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The GDP of nation is contributed by three sectors (primary, secondary and service). The transformation of economy from one sector to another is called structural transformation. Structural Transformation has usually positive impact on economic growth of Nepal. This research aims to answer the questions about what are the effects of structural Transformation on growth in Nepalese economy. Economic performance is measured by Per Capita Income. This study tries to find out which sectors a government should make better strategies to uplift and which sector to give less priority based on its contribution on economic growth. Time series data from 1975 AD to 2020 AD have been taken. Auto Regressive Distributed Lag (ARDL) Model is used as econometric tool to analyze the data. The expected result is that there is a long run association between per capita GDP and sector wise GDP. Also there is a significant relationship in structural transformation and economic growth in Nepal. So government should give more concern to develop service sector followed by primary sector and secondary sector.

There is a significant need for new small molecule anti-inflammatory compounds. Curcumin, a small molecule natural product from the Turmeric (Curcuma longa) plant, has well-known anti-oxidant properties, resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability and biodistribution characteristics are an impediment to its use. To circumvent these issues while retaining curcumin’s biological activity, we synthesized twenty-one diarylidene-N-methyl-4-piperidones (DANMPs), four diheteroarylidene-N-methyl-4-piperidones (DHANMPs), and five spirobibenzopyran (SBP) derivatives. All were screened in terms of anti-oxidant activity via a cell-free 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and for drug-like properties in silico. In the former, some compounds possessed improved radical scavenging behavior versus ascorbic acid, which was used as a benchmark. Conformity to simulated Lipinski’s parameters and Absorption, Distribution, Metabolism, and Excretion (ADME) studies indicated the DANMPs, DHANMPs, and SBPs to be potentially useful compounds. A subset of molecules was investigated in terms of their aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of the cellular and anti-inflammatory effects of these compounds were conducted using RAW264.7 macrophages. RT-PCR and Griess assays were used to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation, respectively. While the compounds did not affect non-stimulated (naïve) macrophages, they did reduce levels of markers and NO to extents similar to or better than curcumin in inflamed cells. Our results indicate that these pharmacophores possess anti-inflammatory properties and can be used as curcumin-substitutes with improved characteristics. Further investigation into their mechanisms of action and potential use in the treatment of inflammatory diseases is merited.

Altered protein phosphorylation in cancer cells often leads to surface presentation of phosphopeptide neoantigens. However, their role in cancer immunogenicity remains unclear. Here we describe a mechanism by which an HLA-B*0702-specific acute myeloid leukemia phosphoneoantigen pMLL747-755 (EPR(pS)PSHSM) is recognized by cognate TCR27, which is a candidate for immunotherapy of AML. We show that the replacement of phosphoserine P4 with serine or phosphomimetics does not affect the pMHC conformation or peptide-MHC affinity but abrogates the TCR27-dependent T cell activation and weakens binding between TCR27 and pMHC. We determined the crystal structures for TCR27 and cognate pMHC, mapped the pMHC-TCR interface by TROSY-NMR, generated a ternary pMHC-TCR complex using information-driven protein docking, and identified key polar interactions between phosphate group at P4 and TCR27 that are crucial for ternary complex stability and TCR27 specificity. These data will support development of cancer immunotherapy through target expansion and TCR optimization. *The authors would like to note that Yury Patskovsky and Aswin Natarajan contributed equally.

Realizing myxobacteria as a potential source of antimicrobial metabolites, we pursued research to isolate myxobacteria showing antimicrobial properties. We have successfully isolated three strains (NR-1, NR-2, NR-3) using the Escherichia coli baiting technique. These isolates showed typical myxobacterial growth characteristics. Phylogenetic analysis showed that all the strains (NR-1, NR-2, NR-3) belong to the family Archangiaceae, suborder Cystobacterineae, and order Myxococcales. Furthermore, 16S rRNA gene sequence similarity searched through BLAST revealed that strain NR-1 showed the closest similarity (91.8 %) to the type strain Vitiosangium cumulatum (NR-156939), NR-2 showed (98.8 %) to the type of Cystobacter badius (NR-043940), and NR-3 showed the closest similarity (83.5 %) to the type of strain Cystobacter fuscus (KP-306730). All isolates showed better growth in 0.5-1 % NaCl and pH around 7.0, whereas no growth was observed at pH 9.0 and below 5.0. All strains showed better growth at 32° C and hydrolyzed starch, whereas casein was efficiently hydrolyzed by NR-1 and NR-2. Besides, preliminary antimicrobial tests from crude extracts showed activities against Gram-positive, Gram-negative bacteria, and fungi. Our findings suggest that the arcane soil habitats of Nepal harbor myxobacteria with the capability to produce diverse antimicrobial activities that may be explored to overcome the rapidly rising global concern about antibiotic resistance.

