Distribution of selenium in zebrafish larvae after exposure to organic and inorganic selenium forms

Selenium is an essential micronutrient for many organisms, and in vertebrates has a variety of roles associated with protection from reactive oxygen species. Over the past two decades there have been conflicting reports upon human health benefits and detriments arising from consumption of selenium dietary supplements. Thus, early studies report a decrease in the incidence of certain types of cancer, whereas subsequent studies did not observe any anti-cancer effect, and adverse effects such as increased risks for type 2 diabetes have been reported. A possible contributing factor may be that different chemical forms of selenium were used in different studies. Using larval stage zebrafish (Danio rerio) as a model organism, we report a comparison of the toxicities and tissue selenium distributions of four different chemical forms of selenium. We find that the organic forms of selenium tested (Se-methyl-l-selenocysteine and l-selenomethionine) show considerably more toxicity than inorganic forms (selenite and selenate), and that this appears to be correlated with the level of bioaccumulation. Despite differences in concentrations, the tissue specific pattern of selenium accumulation was similar for the chemical forms tested; selenium was found to be highly concentrated in pigment (melanin) containing tissues especially for the organic selenium treatments, with lower concentrations in eye lens, yolk sac and heart. These results suggest that pigmented tissues might serve as a storage reservoir for selenium. © 2016 The Royal Society of Chemistry

Development and Application of a Simple Plaque Assay for the Human Malaria Parasite Plasmodium falciparum.

Malaria is caused by an obligate intracellular protozoan parasite that replicates within and destroys erythrocytes. Asexual blood stages of the causative agent of the most virulent form of human malaria, Plasmodium falciparum, can be cultivated indefinitely in vitro in human erythrocytes, facilitating experimental analysis of parasite cell biology, biochemistry and genetics. However, efforts to improve understanding of the basic biology of this important pathogen and to develop urgently required new antimalarial drugs and vaccines, suffer from a paucity of basic research tools. This includes a simple means of quantifying the effects of drugs, antibodies and gene modifications on parasite fitness and replication rates. Here we describe the development and validation of an extremely simple, robust plaque assay that can be used to visualise parasite replication and resulting host erythrocyte destruction at the level of clonal parasite populations. We demonstrate applications of the plaque assay by using it for the phenotypic characterisation of two P. falciparum conditional mutants displaying reduced fitness in vitro

Cascades on clique-based graphs

peer-reviewedWe present an analytical approach to determining the expected cascade size in a broad range of dynamical models on the class of highly clustered random graphs introduced by Gleeson [J. P. Gleeson, Phys. Rev. E 80, 036107 (2009)]. A condition for the existence of global cascades is also derived. Applications of this approach include analyses of percolation, and Watts's model. We show how our techniques can be used to study the effects of in-group bias in cascades on social networks.PUBLISHEDpeer-reviewe

Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse in Plasmodium falciparum egress.

In the asexual blood stages of malarial infection, merozoites invade erythrocytes and replicate within a parasitophorous vacuole to form daughter cells that eventually exit (egress) by sequential rupture of the vacuole and erythrocyte membranes. The current model is that PKG, a malarial cGMP-dependent protein kinase, triggers egress, activating malarial proteases and other effectors. Using selective inhibitors of either PKG or cysteine proteases to separately inhibit the sequential steps in membrane perforation, combined with video microscopy, electron tomography, electron energy loss spectroscopy, and soft X-ray tomography of mature intracellular Plasmodium falciparum parasites, we resolve intermediate steps in egress. We show that the parasitophorous vacuole membrane (PVM) is permeabilized 10-30 min before its PKG-triggered breakdown into multilayered vesicles. Just before PVM breakdown, the host red cell undergoes an abrupt, dramatic shape change due to the sudden breakdown of the erythrocyte cytoskeleton, before permeabilization and eventual rupture of the erythrocyte membrane to release the parasites. In contrast to the previous view of PKG-triggered initiation of egress and a gradual dismantling of the host erythrocyte cytoskeleton over the course of schizont development, our findings identify an initial step in egress and show that host cell cytoskeleton breakdown is restricted to a narrow time window within the final stages of egress

