Investigation of Anaplasma marginale Seroprevalence in a Traditionally Managed Large California Beef Herd.

Recent observations by stakeholders suggested that ecosystem changes may be driving an increased incidence of bovine erythrocytic anaplasmosis, resulting in a reemerging cattle disease in California. The objective of this prospective cohort study was to estimate the incidence of Anaplasma marginale infection using seroconversion in a northern California beef cattle herd. A total of 143 Black Angus cattle (106 prebreeding heifers and 37 cows) were enrolled in the study. Serum samples were collected to determine Anaplasma marginale seroprevalence using a commercially available competitive enzyme-linked immunosorbent assay test kit. Repeat sampling was performed in seronegative animals to determine the incidence density rate from March through September (2013). Seroprevalence of heifers was significantly lower than that of cows at the beginning of the study (P < 0.001) but not at study completion (P = 0.075). Incidence density rate of Anaplasma marginale infection was 8.17 (95% confidence interval: 6.04, 10.81) cases per 1000 cow-days during the study period. Study cattle became Anaplasma marginale seropositive and likely carriers protected from severe clinical disease that might have occurred had they been first infected as mature adults. No evidence was found within this herd to suggest increased risk for clinical bovine erythrocytic anaplasmosis

Kimberlites reveal 2.5-billion-year evolution of a deep, isolated mantle reservoir

The widely accepted paradigm of Earth's geochemical evolution states that the successive extraction of melts from the mantle over the past 4.5 billion years formed the continental crust, and produced at least one complementary melt-depleted reservoir that is now recognized as the upper-mantle source of mid-ocean-ridge basalts1. However, geochemical modelling and the occurrence of high 3He/4He (that is, primordial) signatures in some volcanic rocks suggest that volumes of relatively undifferentiated mantle may reside in deeper, isolated regions2. Some basalts from large igneous provinces may provide temporally restricted glimpses of the most primitive parts of the mantle3,4, but key questions regarding the longevity of such sources on planetary timescales—and whether any survive today—remain unresolved. Kimberlites, small-volume volcanic rocks that are the source of most diamonds, offer rare insights into aspects of the composition of the Earth’s deep mantle. The radiogenic isotope ratios of kimberlites of different ages enable us to map the evolution of this domain through time. Here we show that globally distributed kimberlites originate from a single homogeneous reservoir with an isotopic composition that is indicative of a uniform and pristine mantle source, which evolved in isolation over at least 2.5 billion years of Earth history—to our knowledge, the only such reservoir that has been identified to date. Around 200 million years ago, extensive volumes of the same source were perturbed, probably as a result of contamination by exogenic material. The distribution of affected kimberlites suggests that this event may be related to subduction along the margin of the Pangaea supercontinent. These results reveal a long-lived and globally extensive mantle reservoir that underwent subsequent disruption, possibly heralding a marked change to large-scale mantle-mixing regimes. These processes may explain why uncontaminated primordial mantle is so difficult to identify in recent mantle-derived melts

Discovery of fevipiprant (NVP-QAW039), a potent and selective DP2 receptor antagonist for treatment of asthma

Further optimization of an initial DP2 receptor antagonist clinical candidate NVPQAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2- (trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Development of corticosteroid liposomes for delivery to airway macrophages

This study aimed to explore the feasibility of directing a corticosteroid entrapped in a liposome to the airway macrophage and the following conclusions were reached:1. Small unilamellar lipsomes could be prepared incorporating a corticosteroid and a phospholipid: corticosteroid ratio of 100:1 w:w resulted in 100% corticosteroid entrapment.2. Guinea pig airway macrophages internalised liposomes in a manner dependent on the incubation temperature, time and the liposome concentration. The extent of internalisation was dependent on the concentration of phosphatidyl serine in the liposome. The mechanism of internalisation was probably receptor mediated endocytosis via the coated pit pathway. The receptor may be the scavenger receptor.3. Serum proteins inhibited the internalisation of liposomes by macrophages and proteins derived from lung lavage had a similar effect. The mechanism of the inhibition was investigated.4. Liposomes interacted with lung surfactant in vitro. Under calcium free conditions, lung surfactant appeared to bind to liposomes, whereas in the presence of millimolar calcium ions, components of lung surfactant interacted with the liposome structure. Lung surfactant proteins B and C appeared to be of importance for this interaction.5. Liposome entrapped corticosteroid inhibited the release of plasminogen activator from quiescent J774 cells and PGE2 from LPS stimulated J774 cells in vitro. The effect was equivalent to free corticosteroid. Liposomes without corticosteroid were ineffective.6. Liposomes were localised in airway macrophages and with the surfactant pool in vivo after intra tracheal instillation. The interaction with lung surfactant occurred with time.7. Liposome entrapped corticosteroid inhibited allergen induced eosinophilia in rats and the response was equivalent to free corticosteroid. Liposomes without corticosteroid were ineffective.Therefore, liposomes can be used for the delivery of therapeutic agents to the lungs and may have potential for the therapy of lung diseases.</p