Bacterial extracellular vesicles (EVs) have a vital role in bacterial pathogenesis. However, to date, the small RNA-cargo of EVs released by the opportunistic pathogen Staphylococcus aureus has not been characterized. Here, we shed light on the association of small RNAs with EVs secreted by S. aureus MSSA476 cultured in iron-depleted bacteriologic media supplemented with a subinhibitory dosage of vancomycin to mimic infection condition. Confocal microscopy analysis on intact RNase-treated EVs indicated that RNA is associated with EV particles. Transcriptomic followed by bioinformatics analysis of EV-associated RNA revealed the presence of potential gene regulatory small RNAs and high levels of tRNAs. Among the EV-associated enriched small RNAs were SsrA, RsaC and RNAIII. Our finding invites new insights into the potential role of EV-associated RNA as a modulator of host-pathogen interaction.

Enterococcus faecium is a commensal but also a bacteremia causing pathogen, which is inherently resistant to several antimicrobials and has a great ability to acquire new traits. Bacterial membrane vesicles (MVs) are increasingly recognized as a mode of cell-free communication and a way to deliver virulence factors and/or antimicrobial resistance determinants. These features make MVs interesting research targets in research on critical hospital pathogens. This study describes for the first time that E. faecium strains produce MVs. It presents a morphological as well as a proteomic analysis of MVs isolated from four different, clinically relevant E. faecium strains grown under two different conditions and identifies MV-associated proteins in all of them. Interestingly, 11 virulence factors are found among the MV-associated proteins, including biofilm-promoting proteins and extracellular matrix-binding proteins, which may aid in enterococcal colonization. Additionally, 11 antimicrobial resistance-related proteins were MV-associated. Among those, all proteins encoded by the vanA-cluster of a vancomycin resistant strain were found to be MV-associated. This implies that E. faecium MVs may be utilized by the bacterium to release proteins promoting virulence, pathogenicity and antimicrobial resistance. Significance - Enterococcal infections, especially bacteremia and endocarditis, are challenging to treat because E. faecium have acquired resistance to multiple classes of antimicrobials, including ampicillin, aminoglycosides, and glycopeptides. Thus, research on different modes of enterococcal pathogenicity is warranted. This study utilized a proteomic approach to identify MV-associated proteins of different nosocomial E. faecium strains representing four clinically relevant sequence types (STs), namely ST17, ST18, ST78, and ST192. The presented data suggest that E. faecium MVs are involved in virulence and antimicrobial resistance.

