Quantifying How Staining Methods Bias Measurements of Neuron Morphologies

The process through which neurons are labeled is a key methodological choice in measuring neuron morphology. However, little is known about how this choice may bias measurements. To quantify this bias we compare the extracted morphology of neurons collected from the same rodent species, experimental condition, gender distribution, age distribution, brain region and putative cell type, but obtained with 19 distinct staining methods. We found strong biases on measured features of morphology. These were largest in features related to the coverage of the dendritic tree (e.g., the total dendritic tree length). Understanding measurement biases is crucial for interpreting morphological data

Delayed Onset of Symptoms and Atovaquone-Proguanil Chemoprophylaxis Breakthrough by Plasmodium malariae in the Absence of Mutation at Codon 268 of pmcytb.

Plasmodium malariae is widely distributed across the tropics, causing symptomatic malaria in humans with a 72-hour fever periodicity, and may present after latency periods lasting up to many decades. Delayed occurrence of symptoms is observed in humans using chemoprophylaxis, or patients having received therapies targeting P. falciparum intraerythrocytic asexual stages, but few investigators have addressed the biological basis of the ability of P. malariae to persist in the human host. To investigate these interesting features of P. malariae epidemiology, we assembled, here, an extensive case series of P. malariae malaria patients presenting in non-endemic China, Sweden, and the UK who returned from travel in endemic countries, mainly in Africa. Out of 378 evaluable P. malariae cases, 100 (26.2%) reported using at least partial chemoprophylaxis, resembling the pattern seen with the relapsing parasites P. ovale spp. and P. vivax. In contrast, for only 7.5% of imported UK cases of non-relapsing P. falciparum was any chemoprophylaxis use reported. Genotyping of parasites from six patients reporting use of atovaquone-proguanil chemoprophylaxis did not reveal mutations at codon 268 of the cytb locus of the P. malariae mitochondrial genome. While travellers with P. malariae malaria are significantly more likely to report prophylaxis use during endemic country travel than are those with P. falciparum infections, atovaquone-proguanil prophylaxis breakthrough was not associated with pmcytb mutations. These preliminary studies, together with consistent observations of the remarkable longevity of P. malariae, lead us to propose re-examination of the dogma that this species is not a relapsing parasite. Further studies are needed to investigate our favoured hypothesis, namely that P. malariae can initiate a latent hypnozoite developmental programme in the human hepatocyte: if validated this will explain the consistent observations of remarkable longevity of parasitism, even in the presence of antimalarial prophylaxis or treatment

pfk13-Independent Treatment Failure in Four Imported Cases of Plasmodium falciparum Malaria Treated with Artemether-Lumefantrine in the United Kingdom.

We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015 to 2016. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. Parasite isolates, all of African origin, harbored variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution