Ancient engineering of fish capture and storage in southwest Florida.

In the 16th century, the Calusa, a fisher-gatherer-hunter society, were the most politically complex polity in Florida, and the archaeological site of Mound Key was their capital. Based on historic documents, the ruling elite at Mound Key controlled surplus production and distribution. The question remains exactly how such surplus pooling occurred and when such traditions were elaborated on and reflected in the built environment. Our work focuses on the "watercourts" and associated areas at Mound Key. These subrectangular constructions of shell and other sediments around centralized inundated areas have been variously interpreted. Here, we detail when these enclosures were constructed and their engineering and function. We argue that these structures were for large surplus capture and storage of aquatic resources that were controlled and managed by corporate groups.

Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence.

Mycobacterium tuberculosis (Mtb) encodes five type VII secretion systems (T7SS), designated ESX-1-ESX-5, that are critical for growth and pathogenesis. The best characterized is ESX-1, which profoundly impacts host cell interactions. In contrast, the ESX-3 T7SS is implicated in metal homeostasis, but efforts to define its function have been limited by an inability to recover deletion mutants. We overcame this impediment using medium supplemented with various iron complexes to recover mutants with deletions encompassing select genes within esx-3 or the entire operon. The esx-3 mutants were defective in uptake of siderophore-bound iron and dramatically accumulated cell-associated mycobactin siderophores. Proteomic analyses of culture filtrate revealed that secretion of EsxG and EsxH was codependent and that EsxG-EsxH also facilitated secretion of several members of the proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) protein families (named for conserved PE and PPE N-terminal motifs). Substrates that depended on EsxG-EsxH for secretion included PE5, encoded within the esx-3 locus, and the evolutionarily related PE15-PPE20 encoded outside the esx-3 locus. In vivo characterization of the mutants unexpectedly showed that the ESX-3 secretion system plays both iron-dependent and -independent roles in Mtb pathogenesis. PE5-PPE4 was found to be critical for the siderophore-mediated iron-acquisition functions of ESX-3. The importance of this iron-acquisition function was dependent upon host genotype, suggesting a role for ESX-3 secretion in counteracting host defense mechanisms that restrict iron availability. Further, we demonstrate that the ESX-3 T7SS secretes certain effectors that are important for iron uptake while additional secreted effectors modulate virulence in an iron-independent fashion.

"I'm Just Forgetting and I Don't Know Why": Exploring How People Living With HIV-Associated Neurocognitive Disorder View, Manage, and Obtain Support for Their Cognitive Difficulties.

HIV-associated neurocognitive disorder (HAND) is common, but the lived experience of HAND is not well-understood. In this descriptive qualitative study, we explored how adults with HAND view, manage, and obtain support for cognitive difficulties. We interviewed 25 participants (20% female; median age = 51 years) who were diagnosed with HAND using neuropsychological assessment and a clinical interview. Semistructured interviews, co-developed with community members living with HIV, focused on how cognitive difficulties manifested and progressed, impacted well-being, and were discussed with others. We analyzed interview transcripts using a team-based, thematic approach. Participants described concentration, memory, and multitasking difficulties that fluctuated over time, as well as potential risk factors, management strategies, and psychosocial consequences. They reported they seldom discussed cognitive impairment with health care professionals, and that receiving a HAND diagnosis was validating, informative, yet somewhat disconcerting. Conversations between health care professionals and people living with HIV about HAND may provide opportunities for education, assessment, and support.

Role of Metal-Dependent Regulation of ESX-3 Secretion in Intracellular Survival of Mycobacterium tuberculosis.

