Applying MALDI-TOF MS to resolve morphologic and genetic similarities between two Dermacentor tick species of public health importance.

Hard ticks (Acari: Ixodidae) have been historically identified by morphological methods which require highly specialized expertise and more recently by DNA-based molecular assays that involve high costs. Although both approaches provide complementary data for tick identification, each method has limitations which restrict their use on large-scale settings such as regional or national tick surveillance programs. To overcome those obstacles, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been introduced as a cost-efficient method for the identification of various organisms, as it balances performance, speed, and high data output. Here we describe the use of this technology to validate the distinction of two closely related Dermacentor tick species based on the development of the first nationwide MALDI-TOF MS reference database described to date. The dataset obtained from this protein-based approach confirms that tick specimens collected from United States regions west of the Rocky Mountains and identified previously as Dermacentor variabilis are the recently described species, Dermacentor similis. Therefore, we propose that this integrative taxonomic tool can facilitate vector and vector-borne pathogen surveillance programs in the United States and elsewhere.

Open Capsular Repair with Dermal allograft and tarsal tunnel release in the treatment of Tarsal Tunnel Syndrome in a Young Collegiate Athlete: A Case Report.

Tarsal tunnel syndrome is an entrapment neuropathy of the posterior tibial nerve beneath the flexor retinaculum that can be precipitated by either intrinsic or extrinsic factors. We report a unique case of a posterior medial ankle joint capsular defect with localized fluid extravasation between the flexor digitorum longus and flexor hallucis longus leading to symptoms consistent with tarsal tunnel syndrome in a collegiate tennis player. This patient is a 19-year-old female with no past medical history who presented with symptoms consistent with tarsal tunnel syndrome. After confirmation with magnetic resonance imaging, the patient underwent capsular reconstruction with dermal allograft in combination with a tarsal tunnel release. The patient had improvement in pain and recovery of paresthesia 3 months postoperatively. At the latest follow-up of 1 year postoperatively, the patient has not had a recurrence of symptoms and has returned to the same level of competitive play. Many different causes of tarsal tunnel syndrome are described in the literature, but to our knowledge, there is no current literature that describes a defect in the tibiotalar joint capsule as a cause of tarsal tunnel syndrome.

Symbiotic bacteria and fungi proliferate in diapause and may enhance overwintering survival in a solitary bee.

Host-microbe interactions underlie the development and fitness of many macroorganisms, including bees. Whereas many social bees benefit from vertically transmitted gut bacteria, current data suggests that solitary bees, which comprise the vast majority of species diversity within bees, lack a highly specialized gut microbiome. Here, we examine the composition and abundance of bacteria and fungi throughout the complete life cycle of the ground-nesting solitary bee Anthophora bomboides standfordiana. In contrast to expectations, immature bee stages maintain a distinct core microbiome consisting of Actinobacterial genera (Streptomyces, Nocardiodes) and the fungus Moniliella spathulata. Dormant (diapausing) larval bees hosted the most abundant and distinctive bacteria and fungi, attaining 33 and 52 times their initial copy number, respectively. We tested two adaptive hypotheses regarding microbial functions for diapausing bees. First, using isolated bacteria and fungi, we found that Streptomyces from brood cells inhibited the growth of multiple pathogenic filamentous fungi, suggesting a role in pathogen protection during overwintering, when bees face high pathogen pressure. Second, sugar alcohol composition changed in tandem with major changes in fungal abundance, suggesting links with bee cold tolerance or overwintering biology. We find that A. bomboides hosts a conserved core microbiome that may provide key fitness advantages through larval development and diapause, which raises the question of how this microbiome is maintained and faithfully transmitted between generations. Our results suggest that focus on microbiomes of mature or active insect developmental stages may overlook stage-specific symbionts and microbial fitness contributions during host dormancy.

Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Grouped mixtures of air pollutants and seasonal temperature anomalies and cardiovascular hospitalizations among U.S. Residents.