Infectivity of Plasmodium falciparum in malaria-naive individuals is related to knob expression and cytoadherence of the parasite

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo. However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence

Children\u27s experiences of companion animal maltreatment in households characterized by intimate partner violence

Cruelty toward companion animals is a well-documented, coercive tactic used by abusive partners to intimidate and control their intimate partners. Experiences of co-occurring violence are common for children living in families with intimate partner violence (IPV) and surveys show that more than half are also exposed to abuse of their pets. Given children\u27s relationships with their pets, witnessing such abuse may be traumatic for them. Yet little is known about the prevalence and significance of this issue for children. The present study examines the experiences of children in families with co-occurring pet abuse and IPV. Using qualitative methods, 58 children ages 7–12 who were exposed to IPV were asked to describe their experiences of threats to and harm of their companion animals. Following the interviews, template analysis was employed to systematically develop codes and themes. Coding reliability was assessed using Randolph\u27s free-marginal multirater kappa (kfree = .90). Five themes emerged from the qualitative data, the most common being children\u27s exposure to pet abuse as a power and control tactic against their mother in the context of IPV. Other themes were animal maltreatment to discipline or punish the pet, animal cruelty by a sibling, children intervening to prevent pet abuse, and children intervening to protect the pet during a violent episode. Results indicate that children\u27s experiences of pet abuse are multifaceted, potentially traumatic, and may involve multiple family members with diverse motives

Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

Supersymmetric AdS_5 Solutions of Type IIB Supergravity

We analyse the most general bosonic supersymmetric solutions of type IIB supergravity whose metrics are warped products of five-dimensional anti-de Sitter space AdS_5 with a five-dimensional Riemannian manifold M_5. All fluxes are allowed to be non-vanishing consistent with SO(4,2) symmetry. We show that the necessary and sufficient conditions can be phrased in terms of a local identity structure on M_5. For a special class, with constant dilaton and vanishing axion, we reduce the problem to solving a second order non-linear ODE. We find an exact solution of the ODE which reproduces a solution first found by Pilch and Warner. A numerical analysis of the ODE reveals an additional class of local solutions.Comment: 33 page

Clonal transitions and phenotypic evolution in Barrett esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) is a risk factor for esophageal adenocarcinoma but our understanding of how it evolves is poorly understood. We investigated BE gland phenotype distribution, the clonal nature of phenotypic change, and how phenotypic diversity plays a role in progression. METHODS: Using immunohistochemistry and histology, we analyzed the distribution and the diversity of gland phenotype between and within biopsy specimens from patients with nondysplastic BE and those who had progressed to dysplasia or had developed postesophagectomy BE. Clonal relationships were determined by the presence of shared mutations between distinct gland types using laser capture microdissection sequencing of the mitochondrial genome. RESULTS: We identified 5 different gland phenotypes in a cohort of 51 nondysplastic patients where biopsy specimens were taken at the same anatomic site (1.0-2.0 cm superior to the gastroesophageal junction. Here, we observed the same number of glands with 1 and 2 phenotypes, but 3 phenotypes were rare. We showed a common ancestor between parietal cell-containing, mature gastric (oxyntocardiac) and goblet cell-containing, intestinal (specialized) gland phenotypes. Similarly, we have shown a clonal relationship between cardiac-type glands and specialized and mature intestinal glands. Using the Shannon diversity index as a marker of gland diversity, we observed significantly increased phenotypic diversity in patients with BE adjacent to dysplasia and predysplasia compared to nondysplastic BE and postesophagectomy BE, suggesting that diversity develops over time. CONCLUSIONS: We showed that the range of BE phenotypes represents an evolutionary process and that changes in gland diversity may play a role in progression. Furthermore, we showed a common ancestry between gastric and intestinal-type glands in BE