Whole-organ isolation approach as a basis for tissue-specific analyses in Schistosoma mansoni

As a neglected disease, schistosomiasis is still an enormous problem in the tropics and subtropics. Since the 1980s, Praziquantel (PZQ) has been the drug of choice but can be anticipated to lose efficacy in the future due to emerging resistance. Alternative drugs or efficient vaccines are still lacking, strengthening the need for the discovery of novel strategies and targets for combating schistosomiasis. One avenue is to understand the unique reproductive biology of this trematode in more detail. Sexual maturation of the adult female depends on a constant pairing with the male. This is a crucial prerequisite for the differentiation of the female reproductive organs such as the vitellarium and ovary, and consequently for the production of mature eggs. These are needed for life-cycle maintenance, but they also cause pathogenesis. With respect to adult males, the production of mature sperm is essential for fertilisation and life-cycle progression. In our study we present a convenient and inexpensive method to isolate reproductive tissues from adult schistosomes in high amounts and purity, representing a source for gonad-specific RNA and protein, which will serve for future sub-transcriptome and -proteome studies helping to characterise genes, or to unravel differentiation programs in schistosome gonads. Beyond that, isolated organs may be useful for approaches to establish cell cultures, desperately needed in the post-genomic era

Social and economic value in emerging decentralized energy business models: A critical review

In recent years, numerous studies have explored the opportunities and challenges for emerging decentralized energy systems and business models. However, few studies have focussed specifically on the economic and social value associated with three emerging models: peer-to-peer energy trading (P2P), community self-consumption (CSC) and transactive energy (TE). This article presents the findings of a systematic literature review to address this gap. The paper makes two main contributions to the literature. Firstly, it offers a synthesis of research on the social and economic value of P2P, CSC and TE systems, concluding that there is evidence for a variety of sources of social value (including energy independence, local benefits, social relationships, environmental responsibility and participation and purpose) and economic value (including via self-consumption of renewable electricity, reduced electricity import costs, and improved electricity export prices). Secondly, it identifies factors and conditions necessary for the success of these models, which include willingness to participate, participant engagement with technology, and project engagement of households and communities, among other factors. Finally, it discusses conflicts and trade-offs in the value propositions of the models, how the three models differ from one another in terms of the value they aim to deliver and some of the open challenges that require further attention by researchers and practitioners

Angiographic findings and clinical implications of persistent primitive hypoglossal artery

BACKGROUND: The primitive hypoglossal artery (PHA) is a rare vascular anomaly, which belongs to the group of carotid-basilar anastomosis that may occur in adults. CASE PRESENTATION: Herein is presented a case of a patient with a PHA, who had undergone a cerebral angiography due to investigation of subarachnoid hemorrhage. Additionally, the diagnostic alternatives for detection and assessment of PHA and the spectrum of diseases related to its presence are discussed. CONCLUSIONS: The presence of a persistent PHA can be recognized as an incidental finding in a cerebral angiography without any other clinical implication or may be associated with certain clinical entities such as aneurysm formation and atherosclerotic disease

Oestrogen receptor-α variant mRNA expression in primary human breast tumours and matched lymph node metastases

We have shown previously that the relative expression of a truncated oestrogen receptor-α variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-deleted and exon 7-deleted oestrogen receptor-α variant mRNAs in 15 primary breast tumour samples and in synchronous axillary lymph node metastases. Overall, there were no significant differences between the primary tumours and the matched metastases in the relative expression of these three specific variant mRNAs. Furthermore, the pattern of all deleted oestrogen receptor-α variant mRNAs appeared conserved between any primary and its matched secondary tumour. © 1999 Cancer Research Campaig

Development of emodepside as a possible adulticidal treatment for human onchocerciasis-The fruit of a successful industrial-academic collaboration

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer–DNDi partnership is an outstanding example of “One World Health,” in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area

HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

<p>Abstract</p> <p>Background</p> <p>Hypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma.</p> <p>Methods</p> <p>In this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy) or hypoxic (2-15 Gy) conditions.</p> <p>Results</p> <p>Although siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF₁₀: 1.35 and 1.18) and U343MG (DMF₁₀: 1.78 and 1.48). However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF₁₀: 0.86 and 1.35) and U343MG (DMF₁₀: 1.33 and 1.02) cells.</p> <p>Conclusions</p> <p>Results from this <it>in vitro </it>study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.</p