Background. Infections by microbes (viruses, bacteria, and fungi) and parasites can cause serious diseases in both humans and animals. Heavy use of antimicrobials has created selective pressure and caused resistance to currently available antibiotics, hence the need for finding new and better antibiotics. Natural products, especially from plants, are known for their medicinal properties, including antimicrobial and anthelmintic activities. Geoclimatic variation, together with diversity in ethnomedicinal traditions, has made the Himalayas of Nepal an invaluable repository of traditional medicinal plants. We studied antiviral, antibacterial, antifungal, and anthelmintic activities of medicinal plants, selected based upon ethnobotanical evidence. Methods. Ethanolic and methanolic extracts were tested (1) on a panel of microbes: two Gram-positive bacteria (Staphylococcus aureus and Listeria innocua), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Shigella sonnei), and one fungal species: Candida albicans; (2) against three different viruses: yellow fever, chikungunya, and enterovirus; and (3) on the nematode Caenorhabditis elegans. Also, cytotoxicity was assessed on human hepatoma (Huh), rhabdosarcoma (RD), and Vero (VC) cell lines. Results. Of 18 plants studied, Ampelocissus tomentosa and Aleuritopteris anceps inhibited S. aureus (MIC 35 μg/mL and 649 μg/mL, respectively) and Pseudomonas aeruginosa (MIC 15 μg/mL and 38 μg/mL, respectively). Rhododendron arboreum and Adhatoda vasica inhibited S. enterica (MIC 285 μg/mL and 326 μg/mL, respectively). Kalanchoe pinnata, Ampelocissus tomentosa, and Paris polyphylla were active against chikungunya virus, and Clerodendrum serratum was active against yellow fever virus (EC50 15.9 μg/mL); Terminalia chebula was active against enterovirus (EC50 10.6 μg/mL). Ampelocissus tomentosa, Boenninghausenia albiflora, Dichrocephala integrifolia, and Kalanchoe pinnata significantly reduced C. elegans motility, comparable to levamisole. Conclusions. In countries like Nepal, with a high burden of infectious and parasitic diseases, and a current health system unable to combat the burden of diseases, evaluation of local plants as a treatment or potential source of drugs can help expand treatment options. Screening plants against a broad range of pathogens (bacteria, viruses, fungi, and parasites) will support bioprospecting in Nepal, which may eventually lead to new drug development.

Background: Nepal is very rich in biodiversity, and no extensive effort has yet been carried out to screen plants that are used by traditional healers against parasitic diseases. The aim of this study was to evaluate the in vitro antileishmanial and antimalarial activity of crude methanolic or ethanolic extracts of 29 plant species that are currently used by local people of Nepal for treating different ailments. Methods: Crude extracts of leaves, twigs, aerial parts, and/or roots of the selected plants were evaluated for in vitro inhibitory activity against intracellular amastigotes of Leishmania infantum and against erythrocytic stages of Plasmodium falciparum. To determine the selectivity index (SI), cytotoxicity was assessed on MRC-5 cells in parallel. Results: Three plant species, namely Phragmites vallatoria and Ampelocissus tomentosa, for which no antiprotozoal activity has previously been reported, and Terminalia chebula revealed antiprotozoal activity. The extract of A. tomentosa exhibited moderate activity against L. infantum with an inhibitory concentration 50% (IC50) of 13.2 +/- 4.3 mu g/ml and SI >3, while T. chebula exhibited fairly good antiplasmodial activity with IC50 values of 4.5 +/- 2.4 mu g/ml and SI values >5. Conclusion: In countries like Nepal, where the current health system is unable to combat the burden of endemic parasitic diseases, evaluation of local plants as a potential source of the drug can help in expanding the treatment options. The extent of untapped resources available in these countries provides an opportunity for future bioprospecting.

Advancement in biotechnological methods has increased the potential for the commercial development of second-generation biofuels from lignocellulosic biomass. In this regard, the methods related to pretreatment of lignocellulosic biomass and bioprocesses (second-generation technologies) for production of bioethanol are critical. In spite of all the advances in the field, one of the obstacles continues to be lack of appropriate microorganisms that may be exploited for both the pretreatment of biomass as well as its fermentation. In this chapter, we summarize the advancements in pretreatment methods and discuss the potential of various microbes currently used for ethanol fermentation, their advantages and disadvantages. Efforts have also been made to show the importance of genetically modified organisms and their use in ethanol production wherever possible.