BACKGROUND: Air pollution is a recognized risk factor for cardiovascular disease (CVD). Temperature is also linked to CVD, with a primary focus on acute effects. Despite the close relationship between air pollution and temperature, their health effects are often examined separately, potentially overlooking their synergistic effects. Moreover, fewer studies have performed mixture analysis for multiple co-exposures, essential for adjusting confounding effects among them and assessing both cumulative and individual effects. METHODS: We obtained hospitalization records for residents of 14 U.S. states, spanning 2000-2016, from the Health Cost and Utilization Project State Inpatient Databases. We used a grouped weighted quantile sum regression, a novel approach for mixture analysis, to simultaneously evaluate cumulative and individual associations of annual exposures to four grouped mixtures: air pollutants (elemental carbon, ammonium, nitrate, organic carbon, sulfate, nitrogen dioxide, ozone), differences between summer and winter temperature means and their long-term averages during the entire study period (i.e., summer and winter temperature mean anomalies), differences between summer and winter temperature standard deviations (SD) and their long-term averages during the entire study period (i.e., summer and winter temperature SD anomalies), and interaction terms between air pollutants and summer and winter temperature mean anomalies. The outcomes are hospitalization rates for four prevalent CVD subtypes: ischemic heart disease, cerebrovascular disease, heart failure, and arrhythmia. RESULTS: Chronic exposure to air pollutant mixtures was associated with increased hospitalization rates for all CVD subtypes, with heart failure being the most susceptible subtype. Sulfate, nitrate, nitrogen dioxide, and organic carbon posed the highest risks. Mixtures of the interaction terms between air pollutants and temperature mean anomalies were associated with increased hospitalization rates for all CVD subtypes. CONCLUSIONS: Our findings identified critical pollutants for targeted emission controls and suggested that abnormal temperature changes chronically affected cardiovascular health by interacting with air pollution, not directly.

Rickettsia species identified in adult, host-seeking Dermacentor occidentalis (Acari: Ixodidae) from Baja California, Mexico, and Oregon and Washington, United States.

The Pacific Coast tick (Dermacentor occidentalis Marx, 1892) is a frequently encountered and commonly reported human-biting tick species that has been recorded from most of California and parts of southwestern Oregon, southcentral Washington, and northwestern Mexico. Although previous investigators have surveyed populations of D. occidentalis for the presence of Rickettsia species across several regions of California, populations of this tick have not been surveyed heretofore for rickettsiae from Baja California, Oregon, or Washington. We evaluated 1,367 host-seeking, D. occidentalis adults collected from 2015 to 2022 by flagging vegetation at multiple sites in Baja California, Mexico, and Oregon and Washington, United States, using genus- and species-specific assays for spotted fever group rickettsiae. DNA of Rickettsia 364D, R. bellii, and R. tillamookensis was not detected in specimens from these regions. DNA of R. rhipicephali was detected in D. occidentalis specimens obtained from Ensenada Municipality in Baja California and southwestern Oregon, but not from Washington. All ompA sequences of R. rhipichephali that were amplified from individual ticks in southwestern Oregon were represented by a single genotype. DNA of the Ixodes pacificus rickettsial endosymbiont was amplified from specimens collected in southwestern Oregon and Klickitat County, Washington; to the best of our knowledge, this Rickettsia species has never been identified in D. occidentalis. Collectively, these data are consistent with a relatively recent introduction of Pacific Coast ticks in the northernmost extension of its recognized range.

Group-based trajectory models of integrated vaccine delivery and equity in low- and middle-income countries.

BACKGROUND: Integrated vaccine delivery - the linkage of routine vaccination with provision of other essential health services - is a hallmark of robust primary care systems that has been linked to equitable improvements in population health outcomes. METHODS: We gathered longitudinal data relating to routine immunization coverage and vaccination equity in 78 low- and middle-income countries that have ever received support from Gavi, the Vaccine Alliance, using multiple imputation to handle missing values. We then estimated several group-based trajectory models to describe the relationship between integrated vaccine delivery and vaccination equity in these countries. Finally, we used multinomial logistic regression to identify predictors of group membership. RESULTS: We identified five distinct trajectories of geographic vaccination equity across both the imputed and non-imputed datasets, along with two and four trajectories of socioeconomic vaccination equity in the imputed and non-imputed datasets, respectively. Integration was associated with reductions in the slope index of inequality of measles vaccination in the countries analyzed. Integration was also associated with an increase in the percentage of districts reporting high measles vaccination coverage. CONCLUSIONS: Integrated vaccine delivery is most strongly associated with improvements in vaccination equity in settings with high baseline levels of inequity. Continued scholarship is needed to further characterize the relationship between integration and health equity, as well as to improve measurement of vaccination coverage and integration.

Lessons from assembling UCEs: A comparison of common methods and the case of Clavinomia (Halictidae).

