The Schistosomiasis Research Agenda—What Now?

[Extract] As relatively new schistosomiasis researchers, we awaited with eagerness the publication of the "Schistosomiasis Research Agenda" SRA) put forward by Colley and Secor in the December 2007 issue of PLoS Neglected Tropical Diseases [1]. The SRA is a comprehensive, well-organized list of research activities that reflects the impressive diversity of interests that make up current schistosomiasis research. Colley and Secor went to admirable lengths to solicit the interests of researchers the world over, with special efforts to solicit the opinions of scientists in countries or regions where schistosomiasis is endemic, such as Brazil, China, and Africa. Having attended some of these meetings (11th International Congress of Parasitology, held in Glasgow, United Kingdom in August 2006; and the 55th Annual Meeting of the American Society of Tropical Medicine and Hygiene, held in Atlanta, United States in November 2006) and received the emails, we are confident that the SRA indeed reflects the richness and breadth of current schistosomiasis research

Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance.

--- - Label: BACKGROUND NlmCategory: BACKGROUND content: Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance. - Label: METHODS NlmCategory: METHODS content: We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique. - Label: RESULTS NlmCategory: RESULTS content: None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05). - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention

Proteomes and Signalling Pathways of Antler Stem Cells

As the only known example of complete organ regeneration in mammals, deer antler in the growing or velvet phase is of major interest in developmental biology. This regeneration event initiates from self-renewing antler stem cells that exhibit pluripotency. At present, it remains unclear how the activation and quiescence of antler stem cells are regulated. Therefore, in the present study proteins that were differentially expressed between the antler stem cells and somatic cells (facial periosteum) were identified by a gel-based proteomic technique, and analysed using Ingenuity Pathway Analysis software. Several molecular pathways (PI3K/Akt, ERK/MAPK, p38 MAPK, etc.) were found to be activated during proliferation. Also expressed were the transcription factors POU5F1, SOX2, NANOG and MYC, which are key markers of embryonic stem cells. Expression of these proteins was confirmed in both cultured cells and fresh tissues by Western blot analysis. Therefore, the molecular pathways and transcription factors identified in the current study are common to embryonic and adult stem cells. However, expression of embryonic stem cell transcription factors would suggest that antler stem cells are, potentially, an intermediary stem cell type between embryonic and the more specialized tissue-specific stem cells like those residing in muscle, fat or from a hematopoietic origin. The retention of this embryonic, pluripotent lineage may be of fundamental importance for the subsequent regenerative capacity of antlers

Self-Organizing Circuit Assembly through Spatiotemporally Coordinated Neuronal Migration within Geometric Constraints

Neurons are dynamically coupled with each other through neurite-mediated adhesion during development. Understanding the collective behavior of neurons in circuits is important for understanding neural development. While a number of genetic and activity-dependent factors regulating neuronal migration have been discovered on single cell level, systematic study of collective neuronal migration has been lacking. Various biological systems are shown to be self-organized, and it is not known if neural circuit assembly is self-organized. Besides, many of the molecular factors take effect through spatial patterns, and coupled biological systems exhibit emergent property in response to geometric constraints. How geometric constraints of the patterns regulate neuronal migration and circuit assembly of neurons within the patterns remains unexplored.We established a two-dimensional model for studying collective neuronal migration of a circuit, with hippocampal neurons from embryonic rats on Matrigel-coated self-assembled monolayers (SAMs). When the neural circuit is subject to geometric constraints of a critical scale, we found that the collective behavior of neuronal migration is spatiotemporally coordinated. Neuronal somata that are evenly distributed upon adhesion tend to aggregate at the geometric center of the circuit, forming mono-clusters. Clustering formation is geometry-dependent, within a critical scale from 200 µm to approximately 500 µm. Finally, somata clustering is neuron-type specific, and glutamatergic and GABAergic neurons tend to aggregate homo-philically.We demonstrate self-organization of neural circuits in response to geometric constraints through spatiotemporally coordinated neuronal migration, possibly via mechanical coupling. We found that such collective neuronal migration leads to somata clustering, and mono-cluster appears when the geometric constraints fall within a critical scale. The discovery of geometry-dependent collective neuronal migration and the formation of somata clustering in vitro shed light on neural development in vivo

A synthetic luciferin improves bioluminescence imaging in live mice

Firefly luciferase is the most widely used optical reporter for noninvasive bioluminescence imaging (BLI) in rodents. BLI relies on the ability of the injected luciferase substrate D-luciferin to access luciferase-expressing cells and tissues within the animal. Here we show that injection of mice with a synthetic luciferin, CycLuc1, improves BLI from existing luciferase reporters and enables imaging in the brain that could not be achieved with D-luciferin

Anti-malarial activity of traditional Kampo medicine Coptis rhizome extract and its major active compounds

BACKGROUND: Herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, a variety of Japanese traditional herbal medicine (\u27Kampo\u27) were examined for their potential anti-malarial activities. METHODS: A comprehensive screening methods were designed to identify novel anti-malarial drugs from a library of Kampo herbal extracts (n?=?120) and related compounds (n?=?96). The anti-malarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary adult mouse brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo anti-malarial activity. RESULTS: Out of 120 herbal extracts, Coptis rhizome showed the highest anti-malarial activity (IC50 1.9 μg/mL of 3D7 and 4.85 μg/mL of Dd2) with a high selectivity index (SI)?>?263 (3D7) and?>?103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis rhizome also showed anti-malarial activities with IC50 1.1, 2.6, and 6.0 μM (against 3D7) and 3.1, 6.3, and 11.8 μM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest anti-malarial activity (IC50 1.1 μM against 3D7 and 3.1 μM against Dd2) with SI of 37.8 and 13.2, respectively. Finally, the herbal extract of Coptis rhizome and its major active compound coptisine chloride exhibited significant anti-malarial activity in mice infected with Plasmodium yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P?<?0.05) for Coptis rhizome and from 81 to 89% (P?<?0.01) for coptisine chloride. CONCLUSION: Coptis rhizome and its major active compound coptisine chloride showed promising anti-malarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus, Kampo herbal medicine is a potential natural resource for novel anti-malarial agents

A review identifying the effectiveness of minimum quantity lubrication (MQL) during conventional machining

Government legislation and public opinion are the main drivers behind the movement of manufacturing companies towards sustainable production. Fundamentally, companies want to avoid future financial penalties and the industry is therefore under pressure to adapt new techniques and practices in order to become environmentally friendly. The cost efficiency of metal cutting operations is highly dependent on accuracy, excellent surface finish and minimized tool wear and, to this end, has traditionally made abundant use of cutting fluid in machining operations. However, these cutting fluids have been a major contributor to environmental and health issues. In recent years, an enormous effort to eradicate these adverse effects has been made with one important focus being the implementation of minimum quantity lubrication (MQL). In the present work, the authors have reviewed the current state of the art in MQL with a particular focus on drilling, turning, milling and grinding machining operations. Overall, it is concluded that MQL has huge potential as a substitute for conventional flood cooling