Understanding sources of methylmercury in songbirds with stable mercury isotopes: Challenges and future directions

Mercury (Hg) stable isotope analysis is an emerging technique that has contributed to a better understanding of many aspects of the biogeochemical cycling of Hg in the environment. However, no study has yet evaluated its usefulness in elucidating the sources of methylmercury (MeHg) in songbird species, a common organism for biomonitoring of Hg in forested ecosystems. In the present pilot study, we examined stable mercury isotope ratios in blood of 4 species of songbirds and the invertebrates they are likely foraging on in multiple habitats in a small watershed of mixed forest and wetlands in Acadia National Park in Maine (USA). We found distinct isotopic signatures of MeHg in invertebrates (both massâ dependent fractionation [as δ202Hg] and massâ independent fractionation [as Î 199Hg]) among 3 interconnected aquatic habitats. It appears that the Hg isotopic compositions in bird blood cannot be fully accounted for by the isotopic compositions of MeHg in lower trophic levels in each of the habitats examined. Furthermore, the bird blood isotope results cannot be simply explained by an isotopic offset as a result of metabolic fractionation of δ202Hg (e.g., internal demethylation). Our results suggest that many of the birds sampled obtain MeHg from sources outside the habitat they were captured in. Our findings also indicate that massâ independent fractionation is a more reliable and conservative tracer than massâ dependent fractionation for identifying sources of MeHg in bird blood. The results demonstrate the feasibility of Hg isotope studies of songbirds but suggest that larger numbers of samples and an expanded geographic area of study may be required for conclusive interpretation. Environ Toxicol Chem 2018;37:166â 174. © 2017 SETACPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141144/1/etc3941.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141144/2/etc3941_am.pd

Photodegradation of methylmercury in stream ecosystems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109966/1/lno20135810013.pd

Learning-Facilitated Synaptic Plasticity at CA3 Mossy Fiber and Commissural–Associational Synapses Reveals Different Roles in Information Processing

Subregion-dependent differences in the role of the hippocampus in information processing exist. Recently, it has emerged that a special relationship exists between the expression of persistent forms of synaptic plasticity in hippocampal subregions and the encoding of different types of spatial information. Little is known about this type of information processing at CA3 synapses. We report that in freely behaving rats, long-term potentiation (LTP) is facilitated at both mossy fiber (mf)–CA3 and commissural–associational (AC)–CA3 synapses by exploration of a novel (empty) environment. Exploration of large spatial landmarks facilitates long-term depression (LTD) at mf-CA3 synapses and impairs synaptic depression at AC-CA3 synapses. Novel exploration of small environmental features does not facilitate LTD at mf synapses but facilitates persistent LTD at AC synapses. Thus, depending on the quality of the information synaptic plasticity at AC-CA3 and mf-CA3 synapses is differentially modulated. These data suggest that expression of LTP as a result of environmental change is a common property of hippocampal synapses. However, LTD at mf synapses or AC synapses may subserve distinct and separate functions within the CA3 region

Learning-Facilitated Synaptic Plasticity at CA3 Mossy Fiber and Commissural–Associational Synapses Reveals Different Roles in Information Processing

Subregion-dependent differences in the role of the hippocampus in information processing exist. Recently, it has emerged that a special relationship exists between the expression of persistent forms of synaptic plasticity in hippocampal subregions and the encoding of different types of spatial information. Little is known about this type of information processing at CA3 synapses. We report that in freely behaving rats, long-term potentiation (LTP) is facilitated at both mossy fiber (mf)–CA3 and commissural–associational (AC)–CA3 synapses by exploration of a novel (empty) environment. Exploration of large spatial landmarks facilitates long-term depression (LTD) at mf-CA3 synapses and impairs synaptic depression at AC-CA3 synapses. Novel exploration of small environmental features does not facilitate LTD at mf synapses but facilitates persistent LTD at AC synapses. Thus, depending on the quality of the information synaptic plasticity at AC-CA3 and mf-CA3 synapses is differentially modulated. These data suggest that expression of LTP as a result of environmental change is a common property of hippocampal synapses. However, LTD at mf synapses or AC synapses may subserve distinct and separate functions within the CA3 region

Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis

<p>Abstract</p> <p>Background</p> <p>The objectives of this retrospective study was to evaluate the efficacy of stereotactic body radiation therapy (SBRT) for small non-resectable hepatocellular carcinoma (HCC) and SBRT combined with transarterial chemoembolization (TACE) for advanced HCC with portal vein tumor thrombosis (PVTT).</p> <p>Methods</p> <p>Thirty one patients with HCC who were treated with SBRT were used for the study. We studied 32 HCC lesions, where 23 lesions (22 patients) were treated targeting small non-resectable primary HCC, and 9 lesions (9 patients) targeting PVTT using the Cyberknife. All the 9 patients targeting PVTT received TACE for the advanced HCC. Tumor volume was 3.6–57.3 cc (median, 25.2 cc) and SBRT dose was 30–39 Gy (median, 36 Gy) in 3 fractions for consecutive days for 70–85% of the planned target volume.</p> <p>Results</p> <p>The median follow up was 10.5 months. The overall response rate was 71.9% [small HCC: 82.6% (19/23), advanced HCC with PVTT: 44.4% (4/9)], with the complete and partial response rates of 31.3% [small HCC: 26.1% (6/23), advanced HCC with PVTT: 11.1% (1/9)], and 50.0% [small HCC: 56.5% (13/23), advanced HCC with PVTT: 33.3% (3/9)], respectively. The median survival period of small HCC and advanced HCC with PVTT patients was 12 months and 8 months, respectively. No patient experienced Grade 4 toxicity.</p> <p>Conclusion</p> <p>SBRT for small HCC and SBRT combined with TACE for advanced HCC with PVTT showed feasible treatment modalities with minimal side effects in selected patients with primary HCC.</p

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation

Anthracycline rechallenge using pegylated liposomal doxorubicin in patients with metastatic breast cancer: a pooled analysis using individual data from four prospective trials

BACKGROUND: The aim of this study was to determine the activity of anthracycline rechallenge using pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) previously treated with conventional anthracyclines. METHODS: Pooled individual data from four prospective trials were used, and the primary end point of the pooled analysis was clinical benefit rate (CBR). The studies comprised 935 patients, of whom 274 had received PLD in the metastatic setting after prior exposure to conventional anthracyclines (rechallenge population). RESULTS: The majority of patients were heavily pretreated. Previous anthracycline therapy was administered in the adjuvant (14%) or metastatic setting (46%), or both (40%). The overall CBR from rechallenge with PLD was 37.2% (95% CI, 32.4-42.0). In univariate analyses, the CBR was significantly higher in patients with less exposure to prior chemotherapy, in taxane-naive patients, and in patients with a favourable Eastern Cooperative Group performance status of 0 vs 1 vs 2 (53.3 vs 35.5 vs 18.2%; P<0.001). In multivariate analyses, performance status proved to be the only independent predictor of the CBR achieved with PLD rechallenge (P=0.038). There was no statistically significant difference in CBR regarding the setting, cumulative dose of and/or resistance to prior anthracyclines, or time since prior anthracycline administration. CONCLUSION: Anthracycline rechallenge using PLD is effective in patients with MBC who have a favourable performance status, regardless of setting, resistance, cumulative dose or time since prior conventional anthracycline therapy. British Journal of Cancer (2010) 103, 1518-1523. doi:10.1038/sj.bjc.6605961 www.bjcancer.com Published online 26 October 2010 (C) 2010 Cancer Research U

Functional Differences in the Backward Shifts of CA1 and CA3 Place Fields in Novel and Familiar Environments

Insight into the processing dynamics and other neurophysiological properties of different hippocampal subfields is critically important for understanding hippocampal function. In this study, we compared shifts in the center of mass (COM) of CA3 and CA1 place fields in a familiar and completely novel environment. Place fields in CA1 and CA3 were simultaneously recorded as rats ran along a closed loop track in a familiar room followed by a session in a completely novel room. This process was repeated each day over a 4-day period. CA3 place fields shifted backward (opposite to the direction of motion of the rat) only in novel environments. This backward shift gradually diminished across days, as the novel environment became more familiar with repeated exposures. Conversely, CA1 place fields shifted backward across all days in both familiar and novel environments. Prior studies demonstrated that CA1 place fields on average do not exhibit a backward shift during the first exposure to an environment in which the familiar cues are rearranged into a novel configuration, although CA3 place fields showed a strong backward shift. Under the completely novel conditions of the present study, no dissociation was observed between CA3 and CA1 during the first novel session (although a strong dissociation was observed in the familiar sessions and the later novel sessions). In summary, this is the first study to use simultaneous recordings in CA1 and CA3 to compare place field COM shift and other associated properties in truly novel and familiar environments. This study further demonstrates functional differentiation between CA1 and CA3 as the plasticity of CA1 place fields is affected differently by exposure to a completely novel environment in comparison to an altered, familiar environment, whereas the plasticity of CA3 place fields is affected similarly during both types of environmental novelty