Identification and Characterization of Paramyosin from Cyst Wall of Metacercariae Implicated Protective Efficacy against Clonorchis sinensis Infection

Human clonorchiasis has been increasingly prevalent in recent years and results in a threat to the public health in epidemic regions, motivating current strategies of vaccines to combat Clonorchis sinensis (C. sinensis). In this study, we identified C. sinensis paramyosin (CsPmy) from the cyst wall proteins of metacercariae by proteomic approaches and characterized the expressed recombinant pET-26b-CsPmy protein (101 kDa). Bioinformatics analysis indicated that full-length sequences of paramyosin are conserved in helminthes and numerous B-cell/T-cell epitopes were predicted in amino acid sequence of CsPmy. Western blot analysis showed that CsPmy was expressed at four life stages of C. sinensis, both cyst wall proteins and soluble tegumental components could be probed by anti-CsPmy serum. Moreover, immunolocalization results revealed that CsPmy was specifically localized at cyst wall and excretory bladder of metacercaria, as well as the tegument, oral sucker and vitellarium of adult worm. Both immunoblot and immunolocalization results demonstrated that CsPmy was highly expressed at the stage of adult worm, metacercariae and cercaria, which could be supported by real-time PCR analysis. Both recombinant protein and nucleic acid of CsPmy showed strong immunogenicity in rats and induced combined Th1/Th2 immune responses, which were reflected by continuous high level of antibody titers and increased level of IgG1/IgG2a subtypes in serum. In vaccine trials, comparing with control groups, both CsPmy protein and DNA vaccine exhibited protective effect with significant worm reduction rate of 54.3% (p<0.05) and 36.1% (p<0.05), respectively. In consistence with immune responses in sera, elevated level of cytokines IFN-γ and IL-4 in splenocytes suggested that CsPmy could induce combined cellular immunity and humoral immunity in host. Taken together, CsPmy could be a promising vaccine candidate in the prevention of C. sinensis regarding its high immunogenicity and surface localization

Characterization of S3Pvac Anti-Cysticercosis Vaccine Components: Implications for the Development of an Anti-Cestodiasis Vaccine

Background: Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis.Methodology/ Principal Findings: In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. on the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms.Conclusions/ Significance: These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates

The paradigm shift to precision oncology between political will and cultural acceptance

