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The present article presents the results of a qualitative study whose purpose was to compare the structure and operation of the programs for intellectual property management and technology transfer, and the mechanisms through which to foster entrepreneurship, in five high-profile research institutions across the Americas. The institutions of focus included Stanford University and the University of California, Davis in the United States; the Universidad Católica and the Universidad de Concepción in Chile; and the National Scientific and Technical Research Council in Argentina. The purpose of the study was to elucidate commonalities and differences among these institutions with respect to their technology transfer practices, and to distill methodologies that could be used to establish or refine technology transfer offices in American regions. Research revealed common goals and core activities, shared and implemented in similar ways among all five institutions. However, the analysis also identified divergent areas within the structure and operation of the various technology transfer programs, representing significant differences between the five institutions.

Emerging mycoses are an increasing concern in wildlife and human health. Given the historical rarity of fungal pathogens in warm-bodied vertebrates, there is a need to better understand how to manage mycoses and facilitate recovery in affected host populations. We explore challenges to host survival and mechanisms of host recovery in three bat species (Myotis lucifugus, Perimyotis subflavus, and M. septentrionalis) threatened with extinction by the mycosis, white-nose syndrome (WNS) as it continues to spread across North America. We present evidence from the literature that bats surviving WNS are exhibiting mechanisms of avoidance (by selecting microclimates within roosts) and tolerance (by increasing winter fat reserves), which may help avoid costs of immunopathology incurred by a maladaptive host resistance response. We discuss management actions for facilitating species recovery that take into consideration disease pressures (e.g., environmental reservoirs) and mechanisms underlying persistence, and suggest strategies that alleviate costs of immunopathology and target mechanisms of avoidance (protect or create refugia) and tolerance (increase body condition). We also propose strategies that target population and species-level recovery, including increasing reproductive success and reducing other stressors (e.g., wind turbine mortality). The rarity of fungal pathogens paired with the increasing frequency of emerging mycoses in warm-bodied vertebrate systems, including humans, requires a need to challenge common conventions about how diseases operate, how hosts respond, and how these systems could be managed to increase probability of recovery in host populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Objective: Post-COVID-19 syndrome presents a health and economic challenge affecting ~10% of patients recovering from COVID-19. Accurate assessment of patients with post-COVID-19 syndrome is complicated by health anxiety and coincident symptomatic autonomic dysfunction. We sought to determine whether either symptoms or objective cardiopulmonary exercise testing could predict clinically significant findings., Methods: 113 consecutive military patients were assessed in a comprehensive clinical pathway. This included symptom reporting, history, examination, spirometry, echocardiography and cardiopulmonary exercise testing (CPET) in all, with chest CT, dual-energy CT pulmonary angiography and cardiac MRI where indicated. Symptoms, CPET findings and presence/absence of significant pathology were reviewed. Data were analysed to identify diagnostic strategies that may be used to exclude significant disease., Results: 7/113 (6%) patients had clinically significant disease adjudicated by cardiothoracic multidisciplinary team (MDT). These patients had reduced fitness (V̇O 2 26.7 (±5.1) vs 34.6 (±7.0) mL/kg/min; p=0.002) and functional capacity (peak power 200 (±36) vs 247 (±55) W; p=0.026) compared with those without significant disease. Simple CPET criteria (oxygen uptake (V̇O 2 ) >100% predicted and minute ventilation (VE)/carbon dioxide elimination (V̇CO 2 ) slope <30.0 or VE/V̇CO 2 slope <35.0 in isolation) excluded significant disease with sensitivity and specificity of 86% and 83%, respectively (area under the receiver operating characteristic curve (AUC) 0.89). The addition of capillary blood gases to estimate alveolar-arterial gradient improved diagnostic performance to 100% sensitivity and 78% specificity (AUC 0.92). Symptoms and spirometry did not discriminate significant disease., Conclusions: In a population recovering from SARS-CoV-2, there is reassuringly little organ pathology. CPET and functional capacity testing, but not reported symptoms, permit the exclusion of clinically significant disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Cryptococcus neoformans can invade the central nervous system by crossing the blood-brain barrier via a transcellular mechanism that relies on multiple host factors. In this narrative, we review the evidence that a direct interplay between C. neoformans and brain endothelial cells forms the basis for invasion and transmigration across the brain endothelium. Adherence and internalization of C. neoformans is dependent on transmembrane proteins, including a hyaluronic acid receptor and an ephrin receptor tyrosine kinase. We consider the role of EphA2 in facilitating the invasion of the central nervous system by C. neoformans and highlight experimental evidence supporting macropinocytosis as a potential mechanism of internalization and transcytosis. How macropinocytosis might be conclusively demonstrated in the context of C. neoformans is also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Lanser, Bennett, Vu and Gelli.)

Objectives: The Communication (C), Maintaining Health (M), Independence (I), Services, Support and Self-Determination (S), and Transportation (T) is a framework (C-MIST) for identifying functional needs in an emergency response. A C-MIST documentation tool provides shelter staff with a list of potential client needs and actions to address them. This retrospective review describes the needs and actions indicated on completed C-MIST documentation tools (ie, records) within domestic general population shelters following Hurricane Florence in 2018., Methods: A convenience sample of 1209 records completed by shelter disaster health services personnel was provided by the American Red Cross. The records correspond to client stays in 19 shelters between September and October 2018. Data abstracted from hardcopy forms were de-identified and recorded in a database. Summary statistics were computed., Results: High incidence needs included medical supplies for everyday care (including medications) not related to mobility (15.4%), medically or culturally needed diets (12.2%), durable medical equipment (9.7%), mental health care (8.8%), and transportation (8.4%). High incidence actions included replacement medication (9.3%), refer to Disaster Mental Health Services (6.4%), provide assistive mobility equipment (5.1%), provide diabetes management supplies (5.0%), provide alternative food and beverages (4.1%), and provide transportation (3.9%)., Conclusions: The process for identifying health and functional support needs in shelters should be standardized through the use of the C-MIST framework.

