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•Soil-water partitioning coefficients for antimicrobial peptides were assessed.•All AMPs are transformed in sunlit surface waters.•Bimolecular reaction rate constants with singlet ...oxygen were assessed.•All AMPs were susceptible to transformation by riverine periphyton community.
Antimicrobial peptides (AMPs) are increasingly important as a last resort against multi-drug resistant bacteria due to resistance formation towards conventional antibiotics. However, many AMPs were introduced to the market before environmental risk assessment was required, e.g., by the European Medicines Agency (EMA) since 1998. While AMPs have been administered as antibiotics and growth promotors in feedstock since the 1960s and were reconsidered for human medicine by the EMA in 2013, details about their mobility and persistence in the environment remain unknown. This study investigated the environmental fate of three commonly used AMPs: bacitracins, daptomycin, and polymyxins B and E (Colistin). We observed moderate sorption affinity of daptomycin to standard European soils (Kd = 20.6–48.6), while polymyxins adsorbed irreversibly. Bacitracin variants sorbed slightly to sandy soil (Kd = 5.8–8) and significantly to clayey soil (Kd = 169–250). We further investigated photochemical and microbial transformation processes relevant in surface waters. We demonstrated that phototransformation of all AMPs was enhanced in the presence of dissolved organic matter and fast bimolecular reaction rate constant with singlet oxygen contributed largely to indirect phototransformation (15–41%). Phototransformation product analysis for daptomycin was consistent with expected modifications of the tryptophan and kynurenine moieties. Moreover, riverine biofilm communities demonstrated biotransformation potential for all AMPs. Our findings of sorption behaviour, photo- and biotransformation suggest that these processes play a critical role in the fate of bacitracins, daptomycin, and polymyxins in environmental systems.
Topographically complex regions on land and in the oceans feature hotspots of biodiversity that reflect geological influences on ecological and evolutionary processes. Over geologic time, topographic ...diversity gradients wax and wane over millions of years, tracking tectonic or climatic history. Topographic diversity gradients from the present day and the past can result from the generation of species by vicariance or from the accumulation of species from dispersal into a region with strong environmental gradients. Biological and geological approaches must be integrated to test alternative models of diversification along topographic gradients. Reciprocal illumination among phylogenetic, phylogeographic, ecological, paleontological, tectonic, and climatic perspectives is an emerging frontier of biogeographic research.
Topographically complex regions today feature high taxonomic and ecological diversity.
Ancient topographic diversity gradients arose and declined over millions of years.
Paleontological and modern data are crucial to understand topographic diversity gradients.
Topographically complex regions have high conservation value.
Background
Resistance breathing amplifies the respiratory pump during inspiration, so may be an effective intervention for treatment of hemorrhagic injuries. In animal studies of actual hemorrhage, ...and human studies of simulated hemorrhage, resistance breathing protects arterial pressure, and improves tolerance to this stress. Anecdotally, resistance breathing also increases the coupling between sympathetic nerve activity and arterial pressure. The impact of resistance breathing on overall sympathetic nerve activity, however, has not been examined. We tested the hypothesis that resistance breathing increases sympathetic nerve activity during simulated hemorrhage in healthy humans.
Methods
Lower body negative pressure (LBNP) was used to simulate hemorrhage in five human subjects (3M, 2F; 29.2 ± 6.8 y). Two experiments were conducted (randomized order): 1) a control condition in which LBNP was applied at 3 mmHg/min until the onset of presyncope, and 2) a resistance breathing condition in which the same LBNP protocol was used, but subjects breathed through a resistance device (set at ‐7 cm.H2O) during the final stages of the protocol. Arterial pressure and muscle sympathetic nerve activity (MSNA) of the radial nerve were monitored continuously. Bursts frequency (bursts/min) and burst incidence (burst/ 100 heart beats) were used to quantify MSNA. Coupling between diastolic arterial pressure (DAP) and MSNA was assessed by transfer function analysis coherence within the low frequency range (0.04‐0.15 Hz). Two‐way repeated measures ANOVAs were conducted for assessment of responses in the control and resistance breathing conditions, between baseline and at matched time points late in the LBNP protocol.
Results
While LBNP induced increases in both MSNA burst frequency (P=0.003) and burst incidence (P=0.06), there was no effect of resistance breathing on MSNA for either index during LBNP (control, 57.9 ± 25.9 bursts/min vs. resistance breathing, 50.6 ± 21.7 bursts/min, P=0.99; control, 55.6 ± 25.6 b/100 heart beats vs. resistance breathing, 42.3 ± 18.3 b/100 heart beats, P=0.42). Additionally, there was no effect of resistance breathing on DAP (control, 73.2 ± 9.9 mmHg vs. resistance breathing, 72.8 ± 4.4 mmHg; P=0.99), or coherence between MSNA and DAP during LBNP (control, 0.53 ± 0.21 vs. resistance breathing, 0.69 ± 0.17; P=0.46).