International audienceNo abstract availabl

Lasiurus ebenus Fazzolari-Correa 1994

&lt;i&gt;Lasiurus ebenus&lt;/i&gt; Fazzolari-Corr&ecirc;a, 1994 &lt;p&gt;Black hairy-tailed bat&lt;/p&gt; &lt;p&gt; &lt;b&gt;Holotype.&lt;/b&gt; Adult male collected at Parque Estadual da Ilha do Cardoso (25&deg;05'S, 47&deg;59'W, elev. 40 m), S&atilde;o Paulo, Brazil (Fazzolari-Corr&ecirc;a 1995). Skin, partial skeleton and skull are deposited in the Museu de Zoologia da Universidade de S&atilde;o Paulo (MZUSP 28125).&lt;/p&gt; &lt;p&gt; &lt;b&gt;Other specimen.&lt;/b&gt; Adult male (MN 83982) composed by whole body (in alcohol) with the skull removed, collected at Parque Estadual Carlos Botelho (24&deg;10'S, 47&deg;58'W, elev. 630 m), S&atilde;o Paulo, Brazil.&lt;/p&gt; &lt;p&gt; &lt;b&gt;Diagnosis.&lt;/b&gt; Black wing membranes; dorsal and ventral pelage almost entirely black; first upper premolar present; and medium sized within the genus, with forearm length close to 45.5 mm.&lt;/p&gt; &lt;p&gt; &lt;b&gt;Description.&lt;/b&gt; &lt;i&gt;Lasiurus ebenus&lt;/i&gt; is a medium-sized species (body mass 12.5 g, 14 g; forearm length 45.6 mm, 45.7mm; other measurements are in Table 1). Membranes, muzzle, lip and ear borders are black. One-third to onehalf of the proximal portion of the interfemoral membrane and the ventral region of the humeri and forearms have bone-brown to dark-brown hairs. Ears are broad and rounded; tragus is triangular and measures ca. 50% of the height of the ear; hindfoot small, less than two-thirds of the length of the tibia; the calcar is about twice as long as the hindfoot, and about as long as the free margin of the interfemoral membrane. Pelage color is black in general, with dorsal fur tricolored (black basal band, bone-brown to dark-brown in the middle, black tips), and ventral fur bicolored (ca. 2/3 of the basis is bone-brown, and 1/3 of the tip is black); without stripes, frosting or spots (Fig. 1).&lt;/p&gt; &lt;p&gt;Dental formula is i 1 /3 c 1/1 p 2/ 2 m 3/3 = 32. The second premolar is double-rooted, the rostrum is relatively short, and the braincase is broad, with a low sagittal crest.&lt;/p&gt; &lt;p&gt; &lt;b&gt;Comparisons.&lt;/b&gt; Rostrum short, sagittal crest weak, first upper premolar (P1) present, and fourth upper premolar (P4) double rooted indicate that &lt;i&gt;L. ebenus&lt;/i&gt; belongs to the red bats group (see Baird &lt;i&gt;et al.&lt;/i&gt; 2015), which also includes &lt;i&gt;L. atratus&lt;/i&gt;, &lt;i&gt;L. blossevillii&lt;/i&gt;, &lt;i&gt;L. borealis&lt;/i&gt;, &lt;i&gt;L. castaneus&lt;/i&gt;, &lt;i&gt;L. degelidus&lt;/i&gt;, &lt;i&gt;L. egregius&lt;/i&gt;, &lt;i&gt;L. minor&lt;/i&gt;, &lt;i&gt;L. pfeifferi&lt;/i&gt;, &lt;i&gt;L. seminolus&lt;/i&gt;, and &lt;i&gt;L. varius&lt;/i&gt; (see Baird &lt;i&gt;et al.&lt;/i&gt; 2015; Fazzolari-Corr&ecirc;a 1994). This group is represented in Brazil by &lt;i&gt;L. blossevillii&lt;/i&gt;, &lt;i&gt;L. castaneus&lt;/i&gt;, &lt;i&gt;L. ebenus&lt;/i&gt; and &lt;i&gt;L. egregius&lt;/i&gt; (see Nogueira &lt;i&gt;et al.&lt;/i&gt; 2014). &lt;i&gt;Lasiurus ebenus&lt;/i&gt; can be distinguished from these species by the pelage almost entirely black, and wing membranes black, which are diagnostic for the species. The pelage is reddish above and paler below in &lt;i&gt;L. blossevillii&lt;/i&gt;; chestnut above and dark-brown below, with buffy-yellow and whitish patches on shoulders in &lt;i&gt;L. castaneus&lt;/i&gt;; and reddish above and dark brown below, with bright red tips in &lt;i&gt;L. egregius&lt;/i&gt;. &lt;i&gt;Lasiurus ebenus&lt;/i&gt; (45.6 mm, 45.7 mm) is larger than &lt;i&gt;L. blossevillii&lt;/i&gt; (forearm length: ~ 42 mm) and similar in size to &lt;i&gt;L. castaneus&lt;/i&gt; (~ 45 mm) and &lt;i&gt;L. egregius&lt;/i&gt; (forearm larger than 48 mm). Beyond fur color, &lt;i&gt;L. ebenus&lt;/i&gt; can be distinguished from &lt;i&gt;L. castaneus&lt;/i&gt; in the hindfoot length (11 mm in &lt;i&gt;ebenus&lt;/i&gt;, 8 mm in &lt;i&gt;castaneus&lt;/i&gt;), and the braincase breadth (7.6 mm in &lt;i&gt;ebenus&lt;/i&gt;, 8.2 mm in &lt;i&gt;castaneus&lt;/i&gt;; see Bianconi &amp; Pedro, 2007; Fazzolari-Corr&ecirc;a 1994; Handley 1960; Reid 2009).