Under-connectivity between cerebral cortical association areas may underlie cognitive deficits in neurodevelopmental disorders, including the 22q11.2 deletion syndrome (22q11DS). Using the LgDel ...22q11DS mouse model, we assessed cellular, molecular, and developmental origins of under-connectivity and its consequences for cognitive function. Diminished 22q11 gene dosage reduces long-distance projections, limits axon and dendrite growth, and disrupts mitochondrial and synaptic integrity in layer 2/3 but not 5/6 projection neurons (PNs). Diminished dosage of Txnrd2, a 22q11 gene essential for reactive oxygen species catabolism in brain mitochondria, recapitulates these deficits in WT layer 2/3 PNs; Txnrd2 re-expression in LgDel layer 2/3 PNs rescues them. Anti-oxidants reverse LgDel- or Txnrd2-related layer 2/3 mitochondrial, circuit, and cognitive deficits. Accordingly, Txnrd2-mediated oxidative stress reduces layer 2/3 connectivity and impairs cognition in the context of 22q11 deletion. Anti-oxidant restoration of mitochondrial integrity, cortical connectivity, and cognitive behavior defines oxidative stress as a therapeutic target in neurodevelopmental disorders.
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•Cortical connections decrease in a DiGeorge/22q11 deletion syndrome mouse model•Under-connectivity reflects reduced dendrite, axon, and synapse growth•Txrnd2, a 22q11 gene, regulates mitochondrial metabolism and neuron growth•Cortical connections and behavioral deficits are restored by anti-oxidant therapy
Fernandez et al. use a mouse model of DiGeorge/22q11 deletion syndrome—a genetic neurodevelopmental disorder—to characterize biological mechanisms of neuronal under-connectivity, establish their role in higher-order behavior, and identify an effective pharmacological therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Knowledge of black vulture (Coragyps atratus) and turkey vulture (Cathartes aura) spatial ecology is surprisingly limited despite their vital ecological roles. Fine-scale assessments of space use ...patterns and resource selection are particularly lacking, although development of tracking technologies has allowed data collection at finer temporal and spatial resolution. Objectives of this study were to conduct the first assessment of monthly home range and core area sizes of resident black and turkey vultures with consideration to sex, as well as elucidate differences in monthly, seasonal, and annual activity patterns based on fine-scale movement data analyses. We collected 2.8-million locations for 9 black and 9 turkey vultures from June 2013 -August 2015 using solar-powered GSM/GPS transmitters. We quantified home ranges and core areas using the dynamic Brownian bridge movement model and evaluated differences as a function of species, sex, and month. Mean monthly home ranges for turkey vultures were ~50% larger than those of black vultures, although mean core area sizes did not differ between species. Turkey vulture home ranges varied little across months, with exception to a notable reduction in space-use in May, which corresponds with timing of chick-rearing activities. Black vulture home ranges and core areas as well as turkey vulture core areas were larger in breeding season months (January-April). Comparison of space use between male and female vultures was only possible for black vultures, and space use was only slightly larger for females during breeding months (February-May). Analysis of activity patterns revealed turkey vultures spend more time in flight and switch motion states (between flight and stationary) more frequently than black vultures across temporal scales. This study reveals substantive variability in space use and activity rates between sympatric black and turkey vultures, providing insights into potential behavioral mechanisms contributing to niche differentiation between these species.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is ...focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Environmental reservoirs of antibiotic resistant bacteria are poorly understood. Understanding how the environment selects for resistance traits in the absence of antibiotics is critical in ...developing strategies to mitigate this growing menace. Indirect or co-selection of resistance by environmental pollution has been shown to increase antibiotic resistance. However no attention has been given to the effects of low-level ionizing radiation or the interactions between radiation and heavy metals on the maintenance or selection for antibiotic resistance (AR) traits. Here we explore the effect of radiation and copper on antibiotic resistance. Bacteria were collected from biofilms in two ponds – one impacted by low-level radiocesium and the other an abandoned farm pond. Through laboratory controlled experiments we examined the effects of increasing concentrations of copper on the incidence of antibiotic resistance. Differences were detected in the resistance profiles of the controls from each pond. Low levels (0.01 mM) of copper sulfate increased resistance but 0.5 mM concentrations of copper sulfate depressed the AR response in both ponds. A similar pattern was observed for levels of multiple antibiotic resistance per isolate. The first principal component response of isolate exposure to multiple antibiotics showed significant differences among the six isolate treatment combinations. These differences were clearly visualized through a discriminant function analysis, which showed distinct antibiotic resistance response patterns based on the six treatment groups.
