Inefficacy of mallard flight responses to approaching vehicles.

Vehicle collisions with birds are financially costly and dangerous to humans and animals. To reduce collisions, it is necessary to understand how birds respond to approaching vehicles. We used simulated (i.e., animals exposed to video playback) and real vehicle approaches with mallards (Anas platyrynchos) to quantify flight behavior and probability of collision under different vehicle speeds and times of day (day vs. night). Birds exposed to simulated nighttime approaches exhibited reduced probability of attempting escape, but when escape was attempted, fled with more time before collision compared to birds exposed to simulated daytime approaches. The lower probability of flight may indicate that the visual stimulus of vehicle approaches at night (i.e., looming headlights) is perceived as less threatening than when the full vehicle is more visible during the day; alternatively, the mallard visual system might be incompatible with vehicle lighting in dark settings. Mallards approached by a real vehicle exhibited a delayed margin of safety (both flight initiation distance and time before collision decreased with speed); they are the first bird species found to exhibit this response to vehicle approach. Our findings suggest mallards are poorly equipped to adequately respond to fast-moving vehicles and demonstrate the need for continued research into methods promoting effective avian avoidance behaviors.

Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.

The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against Treponema pallidum (TPA), we used Pyrococcus furiosus thioredoxin (PfTrx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded ß-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant. Rabbits and mice immunized with these five PfTrx constructs produced ECL-specific Abs that promoted opsonophagocytosis of TPA by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. ECL-specific rabbit and mouse Abs also impaired viability, motility, and cellular attachment of spirochetes during in vitro cultivation. The results support the use of ECL-based vaccines and suggest that ECL-specific Abs promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms.

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis.

Cancer initiates as a consequence of genomic mutations and its subsequent progression relies in part on increased production of ribosomes to maintain high levels of protein synthesis for unchecked cell growth. Recently, cytidine deaminases have been uncovered as sources of mutagenesis in cancer. In an attempt to form a connection between these 2 cancer driving processes, we interrogated the cytidine deaminase family of proteins for potential roles in human ribosome biogenesis. We identified and validated APOBEC3A and APOBEC4 as novel ribosome biogenesis factors through our laboratory's established screening platform for the discovery of regulators of nucleolar function in MCF10A cells. Through siRNA depletion experiments, we highlight APOBEC3A's requirement in making ribosomes and specific role within the processing and maturation steps that form the large subunit 5.8S and 28S ribosomal (r)RNAs. We demonstrate that a subset of APOBEC3A resides within the nucleolus and associates with critical ribosome biogenesis factors. Mechanistic insight was revealed by transient overexpression of both wild-type and a catalytically dead mutated APOBEC3A, which both increase cell growth and protein synthesis. Through an innovative nuclear RNA sequencing methodology, we identify only modest predicted APOBEC3A C-to-U target sites on the pre-rRNA and pre-mRNAs. Our work reveals a potential direct role for APOBEC3A in ribosome biogenesis likely independent of its editing function. More broadly, we found an additional function of APOBEC3A in cancer pathology through its function in ribosome biogenesis, expanding its relevance as a target for cancer therapeutics.

Association of Daily Step Count and Postoperative Complication among All of Us Research Participants.

BACKGROUND: The association between preoperative wearable device step counts and surgical outcomes has not been examined using commercial devices linked to electronic health records (EHR). This study measured the association between daily preoperative step counts and postoperative complications. STUDY DESIGN: Data was obtained using the All of Us (AOU) Research program, a nationwide initiative to collect EHR and health-related data from the population. Included were patients who underwent a surgical procedure included in the National Surgical Quality Improvement Program (NSQIP) targeted procedures dataset. Excluded were patients who did not have available physical activity FitBit data. Primary outcome was the development of a postoperative complication. All analyses were performed in the AOU researcher workbench. RESULTS: Of 27,150 patients who underwent a surgical procedure, 475 participants with preoperative wearable data were included. 74.7% were female and 85.2% were White. The average age was 57.2 years. The overall rate of postoperative complications was 12.6%. Patients averaging fewer than 7,500 daily steps were at increased odds for developing a postoperative complication (OR 1.83, 95% CI [1.01, 3.31]). Following adjustment for age, sex, race, comorbid disease, body mass index (BMI), and relative procedure risk, patients with a baseline average steps/day < 7,500 were at increased odds for postoperative complication (aOR = 2.06, 95% CI [1.05, 4.06]). CONCLUSIONS: This study found an increase in overall postoperative complication rate in patients recording lower average preoperative step counts. Patients with a baseline of less than 7,500 steps per day had increased odds of postoperative complications in this cohort. This data supports the use of wearable devices for surgical risk stratification and suggests step count may measure preoperative fitness.

Novel induction of broad-spectrum antibiotics by the human pathogen Legionella.

The majority of antibiotics are natural products, with microorganism-generated molecules and their derivatives being the most prevalent source of drugs to treat infections. Thus, identifying natural products remains the most valuable resource for novel therapeutics. Here, we report the discovery of a series of dormant bacteria in honey that have bactericidal activity toward Legionella, a bacterial pathogen that causes respiratory disease in humans. We show that, in response to bacterial products secreted by Legionella, the honey bacteria release diffusible antimicrobial molecules. Remarkably, the honey bacteria only produce these molecules in response to Legionella spp., when compared to a panel of 24 bacterial pathogens from different genera. However, the molecules induced by Legionella have broad activity against several clinically important pathogens, including many high-priority pathogens. Thus, Legionella spp. are potent drivers of antimicrobial molecule production by uncharacterized bacteria isolated from honey, providing access to new antimicrobial products and an unprecedented strategy for discovering novel antibiotics. IMPORTANCE: Natural products generated by microorganisms remain the most viable and abundant source of new antibiotics. However, their discovery depends on the ability to isolate and culture the producing organisms and to identify conditions that promote antibiotic production. Here, we identify a series of previously undescribed bacteria isolated from raw honey and specific culture conditions that induce the production of antimicrobial molecules that are active against a wide variety of pathogenic bacteria.

Barriers and facilitators to uptake and persistence on prep among key populations in Southern Province, Zambia: a thematic analysis.

BACKGROUND: Especially in high HIV prevalence contexts, such as Zambia, effective biomedical prevention tools are needed for priority populations (PPs), including key populations (KPs), who are at higher risk. HIV pre-exposure prophylaxis (PrEP) has been scaled up nationally in Zambia, but little is known about barriers to PrEP use among specific PPs to date. METHODS: To understand barriers and facilitators to PrEP use in Zambia, we conducted a qualitative case study of PrEP services to PPs including sero-discordant couples (SDCs), female sex workers (FSWs), and men who have sex with men (MSM) in Livingstone. The study conducted in 2021 included in-depth interviews (n = 43) guided by the socio-ecological model, and focus group discussions (n = 4) with clinic and community-based providers and PrEP-eligible clients including users and non-users across PP groups. We used thematic analysis to analyze data using codes derived both deductively and inductively. RESULTS: We found multilevel barriers and facilitators to PrEP use. Cross-cutting barriers shared across PP groups included amplifying effects of PrEP being mistaken for antiretroviral drugs used to treat HIV, including anticipated stigma, and concerns about side-effects based on both misinformation and experience. In addition, stigmatized identities, particularly that of MSM, served as a barrier to PrEP use. The fear of being mislabeled as having HIV was of greatest concern for FSWs. Facilitators to PrEP use primarily included the importance of confidential, KP-sensitive services, and the role of informed, supportive family, friends, and peers. Participants across all PP groups urged expanded education efforts to increase awareness of PrEP within the general population toward mitigating concerns of being mislabeled as living with HIV. CONCLUSION: To our knowledge, this is the first qualitative study of the PrEP cascade among multiple PPs in Zambia. This study provides important explanation for the low rates of PrEP continuation found in earlier demonstration trials among KPs in Zambia. The study also offers recommendations for programming efforts going forward such as inclusive PrEP awareness campaigns, expanded KP sensitivity training, and related efforts to thwart PrEP stigma while expanding access.

As human societies urbanize, so does ecology; taxonomic, geographic, and other research trends in urban vertebrate ecology.

The threat to biodiversity posed by urban expansion is well researched and supported. Since the late 1990s, the field of urban ecology has been expanding along with the developed landscapes it studies. Past reviews have shown unequal publication rates in urban ecology literature for taxonomic groups and research locations. Herein, we explore differences in the publication rate of urban studies by vertebrate groups, but also expand on previous investigations by broadening the scope of the literature searched, exploring trends in subtopics within the urban wildlife literature, identifying geographic patterns of such publications, and comparing the rate at which non-native and threatened and endangered species are studied in urban settings. We used linear and segmented regression to assess publication rates and Fisher's exact tests for comparisons between groups. All vertebrate groups show an increasing proportion of urban studies through time, with urban avian studies accelerating most sharply and herpetofauna appearing to be understudied. Non-native mammals are more studied than non-native birds, and threatened and endangered herpetofauna and mammals are more likely to be studied than threatened and endangered birds in urban areas. The plurality of urban wildlife studies are found in North America, while there is a dearth of studies from Africa, Asia, and South America. Our results can help inform decisions of urban ecologists on how to better fill in knowledge gaps and bring a greater degree of equity into the field.

Targeted recreational hunting can reduce animal-vehicle collisions and generate substantial revenue for wildlife management agencies.

Reduction of conflicts arising from human-wildlife interactions is necessary for coexistence. Collisions between animals and automobiles cost the world's economy billions of dollars, and wildlife management agencies often are responsible for reducing wildlife-vehicle collisions. But wildlife agencies have few proven options for reducing wildlife-vehicle collisions that are effective and financially feasible at large spatiotemporal scales germane to management. Recreational hunting by humans is a primary population management tool available for use with abundant wild ungulates that often collide with automobiles. Therefore, we tested how well policies designed to increase human hunting of deer (longer hunting seasons and increased harvest limits) reduced collisions between white-tailed deer and automobiles along 618 km of high-risk roadways in Indiana, USA. We used a 20-y dataset that compiled >300,000 deer-vehicle collisions. Targeted recreational hunting decreased deer-vehicle collisions by 21.12 % and saved society up to $653,756 (95 % CIs = $286,063-$1,154,118) in economic damages from 2018 to 2022. Potential savings was up to $1,265,694 (95 % CIs = $579,108-$2,402,813) during the same 5-y span if relaxed hunting regulations occurred along all high-risk roadways. Moreover, license sales from targeted hunting generated $206,268 in revenue for wildlife management. Targeted hunting is likely effective in other systems where ungulate-vehicle collisions are prevalent, as behavioral changes in response to human hunting has been documented in many ungulate species across several continents. Our methods are attractive for management agencies with limited funds, as relaxed hunting regulations are relatively inexpensive to implement and may generate substantial additional revenue.

Humidity determines penetrance of a latitudinal gradient in genetic selection on the microbiota by Drosophila melanogaster.

The fruit fly Drosophila melanogaster is a model for understanding how hosts and their microbial partners interact as the host adapts to wild environments. These interactions are readily interrogated because of the low taxonomic and numeric complexity of the flies' bacterial communities. Previous work has established that host genotype, the environment, diet, and interspecies microbial interactions can all influence host fitness and microbiota composition, but the specific processes and characters mediating these processes are incompletely understood. Here, we compared the variation in microbiota composition between wild-derived fly populations when flies could choose between the microorganisms in their diets and when flies were reared under environmental perturbation (different humidities). We also compared the colonization of the resident and transient microorganisms. We show that the ability to choose between microorganisms in the diet and the environmental condition of the flies can influence the relative abundance of the microbiota. There were also key differences in the abundances of the resident and transient microbiota. However, the microbiota only differed between populations when the flies were reared at humidities at or above 50% relative humidity. We also show that elevated humidity determined the penetrance of a gradient in host genetic selection on the microbiota that is associated with the latitude the flies were collected from. Finally, we show that the treatment-dependent variation in microbiota composition is associated with variation in host stress survival. Together, these findings emphasize that host genetic selection on the microbiota composition of a model animal host can be patterned with the source geography, and that such variation has the potential to influence their survival in the wild. Importance: The fruit fly Drosophila melanogaster is a model for understanding how hosts and their microbial partners interact as hosts adapt in wild environments. Our understanding of what causes geographic variation in the fruit fly microbiota remains incomplete. Previous work has shown that the D. melanogaster microbiota has relatively low numerical and taxonomic complexity. Variation in the fly microbiota composition can be attributed to environmental characters and host genetic variation, and variation in microbiota composition can be patterned with the source location of the flies. In this work we explored three possible causes of patterned variation in microbiota composition. We show that host feeding choices, the host niche colonized by the bacteria, and a single environmental character can all contribute to variation in microbiota composition. We also show that penetrance of latitudinally-patterned host genetic selection is only observed at elevated humidities. Together, these results identify several factors that influence microbiota composition in wild fly genotypes and emphasize the interplay between environmental and host genetic factors in determining the microbiota composition of these model hosts.