic hypotheses.

Occupancy maps of 208 chromatin-associated proteins in one human cell type.

Transcription factors are DNA-binding proteins that have key roles in gene regulation1,2. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes3-6. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP-seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium.

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

Transcriptional analysis of the multiple Sry genes and developmental program at the onset of testis differentiation in the rat.

BACKGROUND: The commonly used laboratory rat, Rattus norvegicus, is unique in having multiple Sry gene copies found on the Y chromosome, with different copies encoding amino acid variations that influence the resulting protein function. It is not clear which Sry genes are expressed at the onset of testis differentiation or how their expression correlates with that of other genes in testis-determination pathways. METHODS: Here, two independent E11-E14 developmental RNAseq datasets show that multiple Sry genes are expressed at E12-E13. RESULTS: The identified copies expressed during testis initiation include Sry4A, Sry1, and Sry3C, which are conserved in every strain of Rattus norvegicus with genomes sequenced to date. CONCLUSIONS: This work represents a first step in defining the complex environment of rat testis differentiation that can open the door for generating sex reversal model systems using embryo manipulation techniques that have been available in the mouse but not the rat.

Acute Severe Anaphylaxis in Nepali Patients with Neurotoxic Snakebite Envenoming Treated with the VINS Polyvalent Antivenom.

Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5-11 years) and 10 adults (18-52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.

Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKD.

Background Interpreting genetic variants is one of the greatest challenges impeding analysis of rapidly increasing volumes of genomic data from patients. For example, SHROOM3 is an associated risk gene for CKD, yet causative mechanism(s) of SHROOM3 allele(s) are unknown.Methods We used our analytic pipeline that integrates genetic, computational, biochemical, CRISPR/Cas9 editing, molecular, and physiologic data to characterize coding and noncoding variants to study the human SHROOM3 risk locus for CKD.Results We identified a novel SHROOM3 transcriptional start site, which results in a shorter isoform lacking the PDZ domain and is regulated by a common noncoding sequence variant associated with CKD (rs17319721, allele frequency: 0.35). This variant disrupted allele binding to the transcription factor TCF7L2 in podocyte cell nuclear extracts and altered transcription levels of SHROOM3 in cultured cells, potentially through the loss of repressive looping between rs17319721 and the novel start site. Although common variant mechanisms are of high utility, sequencing is beginning to identify rare variants involved in disease; therefore, we used our biophysical tools to analyze an average of 112,849 individual human genome sequences for rare SHROOM3 missense variants, revealing 35 high-effect variants. The high-effect alleles include a coding variant (P1244L) previously associated with CKD (P=0.01, odds ratio=7.95; 95% CI, 1.53 to 41.46) that we find to be present in East Asian individuals at an allele frequency of 0.0027. We determined that P1244L attenuates the interaction of SHROOM3 with 14-3-3, suggesting alterations to the Hippo pathway, a known mediator of CKD.Conclusions These data demonstrate multiple new SHROOM3-dependent genetic/molecular mechanisms that likely affect CKD.

Self-assembly of oleylamine modified nano-fibrillated cellulose from areca husk fibers into giant vesicles.

Nanotechnology involving cellulosic substrates has generated a great attention owing to their exceptional physical and chemical properties. Self-assembled nanostructures obtained from carbohydrate polymers are of interest in the biomedical field for the biocompatibility and non-toxic nature. In the present study modification of nano-fibrillated cellulose (NFC) synthesised from the husk fibers of Areca catechu nuts (AHF) was studied by controlled regio-selective amidation with oleylamine (OA) and characterized. The modified system (MNFC) with more than 66% OA content showed self-assembly into unilamellar vesicles of 2-5µm diameters with a wall thickness of 300-600nm in tetrahydrofuran (THF) at 2.5mgmL-1. This result is attributed to the folding of MNFC into bilayers driven by long cis-unsaturated aliphatic chains in polar aprotic solvents stabilized by hydrogen bonded interactions within the fibrils. These giant vesicles formed can have applications in storage and delivery of drugs in topical applications.