Flint, Michigan switched to the Flint River as a temporary drinking water source without implementing corrosion control in April 2014. Ten months later, water samples collected from a Flint residence ...revealed progressively rising water lead levels (104, 397, and 707 μg/L) coinciding with increasing water discoloration. An intensive follow-up monitoring event at this home investigated patterns of lead release by flow rate-all water samples contained lead above 15 μg/L and several exceeded hazardous waste levels (>5000 μg/L). Forensic evaluation of exhumed service line pipes compared to water contamination "fingerprint" analysis of trace elements, revealed that the immediate cause of the high water lead levels was the destabilization of lead-bearing corrosion rust layers that accumulated over decades on a galvanized iron pipe downstream of a lead pipe. After analysis of blood lead data revealed spiking lead in blood of Flint children in September 2015, a state of emergency was declared and public health interventions (distribution of filters and bottled water) likely averted an even worse exposure event due to rising water lead levels.
Every country in Europe experienced an adverse impact from the COVID-19 pandemic on life satisfaction, though on average, satisfaction with life in the summer of 2022 is about the same as the ...pre-pandemic value in the autumn of 2019. Typically, an upsurge in the severity of the pandemic (measured by the number of COVID-related deaths) is associated with declining life satisfaction and an ebbing, with increasing life satisfaction. Of the three waves of the pandemic between March 2020 and the autumn of 2022, the most severe impact typically occurred in 2021 during the second wave; in the third wave, the response declined due to the spread of effective vaccines and the takeover of omicron variants.
Of marine eubacteria, the genus
is intriguing because member species are relevant to both marine ecology and human health. Many studies have touted the relationships of
to environmental factors, ...especially temperature and salinity, to predict total
abundance but lacked the taxonomic resolution to identify the relationships among species and the key drivers of
dynamics. To improve next-generation sequencing (NGS) surveys of
, we have conducted both 16S small subunit rRNA and heat shock protein 60 (
) amplicon sequencing of water samples collected at two well-studied locations in the Neuse River Estuary, NC. Samples were collected between May and December 2016 with enhanced sampling efforts in response to two named storms. Using
sequences, 21
species were identified, including the potential human pathogens
,
, and
Changes in the
community mirrored seasonal and storm-related changes in the water column, especially in response to an influx of nutrient-rich freshwater to the estuary after Hurricane Matthew, which initiated dramatic changes in the overall
community. Individual species dynamics were wide ranging, indicating that individual
taxa have unique ecologies and that total
abundance predictors are insufficient for risk assessments of potentially pathogenic species. Positive relationships between
, dinoflagellates, and
were identified, as were intraspecies associations, which further illuminated the interactions of cooccurring
taxa along environmental gradients.
The objectives of this research were to utilize a novel approach to improve sequence-based surveys of
communities and to demonstrate the usefulness of this approach by presenting an analysis of
dynamics in the context of environmental conditions, with a particular focus on species that cause disease in humans and on storm effects. The methods presented here enabled the analysis of
dynamics with excellent taxonomic resolution and could be incorporated into future ecological studies and risk prediction strategies for potentially pathogenic species. Next-generation sequencing of
and other innovative sequence-based approaches are valuable tools and show great promise for studying
ecology and associated public health risks.
Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity ...of the 7-transmembrane protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. A central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Cholesterol activity in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability.
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•Patched structure reveals a hydrophobic conduit with sterol-like contents•Patched mediates Hedgehog-reversible reduction of inner leaflet cholesterol activity•Hydrophobic conduit is essential for cholesterol effect and Smoothened suppression•Inner leaflet cholesterol likely mediates Hedgehog-Patched regulation of Smoothened
Structural and biochemical evidence suggests that the Hedgehog receptor Patched may mediate removal of cholesterol from the inner leaflet of the plasma membrane via a hydrophobic conduit.
Explaining happiness trends in Europe Easterlin, Richard A; O'Connor, Kelsey J
Proceedings of the National Academy of Sciences - PNAS,
09/2022, Letnik:
119, Številka:
37
Journal Article
Recenzirano
Odprti dostop
In Europe, differences among countries in the overall change in happiness since the early 1980s have been due chiefly to the generosity of welfare state programs-increasing happiness going with ...increasing generosity and declining happiness with declining generosity. This is the principal conclusion from a time-series study of 10 Northern, Western, and Southern European countries with the requisite data. In the present study, cross-section analysis of recent data gives a misleading impression that economic growth, social capital, and/or quality of the environment are driving happiness trends, but in the long-term, time-series data, these variables have no relation to happiness.
