Explore the vast range of titles available.

We performed a meta-analysis of published studies and long-term monitoring data sets to evaluate the effects of dreissenid mussels ( Dreissena polymorpha and D. rostriformis bugensis ), two of the world's most problematic biological invaders, on the biogeochemistry, flora, and fauna of lakes and rivers across North America and Eurasia. Dreissenid effects were structured along two distinct energy pathways. For the pelagic-profundal pathway, large mean reductions in phytoplankton (−35% to −78%) and zooplankton (−40% to −77%) biomass occurred and were dependent on habitat type. The largest effects were found in rivers, followed by littoral and pelagic habitats in lakes. In contrast, benthic energy pathways within littoral habitats of lakes and rivers showed dramatic increases in mean benthic algal and macrophyte biomass (+170% to +180%), sediment-associated bacteria (about +2000%), non-dreissenid zoobenthic biomass (+160% to +210%), and total zoobenthic biomass, which includes dreissenid mussel soft tissues (+2000%). Our study quantifies the remarkable ability of these invasive mussels to shift aquatic food webs and energy flow from pelagic-profundal to benthic-littoral energy pathways, and it provides a basis for forecasting their impacts in diverse freshwater ecosystems. Our meta-analysis approach was a powerful tool for moving beyond the idiosyncrasies of individual case studies and may be equally powerful for assessing impacts of other biological invaders.

In light of the disappointing termination of clinical trials with potent complex I inhibitors, such as IACS-010759, justification for oxidative phosphorylation inhibitors and mitochondrial targeting strategies has been called into question. Consideration of these agents’ potency, tissue selectivity and toxicity demonstrate what lessons can be learned from this failure and where new opportunities lie.

In this New York State registry study, outcomes of patients with multivessel coronary disease treated with drug-eluting coronary stents or coronary-artery bypass grafting (CABG) were compared during 18 months of follow-up. The rates of death, death or myocardial infarction, and repeat revascularization were consistently lower after CABG than after treatment with drug-eluting stents. The rates of death, death or myocardial infarction, and repeat revascularization were consistently lower after CABG than after treatment with drug-eluting stents. Several studies have compared the long-term outcomes of coronary-artery bypass grafting (CABG) and coronary stenting. 1 – 5 In 2003, drug-eluting stents were introduced for the purpose of reducing restenosis, which has continued to be a problem associated with the use of bare-metal stents. Many randomized, controlled trials have documented lower rates of clinical and angiographic restenosis, target-lesion revascularization, and major adverse cardiac events with drug-eluting stents. 6 – 20 However, recent reports of the danger of late stent thrombosis among patients with drug-eluting stents 21 , 22 led to a meeting of a Food and Drug Administration (FDA) advisory committee that addressed the safety of . . .

Mind wandering is a pervasive threat to transportation safety, potentially accounting for a substantial number of crashes and fatalities. In the current study, mind wandering was induced through completion of the same task for 5 days, consisting of a 20-min monotonous freeway-driving scenario, a cognitive depletion task, and a repetition of the 20-min driving scenario driven in the reverse direction. Participants were periodically probed with auditory tones to self-report whether they were mind wandering or focused on the driving task. Self-reported mind wandering frequency was high, and did not statistically change over days of participation. For measures of driving performance, participant labeled periods of mind wandering were associated with reduced speed and reduced lane variability, in comparison to periods of on task performance. For measures of electrophysiology, periods of mind wandering were associated with increased power in the alpha band of the electroencephalogram (EEG), as well as a reduction in the magnitude of the P3a component of the event related potential (ERP) in response to the auditory probe. Results support that mind wandering has an impact on driving performance and the associated change in driver's attentional state is detectable in underlying brain physiology. Further, results suggest that detecting the internal cognitive state of humans is possible in a continuous task such as automobile driving. Identifying periods of likely mind wandering could serve as a useful research tool for assessment of driver attention, and could potentially lead to future in-vehicle safety countermeasures.

