The author apply concepts and tools from evolutionary medicine to understanding the SARS-CoV-2 pandemic. The pandemic represents a mismatched conflict, with dynamics and pathology apparently driven ...by three main factors: (i) bat immune systems that rely on low inflammation but high efficacy of interferon-based defenses; (ii) viral tactics that differentially target the human interferon system, leading to substantial asymptomatic and pre-symptomatic transmission; and (ii) high mortality caused by hyper-inflammatory and hyper-coagulatory phenotypes, that represent dysregulated tradeoffs whereby collateral immune-induced damage becomes systemic and severe. This framework can explain the association of mortality with age (which involves immune life-history shifts towards higher inflammation and coagulation and reduced adaptive immunity), and sex (since males senesce faster than females). Genetic-risk factors for COVID-19 mortality can be shown, from a phenome-wide association analysis of the relevant SNPs, to be associated with inflammation and coagulation; the phenome-wide association study also provides evidence, consistent with several previous studies, that the calcium channel blocking drug amlodipine mediates risk of mortality.
: SARS-CoV-2 is a bat virus that jumped into humans. The virus is adapted to bat immune systems, where it evolved to suppress the immune defenses (interferons) that mammals use to tell that they are infected. In humans, the virus can apparently spread effectively in the body with a delay in the production of symptoms and the initiation of immune responses. This delay may then promote overactive immune responses, when the virus is detected, that damage the body as a side effect. Older people are more vulnerable to the virus because they are less adapted to novel infectious agents, and invest less in immune defense, compared to younger people. Genes that increase risk of mortality from SARS-CoV-2 are functionally associated with a drug called amlodipine, which may represent a useful treatment.
The classic evolutionary hypothesis of ecological opportunity proposes that both heterogeneity of resources and freedom from enemies promote phenotypic divergence as a response to increased niche ...availability. Although phenotypic divergence and speciation have often been inferred to be the primary consequences of the release from competition or predation that accompanies a shift to a new adaptive zone, increased phenotypic variation within species is expected to represent the first stage resulting from such a shift. Using measures of intraspecific morphological variation of 30 species of Galápagos endemic land snails in a phylogenetically controlled framework, we show that the number of local congeners and the number of local plant species are associated with lower and higher intraspecific phenotypic variation, respectively. In this clade, ecological opportunity thus explicitly links the role of competition from congeners and the heterogeneity of resources to the extent of intraspecific phenotypic divergence as adaptive radiation proceeds.
Graphite intercalation compounds are formed by inserting guest molecules or ions between sp(2)-bonded carbon layers. These compounds are interesting as synthetic metals and as precursors to graphene. ...For many decades it has been thought that graphite intercalation must involve host-guest charge transfer, resulting in partial oxidation, reduction or covalent modification of the graphene sheets. Here, we revisit this concept and show that graphite can be reversibly intercalated by non-oxidizing Brønsted acids (phosphoric, sulfuric, dichloroacetic and alkylsulfonic acids). The products are mixtures of graphite and first-stage intercalation compounds. X-ray photoelectron and vibrational spectra indicate that the graphene layers are not oxidized or reduced in the intercalation process. These observations are supported by density functional theory calculations, which indicate a dipolar interaction between the guest molecules and the polarizable graphene sheets. The intercalated graphites readily exfoliate in dimethylformamide to give suspensions of crystalline single- and few-layer graphene sheets.
Based on a survey of the inventors of 9,017 European patented inventions, this paper provides new information about the characteristics of European inventors, the sources of their knowledge, the ...importance of formal and informal collaborations, the motivations to invent, and the actual use and economic value of the patents.
Plants adapt to different environmental conditions by constantly forming new organs in response to morphogenetic signals. Lateral roots branch from the main root in response to local auxin maxima. ...How a local auxin maximum translates into a robust pattern of gene activation ensuring the proper growth of the newly formed lateral root is largely unknown. Here, we demonstrate that miR390, TAS3-derived trans-acting short-interfering RNAs (tasiRNAs), and AUXIN RESPONSE FACTORS (ARFs) form an auxin-responsive regulatory network controlling lateral root growth. Spatial expression analysis using reporter gene fusions, tasi/miRNA sensors, and mutant analysis showed that miR390 is specifically expressed at the sites of lateral root initiation where it triggers the biogenesis of tasiRNAs. These tasiRNAs inhibit ARF2, ARF3, and ARF4, thus releasing repression of lateral root growth. In addition, ARF2, ARF3, and ARF4 affect auxin-induced miR390 accumulation. Positive and negative feedback regulation of miR390 by ARF2, ARF3, and ARF4 thus ensures the proper definition of the miR390 expression pattern. This regulatory network maintains ARF expression in a concentration range optimal for specifying the timing of lateral root growth, a function similar to its activity during leaf development. These results also show how small regulatory RNAs integrate with auxin signaling to quantitatively regulate organ growth during development.
The study focuses on the impact exerted on private R&D expenditures by regular and innovative public procurement when taken in combination or insolation with supply-push measures. The econometric ...analysis relies on a pulled sample of 4206 Italian manufacturing firms observed between 2010 and 2014. The empirical exercise confirms previous evidences on the relevance of technology-push instruments in sustaining firms' innovativeness. On the contrary, the ability of public procurement activities in shaping innovative investments is found to depend on a number of instances related to: (i) the adoption of contemporaneous supply side measures; (ii) the inclusion of innovative demand in procurement contracts. The analysis provides important suggestions with respect to the potential effectiveness of demand-side tools when implemented in weak administrative and innovation systems, as in the Italian case. Moreover, it is shown that the design of the policy mix matters, and its effectiveness improves when demand-side and supply-side instruments are jointly implemented.
I review and evaluate genetic and genomic evidence salient to the hypothesis that the development and evolution of psychotic spectrum conditions have been mediated in part by alterations of imprinted ...genes expressed in the brain. Evidence from the genetics and genomics of schizophrenia, bipolar disorder, major depression, Prader‐Willi syndrome, Klinefelter syndrome, and other neurogenetic conditions support the hypothesis that the etiologies of psychotic spectrum conditions commonly involve genetic and epigenetic imbalances in the effects of imprinted genes, with a bias towards increased relative effects from imprinted genes with maternal expression or other genes favouring maternal interests. By contrast, autistic spectrum conditions, including Kanner autism, Asperger syndrome, Rett syndrome, Turner syndrome, Angelman syndrome, and Beckwith‐Wiedemann syndrome, commonly engender increased relative effects from paternally expressed imprinted genes, or reduced effects from genes favouring maternal interests. Imprinted‐gene effects on the etiologies of autistic and psychotic spectrum conditions parallel the diametric effects of imprinted genes in placental and foetal development, in that psychotic spectrum conditions tend to be associated with undergrowth and relatively‐slow brain development, whereas some autistic spectrum conditions involve brain and body overgrowth, especially in foetal development and early childhood. An important role for imprinted genes in the etiologies of psychotic and autistic spectrum conditions is consistent with neurodevelopmental models of these disorders, and with predictions from the conflict theory of genomic imprinting.
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