The MUC1 Cytoplasmic Tail and Tandem Repeat Domains Contribute to Mammary Oncogenesis in FVB Mice

Background: Though the importance of the transmembrane mucin MUC1 in mammary oncogenesis has long been recognized, the relative contributions of the cytoplasmic tail and tandem repeat domains are poorly understood.Methods: To address this, mouse models of mammary carcinogenesis were created expressing full-length, cytoplasmic tail-deleted, or tandem repeat-deleted MUC1 constructs.Results: Overexpression of full-length MUC1 resulted in tumor formation in young mice (12 months); however, loss of either the cytoplasmic tail or the tandem repeat domain abrogated this oncogenic capacity. Aged mice in all strains developed late-onset mammary tumors similar to those previously described for the FVB background.Conclusions: This study is the fi rst spontaneous cancer model to address the relative importance of the cytoplasmic tail and tandem repeat domains to MUC1-driven mammary oncogenesis, and suggests that both of these domains are essential for tumor formation

Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene

Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2+ breast cancer

Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling

Constitutive activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogenic event in certain types of human cancer and is associated with poor patient survival. Small molecule signaling inhibitors have improved the clinical outcomes of patients with various cancer types but attempts to target KRAS have been unsuccessful. Plinabulin represents a novel class of agents that inhibit tubulin polymerization with a favorable safety profile in clinical trials. In the present study, the potency of plinabulin to inhibit tubulin polymerization and growth of KRAS-driven cancer cells was characterized. efficacy of plinabulin was tested in two different mouse models; one being the RCAS/t-va gene transfer system and the other being a xenograft model. cell culture tubulin polymerization assays were used to complement the mouse models. There was improved survival in a KRAS-driven mouse gene transfer glioma model, but lack of benefit in a similar model, without constitutively active KRAS, which supports the notion of a KRAS-specific effect. This survival benefit was mediated, at least in part, by the ability of plinabulin to inhibit tubulin polymerization and disrupt endosomal recycling. It was proposed a mechanism of compromised endosomal recycling of displaced KRAS through targeting microtubules that yields inhibition of protein kinase B, but not extracellular signal regulated kinase (ERK) signaling, therefore lending rationale to combination treatments of tubulin- and ERK-targeting agents in KRAS-driven cancer

Artificial Reproductive Technology (ART) Applied to Female Cervids Adapted from Domestic Ruminants

There are about 150 Cervidae species on the IUCN Red List of Threatened Species. Only a small part is counted among farm animals, and most of them are free roaming. The universality and large numbers of representatives of cervids such as red deer (Cervus elaphus) and roe deer (Capreolus capreolus) may predispose these species to be used as models for research on reintroduction or assisted reproduction of deer at risk of extinction. We outlined the historical fluctuation of cervids in Europe and the process of domestication, which led to breeding management. Consequently, the reproductive techniques used in domestic ruminants were adapted for use in female deer which we reviewed based on our results and other available results. We focused on stress susceptibility in cervids depending on habitat and antropopression and proposed copeptin as a novel diagnostic parameter suitable for stress determination. Some reproductive biotechniques have been adopted for female cervids with satisfactory results, e.g., in vitro fertilization, while others still require methodological refinement, e.g., cryopreservation of oocytes and embryos

Podstawy ekostratygrafii ichtiofaunistycznej osadów oligocenu-wczesnego miocenu basenu zewnętrznych Karpat Polskich

The paper presents the results of an analysis of ichthyofaunal variability throughout the section of the Menilite-Krosno Series (MKS) in the Outer Carpathians of Poland. The studied tanathocoenoses were formed at the bottom of a more than 2,000 m deep northern basin of the Tethys, being largely represented by the continental rise and bottoms of its narrow furrows, and - to a lesser degree - the continental slope and slopes of a submarine high. Lateral variability of statististically representative assemblages of tanathocoenoses hosted in thin, isochro- nous horizons is interpreted as a result of both local changes of ichthyocoenoses and the influence of post-mortem relocation of fishes that mainly dwelled the shelf and upper continental slope. Vertical variability, in turn, is considered as a resulting from changeable conditions of the ecological environment, the input and outflow of taxa whose evolution proceeded in the Indo-Pacific area, and the species extinction. Changeability of ichthyofauna within a ca. 16-m.y.-long interval made it possible to document and formally describe 9 zones and 4 subzones of ichthyofauna of ecostratigraphic character. These zones comprise index, representative and accompanying taxa that belong to different ecological groups. Conceptual models of the origin of ichthyofaunal assemblages of individual zones are presented. It is suggested that the origin of assemblage differentiation resulted from the appearance and disappearance of the oxygen minimum zone in the water column, global and local sea level changes, topography of the basin bottom, as well as final basin infilling by sediments of submarine fans. The described and preserved collection of fossil Carpathian fishes, housed at the Department of Palaeozoology of the University of Wrocław, requires further specialized palaeontological studies in order to reconstruct a more complete composition of the Oligocene-Early Miocene ichthyofauna

The Quality and Fertilizing Potential of Red Deer (<i>Cervus elaphus</i> L.) Epididymal Spermatozoa Stored in a Liquid State

The aim of this study was to assess the quality and fertilizing potential of red deer epididymal spermatozoa stored in a liquid state for up to 11 days (D11). In Experiment 1, sperm quality was determined. In Experiment 2, the efficiency of in vitro fertilization (IVF) and artificial insemination (AI) of stored sperm were evaluated. An analysis of sperm quality on D5 of storage revealed a decrease (p < 0.05) in motility and morphology, and a higher proportion of apoptotic spermatozoa. On D1, D7 and D10, the total motility of sperm for IVF and AI was determined to be 82.6%, 71.0% and 64.8%, respectively. The results of IVF and AI demonstrated that the fertilizing potential of spermatozoa differs between days of storage. The percentage of blastocysts was higher when oocytes were fertilized on D1 (17.4 %) compared to D7 (8.5%) and D10 sperm (10.5%). Differences were noted in the pregnancy rates of inseminated hinds. The insemination with D1, D7 and D10 sperm led to live births (33% from D7 and D10). The results indicate that the quality of red deer epididymal spermatozoa remains satisfactory during ten days of storage in a liquid state, and that these spermatozoa maintain their fertility potential

Accuracy of Objective Physical Activity Monitors in Measuring Steps in Older Adults

Objective: The aim of this study is to evaluate accuracy of research activity monitors in measuring steps in older adults with a range of walking abilities. Method: Participants completed an initial assessment of gait speed. The accuracy of each monitor to record 100 steps was assessed across two walking trials. Results: In all, 43 older adults (age 87 ± 5.7 years, 81.4% female) participated. Overall, the StepWatch had the highest accuracy (99.0% ± 1.5%), followed by the ActivPAL (93.7% ± 11.1%) and the Actigraph (51.4% ± 35.7%). The accuracy of the Actigraph and ActivPAL varied according to assistive device use, and the accuracy of all three monitors differed by gait speed category (all p < .05). StepWatch was highly accurate (⩾97.7) across all conditions. Discussion: The StepWatch and ActivPAL monitor were reasonably accurate in measuring steps in older adults who walk slowly and use an assistive device. The Actigraph significantly undercounted steps in those who walk slow or use an assistive device. Researchers should consider gait speed and the use of assistive devices when selecting an activity monitor