Biofilms are bacterial communities contained within an extracellular matrix, which can colonize both native tissues and artificial surfaces. In particular, indwelling medical devices and prosthetic ...implants are targets for biofilm formation because they facilitate bacterial attachment via host proteins that coat the foreign body. Biofilm infections are particularly challenging to treat, since they are not readily cleared by antibiotics, require invasive procedures to eradicate, and are prone to recurrence. It has been demonstrated that biofilm-derived products can actively suppress proinflammatory immune responses, as evident by the recruitment of myeloid-derived suppressor cells and macrophage (MФ) polarization towards an anti-inflammatory state. Recent studies have shown that alterations in leukocyte metabolism shape their inflammatory phenotype and function. For example, anti-inflammatory MФs are biased towards oxidative phosphorylation whereas proinflammatory MФs favor aerobic glycolysis. This review will compare the immune responses elicited by planktonic and biofilm bacterial infections, with a discussion on the metabolic properties of MФs and neutrophils in response to both bacterial growth conditions.
SUMMARY
Psychological measures are gaining recognition as important determinants of labor performance. This paper demonstrates that people reporting greater subjective well‐being (SWB) are causally ...less likely to be unemployed in the future. The relation exhibits a meaningful magnitude relative to the mean unemployment rate and other determinants. The analysis is based on a longitudinal survey of German households over the period 1996‐2013 (German Socio‐Economic Panel). Analyses include separate dynamic and fixed‐effects regressions, and two instrumental variable approaches. Together, this sample and set of analyses, makes it possible to assess the relation for previously unstudied groups and to assess different mechanisms. Indeed the relation exhibits considerable heterogeneity. It is quadratic and substantially greater for students and people that are presently unemployed (compared to their counterparts). Fixed effects regressions indicate that SWB affects future unemployment in part through within‐person changes in the Big‐Five personality traits (e.g., conscientiousness or emotional stability) but not cognitive ability. The results imply SWB may be used as a proxy for alternative psychological predictors of performance, which is important because SWB is more broadly available than many alternatives (e.g., the Big Five). What is more, policy makers have additional reasons to promote SWB.
Hedgehog signaling specifies tissue patterning and renewal, and pathway components are commonly mutated in certain malignancies. Although central to ensuring appropriate pathway activity in all ...Hedgehog-responsive cells, how the transporter-like receptor Patched1 regulates the seven-transmembrane protein Smoothened remains mysterious, partially due to limitations in existing tools and experimental systems. Here we employ direct, real-time, biochemical and physiology-based approaches to monitor Smoothened activity in cellular and in vitro contexts. Patched1–Smoothened coupling is rapid, dynamic, and can be recapitulated without cilium-specific proteins or lipids. By reconstituting purified Smoothened in vitro, we show that cholesterol within the bilayer is sufficient for constitutive Smoothened activation. Cholesterol effects occur independently of the lipid-binding Smoothened extracellular domain, a region that is dispensable for Patched1–Smoothened coupling. Finally, we show that Patched1 specifically requires extracellular Na⁺ to regulate Smoothened in our assays, raising the possibility that a Na⁺ gradient provides the energy source for Patched1 catalytic activity. Our work suggests a hypothesis wherein Patched1, chemiosmotically driven by the transmembrane Na⁺ gradient common to metazoans, regulates Smoothened by shielding its heptahelical domain from cholesterol, or by providing an inhibitor that overrides this cholesterol activation.
The ratio of syringyl (S) and guaiacyl (G) units in lignin has been regarded as a major factor in determining the maximum monomer yield from lignin depolymerization. This limit arises from the notion ...that G units are prone to C-C bond formation during lignin biosynthesis, resulting in less ether linkages that generate monomers. This study uses reductive catalytic fractionation (RCF) in flow-through reactors as an analytical tool to depolymerize lignin in poplar with naturally varying S/G ratios, and directly challenges the common conception that the S/G ratio predicts monomer yields. Rather, this work suggests that the plant controls C-O and C-C bond content by regulating monomer transport during lignin biosynthesis. Overall, our results indicate that additional factors beyond the monomeric composition of native lignin are important in developing a fundamental understanding of lignin biosynthesis.
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