Conclusion
Contrary to our hypothesis, resistance breathing had no effect on sympathetic nerve activity during LBNP. A limitation of this study is the low sample size (N=5), and high variability of MSNA. Future investigations with a larger sample size are needed to determine if respiratory dynamics can influence the coupling between MSNA and arterial pressure.
Excess nitrogen (N) impairs inland water quality and creates hypoxia in coastal ecosystems. Agriculture is the primary source of N; agricultural management and hydrology together control aquatic ...ecosystem N loading. Future N loading will be determined by how agriculture and hydrology intersect with climate change, yet the interactions between changing climate and water quality remain poorly understood. Here, we show that changing precipitation patterns, resulting from climate change, interact with agricultural land use to deteriorate water quality. We focus on the 2012–2013 Midwestern U.S. drought as a “natural experiment”. The transition from drought conditions in 2012 to a wet spring in 2013 was abrupt; the media dubbed this “weather whiplash”. We use recent (2010–2015) and historical data (1950–2015) to connect weather whiplash (drought-to-flood transitions) to increases in riverine N loads and concentrations. The drought likely created highly N-enriched soils; this excess N mobilized during heavy spring rains (2013), resulting in a 34% increase (10.5 vs. 7.8 mg N L⁻¹) in the flow-weighted mean annual nitrate concentration compared to recent years. Furthermore, we show that climate change will likely intensify weather whiplash. Increased weather whiplash will, in part, increase the frequency of riverine N exceeding E.P.A. drinking water standards. Thus, our observations suggest increased climatic variation will amplify negative trends in water quality in a region already grappling with severe impairments.
During cerebral hypoperfusion induced by lower body negative pressure (LBNP), cerebral tissue oxygenation is protected with oscillatory arterial pressure and cerebral blood flow at low frequencies ...(0.1 Hz and 0.05 Hz), despite no protection of cerebral blood flow or oxygen delivery. However, hypocapnia induced by LBNP contributes to cerebral blood flow reductions, and may mask potential protective effects of hemodynamic oscillations on cerebral blood flow. We hypothesized that under isocapnic conditions, forced oscillations of arterial pressure and blood flow at 0.1 Hz and 0.05 Hz would attenuate reductions in extra- and intracranial blood flow during simulated hemorrhage using LBNP. Eleven human participants underwent three LBNP profiles: a nonoscillatory condition (0 Hz) and two oscillatory conditions (0.1 Hz and 0.05 Hz). End-tidal (et) CO
and etO
were clamped at baseline values using dynamic end-tidal forcing. Cerebral tissue oxygenation (ScO
), internal carotid artery (ICA) blood flow, and middle cerebral artery velocity (MCAv) were measured. With clamped etCO
, neither ICA blood flow (ANOVA
= 0.93) nor MCAv (ANOVA
= 0.36) decreased with LBNP, and these responses did not differ between the three profiles (ICA blood flow: 0 Hz: 2.2 ± 5.4%, 0.1 Hz: -0.4 ± 6.6%, 0.05 Hz: 0.2 ± 4.8%;
= 0.56; MCAv: 0 Hz: -2.3 ± 7.8%, 0.1 Hz: -1.3 ± 6.1%, 0.05 Hz: -3.1 ± 5.0%;
= 0.87). Similarly, ScO
did not decrease with LBNP (ANOVA
= 0.21) nor differ between the three profiles (0 Hz: -2.6 ± 3.3%, 0.1 Hz: -1.6 ± 1.5%, 0.05 Hz: -0.2 ± 2.8%;
= 0.13). Contrary to our hypothesis, cerebral blood flow and tissue oxygenation were protected during LBNP with isocapnia, regardless of whether hemodynamic oscillations were induced.
We examined the role of forcing oscillations in arterial pressure and blood flow at 0.1 Hz and 0.05 Hz on extra- and intracranial blood flow and cerebral tissue oxygenation during simulated hemorrhage (using lower body negative pressure, LBNP) under isocapnic conditions. Contrary to our hypothesis, both cerebral blood flow and cerebral tissue oxygenation were completely protected during simulated hemorrhage with isocapnia, regardless of whether oscillations in arterial pressure and cerebral blood flow were induced. These findings highlight the protective effect of preventing hypocapnia on cerebral blood flow under simulated hemorrhage conditions.
