Biofilms—communities of bacteria encased in a polymer-rich matrix—confer bacteria with the ability to persist in pathologic host contexts, such as the cystic fibrosis (CF) airways. How bacteria ...assemble polymers into biofilms is largely unknown. We find that the extracellular matrix produced by Pseudomonas aeruginosa self-assembles into a liquid crystal through entropic interactions between polymers and filamentous Pf bacteriophages, which are long, negatively charged filaments. This liquid crystalline structure enhances biofilm function by increasing adhesion and tolerance to desiccation and antibiotics. Pf bacteriophages are prevalent among P. aeruginosa clinical isolates and were detected in CF sputum. The addition of Pf bacteriophage to sputum polymers or serum was sufficient to drive their rapid assembly into viscous liquid crystals. Fd, a related bacteriophage of Escherichia coli, has similar biofilm-building capabilities. Targeting filamentous bacteriophage or the liquid crystalline organization of the biofilm matrix may represent antibacterial strategies.
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•Filamentous Pf bacteriophage are produced by Pseudomonas aeruginosa•Pf phage interact with host and microbial polymers to assemble higher order structures•Pf phage increase the viscosity of polymers in cystic fibrosis airway secretions•The Pf-induced liquid crystal biofilm matrix boosts tolerance to desiccation and antibiotics
Filamentous Pf bacteriophage are often highly transcribed in P. aeruginosa biofilms. Secor et al. demonstrate that filamentous Pf bacteriophage interact with host and microbial polymers to assemble higher order liquid crystal structures. The organization of the biofilm matrix into a liquid crystal enhances biofilm adhesion, desiccation survival, and antibiotic tolerance.
All individuals face some risk of ending up old, sick, alone, and poor. Is there a role for social insurance for these risks and, if so, what is a good programme? A large literature has analysed the ...costs and benefits of pay-as-you-go public pensions and found that the costs exceed the benefits. This article, instead, considers means-tested social insurance (MTSI) programmes for retirees such as Medicaid and Supplemental Security Income. We find that the welfare gains from these programmes are large. Moreover, the current scale of MTSI in the U.S. is too small in the following sense. If we condition on the current Social Security programme, increasing the scale of MTSI by 1/3 benefits both the poor and the affluent when a payroll tax is used to fund the increase.
Atomic resolution and coarse-grained simulations of dimyristoylphosphatidylcholine lipid bilayers were analyzed for fluctuations perpendicular to the bilayer using a completely Fourier-based method. ...We find that the fluctuation spectrum of motions perpendicular to the bilayer can be decomposed into just two parts: 1), a pure undulation spectrum proportional to
q
−4 that dominates in the small-
q regime; and 2), a molecular density structure factor contribution that dominates in the large-
q regime. There is no need for a term proportional to
q
−2 that has been postulated for protrusion fluctuations and that appeared to have been necessary to fit the spectrum for intermediate
q. We suggest that earlier reports of such a term were due to the artifact of binning and smoothing in real space before obtaining the Fourier spectrum. The observability of an intermediate protrusion regime from the fluctuation spectrum is discussed based on measured and calculated material constants.
Differential DNA methylation in the brain is associated with many psychiatric diseases, but access to brain tissues is essentially limited to postmortem samples. The use of surrogate tissues has ...become common in identifying methylation changes associated with psychiatric disease. In this study, we determined the extent to which peripheral tissues can be used as surrogates for DNA methylation in the brain. Blood, saliva, buccal, and live brain tissue samples from 27 patients with medically intractable epilepsy undergoing brain resection were collected (age range 5-61 years). Genome-wide methylation was assessed with the Infinium HumanMethylation450 (n = 12) and HumanMethylationEPIC BeadChip arrays (n = 21). For the EPIC methylation data averaged for each CpG across subjects, the saliva-brain correlation (r = 0.90) was higher than that for blood-brain (r = 0.86) and buccal-brain (r = 0.85) comparisons. However, within individual CpGs, blood had the highest proportion of CpGs correlated to brain at nominally significant levels (20.8%), as compared to buccal tissue (17.4%) and saliva (15.1%). For each CpG and each gene, levels of brain-peripheral tissue correlation varied widely. This indicates that to determine the most useful surrogate tissue for representing brain DNA methylation, the patterns specific to the genomic region of interest must be considered. To assist in that objective, we have developed a website, IMAGE-CpG, that allows researchers to interrogate DNA methylation levels and degree of cross-tissue correlation in user-defined locations across the genome.
Summary
Background
Over the last few years, several articles on dermoscopy of non‐neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies.
...Objectives
We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non‐neoplastic dermatoses through an expert consensus.
Methods
The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three‐step iterative procedure (blinded e‐mail interaction in rounds 1 and 3 and a face‐to‐face meeting in round 2). Initial panellists were recruited via e‐mail from all over the world based on their expertise on dermoscopy of non‐neoplastic dermatoses.