The soft tick Carios kelleyi (Cooley and Kohls, 1941) is an ectoparasite of bats that can harbor bacteria known to cause disease in humans, such as Rickettsia spp., Bartonella spp., and relapsing fever Borrelia spp. Human-tick encounters may occur when bats occupy attics or similar dwellings with access points to human-inhabited areas. During May 2021, a partially engorged adult female C. kelleyi was collected from a Vermont home with an attic that was being used as a roost by big brown bats, Eptesicus fuscus (Chiroptera: Vespertilionidae). The source of the blood in the tick was the domestic dog, Canis lupus familiaris. Subsequently, eight C. kelleyi larvae were collected from a rescued E. fuscus adult. This is the first report of a soft tick species from Vermont and it is unknown how long C. kelleyi has been present in this state. Reports of C. kelleyi are on the rise across the northeastern United States but the implications for the health of humans, domestic animals, and bats in northern New England remain unclear. Bat management plans should consider the importance of bat exclusion in preventing tick encounters with members of the household and should include a tick monitoring component if bats are evicted., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The HIV epidemic in King County, Washington has traditionally been highly concentrated among men who have sex with men, and incidence has gradually declined over 2 decades. In 2018, King County experienced a geographically concentrated outbreak of HIV among heterosexual people who inject drugs., Methods: Data sources to describe the 2018 outbreak and King County's response were partner services interview data, HIV case reports, syringe service program client surveys, hospital data, and data from a rapid needs assessment of homeless individuals and people who inject drugs. In 2020, the authors examined the impact of delays in molecular sequence analyses and cluster member size thresholds, for identifying genetically similar clusters, on the timing of outbreak identification., Results: In 2018, the health department identified a North Seattle cluster, growing to 30 people with related HIV infections diagnosed in 2008-2019. In total, 70% of cluster members were female, 77% were people who inject drugs, 87% were homeless, and 27% reported exchanging sex. Intervention activities included a rapid needs assessment, 2,485 HIV screening tests in a jail and other outreach settings, provision of 87,488 clean syringes in the outbreak area, and public communications. A lower cluster size threshold and more rapid receipt and analyses of data would have identified this outbreak 4-16 months earlier., Conclusions: This outbreak shows the vulnerability of people who inject drugs to HIV infection, even in areas with robust syringe service programs and declining HIV epidemics. Although molecular HIV surveillance did not identify this outbreak, it may have done so with a lower threshold for defining clusters and more rapid receipt and analyses of HIV genetic sequences., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Rapid evolution of advantageous traits following abrupt environmental change can help populations recover from demographic decline. However, for many introduced diseases affecting longer-lived, slower reproducing hosts, mortality is likely to outpace the acquisition of adaptive de novo mutations. Adaptive alleles must therefore be selected from standing genetic variation, a process that leaves few detectable genomic signatures. Here, we present whole genome evidence for selection in bat populations that are recovering from white-nose syndrome (WNS). We collected samples both during and after a WNS-induced mass mortality event in two little brown bat populations that are beginning to show signs of recovery and found signatures of soft sweeps from standing genetic variation at multiple loci throughout the genome. We identified one locus putatively under selection in a gene associated with the immune system. Multiple loci putatively under selection were located within genes previously linked to host response to WNS as well as to changes in metabolism during hibernation. Results from two additional populations suggested that loci under selection may differ somewhat among populations. Through these findings, we suggest that WNS-induced selection may contribute to genetic resistance in this slowly reproducing species threatened with extinction., (© 2021 John Wiley & Sons Ltd.)

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation assessments and planning., (© 2021 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Sierra Mixe maize is a landrace variety from Oaxaca, Mexico, that utilizes nitrogen derived from the atmosphere via an undefined nitrogen fixation mechanism. The diazotrophic microbiota associated with the plant's mucilaginous aerial root exudate composed of complex carbohydrates was previously identified and characterized by our group where we found 23 lactococci capable of biological nitrogen fixation (BNF) without containing any of the proposed essential genes for this trait ( nifHDKENB ). To determine the genes in Lactococcus associated with this phenotype, we selected 70 lactococci from the dairy industry that are not known to be diazotrophic to conduct a comparative population genomic analysis. This showed that the diazotrophic lactococcal genomes were distinctly different from the dairy isolates. Examining the pangenome followed by genome-wide association study and machine learning identified genes with the functions needed for BNF in the maize isolates that were absent from the dairy isolates. Many of the putative genes received an 'unknown' annotation, which led to the domain analysis of the 135 homologs. This revealed genes with molecular functions needed for BNF, including mucilage carbohydrate catabolism, glycan-mediated host adhesion, iron/siderophore utilization, and oxidation/reduction control. This is the first report of this pathway in this organism to underpin BNF. Consequently, we proposed a model needed for BNF in lactococci that plausibly accounts for BNF in the absence of the nif operon in this organism.