Sequence data assembly is a foundational step in high-throughput sequencing, with untold consequences for downstream analyses. Despite this, few studies have interrogated the many methods for assembling phylogenomic UCE data for their comparative efficacy, or for how outputs may be impacted. We study this by comparing the most commonly used assembly methods for UCEs in the under-studied bee lineage Nomiinae and a representative sampling of relatives. Data for 63 UCE-only and 75 mixed taxa were assembled with five methods, including ABySS, HybPiper, SPAdes, Trinity and Velvet, and then benchmarked for their relative performance in terms of locus capture parameters and phylogenetic reconstruction. Unexpectedly, Trinity and Velvet trailed the other methods in terms of locus capture and DNA matrix density, whereas SPAdes performed favourably in most assessed metrics. In comparison with SPAdes, the guided-assembly approach HybPiper generally recovered the highest quality loci but in lower numbers. Based on our results, we formally move Clavinomia to Dieunomiini and render Epinomia once more a subgenus of Dieunomia. We strongly advise that future studies more closely examine the influence of assembly approach on their results, or, minimally, use better-performing assembly methods such as SPAdes or HybPiper. In this way, we can move forward with phylogenomic studies in a more standardized, comparable manner.

Porcine Acellular Nerve-Derived Hydrogel Improves Outcomes of Direct Muscle Neurotization in Rats.

Background: The ability to reinnervate a muscle in the absence of a viable nerve stump is a challenging clinical scenario. Direct muscle neurotization (DMN) is an approach to overcome this obstacle; however, success depends on the formation of new muscle endplates, a process, which is often limited due to lack of appropriate axonal pathfinding cues. Objective: This study explored the use of a porcine nerve extracellular matrix hydrogel as a neuroinductive interface between nerve and muscle in a rat DMN model. The goal of the study was to establish whether such hydrogel can be used to improve neuromuscular function in this model. Materials and Methods: A common peroneal nerve-to-gastrocnemius model of DMN was developed. Animals were survived for 2 or 8 weeks following DMN with or without the addition of the hydrogel at the site of neurotization. Longitudinal postural thrust, terminal electrophysiology, and muscle weight assessments were performed to qualify and quantify neuromuscular function. Histological assessments were made to qualify the host response at the DMN site, and to quantify neuromuscular junctions (NMJs) and muscle fiber diameter. Results: The hydrogel-treated group showed a 132% increase in postural thrust at 8 weeks compared with that of the DMN alone group. This was accompanied by an 80% increase in the number of NMJs at 2 weeks, and 26% increase in mean muscle fiber diameter at 8 weeks. Conclusions: These results suggest that a nerve-derived hydrogel may improve the neuromuscular outcome following DNM.

Microbes, the 'silent third partners' of bee-angiosperm mutualisms.

While bee-angiosperm mutualisms are widely recognized as foundational partnerships that have shaped the diversity and structure of terrestrial ecosystems, these ancient mutualisms have been underpinned by 'silent third partners': microbes. Here, we propose reframing the canonical bee-angiosperm partnership as a three-way mutualism between bees, microbes, and angiosperms. This new conceptualization casts microbes as active symbionts, processing and protecting pollen-nectar provisions, consolidating nutrients for bee larvae, enhancing floral attractancy, facilitating plant fertilization, and defending bees and plants from pathogens. In exchange, bees and angiosperms provide their microbial associates with food, shelter, and transportation. Such microbial communities represent co-equal partners in tripartite mutualisms with bees and angiosperms, facilitating one of the most important ecological partnerships on land.

A bioengineered in situ ovary (ISO) supports follicle engraftment and live-births post-chemotherapy.

Female cancer patients who have undergone chemotherapy have an elevated risk of developing ovarian dysfunction and failure. Experimental approaches to treat iatrogenic infertility are evolving rapidly; however, challenges and risks remain that hinder clinical translation. Biomaterials have improved in vitro follicle maturation and in vivo transplantation in mice, but there has only been marginal success for early-stage human follicles. Here, we developed methods to obtain an ovarian-specific extracellular matrix hydrogel to facilitate follicle delivery and establish an in situ ovary (ISO), which offers a permissive environment to enhance follicle survival. We demonstrate sustainable follicle engraftment, natural pregnancy, and the birth of healthy pups after intraovarian microinjection of isolated exogenous follicles into chemotherapy-treated (CTx) mice. Our results confirm that hydrogel-based follicle microinjection could offer a minimally invasive delivery platform to enhance follicle integration for patients post-chemotherapy.

Adding new childhood vaccines to China's National Immunization Program: evidence, benefits, and priorities.

