A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome

<i>Trypanosoma brucei</i> is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other <i>catarrhine</i> primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of <i>T. Brucei</i> have evolved specific mechanisms to overcome this innate resistance, <i>Trypanosoma brucei gambiense</i> and <i>Trypanosoma brucei rhodesiense</i>. In <i>T. b. Rhodesiense</i>, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of <i>T. b. Gambiense</i> is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, <i>T. b. Gambiense</i>-specific glycoprotein <i>(TgsGP)</i>. In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by <i>T. b. Gambiense</i> and <i>T. b. Rhodesiense</i>, with several populations of humans and primates displaying resistance to infection by these two sub-species

Haptoglobin-hemoglobin receptor independent killing of African trypanosomes by human serum and trypanosome lytic factors

The haptoglobin-hemoglobin receptor (HpHbR) of African trypanosomes plays a critical role in human innate immunity against these parasites. Localized to the flagellar pocket of the veterinary pathogen Trypanosoma brucei brucei this receptor binds Trypanosome Lytic Factor-1 (TLF-1), a subclass of human high-density lipoprotein (HDL) facilitating endocytosis, lysosomal trafficking and subsequent killing. Recently, we found that group 1 Trypanosoma brucei gambiense does not express a functional HpHbR. We now show that loss of the TbbHpHbR reduces the susceptibility of T. b. brucei to human serum and TLF-1 by 100- and 10,000-fold, respectively. The relatively high concentrations of human serum and TLF-1 needed to kill trypanosomes lacking the HpHbR indicates that high affinity TbbHpHbR binding enhances the cytotoxicity; however, in the absence of TbbHpHbR, other receptors or fluid phase endocytosis are sufficient to provide some level of susceptibility. Human serum contains a second innate immune factor, TLF-2, that has been suggested to kill trypanosomes independently of the TbbHpHbR. We found that T. b. brucei killing by TLF-2 was reduced in TbbHpHbR-deficient cells but to a lesser extent than TLF-1. This suggests that both TLF-1 and TLF-2 can be taken up via the TbbHpHbR but that alternative pathways exist for the uptake of these toxins. Together the findings reported here extend our previously published studies and suggest that group 1 T. b. gambiense has evolved multiple mechanisms to avoid killing by trypanolytic human serum factors

Imposter syndrome in academic libraries: Indigenous women edition

This is a written proceeding of the LACUNY 2022 panel presentation “Imposter Syndrome in Academic Libraries: Indigenous Women Edition”. The authors discuss personal instances and feelings of the imposter phenomenon (also known as imposter syndrome) as it may relate to their Indigenous identities. Additionally, the authors describe how imposter syndrome may affect their ability to be successful in their careers, and the internal pressure they feel to present a more Indigenous identity (whatever that may entail) for scholarship and positions. The authors also share their experiences with external pressures to exhibit a more “stereotypical Indigenous” appearance for the sake of their role as Indigenous library staff members, peers, or when applying for academic opportunities and how this relates when interacting with other Indigenous people through their work. They speak on the recent developments in academia in terms of hiring Indigenous peoples and avoiding pretendians (people who falsely claim to have Indigenous ancestry). The goal of the authors is to encourage discourse in the vein of Truth and Reconciliation and spreading awareness about imposter syndrome

Comparative phosphoproteomic analysis of the mouse testis reveals changes in phosphopeptide abundance in response to Ppp1cc deletion

AbstractMale Ppp1cc knockout mice are infertile due to failure of spermatogenesis, thought to arise from a deficiency of the predominant testis isoform PPP1CC2. We hypothesize that substrates of the PPP1CC2 will be hyperphosphorylated in Ppp1cc mutant testes. Quantitative RT-PCR and histological data suggest a role for PPP1CC2 by 3 weeks of age in the testis. Comparative phosphoproteomic analysis identified 828 proteins phosphorylated in the 3 week mouse testis, and confidently assigned 1026 unique phosphorylation sites. Thirty-two peptides corresponding to 30 proteins were found to be more abundant in Ppp1cc mutant samples than in wild-type, representing candidate substrates of PPP1CC2

Public Understanding and Knowledge of Rip Currents and Beach Safety in the UK

Rip currents present a severe hazard for water users on beaches and account for the greatest cause of lifeguard rescues worldwide. The physical dynamics of rip currents are well studied, and more recently, the social and behavioural science research surrounding human interaction of rip currents has been expanding, providing a social perspective and feeding into public education strategies. The aim of this study was to assess levels of public understanding of rip currents and beach safety on UK beaches. A questionnaire was undertaken (N = 407) during the summer of 2012 on four beaches. Beach users had a poor knowledge of rip currents (n = 263), but those who have been caught in a rip have a higher level of knowledge. Conversely, beach users had a good understanding of what the beach safety flags indicated (n = 314), and most people complied with this flag system (n = 339). In addition, people previously educated on rip currents had a higher knowledge, and lifeguards proved to be the most effective form of education. The study presents an insight into UK beach users’ knowledge of rip currents and provides more evidence with which to pilot a rip current education scheme within the UK

Novel African trypanocidal agents: membrane rigidifying peptides

The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analysis of lipid-associated peptide suggests a mechanism of phospholipid clamping in which an internal hydrophobic bulge anchors the peptide in the membrane and positively charged moieties at the termini coordinate phosphates of the polar lipid headgroups. This mechanism reveals a necessary phenotype in bloodstream form African trypanosomes, high membrane fluidity, and we suggest that targeting the plasma membrane lipid bilayer as a whole may be a novel strategy for the development of new pharmaceutical agents. Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes

Public Understanding and Knowledge of Rip Currents and Beach Safety

Rip currents present a severe hazard for water users on beaches and account for the greatest cause of lifeguard rescues worldwide. The physical dynamics of rip currents are well studied, and more recently, the social and behavioural science research surrounding human interaction of rip currents has been expanding, providing a social perspective and feeding into public education strategies. The aim of this study was to assess levels of public understanding of rip currents and beach safety on UK beaches. A questionnaire was undertaken (N = 407) during the summer of 2012 on four beaches. Beach users had a poor knowledge of rip currents (n = 263), but those who have been caught in a rip have a higher level of knowledge. Conversely, beach users had a good understanding of what the beach safety flags indicated (n = 314), and most people complied with this flag system (n = 339). In addition, people previously educated on rip currents had a higher knowledge, and lifeguards proved to be the most effective form of education. The study presents an insight into UK beach users’ knowledge of rip currents and provides more evidence with which to pilot a rip current education scheme within the UK