More people die every year from Mycobacterium tuberculosis infection than from infection by any other bacterial pathogen. Type VII secretion systems (T7SS) are used by both environmental and pathogenic mycobacteria to secrete proteins across their complex cell envelope. In the nonpathogen Mycobacterium smegmatis, the ESX-1 T7SS plays a role in conjugation, and the ESX-3 T7SS is involved in metal homeostasis. In M. tuberculosis, these secretion systems have taken on roles in virulence, and they also are targets of the host immune response. ESX-3 secretes a heterodimer composed of EsxG (TB9.8) and EsxH (TB10.4), which impairs phagosome maturation in macrophages and is essential for virulence in mice. Given the importance of EsxG and EsxH during infection, we examined their regulation. With M. tuberculosis, the secretion of EsxG and EsxH was regulated in response to iron and zinc, in accordance with the previously described transcriptional response of the esx-3 locus to these metals. While iron regulated the esx-3 expression in both M. tuberculosis and M. smegmatis, there is a significant difference in the dynamics of this regulation. In M. smegmatis, the esx-3 locus behaved like other iron-regulated genes such as mbtB In M. tuberculosis, both iron and zinc modestly repressed esx-3 expression. Diminished secretion of EsxG and EsxH in response to these metals altered the interaction of M. tuberculosis with macrophages, leading to impaired intracellular M. tuberculosis survival. Our findings detail the regulatory differences of esx-3 in M. tuberculosis and M. smegmatis and demonstrate the importance of metal-dependent regulation of ESX-3 for virulence in M. tuberculosis.

Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking.

Mycobacterium tuberculosis (Mtb) disrupts anti-microbial pathways of macrophages, cells that normally kill bacteria. Over 40 years ago, D'Arcy Hart showed that Mtb avoids delivery to lysosomes, but the molecular mechanisms that allow Mtb to elude lysosomal degradation are poorly understood. Specialized secretion systems are often used by bacterial pathogens to translocate effectors that target the host, and Mtb encodes type VII secretion systems (TSSSs) that enable mycobacteria to secrete proteins across their complex cell envelope; however, their cellular targets are unknown. Here, we describe a systematic strategy to identify bacterial virulence factors by looking for interactions between the Mtb secretome and host proteins using a high throughput, high stringency, yeast two-hybrid (Y2H) platform. Using this approach we identified an interaction between EsxH, which is secreted by the Esx-3 TSSS, and human hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT). ESCRT has a well-described role in directing proteins destined for lysosomal degradation into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs), ensuring degradation of the sorted cargo upon MVB-lysosome fusion. Here, we show that ESCRT is required to deliver Mtb to the lysosome and to restrict intracellular bacterial growth. Further, EsxH, in complex with EsxG, disrupts ESCRT function and impairs phagosome maturation. Thus, we demonstrate a role for a TSSS and the host ESCRT machinery in one of the central features of tuberculosis pathogenesis.

Modeling the potential impact of storm surge and sea level rise on coastal archaeological heritage: A case study from Georgia.

Climate change poses great risks to archaeological heritage, especially in coastal regions. Preparing to mitigate these challenges requires detailed and accurate assessments of how coastal heritage sites will be impacted by sea level rise (SLR) and storm surge, driven by increasingly severe storms in a warmer climate. However, inconsistency between modeled impacts of coastal erosion on archaeological sites and observed effects has thus far hindered our ability to accurately assess the vulnerability of sites. Modeling of coastal impacts has largely focused on medium-to-long term SLR, while observations of damage to sites have almost exclusively focused on the results of individual storm events. There is therefore a great need for desk-based modeling of the potential impacts of individual storm events to equip cultural heritage managers with the information they need to plan for and mitigate the impacts of storm surge in various future sea level scenarios. Here, we apply the Sea, Lake, and Overland Surges from Hurricanes (SLOSH) model to estimate the risks that storm surge events pose to archaeological sites along the coast of the US State of Georgia in four different SLR scenarios. Our results, shared with cultural heritage managers in the Georgia Historic Preservation Division to facilitate prioritization, documentation, and mitigation efforts, demonstrate that over 4200 archaeological sites in Georgia alone are at risk of inundation and erosion from hurricanes, more than ten times the number of sites that were previously estimated to be at risk by 2100 accounting for SLR alone. We hope that this work encourages necessary action toward conserving coastal physical cultural heritage in Georgia and beyond.

The initial spread of peaches across eastern North America was structured by Indigenous communities and ecologies.

