Lamellarin O,a Pyrrole Alkaloid from an Australian Marine Sponge,Ianthella sp., Reverses BCRP Mediated Drug Resistance in Cancer Cells

ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents and lead to multi-drug resistance (MDR) in cancer cells. While the discovery and development of clinically useful inhibitors has proved elusive to date, this molecular target nevertheless remains a promising strategy for addressing and potentially overcoming MDR. In a search for new classes of inhibitor, we used fluorescent accumulation and efflux assays supported by cell flow cytometry and MDR reversal assays, against a panel of sensitive and MDR human cancer cell lines, to evaluate the marine sponge co-metabolites 1–12 as inhibitors of P-gp, BCRP or MRP1 initiated MDR. These studies identified and characterized lamellarin O (11) as a selective inhibitor of BCRP mediated drug efflux. A structure–activity relationship analysis inclusive of the natural products 1–12 and the synthetic analogues 13–19, supported by in silico docking studies, revealed key structural requirements for the lamellarin O (11) BCRP inhibitory pharmacophore.     

Periodic pulsing of characteristic microearthquakes on the San Andreas fault

Deep fault slip information from characteristically repeating microearthquakes reveals previously unrecognized patterns of extensive, large-amplitude, long-duration, quasiperiodic repetition of aseismic events along much of a 175-kilometer segment of the central San Andreas fault. Pulsing occurs both in conjunction with and independent of transient slip from larger earthquakes. It extends to depths of approximately 10 to 11 kilometers but may be deeper, and it may be related to similar phenomena occurring in subduction zones. Over much of the study area, pulse onset periods also show a higher probability of larger earthquakes, which may provide useful information for earthquake forecasting.     

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.     

Biochemical response of grapevine variety ‘Chardonnay’ (Vitis vinifera L.) to infection with grapevine yellows (Bois noir)

This study was carried out on the leaves of phytoplasma susceptible grapevine variety ??Chardonnay?? (Vitis vinifera L.), and included research of the alterations in chlorophyll and carotenoid contents, contents of phenol compounds and in related enzymes activity in the phenylpropanoid pathway during the Bois noir (BN) infection. Phytoplasma-infected leaves showed reduced contents of chlorophylls and carotenoids, which promoted their susceptibility to oxidative reactions. Furthermore, modulation of flavonoid biosynthesis occurred in infected leaves, leading to an increased activity of phenylalanine ammonia lyase, chalcone synthase/chalcone isomerase, flavanone 3-hydroxylase and polyphenoloxidase, but to a decreased peroxidase activity. Phytoplasma infection led to an increase of the contents of hydroxycinnamic acids (caftaric acid, sinapic acid glucose derivate and coutaric acid), flavanols (procyanidin B1, procyanidin dimer 3, catechin, epicatechin) and flavonols (quercetin 3-O-glucuronide, quercetin 3-O-glucoside) especially in the period up to vérasion. The study demonstrated that at certain phenological key-stages infection with phytoplasma (BN) induced different alterations in enzyme activities and in the contents of biochemical compounds from primary and secondary metabolism.     

Where systems biology meets postharvest

According to the dictionary, a system is something like “a group or combination of interrelated, interdependent, or interacting elements forming a collective entity”. In postharvest, fresh harvested food crops can be considered isolated small scale systems. Postharvest research aims to understand the quality of these ‘systems’ as influenced by postharvest conditions. The phenotypic quality of horticultural produce is based on genetic traits that are expressed through a cascade of reactions subject to complex regulatory mechanisms and diverse environmental conditions. Ultimately, to fully understand postharvest phenomena, a systemic approach that links genetic and environmental responses and identifies the underlying biological networks is required. Thanks to the development of high throughput omics techniques such system-wide approaches have become a viable option to support traditional postharvest research. This review provides an overview of systems biology and how it can lead postharvest research into a new era.     

A comparison of techniques for the measurement of growth in adult lobsters

Four non-destructive measures of growth (wet weight in air, wet weight in water, displacement volume and carapace length) were correlated to two destructive measures of growth (dry weight and total body protein level) in adult American lobsters (Homarus americanus). All non-destructive parameters were significantly (P < 0.05) correlated to dry weight and protein for female lobsters. Only wet weight in water was significantly correlated to dry weight and total body protein level in male lobsters.     

