Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants. Arctic indigenous peoples are exposed to PBDEs through a traditional diet high in marine mammals. PBDEs disrupt thyroid ...homeostasis. The aim of this study was to assess the relationship between serum PBDEs and thyroid function in a remote population of St. Lawrence Island Yupik. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska and measured for concentrations of PBDEs, free and total thyroxine (T4), free and total triiodothyronine (T3), and thyroid stimulating hormone (TSH). The relationships between PBDEs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Serum concentrations of several Penta-BDE congeners (BDE-28/33, 47, and 100) were positively associated with concentrations of TSH and free T3, while serum concentration of BDE-153 was negatively associated with total T3 concentrations. Both BDE-47 and 153 remained significantly associated with thyroid hormones when BDE-47, BDE-153, and BDE-209 were covariates in the same model. There were no significant relationships between serum concentrations of PBDEs and either free or total T4. Individual PBDEs are associated with thyroid hormones in serum from a remote population of Alaska Natives, and directions of effect differ by congener.
The spectral shape of reactor antineutrinos measured in recent experiments shows anomalies in comparison to neutrino reference spectra. New precision measurements of the reactor neutrino spectra as ...well as more complete input in nuclear data bases are needed to resolve the observed discrepancies between models and experimental results. This article proposes the combination of experiments at reactors which are highly enriched in U235 with commercial reactors with typically lower enrichment to gain new insights into the origin of the anomalous neutrino spectrum. The presented method clarifies, if the spectral anomaly is either solely or not at all related to the predicted U235 spectrum. Considering the current improvements of the energy scale uncertainty of present-day experiments, a significance of three sigma and above can be reached. As an example, we discuss the option of a direct comparison of the measured shape in the currently running Double Chooz near detector and the upcoming Stereo experiment. A quantitative feasibility study emphasizes that a precise understanding of the energy scale systematics is a crucial prerequisite in recent and next generation experiments investigating the spectral anomaly.
An estimated 25 million people in the US alone rely on implanted medical devices, ∼2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host ...response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ∼50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.
This article reports the measurement of the ionization quenching factor in germanium for nuclear recoil energies in the keV range. Precise knowledge of this factor in this energy range is highly ...relevant for coherent elastic neutrino-nucleus scattering and low mass dark matter searches with germanium-based detectors. Nuclear recoils were produced in a thin high-purity germanium target with a very low energy threshold via irradiation using monoenergetic neutron beams. The energy dependence of the ionization quenching factor was directly measured via kinematically constrained coincidences with surrounding liquid scintillator based neutron detectors. The systematic uncertainties of the measurements are discussed in detail. With measured quenching factors between 0.16 and 0.23 in the 0.4 keV
nr
to 6.3 keV
nr
energy range, the data are compatible with the Lindhard theory with a parameter
k
of 0.162
±
0.004
(stat + sys).
Mammalian hibernation is characterized by prolonged dormancy consisting of pronounced depression of metabolism and body temperature. Though hibernation occurs in at least seven mammalian orders and ...several families of the order Rodentia, the ecology and physiology of hibernation in rodents has been most extensively studied in the family Sciuridae, particularly in the so‐called ground squirrels, that is, the tribe Marmotini. Early studies of these rodents demonstrated the important role of an endogenous circannual clock in the persistence of annual timing and phasing of key seasonal events, including weight gain, hibernation and reproduction. Here, we review the causes and consequences of intraspecific variation in the timing of hibernation and reproduction in these sciurids and examine the physiological mechanisms that contribute to phenotypic plasticity in seasonal timing. Although the duration, annual phasing and predictability of seasonal change in environmental conditions likely promoted the evolution of endogeneity, precision and brevity of breeding seasons in the annual cycles of sciurids, substantial intraspecific variation in hibernation and reproductive phenology exists along latitudinal and altitudinal clines, as well as among locally varying environmental micro‐conditions. We suggest that much of this variation is a function of plasticity in the physiological mechanisms controlling annual cycles. While studies of captive animals have been instrumental in establishing the role of an endogenous rhythm, a greater emphasis on experimental field manipulations is needed to better understand the function, causes and consequences of phenological shifts in wild populations. Ultimately, the capacity of hibernators to adjust their timing in response to changing environmental conditions, either through phenotypic plasticity or microevolution, will be an important determinant of the resilience of sciurid species to changing climate.
