Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Effects of Long-Term Temozolomide Treatment on Glioblastoma and Astrocytoma WHO Grade 4 Stem-like Cells

Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.     

Performing Aboriginality: Desiring Pre-contact Aboriginality in Victoria, 1886–1901

This paper re-investigates notions of performed Aboriginality in relation to photographs made at Lake Tyers Mission Station, Victoria, Australia, and argues that Nicholas Caire's photographs reveal complex Aboriginal subjectivities. The photographs, made originally in 1886 and distributed to tourists, were later reproduced and circulated in book format in 1897. The first presentation of the photographs, whilst focusing on historical Aboriginality, contains traces of cross-cultural hybridity. However, the later presentation of the work reinforces historical and traditional material culture over cross-cultural dialogue. This paper argues that the desire to find historical notions of Aboriginality on mission stations in Victoria was not just due to the establishment of hierarchical racial theories in the latter part of the nineteenth century (generating the idea that Aborigines could not change and adapt to notions of ‘civilisation’) and doubts about the success of mission stations, but also because there was an interest in Aborigines who had experienced little assimilation from more remote parts of the continent of Australia. This curiosity in pre-contact Aboriginality fuelled tourism in Victoria to accessible mission stations such as Lake Tyers.     

Vibrant Photography: Photographs,actants and political ecology

Jane Bennett’s thesis in Vibrant Matter argues that we need to find ways to acknowledge and engage with the agency of all factors that create ecologies and environments, including non-human actants. This essay argues that Richard Misrach and Kate Orff’s project Petrochemical America signals some important strategies that are useful for developing visual political ecologies and understanding non-human actants, including the non-living. Although some of the images are typical scenes of environmental devastation, human and social links are made to foster the understanding that we are looking at an image of ecology rather than nature ravaged. In addition to the titles of images, captions and overall contextualization of the project, Kate Orff’s team SCAPE produce a series of diagrams called Throughlines that situate the subject of petrochemical creation and its impact in the Mississippi River corridor. The cumulative impact of Misrach’s photographic approach, combined with the effective and systematic linking of his images to other forms of relevant information by Kate Orff, produces an understanding of environment as not only inextricably linked to human activity and habitation, but which also contains differing agencies constituting a broader ecology.     

Screening of different agroindustrial by-products for industrial enzymes production by fermentation processes

Agroindustrial by-products are an abundant source of biocompounds that contain valuable nutrients, which are not exploited. In this work, lignocellulosic wastes (LW) were used in submerged fermentation (SmF) and solid-state fermentation (SSF) by Aspergillus niger NRRL3 to obtain valuable enzymes required in industries. SmF using soya bean hulls (SH), wheat bran (WB) and a by-product of wheat flour (F) produced the highest activities of endo-1,4-β-xylanase (Xyl) and endo-1,4-β-D-glucanase (EG) being at least 3 times lower than those obtained by SSF. The highest ratio of Xyl to EG was obtained in SmF with F. Xyl obtained by SmF with WB was the most thermally resistant. The enzymatic extract obtained in SmF using SH presented a high power of saccharification. The production of enzymes for further application such as bioethanol generation process revalue these LW and can help offset growing environmental problems.     

Myocardial infarction classification with multi-lead ECG using hidden Markov models and Gaussian mixture models

This study presented a new diagnosis system for myocardial infarction classification by converting multi-lead ECG data into a density model for increasing accuracy and flexibility of diseases detection. In contrast to the traditional approaches, a hybrid system with HMMs and GMMs was employed for data classification. A hybrid approach using multi-leads, i.e., lead-V1, V2, V3 and V4 for myocardial infarction were developed and HMMs were used not only to find the ECG segmentations but also to calculate the log-likelihood value which was treated as statistical feature data of each heartbeat's ECG complex. The 4-dimension feature vector extracted by HMMs was clustered by GMMs with different numbers of distribution (disease and normal data). SVMs classifier was also examined for comparison with our system in experimental result. There were total 1129 samples of heartbeats from clinical data, including 582 data with myocardial infarction and 547 normal data. The sensitivity of this diagnosis system achieved 85.71%, specificity achieved 79.82% and accuracy achieved 82.50% statistically.