As the main agricultural insect pollinator, the honey bee (Apis mellifera) is exposed to a number of agrochemicals, including glyphosate (GLY), the most widely used herbicide. Actually, GLY has been ...detected in honey and bee pollen baskets. However, its impact on the honey bee brood is poorly explored. Therefore, we assessed the effects of GLY on larval development under chronic exposure during in vitro rearing. Even though this procedure does not account for social compensatory mechanisms such as brood care by adult workers, it allows us to control the herbicide dose, homogenize nutrition and minimize environmental stress. Our results show that brood fed with food containing GLY traces (1.25-5.0 mg per litre of food) had a higher proportion of larvae with delayed moulting and reduced weight. Our assessment also indicates a non-monotonic dose-response and variability in the effects among colonies. Differences in genetic diversity could explain the variation in susceptibility to GLY. Accordingly, the transcription of immune/detoxifying genes in the guts of larvae exposed to GLY was variably regulated among the colonies studied. Consequently, under laboratory conditions, the response of honey bees to GLY indicates that it is a stressor that affects larval development depending on individual and colony susceptibility.
Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. ...Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections.
We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT.
There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55–10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88–12.56).
Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.
•SARS-CoV-2-infected men have a worse clinical outcome than women.•Cancer patients have an increased risk of SARS-CoV-2 infection.•Prostate cancer patients receiving androgen-deprivation therapies appear to be partially protected from the infection.
We show how to use the combinatorial notion of jump sets to parametrize the possible structures of the group of principal units of local fields, viewed as filtered modules. We establish a natural ...bijection between the set of jump sets and the orbit space of a p-adic group of filtered automorphisms acting on a free filtered module. This, together with a Markov process on Eisenstein polynomials, culminates into a mass-formula for unit filtrations. The proof leads in many cases to explicit invariants of Eisenstein polynomials, yielding a link between the filtered structure of the unit group and ramification theory. Finally, with the theory of filtered modules developed here, we recover, with a more conceptual proof, a classification, due to Miki, of the possible sets of upper jumps of a wild character: these are all jump sets, with a set of exceptions explicitly prescribed by the jump set of the local field and the size of its residue field.
Mitochondrial dysfunction and oxidative stress are strongly implicated in Parkinson's disease (PD) pathogenesis and there is evidence that mitochondrially-generated superoxide can activate NADPH ...oxidase 2 (NOX2). Although NOX2 has been examined in the context of PD, most attention has focused on glial NOX2, and the role of neuronal NOX2 in PD remains to be defined. Additionally, pharmacological NOX2 inhibitors have typically lacked specificity. Here we devised and validated a proximity ligation assay for NOX2 activity and demonstrated that in human PD and two animal models thereof, both neuronal and microglial NOX2 are highly active in substantia nigra under chronic conditions. However, in acute and sub-acute PD models, we observed neuronal, but not microglial NOX2 activation, suggesting that neuronal NOX2 may play a primary role in the early stages of the disease. Aberrant NOX2 activity is responsible for the formation of oxidative stress-related post-translational modifications of α-synuclein, and impaired mitochondrial protein import in vitro in primary ventral midbrain neuronal cultures and in vivo in nigrostriatal neurons in rats. In a rat model, administration of a brain-penetrant, highly specific NOX2 inhibitor prevented NOX2 activation in nigrostriatal neurons and its downstream effects in vivo, such as activation of leucine-rich repeat kinase 2 (LRRK2). We conclude that NOX2 is an important enzyme that contributes to progressive oxidative damage which in turn can lead to α-synuclein accumulation, mitochondrial protein import impairment, and LRRK2 activation. In this context, NOX2 inhibitors hold potential as a disease-modifying therapy in PD.
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•We developed a novel assay to detect NADPH oxidase 2 activity with cellular resolution.•Neuronal and microglial NADPH oxidase 2 are active in PD patients.•Neuronal NADPH oxidase 2 activation occurs before microglial NADPH oxidase 2.•PD-related redox unbalance relies on a mitochondrial/ NADPH oxidase 2 interplay.•Targeting NADPH oxidase 2 may represent a promising therapeutic approach in PD.
