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Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and is the leading cause of cancer mortality in Vietnam. Our study aims to discover the partial extracts with the potential cytotoxic effects on HCC cells from the different parts of 24 Vietnamese medicinal plants traditionally used in liver cancer treatment. Out of 52 crude methanol extracts, we found that Luvunga scandens leaves, Hyptis suaveolens roots, and Solanum torvum leaves showed the notable cytotoxic effects against HCC cells. After that, we carried out partial extract of the three methanol extracts with ethyl acetate, water, n-hexane, and 90% methanol. The cytotoxic activity on Huh-7 HCC cells, antioxidant capacity, and total flavonoids content (TFC) of each partial extraction were determined. Methanol, ethyl acetate, and 90% methanol extracts showed moderate to strong cytotoxicity activity against Huh-7 HCC cells. Notably, the ethyl acetate and 90% methanol extract from H. suaveolens roots with high TFC values and strong antioxidant capacity could be promising sources of novel therapeutic modalities for HCC treatment. For the leaves of L. scandens and S. torvum, the ethyl acetate extract showed high TFC value and promising anti-HCC activity, therefore recommended further studies.

Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.

Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance., The tumour microenvironment provides signals to support leukaemic stem cells (LSC) maintenance and chemoresistance. Here, the authors show that disrupting niche-associated signalling by inhibiting receptor-mediated endocytosis with a dynamin GTPase inhibitor overcomes chemoresistance of LSC.

Killing more than one million people each year, tuberculosis remains the leading cause of death from a single infectious agent. The growing threat of multidrug-resistant strains of Mycobacterium tuberculosis stresses the need for alternative therapies. EthR, a mycobacterial transcriptional regulator, is involved in the control of the bioactivation of the second-line drug ethionamide. We have previously reported the discovery of in vitro nanomolar boosters of ethionamide through fragment-based approaches. In this study, we have further explored the structure-activity and structure-property relationships in this chemical family. By combining structure-based drug design and in vitro evaluation of the compounds, we identified a new oxadiazole compound as the first fragment-based ethionamide booster which proved to be active in vivo, in an acute model of tuberculosis infection., info:eu-repo/semantics/published

During investigation on the plant parasitic nematodes on bananas in North and Central provinces of Vietnam carried out in 1995 two new species were found, Hirschmanniella bananae n.sp. and Scutellonema tanlamese n.sp. Hirschmanniella bananae n.sp. is characterized by having 6 annuli in lip region, areolation of entire lateral field and presence of a mid-terminal mucro at the tail end. The new species is close to H. shamini Ahmad, 1972 but differs from H. shamini by longer body length in females (1450-1750 µm vs 1190-1360 mm), longer stylet longer (18-20.5 mm vs 16-19 mm) and longer spicule longer (28-29.5 mm vs 22-25 mm). Scutellonema tanlamese n.sp. is characterized by lip region with three annuli and numerous longitudinal ridges (18) in basal annulus and structure of lateral field at the tail region with inner lines extending to tail terminus. The new species is closest to S. brachyurus type B (African populations) described by Van Den Berg et al. in 2013 but can be distinguished by body length shorter (643-708 µm vs 777-820 µm), stylet length shorter ((24.5-26.5 µm vs 28-29.5 mm, and also by structure of lateral field with two inner lines going throught at tail region and vulval edge distinct with epiptygma appearing double and folded into vagina. Citation: Nguyen Ngoc Chau, 2017. Two new species of plant parasitic nematodes Hirschmanniella bananae n.sp. (Nematoda: Pratylenchidae) and Scutellonema tanlamense n.sp. (Nematoda: Hoplolaimidae) associated with banana in Vienam. Tap chi Sinh hoc, 39(3): 253-263. DOI: 10.15625/0866-7160/v39n3.10665. *Corresponding author: nguyengochau.iebr@gmail.com Received 19 August 2017, accepted 12 September 2017

Morphometry and biomass of nematode communities in different harbours of the Saigon River were investigated in the dry and wet seasons in relation to environmental variables such as total organic carbon, pH, conductivity, salinity and oxygen redox potential, in addition to concentrations of different butyltin compounds. The results indicated that nematodes in contaminated sediments from the Saigon River harbours were mainly characterised by slender morphotypes, whilst very few thin and stout nematodes were observed. Individual nematode biomass was generally low, especially in the wet season. There was no significant correlation between butyltin compounds and nematode morphometrics in the dry season but significant correlations were found for the wet season. Although significant correlations were observed for the wet season, the strong seasonal differences in nematode biomass spectra suggest a potential limitation in their use for environmental monitoring.

