Blue light activation of the photoreceptor CRYPTOCHROME (CRY) evokes rapid depolarization and increased action potential firing in a subset of circadian and arousal neurons in Drosophila melanogaster. Here we show that acute arousal behavioral responses to blue light significantly differ in mutants lacking CRY, as well as mutants with disrupted opsin-based phototransduction. Lightactivated CRY couples to membrane depolarization via a well conserved redox sensor of the voltage-gated potassium (K + ) channel β-subunit (Kvβ) Hyperkinetic (Hk). The neuronal light response is almost completely absent in hk −/− mutants, but is functionally rescued by genetically targeted neuronal expression of WT Hk, but not by Hk point mutations that disable Hk redox sensor function. Multiple K + channel α-subunits that coassemble with Hk, including Shaker, Ether-a-go-go, and Ether-a-go-go-related gene, are ion conducting channels for CRY/Hk-coupled light response. Light activation of CRY is transduced to membrane depolarization, increased firing rate, and acute behavioral responses by the Kvβ subunit redox sensor.phototransduction | potassium channel | redox | cryptochrome

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Phthalate diesters are used as plasticizers in a wide range of consumer products. Because phthalates have been shown in laboratory animal studies to be toxic, human exposure to these chemicals is a matter of concern. Nevertheless, little is known about inhalation exposure to phthalates in the United States. In this study, occurrence of nine phthalates was determined in 60 indoor air samples collected in 2014 in Albany, New York, USA. Airborne particulate and vapor phase samples were collected from various sampling locations by use of a low-volume air sampler. The median concentrations of nine phthalates in air samples collected from homes, offices, laboratories, schools, salons (hair and nail salons), and public places were 732, 143, 170, 371, 2600, and 354 ng/m(3), respectively. Diethyl phthalate (DEP) was found at the highest concentrations, which ranged from 4.83 to 2250 ng/m(3) (median 152) followed by di-n-butyl phthalate, which ranged from 4.05 to 1170 ng/m(3) (median 63.3). The median inhalation exposure dose to phthalates was estimated at 0.845, 0.423, 0.203, 0.089, and 0.070 µg/kg-bw/d for infants, toddlers, children, teenagers, and adults, respectively. Inhalation is an important pathway of human exposure to DEP.

The goal of this study was to characterize the relationship between tumor uptake of Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, includingF-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h afterCu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUV Average intrapatient SUV () was compared between HER2+ and HER2- patients. Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients ( < 0.005 either day). The distributions of overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease ( < 0.005 and 0.001, respectively, on days 1 and 2). By 1 d after injection, uptake ofCu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.

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Residue concentrations of polybrominated diphenyl ethers (PBDEs) in different kinds of samples including consumer products, indoor dust, sediment and fish collected from two e-waste recycling sites, and some industrial, urban and suburban areas in Vietnam were determined to provide a comprehensive assessment of the contamination levels, accumulation pattern, emission potential and human exposure through dust ingestion and fish consumption. There was a large variation of PBDE levels in plastic parts of obsolete electronic equipment (from 1730 to 97,300 ng/g), which is a common result observed in consumer plastic products reported elsewhere. PBDE levels in indoor dust samples collected from e-waste recycling sites ranged from 250 to 8740 ng/g, which were markedly higher than those in industrial areas and household offices. Emission rate of PBDEs from plastic parts of disposed electronic equipment to dust was estimated to be in a range from 3.4 × 10 to 1.2 × 10 (year) for total PBDEs and from 2.9 × 10 to 7.2 × 10 (year) for BDE-209. Some fish species collected from ponds in e-waste recycling villages contained elevated levels of PBDEs, especially BDE-209, which were markedly higher than those in fish previously reported. Overall, levels and patterns of PBDE accumulation in different kinds of samples suggest significant emission from e-waste sites and that these areas are potential sources of PBDE contamination. Intakes of PBDEs via fish consumption were generally higher than those estimated through dust ingestion. Intake of BDE-99 and BDE-209 through dust ingestion contributes a large proportion due to higher concentrations in dust and fish. Body weight normalized daily intake through dust ingestion estimated for the e-waste recycling sites (0.10-3.46 ng/day/kg body wt.) were in a high range as compared to those reported in other countries. Our results highlight the potential releases of PBDEs from informal recycling activities and the high degree of human exposure and suggest the need for continuous investigations on environmental pollution and toxic impacts of e-waste-related hazardous chemicals.

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