In the recent decades, rare earth elements (REE) have undergone a steady spread in several industrial and medical applications, and in agriculture. Relatively scarce information has been acquired to ...date on REE-associated biological effects, from studies of bioaccumulation and of bioassays on animal, plant and models; a few case reports have focused on human health effects following occupational REE exposures, in the present lack of epidemiological studies of occupationally exposed groups. The literature is mostly confined to reports on few REE, namely cerium and lanthanum, whereas substantial information gaps persist on the health effects of other REE. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, analogous to the recognized redox mechanisms observed for other transition elements. Adverse outcomes of REE exposures include a number of endpoints, such as growth inhibition, cytogenetic effects, and organ-specific toxicity. An apparent controversy regarding REE-associated health effects relates to opposed data pointing to either favorable or adverse effects of REE exposures. Several studies have demonstrated that REE, like a number of other xenobiotics, follow hormetic concentration-related trends, implying stimulatory or protective effects at low levels, then adverse effects at higher concentrations. Another major role for REE-associated effects should be focused on pH-dependent REE speciation and hence toxicity. Few reports have demonstrated that environmental acidification enhances REE toxicity; these data may assume particular relevance in REE-polluted acidic soils and in REE mining areas characterized by concomitant REE and acid pollution. The likely environmental threats arising from REE exposures deserve a new line of research efforts.
Systemic hyperuricemia (HyUA) in obesity/type 2 diabetes facilitated by elevated activity of xanthine oxidoreductase (XOR), which is the sole source of uric acid (UA) in mammals, has been proposed to ...contribute to the pathogenesis of insulin resistance/dyslipidemia in obesity. Here, the effects of hepatocyte-specific ablation of
, the gene encoding XOR (HXO), and whole-body pharmacologic inhibition of XOR (febuxostat) on obesity-induced insulin resistance/dyslipidemia were assessed. Deletion of hepatocyte
substantially lowered liver and plasma UA concentration. When exposed to an obesogenic diet, HXO and control floxed (FLX) mice became equally obese, but systemic HyUA was absent in HXO mice. Despite this, obese HXO mice became as insulin resistant and dyslipidemic as obese FLX mice. Similarly, febuxostat dramatically lowered plasma and tissue UA and XOR activity in obese wild-type mice without altering obesity-associated insulin resistance/dyslipidemia. These data demonstrate that hepatocyte XOR activity is a critical determinant of systemic UA homeostasis, that deletion of hepatocyte
is sufficient to prevent systemic HyUA of obesity, and that neither prevention nor correction of HyUA improves insulin resistance/dyslipidemia in obesity. Thus, systemic HyUA, although clearly a biomarker of the metabolic abnormalities of obesity, does not appear to be causative.
Acadia National Park (ANP) is located on Mt. Desert Island, ME on the U.S. Atlantic coast. ANP is routinely a top-ten most popular National Park with over four million visits in 2022. The overall ...contribution and negative effects of long-range atmospheric transport and local sources of dioxin-like contaminants endangering natural and wildlife resources is unknown. Dioxin-like (DL) contaminants polychlorinated dibenzo-p-dioxins (∑PCDD) and polychlorinated dibenzofurans (∑PCDF), non-ortho coplanar PCBs (∑CP4), and polychlorinated naphthalenes (∑PCNs) were measured at the McFarland Hill air monitoring station (44.37⁰N, 68.26⁰W). On a mass/volume basis, total PCNs averaged 90.9 % (788 fg/m3) of DL contaminants measured annually, with 92.9 % of the collected total in the vapor-phase. Alternatively, total dioxin/furans (∑PCDD/Fs) represented 71.6 % of the total toxic equivalence (∑TEQ) (1.018 fg-TEQ/m3), with 69.7 % in the particulate-phase. Maximum concentrations measured for individual sampling events for ∑PCDD/F, ∑CP4, and ∑PCN were 159 (winter), 139 (summer), and 2100 (autumn), fg/m3 respectively. Whereas the maximum ∑TEQ concentrations for individual sampling events for ∑PCDD/F, ∑CP4, and ∑PCN were 2.8 (autumn), 0.38 (summer), and 0.71 (autumn), fg-TEQ/m3 respectively. Pearson correlations were calculated for ∑PCDD/Fs and ∑PCN particulate/vapor-phase air concentrations and PM2.5 wood smoke “indicator” species. The most significant correlations were observed in autumn for particulate-phase ∑PCDD/Fs suggesting a relationship between visitation-generated combustion sources (campfires and/or waste burning) or climate-change mediated forest fires. Significant Clausius-Clapeyron (C–C) correlations observed for particulate-phase ∑PCDDs (r2 = 0.567) as ambient temperatures decreased suggests a connection between localized domestic heating sources or visitor-based burning of wood/trash resources. Alternatively, highly significant C–C vapor-phase ∑CP4-PCBs correlations (r2 = 0.815) implies that the majority of ∑CP4-PCB loading to ANP is from long-range atmospheric transport processes. Based on these findings, Acadia National Park should be classified as a remote site with minor depositional impacts from ∑PCDD/Fs, ∑CP4-PCBs, and ∑PCN atmospheric transport or local diffuse sources.