Penile squamous cell carcinoma is a rare disease with very limited data to guide treatment decisions. In particular, there is minimal evidence for effective therapies in the metastatic setting. Here, ...we present a case of metastatic penile squamous cell carcinoma with response to the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV). EV was selected due to the evidence of the high expression of Nectin-4 in squamous cell carcinomas, including penile carcinoma. The patient had both radiographic and symptomatic improvement after two cycles of treatment, despite having been treated with multiple prior lines of traditional chemotherapy. This case provides support for the use of antibody-drug conjugates (ADC), including EV, in this disease with few other options in the advanced setting. Further studies examining Nectin-4 and ADCs in penile squamous cell carcinoma should be completed, as high-quality evidence is needed to guide treatment after initial progression for these patients.
Early-career researchers (ECRs) make up a large portion of the academic workforce. Yet, most leadership positions in scientific societies are held by senior scientists, and ECRs have little to no say ...over the decisions that will shape the future of research. This article looks at the level of influence ECRs have in 20 scientific societies based in the US and UK, and provides guidelines on how societies can successfully include ECRs in leadership roles.
Obesity research suffers from an overinclusion paradigm whereby all participants with a BMI beyond a certain cutoff value (e.g., 30) are typically combined in a single group and compared to those of ...normal weight. There has been little attempt to identify meaningful subgroups defined by their salient biobehavioral differences. In order to address this limitation, we examined genetic and psychological indicators of hedonic eating in obese adults with (n = 66) and without (n = 70) binge eating disorder (BED). Our analyses focused on dopamine (DA) and opioid genetic markers because of their conjoint association with the functioning of brain reward mechanisms. We targeted three functional polymorphisms related to the D2 receptor (DRD2) gene, as well as the functional A118G polymorphism of the mu‐opioid receptor (OPRM1) gene. We found that significantly more obese controls had the “loss‐of‐function” A1 allele of Taq1A compared to their BED counterparts, whereas the “gain‐of‐function” G allele of A118G occurred with greater frequency in the BED group. A significant gene–gene combination χ2 analysis also indicated that of those participants with the gain‐gain genotype (G+ and A1), 80% were in the BED group whereas only 35% with the loss‐loss genotype (G− and A1+) were in this group. Finally, BED subjects had significantly higher scores on a self‐report measure of hedonic eating. Our findings suggest that BED is a biologically based subtype of obesity and that the proneness to binge eating may be influenced by a hyper‐reactivity to the hedonic properties of food—a predisposition that is easily exploited in our current environment with its highly visible and easily accessible surfeit of sweet and fatty foods.
The kinetic solvent isotope effect (KSIE) is typically utilized in environmental photochemistry to elucidate whether a compound is susceptible to photooxidation by singlet oxygen (1O2), due to its ...known difference in lifetime in water (H2O) versus heavy water (D2O). Here, the overall indirect photodegradation rates of diarylamines in the presence of dissolved organic matter (DOM) were enhanced in D2O to a greater extent than expected based on their reactivity with 1O2. For each diarylamine, the relative contribution of reaction with 1O2 to the observed KSIE was determined from high resolution data of 1O2 lifetimes by time-resolved infrared luminescence spectroscopy. The additional enhancement in D2O beyond reaction with 1O2 contributed significantly to the observed KSIE for diarylamines (8–65%) and diclofenac (100%). The enhancement was ascribed to slower reduction of transient radical species of the diarylamines due to H/D exchange at DOM’s phenolic antioxidant moieties. A slower second-order reaction rate constant with a model antioxidant was verified for mefenamic acid radicals using transient absorption spectroscopy. Changes in lifetime and reactivity with triplet sensitizers were not responsible for the additional KSIE. Other pollutants with quenchable radical intermediates may also be susceptible to such an additional KSIE, which has to be considered when using the KSIE as a diagnostic tool.
Objective: The ADHD–obesity link has been suggested to result from a shared underlying basis of suboptimal dopamine (DA); however, this theory conflicts evidence that an amplified DA signal increases ...the risk for overeating and weight gain. A model was tested in which ADHD symptoms, predicted by hypodopaminergic functioning in the prefrontal cortex, in combination with an enhanced appetitive drive, predict hedonic eating and, in turn, higher body mass index (BMI). Method: DRD2 and DRD4 markers were genotyped. The model was tested using structural equation modeling in a nonclinical sample (N = 421 adults). Results: The model was a good fit to the data. Controlling for education, all parameter estimates were significant, except for the DRD4-ADHD symptom pathway. The significant indirect effect indicates that overeating mediated the ADHD symptoms–BMI association. Conclusion: Results support the hypothesis that overeating and elevated DA in the ventral striatum—representative of a greater reward response—contribute to the ADHD symptom–obesity relationship.
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