A new nematode, <Emphasis Type="Italic">Pongobius hugoti</Emphasis> gen. et sp. n. from the orangutan <Emphasis Type="Italic">Pongo abelii</Emphasis> (Primates: Hominidae)

Summary Light and scanning electron microscopical examination and molecular analysis of pinworm samples collected from the Sumatran orangutan (Pongo abelii) from Sumatra (Indonesia) revealed the presence of a new taxon, Pongobius hugoti gen. et sp. n. (Oxyuridae: Enterobiinae). The monotypic genus Pongobius is characterised by the presence of a triangular mouth, three rounded teeth and three chisel-like inner teeth in the buccal cavity, an oesophagus with a long pharyngeal part, corpus posteriorly slightly enlarged and continuing as a pyriform bulb, isthmus absent. These features differentiate P. hugoti from all members of the subfamily Enterobiinae. The male has a long caudal appendix (> 50% of total tail length). Molecular analysis of the new taxon is presented for more precise identification.     

Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer

Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific β1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch’s response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation.     

Conserved regions of Plasmodium vivax potential vaccine candidate antigens in Sri Lanka:Conscious in silico analysis of prospective conformational epitope regions

Objective:To do mapping and modeling of conformational B cell epitope regions of highly conserved and protective regions of three merozoitecandidate vaccine proteins of Plasmodium vivax(P.vivax),ie.merozoite purface protein-1(PvMSP-1),apical membrane antigen-1 domainⅡ(PvAMA1-DⅡ)and regionⅡof the Duffy binding protein(PvDBPⅡ).and to analyze the immunogenie properties of these predicted epitopes.Methods:3-D structures of amino acid haplotypes from Sri Lanka(available in GeneBank)of PvMSP-1_(19)(n=27),PvAMA1-DⅡ(n=21)and PvDBPⅡ(n=33)were modeled.SEPPA,selected as the best online server was used for conformational epitope predictions,while prediction and moodeling of protein structuve and properties related to immunogenicity was carried out with Geno3D server.SCRATCH Protein Server,NetSurfP Server and standaloneroftware,Genious 5.4.4.Results:SEPPA revealed that regions of predicted conformational epitopes formed 4 clusters in PvMSP-I_(19),and 3 clusters each in PvAMA1-DⅡand PvDBPⅡ,all of which displayed a high degree of hydrophilicity,contained solveut exposed residues,displayed high probability of antigenicity and showed positive antigenic propensity values,that indicated high degree of immunogenicity.Conclusions:Findings of this study revealed and confirmed that different parts of the sequences of each of the conserved regions of the three selected potential vaccine candidate antigens of P.vivax are important with regard to conformational epitope prediction that warrants further laboratory experimental invertigations in in vivo animal models.     

The association between sidewalk length and walking for different purposes in established neighborhoods

ABSTRACT: BACKGROUND: Walking in neighborhood environments is undertaken for different purposes including for transportation and leisure. We examined whether sidewalk availability was associated with participation in, and minutes of neighborhood-based walking for transportation (NWT) and recreation (NWR) after controlling for neighborhood self-selection. METHOD: Baseline survey data from respondents (n=1813) who participated in the RESIDential Environment (RESIDE) project (Perth, Western Australia) were used. Respondents were recruited based on their plans to move to another neighborhood in the following year. Usual weekly neighborhood-based walking, residential preferences, walking attitudes, and demographics were measured. Characteristics of the respondent's baseline neighborhood were measured including transportation-related walkability and sidewalk length. A Heckman two-stage modeling approach (multivariate Probit regression for walking participation, followed by a sample selection-bias corrected OLS regression for walking minutes) estimated the relative contribution of sidewalk length to NWT and NWR. RESULTS: After adjustment, neighborhood sidewalk length and walkability were positively associated with a 2.97 and 2.16 percentage point increase in the probability of NWT participation, respectively. For each 10km increase in sidewalk length, NWT increased by 5.38 min/wk and overall neighborhood-based walking increased by 5.26 min/wk. Neighborhood walkability was not associated with NWT or NWR minutes. Moreover, sidewalk length was not associated with NWR minutes. CONCLUSION: Sidewalk availability in established neighborhoods may be differentially associated with walking for different purposes. Our findings suggest that large investments in sidewalk construction alone would yield small increases in walking.     

Two remarkable pinworms (Nematoda: Enterobiinae) parasitizing orangutan (Pongo abelii) in the Sumatra (Indonesia) including Lemuricola (Protenterobius) pongoi n.sp.

Summary  Two species of pinworms (Enterobiinae) were collected from fresh faeces of semi-wild orangutans Pongo abelii Lesson living in northern Sumatra (Indonesia). The female of Enterobius (Enterobius) buckleyi Sandosham, 1950 is redescribed. Lemuricola (Protenterobius) pongoi n. sp. is described on the basis of females (no males are available) and distinguished from L. (P.) nycticebi (Baylis, 1928) by cephalic and mouth morphology (head and teeth superstructures), body (9.85–15.46 mm) and tail (2.34–2.95 mm) length, smaller eggs (48–56 x 22–28 μm), longer vulva distance from anterior extremity (2.05–3.09 mm) and other features. Characteristic is the total body length/oesophagus length ratio (1: 15.3–22.0). Both nematode species were studied using scanning electron microscopy for the first time.     

In vivo targeting of human DC‐SIGN drastically enhances CD8+ T‐cell‐mediated protective immunity

Vaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8⁺ T‐cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC‐SIGN (DC‐specific‐ICAM3‐grabbing‐nonintegrin/CD209) is a C‐type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC‐SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC‐SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti‐DC‐SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti‐DC‐SIGN antibodies conjugated to OVA induced strong and persistent antigen‐specific CD4⁺ and CD8⁺ T‐cell responses, which efficiently protected from infection with OVA‐expressing Listeria monocytogenes. Thus, we propose DC targeting via DC‐SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens.     

<Emphasis Type="Italic">Oochoristica koubeki</Emphasis> n. sp. (Cestoda,Anoplocephalidae) from African <Emphasis Type="Italic">Chamaeleo senegalensis</Emphasis> (Chamaeleonidae) and emendation of the genus <Emphasis Type="Italic">Oochoristica</Emphasis> Lühe, 1898

During a survey of species diversity and ecology of selected West African vertebrates in the Niokolo Koba National Park, Senegal, two Chamaeleo senegalensis Daudin, 1802 (Chamaeleonidae) were collected and examined for parasites. A new species, Oochoristica koubeki n. sp., anoplocephalidian cestode of the genus Oochoristica Lühe, 1898 is described from the intestine of this host. The new species is related to O. theileri Fuhrmann, 1924; O. theileri Fuhrmann, 1924 f. major Baer, 1933; O. celebensis Yamaguti, 1954 and O. rostellata Zschokke, 1905 var. agamicolla Dollfus, 1957. All the forenamed species share characteristic strobila with proglottids wider than long. Oochoristica koubeki n. sp. differs from these species in different proportions of scolex, cirrus sac, ovarium and vitellarium, further differences are in number of testes and presence of reinforced genital atrium. Only O. theileri shares two last mentioned features, however it differs in shape of testes (rounded) and in distribution of testes (two clusters). The new species differs from all other species in extremely high number of egg’s capsules, different host species and zoogeographic distribution. Emendation of genus diagnosis sensu Beveridge (1994) is provided.     

Postural orthostatic tachycardia syndrome associated with multiple sclerosis

BackgroundThe aim of this study was to determine if there is a difference in the frequency of postural orthostatic tachycardia syndrome (POTS) in patients with multiple sclerosis (MS) compared to patients with symptoms of orthostatic intolerance and with no evidence of MS or other neurological illness.MethodsWe analyzed data gathered from 293 patients who underwent the head-up tilt table test protocol. Group 1 included prospectively analyzed 112 with MS and group 2 included retrospectively analyzed 181 patients who were evaluated because of symptoms of orthostatic intolerance, and with no evidence of MS or other neurological illness. If POTS was identified the head-up tilt table test was repeated and supine as well as standing serum epinephrine and norepinephrine were determined.ResultsPOTS was identified in 39 patients: 21 (19%) in the MS group comparing to 18 (10%) in the non MS group (p = 0.035). There was no difference between groups in the occurrence of POTS associated syncope (p = 0.52). There was no difference between groups in the epinephrine or norepinephrine in supine and standing positions. While both standing epinephrine and norepinephrine levels were significantly higher compared to levels in the supine position in the non MS group, only standing norepinephrine levels were significantly higher in the MS group.ConclusionsThe results of this study suggest that POTS is associated with MS.