Bakernema enormese sp. n., collected from rhizosphere of forest wood trees in Muong Phang, Dien Bien Province (north Vietnam) is described and illustrated. The new species is characterized by large body size and stylet. In general, this new species is close to two existing species of the same genus, B. inaequale and B. dauniense by cuticle structure in transparent membranous projections which appear in lateral view as spine-like structures on each annulus. These structure arranged into several rows along the body. In morphology, the new species differs from B. inaequale and B. dauniense by body and stylet length, i.e. 609–842 µm and 143.5–150 µm vs. 391–578 µm and 59–74 µm for B. inaequale and vs. 391–461 µm and 65–74 µm for B. dauniense. In addition, new species can be distinguished from B. inaequale by the longer membranous projection, 8–12 vs. 6–10 µm and vagina shape, curved vs. sigmoid. From B. dauniense, the new species differs by the much longer membranous projection, 8–12 vs. 1.4–2.2 µm and less number annules between vulva and tail end (RV), 3–4 vs. 7.8 annules. The presence of Criconema (Nothocriconemella) graminicola Loof, Wouts & Yeates, in Vietnam with morphometrics, illustrators and remarks given.

Investigations on entomopathogenic and plant parasitic nematodes in some natural forests in the Ngoc Linh mountain (Quang Nam province) and the Thuong Xuan forest (Thanh Hoa province) revealed three new species of plant parasitic nematodes belonging to the genus Helicotylenchus Steiner, 1945 (Nematoda: Hoplolaimidae). These new species were named Helicotylenchus castanus sp. n., Helicotylenchus madhucus sp. n. and Helicotylenchus digitus sp. n. with morphological characteristics described and illustrated. The new species Helicotylenchus castanus sp.n. is characterized by the highly hemispherical shape of the lip region, extremely short and rounded tail without projection. The second new species Helicotylenchus madhucus sp. n. is characterized by high lip region with 4-5 annuli, hemispherical and not set off from body contour, stylet 31.3-35.9 (33.3 ± 1.3) µm long, tail with a short ventral projection and the presence of males in the population. The third new species, Helicotylenchus digitus sp.n. was recognized by broad rounded tail with strong annulated projection in the digital shape, and also the presence of males in population.

Mutations in the DYNAMIN2 (DNM2) gene are frequently detected in human acute T-cell lymphoblastic leukemia (T-ALL), although the mechanisms linking these mutations to disease pathogenesis remain unknown. Using an ENU-based forward genetic screen for mice with erythroid phenotypes, we identified a heterozygous mouse line carrying a mutation in the GTPase domain of Dnm2 (Dnm2V265G) that induced a microcytic anemia. In vitro assays using the V265G mutant demonstrated loss of GTPase activity and impaired endocytosis that was comparable to other DNM2 mutants identified in human T-ALL. To determine the effects of DNM2 mutations in T-ALL, we bred the Dnm2V265G mice with the Lmo2 transgenic mouse model of T-ALL. Heterozygous Dnm2 mutants lacking the Lmo2 transgene displayed normal T-cell development, and did not develop T-ALL. In contrast, compound heterozygotes displayed an accelerated onset of T-ALL compared with mice carrying the Lmo2 oncogene alone. The leukemias from these mice exhibited a more immature immunophenotype and an expansion in leukemic stem cell numbers. Mechanistically, the Dnm2 mutation impaired clathrin-mediated endocytosis of the interleukin (IL)-7 receptor resulting in increased receptor density on the surface of leukemic stem cells. These findings suggest that DNM2 mutations cooperate with T-cell oncogenes by enhancing IL-7 signalling.