&lt;/p&gt; &lt;p&gt; &lt;i&gt;Lasiurus cinereus&lt;/i&gt; and &lt;i&gt;L. ega&lt;/i&gt; also occur in Brazil (see Nogueira &lt;i&gt;et al.&lt;/i&gt; 2014). The pelage of &lt;i&gt;L. ega&lt;/i&gt; varies from pale whitish-buff to yellowish and orange, with ventral fur generally paler. &lt;i&gt;L. cinereus&lt;/i&gt; has dorsal fur tricolored (basis and tips dark-brown, intermediate band yellowish, with a frosting appearance in general), and ventral fur bicolored (basis dark-brown, tips light-brown). These species are allocated in other morphological groups, and can be also distinguished from &lt;i&gt;L. ebenus&lt;/i&gt; by a suite of qualitative and quantitative traits (Barquez &lt;i&gt;et al.&lt;/i&gt; 1999; Gonz&aacute;lez 1989; Kurta &amp; Lehr 1995; Vieira 1942).&lt;/p&gt; &lt;p&gt; &lt;b&gt;Distribution.&lt;/b&gt; &lt;i&gt;L. ebenus&lt;/i&gt; is known from two localities in the south portion of the Serra do Mar mountain chain (Fig. 4), which is the largest remnant of Atlantic Forest in southeastern Brazil. Both localities are composed by ombrophilous dense forest. The holotype comes from Ilha do Cardoso State Park, Canan&eacute;ia, S&atilde;o Paulo, Brazil (25&deg;05'S, 47&deg;59'W, elev. 40 m); and the other specimen (MN 83982) comes from Carlos Botelho State Park, Sete Barras, S&atilde;o Paulo, Brazil, on the eastern slope of the Serra do Mar mountain chain (24&deg;10'S, 47&deg;58'W, elev. 630 m). The second record for the species is 101 kilometers away from the type locality (Fig. 4).&lt;/p&gt; &lt;p&gt; &lt;b&gt;Natural history.&lt;/b&gt; The holotype of &lt;i&gt;L. ebenus&lt;/i&gt; was captured in a mist net placed over a stream in continuous forest. MN 83982 was captured on the lowest shelf of the mist net, which was about 1 m above the water. The water level was about one foot deep, and the substrate is composed by rocks and sand in a lotic water system. Representatives of other species of &lt;i&gt;Lasiurus&lt;/i&gt; are often netted in similar conditions, feeding on insects that fly close to watercourses (Handley 1960, 1996; Kurta &amp; Lehr 1995; Villalobos-Chaves &amp; Dick 2014). We speculate that &lt;i&gt;L. ebenus&lt;/i&gt; forages on watercourses and streams, catching insects in flight, similarly to its congeners. Bat flies collected in the holotype of &lt;i&gt;L. ebenus&lt;/i&gt; were later described by Graciolli (2003) as a new species, &lt;i&gt;Basilia insularis&lt;/i&gt;, from which the only reported host is still &lt;i&gt;L. ebenus&lt;/i&gt; (Graciolli &lt;i&gt;et al.&lt;/i&gt; 2007).&lt;/p&gt;Published as part of &lt;i&gt;Cláudio, Vinícius C., Barbosa, Gedimar P., Novaes, Roberto Leonan M., Rassy, Fabrício B., Rocha, Vlamir J. &amp; Moratelli, Ricardo, 2018, Second record of Lasiurus ebenus (Chiroptera, Vespertilionidae), with comments on its taxonomic status, pp. 513-522 in Zootaxa 4403 (3)&lt;/i&gt; on pages 516-519, DOI: 10.11646/zootaxa.4403.3.5, &lt;a href="http://zenodo.org/record/1212931"&gt;http://zenodo.org/record/1212931&lt;/a&gt

Unraveling the Wide Spectrum of Melanoma Biomarkers.

The use of biomarkers in medicine has become essential in clinical practice in order to help with diagnosis, prognostication and prediction of treatment response. Since Alexander Breslow's original report on "melanoma and prognostic values of thickness", providing the first biomarker for melanoma, many promising new biomarkers have followed. These include serum markers, such as lactate dehydrogenase and S100 calcium-binding protein B. However, as our understanding of the DNA mutational profile progresses, new gene targets and proteins have been identified. These include point mutations, such as mutations of the BRAF gene and tumour suppressor gene tP53. At present, only a small number of the available biomarkers are being utilised, but this may soon change as more studies are published. The aim of this article is to provide a comprehensive review of melanoma biomarkers and their utility for current and, potentially, future clinical practice