PV1 Down-Regulation via shRNA Inhibits the Growth of Pancreatic Adenocarcinoma Xenografts

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two different human pancreatic adenocarcinoma cell lines (AsPC-1 and BxPC-3). The effect observed is because of down-regulation of PV1 in the tumour endothelial cells of host origin, PV1 being specifically expressed in tumour vascular endothelial cells and not in cancer or other stromal cells. There are no differences in vascular density of tumours treated or not with PV1 shRNA, and gain and loss of function of PV1 in endothelial cells does not modify either their proliferation or migration, suggesting that tumour angiogenesis is not impaired. Together, our data argue that down-regulation of PV1 in tumour endothelial cells results in the inhibition of tumour growth via a mechanism different from inhibiting angiogenesis

Caveolae, Fenestrae and Transendothelial Channels Retain PV1 on the Surface of Endothelial Cells

PV1 protein is an essential component of stomatal and fenestral diaphragms, which are formed at the plasma membrane of endothelial cells (ECs), on structures such as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice results in in utero and perinatal mortality. To be able to interpret the complex PV1 knockout phenotype, it is critical to determine whether the formation of diaphragms is the only cellular role of PV1. We addressed this question by measuring the effect of complete and partial removal of structures capable of forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking out caveolin-1 or cavin-1 resulted in a dramatic reduction of PV1 protein level in lungs but not kidneys. The magnitude of PV1 reduction correlated with the abundance of structures capable of forming diaphragms in the microvasculature of these organs. The absence of caveolae in the lung ECs did not affect the transcription or translation of PV1, but it caused a sharp increase in PV1 protein internalization rate via a clathrin- and dynamin-independent pathway followed by degradation in lysosomes. Thus, PV1 is retained on the cell surface of ECs by structures capable of forming diaphragms, but undergoes rapid internalization and degradation in the absence of these structures, suggesting that formation of diaphragms is the only role of PV1

Burbot Early Life History Strategies in the Great Lakes

Burbot Lota lota exhibit four previously known reproductive strategies in the Great Lakes region. In this paper we review those strategies and provide evidence for a fifth one—delayed deepwater spawning. The four known, shallow‐water strategies are as follows: (1) spawning by self‐sustaining, landlocked populations, (2) spawning in tributaries in winter and the exit of larvae to a Great Lake, (3) spawning by residents in a spawning stream with access to a Great Lake, and (4) spawning on unconsolidated and rocky areas in shallow water in winter in the lake proper. Resident, landlocked populations exist in some Michigan and Wisconsin rivers (e.g., the Muskegon River in Michigan). The evidence for winter tributary spawning is the appearance of newly hatched Burbot in the St. Marys and Bark rivers during April–June. Evidence for Burbot juveniles leaving spawning streams is U.S. Fish and Wildlife Service tributory mouth trap data. The evidence for winter nearshore spawning comes from power plant monthly entrainment studies (Mansfield et al. 1983). Our proposed fifth strategy is spring and summer spawning at deep reefs, where there is probably cobble or boulder habitat. Our evidence comes from midlake reefs in Lake Michigan and offshore areas of Lake Huron: (1) we collected adult Burbot at midlake reefs in Lake Michigan, (2) we collected many Burbot larvae (many of which were newly hatched) from Lakes Michigan and Huron in June–August, and (3) we collected a Burbot egg in a PONAR grab in mid‐July from 73 m in southern Lake Huron. An important question remains, namely, which life history strategy provides the highest recruitment success for this species. It may be that adaptability ensures the survival of this important, top‐predator fish during periods of crisis (e.g., encounters with dams, Sea Lamprey Petromyzon marinus predation).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141895/1/tafs1733.pd

Vertical distribution, seasonal differentiation and trajectory of movement of zooplankton and pelagic fish of Lake Baikal

