Notes

Losartan Guards Podocytes towards High Glucose-induced Damage by Inhibiting B7-1 Expression.
The United States Environmental Protection Agency (EPA) Science Advisory Board (SAB) provides expert advice to inform agency decision-making. Recent regulations have decreased the representation of academic scientists on the EPA SAB and increased the representation of industry scientists. selleck chemicals llc In an experiment, we asked how the US public views the goals and legitimacy of the board as a function of its composition. Respondents perceived SABs with a majority of industry scientists to be more likely to promote business interests than SABs with a majority of academic scientists. Liberals were less likely than conservatives to perceive industry-majority SABs as promoting human health and the environment, and making unbiased and evidence-based decisions. Our findings underscore the potential for politicization of scientific advice to the government.Exposure to even subtle forms of misleading information can significantly alter memory for past events. Memory distortion due to misinformation has been linked to faulty reconstructive processes during memory retrieval and the reactivation of brain regions involved in the initial encoding of misleading details (cortical reinstatement). The current study investigated whether warning participants about the threat of misinformation can modulate cortical reinstatement during memory retrieval and reduce misinformation errors. Participants watched a silent video depicting a crime (original event) and were given an initial test of memory for the crime details. Then, participants listened to an auditory narrative describing the crime in which some original details were altered (misinformation). Importantly, participants who received a warning about the reliability of the auditory narrative either before or after exposure to misinformation demonstrated less susceptibility to misinformation on a final test of memory compared to unwarned participants. Warned and unwarned participants also demonstrated striking differences in neural activity during the final memory test. Compared to participants who did not receive a warning, participants who received a warning (regardless of its timing) demonstrated increased activity in visual regions associated with the original source of information as well as decreased activity in auditory regions associated with the misleading source of information. Stronger visual reactivation was associated with reduced susceptibility to misinformation, whereas stronger auditory reactivation was associated with increased susceptibility to misinformation. Together, these results suggest that a simple warning can modulate reconstructive processes during memory retrieval and reduce memory errors due to misinformation.In higher plants, molecular responses to exogenous hypoxia are driven by group VII ethylene response factors (ERF-VIIs). These transcriptional regulators accumulate in the nucleus under hypoxia to activate anaerobic genes but are destabilized in normoxic conditions through the action of oxygen-sensing plant cysteine oxidases (PCOs). The PCOs catalyze the reaction of oxygen with the conserved N-terminal cysteine of ERF-VIIs to form cysteine sulfinic acid, triggering degradation via the Cys/Arg branch of the N-degron pathway. The PCOs are therefore a vital component of the plant oxygen signaling system, connecting environmental stimulus with cellular and physiological response. Rational manipulation of PCO activity could regulate ERF-VII levels and improve flood tolerance, but requires detailed structural information. We report crystal structures of the constitutively expressed PCO4 and PCO5 from Arabidopsis thaliana to 1.24 and 1.91 Å resolution, respectively. The structures reveal that the PCOs comprise a cupin-like scaffold, which supports a central metal cofactor coordinated by three histidines. While this overall structure is consistent with other thiol dioxygenases, closer inspection of the active site indicates that other catalytic features are not conserved, suggesting that the PCOs may use divergent mechanisms to oxidize their substrates. Conservative substitution of two active site residues had dramatic effects on PCO4 function both in vitro and in vivo, through yeast and plant complementation assays. Collectively, our data identify key structural elements that are required for PCO activity and provide a platform for engineering crops with improved hypoxia tolerance.The recently discovered, chlorophyll-f-containing, far-red photosystem II (FR-PSII) supports far-red light photosynthesis. Participation and kinetics of spectrally shifted far-red pigments are directly observable and separated from that of bulk chlorophyll-a We present an ultrafast transient absorption study of FR-PSII, investigating energy transfer and charge separation processes. Results show a rapid subpicosecond energy transfer from chlorophyll-a to the long-wavelength chlorophylls-f/d The data demonstrate the decay of an ∼720-nm negative feature on the picosecond-to-nanosecond timescales, coinciding with charge separation, secondary electron transfer, and stimulated emission decay. An ∼675-nm bleach attributed to the loss of chl-a absorption due to the formation of a cation radical, PD1+•, is only fully developed in the nanosecond spectra, indicating an unusually delayed formation. A major spectral feature on the nanosecond timescale at 725 nm is attributed to an electrochromic blue shift of a FR-chlorophyll among the reaction center pigments. These time-resolved observations provide direct experimental support for the model of Nürnberg et al. [D. J. Nürnberg et al., Science 360, 1210-1213 (2018)], in which the primary