The development of a (Z)-5-((6,8-dichloro-4-oxo-4H-chromen-3-yl)methylene)-2-thioxothiazolidin-4-one (2), rhodanine-based lead that led to the Pitstop® 2 family of clathrin inhibitors is described herein. Head group substitution and bioisosteric replacement of the rhodanine core with a 2-aminothiazol-4(5H)-one scaffold eliminated off target dynamin activity. A series of N-substituents gave first phenylglycine (20, IC50 ∼ 20 μM) then phenyl (25, IC50 ∼ 7.1 μM) and 1-napthyl sulfonamide (26, Pitstop® 2 compound, IC50 ∼ 1.9 μM) analogues with good activity, validating this approach. A final library exploring the head group resulted in three analogues displaying either slight improvements or comparable activity (33, 38, and 29 with IC50 ∼ 1.4, 1.6 and 1.8 μM respectively) and nine others with IC50 < 10 μM. These results were rationalized using in silico docking studies. Docking studies predicted enhanced Pitstop® 2 family binding, not a loss of binding, within the Pistop® groove of the reported clathrin mutant invalidating recent assumptions of poor selectivity for this family of clathrin inhibitors.

We report human pegivirus 2 (HPgV-2) infection in Vietnam. We detected HPgV-2 in some patients with hepatitis C virus/HIV co-infection but not in patients with HIV or hepatitis A, B, or C virus infection, nor in healthy controls. HPgV-2 strains in Vietnam are phylogenetically related to global strains.

Chlorpromazine is a phenothiazine-derived antipsychotic drug (APD) that inhibits clathrin-mediated endocytosis (CME) in cells by an unknown mechanism. We examined whether its action and that of other APDs might be mediated by the GTPase activity of dynamin. Eight of eight phenothiazine-derived APDs inhibited dynamin I (dynI) in the 2-12 µm range, the most potent being trifluoperazine (IC50 2.6 ± 0.7 µm). They also inhibited dynamin II (dynII) at similar concentrations. Typical and atypical APDs not based on the phenothiazine scaffold were 8- to 10-fold less potent (haloperidol and clozapine) or were inactive (droperidol, olanzapine and risperidone). Kinetic analysis showed that phenothiazine-derived APDs were lipid competitive, while haloperidol was uncompetitive with lipid. Accordingly, phenothiazine-derived APDs inhibited dynI GTPase activity stimulated by lipids but not by various SH3 domains. All dynamin-active APDs also inhibited transferrin (Tfn) CME in cells at related potencies. Structure-activity relationships (SAR) revealed dynamin inhibition to be conferred by a substituent group containing a terminal tertiary amino group at the N2 position. Chlorpromazine was previously proposed to target AP-2 recruitment in the formation of clathrin-coated vesicles (CCV). However, neither chlorpromazine nor thioridazine affected AP-2 interaction with amphiphysin or clathrin. Super-resolution microscopy revealed that chlorpromazine blocks neither clathrin recruitment by AP-2, nor AP-2 recruitment, showing that CME inhibition occurs downstream of CCV formation. Overall, potent dynamin inhibition is a shared characteristic of phenothiazine-derived APDs, but not other typical or atypical APDs, and the data indicate that dynamin is their likely in-cell target in endocytosis.

