First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

The Deadly Chytrid Fungus: A Story of an Emerging Pathogen

[Extract] Emerging infectious diseases present a great challenge for the health of both humans and wildlife. The increasing prevalence of drug-resistant fungal pathogens in humans [1] and recent outbreaks of novel fungal pathogens in wildlife populations [2] underscore the need to better understand the origins and mechanisms of fungal pathogenicity. One of the most dramatic examples of fungal impacts on vertebrate populations is the effect of the amphibian disease chytridiomycosis, caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd).\ud Amphibians around the world are experiencing unprecedented population losses and local extinctions [3]. While there are multiple causes of amphibian declines, many catastrophic die-offs are attributed to Bd [4],[5]. The chytrid pathogen has been documented in hundreds of amphibian species, and reports of Bd's impact on additional species and in additional geographic regions are accumulating at an alarming rate (e.g., see http://www.spatialepidemiology.net/bd). Bd is a microbial, aquatic fungus with distinct life stages. The motile stage, called a zoospore, swims using a flagellum and initiates the colonization of frog skin. Within the host epidermal cells, a zoospore forms a spherical thallus, which matures and produces new zoospores by dividing asexually, renewing the cycle of infection when zoospores are released to the skin surface (Figure 1). Bd is considered an emerging pathogen, discovered and described only a decade ago [6],[7]. Despite intensive ecological study of Bd over the last decade, a number of unanswered questions remain. Here we summarize what has been recently learned about this lethal pathogen

Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission

Background: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. Method: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of,1%. Results: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86 % took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70 % displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three wome

Is Chytridiomycosis an Emerging Infectious Disease in Asia?

The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has caused dramatic amphibian population declines and extinctions in Australia, Central and North America, and Europe. Bd is associated with >200 species extinctions of amphibians, but not all species that become infected are susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of the world, such as in Australia, USA, and throughout Central and South America, causing population and species collapse. The mechanism behind the rapid global emergence of the disease is poorly understood, in part due to an incomplete picture of the global distribution of Bd. At present, there is a considerable amount of geographic bias in survey effort for Bd, with Asia being the most neglected continent. To date, Bd surveys have been published for few Asian countries, and infected amphibians have been reported only from Indonesia, South Korea, China and Japan. Thus far, there have been no substantiated reports of enigmatic or suspected disease-caused population declines of the kind that has been attributed to Bd in other areas. In order to gain a more detailed picture of the distribution of Bd in Asia, we undertook a widespread, opportunistic survey of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea. Survey sites spanned 15 countries, approximately 36° latitude, 111° longitude, and over 2000 m in elevation. Bd prevalence was very low throughout our survey area (2.35% overall) and infected animals were not clumped as would be expected in epizootic events. This suggests that Bd is either newly emerging in Asia, endemic at low prevalence, or that some other ecological factor is preventing Bd from fully invading Asian amphibians. The current observed pattern in Asia differs from that in many other parts of the world

P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia

Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them

Within- and Among-Population Variation in Chytridiomycosis-Induced Mortality in the Toad Alytes obstetricans

Background Chytridiomycosis is a fungal disease linked to local and global extinctions of amphibians. Susceptibility to chytridiomycosis varies greatly between amphibian species, but little is known about between- and within-population variability. However, this kind of variability is the basis for the evolution of tolerance and resistance evolution to disease. Methodology/Principal Findings In a common garden experiment, we measured mortality after metamorphosis of Alytes obstetricans naturally infected with Batrachochytrium dendrobatidis. Mortality rates differed significantly among populations and ranged from 27 to 90%. Within populations, mortality strongly depended on mass at and time through metamorphosis. Conclusions/Significance Although we cannot rule out that the differences observed resulted from differences in skin microbiota, different pathogen strains or environmental effects experienced by the host or the pathogen prior to the start of the experiment, we argue that genetic differences between populations are a likely source of at least part of this variation. To our knowledge, this is the first study showing differences in survival between and within populations under constant laboratory conditions. Assuming that some of this intraspecific variation has a genetic basis, this may suggest that there is the potential for the evolution of resistance or tolerance, which might allow population persistence

Informed decision making about predictive DNA tests: arguments for more public visibility of personal deliberations about the good life

Since its advent, predictive DNA testing has been perceived as a technology that may have considerable impact on the quality of people’s life. The decision whether or not to use this technology is up to the individual client. However, to enable well considered decision making both the negative as well as the positive freedom of the individual should be supported. In this paper, we argue that current professional and public discourse on predictive DNA-testing is lacking when it comes to supporting positive freedom, because it is usually framed in terms of risk and risk management. We show how this ‘risk discourse’ steers thinking on the good life in a particular way. We go on to argue that empirical research into the actual deliberation and decision making processes of individuals and families may be used to enrich the environment of personal deliberation in three ways: (1) it points at a richer set of values that deliberators can take into account, (2) it acknowledges the shared nature of genes, and (3) it shows how one might frame decisions in a non-binary way. We argue that the public sharing and discussing of stories about personal deliberations offers valuable input for others who face similar choices: it fosters their positive freedom to shape their view of the good life in relation to DNA-diagnostics. We conclude by offering some suggestions as to how to realize such public sharing of personal stories

Ancient origins determine global biogeography of hot and cold desert cyanobacteria

Factors governing large-scale spatio-temporal distribution of microorganisms remain unresolved, yet are pivotal to understanding ecosystem value and function. Molecular genetic analyses have focused on the influence of niche and neutral processes in determining spatial patterns without considering the temporal scale. Here, we use temporal phylogenetic analysis calibrated using microfossil data for a globally sampled desert cyanobacterium, Chroococcidiopsis, to investigate spatio-temporal patterns in microbial biogeography and evolution. Multilocus phylogenetic associations were dependent on contemporary climate with no evidence for distance-related patterns. Massively parallel pyrosequencing of environmental samples confirmed that Chroococcidiopsis variants were specific to either hot or cold deserts. Temporally scaled phylogenetic analyses showed no evidence of recent inter-regional gene flow, indicating populations have not shared common ancestry since before the formation of modern continents. These results indicate that global distribution of desert cyanobacteria has not resulted from widespread contemporary dispersal but is an ancient evolutionary legacy. This highlights the importance of considering temporal scales in microbial biogeography

DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain

Eukaryotic replisomes are multiprotein complexes. Here the authors reveal two distinct stressed replisomes, associated with DONSON and FANCM, displaying a bias in replication timing and chromatin domain