The development of the human malaria parasitePlasmodium falciparumis controlled by coordinated changes in gene expression throughout its complex life cycle, but the corresponding regulatory mechanisms are incompletely understood. To study the relationship between genome architecture and gene regulation inPlasmodium, we assayed the genome architecture ofP. falciparumat three time points during its erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), we obtained high-resolution chromosomal contact maps, which we then used to construct a consensus three-dimensional genome structure for each time point. We observed strong clustering of centromeres, telomeres, ribosomal DNA, and virulence genes, resulting in a complex architecture that cannot be explained by a simple volume exclusion model. Internal virulence gene clusters exhibit domain-like structures in contact maps, suggesting that they play an important role in the genome architecture. Midway during the erythrocytic cycle, at the highly transcriptionally active trophozoite stage, the genome adopts a more open chromatin structure with increased chromosomal intermingling. In addition, we observed reduced expression of genes located in spatial proximity to the repressive subtelomeric center, and colocalization of distinct groups of parasite-specific genes with coordinated expression profiles. Overall, our results are indicative of a strong association between theP. falciparumspatial genome organization and gene expression. Understanding the molecular processes involved in genome conformation dynamics could contribute to the discovery of novel antimalarial strategies.

Olfactory stimulation is an often overlooked method of environmental enrichment for cats in captivity. The best known example of olfactory enrichment is the use of catnip, a plant that can cause an apparently euphoric reaction in domestic cats and most of the Pantherinae. It has long been known that some domestic cats and most tigers do not respond to catnip. Although many anecdotes exist of other plants with similar effects, data are lacking about the number of cats that respond to these plants, and if cats that do not respond to catnip respond to any of them. Furthermore, much is still unknown about which chemicals in these plants cause this response. We tested catnip, silver vine, Tatarian honeysuckle and valerian root on 100 domestic cats and observed their response. Each cat was offered all four plant materials and a control, multiple times. Catnip and silver vine also were offered to nine tigers. The plant materials were analyzed by gas chromatography coupled with mass spectrometry to quantify concentrations of compounds believed to exert stimulating effects on cats. Nearly all domestic cats responded positively to olfactory enrichment. In agreement with previous studies, one out of every three cats did not respond to catnip. Almost 80% of the domestic cats responded to silver vine and about 50% to Tatarian honeysuckle and valerian root. Although cats predominantly responded to fruit galls of the silver vine plant, some also responded positively to its wood. Of the cats that did not respond to catnip, almost 75% did respond to silver vine and about one out of three to Tatarian honeysuckle. Unlike domestic cats, tigers were either not interested in silver vine or responded disapprovingly. The amount of nepetalactone was highest in catnip and only present at marginal levels in the other plants. Silver vine contained the highest concentrations of all other compounds tested. Olfactory enrichment for cats may have great potential. Silver vine powder from dried fruit galls and catnip were most popular among domestic cats. Silver vine and Tatarian honeysuckle appear to be good alternatives to catnip for domestic cats that do not respond to catnip.

Malaria, caused by Plasmodium parasites, still contributes to a high global burden of disease, mainly in children under 5 years of age. Chronic and recurrent Plasmodium infections affect the development of B cell memory against the parasite and promote the accumulation of atypical memory B cells (atMBCs), which have an unclear function in the immune response.

SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n = 8) or severe (n = 5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG⁺ B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG⁺ B cells showed increased expression of markers associated with durable B cell memory, including T-bet and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet⁺ spike-specific IgG⁺ B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet⁺ IgG⁺ memory B cells decreased to baseline levels. Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

AIDS develops typically after 7–11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.