In Lake Baikal, the majority (87%) of fish biomass is generated in the pelagic zone. Two species of Comephorus, three species of Cottocomephorus and Coregonus migratorius inhabit in the pelagic zone of the lake. Currently, only C. migratorius is considered a resource species, the harvest of which accounts for about 50% of the total fish harvest. Food items for pelagic fish are copepods Epischura baikalensis and pelagic amphipods Macrohectopus branickii. The seasonal distribution and formation of zooplankton concentrations determine the food migrations of fish. The patterns of the seasonal distribution of zooplankton and pelagic fish were described by M.M.Kozhov (1954, 1964). Comparative analysis of the abundance of zooplankton in South Baikal over time, showed that during the period of maximum development of E. baikalensis in the months of July, August, and October, zooplankton concentration in the decade 1997 to 2007 was twice more than in 1951 (Kozhov 1954; Kiprushina 2010). The distribution of E. baikalensis is directly dependent on the water temperature. Yet there is an inverse relationship in the surface layer 0–25 meters. During warming up of the surface water layers, which had been observed in 2002 year E. baikalensis left the upper zone and migrated deeper, to a layer of 50–100 meters. In other months of the year, no changes in the average values of the E. baikalensis abundance were revealed. At present, when the ecosystem of Lake Baikal is changing, there is a need to restart such complex studies, and to use the results obtained by M.M. Kozhov for comparative analysis.</jats:p

Glutathione-S-transferase genes and asthma phenotypes: a Human Genome Epidemiology (HuGE) systematic review and meta-analysis including unpublished data

Background: oxidative stress is thought to be involved in the pathogenesis of asthma. Glutathione-S-transferase (GST) enzymes, which play an important role in antioxidant defences, may therefore influence asthma risk. Two common deletion polymorphisms of GSTM1 and GSTT1 genes and the GSTP1 Ile105Val polymorphism have been associated with asthma in children and adults, but results are inconsistent across studies.Methods: systematic review and meta-analysis of the effects of GST genes on asthma, wheezing and bronchial hyper-responsiveness (BHR), with inclusion of unpublished data from three studies, including the large Avon Longitudinal Study of Parents and Children (ALSPAC). Random effect or fixed effect models were used as appropriate, and sensitivity analyses were performed to assess the impact of study characteristics and quality on pooled results.Results: the meta-analyses of GSTM1 (n = 22 studies) and GSTT1 (n = 19) showed increased asthma risk associated with the null genotype, but there was extreme between-study heterogeneity and publication bias and the association disappeared when meta-analysis was restricted to the largest studies. Meta-analysis of GSTP1 Ile105Val (n = 17) and asthma suggested a possible protective effect of the Val allele, but heterogeneity was extreme. Few studies evaluated wheezing and BHR and most reported no associations, although weak evidence was found for positive associations of GSTM1 null and GSTP1 Val allele with wheezing and a negative association of GSTP1 Val allele with BHR.Conclusions: our findings do not support a substantial role of GST genes alone in the development of asthma. Future studies of large size should focus on interactions of GST genes with environmental oxidative exposures and with other genes involved in antioxidant pathways. Quality of study conduct and reporting needs to be improved to increase credibility of the evidence accumulating over tim

A Review of Sculpins (COTTOIDEI) of Middle Asia with a Revalidation of the Species Cottus jaxartensis and Description of a New Species Cottus nudus sp. nova

Abstract— Based on the investigations of the representatives of the genus Cottus from Middle Asia, the species status of C. spinulosus is supported, and its diagnostic characters are specified. The validity of С.jaxartensis is resumed and a degree of its distinction from C. gobio is evaluated. A comparative analysis of morphological characters of the C. nasalis holotype and С.jaxartensis specimens of the same body size shows identity of these species, and, thus, C.nasalis has been included in the synonymy of C.jaxartensis. A new species C. nudus sp. nova is described. The representatives of this species differ from other Asian species of the genus in the following characters: absence of bony spickles nd dermal tubercles on the skin of the head and trunk; elongated upper jaw terminated near the vertical through posterior margin of orbit; presence of teeth on palatine bones; short sensory canal on the trunk with 23 pores; monochrome light coloration of the fins; and widened distal ends of neural and/or hemal spines in seven caudal centra. A key for the identification of three Middle Asian species (C. spinulosus, C. jaxartensis, and C.nudus sp. nova) is given. </jats:sec