Neurocysticercosis (NCC) is a public health burden in Nepal. In patients burdened by this disease epileptic seizures are common. Computerized tomography scan (CT-scan) and Magnetic resonance imaging (MRI) techniques are most commonly used investigative tools for the diagnosis of NCC. Radio imaging techniques combined with serological techniques such as Enzyme linked immunosorbent assay (ELISA) and/or Enzyme linked immunoelectrotransfer blot (EITB) are commonly used as confirmatory diagnostic tools for this disease. Poor sanitation and hygiene accompanied with free range system of keeping pigs, deliberate use of human feces as pig feeds and social economic status of the society were reviewed the main causes for the persistence of Neurocysticercosis in Nepal. It was found that NCC exists in various development stages in the human brain as vesicular, colloidal, granular nodular and calcified forms. Based on the developmental stage and location of the cyst, a patient may present a focal seizure (FS), focalised Review Article International Journal of TROPICAL DISEASE & Health, 4(2): 204-223, 2014 205 seizure secondary generalised (FSSG), generalised toniclonic seizure (GTCS), intractable seizures, headache, vomiting, impaired vision and or cognitive dysfunctions. Radio-imaging (CT scan and MRI) techniques and immunodiagnostic kits (ELISA, EITB, Dot Blots, and Western Blots) were found to be the main tools for diagnosis of NCC/Cysticercosis in Nepal. The chemotherapeutic treatment for NCC associated epilepsy was found to be analgesics, corticosteroids, and/or a combination of both. Albendazole was found the most used and effective anthelminthic drug for the treatment of multiple lesion. NCC is an easily preventable disease of poor and the neglected people. In a resource limited setting like Nepal, effective diagnostic techniques and treatment routines in place is very difficult. It is recommended that provision of education to the public on the epidemiology of the disease, promotion of safe pork production practices, supply of tap water, improvement of personal hygiene and sanitation would play a bigger role in eradicating the disease.

At present, few organisms are known to and capable of naturally producing laccases and white rot fungi are one such group. In the present study, three fungal species, namely, Ganoderma lucidum-CDBT1, Ganoderma japonicum, and Lentinula edodes, isolated from their native habitat in Nepal were screened for laccase production, and G. lucidum-CDBT1 was found to express highest levels of enzyme (day 10 culture media showed 0.92 IU/mg total protein or 92 IU/mL laccase activity with ABTS as substrate). Lignin extracted from rice straw was used in Olga medium for laccase production and isolation from G. lucidum-CDBT1. Presence of lignin (5 g/L) and copper sulfate (30 μM) in the media increased the extracellular laccase content by 111% and 114%, respectively. The laccase enzyme produced by G. lucidum-CDBT1 was fractionated by ammonium sulfate and purified by DEAE Sepharose anion exchange chromatography. The purified enzyme was found to have a molecular mass of 43 kDa and exhibits optimal activity at pH 5.0 and 30°C. The isolated laccase was thermally stable for up to 70°C for 1 h and exhibited broad pH stability. The kinetic constants, K m, V max, and K cat, determined using 2,2′-azinobis-(-3-ethylbenzothiazoline-6-sulfonic acid) as substrate were found to be 110 μM, 36 μmol/min/mg, and 246 min−1, respectively. The isolated thermostable laccase will be used in future experiments for delignification process.

At present, few organisms are known to and capable of naturally producing laccases and white rot fungi are one such group. In the present study, three fungal species, namely,Ganoderma lucidum-CDBT1, Ganoderma japonicum,andLentinula edodes, isolated from their native habitat in Nepal were screened for laccase production, andG. lucidum-CDBT1 was found to express highest levels of enzyme (day 10 culture media showed 0.92 IU/mg total protein or 92 IU/mL laccase activity with ABTS as substrate). Lignin extracted from rice straw was used in Olga medium for laccase production and isolation fromG. lucidum-CDBT1. Presence of lignin (5 g/L) and copper sulfate (30 μM) in the media increased the extracellular laccase content by 111% and 114%, respectively. The laccase enzyme produced byG. lucidum-CDBT1 was fractionated by ammonium sulfate and purified by DEAE Sepharose anion exchange chromatography. The purified enzyme was found to have a molecular mass of 43 kDa and exhibits optimal activity at pH 5.0 and 30°C. The isolated laccase was thermally stable for up to 70°C for 1 h and exhibited broad pH stability. The kinetic constants,Km,Vmax, andKcat, determined using 2,2′-azinobis-(-3-ethylbenzothiazoline-6-sulfonic acid) as substrate were found to be 110 μM, 36 μmol/min/mg, and 246 min−1, respectively. The isolated thermostable laccase will be used in future experiments for delignification process.