electron donor is a FR-chlorophyll and the secondary donor is chlorophyll-a (PD1 of the central chlorophyll pair). Efficient charge separation also occurs using selective excitation of long-wavelength chlorophylls-f/d, and the localization of the excited state on P720* points to a smaller (entropic) energy loss compared to conventional PSII, where the excited state is shared over all of the chlorin pigments. This has important repercussions on understanding the overall energetics of excitation energy transfer and charge separation reactions in FR-PSII.The sensitive and accurate quantification of protein biomarkers plays important roles in clinical diagnostics and biomedical research. Sandwich ELISA and its variants accomplish the capture and detection of a target protein via two antibodies that tightly bind at least two distinct epitopes of the same antigen and have been the gold standard for sensitive protein quantitation for decades. However, existing antibody-based assays cannot distinguish between signal arising from specific binding to the protein of interest and nonspecific binding to assay surfaces or matrix components, resulting in significant background signal even in the absence of the analyte. As a result, they generally do not achieve single-molecule sensitivity, and they require two high-affinity antibodies as well as stringent washing to maximize sensitivity and reproducibility. Here, we show that surface capture with a high-affinity antibody combined with kinetic fingerprinting using a dynamically binding, low-affinity fluorescent antibody fragment differentiates between specific and nonspecific binding at the single-molecule level, permitting the direct, digital counting of single protein molecules with femtomolar-to-attomolar limits of detection (LODs). We apply this approach to four exemplary antigens spiked into serum, demonstrating LODs 55- to 383-fold lower than commercially available ELISA. As a real-world application, we establish that endogenous interleukin-6 (IL-6) can be quantified in 2-µL serum samples from chimeric antigen receptor T cell (CAR-T cell) therapy patients without washing away excess serum or detection probes, as is required in ELISA-based approaches. This kinetic fingerprinting thus exhibits great potential for the ultrasensitive, rapid, and streamlined detection of many clinically relevant proteins.Most Republicans in a January 2020 survey agreed that "the traditional American way of life is disappearing so fast that we may have to use force to save it." More than 40% agreed that "a time will come when patriotic Americans have to take the law into their own hands." (In both cases, most of the rest said they were unsure; only one in four or five disagreed.) I use 127 survey items to measure six potential bases of these and other antidemocratic sentiments partisan affect, enthusiasm for President Trump, political cynicism, economic conservatism, cultural conservatism, and ethnic antagonism. The strongest predictor by far, for the Republican rank-and-file as a whole and for a variety of subgroups defined by education, locale, sex, and political attitudes, is ethnic antagonism-especially concerns about the political power and claims on government resources of immigrants, African-Americans, and Latinos. The corrosive impact of ethnic antagonism on Republicans' commitment to democracy underlines the significance of ethnic conflict in contemporary US politics.Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women. A subsample of 27 also completed personality measures to examine the relationship between aromatase and personality traits related to self-regulation and inhibitory control. Results indicated that aromatase availability in the amygdala was negatively associated with body mass index (BMI) (in kilograms per square meter) and positively correlated with scores of the personality trait constraint independent of sex or age. Individual variations in the brain's capacity to synthesize estrogen may influence the risk of obesity and self-control in men and women.Tropical cyclones (TC) are one of the most severe storm systems on Earth and cause significant loss of life and property upon landfall in coastal areas. A better understanding of their variability mechanisms will help improve the TC seasonal prediction skill and mitigate the destructive impacts of the storms. Early studies focused primarily on tropical processes in regulating the variability of TC activity, while recent studies suggest also some long-range impacts of extratropical processes, such as lateral transport of dry air and potential vorticity by large-scale waves. Here we show that stationary waves in the Northern Hemisphere integrate tropical and extratropical impacts on TC activity in July through October. In particular, tropical upper-tropospheric troughs (TUTTs), as part of the summertime stationary waves, are associated with the variability of large-scale environmental conditions in the tropical North Atlantic and North Pacific and significantly correlated to the variability of TC activity in these basins. TUTTs are subject to the modulation of diabatic heating in various regions and are the preferred locations for extratropical Rossby wave breaking (RWB). A strong TUTT in a basin is associated with enhanced RWB and tropical-extratropical stirring in that basin, and the resultant changes in the tropical atmospheric conditions modulate TC activity. In addition, the anticorrelation of TUTTs between the North Atlantic and North Pacific makes the TC activity indices over the two basins compensate each other, rendering the global TC activity less variable than otherwise would be the case if TUTTs were independent.
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