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Incorporating archaeology within the high school curricula fosters an interest in archaeology and site preservation. The Milton High School Archaeology Project provides students the opportunity to experience and participate in archaeological research. At a 19th-century brickyard, students learn anthropology and their local history through hands-on excavations. Through the use of Project-Based Learning (PBL), students conducted archaeological and historical research and presented their work in the form of a museum exhibit at the Florida Public Archaeological Network’s Destination Archaeology Resources Center museum for the public and their parents. The Milton High School Archaeology Project provides an example of how archaeology can easily and effectively be integrated into high school educational standards. Quantitative and qualitative data collected throughout the 2016-2017 school year shows how archaeology education leads to increased awareness of and appreciation for heritage sites.

The U.S. Department of Energy Systems Biology Knowledgebase (KBase) is an open-source software and data platform designed to meet the grand challenge of systems biology - predicting and designing biological function from the biomolecular (small scale) to the ecological (large scale). KBase is available for anyone to use, and enables researchers to collaboratively generate, test, compare, and share hypotheses about biological functions; perform large-scale analyses on scalable computing infrastructure; and combine experimental evidence and conclusions that lead to accurate models of plant and microbial physiology and community dynamics. The KBase platform has (1) extensible analytical capabilities that currently include genome assembly, annotation, ontology assignment, comparative genomics, transcriptomics, and metabolic modeling; (2) a web-browser-based user interface that supports building, sharing, and publishing reproducible and well-annotated analyses with integrated data; (3) access to extensive computational resources; and (4) a software development kit allowing the community to add functionality to the system.

In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF) and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic-di-GMP (c-di-GMP), and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol stimulation of c-di-GMP. Multiple lines of evidence indicate that ethanol stimulates WspR signaling through its cognate sensor WspA, and promotes WspR-dependent activation of Pel exopolysaccharide production, which contributes to biofilm maturation. We also found that ethanol stimulation of WspR promoted P. aeruginosa colonization of CF airway epithelial cells. P. aeruginosa production of phenazines occurs both in the CF lung and in culture, and phenazines enhance ethanol production by C. albicans. Using a C. albicans adh1/adh1 mutant with decreased ethanol production, we found that fungal ethanol strongly altered the spectrum of P. aeruginosa phenazines in favor of those that are most effective against fungi. Thus, a feedback cycle comprised of ethanol and phenazines drives this polymicrobial interaction, and these relationships may provide insight into why co-infection with both P. aeruginosa and C. albicans has been associated with worse outcomes in cystic fibrosis.

Cells must access resources to survive, and the anatomy of multicellular structures influences this access. In diverse multicellular eukaryotes, resources are provided by internal conduits that allow substances to travel more readily through tissue than they would via diffusion. Microbes growing in multicellular structures, called biofilms, are also affected by differential access to resources and we hypothesized that this is influenced by the physical arrangement of the cells. In this study, we examined the microanatomy of biofilms formed by the pathogenic bacterium Pseudomonas aeruginosa and discovered that clonal cells form striations that are packed lengthwise across most of a mature biofilm’s depth. We identified mutants, including those defective in pilus function and in O-antigen attachment, that show alterations to this lengthwise packing phenotype. Consistent with the notion that cellular arrangement affects access to resources within the biofilm, we found that while the wild type shows even distribution of tested substrates across depth, the mutants show accumulation of substrates at the biofilm boundaries. Furthermore, we found that altered cellular arrangement within biofilms affects the localization of metabolic activity, the survival of resident cells, and the susceptibility of subpopulations to antibiotic treatment. Our observations provide insight into cellular features that determine biofilm microanatomy, with consequences for physiological differentiation and drug sensitivity.

Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity that can lead to limited functional recovery. Because many PNIs are not amenable to repair with traditional techniques, cell therapies have emerged as a treatment option. Exosomes, which can be secreted by Schwann cells (SC), carry cellular signaling molecules that facilitate intercellular communication. Our laboratory and others have success using SC-derived exosomes in preclinical PNI models; however, there is no study that directly compares recovery from different PNIs after exosome treatment. Thus, the currently study investigated if SC-derived exosomes can effectively treat different types of PNI, as measured by axonal regeneration and functional recovery. Adult male Fischer rats were divided into several treatment groups, including nerve transection, reversed autograft, conduit + exosomes, nerve crush, and nerve crush + exosomes. Animals underwent functional assessment through the duration of the experiment and at the conclusion (11 weeks), electrophysiological and histological characteristics were assessed. Results indicate an injury-specific effect of SC-derived exosome treatment. Specifically, exosome treatment improved axon regeneration/myelination, muscle recovery, and gait characteristics for severe, large-gap injuries. These SC-exosome based effects were not observed in crush injuries. Taken together, the results of the current study indicate that there may be differences in recovery based on injury type after PNI and treatment with SC-derived exosomes, potentially due to differences in exosome retention/distribution at the injury site. Future studies should explore how exosomes are distributed following administration across various PNI models, as their therapeutic effects may be more pronounced in upstream regions.

Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity, often leading to limited functional recovery and pain. Many PNIs are not amenable to repair with traditional techniques; however, cell therapies, particularly Schwann cells (SCs), offer the promise of neural tissue replacement and functional improvement. Exosomes, which carry cellular signaling molecules, can be secreted by SCs and have shown promise in PNI. Our laboratory has had success using SCs in preclinical and clinical treatment settings. Transplanted cells have several known limitations, which exosomes mitigate. To that end, the current study investigated if implanted SC-derived exosomes in conduits, conduits with SCs, reverse autograft, or empty conduits comparably improve axonal regeneration and pain outcomes 16-weeks after repair of a long gap PNI in adult rats. Results show that there were no differences between groups in the von Frey filament testing or in the Hargreaves test. Electrophysiological testing showed a significant difference between the injured (ipsilateral) and uninjured (contralateral) limbs while histological assessment showed a significant difference between axonal counts in different areas of the conduit. Based on the results of the current study, more research is needed to understand the therapeutic role of exosomes in PNI.

An advanced LIGO and Virgo’s third observing run brought another binary neutron star merger (BNS) and the first neutron-star black hole mergers. While no confirmed kilonovae were identified in conjunction with any of these events, continued improvements of analyses surrounding GW170817 allow us to project constraints on the Hubble Constant (H 0), the Galactic enrichment from r-process nucleosynthesis, and ultra-dense matter possible from forthcoming events. Here, we describe the expected constraints based on the latest expected event rates from the international gravitational-wave network and analyses of GW170817. We show the expected detection rate of gravitational waves and their counterparts, as well as how sensitive potential constraints are to the observed numbers of counterparts. We intend this analysis as support for the community when creating scientifically driven electromagnetic follow-up proposals. During the next observing run O4, we predict an annual detection rate of electromagnetic counterparts from BNS of 0.43−0.26+0.58 ( 1.97−1.2+2.68 ) for the Zwicky Transient Facility (Rubin Observatory).

Climatic conditions that challenge human thermoregulatory capacity currently affect around a quarter of the world’s population annually. Such conditions are projected to increase in line with CO 2 emissions particularly in the humid tropics. Climate change can increase the risk of conditions that exceed human thermoregulatory capacity 1 , 2 , 3 , 4 , 5 , 6 . Although numerous studies report increased mortality associated with extreme heat events 1 , 2 , 3 , 4 , 5 , 6 , 7 , quantifying the global risk of heat-related mortality remains challenging due to a lack of comparable data on heat-related deaths 2 , 3 , 4 , 5 . Here we conducted a global analysis of documented lethal heat events to identify the climatic conditions associated with human death and then quantified the current and projected occurrence of such deadly climatic conditions worldwide. We reviewed papers published between 1980 and 2014, and found 783 cases of excess human mortality associated with heat from 164 cities in 36 countries. Based on the climatic conditions of those lethal heat events, we identified a global threshold beyond which daily mean surface air temperature and relative humidity become deadly. Around 30% of the world’s population is currently exposed to climatic conditions exceeding this deadly threshold for at least 20 days a year. By 2100, this percentage is projected to increase to ∼48% under a scenario with drastic reductions of greenhouse gas emissions and ∼74% under a scenario of growing emissions. An increasing threat to human life from excess heat now seems almost inevitable, but will be greatly aggravated if greenhouse gases are not considerably reduced.

HIV remains a leading contributor to the disease burden in sub-Saharan Africa, with adolescents and young people disproportionately affected. Optimising pre-exposure prophylaxis (PrEP) uptake has predominantly focused on women and adult men who have sex with men. We explore adolescent boys and young men's PrEP uptake preferences in South Africa, Uganda, and Zimbabwe. A cross-sectional sequential exploratory mixed-methods study amongst males aged 13-24 years was conducted between April and September 2019 as part of the CHAPS trial. Group discussions (GDs) and In-Depth Interviews (IDIs) focused on motivations and hindrances for HIV testing, PrEP preference, and reasons for the uptake of PrEP. A thematic approach was used to analyse the qualitative data. A quantitative survey following the qualitative work covered questions on demographics, HIV risk and PrEP preferences (on-demand vs. daily). For quantitative analysis, we fitted logistic regression models to determine factors associated with on-demand vs daily PrEP preference. Overall, 647 adolescent boys and young men (median age 20, IQR: 17-22) were enrolled. Of these, 422 (65.22%) preferred on-demand PrEP (South Africa 45.45%, Uganda 76.80%, Zimbabwe 70.35%; p<0.001). Factors independently associated with on-demand PrEP included country (South Africa, adjusted odds ratio (aOR) = 0.19 [95%CI:0.1-0.3] compared to Uganda) and advanced planning of sex [>24 hours in advance aOR = 1.4 (0.9-2.3) compared to <2 hours]. Qualitatively, participants commonly believed they were not at risk of HIV acquisition most of the time and thought that on-demand PrEP would be suitable as they tend to plan sexual activity in advance. Preference for on-demand PrEP is high in young males. The qualitative data support a preference for on-demand PrEP in those who plan sex in advance. HIV intervention programs should offer both on-demand and daily PrEP to engage more adolescent boys and young men in HIV prevention practices.