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Evidence of Increased Hydrophobicity and Dynamics inside the Tail Region of Glycolipid Self-Assemblies Using 2-n-Alkyl-Pyrene Derivatives to Probe Different Locations

Zahid NI, Ji L, Khyasudeen MF, Friedrich A, Hashim R, Marder TB, et al.

Langmuir, 2019 07 23;35(29):9584-9592.
PMID: 31287700 DOI: 10.1021/acs.langmuir.9b01767

New designer biofluorophores are being increasingly used in the investigation of complex cellular processes. In this study, we utilized new derivatives of pyrene (Py), i.e., 2-n-alkyl-pyrenes (Py-C4 and Py-C8), in order to probe different regions inside the hydrophobic tail of n-dodecyl β-d-maltoside (βMal-C12) in two different phases (cubic ↔ lamellar). Although the sensitivity to the local environment is reduced compared to that of Py, attaching C4 and C8 at the 2-position of Py can provide a possible means to probe the local hydrophobicity in different parts of the tail region. The absence of excimer fluorescence and the ratio of the vibronic fluorescence peak intensities (I1/I3) in a lipid environment indicate the existence of Py as monomers in the hydrophobic region, similar to hydrophobic solvation, yet close to the headgroup region. When Py is replaced by Py-C4 and Py-C8, there is a small increase in hydrophobicity (reduction in I1/I3) as the Py moiety is pulled deeper inside the tail region of both cubic and lamellar phases. The larger space of the tail region in the lamellar phase is reflected as more local hydrophobicity measured by the probes which can penetrate deep inside, whereas the curved structure of the cubic phase limits the available space for the probes. Three fluorescence lifetime components were measured in lipid, indicating the heterogeneous nature of the hydrophobic region. In the lamellar phase, a large reduction in the average lifetime value, led by the long decay component, was measured for Py-C4 (reduction by 25%) and Py-C8 (45%) compared to that of the parent Py. This observation suggests the presence of a mechanism of interaction more collisional than static between the Py moiety and the tail region of the bilayer unit due to the ample space provided by the lamellar phase as the probe is buried deeper inside the hydrophobic region. A much smaller effect was observed in the cubic phase and was correlated with the tight environment around the probes, which stems from the increased curvature of the cubic phase. The current results provide a deeper understanding of the hydrophobic region during phase transition of lipid self-assembly which is important for better control during the process of membrane-protein crystallization.
Fulltext Reductive Coupling of Diynes at Rhodium Gives Fluorescent Rhodacyclopentadienes or Phosphorescent Rhodium 2,2'-Biphenyl Complexes

Sieck C, Tay MG, Thibault MH, Edkins RM, Costuas K, Halet JF, et al.

Chemistry, 2016 Jul 18;22(30):10523-32.
PMID: 27355689 DOI: 10.1002/chem.201601912

Reactions of [Rh(κ(2) -O,O-acac)(PMe3 )2 ] (acac=acetylacetonato) and α,ω-bis(arylbutadiynyl)alkanes afford two isomeric types of MC4 metallacycles with very different photophysical properties. As a result of a [2+2] reductive coupling at Rh, 2,5-bis(arylethynyl)rhodacyclopentadienes (A) are formed, which display intense fluorescence (Φ=0.07-0.54, τ=0.2-2.5 ns) despite the presence of the heavy metal atom. Rhodium biphenyl complexes (B), which show exceptionally long-lived (hundreds of μs) phosphorescence (Φ=0.01-0.33) at room temperature in solution, have been isolated as a second isomer originating from an unusual [4+2] cycloaddition reaction and a subsequent β-H-shift. We attribute the different photophysical properties of isomers A and B to a higher excited state density and a less stabilized T1 state in the biphenyl complexes B, allowing for more efficient intersystem crossing S1 →Tn and T1 →S0 . Control of the isomer distribution is achieved by modification of the bis- (diyne) linker length, providing a fundamentally new route to access photoactive metal biphenyl compounds.
Fulltext Motivations for Industry Stakeholders in China, Vietnam, Thailand and Malaysia to Improve Livestock Welfare

Sinclair M, Idrus Z, Nhiem DV, Katawatin S, Todd B, Burn GL, et al.

Animals (Basel), 2019 Jul 04;9(7).
PMID: 31277448 DOI: 10.3390/ani9070416

Understanding what might motivate livestock stakeholders to improve animal welfare is useful information when developing initiatives that benefit from stakeholder engagement. This study was designed to assess the strength of motivating drivers in the development of attitudes to animal welfare, and the factors that impacted their ability to improve animal welfare. During a series of qualitative focus group sessions with livestock leaders across the same countries (Malaysia, China, Vietnam and Thailand), the current study presented livestock leaders (n = 139) with the most significant results in their country, and collected data pertaining to the meaning and applicability of these results. This data was then subject to thematic analysis to identify salient and repeated motivating factors and meanings. This process revealed a complex picture of relationships between motivators and the contexts that drive them. Figures are presented to begin illustrating these relationships. Some strong motivators were uncovered that were previously rated low in the survey (i.e., financial benefit) or not included at all (e.g., food safety). This paper also presents the opportunity to better understand the strength and relationship of extrinsic and intrinsic motivational forces behind animal welfare improvement.
Fulltext Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis

WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, et al.

JAMA, 2021 Aug 10;326(6):499-518.
PMID: 34228774 DOI: 10.1001/jama.2021.11330

IMPORTANCE: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.
OBJECTIVE: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.
DATA SOURCES: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.
STUDY SELECTION: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.
DATA EXTRACTION AND SYNTHESIS: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.
MAIN OUTCOMES AND MEASURES: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.
RESULTS: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P