Genetic continuity and change among the Indigenous peoples of California.

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.

Climate change, human health, and resilience in the Holocene.

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations-commonly known as "collapse." This survey of Holocene human-environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address.

Symbolic bones and interethnic violence in a frontier zone, northwest Mexico, ca. 500-900 C.E.

Although extensive deposits of disarticulated, commingled human bones are common in the prehispanic Northern Frontier of Mesoamerica, detailed bioarchaeological analyses of them are not. To our knowledge, this article provides the first such analysis of bone from a full residential-ceremonial complex and evaluates multiple hypotheses about its significance, concluding that the bones actively represented interethnic violence as well as other relationships among persons living and dead. Description of these practices is important to the discussion of multiethnic societies because the frontier was a context where urbanism and complexity were emerging and groups with the potential to form multiethnic societies were interacting, possibly in the same ways that groups did before the formation of larger multiethnic city-states in the core of Mesoamerica.

Bioarchaeological contributions to the study of violence.

The bioarchaeological record has an abundance of scientific evidence based on skeletal indicators of trauma to argue for a long history of internal and external group conflict. However, the findings also suggest variability, nuance, and unevenness in the type, use, and meaning of violence across time and space and therefore defy generalizations or easy quantification. Documenting violence-related behaviors provides an overview of the often unique and sometimes patterned cultural use of violence. Violence (lethal and nonlethal) is often associated with social spheres of influence and power connected to daily life such as subsistence intensification, specialization, competition for scarce resources, climate, population density, territorial protection and presence of immigrants, to name just a few. By using fine-grained biocultural analyses that interrogate trauma data in particular places at particular times in reconstructed archaeological contexts, a more comprehensive view into the histories and experiences of violence emerges. Moreover, identifying culturally specific patterns related to age, sex, and social status provide an increasingly complex picture of early small-scale groups. Some forms of ritual violence also have restorative and regenerative aspects that strengthen community identity. Bioarchaeological data can shed light on the ways that violence becomes part of a given cultural landscape. Viewed in a biocultural context, evidence of osteological trauma provides rich insights into social relationships and the many ways that violence is embedded within those relationships.

Zoonotic diseases: New directions in human-animal pathology.

Zoonotic diseases-human diseases of animal origin-represent one of the world's greatest health challenges, both today and in the past. Since the Neolithic, zoonotic diseases have been one of the major factors shaping and influencing human adaptation. Archaeology is ideally situated to provide the long view on human-animal-pathogen relationships through combining cultural, environmental and biological datasets, yet long-term studies of linked human and animal records have often been overlooked and undertheorized. The seven papers in this special issue "Zoonotic diseases: New directions in human-animal pathology" cover a range of diseases caused by bacterial, viral, and parasitic pathogens, from case studies drawn from across Europe, Asia, Africa and the Americas. They speak to the diversity of human-animal-environment interactions that shaped disease emergence and transmission. They also review methodological advancements relating to disease identification and interpretation and discuss interdisciplinary approaches to effectively investigate these complex processes in the past. This introduction highlights their key themes and outcomes and identifies research priorities moving forward.

Twenty-first century bioarchaeology: Taking stock and moving forward.

This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop's overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States. Ultimately, we focused on two related aims: (1) best practices for improving research designs and training and (2) evaluating topics of contemporary significance that reverberate through history and beyond as promising trajectories for bioarchaeological research. Among the former were contextual grounding, research question/hypothesis generation, statistical procedures appropriate for small samples and mixed qualitative/quantitative data, the salience of Bayesian methods, and training program content. Topical foci included ethics, social inequality, identity (including intersectionality), climate change, migration, violence, epidemic disease, adaptability/plasticity, the osteological paradox, and the developmental origins of health and disease. Given the profound changes required globally to address decolonization in the 21st century, this concern also entered many formal and informal discussions.

Refractory heartburn: comparison of intercellular space diameter in documented GERD vs. functional heartburn.

OBJECTIVES: Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH. METHODS: In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs). RESULTS: In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 µm, P=0.003) and FH (0.87 vs. 0.42 µm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 µm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014). CONCLUSIONS: ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.

Introduction of agriculture and its effects on women's oral health.

