A new species of freshwater sponge (Porifera:Spongillidae) of the genus Radiospongilla from Lake Pedder in Tasmania

Lake Pedder is the home of a number of relictual organisms. One of those, a new species of freshwater sponge of the genus Radiospongilla, is described herein. Radiospongilla pedderensis sp. nov. occurs throughout most of the lake and often is found in very large numbers in many bays. Radiospongilla is widely distributed in tropical and sub-tropical regions of all continents. The pneumatic layer of the gemmule contains numerous abnormal gemmoscleres a condition probably caused by the chemistry of the lake. The morphology and dimensions of the megascleres, gemmoscleres and aberrant gemmoscleres, as well as the location, structure and size of gemmules, are provided for R. pedderensis. The sponge is a bright green colour due to intracellular zoochlorellae. Their presence in local members of Radiospongilla has been the subject of considerable speculation but herein they are illustrated for the first time in an Australian species

Body Measures in Endangered Domestic Balkan Donkey Breed

Information regarding morphology of endangered autochthonous donkey breed in Serbia is insufficient. The aim of the study was to establish 18 morphometric values for the Balkan donkey breed and to explore possible age dependence of the parameters tested. In addition, inter-breed similarity of morphometric parameters was assessed by comparing the data obtained for the Balkan donkey with available morphometric measurements of several previously characterized donkey breeds. The study population included 74 donkeys, divided in two age groups (group A ≤ 3 years; group B > 3 years). Significant morphometric differences (p<0.05) in body length, head length, chest circumference and body weight were found between two age groups. Significant differences in morphological parameters were revealed among the Balkan donkey and other donkey breeds (Catalonian, Croatian and Albanian). However, the smallest distance was between the Balkan donkey and Albanian donkeys as demonstrated by the results of cluster analysis. The results of morphometric analyses showed consistency of the obtained values within the breed, and diversity as compared to other donkey breeds, and, thus, could be taken as referent for the Domestic Balkan donkey. The information gained through this comprehensive morphometric characterization of the Balkan donkey breed provides a basis for conservation and development of the breed standard

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

BACKGROUND: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain. METHODS: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses. RESULTS: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working fulltime and the proportion of patients who were able to return to work. CONCLUSION: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain

OnabotulinumtoxinA in the treatment of overactive bladder: a cost-effectiveness analysis versus best supportive care in England and Wales

The cost-effectiveness of onabotulinumtoxinA (BOTOX®) 100 U + best supportive care (BSC) was compared with BSC alone in the management of idiopathic overactive bladder in adult patients who are not adequately managed with anticholinergics. BSC included incontinence pads and, for a proportion of patients, anticholinergics and/or occasional clean intermittent catheterisation. A five-state Markov model was used to estimate total costs and outcomes over a 10-year period. The cohort was based on data from two placebo-controlled trials and a long-term extension study of onabotulinumtoxinA. After discontinuation of initial treatment, a proportion of patients progressed to downstream sacral nerve stimulation (SNS). Cost and resource use was estimated from a National Health Service perspective in England and Wales using relevant reference sources for 2012 or 2013. Results showed that onabotulinumtoxinA was associated with lower costs and greater health benefits than BSC in the base case, with probabilistic sensitivity analysis indicating an 89 % probability that the incremental cost-effectiveness ratio would fall below £20,000. OnabotulinumtoxinA remained dominant over BSC in all but two scenarios tested; it was also economically dominant when compared directly with SNS therapy. In conclusion, onabotulinumtoxinA appears to be a cost-effective treatment for overactive bladder compared with BSC alone

Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

Plasmodium Strain Determines Dendritic Cell Function Essential for Survival from Malaria

The severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. However, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. Identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. Since immunity is initiated by dendritic cells (DCs), we compared their phenotype and function following infection with either a nonlethal or lethal strain of the rodent parasite, Plasmodium yoelii, to identify their contribution to disease severity. DCs from nonlethal infections were fully functional and capable of secreting cytokines and stimulating T cells. In contrast, DCs from lethal infections were not functional. We then transferred DCs from mice with nonlethal infections to mice given lethal infections and showed that these DCs mediated control of parasitemia and survival. IL-12 was necessary for survival. To our knowledge, our studies have shown for the first time that during a malaria infection, DC function is essential for survival. More importantly, the functions of these DCs are determined by the strain of parasite. Our studies may explain, in part, why natural malaria infections may have different outcomes

Multi-target drug with potential applications: violacein in the spotlight

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein’s action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.Fil: Durán, Nelson. Universidade Estadual de Campinas; BrasilFil: Nakazato, Gerson. Universidade Estadual de Londrina; BrasilFil: Durán, Marcela. Universidade Estadual de Campinas; BrasilFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Stanisic, Danijela. Universidade Estadual de Campinas; BrasilFil: Brocchi, Marcelo. Universidade Estadual de Campinas; BrasilFil: Fávaro, Wagner J.. Universidade Estadual de Campinas; BrasilFil: Ferreira Halder, Carmen V.. Universidade Estadual de Campinas; BrasilFil: Justo, Giselle Z.. Universidade Federal de Sao Paulo.; BrasilFil: Tasic, Ljubica. Universidade Estadual de Campinas; Brasi

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens