The relevance of the acyl homoserine lactone (acyl-HSL) quorum signals N-3-oxododecanoyl-homoserine lactone (3OC12HSL) and N-butanoyl-homoserine lactone to the biology and virulence of Pseudomonas aeruginosa is well investigated. Previously, P. aeruginosa was shown to degrade long-chain, but not short-chain, acyl-HSLs as sole carbon and energy sources (J. J. Huang, J.-I. Han, L.-H. Zhang, and J. R. Leadbetter, Appl. Environ. Microbiol. 69:5941-5949, 2003). A gene encoding an enzyme with acyl-HSL acylase activity, pvdQ (PA2385), was identified, but it was not required for acyl-HSL utilization. This indicated that P. aeruginosa encodes another acyl-HSL acylase, which we identify here. A comparison of total cell proteins of cultures grown with long-acyl acyl-HSLs versus other substrates implicated the involvement of a homolog of PvdQ, the product of gene PA1032, for which we propose the name QuiP. Transposon mutants of quiP were defective for growth when P. aeruginosa was cultured in medium containing decanoyl-HSL as a sole carbon and energy source. Complementation with a functional copy of quiP rescued this growth defect. When P. aeruginosa was grown in buffered lysogeny broth, constitutive expression of QuiP in P. aeruginosa led to decreased accumulations of the quorum signal 3OC12HSL, relative to the wild type. Heterologous expression of QuiP was sufficient to confer long-chain acyl-HSL acylase activity upon Escherichia coli. Examination of gene expression patterns during acyl-HSL-dependent growth of P. aeruginosa further supported the involvement of quiP in signal decay and revealed other genes also possibly involved. It is not yet known under which "natural" conditions quiP is expressed or how P. aeruginosa balances the expression of its quorum-sensing systems with the expression of its acyl-HSL acylase activities.
ABSTRACT We report the identification of methoxymethanol (CH3OCH2OH) as a photochemistry product of condensed methanol (CH3OH) based on temperature-programmed desorption studies conducted following photon irradiation at energies below the ionization threshold (9.8 eV) of condensed methanol. The first detection of methoxymethanol in the interstellar medium was reported in 2017 based on data from Bands 6 and 7 from the Atacama Large Millimeter/submillimeter Array (ALMA). The cosmic synthesis of ‘complex’ organic molecules such as methyl formate (HCOOCH3), dimethyl ether (CH3OCH3), acetic acid (CH3COOH), ethylene glycol (HOCH2CH2OH), and glycolaldehyde (HOCH2CHO) has been attributed to UV photolysis of condensed methanol found in interstellar ices. Experiments conducted in 1995 demonstrated that electron-induced radiolysis of methanol cosmic ice analogues yields methoxymethanol. In three recent publications (2016, 2017, and 2018), methoxymethanol was considered as a potential tracer for reactions induced by secondary electrons resulting from the interaction of cosmic rays with interstellar ices. However, the results presented in this study suggest that methoxymethanol can be formed from both radiation chemistry and photochemistry of condensed methanol.
The global coronavirus disease 2019 (COVID-19) pandemic and the search for ways in which to provide the best available care have created unprecedented times in terms of rapidly evolving reports of available treatment options. The primary objective of our analysis was to categorize online, open-source guidance to determine how US institutions approached their recommendations for management of patients with COVID-19 in the early weeks of the pandemic.A search for open-source, online institutional guidelines for the treatment of COVID-19 was conducted using predefined criteria. The search was limited to the United States and conducted from April 12 through 14, 2020, and again on April 22, 2020. Searches were conducted at 2 points in time in order to identify changes in treatment recommendations due to evolving literature or institutional experience. Treatment recommendations, including guidance on antiviral therapy, corticosteroid and interleukin-6 inhibitor use, and nutritional supplementation were compared.Of the 105 institutions that met initial screening criteria, 14 institutions (13.3%) had online COVID-19 guidance available. Supportive care and clinical trial enrollment were the primary recommendations in all evaluated guidance. Recommendations to consider antimicrobial and adjunctive therapy varied. Eighty-six percent of guidelines contained recommendations for use, or consideration of use, of hydroxychloroquine. Guidance from 2 institutions mentioned use of hydroxychloroquine and azithromycin in combination. Of the 13 institutions listing hydroxychloroquine dosing recommendations, 62% recommended maintenance dosing of 200 mg twice daily. Infectious diseases or other specialty consultation was required by 89% of institutions using interleukin-6 inhibitors for COVID-19 management.Overall, the analysis revealed variability in treatment or supplemental pharmacologic therapy for the management of COVID-19.
Pseudomonas syringae cultured in a defined citrate medium supplemented with 1 mM aluminium, chromium and manganese, respectively, appeared to elicit disparate biochemical responses. At the stationary phase of growth aluminium was predominantly present as an insoluble residue. Although virtually none of this metallic element was detected in the supernatant, the bacterial cells appeared to contain some aluminium. Following the initial uptake of chromium the microbe secreted the metal in the supernatant. Only a small fraction of the chromium was localised in the bacterial cells; 91% manganese was biotransformed into an insoluble pellet. No citrate was detected in the exocellular fluid at cessation of cellular growth.
