Chemical analysis shows that honey bees (Apis mellifera) and hive products contain many pesticides derived from various sources. The most abundant pesticides are acaricides applied by beekeepers to ...control Varroa destructor. Beekeepers also apply antimicrobial drugs to control bacterial and microsporidial diseases. Fungicides may enter the hive when applied to nearby flowering crops. Acaricides, antimicrobial drugs and fungicides are not highly toxic to bees alone, but in combination there is potential for heightened toxicity due to interactive effects.
Laboratory bioassays based on mortality rates in adult worker bees demonstrated interactive effects among acaricides, as well as between acaricides and antimicrobial drugs and between acaricides and fungicides. Toxicity of the acaricide tau-fluvalinate increased in combination with other acaricides and most other compounds tested (15 of 17) while amitraz toxicity was mostly unchanged (1 of 15). The sterol biosynthesis inhibiting (SBI) fungicide prochloraz elevated the toxicity of the acaricides tau-fluvalinate, coumaphos and fenpyroximate, likely through inhibition of detoxicative cytochrome P450 monooxygenase activity. Four other SBI fungicides increased the toxicity of tau-fluvalinate in a dose-dependent manner, although possible evidence of P450 induction was observed at the lowest fungicide doses. Non-transitive interactions between some acaricides were observed. Sublethal amitraz pre-treatment increased the toxicity of the three P450-detoxified acaricides, but amitraz toxicity was not changed by sublethal treatment with the same three acaricides. A two-fold change in the toxicity of tau-fluvalinate was observed between years, suggesting a possible change in the genetic composition of the bees tested.
Interactions with acaricides in honey bees are similar to drug interactions in other animals in that P450-mediated detoxication appears to play an important role. Evidence of non-transivity, year-to-year variation and induction of detoxication enzymes indicates that pesticide interactions in bees may be as complex as drug interactions in mammals.
Tuberous sclerosis complex (TSC) is a multisystem developmental disorder caused by mutations in the TSC1 or TSC2 genes, whose protein products are negative regulators of mechanistic target of ...rapamycin complex 1 signaling. Hallmark pathologies of TSC are cortical tubers-regions of dysmorphic, disorganized neurons and glia in the cortex that are linked to epileptogenesis. To determine the developmental origin of tuber cells, we established human cellular models of TSC by CRISPR-Cas9-mediated gene editing of TSC1 or TSC2 in human pluripotent stem cells (hPSCs). Using heterozygous TSC2 hPSCs with a conditional mutation in the functional allele, we show that mosaic biallelic inactivation during neural progenitor expansion is necessary for the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids. Our findings provide support for the second-hit model of cortical tuber formation and suggest that variable developmental timing of somatic mutations could contribute to the heterogeneity in the neurological presentation of TSC.
Mosquito-borne arboviruses cause serious diseases in humans that are increasingly becoming public health problems, yet arbovirus infections cause minimal pathology in the mosquito vector, allowing ...persistent infections and lifelong virus transmission. The principal mosquito innate immune response to virus infections, RNAi, differs substantially from the human immune response and this difference could be the basis for the disparate outcomes of infection in the two hosts. Understanding the mosquito antiviral immune response could lead to strategies for interruption of arbovirus transmission and greatly reduce disease. Research focused on RNAi as the primary mosquito antiviral response has the greatest potential for developing a full understanding of mosquito innate immunity. This article reviews our current knowledge of mosquito antiviral RNAi and charts some of the future directions needed to fill knowledge gaps.
•Pharmaceuticals and personal care products (PPCPs) were monitored in Lake Michigan.•Fifty-four PPCPs were assessed in surface water and sediment on six dates.•Many PPCPs, such as metformin, were ...detected 3.2km away from the shore.•Hydrophobic compounds were detected in sediment at concentrations up to 510ngg−1.•Using a risk quotient, the ecosystem risk was found to be high for many PPCPs.
The monitoring of pharmaceuticals and personal care products (PPCPs) has focused on the distribution in rivers and small lakes, but data regarding their occurrence and effects in large lake systems, such as the Great Lakes, are sparse. Wastewater treatment processes have not been optimized to remove influent PPCPs and are a major source of PPCPs in the environment. Furthermore, PPCPs are not currently regulated in wastewater effluent. In this experiment we evaluated the concentration, and corresponding risk, of PPCPs from a wastewater effluent source at varying distances in Lake Michigan. Fifty-four PPCPs and hormones were assessed on six different dates over a two-year period from surface water and sediment samples up to 3.2km from a wastewater treatment plant and at two sites within a harbor. Thirty-two PPCPs were detected in Lake Michigan and 30 were detected in the sediment, with numerous PPCPs being detected up to 3.2km away from the shoreline. The most frequently detected PPCPs in Lake Michigan were metformin, caffeine, sulfamethoxazole, and triclosan. To determine the ecological risk, the maximum measured environmental concentrations were compared to the predicted no-effect concentration and 14 PPCPs were found to be of medium or high ecological risk. The environmental risk of PPCPs in large lake systems, such as the Great Lakes, has been questioned due to high dilution; however, the concentrations found in this study, and their corresponding risk quotient, indicate a significant threat by PPCPs to the health of the Great Lakes, particularly near shore organisms.
A
bstract
We consider a non-relativistic limit of the bosonic sector of eleven-dimensional supergravity, leading to a theory based on a covariant ‘membrane Newton-Cartan’ (MNC) geometry. The local ...tangent space is split into three ‘longitudinal’ and eight ‘transverse’ directions, related only by Galilean rather than Lorentzian symmetries. This generalises the ten-dimensional stringy Newton-Cartan (SNC) theory. In order to obtain a finite limit, the field strength of the eleven-dimensional four-form is required to obey a transverse self-duality constraint, ultimately due to the presence of the Chern-Simons term in eleven dimensions. The finite action then gives a set of equations that is invariant under longitudinal and transverse rotations, Galilean boosts and local dilatations. We supplement these equations with an extra Poisson equation, coming from the subleading action. Reduction along a longitudinal direction gives the known SNC theory with the addition of RR gauge fields, while reducing along a transverse direction yields a new non-relativistic theory associated to D2 branes. We further show that the MNC theory can be embedded in the U-duality symmetric formulation of exceptional field theory, demonstrating that it shares the same exceptional Lie algebraic symmetries as the relativistic supergravity, and providing an alternative derivation of the extra Poisson equation.
The desire to develop artificial cells to imitate living cells in synthetic vesicle platforms has continuously increased over the past few decades. In particular, heterogeneous synthetic vesicles ...made from two or more building blocks have attracted attention for artificial cell applications based on their multifunctional modules with asymmetric structures. In addition to the traditional liposomes or polymersomes, polypeptides and proteins have recently been highlighted as potential building blocks to construct artificial cells owing to their specific biological functionalities. Incorporating one or more functionally folded, globular protein into synthetic vesicles enables more cell-like functions mediated by proteins. This Review highlights the recent research about synthetic vesicles toward artificial cell models, from traditional synthetic vesicles to protein-assembled vesicles with asymmetric structures. We aim to provide fundamental and practical insights into applying knowledge on molecular self-assembly to the bottom-up construction of artificial cell platforms with heterogeneous building blocks.
Purpose
To propose guidelines based on an expert-panel-derived unified approach to the technical performance, interpretation, and reporting of MRI for baseline and post-treatment staging of rectal ...carcinoma.
Methods
A consensus-based questionnaire adopted with permission and modified from the European Society of Gastrointestinal and Abdominal Radiologists was sent to a 17-member expert panel from the Rectal Cancer Disease-Focused Panel of the Society of Abdominal Radiology containing 268 question parts. Consensus on an answer was defined as ≥ 70% agreement. Answers not reaching consensus (< 70%) were noted.
Results
Consensus was reached for 87% of items from which recommendations regarding patient preparation, technical performance, pulse sequence acquisition, and criteria for MRI assessment at initial staging and restaging exams and for MRI reporting were constructed.
Conclusion
These expert consensus recommendations can be used as guidelines for primary and post-treatment staging of rectal cancer using MRI.
A large and complex suite of 295 legacy and new halogenated persistent organic pollutants (POPs) were investigated in fat or liver tissue samples of polar bears collected in 2013–2014 from Southern ...(SHB) and Western (WHB) subpopulations of the Canadian Arctic contaminants hotspot of Hudson Bay. A total of 210 POPs were detected and/or quantifiable with some frequency in all fat or liver samples. POP profile and concentration differences were investigated both within (e.g. age and sex) and between the two subpopulations. Two time-point comparisons were made relative to POPs reported for Hudson Bay polar bears harvested in 2007–2008. ΣPolychlorinated biphenyl (PCB) concentrations at both time points were the most concentrated of the POP groups, and were spatially uniform with no detectable influence of sex or age, as were concentrations of the dominant congener CB153. ΣChlordanes (ΣCHLs, 74–79% oxychlordane) and the Σperfluoroalkyl substances (ΣPFASs, ≈60% perfluorooctane sulfonate (PFOS)) had the second greatest POP group concentrations in SHB and WHB respectively, with ΣPFASs and ΣCHLs being significantly influenced by age and/or sex. ΣCHLs were spatially uniform but ΣPFASs were greater in the SHB bears, as were e.g. some flame retardants, due to e.g. local contamination and/or changes in bear behavior and diet. Endosulfans and hexabromocyclododecane were detectable in samples from 2007–2008 but not from 2013–2014, which is consistent with their global POP regulations. ΣPolychlorinated naphthalenes (ΣPCNs) were consistently detected at relatively high concentrations compared to other arctic wildlife, however these concentrations were low relative to legacy POPs. ΣShort-chain chlorinated paraffins (ΣSCCPs) were major contributors to the overall POPs burden with concentrations comparable to other legacy POPs, though there was no significant difference between or within subpopulations for PCNs or SCCPs. Except for octachlorostyrene, POPs concentrations were generally lower in female and male bears from SHB in 2013–2014 relative to 2007–2008, however those of WHB males were greater over the same timeframe for almost all POPs.
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•210 out of 295 legacy and new POPs were present in Hudson Bay (HB) polar bears.•ΣPCBs, ΣCHLs and PFOS were the dominant POPs in fat or liver samples.•Some POPs (e.g. ΣPFASs and ΣCHLs) were influenced by age, sex and/or subpopulation.•Some new POP concentrations were comparable (ΣSCCPs) and some lower (ΣPCNs) to legacy POPs.
We use high-quality, medium-resolution Hubble Space Telescope/Cosmic Origins Spectrograph (HST/COS) observations of 82 UV-bright active galactic nuclei (AGNs) at redshifts zAGN < 0.85 to construct ...the largest survey of the low-redshift intergalactic medium (IGM) to date: 5138 individual extragalactic absorption lines in H i and 25 different metal-ion species grouped into 2611 distinct redshift systems at zabs < 0.75 covering total redshift pathlengths ?zH i = 21.7 and zO vi = 14.5. Our semi-automated line-finding and measurement technique renders the catalog as objectively defined as possible. We find substantial clustering of H i absorbers on scales of v = 50-300 km s-1 with no significant clustering at v gsim 1000 km s-1. Splitting the sample into strong and weak absorbers, we see that most of the clustering occurs in strong, NH i gsim 1013.5 cm-2, metal-bearing IGM systems.
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