Evaluation of Research Careers fully acknowledging Open Science Practices - Rewards, incentives and/or recognition for researchers practicing Open Science

Changing practices from the traditional approach in most disciplines will require a fundamental change in the way scientisits carry out research in an Open Science Environment. In order for this to be encouraged and incentivised, this change apprroach must be recognised and rewarded by both employers (when recruiting and promoting researchers) and research funders (when performing peer review of researchers in grant applications). Moreover, senior researchers must play a key role in this change as they are highly influential in the recruitment/promotion of researchers and conduct peer review both for funding agencies and publishers. The report rpovides background information on Open Science, researcher assessment and career Framework. It also describes different aspects of OS. The limitations of current recognition and reward processes are presented, with suggestions on how to alleviate these and how new paradigms can be envisioned and implemented

Isotopic analyses of clinopyroxenes demonstrate the effects of kimberlite melt metasomatism upon the lithospheric mantle

The trace element and radiogenic isotope systematics of clinopyroxene have frequently been used to characterise mantle metasomatic processes, because it is the main host of most lithophile elements in the lithospheric mantle. To further our understanding of mantle metasomatism, both solution-mode Sr-Nd-Hf-Pb and in situ trace element and Sr isotopic data have been acquired for clinopyroxene grains from a suite of peridotite (lherzolites and wehrlites), MARID (Mica-Amphibole-Rutile-Ilmenite-Diopside), and PIC (Phlogopite-Ilmenite-Clinopyroxene) rocks from the Kimberley kimberlites (South Africa). The studied mantle samples can be divided into two groups on the basis of their clinopyroxene trace element compositions, and this subdivision is reinforced by their isotopic ratios. Type 1 clinopyroxene, which comprises PIC, wehrlite, and some sheared lherzolite samples, is characterised by low Sr (~100–200 ppm) and LREE concentrations, moderate HFSE contents (e.g., ~40–75 ppm Zr; La/Zr ~ 0.05. The isotopic compositions of Type 2 clinopyroxenes are more variable and extend from compositions resembling the “enriched mantle” towards those of Type 1 rocks (e.g., εNdi = −12.7 to −4.4). To constrain the source of these variations, in situ Sr isotope analyses of clinopyroxene were undertaken, including zoned grains in Type 2 samples. MARID and lherzolite clinopyroxene cores display generally radiogenic but variable 87Sr/86Sri values (0.70526–0.71177), which are correlated with Sr contents and La/Zr ratios, and which might be explained by the interaction between peridotite and melts from different enriched sources within the lithospheric mantle. Most notably, the rims of these Type 2 clinopyroxenes trend towards compositions similar to those of the host kimberlite and Type 1 clinopyroxene from PIC and wehrlites. These results are interpreted to represent clinopyroxene overgrowth during late-stage (shortly before/during entrainment) metasomatism by kimberlite magmas. Our study shows that a pervasive, alkaline metasomatic event caused MARID to be generated and harzburgites to be converted to lherzolite in the lithospheric mantle beneath the Kimberley area, which was followed by kimberlite metasomatism during Cretaceous magmatism. This latter event is the time at which discrete PIC, wehrlite, and sheared lherzolite lithologies were formed, and MARID and granular lherzolites were partly modified.ISSN:0024-493