A novel MCT1 and MCT4 dual inhibitor reduces mitochondrial metabolism and inhibits tumour growth of feline oral squamous cell carcinoma

Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC. Feline oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy resembling advanced or recurrent HNSCC. The goals of this study were to investigate the effects of a previously characterized dual MCT1 and MCT4 inhibitor, MD‐1, in OSCC as a novel treatment approach for feline oral cancer. We also sought to determine the potential of feline OSCC as a large animal model for the further development of MCT inhibitors to treat human HNSCC. In vitro, MD‐1 reduced the viability of feline OSCC and human HNSCC cell lines, altered glycolytic and mitochondrial metabolism and synergized with platinum‐based chemotherapies. While MD‐1 treatment increased lactate concentrations in an HNSCC cell line, the inhibitor failed to alter lactate levels in feline OSCC cells, suggesting an MCT‐independent activity. In vivo, MD‐1 significantly inhibited tumour growth in a subcutaneous xenograft model and prolonged overall survival in an orthotopic model of feline OSCC. Our results show that MD‐1 may be an effective therapy for the treatment of feline oral cancer. Our findings also support the further investigation of feline OSCC as a large animal model to inform the development of MCT inhibitors and future clinical studies in human HNSCC.     

Diversity and evolution of major Panax species revealed by scanning the entire chloroplast intergenic spacer sequences

Ginseng is an important medicinal plant, but almost no genomic information is known for it. For the primary step to understand the Panax genome, we inspected the chloroplast genome sequence diversity and used that to infer the evolution of Panax species using them. We inspected a total of 101 intergenic spacers (IGS) covering 44,563 bp (96.8 % of the total IGS) from four Panax species. Diversity was inspected by three steps: gel electrophoresis, high resolution melting (HRM) analysis, and further confirmation by sequencing. Even though low levels of InDel polymorphism were detected by gel electrophoresis, high levels of reproducible polymorphisms were identified by HRM analysis. Sequencing of the HRM-polymorphic spaces and pair-wise multiple sequence alignments revealed up to 247 sequence variations between species. We have identified 62 IGS showing polymorphism between species. Among them, the trnE-trnT, trnT-psbD, ndhF-rpl32, and rpl14-rpl16 spaces are more informative for studying the diversity of Panax relatives. Phylogenetic analysis and molecular evolution studies revealed that P. notoginseng is most diverged from the other Panax species, with a nucleotide substitution rate of 0.0039. P. quinquefolius shows a close relationship with P. ginseng and P. japonicus, with a nucleotide substitution rate of 0.0009. Meanwhile, no sequence variation was detected between P. ginseng and P. japonicus. Calculation of molecular clocks revealed that P. notoginseng diverged more than 1.30 million years ago from the other Panax species and then, P. quinquefolius diverged from P. ginseng by migration in the American continent more than 0.29 million years ago.     

Microsatellite-based analysis of genetic diversity in 91 commercial Brassica oleracea L. cultivars belonging to six varietal groups

Brassica oleracea L. includes various types of important vegetables that show extremely diverse phenotypes. To elucidate the genetic diversity and relationships among commercial cultivars derived by different companies throughout the world, we characterized the diversity and genetic structure of 91 commercial B. oleracea cultivars belonging to six varietal groups, including cabbage, broccoli, cauliflower, kohlrabi, kale and kai-lan. We used 69 polymorphic microsatellite markers showing a total of 359 alleles with an average number of 5.20 alleles per locus. Polymorphism information content (PIC) values ranged from 0.06 to 0.73, with an average of 0.40. Among the six varietal groups, kohlrabi cultivars exhibited the highest heterozygosity level, whereas kale cultivars showed the lowest. Based on genetic similarity values, an UPGMA clustering dendrogram and a two-dimensional scale diagram (PCoA) were generated to analyze genetic diversity. The cultivars were clearly separated into six different clusters with a tendency to cluster into varietal groups. Model-based structure analysis revealed six genetic groups, in which cabbage cultivars were divided into two subgroups that were differentiated by their head shape, whereas cauliflower and kai-lan cultivars clustered together into a single group. Furthermore, we identified 18 SSR markers showing 27 unique alleles specific to only one cultivar that can be used to discriminate 22 cultivars from the others. Our phylogenetic and population structure analysis presents new insights into the genetic structure and relationships among 91 B. oleracea cultivars and provides valuable information for breeding of B. oleracea species. In addition, we demonstrate the utility of SSR markers as a powerful tool for discriminating between the cultivars. The SSR markers described herein will also be helpful for Distinctness, Uniformity and Stability (DUS) test of new cultivars.     

