Intergenerational effects of CO2‐induced stream acidification in the Trinidadian guppy (Poecilia reticulata)

Rising atmospheric carbon dioxide levels are driving decreases in aquatic pH. As a result, there has been a surge in the number of studies examining the impact of acidification on aquatic fauna over the past decade. Thus far, both positive and negative impacts on the growth of fish have been reported, creating a disparity in results. Food availability and single‐generation exposure have been proposed as some of the reasons for these variable results, where unrealistically high food treatments lead to fish overcoming the energetic costs associated with acclimating to decreased pH. Likewise, exposure of fish to lower pH for only one generation may not capture the likely ecological response to acidification that wild populations might experience over two or more generations. Here we compare somatic growth rates of laboratory populations of the Trinidadian guppy (Poecilia reticulata) exposed to pH levels that represent the average and lowest levels observed in streams in its native range. Specifically, we test the role of maternal acclimation and resource availability on the response of freshwater fishes to acidification. Acidification had a negative impact on growth at more natural, low food treatments. With high food availability, fish whose mothers were acclimated to the acidified treatment showed no reduction in growth, compared to controls. Compensatory growth was observed in both control–acidified (maternal–natal environment) and acidified–control groups, where fish that did not experience intergenerational effects achieved the same size in response to acidification as those that did, after an initial period of stunted growth. These results suggest that future studies on the effects of shifting mean of aquatic pH on fishes should take account of intergenerational effects and compensatory growth, as otherwise effects of acidification may be overestimated.     

Characterization of genetic instability in radiation- and benzene-induced murine acute leukemia.

This study, using the CBA/Ca mouse as a model, compares genetic lesions associated with radiation- and benzene-induced acute leukemias. Specific types of leukemia included in the analyses are radiation-induced acute myeloid leukemia (ML), and benzene-induced lymphoblastic leukemias, lymphomas, or mix-lineage leukemias. These leukemias have histopathological characteristics similar to those seen in human acute leukemias. G-band cytogenetic analysis showed that specific deletions involving regions D-E of one copy of mouse chromosome 2 [del(2)(D-E)] were frequently associated in both radiation- and benzene-induced acute leukemias. In addition, translocations of chr2(D-E) were also observed in some cases. These results suggest an important role of chr2 (D-E) deletions and translocations in the development of radiation- and benzene-induced murine acute leukemias. Fluorescence in situ hybridization with DNA probes specific for 2(D-E), constructed in our laboratory by means of chromosomal microdissection and PCR amplification, also demonstrate 2(D-E) deletions and/or translocations in these leukemic cells. Aneuploidy of chromosomes 3, 15, 16, and Y were also frequently detected in benzene-induced leukemic cells with or without lesions on chr2. These cytogenetic findings support the previous observations that metabolites of benzene lead to spindle-fiber disruption or abnormal cytokinesis in exposed animals. In summary, genetic instabilities observed in leukemic cells isolated from mice that had developed leukemia after exposure to radiation or benzene are syntenic with those frequently detected in patients with myelodysplastic syndrome, acute ML, and acute lymphoblastic leukemia. Thus, the CBA/Ca mouse has several characteristics that make it an excellent model for the study of radiation or benzene leukemogenesis in humans.     

Extracellular vesicle-mediated transport: Reprogramming a tumor microenvironment conducive with breast cancer progression and metastasis

Breast cancer metastatic progression to critical secondary sites is the second leading cause of cancer-related mortality in women. While existing therapies are highly effective in combating primary tumors, metastatic disease is generally deemed incurable with a median survival of only 2, 3 years. Extensive efforts have focused on identifying metastatic contributory targets for therapeutic antagonism and prevention to improve patient survivability. Excessive breast cancer release of extracellular vesicles (EVs), whose contents stimulate a metastatic phenotype, represents a promising target. Complex breast cancer intercellular communication networks are based on EV transport and transference of molecular information is in bulk resulting in complete reprogramming events within recipient cells. Other breast cancer cells can acquire aggressive phenotypes, endothelial cells can be induced to undergo tubule formation, and immune cells can be neutralized. Recent advancements continue to implicate the critical role EVs play in cultivating a tumor microenvironment tailored to cancer proliferation, metastasis, immune evasion, and conference of drug resistance. This literature review serves to frame the role of EV transport in breast cancer progression and metastasis. The following five sections will be addressed: (1) Intercellular communication in developing a tumor microenvironment & pre-metastatic niche. (2) Induction of the epithelial-to-mesenchymal transition (EMT). (3). Immune suppression & evasion. (4) Transmission of drug resistance mechanisms. (5) Precision medicine: clinical applications of EVs.