The Federal Emergency Management Agency prescribes a 48-h timeline between the declaration of an emergency and the treatment of the last person with Strategic National Stockpile (SNS) medical countermeasures (MCM). Many states struggle to meet the 48-h window. Issues surrounding adequate staffing, critical to maintaining necessary Points Of Dispensing (POD) throughput, are noted in the literature. The use of public and private partnerships in the health-care sector may improve POD throughput. This study describes a novel strategy for partnering with home health agencies (HHAs) to augment MCM distribution. The HHA In-Home Dispensing Model we propose authorizes HHAs to act as Closed PODs following a head of household model. Here, we evaluate the effectiveness of the model using a case study. First, we provide an overview of the methods used to estimate the duration of in-home nurse dispensing shifts. We then present the results for our case study area. Next, we discuss how the model can be used and its limitations. We conclude that the HHA In-Home SNS Dispensing Model shows promise and should receive further consideration, as it can decrease demand at open PODs and increase the reach of MCMs to vulnerable populations who might otherwise have difficulty receiving them.

A geographically isolated maize landrace cultivated on nitrogen-depleted fields without synthetic fertilizer in the Sierra Mixe region of Oaxaca, Mexico utilizes nitrogen derived from the atmosphere and develops an extensive network of mucilage-secreting aerial roots that harbors a diazotrophic (N2-fixing) microbiota. Targeting these diazotrophs, we selected nearly 600 microbes of a collection obtained from mucilage and confirmed their ability to incorporate heavy nitrogen (15N2) metabolites in vitro. Sequencing their genomes and conducting comparative bioinformatic analyses showed that these genomes had substantial phylogenetic diversity. We examined each diazotroph genome for the presence of nif genes essential to nitrogen fixation (nifHDKENB) and carbohydrate utilization genes relevant to the mucilage polysaccharide digestion. These analyses identified diazotrophs that possessed the canonical nif gene operons, as well as many other operon configurations with concomitant fixation and release of >700 different 15N labeled metabolites. We further demonstrated that many diazotrophs possessed alternative nif gene operons and confirmed their genomic potential to derive chemical energy from mucilage polysaccharide to fuel nitrogen fixation. These results confirm that some diazotrophic bacteria associated with Sierra Mixe maize were capable of incorporating atmospheric nitrogen into their small molecule extracellular metabolites through multiple nif gene configurations while others were able to fix nitrogen without the canonical (nifHDKENB) genes., Competing Interests: The authors declare no conflicts of interests relevant to this work for employment, consultancy, patents, products in development, or marketed products. None of the authors are employed by the major funding agency of this work, MARS, Inc., but were employed by UC Davis. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Sierra Mixe maize is a geographically remote landrace variety grown on nitrogen-deficient fields in Oaxaca, Mexico that meets its nutritional requirements without synthetic fertilizer by associating with free-living diazotrophs comprising the microbiota of its aerial root mucilage. We selected nearly 500 diazotrophic (N2-fixing) bacteria isolated from Sierra Mixe maize mucilage and sequenced their genomes. Comparative genomic analysis demonstrated that isolates represented diverse genera and composed three major diazotrophic groups based on nitrogen fixation gene content. In addition to nitrogen fixation, we examined deamination of 1-amino-1-cyclopropanecarboxylic acid, biosynthesis of indole-3-acetic acid, and phosphate solubilization as alternative mechanisms of direct plant growth promotion (PGP). Genome mining showed that isolates of all diazotrophic groups possessed marker genes for multiple mechanisms of direct plant growth promotion (PGP). Implementing in vitro assays corroborated isolate genotypes by measuring each isolate's potential to confer the targeted PGP traits and revealed phenotypic variation among isolates based on diazotrophic group assignment. Investigating the ability of mucilage diazotrophs to confer PGP by direct inoculation of clonally propagated potato plants in planta led to the identification of 16 bio-stimulant candidates. Conducting nitrogen-stress greenhouse experiments demonstrated that potato inoculation with a synthetic community of bio-stimulant candidates, as well as with its individual components, resulted in PGP phenotypes. We further demonstrated that one diazotrophic isolate conferred PGP to a conventional maize variety under nitrogen-stress in the greenhouse. These results indicate that, while many diazotrophic isolates from Sierra Mixe maize possessed genotypes and in vitro phenotypes for targeted PGP traits, a subset of these organisms promoted the growth of potato and conventional maize, potentially through the use of multiple promotion mechanisms., Competing Interests: The authors have declared that no competing interests exist.

Nitrogen-fixing microbial associations with cereals have been of intense interest for more than a century (Roesch et al., Plant Soil 2008;302:91-104; Triplett, Plant Soil 1996;186:29-38; Mus et al., Appl. Environ. Microbiol. 2016;82:3698-3710; Beatty and Good, Science 2011;333:416-417). A recent report demonstrated that an indigenous Sierra Mixe maize landrace, characterized by an extensive development of aerial roots that secrete large amounts of mucilage, can acquire 28-82% of its nitrogen from atmospheric dinitrogen (Van Deynze et al., PLoS Biol. 2018;16:e2006352). Although the Sierra Mixe maize landrace is unique in the large quantity of mucilage produced, other cereal crops secrete mucilage from underground and aerial roots and we hypothesize that this may represent a general mechanism for cereals to support associations with microbial diazotrophs. We propose a model for the association of nitrogen-fixing microbes with maize mucilage and identify the four main functionalities for such a productive diazotrophic association., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Immunosuppression increases the risk of cancers that are associated with viral infection 1 . In particular, the risk of squamous cell carcinoma of the skin-which has been associated with beta human papillomavirus (β-HPV) infection-is increased by more than 100-fold in immunosuppressed patients 2-4 . Previous studies have not established a causative role for HPVs in driving the development of skin cancer. Here we show that T cell immunity against commensal papillomaviruses suppresses skin cancer in immunocompetent hosts, and the loss of this immunity-rather than the oncogenic effect of HPVs-causes the markedly increased risk of skin cancer in immunosuppressed patients. To investigate the effects of papillomavirus on carcinogen-driven skin cancer, we colonized several strains of immunocompetent mice with mouse papillomavirus type 1 (MmuPV1) 5 . Mice with natural immunity against MmuPV1 after colonization and acquired immunity through the transfer of T cells from immune mice or by MmuPV1 vaccination were protected against skin carcinogenesis induced by chemicals or by ultraviolet radiation in a manner dependent on CD8 + T cells. RNA and DNA in situ hybridization probes for 25 commensal β-HPVs revealed a significant reduction in viral activity and load in human skin cancer compared with the adjacent healthy skin, suggesting a strong immune selection against virus-positive malignant cells. Consistently, E7 peptides from β-HPVs activated CD8 + T cells from unaffected human skin. Our findings reveal a beneficial role for commensal viruses and establish a foundation for immune-based approaches that could block the development of skin cancer by boosting immunity against the commensal HPVs present in all of our skin.

The recruitment of a bacterial consortium by the host is a strategy not limited to animals but is also used in plants. A maize aerial root mucilage has been found that harbors nitrogen fixing bacteria that are attracted to the carbohydrate rich environment. This synbiotic relationship is facilitated by a polysaccharide, whose complicated structure has been previously unknown. In this report, we present the characterization of the maize polysaccharide by employing new analytical strategies combining chemical depolymerization, oligosaccharide sequencing, and monosaccharide and glycosidic linkage quantitation. The mucilage contains a single heterogeneous polysaccharide composed of a highly fucosylated and xylosylated galactose backbone with arabinan and mannoglucuronan branches. This unique polysaccharide structure may select for the diazotrophic community by containing monosaccharides and linkages that correspond to the glycosyl hydrolases associated with the microbial community. The elucidation of this complicated structure illustrates the power of the analytical methods, which may serve as a general platform for polysaccharide analysis in the future.

Urbanization has detrimental effects on biodiversity and ecosystem functioning, as agricultural and semi-natural habitats are converted into landscapes dominated by built features. Urban agricultural sites are a growing component of urban landscapes and have potential to serve as a source of biodiversity conservation and ecosystem service provisioning in urban areas. In 19 urban agricultural sites, we investigated how surrounding land cover and local site variables supported bees and pollination services. We found the abundance of bees differentially responded to landscape and local scale variables depending on body size and nesting habit. Large-bodied bees, Bombus and Apis species, were positively associated with increasing amounts of impervious cover, while the abundance of small-bodied soil nesting Halictus species increased as the proportion of flower area, a local variable, increased. Bee richness declined with increasing levels of impervious cover, while bee community composition changed along a gradient of increasing impervious cover. Pollination services, measured at each site using sentinel cucumber plants, declined as hardscape, a local variable, increased. To improve bee conservation and pollination services in urban agricultural sites, our results suggest urban planning strategies should minimize impervious cover at large spatial scales while land managers should focus locally on incorporating floral resources, which increases food and nesting resources especially for smaller bee species. Local site design coupled with regional urban planning can advance the success of urban agriculture, while benefiting biodiversity by creating opportunities for pollinator conservation in urban landscapes., Competing Interests: The authors have declared that no competing interests exist.

Although rare, cutaneous metastases portend a poor prognosis and are often an indicator of widespread disease. Breast cancer and melanoma are the most common types of cancer that are associated with spread to and within the skin; however, other malignancies, such as lung, colon, head and neck, and hematologic, have been described with a degree of relative frequency. A variety of clinical appearances and syndromes of cutaneous metastases are presented and described in this article. Possible treatment options, including skin-directed therapies and immunotherapies, are also discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

An indigenous maize landrace from the Sierra Mixe region of Oaxaca, Mexico exhibits extensive formation of aerial roots which exude large volumes of a polysaccharide-rich gel matrix or "mucilage" that harbors diazotrophic microbiota. We hypothesize that the mucilage associated microbial community carries out multiple functions, including disassembly of the mucilage polysaccharide. In situ, hydrolytic assay of the mucilage revealed endogenous arabinofuranosidase, galactosidase, fucosidase, mannosidase and xylanase activities. Screening the mucilage against plant cell wall glycan-specific monoclonal antibodies recognized the presence of carbohydrate epitopes of hemicellulosic polysaccharides like xyloglucan (both non-fucosylated and fucosylated), xylan (both substituted and unsubstituted xylan domains) and pectic-arabinogalactans, all of which are potential carbon sources for mucilage microbial residents. Mucilage metagenome annotation using MG-RAST identified the members forming the microbial community, and gene fragments with predicted functions associated with carbohydrate disassembly. Data from the in situ hydrolytic activity and monoclonal antibody screening assays were used to guide the selection of five full length genes with predicted glycosyl hydrolase function from the GenBank database that were similar to gene fragments of high relative abundance in the mucilage metagenomes. These five genes were then synthesized for recombinant production in Escherichia coli. Here we report the characterization of an α-N-arabinofuranosidase (GH51) and an oligosaccharide reducing-end xylanase (GH8) from Flavobacterium johnsoniae; an α-L-fucosidase (GH29) and a xylan β-1,4 xylosidase (GH39) from Spirosoma linguale, and a β-mannosidase (GH2) from Agrobacterium fabrum. Biochemical characterization of these enzymes revealed a β-Mannosidase that also exhibits a secondary activity towards the cleavage of galactosyl residues. We also describe two xylanases (GH8 and GH39) from underexplored glycosyl hydrolase families, one thermostable α-L-Fucosidase (GH29) and a thermostable α-N-Arabinofuranosidase (GH51)., Competing Interests: The authors declare no competing interests. Sivakumar Pattathil is presently affiliated with Mascoma LLC (Lallemand Inc.), which is a commercial entity that is not and has never been associated with the work presented in this study.

Plants are associated with a complex microbiota that contributes to nutrient acquisition, plant growth, and plant defense. Nitrogen-fixing microbial associations are efficient and well characterized in legumes but are limited in cereals, including maize. We studied an indigenous landrace of maize grown in nitrogen-depleted soils in the Sierra Mixe region of Oaxaca, Mexico. This landrace is characterized by the extensive development of aerial roots that secrete a carbohydrate-rich mucilage. Analysis of the mucilage microbiota indicated that it was enriched in taxa for which many known species are diazotrophic, was enriched for homologs of genes encoding nitrogenase subunits, and harbored active nitrogenase activity as assessed by acetylene reduction and 15N2 incorporation assays. Field experiments in Sierra Mixe using 15N natural abundance or 15N-enrichment assessments over 5 years indicated that atmospheric nitrogen fixation contributed 29%-82% of the nitrogen nutrition of Sierra Mixe maize., Competing Interests: Howard-Yana Shapiro is affiliated with Mars, Incorporated, one of the research sponsors. Author Cristobal Heitmann was unable to confirm authorship or contributions himself, and this was carried out collectively by the other co-authors.

This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED ( N = 19) and HNSCC ( N = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 ( p = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis., Competing Interests: CONFLICTS OF INTEREST All authors have no conflicts of interest.

To better understand country of birth-related shifts in the demography of people newly diagnosed with HIV infection, we compared demographic and clinical characteristics of foreign-born and U.S.-born residents of King County, WA diagnosed with HIV from 2006 to 2015. The proportion of cases that were foreign-born increased from 23 to 34% during this time. Most foreign-born cases were born in Africa (34%), Latin America (32%), Asia (22%), or Europe (7%). Latin Americans and Asians were similar to U.S.-born individuals by HIV risk factor and gender, while Africans were more likely to be female and less often men who have sex with men. In 2015, approximately 15% of cases presumptively newly diagnosed in King County were foreign-born individuals who self-reported a pre-immigration HIV diagnosis. Increases in foreign-born individuals previously diagnosed out of country may lead to inaccuracy in the count of new diagnoses, including an over-estimate of community-acquired HIV in King County.

Objectives: To assess how integration of HIV surveillance and field services might influence surveillance data and linkage to care metrics., Methods: We used HIV surveillance and field services data from King County, Washington, to assess potential impact of misclassification of prior diagnoses on numbers of new diagnoses. The relationship between partner services and linkage to care was evaluated with multivariable log-binomial regression models., Results: Of the 2842 people who entered the King County HIV Surveillance System in 2010 to 2015, 52% were newly diagnosed, 41% had a confirmed prior diagnosis in another state, and 7% had an unconfirmed prior diagnosis. Twelve percent of those classified as newly diagnosed for purposes of national HIV surveillance self-reported a prior HIV diagnosis that was unconfirmed. Partner services recipients were more likely than nonrecipients to link to care within 30 days (adjusted risk ratio [RR] = 1.10; 95% confidence interval [CI] = 1.03, 1.18) and 90 days (adjusted RR = 1.07; 95% CI = 1.01, 1.14) of diagnosis., Conclusions: Integration of HIV surveillance, partner services, and care linkage efforts may improve the accuracy of HIV surveillance data and facilitate timely linkage to care.