Impact of 12-year field treatments with organic and inorganic fertilizers on crop productivity and mycorrhizal community structure

The effect of manure and mineral fertilization on the arbuscular mycorrhizal (AM) fungal community structure of sunflower (Helianthus annuus L.) plants was studied. Soils were collected from a field experiment treated for 12 years with equivalent nitrogen (N) doses of inorganic N, dairy manure slurry, or without N fertilization. Fresh roots of tall fescue (Festuca arundinacea Schreb.) grass collected from the field plots without N fertilization and unfumigated field soils were used as native microbial inoculum sources. Sunflower plants were sown in pots containing these soils, and three different means of manipulating the microbial community were set: unfumigated soil with fresh grass roots, fumigated soil with fresh grass roots, or fumigated soil with sterilized grass roots. Assessing the implications with respect to plant productivity and mycorrhizal community structure was investigated. Twelve AM fungal OTUs were identified from root or soil samples as different taxa of Acaulospora, Claroideoglomus, Funneliformis, Rhizophagus, and uncultured Glomus, using PCR-DGGE and sequencing of an 18S rRNA gene fragment. Sunflower plants grown in manure-fertilized soils had a distinct AMF community structure from plants either fertilized with mineral N or unfertilized, with an abundance of Rhizophagus intraradices-like (B2). The results also showed that AM inoculation increased P and N contents in inorganic N-fertilized or unfertilized plants, but not in manure-fertilized plants.     

Spatiotemporally variable area: Mass relationship of Russet Burbank potato leaflets: Implications to potato production models

The relationship between area and mass of fresh Russet Burbank potato leaflets was monitored in two fields throughout two growing seasons in southern Manitoba. A simple ratio was adequate to describe the relationship between leaflet area and mass. The ratio changed non-linearly over the growing season in each field; this time trend differed among fields. During the middle of the growing season, the ratios differed significantly among all trials. In one season, Colorado potato beetles completely defoliated plants in one field; from shortly after plant emergence until no leaves remained, the area:mass ratio in this field was significantly lower than in all other fields. When the area:mass ratio is assumed to be constant or to change linearly over time, estimated leaf area per plant is consistently erroneous. Where models make either assumption, such bias may contribute to site-specificity, or to the inability to accurately simulate the effects of insect attack.     

Combating plant diseases—the Darwin connection

Although Darwin knew of plant diseases, he did not study them as part of his analysis of natural selection. Effective plant disease control has only been developed after his death. This article explores the relevance of Darwin's ideas to three problem areas with respect to diseases caused by fungi: emergence of new diseases, loss of disease resistance bred into plants and development of fungicide resistance. Darwin's concept of change through natural or artificial selection relied on selection of many small changes, but subsequent genetic research has shown that change can also occur through large steps. Appearance of new diseases can involve gene duplication, transfer or recombination, but all evidence points to both host plant resistance and fungicide susceptibility being overcome through point mutations. Because the population size of diseases such as rusts and powdery and downy mildews is so large, all possible point mutations are likely to occur daily, even during moderate epidemics. Overcoming control measures therefore reflects the overall fitness of these mutants, and much resource effort is being directed towards assessment of their fitness, both in the presence and in the absence of selection. While recent developments in comparative genomics have caused some revision of Darwin's ideas, experience in managing plant disease control measures clearly demonstrates the relevance of concepts he introduced 150 years ago. It also reveals the remarkable speed and the practical impact of adaptation in wild microorganism populations to changes in their environment, and the difficulty of stopping or delaying such adaptation. Copyright © 2009 Society of Chemical Industry     

Unilateral ventral strabismus in an aquarium Silver Arowana (Osteoglossum bicirrhosum)

An adult silver arowana (Osteoglossum bicirrhosum) presented with a 2‐month history of acute onset ventral strabismus of the right eye associated with a cystic structure overlying the dorsal aspect of the globe. Aspiration of the cyst, removal of redundant conjunctival tissue, and apposition of the surgical edges of the conjunctiva did not correct the strabismus. Magnetic resonance imaging of the head and histopathology of the eye did not reveal significant differences between affected and unaffected eyes except for a more posterior dorsal rectus muscle insertion site in the affected eye. This case report documents and describes a syndrome well known among arowana hobbyists as ‘drop eye’.     

Magnetic resonance imaging of the femoral head of normal dogs and dogs with avascular necrosis.

The purpose of this study was to describe the appearance of the femoral head of normal, young, small breed dogs, and dogs with avascular necrosis using low-field (0.3 T) magnetic resonance (MR) imaging. Images of the femoral heads were obtained in the dorsal plane, and included T1-weighted spin-echo, T2-weighted fast spin-echo, fast spin echo-inversion recovery, and fluid attenuated inversion recovery pulse sequences. MR imaging features of the asymptomatic femoral heads and necks included uniform high signal intensity compared with muscle on T1- and T2-weighted images. There was either uniform enhancement or no enhancement on postcontrast T1-weighted images. The MR imaging findings of dogs affected with avascular necrosis differed from those of asymptomatic dogs. Typically, the affected dogs had inhomogeneous intermediate to low-signal intensity within the femoral head and neck compared with muscle on T1-weighted images, inhomogeneous enhancement of the femoral head and/or neck on postcontrast T1-weighted images, and inhomogeneous low- to high- signal intensity within the femoral head and neck on T2-weighted images.