The hierarchical model posits that acute leukemias arise from leukemia stem cells (LSCs), which display stem cell-like properties like long-term self-renewal and differentiation to generate the heterogeneity observed in the tumor at diagnosis. Elimination of LSCs and their ancestral clones, pre-leukemic stem cells (pre-LSCs), is critical for long-term cure as they are the source of relapse. How these cells survive high-dose therapy remains poorly defined, but may include quiescence and pro-survival signals provided by the microenvironment. Strategies to interfere with specific signals from the niche have shown promising results, but may be subject to compensatory mechanisms due to the inherent plasticity of LSCs. The transactivation of signalling pathways downstream of growth factors from the niche is dependent on receptor-mediated endocytosis, a generic process dependent on Dynamins. Given the important role of the microenvironment for relapse-inducing cells, we postulated that inhibition of Dynamin might impair their properties and sensitize them to chemotherapy. Here, we show that the Dynamin small molecule inhibitor Dynole 34-2 blocks multiple signalling pathways in pre-LSCs and LSCs by preventing endocytosis. Using the Lmo2-transgenic mouse model of T-cell acute lymphoblastic leukemia (T-ALL), we found that Dynole 34-2 impairs self-renewal of pre-LSCs and sensitizes relapse-inducing cells to chemotherapy. We also found that Dynole 34-2 delayed leukemia onset in mice treated with high-dose therapy. Treatment of different patient-derived xenografts revealed that that inhibition of Dynamin activity with Dynole 34-2 represents an effective therapeutic strategy for different subtypes of human T-ALL. In summary, our finding that Dynamin activity is essential for LSC activity and chemoresistance in acute leukemia paves the way for novel therapeutic strategies.

We reported the first small molecule inhibitors of the interaction between the clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., clathrin inhibition1). Initial screening of a ∼17 000 small molecule ChemBioNet library identified 1. Screening of an existing in-house propriety library identified four substituted 1,8-napthalimides as ∼80-120 μM clathrin inhibitors. Focused library development gave 3-sulfo-N-(4-aminobenzyl)-1,8-naphthalimide, potassium salt (18, IC50 ≈ 18 μM). A second library targeting the 4-aminobenzyl moiety was developed, and four analogues displayed comparable activity (26, 27, 28, 34 with IC50 values of 22, 16, 15, and 15 μM respectively) with a further four (24, 25, 32, 33) more active than 18 with IC50 values of 10, 6.9, 12, and 10 μM, respectively. Docking studies rationalized the structure-activity relationship (SAR) with the biological data. 3-Sulfo-N-benzyl-1,8-naphthalimide, potassium salt (25) with an IC50 ≈ 6.9 μM, is the most potent clathrin terminal domain-amphiphysin inhibitor reported to date.

Dynamin is required for clathrin-mediated endocytosis (CME). Its GTPase activity is stimulated by phospholipid binding to its PH domain, which induces helical oligomerization. We have designed a series of novel pyrimidine-based "Pyrimidyn" compounds that inhibit the lipid-stimulated GTPase activity of full length dynamin I and II with similar potency. The most potent analogue, Pyrimidyn 7, has an IC50 of 1.1 μM for dynamin I and 1.8 μM for dynamin II, making it among the most potent dynamin inhibitors identified to date. We investigated the mechanism of action of the Pyrimidyn compounds in detail by examining the kinetics of Pyrimidyn 7 inhibition of dynamin. The compound competitively inhibits both GTP and phospholipid interactions with dynamin I. While both mechanisms of action have been previously observed separately, this is the first inhibitor series to incorporate both and thereby to target two distinct domains of dynamin. Pyrimidyn 6 and 7 reversibly inhibit CME of both transferrin and EGF in a number of non-neuronal cell lines as well as inhibiting synaptic vesicle endocytosis (SVE) in nerve terminals. Therefore, Pyrimidyn compounds block endocytosis by directly competing with GTP and lipid binding to dynamin, limiting both the recruitment of dynamin to membranes and its activation. This dual mode of action provides an important new tool for molecular dissection of dynamin's role in endocytosis.

