A candidate gene cluster for the bioactive natural product gyrophoric acid in lichen-forming fungi

Natural products of lichen-forming fungi are structurally diverse and have a variety of medicinal properties. Yet they a have limited implementation in industry as for most of the natural products, the corresponding genes remain unknown. Here we implement a long-read sequencing and bioinformatic approach to identify the biosynthetic gene cluster of the bioactive natural product gyrophoric acid (GA). Using 15 high-quality genomes representing nine GA-producing species of the lichen-forming fungal genus Umbilicaria, we identify the most likely GA cluster and investigate cluster gene organization and composition across the nine species. Our results show that GA clusters are promiscuous within Umbilicaria with only three genes that are conserved across species, including the PKS gene. In addition, our results suggest that the same cluster codes for different but structurally similar NPs, i.e., GA, umbilicaric acid and hiascic acid, bringing new evidence that lichen metabolite diversity is also generated through regulatory mechanisms at the molecular level. Ours is the first study to identify the most likely GA cluster. This information is essential for opening up avenues for biotechnological approaches to producing and modifying GA, and possibly other lichen compounds. We show that bioinformatics approaches are useful in linking genes and potentially associated natural products. Genome analyses help unlocking the pharmaceutical potential of organisms such as lichens, which are biosynthetically diverse, but slow growing, and usually uncultivable due to their symbiotic nature.

Partial sex linkage and linkage disequilibrium on the guppy sex chromosome

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex-linkage has evolved across about 3 Mb surrounding the sex-determining locus of this fish, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger evolutionary strata. Sequences of the guppy genome show that Y is very similar to the X chromosome, making it important to understand which parts of the Y are completely non-recombining, and whether there is indeed a large completely non-recombining region. Here, we describe new evidence that supports a different interpretation of the data that suggested the presence of such a region. We analysed PoolSeq data in samples from multiple natural populations from Trinidad. This yields evidence for linkage disequilibrium (LD) between sequence variants and the sex-determining locus. Downstream populations have higher diversity than upstream ones (which display the expected signs of bottlenecks). The associations we observe conform to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. They also suggest the region in which the sex-determining locus must be located. However, no consistently male-specific variants were found, supporting the suggestion that any completely sex-linked region may be very small.

Supporting the development of scientific understanding when constructing an evolving explanation

We explore how students developed an integrated understanding of scientific ideas and how they applied their understandings in new situations. We examine the incremental development of 7th grade students’ scientific ideas across four iterations of a scientific explanation related to a freshwater system. We demonstrate that knowing how to make use of scientific ideas to explain phenomena needs to be learned just as developing integrated understanding of scientific ideas needs to be learned. Students participated in an open-ended, long-term project-based learning unit, constructing one explanation over time to address, “How healthy is our stream for freshwater organisms and how do our actions on land potentially impact the water quality of the stream?” The explanation developed over several weeks as new data were collected and analyzed. Students discussed evidence by revisiting scientific ideas and including new scientific ideas. This research investigates two questions: (1) As students engage in writing a scientific explanation over time, to what extent do they develop integrated understanding of appropriate scientific ideas? and (2) When writing about new evidence, do these earlier experiences of writing explanations enable students to make use of new scientific ideas in more sophisticated ways? In other words, do earlier experiences allow students to know how to make use of their ideas in these new situations? The results indicated statistically significant effects. Through various iterations of the explanation students included richer discussion using appropriate scientific ideas. Students were also able to make better use of new knowledge in new situations.

HERV-K and HERV-H env Proteins Induce a Humoral Response in Prostate Cancer Patients

A higher expression of human endogenous retroviruses (HERVs) has been associated with several malignancies, including prostate cancer, implying a possible use as a diagnostic or prognostic cancer biomarker. For this reason, we examined the humoral response against different epitopes obtained from the envelope protein of HERV-K (HERV-K env-su19–37, HERV-K env-su109–126), HERV-H (HERV-H env-su229–241, HERV-H env387–399) and HERV-W (HERV-W env-su93–108, HERV-W env-su248–262) in the plasma of patients affected by prostate cancer (PCa), and compared to that of benign prostate hyperplasia (BPH) and a borderline group of patients with atypical small acinar proliferation (ASAP) and prostate intraepithelial neoplasia (PIN) and healthy controls. A significant antibody response was observed against HERV-K env-su109–126 (p = 0.004) and HERV-H env-su229–241 (p < 0.0001) in PCa patients compared to HCs, BPH and borderline cohorts, whilst no significance difference was found in the antibodies against HERV-W env-su93–108 and HERV-W env-su248–262 in patients with PCa. Our results provided further proof of the association between HERV-K and PCa and added new evidence about the possible involvement of HERV-H in PCa pathogenesis, highlighting their possibility of being used as biomarkers of the disease.

Silica Nanoparticles Promote α-Synuclein Aggregation and Parkinson’s Disease Pathology

Silica nanoparticles (SiO2 NPs) are increasingly investigated for their potential in drug delivery systems. However, the neurotoxicity of SiO2 NPs remains to be fully clarified. Previously SiO2 NPs have been reported to be detected in the central nervous system, especially in the dopaminergic neurons which are deeply involved in Parkinson’s disease (PD). In this article, we characterized the effects of SiO2 NPs on inducing PD-like pathology both in vitro and in vivo. Results showed that SiO2 NPs promote more severe hyperphosphorylation and aggregation of α-synuclein, mitochondria impairment, oxidative stress, autophagy dysfunction, and neuronal apoptosis in the α-Syn A53T transgenic mice intranasally administrated with SiO2 NPs compared with the control group. Our findings provide new evidence supporting that SiO2 NPs exposure might have a strong capability of promoting the initiation and development of PD.