Objectives: Reported cytologic alterations associated with high-risk human papillomavirus (HR-HPV) in oral epithelial dysplasia (HPV-OED) need further characterization., Study Design: Archival cases of high-grade oral epithelial dysplasia (hgOED) (N = 38) were assigned a cytologic score (CS) based on the average number of mitotic, karyorrhectic, and apoptotic cells per high-power field. Three groups were then generated on the basis of increasing CS: Focal (group 1, N = 14), Intermediate (group 2, N = 12), and Diffuse (group 3, N = 12). Polymerase chain reaction-based HPV genotyping and p16 immunohistochemistry were performed., Results: HR-HPV was found significantly more in group 3 (83.3%) compared with groups 1 and 2 (group 1&2; 42.9% and 41.7%, respectively; P = .047). HPV16 predominated in HR-HPV-positive cases (90.5%). By location, the tongue or the floor of mouth was associated with all groups (P = .04). Increasing CS was associated with a slightly younger age (P = .04) and increased expression of p16 (P = .005). CS and p16 expression were not sensitive but were highly specific predictors for HR-HPV presence. Based on limited follow-up information, HPV-OED does not differ in clinical aggressiveness compared with conventional OED., Conclusions: Increased CS in hgOED is strongly associated with HR-HPV (mostly HPV16) and p16 expression. CS and p16 expression are specific predictors of HR-HPV presence. Further molecular study and long-term follow-up of HPV-OED are needed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The relative effectiveness of in-person versus telephone interviews for human immunodeficiency virus (HIV)/sexually transmitted disease partner services (PS) is uncertain., Methods: We compared outcomes of in-person versus telephone PS interviews for early syphilis (ES) and newly diagnosed HIV in King County, Washington from 2010 to 2014. We used multivariable Poisson regression to evaluate indices (number of partners per original patient [OP]) for partners named, notified, tested, diagnosed, and treated (ES only). Analyses controlled for OP age, sex, race/ethnicity, sexual orientation, time to interview, place of diagnosis, and staff performing interviews., Results: For ES, 682 and 646 OPs underwent in-person and telephone interviews, respectively. In-person syphilis PS were associated with higher indices of partners named (in-person index [IPI], 3.43; telephone index [TI], 2.06; adjusted relative risk [aRR], 1.68; 95% confidence interval [CI], 1.55-1.82), notified (IPI, 1.70; TI, 1.13; aRR, 1.39; 95% CI, 1.24-1.56), tested (IPI, 1.15; TI, 0.72; aRR, 1.34; 95% CI, 1.16-1.54), and empirically treated (IPI, 1.03; TI, 0.74; aRR, 1.19; 95% CI, 1.03-1.37), but no difference in infected partners treated (IPI, 0.28; TI, 0.24; aRR, 0.93; 95% CI, 0.72-1.21). For HIV, 358 and 489 OPs underwent in-person and telephone interviews, respectively. In-person HIV PS were associated with higher indices of partners named (IPI, 1.87; TI, 1.28; aRR, 1.38; 95% CI, 1.18-1.62), notified (IPI, 1.38; TI, 0.92; aRR, 1.24; 95% CI, 1.03-1.50), and newly diagnosed with HIV (IPI, 0.10; TI, 0.05; aRR, 2.17; 95% CI, 1.04-4.50), but no difference in partners tested (IPI, 0.61; TI, 0.48; aRR, 1.15; 95% CI, 0.88-1.52)., Conclusions: Although in-person syphilis PS were associated with some increased PS indices, they did not increase the treatment of infected partners. In contrast, in-person HIV PS resulted in increased HIV case finding. These data support prioritizing in-person PS for HIV and suggest that in-person PS for syphilis may not have major public health benefit.

Background: Little is known about the lifetime risk of human immunodeficiency virus (HIV) diagnosis among US men who have sex with men (MSM), trends in risk and how risk varies between populations., Methods: We used census and HIV surveillance data to construct life tables to estimate the cumulative risk of HIV diagnosis among cohorts of MSM born 1940 to 1994 in King County, Washington (KC) and Mississippi (MS)., Results: The cumulative risk of HIV diagnosis progressed in 3 phases. In phase 1, risk increased among MSM in successive cohorts born 1940 to 1964. Among men born 1955 to 1965 (the peak risk cohort), by age 55 years, 45% of white KC MSM, 65% of black KC MSM, 22% of white MS MSM, and 51% of black MS MSM had been diagnosed with HIV. In phase 2, men born 1965 to 1984, risk of diagnosis among KC MSM declined almost 60% relative to the peak risk cohort. A similar pattern of decline occurred in white MS MSM, with a somewhat smaller decline observed in black MS MSM. In phase 3, men born 1985 to 1994, the pattern of risk diverged. Among white KC MSM, black KC MSM, and white MS MSM, HIV risk increased slightly compared with men born 1975 to 1984, with 6%, 14%, and 2% diagnosed by age 27 years, respectively. Among black MS MSM born 1985 to 1994, HIV risk rose dramatically, with 35% HIV diagnosed by age 27 years., Conclusions: The lifetime risk of HIV diagnosis has substantially declined among MSM in KC and among white MSM in MS, but is rising dramatically among black MSM in MS.

A broad range of cytokines are secreted during the inflammatory response by the immune system. Some cytokines promote inflammation, while others inhibit inflammation. Inflammatory cytokines work in harmony when they encounter external pathogens or internal dangers. Inflammation is resolved after the cause is eliminated. However, if the cause persists, it can lead to significant diseases. The pro-inflammatory cytokine TNFα is a biomarker for the inflammatory response. The AO herbal mixture extracted from 10 medicinal herbs has been investigated for its ability to control the inflammatory process and to inhibit TNFα activity. To find the treatment for inflammation related diseases, we examined whether the AO herbal extract is able to affect the activities of other cytokines. Here we present that the AO herbal extract is able to inhibit pro-inflammatory factor activities including IL-1α. However, it does not affect the activities of IL-1β and IL-6. Interestingly, it promotes the activity of anti-inflammatory factors including IL-4 and IL-13., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Our objective was to describe the types of providers who refer children with autism spectrum disorder (ASD) for brain magnetic resonance imaging (MRI), the referral reason, and MRI results. The most common referral reasons were autism spectrum disorder with seizures (33.7%), autism spectrum disorder alone (26.3%), and autism spectrum disorder with abnormal neurologic examination or preexisting finding (24%). Neurology (62.5%), general pediatric (22.3%), and developmental/behavioral practitioners (8.9%) referred the most patients. The prevalence of definite pathology was highest in children referred for autism spectrum disorder with abnormal neurologic examination/preexisting finding (26.2%, 95% CI: 16.8%-36%), headaches (25.7%, 95% CI: 11.2%-40.2%), or seizures (22%, 95% CI: 14.6%-29.5%), and was lowest in children referred for autism spectrum disorder alone (6.5%, 95% CI: 1.5%-11.6%). We concluded that there is a low prevalence of definite pathology in children with autism spectrum disorder undergoing brain MRI. In children with abnormal neurologic examination or preexisting finding, seizures, or headaches, one may consider performing brain MRI given the higher prevalence of pathology., (© The Author(s) 2016.)