Calcineurin is a phosphatase that is activated at the last known stage of mitosis, abscission. Among its many substrates, it dephosphorylates dynamin II during cytokinesis at the midbody of dividing cells. However, dynamin II has several cellular roles including clathrin-mediated endocytosis, centrosome cohesion and cytokinesis. It is not known whether dynamin II phosphorylation plays a role in any of these functions nor have the phosphosites involved in cytokinesis been directly identified. We now report that dynamin II from rat lung is phosphorylated to a low stoichiometry on a single major site, Ser-764, in the proline-rich domain. Phosphorylation on Ser-764 also occurred in asynchronously growing HeLa cells and was greatly increased upon mitotic entry. Tryptic phospho-peptides isolated by TiO2 chromatography revealed only a single phosphosite in mitotic cells. Mitotic phosphorylation was abolished by roscovitine, suggesting the mitotic kinase is cyclin-dependent kinase 1. Cyclin-dependent kinase 1 phosphorylated full length dynamin II and Glutathione-S-Transferase-tagged–dynamin II–proline-rich domain in vitro, and mutation of Ser-764 to alanine reduced proline-rich domain phosphorylation by 80%, supporting that there is only a single major phosphosite. Ser-764 phosphorylation did not affect clathrin-mediated endocytosis or bulk endocytosis using penetratin-based phospho-deficient or phospho-mimetic peptides or following siRNA depletion/rescue experiments. Phospho-dynamin II was enriched at the mitotic centrosome, but this targeting was unaffected by the phospho-deficient or phospho-mimetic peptides. In contrast, the phospho-mimetic peptide displaced endogenous dynamin II, but not calcineurin, from the midbody and induced cytokinesis failure. Therefore, phosphorylation of dynamin II primarily occurs on a single site that regulates cytokinesis downstream of calcineurin, rather than regulating endocytosis or centrosome function.

Meiobenthos assemblages in eight estuaries of the Mekong river system were investigated in August 2008 (from the Cua Tieu estuary to the Tran De estuary). In each estuary, one sampling station was established for meiobenthos sampling. Twelve major taxa of meiobenthos were recorded in this estuarine system, including Nematoda, Copepoda, Turbellaria, Polychaeta, Oligochaeta, Tardigrada, Bivalvia, Ostracoda, Amphipoda, Cumacea, Gastrotricha, Gastropoda, and Crustacean Nauplii larvae. The densities of the meiobenthos range from 581 to 3168 inds/10 cm2. Nematodes always occupy the highest numbers with a percentage ranging from 64–99%. There are 135 nematode genera recorded in this study with the following as dominant genera Desmodora, Leptolaimus, Halalaimus, Thalassomonhystera, Theristus, Daptonema, Rhynchonema, Parodontophora, and Oncholaimus. Although the biodiversity of the meiobenthos at higher taxa level is not high compared to other marine environments, the estimates of nematode biodiversity at the genus level indicates high values. The increase in number of genera with increasing sampling intensity illustrate that the diversity is underestimated and would have been higher if the authors had considered a larger number of individuals, more replicates per station, and more sampling stations.

Screening identified two bisindolylmaleimides as 100 microM inhibitors of the GTPase activity of dynamin I. Focused library approaches allowed development of indole-based dynamin inhibitors called dynoles. 100-Fold in vitro enhancement of potency was noted with the best inhibitor, 2-cyano-3-(1-(2-(dimethylamino)ethyl)-1H-indol-3-yl)-N-octylacrylamide (dynole 34-2), a 1.3 +/- 0.3 microM dynamin I inhibitor. Dynole 34-2 potently inhibited receptor mediated endocytosis (RME) internalization of Texas red-transferrin. The rank order of potency for a variety of dynole analogues on RME in U2OS cells matched their rank order for dynamin inhibition, suggesting that the mechanism of inhibition is via dynamin. Dynoles are the most active dynamin I inhibitors reported for in vitro or RME evaluations. Dynole 34-2 is 15-fold more active than dynasore against dynamin I and 6-fold more active against dynamin mediated RME (IC(50) approximately 15 microM; RME IC(50) approximately 80 microM). The dynoles represent a new series of tools to better probe endocytosis and dynamin-mediated trafficking events in a variety of cells.

Investigation of an extract of the Australian marine sponge Psammoclema sp. for dynamin I inhibitory activity led to the isolation of four new trihydroxysterols (1-4) related to aragusterol G. These compounds were largely identified by 1D and 2D NMR spectroscopic methods. While 1 was found to be inactive in the dynamin bioassay, bioassays did reveal that compounds 1-4 inhibited the growth of colorectal, breast, ovarian, and prostate cancer cell lines (GI(50) 5-27 microM). The additional insight that these new compounds give to previous SAR studies is discussed briefly.

Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Sydney, Australia (A.Q., A.B.M., E.M.v.D., J.R., N.C., C.S.M., P.J.R.); Chemistry, School of Environmental and Life Sciences, University of Newcastle, Newcastle, Australia (A.M.); Department of Human Physiology, Flinders University, Adelaide, Australia (D.J.K.), Prince Henry's Institute of Medical Research, Victoria, Australia (C.C.); and, Membrane Biology Group, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland (M.A.C) Dynamin is a GTPase enzyme involved in membrane constriction and fission during endocytosis. Phospholipid binding via its pleckstrin homology domain maximally stimulates dynamin activity. We developed a series of surface-active small-molecule inhibitors, such as myristyl trimethyl ammonium bromide (MiTMAB) and octadecyltrimethyl ammonium bromide (OcTMAB), and we now show MiTMAB targets the dynamin-phospholipid interaction. MiTMAB inhibited dynamin GTPase activity, with a Ki of 940 ± 25 nM. It potently inhibited receptor-mediated endocytosis (RME) of transferrin or epidermal growth factor (EGF) in a range of cells without blocking EGF binding, receptor number, or autophosphorylation. RME inhibition was rapidly reversed after washout. The rank order of potency for a variety of MiTMAB analogs on RME matched the rank order for dynamin inhibition, suggesting dynamin recruitment to the membrane is a primary cellular target. MiTMAB also inhibited synaptic vesicle endocytosis in rat brain nerve terminals (synaptosomes) without inducing depolarization or morphological defects. Therefore, the drug rapidly and reversibly blocks multiple forms of endocytosis with no acute cellular damage. The unique mechanism of action of MiTMAB provides an important tool to better understand dynamin-mediated membrane trafficking events in a variety of cells.

A survey of entomopathogenic nematodes in Vietnam yielded several Heterorhabditis isolates. The majority belonged to H. indica; their morphometrics are given in this paper. Three isolates collected in forests in Backan, Ninhbinh and Kontum provinces, Vietnam are here described as a new species Heterorhabditis baujardi sp. n. The new species is distinguished from the other ten valid Heterorhabditis species by a combination of morphological, morphometrical, and DNA characters. Heterorhabditis baujardi sp. n. is morphometrically similar to H. indica, but can be separated from this species by the shape of the gubernaculum and the number of normal pairs of genital papillae. The gubernaculum of H. baujardi sp. n. with the proximal end ventrally curved resembles that of H. bacteriophora. Heterorhabditis baujardi sp. n. can be separated from this latter species by a shorter body length of infective juveniles and longer spicules, longer gubernaculum, and a higher spicule length to anal body diameter ratio of males. The canonical discriminant analysis of morphometrical characters of both infective juveniles and males failed to discriminate Heterorhabditis baujardi sp. n. from H. indica. However, the new species was easily distinguished from H. downesi, H. marelatus, H. megidis and H. bacteriophora. Heterorhabditis baujardi sp. n. was slightly separated from H. bacteriophora by variables of the infective juveniles, but was clearly distinguished by variables of the males. Cross-breeding tests using isolates of the new species and H.indica did not yield fertile progeny. Analysis of the ITS1 sequence of rDNA of H. baujardi sp. n. revealed substantial differences with other known ITS1 Heterorhabditis sequences. Phylogenetic relationships between Heterorhabditis species and the usefulness of morphological and molecular characters for identification of species from this group are discussed.

Two new species of Steinernema (Rhabditida), Steinernema loci sp. n. and S. thanhi sp. n., were isolated from beach soil in Thanhhoa and Hatinh provinces in the northern part of Vietnam. A combination of morphological, morphometric and rDNA-RFLP features indicated the distinctness of both species from other Steinernema spp. Diagnostic characters of Steinernema loci sp. n. include: total body length (896-1072 μm), distance from anterior end to excretory pore (EP = 71-86 μm), tail length (66-83 μm), lateral field in mid-body with eight ridges (nine distinct lines) and rounded, broad and smooth anterior end of the third stage infective juvenile; first generation males were characterised by body width, spicule length and the ratio spicule length : anal body width (SW). Diagnostic characters of Steinernema thanhi sp. n. third stage infective juveniles include: total body length (720-960 μm), EP (68-84 μm), tail length (52-72 μm), lateral field in mid-body with eight ridges (nine distinct lines) and rounded, broad and smooth anterior end. Spicule length, ratio SW and arrangement of genital papillae characterised the first generation males.

