Correlations Between Life-Detection Techniques and Implications for Sampling Site Selection in Planetary Analog Missions

We conducted an analog sampling expedition under simulated mission constraints to areas dominated by basaltic tephra of the Eldfell and Fimmvorouhals lava fields (Iceland). Sites were selected to be homogeneous at a coarse remote sensing resolution (10-100m) in apparent color, morphology, moisture, and grain size, with best-effort realism in numbers of locations and replicates. Three different biomarker assays (counting of nucleic-acid-stained cells via fluorescent microscopy, a luciferin/luciferase assay for adenosine triphosphate, and quantitative polymerase chain reaction (qPCR) to detect DNA associated with bacteria, archaea, and fungi) were characterized at four nested spatial scales (1m, 10m, 100m, and >1km) by using five common metrics for sample site representativeness (sample mean variance, group F tests, pairwise t tests, and the distribution-free rank sum H and u tests). Correlations between all assays were characterized with Spearman's rank test. The bioluminescence assay showed the most variance across the sites, followed by qPCR for bacterial and archaeal DNA; these results could not be considered representative at the finest resolution tested (1m). Cell concentration and fungal DNA also had significant local variation, but they were homogeneous over scales of >1km. These results show that the selection of life detection assays and the number, distribution, and location of sampling sites in a low biomass environment with limited a priori characterization can yield both contrasting and complementary results, and that their interdependence must be given due consideration to maximize science return in future biomarker sampling expeditions. Key Words: AstrobiologyBiodiversityMicrobiologyIcelandPlanetary explorationMars mission simulationBiomarker. Astrobiology 17, 1009-1021

Sexual Dimorphism of the Zebra Finch Syrinx Indicates Adaptation for High Fundamental Frequencies in Males

In many songbirds the larger vocal repertoire of males is associated with sexual dimorphism of the vocal control centers and muscles of the vocal organ, the syrinx. However, it is largely unknown how these differences are translated into different acoustic behavior.Here we show that the sound generating structures of the syrinx, the labia and the associated cartilaginous framework, also display sexual dimorphism. One of the bronchial half rings that position and tense the labia is larger in males, and the size and shape of the labia differ between males and females. The functional consequences of these differences were explored by denervating syringeal muscles. After denervation, both sexes produced equally low fundamental frequencies, but the driving pressure generally increased and was higher in males. Denervation strongly affected the relationship between driving pressure and fundamental frequency.The syringeal modifications in the male syrinx, in concert with dimorphisms in neural control and muscle mass, are most likely the foundation for the potential to generate an enhanced frequency range. Sexually dimorphic vocal behavior therefore arises from finely tuned modifications at every level of the motor cascade. This sexual dimorphism in frequency control illustrates a significant evolutionary step towards increased vocal complexity in birds

Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous inherited human disorder displaying a pleotropic phenotype. Many of the symptoms characterized in the human disease have been reproduced in animal models carrying deletions or knock-in mutations of genes causal for the disorder. Thinning of the cerebral cortex, enlargement of the lateral and third ventricles, and structural changes in cilia are among the pathologies documented in these animal models. Ciliopathy is of particular interest in light of recent studies that have implicated primary neuronal cilia (PNC) in neuronal signal transduction. In the present investigation, we tested the hypothesis that areas of the brain responsible for learning and memory formation would differentially exhibit PNC abnormalities in animals carrying a deletion of the Bbs4 gene (Bbs4-/-). Immunohistochemical localization of adenylyl cyclase-III (ACIII), a marker restricted to PNC, revealed dramatic alterations in PNC morphology and a statistically significant reduction in number of immunopositive cilia in the hippocampus and amygdala of Bbs4-/- mice compared to wild type (WT) littermates. Western blot analysis confirmed the decrease of ACIII levels in the hippocampus and amygdala of Bbs4-/- mice, and electron microscopy demonstrated pathological alterations of PNC in the hippocampus and amygdala. Importantly, no neuronal loss was found within the subregions of amygdala and hippocampus sampled in Bbs4-/- mice and there were no statistically significant alterations of ACIII immunopositive cilia in other areas of the brain not known to contribute to the BBS phenotype. Considered with data documenting a role of cilia in signal transduction these findings support the conclusion that alterations in cilia structure or neurochemical phenotypes may contribute to the cognitive deficits observed in the Bbs4-/- mouse mode. © 2014 Agassandian et al

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information

Bordetella pertussis Infection or Vaccination Substantially Protects Mice against B. bronchiseptica Infection

Although B. bronchiseptica efficiently infects a wide range of mammalian hosts and efficiently spreads among them, it is rarely observed in humans. In contrast to the many other hosts of B. bronchiseptica, humans are host to the apparently specialized pathogen B. pertussis, the great majority having immunity due to vaccination, infection or both. Here we explore whether immunity to B. pertussis protects against B. bronchiseptica infection. In a murine model, either infection or vaccination with B. pertussis induced antibodies that recognized antigens of B. bronchiseptica and protected the lower respiratory tract of mice against three phylogenetically disparate strains of B. bronchiseptica that efficiently infect naïve animals. Furthermore, vaccination with purified B. pertussis-derived pertactin, filamentous hemagglutinin or the human acellular vaccine, Adacel, conferred similar protection against B. bronchiseptica challenge. These data indicate that individual immunity to B. pertussis affects B. bronchiseptica infection, and suggest that the high levels of herd immunity against B. pertussis in humans could explain the lack of observed B. bronchiseptica transmission. This could also explain the apparent association of B. bronchiseptica infections with an immunocompromised state

ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p

State of the climate in 2017

In 2017, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-reached new record highs. The annual global average carbon dioxide concentration at Earth's surface for 2017 was 405.0 ± 0.1 ppm, 2.2 ppm greater than for 2016 and the highest in the modern atmospheric measurement record and in ice core records dating back as far as 800 000 years. The global growth rate of CO2 has nearly quadrupled since the early 1960s. With ENSO-neutral conditions present in the central and eastern equatorial Pacific Ocean during most of the year and weak La Niña conditions notable at the start and end, the global temperature across land and ocean surfaces ranked as the second or third highest, depending on the dataset, since records began in the mid-to-late 1800s. Notably, it was the warmest non-El Niño year in the instrumental record. Above Earth's surface, the annual lower tropospheric temperature was also either second or third highest according to all datasets analyzed. The lower stratospheric temperature was about 0.2°C higher than the record cold temperature of 2016 according to most of the in situ and satellite datasets. Several countries, including Argentina, Uruguay, Spain, and Bulgaria, reported record high annual temperatures. Mexico broke its annual record for the fourth consecutive year. On 27 January, the temperature reached 43.4°C at Puerto Madryn, Argentina-the highest temperature recorded so far south (43°S) anywhere in the world. On 28 May in Turbat, western Pakistan, the high of 53.5°C tied Pakistan's all-time highest temperature and became the world-record highest temperature for May. In the Arctic, the 2017 land surface temperature was 1.6°C above the 1981-2010 average, the second highest since the record began in 1900, behind only 2016. The five highest annual Arctic temperatures have all occurred since 2007. Exceptionally high temperatures were observed in the permafrost across the Arctic, with record values reported in much of Alaska and northwestern Canada. In August, high sea surface temperature (SST) records were broken for the Chukchi Sea, with some regions as warm as +11°C, or 3° to 4°C warmer than the longterm mean (1982-present). According to paleoclimate studies, today's abnormally warm Arctic air and SSTs have not been observed in the last 2000 years. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 7 March, sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, covering 8% less area than the 1981-2010 average. The Arctic sea ice minimum on 13 September was the eighth lowest on record and covered 25% less area than the long-term mean. Preliminary data indicate that glaciers across the world lost mass for the 38th consecutive year on record; the declines are remarkably consistent from region to region. Cumulatively since 1980, this loss is equivalent to slicing 22 meters off the top of the average glacier. Antarctic sea ice extent remained below average for all of 2017, with record lows during the first four months. Over the continent, the austral summer seasonal melt extent and melt index were the second highest since 2005, mostly due to strong positive anomalies of air temperature over most of the West Antarctic coast. In contrast, the East Antarctic Plateau saw record low mean temperatures in March. The year was also distinguished by the second smallest Antarctic ozone hole observed since 1988. Across the global oceans, the overall long-term SST warming trend remained strong. Although SST cooled slightly from 2016 to 2017, the last three years produced the three highest annual values observed; these high anomalies have been associated with widespread coral bleaching. The most recent global coral bleaching lasted three full years, June 2014 to May 2017, and was the longest, most widespread, and almost certainly most destructive such event on record. Global integrals of 0-700-m and 0-2000-m ocean heat content reached record highs in 2017, and global mean sea level during the year became the highest annual average in the 25-year satellite altimetry record, rising to 77 mm above the 1993 average. In the tropics, 2017 saw 85 named tropical storms, slightly above the 1981-2010 average of 82. The North Atlantic basin was the only basin that featured an above-normal season, its seventh most active in the 164-year record. Three hurricanes in the basin were especially notable. Harvey produced record rainfall totals in areas of Texas and Louisiana, including a storm total of 1538.7 mm near Beaumont, Texas, which far exceeds the previous known U.S. tropical cyclone record of 1320.8 mm. Irma was the strongest tropical cyclone globally in 2017 and the strongest Atlantic hurricane outside of the Gulf of Mexico and Caribbean on record with maximum winds of 295 km h-1. Maria caused catastrophic destruction across the Caribbean Islands, including devastating wind damage and flooding across Puerto Rico. Elsewhere, the western North Pacific, South Indian, and Australian basins were all particularly quiet. Precipitation over global land areas in 2017 was clearly above the long-term average. Among noteworthy regional precipitation records in 2017, Russia reported its second wettest year on record (after 2013) and Norway experienced its sixth wettest year since records began in 1900. Across India, heavy rain and flood-related incidents during the monsoon season claimed around 800 lives. In August and September, above-normal precipitation triggered the most devastating floods in more than a decade in the Venezuelan states of Bolívar and Delta Amacuro. In Nigeria, heavy rain during August and September caused the Niger and Benue Rivers to overflow, bringing floods that displaced more than 100 000 people. Global fire activity was the lowest since at least 2003; however, high activity occurred in parts of North America, South America, and Europe, with an unusually long season in Spain and Portugal, which had their second and third driest years on record, respectively. Devastating fires impacted British Columbia, destroying 1.2 million hectares of timber, bush, and grassland, due in part to the region's driest summer on record. In the United States, an extreme western wildfire season burned over 4 million hectares; the total costs of $18 billion tripled the previous U.S. annual wildfire cost record set in 1991