We conduct a synthetic archaeological and ethnohistoric dating program to assess the timing and tempo of the spread of peaches, the first Eurasian domesticate to be adopted across Indigenous eastern North America, into the interior American Southeast by Indigenous communities who quickly "Indigenized" the fruit. In doing so, we present what may be the earliest absolute dates for archaeological contexts containing preserved peach pits in what is today the United States in the early to mid-16th century. Along with our broader chronological modeling, these early dates suggest that peaches were likely in the interior prior to permanent Spanish settlement in the American Southeast and that peaches spread independently of interactions with Spanish colonizers. We further argue that that eventual spread of peaches was structured exclusively by Indigenous communities and the ecologies produced through long-term Indigenous land management and land use practices, highlighting and centering the agency of Indigenous societies in the socioecological process of colonization.

The dynamics of fishing villages along the South Atlantic Coast of North America (ca. 5000-3000 years BP).

We present new chronologies that inform the timing and tempo of shell ring and shell mound construction on the South Atlantic Bight. Our project combines recently acquired dates with legacy radiocarbon dates from over 25 rings and mounds to provide a higher-resolution chronology regarding the occupation and formation of this larger landscape of the earliest fishing villages along the East Coast of the United States. We resolve the ordering and timing of occupation of these rings and mounds through Bayesian statistical modeling. These new models historicize and contextualize these shell rings in ways previously impossible. Specifically, our new chronologies of these villages indicate that the earliest villages were established prior to the invention of pottery. The early period of village establishment evidences isolated village rings, whereas later periods seem to have more villages, but these appear to have been relocated to other areas and/or islands over time. Shell mounds are fewer in number, are spread throughout the time period, and may represent special purpose sites compared to shell-rings. Once villages spread, they quickly adopted new technologies (i.e., pottery) and created new institutions and practiced village relocation, which allowed this way of life to persist for more than a thousand years.

Shellfishing, sea levels, and the earliest Native American villages (5000-3800 yrs. BP) of the South Atlantic Coast of the U.S.

Shell ring archaeological sites are one of the most visible site types along the lower South Atlantic Coast of the United States. These cultural sites are large, circular to arcuate piles of mollusk shells with some reaching over three meters in elevation and over 100 m in diameter. They are comprised largely of mollusk shells (e.g., Eastern oyster, Crassostrea virginica), but also contain early pottery, nonhuman faunal remains, and other artifacts. Our work establishes that they represent the earliest widespread Native American villages occupied year-round in the Eastern Woodlands of North America. Significantly, our results from sea-level modelling and isotope geochemistry on mollusks establish that the inhabitants of these earliest villages (ca. 5000-3800 yrs. BP) lived within a fluctuating coastal environment, harvested certain resources year-round, and targeted diverse habitats across the estuaries. Both the growth and decline of these earliest villages are associated with a concomitant rise and lowering of sea level that impacted the productivity of the oyster reef fishery along the South Atlantic Coast. Despite these large-scale environmental changes, this research indicates that Native American fishing villages persisted along the coast for over 1000 years.

Correction: A multi-proxy assessment of the impact of environmental instability on Late Holocene (4500-3800 BP) Native American villages of the Georgia coast.

[This corrects the article DOI: 10.1371/journal.pone.0258979.].

The glutathione peroxidase 1-protein tyrosine phosphatase 1B-protein phosphatase 2A axis. A key determinant of airway inflammation and alveolar destruction.

Protein phosphatase-2A (PP2A) is a primary serine-threonine phosphatase that modulates inflammatory responses in asthma and chronic obstructive pulmonary disease (COPD). Despite its importance, the mechanisms that regulate lung PP2A activity remain to be determined. The redox-sensitive enzyme protein tyrosine phosphatase-1B (PTP1B) activates PP2A by dephosphorylating the catalytic subunit of the protein at tyrosine 307. This study aimed to identify how the interaction between the intracellular antioxidant glutathione peroxidase-1 (GPx-1) and PTP1B affected lung PP2A activity and airway inflammation. Experiments using gene silencing techniques in mouse lung or human small airway epithelial cells determined that knocking down PTP1B expression blocked GPx-1's activation of PP2A and negated the anti-inflammatory effects of GPx-1 protein in the lung. Similarly, the expression of human GPx-1 in transgenic mice significantly increased PP2A and PTP1B activities and prevented chronic cigarette smoke-induced airway inflammation and alveolar destruction. GPx-1 knockout mice, however, exhibited an exaggerated emphysema phenotype, correlating with a nonresponsive PP2A pathway. Importantly, GPx-1-PTP1B-PP2A signaling becomes inactivated in advanced lung disease. Indeed, PTP1B protein was oxidized in the lungs of subjects with advanced emphysema, and cigarette smoke did not increase GPx-1 or PTP1B activity within epithelial cells isolated from subjects with COPD, unlike samples of healthy lung epithelial cells. In conclusion, these findings establish that the GPx-1-PTP1B-PP2A axis plays a critical role in countering the inflammatory and proteolytic responses that result in lung-tissue destruction in response to cigarette smoke exposure.