Obesity is a growing global health problem, but few drugs are available for the treatment of obesity. Several classes of compounds have been studied and demonstrated for the human lipase inhibition activity - a target in obesity prevention. This study was about design, synthesis and biological evaluation of some synthetic chalcones as pancreatic lipase inhibitors. FlexX software integrated in LeadIT was used for molecular docking studies of 66 chalcone derivatives. 6 derivatives with low docking scores (good binding affinity) were selected for synthesis using both classical and microwave-assisted Claisen-Schmidt condensation reactions.Biological evaluation on pancreatic lipase indicated that some chalcones showed good lipase inhibition activities and that there were correlations between in silico model and biological activities. These presented the possibility to apply virtual screening tools in finding potential agents with high obesity-prevention capacity.

The temporal variation of nematode communities in eight mouth stations of the Mekong River system was investigated in order to compare the change between the dry and the wet season. The nematode data was analysed by multivariate techniques such as SIMPROF, MDS, ANOSIM and SIMPER in the software PRIMER v.6 – PERMANOVA. Our results showed that average dissimilarity between seasons of the nematode communities in each station was high. Seasonal factor did not affect strongly their distribution pattern. Dominant genera Desmodora and Oncholaimellus usually occurred in the sand stations and Parodontophora and Halalaimus were characteristic for the silty group in both seasons. The spatial variations in this estuarine area have an influence that is larger than seasonal factors. Sự phân bố theo thời gian của quần xã tuyến trùng sống tự do vùng cửa sông Mekong được nghiên cứu nhằm đánh giá sự khác biệt của chúng trong mùa mưa và mùa khô. Dữ liệu của tuyến trùng được xử lý và phân tích đa biến như SIMPROF, MDS, ANOSIM và SIMPER bằng phần mềm PRIMER v.6 – PERMANOVA. Kết quả nghiên cứu cho thấy sự khác biệt theo mùa trong quần xã tuyến trùng tại mỗi điểm là khá lớn nhưng yếu tố mùa không ảnh hưởng gì tới mô hình phân bố của chúng. Một số giống ưu thế trong nền đáy cát như Desmodora and Oncholaimellus trong khi đó Parodontophora và Halalaimus thích nghi nền bùn sét phù sa vẫn hiễn diện trong cả 2 mùa. Kết quả nghiên cứu cũng cho thấy sự biến động trong không gian ở đây lớn hơn sự biến động về mùa vụ., Journal of Vietnamese Environment, Vol 4 No 1 (2013)

International audience; The botulinum neurotoxins (BoNTs) are di-chain bacterial proteins responsible for the paralytic disease botulism. Following binding to the plasma membrane of cholinergic motor nerve terminals, BoNTs are internalized into an endocytic compartment. Although several endocytic pathways have been characterized in neurons, the molecular mechanism underpinning the uptake of BoNTs at the presynaptic nerve terminal is still unclear. Here, a recombinant BoNT/A heavy chain binding domain (Hc) was used to unravel the internalization pathway by fluorescence and electron microscopy. BoNT/A-Hc initially enters cultured hippocampal neurons in an activity-dependent manner into synaptic vesicles and clathrin-coated vesicles before also entering endosomal structures and multivesicular bodies. We found that inhibiting dynamin with the novel potent Dynasore analog, Dyngo-4a(TM), was sufficient to abolish BoNT/A-Hc internalization and BoNT/A-induced SNAP25 cleavage in hippocampal neurons. Dyngo-4a also interfered with BoNT/A-Hc internalization into motor nerve terminals. Furthermore, Dyngo-4a afforded protection against BoNT/A-induced paralysis at the rat hemidiaphragm. A significant delay of >30% in the onset of botulism was observed in mice injected with Dyngo-4a. Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms.

A series of halogen containing 1,4-naphthoquinon derivatives (1-4,5a-f) were synthesized and studied for their antifungal activities against C. albicans ATCC10231, C. albicans 955, T. mentagrophytes and M. gypseum. The results indicate that compound 2-hydroxy-3-chloro-1,4-naphthoquinone (2), 2-(N-acetyl)- acetamido-3-chloro- 1,4-napthoquinone (3) and 2-(N-acetyl)-acetamido-3-chloro- 1,4- napthoquinone (4) have potent antifungal activity. Among these promising antifungal candidates, 2 and 4 showed better activity than that of clinically antifungal drug clotrimazole (MIC = 8 μg/ml) with MIC = 1 μg/ml and 4 μg/ml, respectively against C.albicans ATCC10231. Compound 2 also exhibited an extremely potent activity (MIC = 0.25 μg/ml) against C.albicans 955 strain compared with clotrimazole (MIC = 16 μg/ml). Structure and activity relationship (SAR) study demonstrated that replacing of 3-position in 1,4- naphthoquinon by a Cl group is essential for antifungal activity. Meanwhile, antifungal activity was decreased considerably when the hydrogen atom at position-2 in naphthoquinone structure were replaced by a bulky group (e.g. diacetyl of phenyl group).

Synaptic vesicles (SVs) are retrieved by more than one mode in central nerve terminals. During mild stimulation, the dominant SV retrieval pathway is classical clathrin-mediated endocytosis (CME). During elevated neuronal activity, activity-dependent bulk endocytosis (ADBE) predominates, which requires activation of the calcium-dependent protein phosphatase calcineurin. We now report that calcineurin dephosphorylates dynamin I in nerve terminals only above the same activity threshold that triggers ADBE. ADBE was arrested when the two major phospho-sites on dynamin I were perturbed, suggesting that dynamin I dephosphorylation is a key step in its activation. Dynamin I dephosphorylation stimulates a specific dynamin I-syndapin I interaction. Inhibition of this interaction by competitive peptides or by site-directed mutagenesis exclusively inhibited ADBE but did not affect CME. The results reveal that the phospho-dependent dynamin-syndapin interaction recruits ADBE to massively increase SV endocytosis under conditions of elevated neuronal activity.

The proteins of homeobox (HOX) genes are transcription regulators involved in cell type-specific differentiation and patterning of the body plan in vertebrates. Particularly, the HOXD family is involved in limb formation in mice and chicks. There is also some evidence that the HOXD9 gene, a member of the HOXD family, is involved in the pathology of rheumatoid arthritis (RA). The purpose of the present study was to determine if the HOXD9 protein was expressed in RA synovium and then to characterize the HOXD9-expressing cell. Western blotting and immunohistochemical analysis showed that the HOXD9 protein was expressed in the synovium from patients with RA, but not in those from patients with osteoarthritis or healthy individuals. The HOXD9-positive cells were localized in both the lining and sublining areas of the synovium. Furthermore, fluorescent double-staining showed that the HOXD9 protein was expressed in fibroblast-like synoviocytes (FLS). These findings not only indicate that the HOXD9 gene is exclusively expressed in the RA synovium but also suggest that the HOXD9 gene contributes to the pathology of rheumatoid arthritis through the FLS.

SummaryClathrin-mediated endocytosis (CME) regulates many cell physiological processes such as the internalization of growth factors and receptors, entry of pathogens, and synaptic transmission. Within the endocytic network, clathrin functions as a central organizing platform for coated pit assembly and dissociation via its terminal domain (TD). We report the design and synthesis of two compounds named pitstops that selectively block endocytic ligand association with the clathrin TD as confirmed by X-ray crystallography. Pitstop-induced inhibition of clathrin TD function acutely interferes with receptor-mediated endocytosis, entry of HIV, and synaptic vesicle recycling. Endocytosis inhibition is caused by a dramatic increase in the lifetimes of clathrin coat components, including FCHo, clathrin, and dynamin, suggesting that the clathrin TD regulates coated pit dynamics. Pitstops provide new tools to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry and as modulators of cell signaling.