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•Thermal combustion sources are important contributors to contaminant deposition.•Depositional pathways are due to both air-surface exchange and combustion byproducts.•Wood smoke indicator particulates, PCDD/Fs, and PCNs were seasonally correlated.•Forest fires and visitor biomass combustion likely contribute to contaminant deposition.
Observation of a prethermal discrete time crystal Kyprianidis, A.; Machado, F.; Morong, W. ...
Science (American Association for the Advancement of Science),
06/2021, Letnik:
372, Številka:
6547
Journal Article
Recenzirano
Prethermal time crystal
Characterizing and understanding different phases of matter in equilibrium is usually associated with the process of thermalization, where the system equilibrates. Recent ...efforts probing nonequilibrium systems have revealed that periodic driving of the system can suppress the natural tendency for equilibration yet still form new, nonequilibrium phases. Kyprianidis
et al.
used a quantum simulator composed of 25 trapped ion qubits and spins to observe such a nonequilibrium phase of matter: the disorder-free prethermal discrete time crystal. The flexibility and tunability of their quantum simulator provide a powerful platform with which to study the exotic phases of matter.
Science
, abg8102, this issue p.
1192
An ion trap quantum simulator was used to observe signatures of a prethermal discrete time crystal.
Extending the framework of statistical physics to the nonequilibrium setting has led to the discovery of previously unidentified phases of matter, often catalyzed by periodic driving. However, preventing the runaway heating that is associated with driving a strongly interacting quantum system remains a challenge in the investigation of these newly discovered phases. In this work, we utilize a trapped-ion quantum simulator to observe the signatures of a nonequilibrium driven phase without disorder—the prethermal discrete time crystal. Here, the heating problem is circumvented not by disorder-induced many-body localization, but rather by high-frequency driving, which leads to an expansive time window where nonequilibrium phases can emerge. Floquet prethermalization is thus presented as a general strategy for creating, stabilizing, and studying intrinsically out-of-equilibrium phases of matter.
Since 2011, the evolving dynamics of the Libyan civil war combined with the EU's efforts to delegate sea patrolling in the Central Mediterranean to Libyan entities, resulted in Tunisia witnessing a ...surge in border crossings through Libya. This article argues that southeastern Tunisia consequently morphed into a humanitarian borderscape, where the personnel of International Organizations and their partner NGOs entrusted with the assistance and protection of mobile populations, de facto contributed to border enforcement. Based on interviews and informal conversations conducted in 2018 and 2019 with Tunisian NGOs, local institutional actors, national and international activists, refugees, asylum seekers, and irregularized migrants, this contribution demonstrates how such a metamorphosis impacted spontaneous solidarity networks that emerged post-2011. It also illuminates tensions and disruptions experienced by both borderland citizens and displaced individuals, particularly from Northeast Africa, as they negotiate an active presence within these altered border dynamics.
The stability of dc microgrids (MGs) depends on the control strategy adopted for each mode of operation. In an islanded operation mode, droop control is the basic method for bus voltage stabilization ...when there is no communication among the sources. In this paper, it is shown the consequences of droop implementation on the voltage stability of dc power systems, whose loads are active and nonlinear, e.g., constant power loads. The set of parallel sources and their corresponding transmission lines are modeled by an ideal voltage source in series with an equivalent resistance and inductance. This approximate model allows performing a nonlinear stability analysis to predict the system qualitative behavior due to the reduced number of differential equations. Additionally, nonlinear analysis provides analytical stability conditions as a function of the model parameters and it leads to a design guideline to build reliable (MGs) based on safe operating regions.
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