This study examined the impact of U.S. chain restaurant food consumption in China and South Korea from an ecological perspective. Specifically, it explored the relationships among several environmental and individual variables that have been found to affect obesity/weight management in previous research, including the prevalence/popularity of U.S. chain restaurants in these countries, frequency of U.S. chain restaurant food consumption, self-efficacy in weight management, willingness to communicate about weight/diet, self-perceptions of weight/obesity stigma, body mass index (BMI), and depression. The results indicated that willingness to communicate about weight/diet predicted increased self-efficacy in weight management. Higher BMI scores were found to predict increased weight/obesity stigma, and increased frequency of U.S. restaurant food consumption, weight/obesity stigma, and reduced self-efficacy in weight management were found to predict increased levels of depression. The theoretical and practical implications of the findings are discussed, along with limitations and directions for future research.

Cervical cancer is the most common malignancy among women particularly in developing countries, with human papillomavirus (HPV) 16 causing 50% of invasive cervical cancers. A plant-based HPV vaccine is an alternative to the currently available virus-like particle (VLP) vaccines, and would be much less expensive. We optimized methods to express HPV16 L1 protein and purify VLPs from tobacco (Nicotiana benthamiana) leaves transfected with the magnICON deconstructed viral vector expression system. L1 proteins were extracted from agro-infiltrated leaves using a series of pH and salt mediated buffers. Expression levels of L1 proteins and VLPs were verified by immunoblot and ELISA, which confirmed the presence of sequential and conformational epitopes, respectively. Among three constructs tested (16L1d22, TPL1d22, and TPL1F), TPL1F, containing a full-length L1 and chloroplast transit peptide, was best. Extraction of HPV16 L1 from leaf tissue was most efficient (> 2.5% of total soluble protein) with a low-salt phosphate buffer. VLPs were purified using both cesium chloride (CsCl) density gradient and size exclusion chromatography. Electron microscopy studies confirmed the presence of assembled forms of HPV16 L1 VLPs. Collectively; our results indicated that chloroplast-targeted transient expression in tobacco plants is promising for the production of a cheap, efficacious HPV16 L1 VLP vaccine. Studies are underway to develop plant VLPs for the production of a cervical cancer vaccine.

Background: The US National HIV/AIDS Strategy defines national objectives related to HIV prevention and care. The extent to which US cities are meeting those objectives is uncertain., Methods: We analyzed King County, WA, HIV surveillance data collected between 2004 and 2013. The study population included 9539 persons diagnosed as having and living with HIV infection and 3779 persons with newly diagnosed HIV infection., Results: Between 2004 and 2013, the rate of new HIV diagnosis decreased from 18.4 to 13.2 per 100,000 residents (decline of 28%); AIDS diagnosis rates declined 42% from 12 to 7 per 100,000; and age-adjusted death rates decreased from 27 to 15 per 1000 persons living with HIV/AIDS (decline of 42%; P<0.0001 for all 3 trends). The rate of new HIV diagnosis declined 26% among men who have sex with men (MSM; P=0.0002), with the largest decline occurring in black MSM (44%). Among 8679 individuals with laboratory results reported to National HIV Surveillance System from 2006 through 2013, viral suppression (viral load<200 copies/mL) increased from 45% to 86% (P<0.0001), with all racial/ethnic groups achieving greater than 80% viral suppression in 2013., Interpretation: The rates of new HIV diagnosis, AIDS diagnoses, and mortality in persons living with HIV in King County, WA, have significantly declined over the last decade. These changes have occurred concurrent with a dramatic increase in HIV viral suppression and have affected diverse populations, including MSM and African American MSM. These findings demonstrate substantial local success in achieving the goals of the National HIV/AIDS Strategy.

The inflammatory response is one of the first defenses our body has to fight against potential endangerments. It plays a critical role in host defense, clearing and slowing the infection in the case of microbial invasion. During an inflammatory response, a variety of cytokines are produced by cells and trigger or enhance the specific inflammation response. TNFα, one of these factors, plays a crucial role in many immune and inflammatory processes, such as proliferation, apoptosis, necrosis, and cell survival. It acts in orchestrating the cytokine cascade and the major regulator of inflammatory cytokine production. Abnormality of TNFα signaling leads to many diseases, including rheumatoid arthritis, psoriasis, Crohn's disease, atherosclerosis, and cancer. Due to the importance of TNFα, regulating TNFα activity is a key to treat the related diseases. There is a long history of using medicinal herbs to treat diseases related to inflammation. We searched for an ingredient that has the ability to inhibit TNFα, we examined AO herbal extract, containing 10 individual herbs and most of these herbs have anti-inflammatory activity within humans. We have tested the anti-inflammatory ability of AO herbal extract on mice. Furthermore, we used macrophage cell from young mice and found that AO extract has the ability to reduce the inflammation by inhibiting TNFα level., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer.

