Over the last 50 years, we argue that incentives for academic scientists have become increasingly perverse in terms of competition for research funding, development of quantitative metrics to measure performance, and a changing business model for higher education itself. Furthermore, decreased discretionary funding at the federal and state level is creating a hypercompetitive environment between government agencies (e.g., EPA, NIH, CDC), for scientists in these agencies, and for academics seeking funding from all sources—the combination of perverse incentives and decreased funding increases pressures that can lead to unethical behavior. If a critical mass of scientists become untrustworthy, a tipping point is possible in which the scientific enterprise itself becomes inherently corrupt and public trust is lost, risking a new dark age with devastating consequences to humanity. Academia and federal agencies should better support science as a public good, and incentivize altruistic and ethical outcomes, while de-emphasizing output.
Capping protein (CP) regulates actin polymerization by binding the barbed end of an actin filament, which blocks addition and loss of actin subunits. Recent structural and biochemical studies provide new insight into how cells control the actin capping activity of CP. Several molecules indirectly regulate CP by interacting with filament barbed ends and preventing binding of CP; others bind directly to CP and sterically block its interaction with an actin filament. A diverse and otherwise unrelated set of proteins contains a motif for CP regulation termed the “Capping Protein Interaction” (CPI) motif. These proteins bind directly to CP, recruit or target CP to a subcellular location, and modulate its actin-capping activity via allosteric effects.
SUMMARY
The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behavior of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing PIP2 levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: The threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued. Conversely, innately keratocyte-like and oscillatory cells were promptly converted to amoeboid by inhibition of Ras effectors with restoration of directed migration. We use computational analysis to explain how thresholds control cell migration and discuss the architecture of the signal transduction network that gives rise to excitability.
ABSTRACTThe spread of opportunistic pathogens via public water systems is of growing concern. The purpose of this study was to identify patterns of occurrence among three opportunistic pathogens (Legionella pneumophila,Mycobacterium avium, andPseudomonas aeruginosa) relative to biotic and abiotic factors in two representative chloraminated drinking water distribution systems using culture-independent methods. Generally, a high occurrence ofLegionella(≥69.0%) and mycobacteria (100%), lower occurrence ofL. pneumophila(≤20%) andM. avium(≤33.3%), and rare detection ofPseudomonas aeruginosa(≤13.3%) were observed in both systems according to quantitative PCR. Also,Hartmanella vermiformiswas more prevalent thanAcanthamoeba, both of which are known hosts for opportunistic pathogen amplification, the latter itself containing pathogenic members. Three-minute flushing served to distinguish distribution system water from plumbing in buildings (i.e., premise plumbing water) and resulted in reduced numbers of copies ofLegionella, mycobacteria,H. vermiformis, and 16S rRNA genes (P< 0.05) while yielding distinct terminal restriction fragment polymorphism (T-RFLP) profiles of 16S rRNA genes. Within certain subgroups of samples, some positive correlations, including correlations of numbers of mycobacteria and total bacteria (16S rRNA genes),H. vermiformisand total bacteria, mycobacteria andH. vermiformis, andLegionellaandH. vermiformis, were noted, emphasizing potential microbial ecological relationships. Overall, the results provide insight into factors that may aid in controlling opportunistic pathogen proliferation in real-world water systems.
A switch from free chlorine to chloramine disinfectant triggered problems with excessive lead in Washington, D.C., drinking water. High levels of lead originated in the service lines, but excessive lead was also derived from solder or brass plumbing materials. In many cases, the highest lead concentrations emerged from the tap after about 1 min of flushing—a troublesome outcome, given that routine public notification recommended that consumers flush for about a minute to minimize lead exposure. Bench‐scale testing found that chlorine reacts with soluble Pb+2 to rapidly precipitate a red–brown‐colored lead solid that was insoluble even at pH 1.9 for 12 weeks; this solid did not form in the presence of chloramine. Further experiments indicated that chloramines sometimes dramatically worsened lead leaching from brass relative to free chlorine, whereas new lead pipe was not strongly affected.
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.
Incidence of EBL (blood lead > or =10 microg/dL) for children aged < or = 1.3 years in Washington, DC increased more than 4 times comparing 2001-2003 when lead in water was high versus 2000 when lead in water was low. The incidence of EBL was highly correlated (R2 = 0.81) to 90th percentile lead in water lead levels (WLLs) from 2000 to 2007 for children aged < or = 1.3 years. The risk of exposure to high water lead levels varied markedly in different neighborhoods of the city. For children aged < or =30 months there were not strong correlations between WLLs and EBL, when analyzed for the city as a whole. However, the incidence of EBL increased 2.4 times in high-risk neighborhoods, increased 1.12 times in moderate-risk neighborhoods, and decreased in low-risk neighborhoods comparing 2003 to 2000. The incidence of EBL for children aged < or =30 months also deviated from national trends in a manner that was highly correlated with 90th percentile lead in water levels from 2000 to 2007 (R2 = 0.83) in the high-risk neighborhoods. These effects are consistent with predictions based on biokinetic models and prior research.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.