Results
Twenty‐four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) ‘other structures’ (including colour and morphology); and (v) ‘specific clues’. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure).
Conclusions
This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.
What's already known about this topic?
Over the last few years, several papers have been published attempting to describe the dermoscopic features of non‐neoplastic dermatoses, yet there is poor consistency in the terminology among different studies.
What does this study add?
The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses.
This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.
Linked Editorial: Bahadoran. Br J Dermatol 2020; 182:260–261.
Plain language summary available online
BCL-2 is a negative regulator of apoptosis implicated in homeostatic and pathologic cell survival. The canonical anti-apoptotic mechanism involves entrapment of activated BAX by a groove on BCL-2, ...preventing BAX homo-oligomerization and mitochondrial membrane poration. The BCL-2 BH4 domain also confers anti-apoptotic functionality, but the mechanism is unknown. We find that a synthetic α-helical BH4 domain binds to BAX with nanomolar affinity and independently inhibits the conformational activation of BAX. Hydrogen-deuterium exchange mass spectrometry demonstrated that the N-terminal conformational changes in BAX induced by a triggering BIM BH3 helix were suppressed by the BCL-2 BH4 helix. Structural analyses localized the BH4 interaction site to a groove formed by residues of α1, α1–α2 loop, and α2–α3 and α5–α6 hairpins on the BAX surface. These data reveal a previously unappreciated binding site for targeted inhibition of BAX and suggest that the BCL-2 BH4 domain may participate in apoptosis blockade by a noncanonical interaction mechanism.
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•Stapled BCL-2 BH4 domain helices directly bind to and inhibit pro-apoptotic BAX•BCL-2 BH4 SAHBs block the conformational activation of BH3-triggered BAX•BCL-2 BH4 domain helices inhibit BAX at a novel interaction site•The BH4-in-groove interaction represents a distinct mechanism for BAX blockade
The established paradigm for BCL-2 suppression of apoptosis involves BAX entrapment by a BH3-in-groove mechanism. Barclay et al. discover that a stapled BH4 domain helix of BCL-2 inhibits the conformational activation of BAX by engaging a previously uncharacterized interaction site, revealing a distinct mechanism for BAX blockade and apoptosis modulation.
Abstract The practice of waterpipe smoking (hookah) has rapidly increased in popularity among young adults yet burgeoning research suggests that its use is associated with nicotine dependence and ...other negative smoking-related health consequences. Moreover, descriptive studies indicate that consumers may hold the belief that hookah smoking is safer than smoking cigarettes. The current study extended previous work by conducting a comprehensive assessment of patterns and contexts of hookah use, psychological correlates of use, co-occurring substance use as well as social norms and health perceptions surrounding the practice. Participants were 143 ethnically diverse undergraduate students at a large urban US university. Approximately half of the sample (48%) reported life-time use of hookah and 22% reported use within the past 30 days. Relative to cigarette smoking, hookah smoking was associated with less perceived harm and addiction potential and higher social approval. Participants who reported life-time hookah use, as compared to those who did not, perceived less associated harm, had a greater number of friends who had tried and approved of hookah, were more likely to use cigarettes, marijuana, and alcohol and in higher frequencies and quantities and were at higher risk for problem tobacco and alcohol use. Among participants who were not current smokers, those with hookah experience were more likely to endorse intent to try a cigarette soon. Hookah users did not differ from non-users on measures of trait anxiety, depression and impulsivity though they were more likely to drink alcohol for coping, social and enhancement purposes than non-users. Implications are discussed for public health initiatives to educate young adults about the potential consequences of hookah smoking.
Electrical energy storage (EES) is an important component of the future electric grid. Given that no other widely available technology meets all the EES requirements, reversible (or regenerative) ...solid oxide cells (ReSOCs) working in both fuel cell (power producing) and electrolysis (fuel producing) modes are envisioned as a technology capable of providing highly efficient and cost-effective EES. However, there are still many challenges and questions from cell materials development to system level operation of ReSOCs that should be addressed before widespread application. This paper presents a novel system based on ReSOCs that employ a thermal management strategy of promoting exothermic methanation within the ReSOC cell-stack to provide thermal energy for the endothermic steam/CO2 electrolysis reactions during charging mode (fuel producing). This approach also serves to enhance the energy density of the stored gases. Modeling and parametric analysis of an energy storage concept is performed using a physically based ReSOC stack model coupled with thermodynamic system component models. Results indicate that roundtrip efficiencies greater than 70% can be achieved at intermediate stack temperature (680 °C) and elevated stack pressure (20 bar). The optimal operating condition arises from a tradeoff between stack efficiency and auxiliary power requirements from balance of plant hardware.
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•An electrical energy storage system using reversible solid oxide cells is modeled.•Thermal management with carbonaceous reactant species increases system efficiency.•System modeling reveals tradeoffs between roundtrip efficiency and energy density.•Roundtrip efficiency >70% is achieved by operating the stack at 20 bar and 680 °C.
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