This study explores the dynamic relationship between the introduction of agriculture and its effects on women's oral health by testing the hypothesis that female reproductive physiology contributes to an oral environment more susceptible to chronic oral disease and that, in a population undergoing the foraging to farming transition, females will exhibit a higher prevalence of oral pathology than males. This is tested by comparing the presence, location, and severity of caries lesions and antemortem tooth loss across groups of reproductive aged and postreproductive females (n = 71) against corresponding groups of males (n = 71) in an Early Agricultural period (1600 B.C.-A.D. 200) skeletal sample from northwest Mexico. Caries rates did not differ by sex across age groups in the sample; however, females were found to exhibit significantly more antemortem tooth loss than males (P > 0.01). Differences were initially minimal but increased by age cohort until postreproductive females experienced a considerable amount of tooth loss, during a life stage when the accumulation of bodily insults likely contributed to dental exfoliation. Higher caries rates in females are often cited as the result of gender differences and dietary disparities in agricultural communities. In an early farming community, with diets being relatively equal, women were found to experience similar caries expression but greater tooth loss. We believe this differential pattern of oral pathology provides new evidence in support of the interpretation that women's oral health is impacted by effects relating to reproductive biology.

Functional analysis of the host defense peptide Human Beta Defensin-1: new insight into its potential role in cancer.

Although it is known that innate immunity is key for protecting the body against foreign agents such as bacteria, little is known about elements of the innate immune system that have anti-tumor activity. Human Beta Defensin-1 (hBD-1), an important component of the innate immune response, is lost at high frequencies in malignant prostatic tissue, while high levels of expression are maintained in adjacent benign regions. In prostate carcinoma, frequent genetic alterations occur in the 8p22-23 region and several studies indicate there may be multiple tumor suppressor genes present within this region. The high incidence of loss of hBD-1 expression in prostate cancer, along with its chromosomal location of 8p23.2, raised the possibility that it may play a role in tumor suppression. To gain insight as to its function in prostate cancer, hBD-1 was cloned and ectopically expressed in four prostate cancer cell lines. Induction of hBD-1 expression resulted in a decrease in cellular growth in DU145 and PC3 cells. However, hBD-1 has no effect on the growth of androgen receptor (AR) positive LNCaP prostate cancer cells, but was again growth suppressive to PC3 cells with ectopic AR expression (PC3/AR+). hBD-1 also caused rapid induction of cytolysis and caspase-mediated apoptosis in DU145 and PC3 prostate cancer cells. Although the regulation of hBD-1 was not addressed in this study, our preliminary data demonstrated that the pathways involved may include cMYC and PAX2. Data presented here are the first to provide evidence of its potential role in prostate cancer cell death.

Assessing stakeholder perceptions of the american society for biochemistry and molecular biology accreditation program for baccalaureate degrees.

The American Society for Biochemistry and Molecular Biology (ASBMB) began an accreditation program in 2013. The criteria for accreditation of undergraduate programs include sufficient infrastructure - number and expertise of faculty, physical space and equipment, support for faculty and students - and incorporation of core concepts in the curriculum - structure and function of biomolecules; information storage; energy transfer; and quantitative skills. Students in accredited programs are able to have their degrees ASBMB certified by taking an exam focused on knowledge or skills across the four core concept areas. Members of the accreditation committees administered a survey to key stakeholders in the BMB community: undergraduate programs, both those that have applied for accreditation and those that have not; alumni/ae of accredited programs; graduate and professional programs; and employers. The goals of the study were to gauge the success of the program and determine necessary areas of improvement. The results indicate that the major benefits of applying for accreditation are the impetus to gather data and analysis not generally collected, and access to assessment data via the exam. However, stakeholders outside of the undergraduate community showed little awareness of the accreditation program. Additionally, the application process itself was seen to be very time consuming. This feedback will be used to improve the process and engage in further outreach. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):464-471, 2018.

Gene expression profiling of favorable histology Wilms tumors and its correlation with clinical features.

The aims of this study were to understand the underlying molecular mechanisms of favorable histology Wilms tumors (WTs) and to classify them based on their molecular signatures. We studied a total of 15 favorable histology WTs using microarrays containing 19,968 cDNAs. First, we found commonly altered genes in WT. A total of 267 cDNAs were significantly overexpressed at least 3-fold in all of the tumors compared with noncancerous kidney and contained known WT-related genes such as IGF II and WT1. The gene with the highest expression change compared with noncancerous kidney was topoisomerase IIalpha. By hierarchical clustering, there was a clear distinction between high-stage and low-stage tumors. A total of 30 cDNAs were found differentially expressed between the high- and low-stage groups. One of them, Stathmin 1, which is involved in the microtubule system, was highly expressed in high-stage tumors compared with the low-stage tumors. The present chemotherapy regimens for WT consist mainly of topoisomerase II inhibitors (i.e., actinomycin D, doxorubicin, and etoposide) and antimicrotubule agents (i.e., vincristine and paclitaxel). Our data suggest that high expression of topoisomerase IIalpha and microtubule-related genes such as tubulin and stathmin 1 may be related to the high chemosensitivity of WT. In addition, retinol-related genes such as CRABP2 and retinol-binding protein 1 were overexpressed in WT, and CRABP2 was more highly expressed in the poor outcome patients, which suggests that retinoid acid may be a potential drug. In summary, our findings suggest that the integration of gene expression data and clinical parameters could aid in detecting aggressive tumors among favorable histology WT and lead to the discovery of new drugs for WT.