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell disorders with a poor prognosis, especially for elderly patients. Increasing evidence suggests that ...alterations in the non-hematopoietic microenvironment (bone marrow niche) can contribute to or initiate malignant transformation and promote disease progression. One of the key components of the bone marrow (BM) niche are BM stromal cells (BMSC) that give rise to osteoblasts and adipocytes. It has been shown that the balance between these two cell types plays an important role in the regulation of hematopoiesis. However, data on the number of BMSC and the regulation of their differentiation balance in the context of hematopoietic malignancies is scarce. We established a stringent flow cytometric protocol for the prospective isolation of a CD73
CD105
CD271
BMSC subpopulation from uncultivated cryopreserved BM of MDS and AML patients as well as age-matched healthy donors. BMSC from MDS and AML patients showed a strongly reduced frequency of CFU-F (colony forming unit-fibroblast). Moreover, we found an altered phenotype and reduced replating efficiency upon passaging of BMSC from MDS and AML samples. Expression analysis of genes involved in adipo- and osteogenic differentiation as well as Wnt- and Notch-signalling pathways showed significantly reduced levels of DLK1, an early adipogenic cell fate inhibitor in MDS and AML BMSC. Matching this observation, functional analysis showed significantly increased in vitro adipogenic differentiation potential in BMSC from MDS and AML patients. Overall, our data show BMSC with a reduced CFU-F capacity, and an altered molecular and functional profile from MDS and AML patients in culture, indicating an increased adipogenic lineage potential that is likely to provide a disease-promoting microenvironment.
The aerobic biotransformation of 6:2 FTS salt F(CF
2)
6CH
2CH
2
SO
3
-
K
+ was determined in closed bottles for 90
d in diluted activated sludge from three waste water treatment plants (WWTPs) to ...compare its biotransformation potential with that of 6:2 FTOH F(CF
2)
6CH
2CH
2OH. The 6:2 FTS biotransformation was relatively slow, with 63.7% remaining at day 90 and all observed transformation products together accounting for 6.3% of the initial 6:2 FTS applied. The overall mass balance (6:2 FTS plus observed transformation products) at day 90 in live and sterile treatments averaged 70% and 94%, respectively. At day 90, the stable transformation products observed were 5:3 acid F(CF
2)
5CH
2CH
2COOH, 0.12%, PFBA F(CF
2)
3COOH, 0.14%, PFPeA F(CF
2)
4COOH, 1.5%, and PFHxA F(CF
2)
5COOH 1.1%. In addition, 5:2 ketone F(CF
2)
5C(O)CH
3 and 5:2 sFTOH F(CF
2)
5CH(OH)CH
3 together accounted for 3.4% at day 90. The yield of all the stable transformation products noted above (2.9%) was 19 times lower than that of 6:2 FTOH in aerobic soil. Thus 6:2 FTS is not likely to be a major source of PFCAs and polyfluorinated acids in WWTPs. 6:2 FTOH, 6:2 FTA F(CF
2)
6CH
2COOH, and PFHpA F(CF
2)
6COOH were not observed during the 90-d incubation. 6:2 FTS primary biotransformation bypassed 6:2 FTOH to form 6:2 FTUA F(CF
2)
5CF
=
CHCOOH, which was subsequently degraded via pathways similar to 6:2 FTOH biotransformation. A substantial fraction of initially dosed 6:2 FTS (24%) may be irreversibly bound to diluted activated sludge catalyzed by microbial enzymes. The relatively slow 6:2 FTS degradation in activated sludge may be due to microbial aerobic de-sulfonation of 6:2 FTS, required for 6:2 FTS further biotransformation, being a rate-limiting step in microorganisms of activated sludge in WWTPs.
Seasonally breeding mammals must make constant adjustments in behavior and physiology to manage energetic trade-offs between survival and reproduction. Despite encountering high levels of climate and ...resource variability across the year, specialist Abert’s squirrels (
Sciurus aberti
), lack the capacity to express hibernation or pronounced morphological adaptations to seasonality. Using accelerometer and GPS devices, we assessed how abiotic environmental factors, reproduction, and resource abundance influenced levels of activity and daily range size in a rural and food-supplemented suburban population of squirrels. We also quantified fecal cortisol metabolites (FCM) in squirrels to assess patterns of glucocorticoid secretion. While changes in weather predicted activity levels in both populations, seasonal variation in activity levels were reduced in food-supplemented compared to rural squirrels. In contrast to activity, daily range size was not affected by weather but was a better predictor of sex-specific reproductive investment. Comparisons between populations suggest that food-supplemented squirrels forage more efficiently within smaller areas. Across both sexes and populations, squirrels showed no sexual dimorphism in body size, no major patterns of seasonal weight change, and no associations between body mass and FCM concentrations; however, FCMs were lower in the food-supplemented compared to rural population during late-spring. Taken together, activity levels and FCM concentrations appear primarily influenced by weather and seasonal fluctuations in food availability, whereas daily range size reflects sexual asymmetries in seasonal reproductive investment. Overall, squirrels appear to rely largely on behavioral adjustments to cope with novel environmental heterogeneity, rather than changes in morphology or GC secretion.
PDF
