Timing of host feeding drives rhythms in parasite replication

Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites. Asexual replication is responsible for the severity of malaria and fuels transmission of the disease, yet, how parasite rhythms are driven remains a mystery. We perturbed feeding rhythms of hosts by 12 hours (i.e. diurnal feeding in nocturnal mice) to desynchronise the hosts' peripheral oscillators from the central, light-entrained oscillator in the brain and their rhythmic outputs. We demonstrate that the rhythms of rodent malaria parasites in day-fed hosts become inverted relative to the rhythms of parasites in night-fed hosts. Our results reveal that the hosts' peripheral rhythms (associated with the timing of feeding and metabolism), but not rhythms driven by the central, light-entrained circadian oscillator in the brain, determine the timing (phase) of parasite rhythms. Further investigation reveals that parasite rhythms correlate closely with blood glucose rhythms. In addition, we show that parasite rhythms resynchronise to the altered host feeding rhythms when food availability is shifted, which is not mediated through rhythms in the host immune system. Our observations suggest that parasites actively control their developmental rhythms. Finally, counter to expectation, the severity of disease symptoms expressed by hosts was not affected by desynchronisation of their central and peripheral rhythms. Our study at the intersection of disease ecology and chronobiology opens up a new arena for studying host-parasite-vector coevolution and has broad implications for applied bioscience

Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice

Objectives:The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support.Methods:Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 μL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs.Measurements:And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml).Conclusions:The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia. © 2013 Watanabe et al

Biodiversity of Fusarium species in Mexico associated with ear rot in maize, and their identification using a phylogenetic approach

Fusariumproliferatum, F. subglutinans, and F. verticillioides are known causes of ear and kernel rot in maize worldwide. In Mexico, only F. verticillioides and F. subglutinans, have been reported previously as causal agents of this disease. However, Fusarium isolates with different morphological characteristics to the species that are known to cause this disease were obtained in the Highland-Valley region of this country from symptomatic and symptomless ears of native and commercial maize genotypes. Moreover, while the morphological studies were not sufficient to identify the correct taxonomic position at the species level, analyses based in the Internal Transcribed Spacer region and the Nuclear Large Subunit Ribosomal partial sequences allowed for the identification of F. subglutinans, F. solani, and F. verticillioides, as well as four species (F. chlamydosporum, F. napiforme, F. poae, and F. pseudonygamai) that had not previously been reported to be associated with ear rot. In addition, F. napiforme and F. solani were absent from symptomless kernels. Phylogenetic analysis showed genetic changes in F. napiforme, and F. pseudonygamai isolates because they were not true clones, and probably constitute separate sibling species. The results of this study suggest that the biodiversity of Fusarium species involved in ear rot in Mexico is greater than that reported previously in other places in the world. This new knowledge will permit a better understanding of the relationship between all the species involved in ear rot disease and their relationship with maize

Glassy State Lead Tellurite Nanobelts: Synthesis and Properties

The lead tellurite nanobelts have been first synthesized in the composite molten salts (KNO3/LiNO3) method, which is cost-effective, one-step, easy to control, and performed at low-temperature and in ambient atmosphere. Scanning electron microscopy, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectrum, energy dispersive X-ray spectroscopy and FT-IR spectrum are used to characterize the structure, morphology, and composition of the samples. The results show that the as-synthesized products are amorphous and glassy nanobelts with widths of 200–300 nm and lengths up to tens of microns and the atomic ratio of Pb:Te:O is close to 1:1.5:4. Thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC) and investigations of the corresponding structure and morphology change confirm that the nanobelts have low glass transition temperature and thermal stability. Optical diffuse reflectance spectrum indicates that the lead tellurite nanobelts have two optical gaps at ca. 3.72 eV and 4.12 eV. Photoluminescence (PL) spectrum and fluorescence imaging of the products exhibit a blue emission (round 480 nm)

Connected parents: combining online and off-line parenthood in vlogs and blogs

This article explores evaluative discourse in a corpus sample of parents' vlogs (video blogs) and blogs (henceforth v/ blogs) dealing with family tasks and responsibilities, as a reflection of underlying values concerning parenthood. It pays special attention to the important role played by the expression of attitude, understood as "ways of feeling" and including the meanings of affect, judgement and appreciation, together with positive politeness in the social practices of the discursive construction of online and off-line parenthood. Analysis and description of the data show two main patterns in parents' practices, either aiming at perfection through juggling and multi-tasking or building resistance to the demands of families and society. Results show that parents frequently exploit the system of affect for building positive face and rapport, while indirectly expressing judgement of social esteem and social sanction, which construct their identities as mothers and fathers and those of the members of their communities of practice. The corpus for the study consists of a random sample of 400 evaluative units in posts and comments on v/ blogs dealing with family tasks and responsibilities (200 in English and 200 in Spanish, with half the sample being drawn from fathers' and the other half from mothers' v/ blogs). I will approach the analysis of the data from appraisal (Martin and White 2005, Bednarek 2008) and politeness theory (Brown and Levinson 1987) in order to explore the features of evaluative discourse and the management of face. The methodology for processing the data borrows quantitative techniques from Corpus Linguistics, including the coding and statistical treatment of the sample with UAM Corpus Tools (O'Donnell 2011), together with Pragmatics and Discourse Analysis (DA), as done in some previous research (Santamaría-García 2011, 2014).Project "EMO-FUNDETT: EMOtion and language at work", I+D FFI2013-47792-C2-1-P, sponsored by the Spanish Ministry of Science and Innovatio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The Use of N4 in a Grounded Theory Study

Porosity in structural materials limits their ultimate strength and hence their utility. Recently several studies which discuss the porosity induced ultrasonic attenuation have appeared [1–8]. Porosity assessment by ultrasonic attenuation measurement involves two principal problems: first, how to relate the porosity induced ultrasonic attenuation to porosity parameters such as average pore radius and volume fraction, and second, how to separate the sought porosity induced attenuation from other components contributing to the actually measured total attenuation

Sonographic Evaluation and Sonographic-Guided Therapeutic Options of Lateral Ankle Pain: Peroneal Tendon Pathology Associated with the Presence of an Os Peroneum

Clinical implications of acute injuries of the os peroneum have been described, with the recommendation in some cases being the excision of the bone fragments. We describe the spectrum of sonographic appearances associated with pain in the region of the os peroneum, document associated peroneal tendon pathology, and describe the use of sonography to direct and guide therapeutic and/or diagnostic injections. All sonographic examinations in our ultrasound database from Jan 1, 2001–Jan 30, 2007 with the words “os peroneum” were reviewed. Patients were cross-referenced in our radiology database to find relevant foot or ankle radiographs for correlation. There were 47 patients (18 men and 29 women, age range 16 to 83) referred for sonographic evaluation of lateral foot and/or ankle pain who had an os peroneum identified during the sonographic evaluation. Eighteen patients were referred specifically for targeted injection of the lateral ankle, including peroneal tendon sheath injections (N = 10), calcaneocuboid joint injections (N = 1), and injections around symptomatic os peroneum (N = 7). All 47 patients had tendinosis of the peroneus longus, in varying degrees of severity. Radiographs were available for correlation in 28 patients. The causes of lateral ankle pain with a co-existent os peroneum are multifactorial and may not directly relate to the presence of an os peroneum. Ultrasound can be of value in separating out the specific etiology for pain, as well as provide a method for problem solving by the performance of targeted diagnostic or therapeutic injections in the lateral ankle