A multi-proxy assessment of the impact of environmental instability on Late Holocene (4500-3800 BP) Native American villages of the Georgia coast.

Circular shell rings along the South Atlantic Coast of North America are the remnants of some of the earliest villages that emerged during the Late Archaic (5000-3000 BP). Many of these villages, however, were abandoned during the Terminal Late Archaic (ca 3800-3000 BP). We combine Bayesian chronological modeling with mollusk shell geochemistry and oyster paleobiology to understand the nature and timing of environmental change associated with the emergence and abandonment of circular shell ring villages on Sapelo Island, Georgia. Our Bayesian models indicate that Native Americans occupied the three Sapelo shell rings at varying times with some generational overlap. By the end of the complex's occupation, only Ring III was occupied before abandonment ca. 3845 BP. Ring III also consists of statistically smaller oysters harvested from less saline estuaries compared to earlier occupations. Integrating shell biochemical and paleobiological data with recent tree ring analyses shows a clear pattern of environmental fluctuations throughout the period in which the rings were occupied. We argue that as the environment became unstable around 4300 BP, aggregation at villages provided a way to effectively manage fisheries that are highly sensitive to environmental change. However, with the eventual collapse of oyster fisheries and subsequent rebound in environmental conditions ca. post-3800 BP, people dispersed from shell rings, and shifted to non-marine subsistence economies and other types of settlements. This study provides the most comprehensive evidence for correlations between large-scale environmental change and societal transformations on the Georgia coast during the Late Archaic period.

Indigenous oyster fisheries persisted for millennia and should inform future management.

Historical ecology has revolutionized our understanding of fisheries and cultural landscapes, demonstrating the value of historical data for evaluating the past, present, and future of Earth's ecosystems. Despite several important studies, Indigenous fisheries generally receive less attention from scholars and managers than the 17th-20th century capitalist commercial fisheries that decimated many keystone species, including oysters. We investigate Indigenous oyster harvest through time in North America and Australia, placing these data in the context of sea level histories and historical catch records. Indigenous oyster fisheries were pervasive across space and through time, persisting for 5000-10,000 years or more. Oysters were likely managed and sometimes "farmed," and are woven into broader cultural, ritual, and social traditions. Effective stewardship of oyster reefs and other marine fisheries around the world must center Indigenous histories and include Indigenous community members to co-develop more inclusive, just, and successful strategies for restoration, harvest, and management.

Ecosystem stability and Native American oyster harvesting along the Atlantic Coast of the United States.

The eastern oyster (Crassostrea virginica) is an important proxy for examining historical trajectories of coastal ecosystems. Measurement of ~40,000 oyster shells from archaeological sites along the Atlantic Coast of the United States provides a long-term record of oyster abundance and size. The data demonstrate increases in oyster size across time and a nonrandom pattern in their distributions across sites. We attribute this variation to processes related to Native American fishing rights and environmental variability. Mean oyster length is correlated with total oyster bed length within foraging radii (5 and 10 km) as mapped in 1889 and 1890. These data demonstrate the stability of oyster reefs despite different population densities and environmental shifts and have implications for oyster reef restoration in an age of global climate change.

Market share and recent hiring trends in anthropology faculty positions.

