COVID-19 and “natural” experiments arising from physical distancing: a hypothetical case study from chronobiology

ABSTRACT

With countless “natural” experiments triggered by the COVID-19-associated physical distancing, one key question comes from chronobiology: “When confined to homes, how does the reduced exposure to natural daylight arising from the interruption of usual outdoor activities plus lost temporal organization ordinarily provided from workplaces and schools affect the circadian timing system (the internal 24 h clock) and, consequently, health of children and adults of all ages?” Herein, we discuss some ethical and scientific facets of exploring such natural experiments by offering a hypothetical case study of circadian biology.     

A theoretical and experimental case study of the hydrogen bonding predilection of S-methylcysteine

S-containing amino acids can lead to two types of local NH···S interactions which bridge backbone NH sites to the side chain to form either intra- or inter-residue H-bonds. The present work reports on the conformational preferences of S-methyl-l-cysteine, Cys(Me), using a variety of investigating tools, ranging from quantum chemistry simulations, gas-phase UV and IR laser spectroscopy, and solution state IR and NMR spectroscopies, on model compounds comprising one or two Cys(Me) residues. We demonstrate that in gas phase and in low polarity solution, the C- and N-capped model compound for one Cys(Me) residue adopts a preferred C5–C6γ conformation which combines an intra-residue N–H···O=C backbone interaction (C5) and an inter-residue N–H···S interaction implicating the side-chain sulfur atom (C6γ). In contrast, the dominant conformation of the C- and N-capped model compound featuring two consecutive Cys(Me) residues is a regular type I β-turn. This structure is incompatible with concomitant C6γ interactions, which are no longer in evidence. Instead, C5γ interactions occur, that are fully consistent with the turn geometry and additionally stabilize the structure. Comparison with the thietane amino acid Attc, which exhibits a rigid cyclic side chain, pinpoints the significance of side chain flexibility for the specific conformational behavior of Cys(Me).

     

THE COMBINATION OF EDESTIN WITH HYDROCHLORIC ACID

Electromotive force measurements of cells without liquid junction, of the type Ag, AgCl, HCl + protein, H₂, lead to the conclusion that 1 gm. of edestin (or, more probably, edestan) combines with a maximum of 13.4 x 10^–4 equivalents of H⁺ and 3.9 x 10^–4 equivalents of Cl^-, when the protein is dissolved in 0.1 M HCl.     

Quantifying spatial classification uncertainties of the historical Wisconsin landscape (USA)

Landscape feature can be classified by creating categories based on aggregation of spatially explicit information. However, many landscape features appear continuous rather than discrete. The aggregation process likely involves loss of information and introduces a variety of uncertainties whose degree and extent may differ spatially. Since landscape classifications have found wide application in e.g. natural resource policies or ecological research, assessments of spatial classification uncertainties are required.
We present a quantitative framework to identify the degree of landscape continuity (fuzziness) and structure (categorization) based on fuzzy classification and offer measures to quantify uncertainties originating from aggregating features into categories. Fuzzy classification is a non-hierarchical, quantitative method of assessing class definitions using degrees of association between features and class. This results in classes which are well defined and compositionally distinct, as well as classes which are less clearly defined but which, to various degrees, share characteristics with some or all classes. The spatial variation in the degree of class definition on the landscape is used to assess classification uncertainties. The two aspects of uncertainty investigated are the degree of association of a feature with the overall class definitions (membership diffusion), and the class-specific degree of association of each pixel on the landscape with each class (membership saturation).
Three classification scenarios, one fuzzy and one discrete, of the historical landscape of Wisconsin (USA) were compared for spatial classification uncertainties. Membership diffusion is highest in topographically heterogeneous environments, or areas characterized by many species occupying similar ecological niches. Classification uncertainties for individual classes show that differentiated species distributions can be identified, not only distribution centers.     

Structure and Sequence Conservation of hao Cluster Genes of Autotrophic Ammonia-Oxidizing Bacteria: Evidence for Their Evolutionary History

Comparison of the organization and sequence of the hao (hydroxylamine oxidoreductase) gene clusters from the gammaproteobacterial autotrophic ammonia-oxidizing bacterium (aAOB) Nitrosococcus oceani and the betaproteobacterial aAOB Nitrosospira multiformis and Nitrosomonas europaea revealed a highly conserved gene cluster encoding the following proteins: hao, hydroxylamine oxidoreductase; orf2, a putative protein; cycA, cytochrome c₅₅₄; and cycB, cytochrome c_m552. The deduced protein sequences of HAO, c₅₅₄, and c_m552 were highly similar in all aAOB despite their differences in species evolution and codon usage. Phylogenetic inference revealed a broad family of multi-c-heme proteins, including HAO, the pentaheme nitrite reductase, and tetrathionate reductase. The c-hemes of this group also have a nearly identical geometry of heme orientation, which has remained conserved during divergent evolution of function. High sequence similarity is also seen within a protein family, including cytochromes c_m552, NrfH/B, and NapC/NirT. It is proposed that the hydroxylamine oxidation pathway evolved from a nitrite reduction pathway involved in anaerobic respiration (denitrification) during the radiation of the Proteobacteria. Conservation of the hydroxylamine oxidation module was maintained by functional pressure, and the module expanded into two separate narrow taxa after a lateral gene transfer event between gamma- and betaproteobacterial ancestors of extant aAOB. HAO-encoding genes were also found in six non-aAOB, either singly or tandemly arranged with an orf2 gene, whereas a c₅₅₄ gene was lacking. The conservation of the hao gene cluster in general and the uniqueness of the c₅₅₄ gene in particular make it a suitable target for the design of primers and probes useful for molecular ecology approaches to detect aAOB.     

Expression of mutant human epidermal receptor 3 attenuates lung fibrosis and improves survival in mice.

Neuregulin-1 (NRG-1), binding to the human epidermal growth factor receptor HER2/HER3, plays a role in pulmonary epithelial cell proliferation and recovery from injury in vitro. We hypothesized that activation of HER2/HER3 by NRG-1 would also play a role in recovery from in vivo lung injury. We tested this hypothesis using bleomycin lung injury of transgenic mice incapable of signaling through HER2/HER3 due to lung-specific dominant-negative HER3 (DNHER3) expression. In animals expressing DNHER3, protein leak, cell infiltration, and NRG-1 levels in bronchoalveolar lavage fluid increased after injury, similar to that in nontransgenic littermate control animals. However, HER2/HER3 was not activated, and DNHER3 animals displayed fewer lung morphological changes at 10 and 21 days after injury (P = 0.01). In addition, they contained 51% less collagen in injured lungs (P = 0.04). Transforming growth factor-beta1 did not increase in bronchoalveolar lavage fluid from DNHER3 mice compared with nontransgenic littermate mice (P = 0.001), suggesting that a mechanism for the decreased fibrosis was lack of transforming growth factor-beta1 induction in DNHER3 mice. Severe lung injury (0.08 units bleomycin) resulted in 80% mortality of nontransgenic mice, but only 35% mortality of DNHER3 transgenic mice (P = 0.04). Thus inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival.     

Synthesis and activity of 2-oxoamides containing long chain beta-amino acids.

2-Oxoamides based on long chain beta-amino acids were synthesized. 1-Benzyl substituted long chain amines, needed for such synthesis, were synthesized starting from Boc-phenylalaninol. The oxidative conversion of a phenyl group to a carboxyl group was used as the key transformation synthetic step. The compounds synthesized were studied for their activity against GIVA PLA(2), and were proven to be weak inhibitors.