Matthews, H. | Search bioRxiv

bioRxiv2018

Marker-based watershed transform method for fully automatic mandibular segmentation from low-dose CBCT images

Introduction Introduction Methods and materials Results Discussion Conclusions Funding References Three-dimensional mandibular models are useful for planning maxillofacial surgery and orthodontic treatment.1,2 In studies of growth, mandibular models are important for assessing morphological changes over time.3,4 Such models are typically obtained from conventional computed tomography (CT), using high radiation dose to capture fine detail of the bony structure. Cone beam computed tomography (CBCT) shows promise for oral and craniofacial imaging applications due to lower radiation dose, lower cost and shorter acquisition time compared to CT. However, CBCT images have lower contrast and higher levels of ...

bioinformatics↗

bioRxiv2018

A high-throughput in vitro translation screen towards discovery of novel antimalarial protein translation inhibitors

Drugs that target protein synthesis are well-validated for use as antimicrobials, yet specific high throughput (HTP) methods to screen for those targeting malaria are lacking. Here, we have developed a cell free in vitro translation (IVT) assay for the human malaria parasite, Plasmodium falciparum, which reconstitutes the native parasite protein translation machinery. Combining clarified IVT lysate with a click beetle luciferase reporter gene fused to untranslated regions of Pf histidine-rich proteins (hrp)-2 and 3, the HTP IVT assay accurately reports protein translation in a 384-well plate format using a standard spectrofluorometer. We validate the assay as effective in detecting compounds targeting the ribosome, ribosome co-factors (elongation factor 2) and cytosolic tRNA synthetases as well as its ability to find translation inhibitors in a blind screen using a high-density assay format amenable for high throughput. This demonstrates an ability to reconstitute the breadth of the parasite eukaryotic protein translation machinery in vitro and use it as a powerful platform for antimalarial drug discovery.

microbiology↗