China's National Immunization Program has made remarkable achievements but does not include several important childhood vaccines that are readily available in the private market, such as pneumococcal conjugate vaccine (PCV), rotavirus vaccine, Haemophilus influenzae serotype b (Hib) vaccine, and varicella vaccine. We reviewed the literature to assess these four non-National Immunization Program vaccines in terms of their disease burdens, coverage, inequalities, and cost-effectiveness in China and aimed to recommend priorities for introducing them to the National Immunization Program. Based on our calculations using the available evidence, incorporating these vaccines into China's National Immunization Program in 2019 could have averted 11 761 deaths among children younger than 5 years, accounting for 10·29% of the total deaths in children younger than 5 years and reducing the mortality rate from 7·8 per 1000 to 7·0 per 1000. The review showed that 13-valent PCV (PCV13) had the lowest and most inequitable coverage but could prevent the highest number of deaths. In a budgetary analysis for the cohort of newborns in 2023, we estimated that the projected aggregate government costs were US$1954·92 million for PCV13, $1273·13 million for pentavalent rotavirus vaccine, $415·30 million for Hib vaccine, and $221·64 million for varicella vaccine. Our overall multicriteria decision analysis suggested the following priority order for introducing these four non-programme vaccines to the National Immunization Program to benefit the Chinese population: PCV13, rotavirus vaccine, Hib vaccine, and varicella vaccine.

Floral Diversity and Pollination Syndromes in Agave subgenus Manfreda.

The genus Agave is an ecological keystone of American deserts and both culturally and economically important in Mexico. Agave is a large genus of about 250 species. The radiation of Agave is marked by an initial adaptation to desert environments and then a secondary diversification of species associated with pollinator groups, such as hummingbirds and nocturnal moths. Phylogenetic analyses place Agave subgenus Manfreda, or the "herbaceous agaves," in a monophyletic clade that likely evolved in part as an adaptation to novel pollination vectors. Here, we present a morphological and observational study assessing the evolution of floral form in response to pollinator specialization within this understudied group. We found significant visitation by hummingbirds and nocturnal moths to several species within the Agave subgenus Manfreda. These observations also align with our morphological analyses of floral organs and support the evolution of distinct pollination syndromes. We found that not all floral morphology is consistent within a pollination syndrome, suggesting hidden diversity in the evolution of floral phenotypes in Agave. We also characterize the morphological variation between herbarium and live specimens, demonstrating that special consideration needs to be made when combining these types of data. This work identifies the potential for studying the functional evolution of diverse floral forms within Agave and demonstrates the need to further explore ecological and evolutionary relationships to understand pollinator influence on diversification in the genus.

An observation-based, reduced-form model for oxidation in the remote marine troposphere.

The hydroxyl radical (OH) fuels atmospheric chemical cycling as the main sink for methane and a driver of the formation and loss of many air pollutants, but direct OH observations are sparse. We develop and evaluate an observation-based proxy for short-term, spatial variations in OH (ProxyOH) in the remote marine troposphere using comprehensive measurements from the NASA Atmospheric Tomography (ATom) airborne campaign. ProxyOH is a reduced form of the OH steady-state equation representing the dominant OH production and loss pathways in the remote marine troposphere, according to box model simulations of OH constrained with ATom observations. ProxyOH comprises only eight variables that are generally observed by routine ground- or satellite-based instruments. ProxyOH scales linearly with in situ [OH] spatial variations along the ATom flight tracks (median r2 = 0.90, interquartile range = 0.80 to 0.94 across 2-km altitude by 20° latitudinal regions). We deconstruct spatial variations in ProxyOH as a first-order approximation of the sensitivity of OH variations to individual terms. Two terms modulate within-region ProxyOH variations-water vapor (H2O) and, to a lesser extent, nitric oxide (NO). This implies that a limited set of observations could offer an avenue for observation-based mapping of OH spatial variations over much of the remote marine troposphere. Both H2O and NO are expected to change with climate, while NO also varies strongly with human activities. We also illustrate the utility of ProxyOH as a process-based approach for evaluating intermodel differences in remote marine tropospheric OH.

An Estimate Of The Return On Investment Of A Malaria Vaccine In 20 Sub-Saharan African Countries, 2021-30.

Malaria is a leading global health problem that was responsible for an estimated 619,000 deaths worldwide in 2021. We modeled the return on investment (ROI) for the introduction and continuation of a four-dose malaria vaccine, RTS,S/AS01, from 2021 to 2030 in twenty sub-Saharan African countries supported by Gavi, the Vaccine Alliance. We used the Decade of Vaccine Economics benefits and costing outputs to calculate an ROI using health impact data modeled by the Swiss Tropical and Public Health Institute (hereafter "Swiss") and Imperial College London (hereafter "Imperial"). The Swiss estimates with a base vaccine price of US$7.00 resulted in an ROI of 0.42, and the Imperial impact estimates with the same base vaccine price resulted in an ROI of 2.30. Inclusion of the fifth seasonal dose for ten countries exhibiting high seasonal disease burden increased the Swiss ROI by 143 percent, to 1.02, and the Imperial ROI by 23.5 percent, to 2.84. To improve ROI, decision makers should continue to improve delivery platforms, decrease vaccine delivery costs, deliver the malaria vaccine in fewer doses, and provide access to vaccine resources.