Purpose: Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer., Methods and Materials: Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10(6) IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m(2)) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years., Results: Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy-related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths., Conclusions: Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The trends predicted an inferior outcome with the RA-IFN combination., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Human papillomavirus (HPV) typing of oral lesions microscopically consistent with multifocal epithelial hyperplasia (MEH) was performed to identify potential novel clinical presentations., Study Design: MEH (N = 22 lesions, 17 patients) and squamous papilloma control samples (N = 9 lesions, 9 patients) were compared by using polymerase chain reaction-based HPV genotyping. Student's t tests were used to compare continuous characteristics., Results: Of the study cases, 86.4% of MEH and only 11% of controls were positive for HPV (P = .0002). In MEH lesions, 45.5% contained HPV32, 36.4% HPV6, and 4.5% HPV40. MEH lesions were mostly multifocal (50%) and occurred in HIV-negative patients (81.3%). They predominated on the labial/buccal mucosa (63.3%), and there were significant differences between groups by anatomic site (P < .0001). HPV32, but not HPV6, was detected in known HIV-positive patients., Conclusions: A novel clinical presentation of MEH associated with HPV32 in HIV-negative, middle-aged to older adults is reported here. One case with HPV40 is the first to be reported. Future detection protocols should include HPV32, as it may be currently overlooked., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with improved survival and treatment response as compared to HPV-negative cancers. P16 overexpression is widely accepted as a surrogate marker for HPV positivity., Methods: A total of 92 serum samples from 75 head and neck squamous cell carcinoma (HNSCC) patients were examined for HPV16 and 18 E7 antibodies by ELISA. Available tissue was tested for HPV-DNA by PCR, and p16 immunohistochemistry was obtained from a deidentified database., Results: Of 75 HNSCC patients, 25 were HPV E7 seropositive. Seropositivity was strongly associated with cancers of the oropharynx, and correlated with positive p16 immunohistochemistry (IHC) and HPV-DNA. Post-treatment serum was available in a limited subset of patients, revealing a decrease in antibody titers following response to treatment., Conclusions: HPV E7 seropositivity correlated with positive tumor HPV-DNA and p16 expression, and was strongly associated with cancers of the oropharynx. E7 serology warrants further study as a potential biomarker in HPV-positive HNSCC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Current vaccines against Human Papillomavirus (HPV) are highly effective and based on recombinant virus-like particles (VLPs) of the major capsid protein L1. Since these vaccines are HPV type-specific and expensive for global implementation, an alternative, broader-spectrum immunogen would be the N-terminus of the minor capsid protein L2 that induces low titered broadly cross-neutralizing antibodies. Here we analyzed the reactivity of different synthetic L2 peptides containing N-terminus amino acids 17-36 in order to test their antigenicity., Methods: Different synthetic peptides were designed to target the 17-36 amino acid sequences, present in highly antigenic amino-terminus of L2 protein. Six different peptides including Cys22-Cys28 disulfide bonded cyclized L2 peptide were examined for their antigenicity against mouse monoclonal antibody RG-1 and rabbit polyclonal antisera to HPV L2 by enzyme-linked immunosorbent assay (ELISA)., Results: Here we report that the cyclized form of synthetic L2 peptide, which is formed through Cys22-Cys28 disulfide bridges, has the highest reactivity to antibodies than other synthetic L2 peptides., Conclusion: A cyclized L2 peptide has potential to be an excellent candidate to formulate a low-cost, broadly protective pan-oncogenic HPV vaccine., (Copyright © 2015. Published by Elsevier Inc.)

Compared to conventional hemodialysis dialysis, nocturnal hemodialysis represents a more effective modality for receiving hemodialysis and has been associated with a 25% reduction in risk of death and improved quality of life. This article identifies the evidence about the mortality and morbidity risk for patients undergoing conventional hemodialysis vs. nocturnal hemodialysis.

Papillomaviruses (PVs) induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), was horizontally transmitted within an inbred colony of NMRI-Foxn1(nu)/Foxn1nu (nude; T cell deficient) mice of an unknown period of time. A ground-up, filtered papilloma inoculum was not capable of infecting C57BL/6J wild-type mice; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1(nu) and B6.Cg-Foxn1(nu), but not NU/J-Foxn1(nu), mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, lacking B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail, and condylomas of the vaginal lining which could be induced by separate scarification or simultaneous scarification of MmuPV1 at all four sites. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Although trichoepitheliomas are benign, aggressive tumors, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were highly dysregulated.

In the United States, policy initiatives aimed at increasing sources of renewable energy are advancing bioenergy production, especially in the Midwest region, where agricultural landscapes dominate. While policy directives are focused on renewable fuel production, biodiversity and ecosystem services will be impacted by the land-use changes required to meet production targets. Using data from field observations, we developed empirical models for predicting abundance, diversity, and community composition of flower-visiting bees based on land cover. We used these models to explore how bees might respond under two contrasting bioenergy scenarios: annual bioenergy crop production and perennial grassland bioenergy production. In the two scenarios, 600,000 ha of marginal annual crop land or marginal grassland were converted to perennial grassland or annual row crop bioenergy production, respectively. Model projections indicate that expansion of annual bioenergy crop production at this scale will reduce bee abundance by 0 to 71%, and bee diversity by 0 to 28%, depending on location. In contrast, converting annual crops on marginal soil to perennial grasslands could increase bee abundance from 0 to 600% and increase bee diversity between 0 and 53%. Our analysis of bee community composition suggested a similar pattern, with bee communities becoming less diverse under annual bioenergy crop production, whereas bee composition transitioned towards a more diverse community dominated by wild bees under perennial bioenergy crop production. Models, like those employed here, suggest that bioenergy policies have important consequences for pollinator conservation.