Differential diagnosis of a progressive neuromuscular disorder using bioarchaeological and biogeochemical evidence from a bronze age skeleton in the UAE.

Bioarchaeologists frequently rely on differential diagnoses to examine pathological conditions in ancient human skeletons. However, this method is often hindered by the skeleton's limited response abilities, resulting in similar skeletal expressions across multiple diseases. These diseases can be placed into perspective by using stable isotope analysis to explore the life course of an individual. In the current study, strontium, oxygen, and carbon isotope values from the dental enamel of a young (18-20 year old) paraplegic female interred within the Bronze Age Tomb of Tell Abraq are used to explore her life course and give perspective on a previously indeterminate differential diagnosis involving a progressive neuromuscular disorder. This individual's isotope values show that she was a non-local migrant who arrived at Tell Abraq sometime after 15 years of age and that her immigrant status may have placed her at enhanced immunological risk for developing paralytic poliomyelitis. We argue that biogeochemical analysis can be used to go beyond questions of residential mobility to examine the lifeways and broader cultural practices of ancient peoples.

A national comparison of biochemistry and molecular biology capstone experiences.

Recognizing the increasingly integrative nature of the molecular life sciences, the American Society for Biochemistry and Molecular Biology (ASBMB) recommends that Biochemistry and Molecular Biology (BMB) programs develop curricula based on concepts, content, topics, and expected student outcomes, rather than courses. To that end, ASBMB conducted a series of regional workshops to build a BMB Concept Inventory containing validated assessment tools, based on foundational and discipline-specific knowledge and essential skills, for the community to use. A culminating activity, which integrates the educational experience, is often part of undergraduate molecular life science programs. These "capstone" experiences are commonly defined as an attempt to measure student ability to synthesize and integrate acquired knowledge. However, the format, implementation, and approach to outcome assessment of these experiences are quite varied across the nation. Here we report the results of a nation-wide survey on BMB capstone experiences and discuss this in the context of published reports about capstones and the findings of the workshops driving the development of the BMB Concept Inventory. Both the survey results and the published reports reveal that, although capstone practices do vary, certain formats for the experience are used more frequently and similarities in learning objectives were identified. The use of rubrics to measure student learning is also regularly reported, but details about these assessment instruments are sparse in the literature and were not a focus of our survey. Finally, we outline commonalities in the current practice of capstones and suggest the next steps needed to elucidate best practices.

Identification and characterization of an L-type Cav1.2 channel in spiral ligament fibrocytes of gerbil inner ear.

Intracellular free Ca2+ levels are critical to the activity of BK channels in inner ear type I spiral ligament fibrocytes. However, the mechanisms for regulating intracellular Ca2+ levels in these cells are currently poorly understood. Using patch-clamp technique, we have identified a voltage-dependent L-type Ca2+ channel in type I spiral ligament fibrocytes cultured from gerbil inner ear. With 10 mM Ba2+ as the conductive cation, an inwardly rectifying current was elicited with little inactivation by membrane depolarization. The voltage activation threshold and the half-maximal voltage activation were -40 and -6 mV, respectively. This inward whole-cell current reached its peak at around 10 mV of membrane potential. The amplitude of the peak current varied among cells ranging from 50 to 274 pA with an average of 132.4 +/- 76.2 pA (n = 19); 10(-6) M nifedipine significantly inhibited the inward currents by 90.3 +/- 1.2% (n = 11). RT-PCR analysis revealed that cultured type I spiral ligament fibrocytes express the alpha1C isoform of the L-type Ca2+ channels encoded by the Cav1.2 gene. The expression of this channel in gerbil inner ear was confirmed by RT-PCR analysis using freshly isolated spiral ligament tissues. The Cav1.2 channel may function in conjunction with a previously identified intracellular Ca-ATPase (SERCA) to regulate intracellular free Ca2+ levels in type I spiral ligament fibrocytes, and thus modulate BK channel activity in these cells.