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•Effects of radiocesium and copper in the environment on antibiotic resistance in lentic biofilm bacteria are determined.•Differences in antibiotic resistance profiles differ initially between ponds with and without chronic radiation pollution.•Resistance profile converge with increasing levels of copper exposure.
The effects of chronic ionizing radiation and heavy metal pollution are determined on the incidence of antibiotic resistance traits in lentic biofilm bacteria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Low-level releases of radiocesium into former nuclear reactor cooling-reservoirs on the U.S. Department of Energy's Savannah River Site (SRS) in South Carolina, USA, dating primarily to the late ...1950s and early 1960s, have allowed examination of long-term contaminant attenuation in biota occupying these habitats. Periodic collections of migratory game birds since the 1970s have documented 137Cs (radiocesium) activity concentrations in birds of SRS reservoirs, including mainly Par Pond and Pond B. In this study, during 2014 and 2015 we released wild-caught American coots (Fulica americana) and ring-necked ducks (Aythya collaris) onto Pond B. We made lethal collections of these same birds with residence times ranging from 32 to 173 days to examine radiocesium uptake and estimate the rate of natural attenuation. The two species achieved asymptotic whole-body activity concentrations of radiocesium at different times, with ring-necked ducks requiring almost three times longer than the 30–35 days needed by coots. We estimated ecological half-life (Te) for Pond B coots over a 28-yr period as 16.8 yr (95% CI = 12.9–24.2 yr). Pond B coot Te was nearly four times longer than Te for coots at nearby Par Pond where radiocesium bioavailability had been constrained for decades by pumping of potassium-enriched river water into that reservoir. Te could not be estimated from long-term data for radiocesium in Pond B diving ducks, including ring-necked ducks, likely because of high variability in residence times of ducks on Pond B. Our results highlight the importance: (1) for risk managers to understand site-specific bio-geochemistry of radiocesium for successful implementation of countermeasures at contaminated sites and (2) of residence time as a critical determinant of observed radiocesium activity concentrations in highly mobile wildlife inhabiting contaminated habitats.
•Pond B137Cs ecological half-life (Te) for migrant American coots was 16.8 yr.•Pond B biota Te was about four times longer than Te for biota at nearby Par Pond.•Pumping potassium-enriched water into Par Pond constrained 137Cs bioavailability.•Positive mitigation relies on understanding 137Cs bio-geochemistry in environment.•Residence time is a critical determinant of 137Cs levels in highly mobile wildlife.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
The Department of Energy’s (DOE) Savannah River Site (SRS) faces a legacy of radionuclide and metal contamination from industrial processes that occurred throughout the site. Northern river otters (
...Lontra canadensis
) are appropriate receptors for studying the effects of long-term, low-level contamination because they are long-lived, higher trophic level organisms susceptible to accumulating high levels of pollutants. The purpose of this study was to use latrine surveys to examine patterns of wetland latrine usage; explicitly model northern river otter resource selection on the landscape level; and utilize the model results within an ecological risk assessment (ERA) framework to assess potential effects of metals and radiocesium (
137
Cs) on the population for the SRS as a case study. River drainages and associated wetlands were surveyed for latrine sites and scats were collected and analyzed for
137
Cs activity to validate model results. The spatially explicit resource model predicted otter drainage reach use and was used in an ERA to develop exposure models for nine heavy metals as well as
137
Cs on the SRS population of river otters. The evaluation predicted that the only contaminant occurring at high enough levels to cause population effects was mercury and that the observed concentrations were probably not high enough to cause significant impairment. However, multiple metals were above action level thresholds. The field validation process showed an unexpected preference for one man-made treatment wetland that was heavily contaminated, showing that the ERA process is complex and must be approached using multiple scales.
Implementation science measures are rarely used by stakeholders to inform and enhance clinical program change. Little is known about what makes implementation measures pragmatic (i.e., practical) for ...use in community settings; thus, the present study's objective was to generate a clinical stakeholder-driven operationalization of a pragmatic measures construct.
The pragmatic measures construct was defined using: 1) a systematic literature review to identify dimensions of the construct using PsycINFO and PubMed databases, and 2) interviews with an international stakeholder panel (N = 7) who were asked about their perspectives of pragmatic measures.
Combined results from the systematic literature review and stakeholder interviews revealed a final list of 47 short statements (e.g., feasible, low cost, brief) describing pragmatic measures, which will allow for the development of a rigorous, stakeholder-driven conceptualization of the pragmatic measures construct.