Salmonella enterica serovar Kentucky recovered from human clinical cases in Maryland,USA (2011–2015)

Salmonella Kentucky is among the most frequently isolated S. enterica serovars from food animals in the United States. Recent research on isolates recovered from these animals suggests there may be geographic and host specificity signatures associated with S. Kentucky strains. However, the sources and genomic features of human clinical S. Kentucky isolated in the United States remain poorly described. To investigate the characteristics of clinical S. Kentucky and the possible sources of these infections, the genomes of all S. Kentucky isolates recovered from human clinical cases in the State of Maryland between 2011 and 2015 (n = 12) were sequenced and compared to a database of 525 previously sequenced S. Kentucky genomes representing 12 sequence types (ST) collected from multiple sources on several continents. Of the 12 human clinical S. Kentucky isolates from Maryland, nine were ST198, two were ST152, and one was ST314. Forty‐one per cent of isolates were recovered from patients reporting recent international travel and 58% of isolates encoded genomic characteristics similar to those originating outside of the United States. Of the five isolates not associated with international travel, three encoded antibiotic resistance genes conferring resistance to tetracycline or aminoglycosides, while two others only encoded the cryptic aac(6′)‐Iaa gene. Five isolates recovered from individuals with international travel histories (ST198) and two for which travel was not recorded (ST198) encoded genes conferring resistance to between 4 and 7 classes of antibiotics. Seven ST198 genomes encoded the Salmonella Genomic Island 1 and substitutions in the gyrA and parC genes known to confer resistance to ciprofloxacin. Case report data on food consumption and travel were, for the most part, consistent with the inferred S. Kentucky phylogeny. Results of this study indicate that the majority of S. Kentucky infections in Maryland are caused by ST198 which may originate outside of North America.     

Distribution of Salmonella serovars and phage types on 80 Ontario swine farms in 2004

The objective of this study was to describe the distribution of Salmonella spp. on Ontario grower-finisher pig farms. Eighty swine farms were visited from January through July 2004. On each farm, fecal samples were collected from 5 pens, 2 rectal samples and 1 pooled sample from fresh manure on the floor per pen. Salmonella was isolated from 91 (11%) of the 800 rectal samples and 73 (18%) of the 397 pooled samples. Overall, Salmonella was recovered from 37 (46%) of the 80 farms. On each positive farm, Salmonella was cultured from 1 to 7 pigs or 1 to 5 pens. Of the 37 farms, 18, 13, 5, and 1 yielded 1, 2, 3, and 4 serovars, respectively. The most common serovars were S. Typhimurium var. Copenhagen, S. Infantis, S. Typhimurium, S. Derby, S. Agona, S. Havana, and S. enterica subsp. I:Rough-O. The 3 most frequent phage types were PT 104, PT 104a, and PT 104b. There was a statistically fair agreement between samples collected directly from pigs and pooled pen samples in determining the Salmonella status at the pen and farm level (kappa = 0.6, P < 0.0001). However, in 62 pens, Salmonella status, serovars, or phage types differed between the pig and pooled pen samples. The distribution of Salmonella on the swine farms in this study indicates that, in developing an intervention strategy, priority should be given to farms positive for S. Typhimurium var. Copenhagen. Also, the variation in Salmonella status between pig and pooled pen samples deserves consideration in a sampling strategy.     

Multi‐decadal climate and fishing predictors of abundance for U.S. South Atlantic coastal fishes and invertebrates

Abundance of marine stocks fluctuates in response to both internal processes (e.g., density dependence) and exogenous drivers, including the physical environment, fishing, and trophodynamic interactions. In the United States, research investigating ecosystem drivers has been focused in data‐rich systems, primarily in the North Atlantic and North Pacific. To develop a more holistic understanding of important ecosystem drivers in the Southeast U.S. continental shelf Large Marine Ecosystem, we applied generalized linear and dynamic linear modeling to investigate the effects of climate and fishing covariates on the relative abundance trends of 71 demersal fish and invertebrate species sampled by a coastal trawl survey during 1990–2013. For the assemblage as a whole, fishing effects predominated over climate effects. In particular, changes in trawling effort within the penaeid shrimp fishery governed abundance trends of bony fishes, invertebrates, and elasmobranchs, a likely result of temporal changes in bycatch mortality. Changes in trawling intensity induced changes in overall community composition and appear to have altered trophic interactions among particular species. Among climate indices investigated, the Pacific Decadal Oscillation and the Western Bermuda High Index were most prevalent in well‐supported dynamic linear models. Observed annual abundance trends were synchronous among some taxonomically related species, highlighting similar responses to exogenous influences based on life history. This study strengthens the foundation for generating hypotheses and advancing ecosystem‐based fisheries research within the region.