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When a global pandemic hits during a longitudinal study of biology student success, researchers can unearth rich information about student resilience. By sharing case studies from two demographically different midsized 4-year institutions, this article illustrates the aspects of student self-efficacy beliefs that were undercut by the shift to emergency remote instruction (ERI) in introductory biology courses in Spring 2020: agency and belonging. By assessing student predictions of exam performance and analyzing themes from 276 student narrative surveys, we highlight the power of a careful balance between cognitive and social interventions to help students recover. Students in this study showed a 50% loss of efficacy beliefs after ERI (midsemester) but were able to improve to at least 75% above starting efficacy beliefs after instructor interventions. Thus, we also show how academic efficacy is highly malleable and is mediated in relationships. In turn, we demonstrate a new assessment model that uses student narrative writing to reveal "invisible" threats to students' perceptions of their capacity to succeed. Finally, we generalize from their findings to provide recommendations for effective strategies for supporting those students for whom every semester feels like a pandemic.

Trichomonas vaginalis causes the most common, nonviral sexually transmitted infection. Only metronidazole (Mz) and tinidazole are approved for treating trichomoniasis, yet resistance is a clinical problem. The gold(I) complex, auranofin, is active against T. vaginalis and other protozoa but has significant human toxicity. In a systematic structure-activity exploration, we show here that diversification of gold(I) complexes, particularly as halides with simple C1-C3 trialkyl phosphines or as bistrialkyl phosphine complexes, can markedly improve potency against T. vaginalis and selectivity over human cells compared to that of the existing antirheumatic gold(I) drugs. All gold(I) complexes inhibited the two most abundant isoforms of the presumed target enzyme, thioredoxin reductase, but a subset of compounds were markedly more active against live T. vaginalis than the enzyme, suggesting that alternative targets exist. Furthermore, all tested gold(I) complexes acted independently of Mz and were able to overcome Mz resistance, making them candidates for the treatment of Mz-refractory trichomoniasis.

When a global pandemic hits during a longitudinal study of biology student success, researchers can unearth rich information about student resilience. By sharing case studies from two demographically different midsized 4-year institutions, this article illustrates the aspects of student self-efficacy beliefs that were undercut by the shift to emergency remote instruction (ERI) in introductory biology courses in Spring 2020: agency and belonging. By assessing student predictions of exam performance and analyzing themes from 276 student narrative surveys, we highlight the power of a careful balance between cognitive and social interventions to help students recover. Students in this study showed a 50% loss of efficacy beliefs after ERI (midsemester) but were able to improve to at least 75% above starting efficacy beliefs after instructor interventions. Thus, we also show how academic efficacy is highly malleable and is mediated in relationships. In turn, we demonstrate a new assessment model that uses student narrative writing to reveal "invisible" threats to students' perceptions of their capacity to succeed. Finally, we generalize from their findings to provide recommendations for effective strategies for supporting those students for whom every semester feels like a pandemic.

In response to calls for pedagogical reforms in undergraduate biology courses to decrease student attrition rates and increase active learning, this article describes one faculty member's conversion from traditional teaching methods to more engaging forms of practice. Partially told as a narrative, this article illustrates a.) the way many faculty initially learn to teach by modeling the pedagogy from their own undergraduate programs; b.) the kind of support biology faculty may need to break out of traditional molds; c.) how writing can promote active learning; and d.) the impact of reformed pedagogy on student levels of engagement. The latter will be demonstrated through assessment results gathered from student surveys, reflective writing, and focus group interview. Ultimately, the study challenges misunderstandings some faculty might have regarding the value of writing in science classes and offers inspiration, urging critical reflection and persistence.

Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated "chemosensitization" as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen Aspergillus fumigatus. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.

The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection.

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common, non-viral, sexually transmitted infection in the world, but only two closely related nitro drugs are approved for its treatment. New antimicrobials against trichomoniasis remain an urgent need. Several organic gold compounds were tested for activity against T. vaginalis thioredoxin reductase (TrxR) in cell-free systems as well as for activity against different trichomonads in vitro and in a murine infection model. The organic gold(I) compounds auranofin and chloro(diethylphenylphosphine)gold(I) inhibited TrxR in a concentration-dependent manner in assays with recombinant purified reductase and in cytoplasmic extracts of T. vaginalis transfected with a haemagglutinin epitope-tagged form of the reductase. Auranofin potently suppressed the growth of three independent clinical T. vaginalis isolates as well as several strains of another trichomonad (Tritrichomonas foetus) in a 24 h-assay, with 50% inhibitory concentrations of 0.7-2.5 µM and minimum lethal concentrations of 2-6 µM. The drug also compromised the ability of the parasite to overcome oxidant stress, supporting the notion that auranofin acts, in part, by inactivating TrxR-dependent antioxidant defences. Chloro(diethylphenylphosphine)gold(I) was 10-fold less effective against T. vaginalis in vitro than auranofin. Oral administration of auranofin for 4 days cleared the parasites in a murine model of vaginal T. foetus infection without displaying any apparent adverse effects. The approved human drug auranofin may be a promising agent as an alternative treatment of trichomoniasis in cases when standard nitro drug therapies have failed.

Trichomonas gallinae is a ubiquitous flagellated protozoan parasite, and the most common etiologic agent of epidemic trichomonosis in columbid and passerine species. In this study, free-ranging Pacific Coast band-tailed pigeons (Patagioenas fasciata monilis) in California (USA) were found to be infected with trichomonad protozoa that were genetically and morphologically distinct from T. gallinae. In microscopic analysis, protozoa were significantly smaller in length and width than T. gallinae and were bimodal in morphology. Phylogenetic analysis of the ITS1/5.8S/ITS2, rpb1, and hydrogenosomal Fe-hydrogenase regions revealed that the protozoan shares an ancestor with Trichomonas vaginalis, the sexually-transmitted agent of trichomoniasis in humans. Clinical and pathologic features of infected birds were similar to infections with T. gallinae. Evidence presented here strongly support taxonomical distinction of this parasite, which we hereby name Trichomonas stableri n. sp. This work contributes to a growing body of evidence that T. gallinae is not the sole etiologic agent of avian trichomonosis, and that the incorporation of molecular tools is critical in the investigation of infectious causes of mortality in birds.

Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium parvum, can stunt infant growth and can be lethal in immunocompromised individuals. The most widely used drugs for treating cryptosporidiosis are nitazoxanide and paromomycin, although both exhibit limited efficacy. To investigate an alternative approach to therapy, we demonstrate that the clan CA cysteine protease inhibitor N-methyl piperazine-Phe-homoPhe-vinylsulfone phenyl (K11777) inhibits C. parvum growth in mammalian cell lines in a concentration-dependent manner. Further, using the C57BL/6 gamma interferon receptor knockout (IFN-γR-KO) mouse model, which is highly susceptible to C. parvum, oral or intraperitoneal treatment with K11777 for 10 days rescued mice from otherwise lethal infections. Histologic examination of untreated mice showed intestinal inflammation, villous blunting, and abundant intracellular parasite stages. In contrast, K11777-treated mice (210 mg/kg of body weight/day) showed only minimal inflammation and no epithelial changes. Three putative protease targets (termed cryptopains 1 to 3, or CpaCATL-1, -2, and -3) were identified in the C. parvum genome, but only two are transcribed in infected mammals. A homology model predicted that K11777 would bind to cryptopain 1. Recombinant enzymatically active cryptopain 1 was successfully targeted by K11777 in a competition assay with a labeled active-site-directed probe. K11777 exhibited no toxicity in vitro and in vivo, and surviving animals remained free of parasites 3 weeks after treatment. The discovery that a cysteine protease inhibitor provides potent anticryptosporidial activity in an animal model of infection encourages the investigation and development of this biocide class as a new, and urgently needed, chemotherapy for cryptosporidiosis.

Introductory science, math, and engineering courses often have problems related to student engagement, achievement, and course completion. To begin examining these issues in greater depth, this pilot study compared student engagement, achievement, and course completion in a small and large section of an introductory biology class. Results based on t-tests indicate that students in the small section of the course were more engaged and had higher achievement scores than students in the large section. Additionally, students in the small section were more likely to complete the course than students in the large section. Although further research is needed, reduced class size has the potential to be an effective strategy for improving student engagement, achievement, and course completion in an introductory biology course that has too often been a gatekeeper instead of a gateway for students who intend to be science, technology, engineering, and math majors.

Introductory biology courses are supposed to serve as gateways for many majors, but too often they serve instead as gatekeepers. Reliance on lectures, large classes, and multiple-choice tests results in high drop and failure rates. Critiques of undergraduate science education are clear about the problems with conventional introductory science courses, and yet the problems persist. As David Hanauer and Cynthia Bauerle explain, "Given the potential for science to address important problems, undergraduate programs ought to be functioning as busy portals for engaging students' innate fascination and developing their understanding of the nature and practice of science. Instead, recent studies suggest, the opposite is true: over half of the students who enter college with an interest in science do not persist in their training beyond the first year or two of introductory coursework." Researchers and expert practitioners have long proposed using student-centered, active learning strategies to improve engagement, learning, and achievement. Others have documented the ways class size is important for student-centered pedagogy. Following Hanauer and Bauerle, who recommend using assessment reform to facilitate such curricular innovations, the authors contend that the better the assessment and the more focused the guidance provided to the instructor, the greater the leverage. This article presents findings from a pilot study suggesting that authentic assessment embedded in best teaching practices can show what kind of change is needed. The study allowed the authors to observe the relative impacts of both class size and the use of writing as an assessment strategy, and thus to identify the sequence reform efforts must take. The purposes of this article are, first, to report on the experience responding to Hanauer and Bauerle's call, and second, to identify the key components that gave that "reform lever" additional power: the careful selection and preliminary testing of essay questions requiring critical thinking, the reduced size of one section of an entry-level biology course, the support of a networked improvement community, and guidance for the instructor during the testing of new methods.