Results revealed significant overlap between terms related to the pragmatic construct in the existing literature and stakeholder interviews. However, a number of terms were unique to each methodology. This underscores the importance of understanding stakeholder perspectives of criteria measuring the pragmatic construct. These results will be used to inform future phases of the project where stakeholders will determine the relative importance and clarity of each dimension of the pragmatic construct, as well as their priorities for the pragmatic dimensions. Taken together, these results will be incorporated into a pragmatic rating system for existing implementation science measures to support implementation science and practice.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Former nuclear weapons material production at the U.S. Department of Energy’s Savannah River Site (SRS) has resulted in contamination of certain terrestrial and aquatic ecosystems on site with legacy ...wastes such as radiocesium (
137
Cs), tritium (
3
H), and metals. We collected fish and invertebrates from five beaver ponds (sites) above, adjacent, and downgradient of three SRS facilities (H-, F-, and C-Areas) to evaluate whether the accumulation of metals and radionuclides in biota were associated with specific facility operations and if the measured levels could pose risks to aquatic organisms. We compared concentrations of various metals,
137
Cs, and
3
H in fish, as well as in water (
3
H only), among sites along the stream gradient. Fish collected from sites adjacent to H-Area had significantly higher
137
Cs concentrations compared to fish from other sites. Both biota and water samples indicated significantly greater levels of
3
H in sites adjacent to and downstream of C-Area. Concentrations of zinc (Zn), copper (Cu), and mercury (Hg) in some samples exceeded effects levels reported for fish and may pose a risk to fish populations. This study reported fish tissue concentrations of
137
Cs and
3
H, which have not been documented extensively in ecotoxicological studies. Our results suggested that industrial operations such as nuclear material production at SRS could have long-lasting impact on the aquatic ecosystem via the release of radionuclides and metals, and long-term monitoring of physiological effects and population level impact in biota exposed to these contaminants are recommended.
The aquatic cooling canal system associated with a nuclear reactor built in the early 1950s received accidental releases of radiocesium (137Cs) from the reactor between 1954 and 1964, resulting in ...the dispersion of ~8.2 × 1012 Bq of 137Cs into the associated canals and ponds. The primary purpose of this study was to document concentrations of 137Cs in littoral zone fish currently occupying components of the cooling canal system, 3 canals and 2 impoundments, to determine how concentrations varied among these various components. Secondarily, we examined for potential influence of weirs within the canal system on concentrations in fish as well as the potential relationship between fish species and body size and on 137Cs concentrations in fish. We collected samples of sediment, biofilm, and fish from each component of the R-Reactor cooling system and compared 137Cs among sites and species in individual sites. Concentrations of 137Cs in sediments, biofilms and mosquitofish varied significantly among sampling areas with higher concentrations in RCAN1, a canal segment that was the closest to the reactor and received reactor effluent for a longer period than other components. Comparisons among other components of the cooling system, and species comparisons relative to presumed trophic positions and fish length were not consistent. However, littoral zone fish in the cooling canal system continue to bioaccumulate 137Cs >50 years after the original releases of contamination.
•Fish in the shallow canals and ponds of a reactor cooling system were assayed for legacy 137Cs > 50 years post-release.•All fish monitored within the cooling system had measurable levels of 137Cs.•Fish in the canal closest to the reactor, which received reactor effluent for a longer period, had the highest 137Cs levels.•There was no support for biomagnification or size effects for 137Cs accumulation, likely due to a narrow range of fish sizes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The importance of nonlinear acoustic wave propagation and ultrasound-induced cavitation in the acceleration of thermal lesion production by high intensity focused ultrasound was investigated ...experimentally and theoretically in a transparent protein-containing gel. A numerical model that accounted for nonlinear acoustic propagation was used to simulate experimental conditions. Various exposure regimes with equal total ultrasound energy but variable peak acoustic pressure were studied for single lesions and lesion stripes obtained by moving the transducer. Static overpressure was applied to suppress cavitation. Strong enhancement of lesion production was observed for high amplitude waves and was supported by modeling. Through overpressure experiments it was shown that both nonlinear propagation and cavitation mechanisms participate in accelerating lesion inception and growth. Using B-mode ultrasound, cavitation was observed at normal ambient pressure as weakly enhanced echogenicity in the focal region, but was not detected with overpressure. Formation of tadpole-shaped lesions, shifted toward the transducer, was always observed to be due to boiling. Boiling bubbles were visible in the gel and were evident as strongly echogenic regions in B-mode images. These experiments indicate that nonlinear propagation and cavitation accelerate heating, but no lesion displacement or distortion was observed in the absence of boiling.
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