The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers

Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown. Among other Aspergilli, it is known that A. flavus has a moderately high recombination rate with an average of 4.2 crossovers per chromosome pair, whereas A. nidulans has in contrast a higher rate with 9.3 crossovers per chromosome pair. Here, we show in a cross between A. fumigatus strains that they produce an average of 29.9 crossovers per chromosome pair and large variation in total map length across additional strain crosses. This rate of crossovers per chromosome is more than twice that seen for any known organism, which we discuss in relation to other genetic model systems. We validate this high rate of crossovers through mapping of resistance to the laboratory antifungal acriflavine by using standing variation in an undescribed ABC efflux transporter. We then demonstrate that this rate of crossovers is sufficient to produce one of the common multidrug resistant haplotypes found in the cyp51A gene (TR34/L98H) in crosses among parents harboring either of 2 nearby genetic variants, possibly explaining the early spread of such haplotypes. Our results suggest that genomic studies in this species should reassess common assumptions about linkage between genetic regions. The finding of an unparalleled crossover rate in A. fumigatus provides opportunities to understand why these rates are not generally higher in other eukaryotes

Efficient Generation of Germ Line Transmitting Chimeras from C57BL/6N ES Cells by Aggregation with Outbred Host Embryos

Genetically modified mouse strains derived from embryonic stem (ES) cells have become essential tools for functional genomics and biomedical research. Large scale mutagenesis projects are producing libraries of mutant C57BL/6 (B6) ES cells to enable the functional annotation of every gene of the mouse genome. To realize the utility of these resources, efficient and accessible methods of generating mutant mice from these ES cells are necessary. Here, we describe a combination of ICR morula aggregation and a chemically-defined culture medium with widely available and accessible components for the high efficiency generation of germline transmitting chimeras from C57BL/6N ES cells. Together these methods will ease the access of the broader biomedical research community to the publicly available B6 ES cell resources

Eating and conserving bushmeat in Africa

In Africa, overhunting of tropical wildlife for food remains an intractable issue. Donors and governments remain committed to invest in efforts to both conserve and allow the sustainable use of wildlife. Four principal barriers need to be overcome: (i) communities are not motivated to conserve wildlife long-term because they have no formal rights to benefit from wildlife, or to exclude others from taking it on their land; (ii) multispecies harvests, typical of bushmeat hunting scenarios, place large-bodied species at risk of extinction; (iii) wildlife production cannot expand, in the same way that livestock farming can, to meet the expected growth in consumer demand; and (iv) wildlife habitat is lost through conversion to agriculture, housing, transportation networks and extractive industries. In this review, we examine the actors involved in the use of wildlife as food and discuss the possible solutions required to address urban and rural bushmeat consumption. Interventions must tackle use and conservation of wildlife through the application of context-relevant interventions in a variety of geographies across Africa. That said, for any bushmeat solution to work, there needs to be concurrent and comparable investment in strengthening the effectiveness of protected area management and enforcement of wildlife conservation laws

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T&gt;G and c.3113G&gt;A, CHEK2c.349A&gt;G, c.538C&gt;T, c.715G&gt;A, c.1036C&gt;T, c.1312G&gt;T, and c.1343T&gt;G and ATM c.7271T&gt;G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G&gt;A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T&gt;G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A&gt;G OR 2.26 (95% CI 1.29 to 3.95), c.1036C&gt;T OR 5.06 (95% CI 1.09 to 23.5) and c.538C&gt;T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T&gt;G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G&gt;T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.</p

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties

Sex Bias and Social Influences on Savanna Chimpanzee (Pan troglodytes verus) Nest Building Behavior

Many primates show sex differences in behavior, particularly social behavior, but also tool use for extractive foraging. All great apes learn to build a supportive structure for sleep. Whether sex differences exist in building, as in extractive foraging, is unknown, and little is known about how building skills develop and vary between individuals in the wild. We therefore aimed to describe the nesting behavior of savanna chimpanzees (Pan troglodytes verus) in Fongoli, Senegal, to provide comparative data and to investigate possible sex or age differences in nest building behaviors and nest characteristics. We followed chimpanzee groups to their night nesting sites to record group (55 nights) and individual level data (17 individuals) on nest building initiation and duration (57 nests) during the dry season between October 2007 and March 2008. We returned the following morning to record nest and tree characteristics (71 nests built by 25 individuals). Fongoli chimpanzees nested later than reported for other great apes, but no sex differences in initiating building emerged. Observations were limited but suggest adult females and immature males to nest higher, in larger trees than adult males, and adult females to take longer to build than either adult or immature males. Smaller females and immature males may avoid predation or access thinner, malleable branches, by nesting higher than adult males. These differences suggest that sex differences described for chimpanzee tool use may extend to nest-building, with females investing more time and effort in constructing a safe, warm structure for sleep than males do

Polymorphisms in CYP17 and CYP3A4 and Prostate Cancer in Men of African Descent

Geneeskunde en GesondheidswetenskappeUrologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]