Understanding the pharmacological properties of a metabolic PET tracer in prostate cancer

Generally, solid tumors (\u3e400 mm3) are inherently acidic, with more aggressive growth producing greater acidity. If the acidity could be targeted as a biomarker, it would provide a means to gauge the pace of tumor growth and degree of invasiveness, as well as providing a basis for predicting responses to pH-dependent chemotherapies. We have developed a 64Cu pH (low) insertion peptide (pHLIP) for targeting, imaging, and quantifying acidic tumors by PET, and our findings reveal utility in assessing prostate tumors. The new pHLIP version limits indiscriminate healthy tissue binding, and we demonstrate its targeting of extracellular acidification in three different prostate cancer models, each with different vascularization and acid-extruding protein carbonic anhydrase IX (CAIX) expression. We then describe the tumor distribution of this radiotracer ex vivo, in association with blood perfusion and known biomarkers of acidity, such as hypoxia, lactate dehydrogenase A, and CAIX. We find that the probe reveals metabolic variations between and within tumors, and discriminates between necrotic and living tumor areas

Differential mortality and high viral load in naive pacific oyster families exposed to oshv-1 suggests tolerance rather than resistance to infection

Pacific oysters, Crassostrea gigas, are one of the most productive aquaculture species in the world. However, they are threatened by the spread of Ostreid herpesvirus-1 (OsHV-1) and its microvariants (collectively “µvars”), which cause mass mortalities in all life stages of Pacific oysters globally. Breeding programs have been successful in reducing mortality due to OsHV-1 variants following viral outbreaks; however, an OsHV-1-resistant oyster line does not yet exist in the United States (US), and it is unknown how OsHV-1 µvars will affect US oyster populations compared to the current variant, which is similar to the OsHV-1 reference, found in Tomales Bay, CA. The goals of this study were to investigate the resistance of C. gigas juveniles produced by the Molluscan Broodstock Program (MBP) to three variants of OsHV-1: a California reference OsHV-1, an Australian µvar, and a French µvar. This is the first study to directly compare OsHV-1 µvars to a non-µvar. The survival probability of oysters exposed to the French (FRA) or Australian (AUS) µvar was significantly lower (43% and 71%, respectively) than to the reference variant and controls (96%). No oyster family demonstrated resistance to all three OsHV-1 variants, and many surviving oysters contained high copy numbers of viral DNA (mean ~3.53 × 108). These results indicate that the introduction of OsHV-1 µvars could have substantial effects on US Pacific oyster aquaculture if truly resistant lines are not achieved, and highlight the need to consider resistance to infection in addition to survival as traits in breeding programs to reduce the risk of the spread of OsHV-1 variants. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Differential Mortality and High Viral Load in Naive Pacific Oyster Families Exposed to OsHV-1 Suggests Tolerance Rather than Resistance to Infection

Pacific oysters, Crassostrea gigas, are one of the most productive aquaculture species in the world. However, they are threatened by the spread of Ostreid herpesvirus-1 (OsHV-1) and its microvariants (collectively “µvars”), which cause mass mortalities in all life stages of Pacific oysters globally. Breeding programs have been successful in reducing mortality due to OsHV-1 variants following viral outbreaks; however, an OsHV-1-resistant oyster line does not yet exist in the United States (US), and it is unknown how OsHV-1 µvars will affect US oyster populations compared to the current variant, which is similar to the OsHV-1 reference, found in Tomales Bay, CA. The goals of this study were to investigate the resistance of C. gigas juveniles produced by the Molluscan Broodstock Program (MBP) to three variants of OsHV-1: a California reference OsHV-1, an Australian µvar, and a French µvar. This is the first study to directly compare OsHV-1 µvars to a non-µvar. The survival probability of oysters exposed to the French (FRA) or Australian (AUS) µvar was significantly lower (43% and 71%, respectively) than to the reference variant and controls (96%). No oyster family demonstrated resistance to all three OsHV-1 variants, and many surviving oysters contained high copy numbers of viral DNA (mean ~3.53 × 108). These results indicate that the introduction of OsHV-1 µvars could have substantial effects on US Pacific oyster aquaculture if truly resistant lines are not achieved, and highlight the need to consider resistance to infection in addition to survival as traits in breeding programs to reduce the risk of the spread of OsHV-1 variant

Genetic and Genomic Approaches for Adaptation of Grapevine to Climate Change

The necessity to adapt to climate change is even stronger for grapevine than for other crops, because grape berry composition—a key determinant of fruit and wine quality, typicity and market value— highly depends on “terroir” (complete natural environment), on vintage (annual climate variability), and on their interactions. In the same time, there is a strong demand to reduce the use of pesticides. Thus, the equation that breeders and grape growers must solve has three entries that cannot be dissociated: adaptation to climate change, reduction of pesticides, and maintenance of wine typicity. Although vineyard management may cope to some extent to the short–medium-term effects of climate change, genetic improvement is necessary to provide long-term sustainable solutions to these problems. Most vineyards over the world are planted using vines that harbor two grafted plants’ genomes. Although this makes the range of interactions (scion-atmosphere, rootstock-soil, scion-rootstock) more complex, it also opens up wider possibilities for the genetic improvement of either or both the grafted genotypes. Positive aspects related to grapevine breeding are as follows: (a) a wide genetic diversity of rootstocks and scions that has not been thoroughly explored yet; (b) progress in sequencing technologies that allows high-throughput sequencing of entire genomes, faster mapping of targeted traits and easier determination of genetic relationships; (c) progress in new breeding technologies that potentially permit precise modifications on resident genes; (d) automation of phenotyping that allows faster and more complete monitoring of many traits on relatively large plant populations; (e) functional characterization of an increasing number of genes involved in the control of development, berry metabolism, disease resistance, and adaptation to environment. Difficulties involve: (a) the perennial nature and the large size of the plant that makes field testing long and demanding in manpower; (b) the low efficiency of transformation, regeneration and small size of breeding populations; (c) the complexity of the adaptive traits and the need to define more clearly future ideotypes; (d) the lack of shared and integrative platforms allowing a complete appraisal of the genotype-phenotype-environmental links; (e) legal, market and consumer acceptance of new genotypes. The present chapter provides an overview of suitable strategies and challenges linked to the adaptation of viticulture to a changing environment