Between 1985 and 2014, the number of US doctoral graduates in Anthropology increased from about 350 to 530 graduates per year. This rise in doctorates entering the work force along with an overall decrease in the numbers of tenure-track academic positions has resulted in highly competitive academic job market. We estimate that approximately79% of US anthropology doctorates do not obtain tenure-track positions at BA/BS, MA/MS, and PhD institutions in the US. Here, we examine where US anthropology faculty obtained their degrees and where they ultimately end up teaching as tenure-track faculty. Using data derived from the 2014-2015 AnthroGuide and anthropology departmental web pages, we identify and rank PhD programs in terms of numbers of graduates who have obtained tenure-track academic jobs; examine long-term and ongoing trends in the programs producing doctorates for the discipline as a whole, as well as for the subfields of archaeology, bioanthropology, and sociocultural anthropology; and discuss gender inequity in academic anthropology within the US.

Ground penetrating radar data used in discovery of the early Christian church of Notre Dame de Baudes near Labastide-du-Temple, France.

Data on ground-penetrating radar transect files are provided that support the research presented in "Discovery and Appraisal of the Early Christian Church of Notre Dame de Baudes near Labastide-du-Temple, France" [1]. Data consist of 102 transect files obtained with a GSSI SIR-3000 controller and a 400 MHz center frequency antenna in two grid blocks covering ca. 2700 m(2). The data are distributed raw without post-processing in SEG-Y rev. 1 format (little endian).

From Shell Midden to Midden-Mound: The Geoarchaeology of Mound Key, an Anthropogenic Island in Southwest Florida, USA.

Mound Key was once the capital of the Calusa Kingdom, a large Pre-Hispanic polity that controlled much of southern Florida. Mound Key, like other archaeological sites along the southwest Gulf Coast, is a large expanse of shell and other anthropogenic sediments. The challenges that these sites pose are largely due to the size and areal extent of the deposits, some of which begin up to a meter below and exceed nine meters above modern sea levels. Additionally, the complex depositional sequences at these sites present difficulties in determining their chronology. Here, we examine the development of Mound Key as an anthropogenic island through systematic coring of the deposits, excavations, and intensive radiocarbon dating. The resulting data, which include the reversals of radiocarbon dates from cores and dates from mound-top features, lend insight into the temporality of site formation. We use these insights to discuss the nature and scale of human activities that worked to form this large island in the context of its dynamic, environmental setting. We present the case that deposits within Mound Key's central area accumulated through complex processes that represent a diversity of human action including midden accumulation and the redeposition of older sediments as mound fill.

The application of an automated allele concordance analysis system (CompareCalls) to ensure the accuracy of single-source STR DNA profiles.

A powerful method for validating a scientific result is to confirm specific results utilizing independent methodologies and processing pathways. Thus, we have designed, developed and validated an automated allele concordance analysis system (CompareCalls, patent pending) that performs comparisons between two independent DNA analysis platforms to ensure the highest accuracy for allele calls. Application of this system in a quality assurance role has shown the potential to eliminate greater than 90% of the STR analysis required of a DNA data analyst. While this system is broadly applicable for use with any two independent STR analysis programs, either prior to or following human data review, we are presenting its application to data generated with the ABI Prism Genotyper software system versus data generated with the SurelockID system. With the automated allele concordance analysis system, the GeneScan DNA fragment data generated from an ABI 377 gel image are analyzed in two independent pathways. In one analysis pathway, the GeneScan data are imported into Genotyper software where STR labels are assigned to the fragment data based upon the criteria of the Kazam 20% macro. The "Kazam" macro provided with the Genotyper program works by labeling all peaks in a category (or locus) and then filtering (or removing) the labels from peaks, such as those in stutter positions, that meet predefined criteria. In the second pathway, the GeneScan data are imported into the SurelockID analysis platform where STR labels and error messages are assigned to the fragment data based upon hard-coded allele calling criteria and quality parameters. The resulting STR allele calls for each analysis platform are then compared, utilizing the automated allele concordance analysis system. Any differences in the STR allele calls between the two systems are flagged in a discordance report for further review by a qualified DNA data analyst. The automated allele concordance analysis system guides the DNA data analyst to the discordant data generated by either analysis platform. Additionally, the analyst is also directed to data that are of less than pristine quality which may have an increased potential for errors in interpretation by either analysis platform or by a human DNA data analyst. Implementation of an automated allele concordance analysis system will yield high-quality data for CODIS and free the human DNA data analyst to perform other critical duties within the laboratory.

Predisposition locus for major depression at chromosome 12q22-12q23.2.

Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2.