Evolutionary Origins and Patterns of Diversification in Animal Brood Parasitism.

AbstractBrood parasitism involves the exploitation of host parental care rather than the extraction of resources directly from hosts. We identify defining characteristics of this strategy and consider its position along continua with adjacent behaviors but focus on canonical brood parasites, where parasitism is obligate and hosts are noneusocial (thereby distinguishing from social parasitism). A systematic literature survey revealed 59 independently derived brood parasitic lineages with most origins (49) in insects, particularly among bees and wasps, and other origins in birds (seven) and fish (three). Insects account for more than 98% of brood parasitic species, with much of that diversity reflecting ancient (≥100-million-year-old) brood parasitic lineages. Brood parasites usually, but not always, evolve from forms that show parental care. In insects, brood parasitism often first evolves through exploitation of a closely related species, following Emery's rule, but this is less typical in birds, which we discuss. We conducted lineage-level comparisons between brood parasitic clades and their sister groups, finding mixed results but an overall neutral to negative effect of brood parasitism on species richness and diversification. Our review of brood parasites reveals many unanswered questions requiring new research, including further modeling of the coevolutionary dynamics of brood parasites and their hosts.

Additive effects of 10-year exposures to PM2.5 and NO2 and primary cancer incidence in American older adults.

Epidemiologic evidence on the relationships between air pollution and the risks of primary cancers other than lung cancer remained largely lacking. We aimed to examine associations of 10-year exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with risks of breast, prostate, colorectal, and endometrial cancers. Methods: For each cancer, we constructed a separate cohort among the national Medicare beneficiaries during 2000 to 2016. We simultaneously examined the additive associations of six exposures, namely, moving average exposures to PM2.5 and NO2 over the year of diagnosis and previous 2 years, previous 3 to 5 years, and previous 6 to 10 years, with the risk of first cancer diagnosis after 10 years of follow-up, during which there was no cancer diagnosis. Results: The cohorts included 2.2 to 6.5 million subjects for different cancers. Exposures to PM2.5 and NO2 were associated with increased risks of colorectal and prostate cancers but were not associated with endometrial cancer risk. NO2 was associated with a decreased risk of breast cancer, while the association for PM2.5 remained inconclusive. At exposure levels below the newly updated World Health Organization Air Quality Guideline, we observed substantially larger associations between most exposures and the risks of all cancers, which were translated to hundreds to thousands new cancer cases per year within the cohort per unit increase in each exposure. Conclusions: These findings suggested substantial cancer burden was associated with exposures to PM2.5 and NO2, emphasizing the urgent need for strategies to mitigate air pollution levels.

PRAME expression in cutaneous melanoma does not correlate with disease-specific survival.

BACKGROUND: Immunohistochemistry-based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki-67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki-67. METHODS: We analyzed the immunohistochemical expression of PRAME and Ki-67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. The percentage of Ki-67-positive tumor nuclei was used to calculate the proliferation index. RESULTS: PRAME and Ki-67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki-67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki-67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki-67 index (p = 0.007). Increased Ki-67 index correlated with worse disease-specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease-specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki-67 index were each independent predictors of disease-specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease-specific survival (p = 0.64). CONCLUSION: Ki-67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki-67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki-67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions.

The evolutionary history of bees in time and space.

Bees are the most significant pollinators of flowering plants. This partnership began ca. 120 million years ago, but the uncertainty of how and when bees spread across the planet has greatly obscured investigations of this key mutualism. We present a novel analysis of bee biogeography using extensive new genomic and fossil data to demonstrate that bees originated in Western Gondwana (Africa and South America). Bees likely originated in the Early Cretaceous, shortly before the breakup of Western Gondwana, and the early evolution of any major bee lineage is associated with either the South American or African land masses. Subsequently, bees colonized northern continents via a complex history of vicariance and dispersal. The notable early absences from large landmasses, particularly in Australia and India, have important implications for understanding the assembly of local floras and diverse modes of pollination. How bees spread around the world from their hypothesized Southern Hemisphere origin parallels the histories of numerous flowering plant clades, providing an essential step to studying the evolution of angiosperm pollination syndromes in space and time.