We elucidate mechanisms of electron-induced radiolysis in cosmic (interstellar, planetary, and cometary) ice analogs of ammonia (NH3), likely the most abundant nitrogen-containing compound in the interstellar medium (ISM). Astrochemical processes were simulated under ultrahigh vacuum conditions by high-energy (1 keV) and low-energy (7 eV) electron-irradiation of nanoscale thin films of ammonia deposited on cryogenically cooled metal substrates. Irradiated films were analyzed by temperature-programmed desorption (TPD). Experiments with ammonia isotopologues provide convincing evidence for the electron-induced formation of hydrazine (N2H4) and diazene (N2H2) from condensed NH3. To understand the dynamics of ammonia radiolysis, the dependence of hydrazine and diazene yields on incident electron energy, electron flux, electron fluence, film thickness, and ice temperature were investigated. Radiolysis yield measurements versus (1) irradiation time and (2) film thickness are semiquantitatively consistent with a reaction mechanism that involves a bimolecular step for the formation of hydrazine and diazene from the dimerization of amidogen (NH2) and imine (NH) radicals, respectively. The apparent decrease in radiolysis yield of hydrazine and diazene with decreasing electron flux at constant fluence may be due to the competing desorption of these radicals at 90 K under low incident electron flux conditions. The production of hydrazine at electron energies as low as 7 eV and an ice temperature of 22 K is consistent with condensed phase radiolysis being mediated by low-energy secondary electrons produced by the interaction of high-energy radiation with matter. These results provide a basis from which we can begin to understand the mechanisms by which ammonia can form more complex species in cosmic ices.
Humans have long had an urge to neatly label and categorize everything in the mysterious and often chaotic natural world — including other humans. Given the countless personality types, is there a good way to identify key traits and classify personalities into a few broad yet descriptive categories? Besides relying on sheer intuition, is there a methodical and unbiased way of “sizing people up?” In Making Sense of People, Samuel Barondes attempts a systematic approach to the science of evaluating people’s personalities. Referencing the works of modern researchers, Barondes, himself a professor of psychiatry, summarizes important findings in a guidebook intended for those outside the field. Making Sense of People is aimed at the general audience, and at 240 pages, it is a light and engaging read. The book is divided into three parts, each several chapters. Part One attempts to describe personality differences, Part Two gives an overview and brief explanation of those personality differences at the biological and physiological levels, and Part Three relates an individual’s personality to the context of the whole person and personal life story.
Barondes relies heavily on the “Big Five” factors of personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness) used in modern psychology. Introduced in the first chapter, the Big Five are referred back to regularly in subsequent chapters. The Big Five method is fleshed out with examples using famous individuals like Bill Clinton. Barondes uses evidence from media reports of Clinton as the basis for his personality analysis, but confounding factors such as possible media bias are ignored. Perhaps this is inevitable, since readers might only be able to recognize familiar, sometimes polarizing, public figures, but at the cost of the author not having a firsthand perspective of said public figure. In any case, the rest of the text is similarly peppered with diverse personalities from popular culture, from Steve Jobs to Oprah Winfrey.
Part One of the book is devoted to the Big Five framework and the history behind it. Part Two delves deeper into the mechanisms of the human brain, from gene expression to critical periods in brain development. Barondes also posits the age-old question of nature versus nurture. Finally, Part Three paints a bigger picture, examining personality alongside related notions of character and identity. Barondes acknowledges that any moral assessments of personality would need to consider differing cultural contexts, but notes the work of Peterson and Seligman, who maintain that there are certain core virtues shared by all cultures worldwide. At the end, Barondes consolidates techniques and offers a step-by-step guide to personality analysis. Making Sense of People is not a textbook and does not read like one. However, one drawback is its short length; without risk of sounding pedantic, several chapters could be further elaborated.
As stated in its introduction, the main aim of the book is “augmenting your pleasure in understanding and dealing with people, whether you like them or not,” and with this book, readers are indeed one step closer to better understanding others.
Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the “S3-site” releases a C-terminal cytoplasmic fragment (Notch intracellular domain) that acts as the intracellular transduction molecule for Notch activation. Missense mutations in the presenilins cause familial Alzheimer's disease by augmenting the “γ-secretase” cleavage of APP and overproducing one of the proteolytic derivatives, the Aβ peptide. Null mutations in PS1 inhibit both γ-secretase cleavage of APP and S3-site cleavage of the Notch receptor. Mice lacking PS1 function have defective Notch signaling and die perinatally with severe skeletal and brain deformities. We report here that a genetic modifier on mouse distal chromosome 1, coinciding with the locus containing Nicastrin , influences presenilin-mediated Notch S3-site cleavage and the resultant Notch phenotype without affecting presenilin-mediated APP γ-site cleavage. Two missense substitutions of residues conserved among vertebrates have been identified in nicastrin. These results indicate that Notch S3-site cleavage and APP γ-site cleavage are distinct presenilin-dependent processes and support a functional interaction between nicastrin and presenilins in vertebrates. The dissociation of Notch S3-site and APP γ-site cleavage activities will facilitate development of γ-secretase inhibitors for treatment of Alzheimer's disease.
