Zinc on the edge—isotopic and geophysical evidence that cratonic edges control world-class shale-hosted zinc-lead deposits

The North Australian Zinc Belt is the largest zinc-lead province in the world, containing three of the ten largest known individual deposits (HYC, Hilton-George Fisher, and Mount Isa). The Northern Cordillera in North America is the second largest zinc-lead province, containing a further two of the world’s top ten deposits (Red Dog and Howards Pass). Despite this world-class endowment, exploration in both mineral provinces during the past 2 decades has not been particularly successful, yielding only two significant discoveries (Teena, Australia, and Boundary, Canada). One of the most important aspects of exploration is to choose mineral provinces and districts within geological belts that have the greatest potential for discovery. Here, we present results from these two zinc belts that highlight previously unused datasets for area selection and targeting. Lead isotope mapping using analyses of mineralized material has identified gradients in μ (238U/204Pb) that coincide closely with many major deposits. Locations of these deposits also coincide with a gradient in the depth of the lithosphere-asthenosphere boundary determined from calibrated surface wave tomography models converted to temperature. Furthermore, gradients in upward-continued gravity anomalies and a step in Moho depth correspond to a pre-existing major crustal boundary in both zinc belts. A spatial association of deposits with a linear mid- to lower-crustal resistivity anomaly from magnetotelluric data is also observed in the North Australian Zinc Belt. The change from thicker to thinner lithosphere is interpreted to localize prospective basins for zinc-lead mineralization and to control the gradient in lead isotope and geophysical data. These data, when combined with data indicative of paleoenvironment and changes in plate motion at the time of mineralization, provide new exploration criteria that can be used to identify prospective mineralized basins and define the most favorable parts of these basins

Antimicrobial protein and Peptide concentrations and activity in human breast milk consumed by preterm infants at risk of late-onset neonatal sepsis

Objective: We investigated the levels and antimicrobial activity of antimicrobial proteins and peptides (AMPs) in breast milk consumed by preterm infants, and whether deficiencies of these factors were associated with late-onset neonatal sepsis (LOS), a bacterial infection that frequently occurs in preterm infants in the neonatal period. Study design: Breast milk from mothers of preterm infants (≤32 weeks gestation) was collected on days 7 (n = 88) and 21 (n = 77) postpartum. Concentrations of lactoferrin, LL-37, beta-defensins 1 and 2, and alpha-defensin 5 were measured by enzyme-linked immunosorbent assay. The antimicrobial activity of breast milk samples against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Streptococcus agalactiae was compared to the activity of infant formula, alone or supplemented with physiological levels of AMPs. Samples of breast milk fed to infants with and without subsequent LOS were compared for levels of AMPs and inhibition of bacterial growth. Results: Levels of most AMPs and antibacterial activity in preterm breast milk were higher at day 7 than at day 21. Lactoferrin was the only AMP that limited pathogen growth >50% when added to formula at a concentration equivalent to that present in breast milk. Levels of AMPs were similar in the breast milk fed to infants with and without LOS, however, infants who developed LOS consumed significantly less breast milk and lower doses of milk AMPs than those who were free from LOS. Conclusions: The concentrations of lactoferrin and defensins in preterm breast milk have antimicrobial activity against common neonatal pathogens

Highly sensitive in vivo imaging of Trypanosoma brucei expressing "red-shifted" luciferase.

BACKGROUND: Human African trypanosomiasis is caused by infection with parasites of the Trypanosoma brucei species complex, and threatens over 70 million people in sub-Saharan Africa. Development of new drugs is hampered by the limitations of current rodent models, particularly for stage II infections, which occur once parasites have accessed the CNS. Bioluminescence imaging of pathogens expressing firefly luciferase (emission maximum 562 nm) has been adopted in a number of in vivo models of disease to monitor dissemination, drug-treatment and the role of immune responses. However, lack of sensitivity in detecting deep tissue bioluminescence at wavelengths below 600 nm has restricted the wide-spread use of in vivo imaging to investigate infections with T. brucei and other trypanosomatids. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a system that allows the detection of fewer than 100 bioluminescent T. brucei parasites in a murine model. As a reporter, we used a codon-optimised red-shifted Photinus pyralis luciferase (PpyRE9H) with a peak emission of 617 nm. Maximal expression was obtained following targeted integration of the gene, flanked by an upstream 5'-variant surface glycoprotein untranslated region (UTR) and a downstream 3'-tubulin UTR, into a T. brucei ribosomal DNA locus. Expression was stable in the absence of selective drug for at least 3 months and was not associated with detectable phenotypic changes. Parasite dissemination and drug efficacy could be monitored in real time, and brain infections were readily detectable. The level of sensitivity in vivo was significantly greater than achievable with a yellow firefly luciferase reporter. CONCLUSIONS/SIGNIFICANCE: The optimised bioluminescent reporter line described here will significantly enhance the application of in vivo imaging to study stage II African trypanosomiasis in murine models. The greatly increased sensitivity provides a new framework for investigating host-parasite relationships, particularly in the context of CNS infections. It should be ideally suited to drug evaluation programmes