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P fimbriae, enabling adherence to colonic and urinary epithelium, and aerobactin, an iron sequestering system, are both colonization factors in the human colon and virulence factors for urinary tract infection. The colonic microbiota is suggested to be a site suitable for the transfer of antibiotic resistance genes. We investigated whether phenotypic resistance to antibiotics in commensal and uropathogenic Escherichia coli from infants and young children is associated with carriage of virulence genes and to phylogenetic group origin and, in the case of fecal strains, to persistence in the gut and fecal population levels. The commensal strains ( n  = 272) were derived from a birth cohort study, while the urinary isolates ( n  = 205) were derived from outpatient clinics. Each strain was assessed for phenotypic antibiotic resistance and for carriage of virulence genes ( fimA , papC , sfaD / E , hlyA , iutA , kfiC , and neuB ), phylogenetic group (A, B1, B2, or D), and markers of particular virulent clones (CGA-D-ST69, O15:H1-D-ST393, and O25b:H4-B2-ST131). Resistance to ampicillin, tetracycline, and trimethoprim was most prevalent. Multivariate analysis showed that resistance to any antibiotic was significantly associated with carriage of genes encoding P fimbriae ( papC ) and aerobactin ( iutA ), and a phylogenetic group D origin. Neither fecal population numbers nor the capacity for long-term persistence in the gut were related to antibiotic resistance among fecal strains. Our study confirms the importance of phylogenetic group D origin for antibiotic resistance in E. coli and identifies the virulence genes papC and iutA as determinants of antibiotic resistance. The reason for the latter association is currently unclear.

Voltage-gated Na + channels (VGSCs) are heteromeric membrane protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in excitable cells, including neurons and muscle cells, where they mediate action potential firing, neurite outgrowth, pathfinding, and migration. VGSCs are also expressed in metastatic cells from a number of cancers. The Na v 1.5 α subunit (encoded by SCN5A ) is expressed in breast cancer (BCa) cell lines, where it enhances migration and invasion. We studied the expression of SCN5A in BCa array data, and tested the effect of the VGSC-blocking anticonvulsant phenytoin (5,5-diphenylhydantoin) on Na + current, migration, and invasion in BCa cells. SCN5A was up-regulated in BCa samples in several datasets, and was more highly expressed in samples from patients who had a recurrence, metastasis, or died within 5 years. SCN5A was also overexpressed as an outlier in a subset of samples, and associated with increased odds of developing metastasis. Phenytoin inhibited transient and persistent Na + current recorded from strongly metastatic MDA-MB-231 cells, and this effect was more potent at depolarized holding voltages. It may thus be an effective VGSC-blocking drug in cancer cells, which typically have depolarized membrane potentials. At a concentration within the therapeutic range used to treat epilepsy, phenytoin significantly inhibited the migration and invasion of MDA-MB-231 cells, but had no effect on weakly metastatic MCF-7 cells, which do not express Na + currents. We conclude that phenytoin suppresses Na + current in VGSC-expressing metastatic BCa cells, thus inhibiting VGSC-dependent migration and invasion. Together, our data support the hypothesis that SCN5A is up-regulated in BCa, favoring an invasive/metastatic phenotype. We therefore propose that repurposing existing VGSC-blocking therapeutic drugs should be further investigated as a potential new strategy to improve patient outcomes in metastatic BCa.

Oridonin, a diterpenoid natural product commonly used in East Asian herbal medicine, is garnering increased attention in the biomedical community due to its extensive biological activities that include antitumor, anti-inflammatory, antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the past decade, significant progress has been made in structure activity relationship and mechanism of action studies of oridonin for the treatment of cancer and other diseases. This review provides a brief summary on oridonin and its analogs in cancer drug discovery and antiinflammation and highlights its emerging therapeutic potential in neuroprotection applications.

Objective:Secretory otitis media (SOM) is characterised by persistent fluid in the middle ear cavity, but the cause is unknown. We investigated the clinical, bacteriological and immunological effects of treatment with probiotic bacteria on SOM.Design:In this double-blind pilot/preliminary study, 60 children with long-standing SOM (median 6 months) who were scheduled for insertion of tympanostomy tubes were randomised to nasal spray treatment with Streptococcus sanguinis, Lactobacillus rhamnosus or placebo for 10 days before surgery. Clinical evaluation was carried out after 10 days of treatment. Middle ear fluid (MEF) was collected during surgery for quantification of cytokines and detection of bacteria by culture and polymerase chain reaction (PCR). Nasopharyngeal swabs were obtained before treatment and at surgery.Results:Complete or significant clinical recovery occurred in 7/19 patients treated with S sanguinis compared to 1/17 patients in the placebo group (p<0.05). In the L rhamnosus treatment group, 3/18 patients were cured or much better (p = 0.60 compared with placebo). Spray treatment did not alter the composition of the nasopharyngeal flora or the cytokine pattern observed in the nasopharynx or MEF, except for a higher level of IL-8 found in the nasopharynx of L rhamnosus treated children.Conclusions:This study shows that spray treatment with S sanguinis may be effective against SOM. The mechanism for the effect remains to be investigated.