Tumour hypoxia renders cancer cells resistant to cancer therapy, resulting in markedly worse clinical outcomes. To find clinical candidate compounds that reduce hypoxia in tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify a number of drugs with this property. For this study we focus on the anti-malarial, atovaquone. Atovaquone rapidly decreases the OCR by more than 80% in a wide range of cancer cell lines at pharmacological concentrations. In addition, atovaquone eradicates hypoxia in FaDu, HCT116 and H1299 spheroids. Similarly, it reduces hypoxia in FaDu and HCT116 xenografts in nude mice, and causes a significant tumour growth delay when combined with radiation. Atovaquone is a ubiquinone analogue, and decreases the OCR by inhibiting mitochondrial complex III. We are now undertaking clinical studies to assess whether atovaquone reduces tumour hypoxia in patients, thereby increasing the efficacy of radiotherapy. Tumour hypoxia reduces the efficacy of radiotherapy. Starting from a drug screen, here the authors demonstrate that the anti-malarial, atovaquone, reduces the oxygen consumption rate of cancer cells by inhibition of mitochondrial complex III and sensitises to radiotherapy by reducing tumour hypoxia.

Photosynthetic species evolved to protect their light-harvesting apparatus from photoxidative damage driven by intracellular redox conditions or environmental conditions. The Fenna–Matthews–Olson (FMO) pigment–protein complex from green sulfur bacteria exhibits redox-dependent quenching behavior partially due to two internal cysteine residues. Here, we show evidence that a photosynthetic complex exploits the quantum mechanics of vibronic mixing to activate an oxidative photoprotective mechanism. We use two-dimensional electronic spectroscopy (2DES) to capture energy transfer dynamics in wild-type and cysteine-deficient FMO mutant proteins under both reducing and oxidizing conditions. Under reducing conditions, we find equal energy transfer through the exciton 4–1 and 4–2-1 pathways because the exciton 4–1 energy gap is vibronically coupled with a bacteriochlorophyll-a vibrational mode. Under oxidizing conditions, however, the resonance of the exciton 4–1 energy gap is detuned from the vibrational mode, causing excitons to preferentially steer through the indirect 4–2-1 pathway to increase the likelihood of exciton quenching. We use a Redfield model to show that the complex achieves this effect by tuning the site III energy via the redox state of its internal cysteine residues. This result shows how pigment–protein complexes exploit the quantum mechanics of vibronic coupling to steer energy transfer.

The physical properties of polymers depend on a range of both structural and chemical parameters, and in particular, on molecular topology. Apparently simple changes such as joining chains at a point to form stars or simply joining the two ends to form a ring can profoundly alter molecular conformation and dynamics, and hence properties. Cyclic polymers, as they do not have free ends, represent the simplest model system where reptation is completely suppressed. As a consequence, there exists a considerable literature and several reviews focused on high molecular weight cyclics where long range dynamics described by the reptation model comes into play. However, this is only one area of interest. Consideration of the conformation and dynamics of rings and chains, and of their mixtures, over molecular weights ranging from tens of repeat units up to and beyond the onset of entanglements and in both solution and melts has provided a rich literature for theory and simulation. Experimental work, particularly neutron scattering, has been limited by the difficulty of synthesizing well-characterized ring samples, and deuterated analogues. Here in the context of the broader literature we review investigations of local conformation and dynamics of linear and cyclic polymers, concentrating on poly(dimethyl siloxane) (PDMS) and covering a wide range of generally less high molar masses. Experimental data from small angle neutron scattering (SANS) and quasi-elastic neutron scattering (QENS), including Neutron Spin Echo (NSE), are compared to theory and computational predictions.

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of NTD non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate NTD non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious viral titers in the lung as potently as neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection from SARS-CoV-2 infection. For therapeutic administration of antibodies, non-nAb effector functions contributed to virus suppression and lessening of lung discoloration, but the presence of neutralization was required for optimal protection from disease. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection.