Background: Liver disease caused by a chronic lesion of the hepatic portion of the inferior vena cava (IVC) is clinically characterized by dilated superficial veins in the body trunk with cephalad flow, hepatomegaly and splenomegaly. Cavography shows stenosis or complete obstruction near the cava-atrial junction. Methods: Early (acute and subacute) forms of the disease were recognized. The early stage of the disease manifested as jaundice, hepatomegaly or ascites and fever. Patients with acute and subacute onset of the illness with no past history of liver disease were studied with inferior vena cavography. Some of the patients had repeat cavography at 6 months and at 1 year after the initial investigations. Results: Three types of cavographic lesions were observed in the early stages of the disease: type 1, linear lucent area in the IVC close to cava-atrial junction; type 2, a smooth or irregular narrowing of almost the whole segment of the hepatic portion of the IVC; and type 3, a constriction or narrowing of a segment of the IVC near the cava-atrial junction. The first two types were associated with the acute stage of the disease and type 3 with the subacute stage. Type 2 and 3 lesions were associated with post-stenotic dilatation (PSD) close to the atrium. Lucent areas resulting from thrombosis are common in PSD. The acute and subacute hepatic IVC diseases in Nepal are commonly associated with bacterial infection. Conclusions: It is postulated that the early cavographic lesions are consistent with thrombosis and thrombophlebitis of the hepatic portion of the IVC, and that resolution of the lesions leads to the development of stenosis and to complete obstruction.

Background: Various primers have been used for detection of Mycobacterium tuberculosis complex (MTBC) DNA using Polymerase chain reaction (PCR). The MPB64 gene has been demonstrated to be a highly specific target for MTBC detection. Aims & Objectives: To detect MTBC DNA using MPB64 primers in clinical specimens of Nepalese patients suspected to have tuberculosis (TB). Materials and Methods: DNA was extracted from 44 clinical specimens of patients suspected of having TB and MPB64 targeted PCR was performed. Results: Bands comprising 240 base pair (bp) of MPB64 sequence were present in 15 of the 44 clinical samples, of which 4 were pulmonary and the remainders were extra-pulmonary samples. The overall positivity of MPB64 targeted PCR was 34.1%. Conclusion: PCR targeting the MPB64 fragment has a potential of detecting the MTBC DNA and has potentially valuable clinical applications in early detection of TB in Nepal.

Countries like Nepal and India have been using crude plants as medicine since Vedic period. A major part of the total population in developing countries still uses traditional folk medicine obtained from plant resources (Farnsworth 1994). With an estimation of WHO that as many as 80% of worlds population living in rural areas rely on herbal traditional medicines as their primary health care, the study on properties and uses of medicinal plants are getting growing interests. In recent years this interest to evaluate plants possessing antibacterial activity for various diseases is growing (Clark and Hufford, 1993). Based on local use of common diseases and Ethnobotanical knowledge, an attempt has been made to assess the antibacterial properties of selected medicinal plants.VIZ. Ocimum sanctum (Tulsi), Origanum majorana (Ram Tulsi), Cinnamomum zeylanicum (Dalchini), and Xanthoxylum armatum (Timur), for potential antibacterial activity against 10 medically important bacterial strains, namely Bacillus subtilis, Bacillus cereus, Bacillus thuringiensis, Staphylococcus aureus, Pseudomonas spp, Proteus spp, Salmonella Typhi, Escherichia coli, Shigella dysentriae, Klebsiella pneumoniae. The antibacterial activity of ethanol extracts was determined by agar well diffusion method. The plant extracts were more active against Gram-positive bacteria than against Gram-negative bacteria. The most susceptible bacteria were B. subtilis, followed by S. aureus, while the most resistant bacteria were E.coli, followed by Shigella dysenteriae, Klebsiella pneumoniae and Salmonella typhi. From the screening experiment, Origanum majorana showed the best antibacterial activity; hence this plant can be further subjected to isolation of the therapeutic antimicrobials and pharmacological evaluation. The largest zone of inhibition was obtained with Xanthoxylum armatum against Bacillus subtilis (23mm) and the minimum bactericidal concentration (MBC) value of 2.5 mg/l was obtained. Key words: Antibacterial property; Gram positive bacteria; Gram negative bacteria; zone of inhibition; minimum bactericidal concentration DOI: 10.3126/kuset.v5i1.2854 Kathmandu University Journal of Science, Engineering and Technology Vol.5, No.1, January 2009, pp 143-150