Health Goals for Perfluorinated Alkyl Substances (PFAS): A Review of Branched Isomers, the Role of Industrial Sources, and the Implications of Pfas in Biosolids on End-of-Life Disposal Methods

Per- and polyfluorinated alkyl substances, or PFAS, have been used for over half a century, but have become an emerging contaminant of significant concern due to their newly found widespread occurrence and recalcitrance in the environment, their tendency to bioaccumulate, and the health effects now associated with a very low level of exposure. Many gaps in knowledge remain about the fate of these chemicals in the environment and the extent of their impacts on biota. This thesis aims to fill some of the recognized gaps in knowledge: differences between linear and branched isomers of PFAS, predicting the presence of PFAS contamination in wells, and the implications of PFAS in municipal biosolids

Adult-Adult and Adult-Child/Adolescent Online Sexual Interactions: An Exploratory Self-Report Study on the Role of Situational Factors

Alcohol intoxication, sexual arousal, and negative emotional states have been found to precede certain sexual behaviors. Using data from an online self-report survey distributed to adults (N&nbsp;=&nbsp;717; 423 men and 304 women), we compared adults with adult online sexual interactions (n&nbsp;=&nbsp;640; 89.3%) to adults with interactions with a child or an adolescent (n&nbsp;=&nbsp;77; 10.7%) on how much they reported being affected by the following factors surrounding the time of the interactions: alcohol intoxication, sexual arousal, sadness, boredom, stress, and shame. We found that those with a child or adolescent contact reported higher sexual arousal and more shame before the interaction, compared with those with an adult contact. In addition, the levels of negative emotional states varied when levels before the interactions were compared with levels after the interactions, suggesting that engaging in online sexual interactions alleviated negative emotional states, at least temporarily. The alleviatory effects, however, were accompanied by higher levels of shame after the interactions. Overall, adults that engage in online sexual interactions have remarkably similar perceptions of the situation surrounding these activities, independent of the age of their online contacts. Limitations of the study are discussed.</p

Valuing Supporting Soil Ecosystem Services in Agriculture: A Natural Capital Approach

Soil biodiversity through its delivery of ecosystem functions and attendant supporting ecosystem services—benefits soil organisms generate for farmers—underpins agricultural production. Yet lack of practical methods to value the long-term effects of current farming practices results, inevitably, in short-sighted management decisions. We present a method for valuing changes in supporting soil ecosystem services and associated soil natural capital—the value of the stock of soil organisms—in agriculture, based on resultant changes in future farm income streams. We assume that a relative change in soil organic C (SOC) concentration is correlated with changes in soil biodiversity and the generation of supporting ecosystem services. To quantify the effects of changes in supporting services on agricultural productivity, we fitted production functions to data from long-term field experiments in Europe and the United States. The different agricultural treatments at each site resulted in significant changes in SOC concentrations with time. Declines in associated services are shown to reduce both maximum yield and fertilizer-use efficiency in the future. The average depreciation of soil natural capital, for a 1% relative reduction in SOC concentration, was 144 € ha⁻¹ (SD 47 € ha⁻¹) when discounting future values to their current value at 3%; the variation was explained by site-specific factors and the current SOC concentration. Moreover, the results show that soil ecosystem services cannot be fully replaced by purchased inputs; they are imperfect substitutes. We anticipate that our results will both encourage and make it possible to include the value of soil natural capital in decisions.Keywords: soil organic carbon, economic valuation, ecological intensification, sustainable agriculture, land us

Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae

Cytokinesis requires coordination of actomyosin ring (AMR) contraction with rearrangements of the plasma membrane and extracellular matrix. In Saccharomyces cerevisiae, new membrane, the chitin synthase Chs2 (which forms the primary septum [PS]), and the protein Inn1 are all delivered to the division site upon mitotic exit even when the AMR is absent. Inn1 is essential for PS formation but not for Chs2 localization. The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Δ cells). The Inn1 N terminus resembles C2 domains but does not appear to bind phospholipids; nonetheless, when overexpressed or fused to Hof1, it can provide Inn1 function even in the absence of the AMR. Thus, Inn1 and Cyk3 appear to cooperate in activating Chs2 for PS formation, which allows coordination of AMR contraction with ingression of the cleavage furrow

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M^(pro)), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M^(pro). In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2

Influence of Ocean Acidification on a Natural Winter-to-Summer Plankton Succession : First Insights from a Long-Term Mesocosm Study Draw Attention to Periods of Low Nutrient Concentrations

Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (similar to 380 mu atm pCO(2)), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (mu 760 mu atm pCO(2)). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.Peer reviewe