It is well established that the idle peripheral intravenous catheter (PIVC) provides no therapeutic value and is a clinical, economic and above all, patient concern. This study aimed to develop a decision aid to assist with clinical decision making to promote clinically indicated peripheral intravenous catheter (CIPIVC) insertion in the emergency department (ED) setting. Providing evidence for a uniform process could assist clinicians in a decision-making process for PIVC insertion. This could enable patients receive appropriate vascular access healthcare. We performed a secondary analysis of data from a multicentre cohort of emergency department clinicians who performed PIVC insertion. We defined CIPIVC a priori as one used for a specific clinical treatment and or procedure such as prescribed intravenous (IV) fluids; prescribed IV medication; or IV contrast (for computerized tomography scans). We sought to refute or validate an assumption if the clinician performing or requesting the insertion decided the patient was >80% likely to need a PIVC. Using logistic regression, we derived a decision aid for CIPIVCs. In 817 patients undergoing PIVC insertion, we observed 68% of these to be CIPIVCs. Admitted patients were significantly more likely to have a CIPIVC, Odds Ratio (OR) = 3.05, 95% confidence interval (CI) = 2.17-4.30, p = <0.0001. Before insertion, patients who definitely needed IV fluids/medicines OR = 3.30, 95% CI = 2.02-5.39, p = <0.0001 and who definitely needed a contrast scan OR = 3.04, 95% CI = 1.15-8.03, p = 0.0250 were significantly more likely to have a device inserted for a clinical indication. Patients who presented with an existing vascular access device were more likely to have a new CIPIVC inserted for use OR = 4.35, 95% CI = 1.58-11.95, p = 0.0043. The clinician's pre-procedural judgment of the likelihood of therapeutic use >80% was independently associated with CIPIVC; OR 3.16, 95% CI = 2.06-4.87, p<0.0001. The area under the receiver operating characteristic curve was 0.81, and at the best cut-off, the model had a specificity of 0.81, sensitivity of 0.71, a positive predictive value of 0.89 and negative predictive value of 0.57. Using the derived decision aid, clinicians could ask:- \"Does this patient need A-PIVC?\" Clinicians can decide to insert a CIPIVCs when: (i) Admission to hospital is anticipated and when (ii) a Procedure requires a PIVC, e.g., computerised tomography scans and where an existing suitable vascular access device is not present and or; (iii) there is an indication for IV fluids and or medicines that cannot be tolerated enterally and are suitable for dilution in peripheral veins; and, (iv) the Clinician's perceived likelihood of use is greater than 80%.

Background Cellular impedance-based assays offer a sensitive, label-free, and non-destructive method to continuously monitor cells in real time, allowing the assessment of both kinetics and degree of migration for breast cancer cells. A scratch assay is one of the most commonly used methods for testing cell migration in a two-dimensional (2D) monolayer culture. Traditional methods to evaluate 2D cancer migration commonly use image analysis to determine the rate of wound closure over a set of timepoints as an indicator of migratory/metastatic potential for cancer cells. An impedance-based assay system was employed towards establishing a modified wound healing assay technique that can measure wound coverage and therefore, 2D cancer migration continuously. This method can also be used to measure a variety of cell characteristics, including proliferation and epithelial barrier integrity. Results Using the Maestro Z Live-cell Analysis System by Axion Biosystems, cell spread, related to single cell morphology, and cell proliferation were observed for multiple breast cancer cell lines. A distinct quantifiable difference in the behavior of aggressive triple-negative breast cancer cells (HCC1806, MDA-MB-231), compared to less aggressive luminal MCF7 cells was determined. With an established assay method, cells were then treated with pro-inflammatory cytokine leptin, which plays a crucial role in metabolism and epithelial to mesenchymal transition (EMT), to verify assay sensitivity. The effects of leptin concentration in media were measurable for MCF7 and HCC1806 cells, and cell barrier integrity was significantly higher in the luminal MCF7 cells as compared to the more aggressive triple-negative cell lines. Cell migration to close a physical wound was measured over 36 hours, with the modified wound healing assay providing quantifiable evidence that the more aggressive breast cancer cells migrated to close the gap. Conclusions This work validates the use of cellular impedance-based assay systems to evaluate multiple cell characteristics. In a single experiment, cell spread, cell proliferation, cell-cell barrier integrity, and 2D cell migration were able to be quantified. These findings parallel previously published data for cell migration of the specific cell lines used, while highlighting the role of leptin in cancer behavior. Overall, the potential for a bioelectronic impedance assay system was demonstrated and its validity in effectively detecting and quantifying cell behaviors was proven.