Dermal absorption of camphor, menthol, and methyl salicylate in humans.

Camphor, menthol, and methyl salicylate occur in numerous over-the-counter products. Although extensively used, there have been no estimates of human exposure following administration via dermal application. Furthermore, there is little information about the pharmacokinetics of those compounds. The authors report the plasma concentrations of the intact compounds as a function of dose following dermal patch application. Three groups of 8 subjects (4 male, 4 female) applied a different number of commercial patches (2, 4, or 8) to the skin for 8 hours. Plasma samples were assayed using sensitive and selective gas-chromatographic methods. For the 8-patch group, the average maximum plasma concentrations (Cmax +/- SD) were 41.0 +/- 5.8 ng/mL, 31.9 +/- 8.8 ng/mL, and 29.5 +/- 10.5 ng/mL for camphor, menthol, and methyl salicylate, respectively. The corresponding values for the 4-patch group were 26.8 +/- 7.2 ng/mL, 19.0 +/- 5.4 ng/mL, and 16.8 +/- 6.8 ng/mL. The harmonic mean terminal half-lives were 5.6 +/- 1.3 hours, 4.7 +/- 1.6 hours, and 3.0 +/- 1.2 hours for camphor, menthol, and methyl salicylate, respectively. The 2-patch group had measurable but low plasma concentrations of each compound. Low-dose dermal application for an extended time results in low plasma concentrations of all 3 compounds. Four and 8 patches, when applied for 8 hours, gave measurable and nearly proportional plasma concentrations. Although unable to determine the absolute dermal bioavailability of these compounds, there appears to be relatively low systemic exposure to these potentially toxic compounds, even when an unrealistically large number of patches are applied for an unusually long time.

BK channels mediate the voltage-dependent outward current in type I spiral ligament fibrocytes.

Recent experimental and clinical studies have provided considerable evidence to support the phenomenon of K(+) recycling in the mammalian cochlea. However, the precise cellular and molecular mechanisms underlying and regulating this process remain only partially understood. Here, we report that cultured type I spiral ligament fibrocytes (SLFs), a major component of the K(+) recycling pathway, have a dominant K(+) membrane conductance that is mediated by BK channels. The averaged half-maximal voltage-dependent membrane potential for the whole-cell currents was 70+/-1.2 mV at 1 nM intracellular free Ca(2+) and shifted to 38+/-0.2 mV at 20 microM intracellular free Ca(2+) (n=4-6). The reversal potential of whole-cell tail currents against different bath K(+) concentrations was 52 mV per decade (n=3-6). The sequence of relative ion permeability of the whole-cell conductance was K(+)>Rb(+)z.Gt;Cs(+)>Na(+) (n=5-17). The whole-cell currents were inhibited by extracellular tetraethylammonium and iberiotoxin (IbTx) with IC(50) values of 0.07 mM and 0.013 microM, respectively (n=3-7). The membrane potentials of type I SLFs measured with conventional zero-current whole-cell configuration were highly K(+)-selective and sensitive to IbTx (n=4-9). In addition, the BK channels in these cells exhibited voltage-dependent and incomplete inactivation properties and the recovery time was estimated to be approximately 6 s with repetitive voltage pulses from -70 to 80 mV (n=3). These data suggest that BK channels in type I SLFs play a major role in regulating the intracellular electrochemical gradient in the lateral wall syncytium responsible for facilitating the K(+) movement from perilymph to the stria vascularis.

Indigenous violence in Northern Mexico on the eve of contact.

La Cueva de Dos Cuchillos, near San Francisco de Borja, is a mortuary cave site in Chihuahua, Mexico. Dating to the late Prehistoric period, commingled human skeletal remains were interred in this cave and are thought to belong to the Tarahumara cultural group. Skeletal analyses indicate that a minimum of 10 adults and 7 subadults were interred at this site. Of these, three individuals exhibited signs of perimortem trauma. This included chop marks on one adult male and perimortem neck fractures on two other individuals. In order to investigate these indications of violence and place the remains in the larger social and political landscape, archeological, ethnographic and ethnohistoric data on the Tarahumara and other groups in the region was examined. This included information on intergroup interactions between the Tarahumara and other local cultures. The results of the analysis indicate that the wounds on these three individuals could be consistent with reports of regional intergroup performative violence. Due to the combination of multiple types of evidence in this case, it is suggested that at least some people at this site were victims of either regional intergroup performative violence, or conflict with non-local groups traveling in this important trade corridor.