Direct involvement of p53 in programmed cell death of oligodendrocytes.

A covalent dimer of interleukin (IL)-2, produced in vitro by the action of a nerve-derived transglutaminase, has been shown previously to be cytotoxic to mature rat brain oligodendrocytes. Here we report that this cytotoxic effect operates via programmed cell death (apoptosis) and that the p53 tumor suppressor gene is involved directly in the process. The apoptotic death of mature rat brain oligodendrocytes in culture following treatment with dimeric IL-2 was demonstrated by chromatin condensation and internucleosomal DNA fragmentation. The peak of apoptosis was observed 16-24 h after treatment, while the commitment to death was already observed after 3-4 h. An involvement of p53 in this process was indicated by the shift in location of constitutively expressed endogenous p53 from the cytoplasm to the nucleus, as early as 15 min after exposure to dimeric IL-2. Moreover, infection with a recombinant retrovirus encoding a C-terminal p53 miniprotein, shown previously to act as a dominant negative inhibitor of endogenous wild-type p53 activity, protected these cells from apoptosis.     

A Penicillium expansum glucose oxidase-encoding gene, GOX2, is essential for gluconic acid production and acidification during colonization of deciduous fruit

Penicillium expansum, the causal agent of blue mold rot, causes severe postharvest maceration of fruit through secretion of total, d-gluconic acid (GLA). Two P. expansum glucose oxidase (GOX)-encoding genes, GOX1 and GOX2, were analyzed. GOX activity and GLA accumulation were strongly related to GOX2 expression, which increased with pH to a maximum at pH 7.0, whereas GOX1 was expressed at pH 4.0, where no GOX activity or extracellular GLA were detected. This differential expression was also observed at the leading edge of the decaying tissue, where GOX2 expression was dominant. The roles of the GOX genes in pathogenicity were further studied through i) development of P. expansum goxRNAi mutants exhibiting differential downregulation of GOX2, ii) heterologous expression of the P. expansum GOX2 gene in the nondeciduous fruit-pathogen P. chrysogenum, and iii) modulation of GLA production by FeSO(4) chelation. Interestingly, in P. expansum, pH and GLA production elicited opposite effects on germination and biomass accumulation: 26% of spores germinated at pH 7.0 when GOX activity and GLA were highest whereas, in P. chrysogenum at the same pH, when GLA did not accumulate, 72% of spores germinated. Moreover, heterologous expression of P. expansum GOX2 in P. chrysogenum resulted in enhanced GLA production and reduced germination, suggesting negative regulation of spore germination and GLA production. These results demonstrate that pH modulation, mediated by GLA accumulation, is an important factor in generating the initial signal or signals for fungal development leading to host-tissue colonization by P. expansum.     

Role and regulation of starvation-induced autophagy in the Drosophila fat body

In response to starvation, eukaryotic cells recover nutrients through autophagy, a lysosomal-mediated process of cytoplasmic degradation. Autophagy is known to be inhibited by TOR signaling, but the mechanisms of autophagy regulation and its role in TOR-mediated cell growth are unclear. Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including ATG1 and ATG5, does not restore growth to TOR mutant cells. Instead, inhibition of autophagy enhances TOR mutant phenotypes, including reduced cell size, growth rate, and survival. Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor.     

Method as a Function of “Disciplinary Landscape”: C.D. Darlington and Cytology, Genetics and Evolution, 1932–1950

This article considers the reception of British cytogeneticist C.D. Darlington’s controversial 1932 book, Recent Advances in Cytology. Darlington’s cytogenetic work, and the manner in which he made it relevant to evolutionary biology, marked an abrupt shift in the status and role of cytology in the life sciences. By focusing on Darlington’s scientific method – a stark departure from anti-theoretical, empirical reasoning to a theoretical and speculative approach based on deduction from genetic first principles – the article characterises the relationships defining the “disciplinary landscape” of the life sciences of the time, namely those between cytology, genetics, and evolutionary theory.     

Cannabinoids inhibit zebra mussel (Dreissena polymorpha) byssal attachment: a potentially green antifouling technology

Man-made submerged structures, including shipwrecks, offering substrata for fouling organisms and fish, have been classified secondarily as artificial reefs (ARs). The current approach in AR design is that of low-profile structures placed on the seabed and attempting to mimic natural reef (NR) communities with the aim of mitigating degraded marine ecosystems. To examine the validity of this concept, a long-term comparison of the developing AR fouling communities to those of nearby NRs is required. A survey of the fouling reefal organisms was conducted on seven shipwrecks (Red Sea, Egypt), comprising three young (ca 20 years old) and four old (?>?100 years old) unplanned ARs, in comparison to nearby NR communities. The hypothesis tested was that the age of the ARs shapes the structure of their fouling coral communities. The results demonstrated distinct differences between ARs and NRs and between young and old ARs. While the species composition on ARs may resemble that of NRs after approximately 20 years, obtaining a similar extent of coral cover may require a full century. Moreover, differences in structural features between ARs and NRs may lead to differences in species composition that persist even after 100 years.     

The interplay between vaccination and social distancing strategies affects COVID19 population-level outcomes

Social distancing is an effective population-level mitigation strategy to prevent COVID19 propagation but it does not reduce the number of susceptible individuals and bears severe social consequences—a dire situation that can be overcome with the recently developed vaccines. Although a combination of these interventions should provide greater benefits than their isolated deployment, a mechanistic understanding of the interplay between them is missing. To tackle this challenge we developed an age-structured deterministic model in which vaccines are deployed during the pandemic to individuals who do not show symptoms. The model allows for flexible and dynamic prioritization strategies with shifts between target groups. We find a strong interaction between social distancing and vaccination in their effect on the proportion of hospitalizations. In particular, prioritizing vaccines to elderly (60+) before adults (20-59) is more effective when social distancing is applied to adults or uniformly. In addition, the temporal reproductive number R_t is only affected by vaccines when deployed at sufficiently high rates and in tandem with social distancing. Finally, the same reduction in hospitalization can be achieved via different combination of strategies, giving decision makers flexibility in choosing public health policies. Our study provides insights into the factors that affect vaccination success and provides methodology to test different intervention strategies in a way that will align with ethical guidelines.