Late winter-to-summer changes (April to July) in ocean acidification state, calcium carbonate (CaCO 3 ) saturation for aragonite ( Ω a ) and calcite ( Ω c ) and biogeochemical properties were investigated in 2013 and 2014 in Kongsfjorden, Svalbard. We investigated physical (salinity, temperature) and chemical (carbonate system, nutrient) properties in the water column from the glacier front in the fjord to the west Spitsbergen shelf. The average range of Ω a in the upper 50 m in the fjord in winter was 1.59–1.74 and in summer 1.65–2.66. The lowest Ω a (1.5) was close to the reported critical threshold for aragonite-forming organisms such as the pteropod Limacina helicina . In summer 2013, Ω a , pH T and salinity were generally lower than in 2014 as a result of a larger influence of high-CO 2 water from the coastal current and less Atlantic water. The inner fjord was influenced by glacial water in summer which decreased Ω a by 0.7. Biological CO 2 consumption based on a winter-to summer decrease in nitrate was larger in 2014 than in 2013, suggesting more primary production in 2014. The influence of freshwater decreased Ω a by the same amount as the biological effect increased Ω a . The seasonal increase in temperature only played a minor role on the increase of Ω a . The biological effect showed more inter-annual variability than the effect of freshwater. Based on this study, we suggest that changes in the inflow of different water masses and freshwater directly influence ocean acidification state, but also indirectly affect the biological drivers of carbonate chemistry in the fjord.

Tidewater glacier fronts can represent important foraging areas for Arctic predators. Their ecological importance is likely to change in a warmer Arctic. Their profitability and use by consumers are expected to vary in time, but the underlying mechanisms driving such variation remain poorly known. The subglacial plume, originating from meltwater discharge, is responsible for the entrainment and transport of zooplankton to the surface, making them more readily available for surface-feeding seabirds. Both discharge and zooplankton abundance are known to fluctuate in time and are thus expected to modulate the foraging profitability of glacier fronts. This study tested the predictions that annual use of glacier fronts by black-legged kittiwakes Rissa tridactyla is positively related to the average glacier discharge and prey biomass in the fjord. To do this, we combined a multiyear dataset of environmental drivers and GPS tracks of birds in Kongsfjorden, Svalbard. Our results confirmed the interannual variation in the use of glacier fronts by kittiwakes; however, contrary to our predictions, these variations were negatively correlated to both glacier discharge and zooplankton abundance. These apparent negative relationships likely reflect non-linear effects and complex interactions between local and regional environmental factors that affect the relative profitability of glacier fronts as foraging areas. Despite their high spatial predictability, glacier fronts may not offer consistent foraging opportunities for marine predators over time.

Zooplankton vertical migration enhances the efficiency of the ocean biological pump by translocating carbon (C) and nitrogen (N) below the mixed layer through respiration and excretion at depth. We measured C and N active transport due to diel vertical migration (DVM) in a Svalbard fjord at 79°N. Multifrequency analysis of backscatter data from an Acoustic Zooplankton Fish Profiler moored from January to September 2014, combined with plankton net data, showed that Thysanoessa spp. euphausiids made up > 90% of the diel migrant biomass. Classical synchronous DVM occurred before and after the phytoplankton bloom, leading to a mismatch with intensive primary production during the midnight sun. Zooplankton DVM resulted in C respiration of 0.9 g m−2 and ammonium excretion of 0.18 g N m−2 below 82 m depth between February and April, and 0.2 g C m−2 and 0.04 g N m−2 from 11 August to 9 September, representing > 25% and > 33% of sinking flux of particulate organic carbon and nitrogen, respectively. Such contribution of DVM active transport to the biological pump in this high-Arctic location is consistent with previous measurements in several equatorial to subarctic oceanic systems of the World Ocean. Climate warming is expected to result in tighter coupling between DVM and bloom periods, stronger stratification of the Barents Sea, and northward advection of boreal euphausiids. This may increase the role of DVM in the functioning of the biological pump on the Atlantic side of the Arctic Ocean, particularly where euphausiids are or will be prevalent in the zooplankton community.

In the first-ever analysis of peer-review scores for postdoctoral fellowship applications, the system is revealed as being riddled with prejudice. The policy of secrecy in evaluation must be abandoned.

Atopic eczema, the most common atopic disease in infants, may pave the way for sensitization and allergy later in childhood. Fatty acids have immune-regulating properties and may regulate skin permeability. Here we examine whether the proportions of fatty acids among the infant and maternal plasma phospholipids at birth were associated with maternal dietary intake during pregnancy and development of atopic eczema during the first year of age in the Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) birth cohort. Dietary data were collected with a semi-quantitative food frequency questionnaire, fatty acids were measured with GC-MS and atopic eczema was diagnosed by a pediatric allergologist at 12 months of age. We found that higher proportions of n-6 PUFAs (including arachidonic acid) but lower proportions of n-3 PUFAs (including DPA) in the infant’s phospholipids at birth were associated with an increased risk of atopic eczema at 12 months of age. The n-6 and n-3 PUFAs were related to maternal intake of meat and fish, respectively. Our results suggest that prenatal exposure to unsaturated fatty acids is associated with eczema development in the infant. Maternal diet during pregnancy may partly explain the fatty acid profiles in utero.