Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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Rapid characterization of spike variants via mammalian cell surface display

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Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the expression of miR-19b and miR-21

Exosomes derived from differentiated P12 cells and MSCs were proved to suppress apoptosis of neuron cells, and phosphatase and tensin homolog pseudogene 1 (PTENP1) was reported to inhibit cell proliferation. In this study, we aimed to investigate the role of PTENP1 in the process of post-spinal cord injury (SCI) recovery, so as to evaluate the therapeutic effects of exosomes derived from MSCs transfected with PTENP1 short hairpin RNA (shRNA), as a type of novel biomarkers in the treatment of SCI. Electron microscopy was used to observe the morphology of different exosomes. Real-time polymerase chain reaction and western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry, Nissl staining, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were conducted to investigate and validate the underlying molecular signaling pathway. PTENP1-shRNA downregulated PTENP1 and PTEN while upregulating miR-21 and miR-19b. PTENP1-shRNA also accelerated cell apoptosis and reduced cell viability. In addition, PTENP1 reduced the miR-21 and miR-19b expression by directly targeting miR-21 and miR-19b. Meanwhile, both miR-21 and miR-19b reduced the expression of PTEN by directly targeting the 3′-untranslated region of PTEN. Furthermore, PTEN level and apoptosis index of neuron cells was the highest in the SCI group, while the treatment with exosomes+PTENP1-shRNA reduced the PTEN expression to a level similar to that in the sham group. Finally, PTENP1 inhibited miR-21 and miR-19b expression but upregulated PTEN expression. The upregulation of miR-21/miR-19b also suppressed the apoptosis of neuron cells by downregulating the PTEN expression. PTENP1 is involved in the recovery of SCI by regulating the expression of miR-19b and miR-21, and exosomes from PTENP1-shRNA-transfected cells may be used as a novel biomarker in SCI treatment.     

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.     

An inordinate fondness for beetles*

The abundance and diversity of insects was the subject of the joint commemorative meeting between the Linnean Society and the Royal Entomological Society of London. This paper gives a brief outline of the foundation and early history of the Entomological Society and its forerunners, and its relations with the Linnean Society at the time. It also shows how the contributions of the founding fellows of the Society, whose interests originated in collecting and insect natural history, laid the foundations of many of the present day fields of entomological research.     

Influence of the ion-balance in the growth medium on the yield and alkaloid content ofDatura stramonium L.

Plants ofDatura stramonium var.tatula L. Torr. were grown for 24 weeks on vermiculite and provided with mineral solutions where the relative proportions of the major anions (N, S, P) and cations (K, Ca, Mg) were varied within a constant total.With all treatments a cyclic transport of alkaloids (hyoscyamine) from the roots to the upper plant parts appeared. The fluctuations in alkaloid content in the leaves followed those in the roots with a delay of 4 weeks.The interionic ratios seemed to influence growth and alkaloid content rather than to affect the ontogenic variations. In general, the response to the different treatments could be divided into two types. The nitrogen treatments which gave at the same time a higher crop yield and an increased hyoscyamine content, and the other treatments where a much lower yield and content was obtained.The scopolamine content on the other hand seemed to be more affected by the developmental stage. Also, the time of maximal yield was not influenced by the ion-balance but rather the climatic conditions.     

Measurement of Free Intracellular Calcium in the Brain by 19F-Nuclear Magnetic Resonance Spectroscopy

We report the first measurement of the free intracellular calcium level in an actively metabolising intact cerebral tissue preparation. To this end, we applied the recently developed 19F-nuclear magnetic resonance calcium chelator, 5,5'-F2-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA), in superfused cerebral cortical slices to give values for the intracellular Ca2+ concentration of 350 and 480 nM, at external calcium concentrations of 1.2 and 2.4 mM, respectively. Under both conditions, the intracellular Ca2+ concentration was increased by depolarisation using a high external K+ concentration. Interleaved 31P spectra showed that the presence of the 5FBAPTA had a deleterious effect on the metabolic state of the tissue with an external Ca2+ concentration of 1.2 mM, but normal viability was maintained using 2.4 mM.     

大花翠雀的新二萜生物碱

从大花翠雀(Delphinium grandiflorum L.)的地上部分分离到两个微量的新二萜生物碱——大花翠雀辛(grandifloricine,Ⅰ)和大花翠雀亭(grandifloritine,Ⅱ)。通过分析光谱信息测定了它们的化学结构,并通过化学反应转变为 takaosamine 而得到确证。     

Stoichiometry of interaction between soluble (—)-dopa melanin and enantiomers of ephedrine by NMR spectroscopy

Synthetic soluble (—)-dopa melanin was prepared in deuteriated buffer, pH 8, by autooxidation of the precursor. At 6 mM of the precursor, the incorporation was over 90%. The changes in the line width measurements of N-CH₃ protons of enantiomers of ephedrine in the soluble melanin were quantified by NMR spectroscopy. The dissociation constants of (—)-1R,2S-ephedrine, (+)-1S,2R-ephedrine, (—)-1R,2R-ψ-ephedrine, and (+)-1S,2S-ψ-ephedrine were 11.7, 4.20, 3.60, and 4.80 mM, respectively. Since the concentration of (—)-dopa was known and since the conversion of (—)-dopa to indole units of melanin was considered as 1:1, the stoichiometry of the interaction between the drug and the indole unit was calculated. Based on the dissociation constants of the enantiomers, it appears that up to four molecules of (—)-ephedrine can interact with one indole unit of the melanin, while such a ratio for other isomers appear to be 2:1. The preference by indole units of melanin is stereoselective. © 1992 Wiley-Liss, Inc.