Isotopic evidence of high reliance on plant food among Later Stone Age hunter-gatherers at Taforalt, Morocco.

The transition from hunting-gathering to agriculture stands as one of the most important dietary revolutions in human history. Yet, due to a scarcity of well-preserved human remains from Pleistocene sites, little is known about the dietary practices of pre-agricultural human groups. Here we present the isotopic evidence of pronounced plant reliance among Late Stone Age hunter-gatherers from North Africa (15,000-13,000 cal BP), predating the advent of agriculture by several millennia. Employing a comprehensive multi-isotopic approach, we conducted zinc (δ66Zn) and strontium (87Sr/86Sr) analysis on dental enamel, bulk carbon (δ13C) and nitrogen (δ15N) and sulfur (δ34S) isotope analysis on dentin and bone collagen, and single amino acid analysis on human and faunal remains from Taforalt (Morocco). Our results unequivocally demonstrate a substantial plant-based component in the diets of these hunter-gatherers. This distinct dietary pattern challenges the prevailing notion of high reliance on animal proteins among pre-agricultural human groups. It also raises intriguing questions surrounding the absence of agricultural development in North Africa during the early Holocene. This study underscores the importance of investigating dietary practices during the transition to agriculture and provides insights into the complexities of human subsistence strategies across different regions.

Enhanced dietary reconstruction of Korean prehistoric populations by combining δ13C and δ15N amino acids of bone collagen.

Compound specific stable isotope analysis of amino acids (CSIA-AA) is a powerful tool for determining dietary behaviors in complex environments and improving dietary reconstructions. Here, we conducted CSIA-AA on human (n = 32) and animal (n = 13) remains from two prehistoric archaeological sites (Mumun, Imdang) to assess in more detail the dietary sources consumed by prehistoric Korean populations. Results of estimated trophic position (TP) using Δ15NGlx-Phe show that the Imdang individuals consumed aquatic resources, as well as terrestrial resources. Principal component analysis (PCA) using δ13C and δ15N essential amino acid (EAA) values show that the Imdang humans closely cluster with game birds and terrestrial herbivores, whilst the Mumun humans closely cluster with C4 plants. Quantitative estimation by a Bayesian mixing model (MixSIAR) indicates that the Imdang humans derived a large proportion of their proteins from terrestrial animals and marine fish, whereas the main protein sources for the Mumun humans were C4 plants and terrestrial animals. Additionally, the comparison between the EAA and bulk isotope models shows that there is a tendency to overestimate the consumption of plant proteins when using bulk isotopic data. Our CSIA-AA approach reveals that in prehistoric Korea there were clear differences in human diets through time. This study adds to a growing body of literature that demonstrates the potential of CSIA-AA to provide more accurate estimations of protein consumption in mixed diets than previous bulk isotopic studies.

Late shellmound occupation in southern Brazil: A multi-proxy study of the Galheta IV archaeological site.

Brazilian coastal archaeology is renowned for its numerous and large shellmounds (sambaquis), which had been continuously occupied from at least 8000 to 1000 years cal BP. However, changes in their structure and material culture in the late Holocene have led to different hypotheses concerning their ecological and cultural changes. The archaeological site Galheta IV (ca. 1300 to 500 years cal BP) offers new insights into the complexity of the late coastal occupation in southern Brazil. Our attempt was to determine whether Galheta IV can be classified as a sambaqui site, or if it belongs to a Southern proto-Jê settlement. Here, we reassessed Galheta's collections and applied a multi-proxy approach using: new 14C dates, zooarchaeology, δ13C and δ15N isotopes in bulk collagen and 87Sr/86Srenamel isotopic ratios from eight human individuals, ceramics analysis, and FTIR. The results indicate an intense exploitation of marine resources, with an area designated for processing animals located at the opposite side of the funerary areas. Bone tools and specific species of animals were found as burial accompaniments. No evidence of human cremations was detected. 87Sr/86Sr results indicate that the eight human individuals always lived on the coast, and did not come from the inland. The pottery analysis confirms the association with Itararé-Taquara, but contrary to what was assumed by previous studies, the pottery seems related to other coastal sites, and not to the highlands. In light of these findings, we propose that Galheta IV can be considered a funerary mound resulting from long and continuous interactions between shellmound and Southern proto-Jê populations. This study not only enhances our understanding of the late coastal occupation dynamics in southern Brazil but also underscores its importance in reshaping current interpretations of shellmound cultural changes over time.

Horner's Syndrome Following Dural Puncture Epidural Analgesia for Labor.

Horner's syndrome has been identified as an adverse outcome associated with the administration of epidural analgesia during labor. This syndrome is attributed to the upward spread of the local anesthetic, which may extend toward the superior cervical sympathetic chain. This process could disrupt the sympathetic pathways supplying the facial and ocular areas. We describe a case of a 26-year-old primigravid female with transient isolated Horner's syndrome following dural puncture epidural analgesia during labor.

Geographic Variation in Qualified Health Plan Coverage and Prior Authorization Requirements for HIV Preexposure Prophylaxis.

Importance: HIV preexposure prophylaxis (PrEP) is a key component of the Ending the HIV Epidemic (EHE) Initiative to curb new HIV diagnoses. In October 2019, emtricitabine/tenofovir alafenamide was added as an approved formulation for PrEP in addition to emtricitabine/tenofovir disoproxil fumarate; despite availability of another formulation with a similar prevention indication, variations in coverage may limit access. Objective: To assess qualified health plan (QHP) coverage, prior authorization (PA) requirements, and specialty tiering for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide following emtricitabine/tenofovir alafenamide approval as a PrEP treatment. Design, Setting, and Participants: This cross-sectional study analyzed QHPs in the US that were compliant with the Patient Protection and Affordable Care Act from 2018 to 2020. QHPs were categorized by region and EHE priority jurisdictions. Data analysis occurred from March 2022 to March 2023. Exposures: Enrollment in a qualified health plan certified by the Patient Protection and Affordable Care Act. Main Outcome and Measures: Annual variation in QHP coverage and PA requirement for emtricitabine/tenofovir disoproxil fumarate and/or emtricitabine/tenofovir alafenamide. Descriptive statistics were reported for all outcomes. A secondary outcome was whether the PrEP formulation was determined by the QHP to be placed on a specialty drug tier. Results: A total of 58 087 QHPs (19 533 for 2018; 17 007 for 2019; and 21 547 for 2020) were analyzed. QHPs covered emtricitabine/tenofovir disoproxil fumarate (19 165 QHPs [98.1%] in 2018; 16 970 QHPs [99.8%] in 2019; 20 045 QHPs [94.8%] in 2020) at a higher rate than emtricitabine/tenofovir alafenamide (17 391 QHPs [91.9%] in 2018; 15 757 QHPs [92.7%] in 2019; 18 836 QHPs [87.4%] in 2020). QHPs in the South required exclusive PA (ie, PA for 1 of the formulations even if the QHP covered both) for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide at the highest rates in all 3 years. In the South, the rate of PA for emtricitabine/tenofovir disoproxil fumarate increased from 806 of 8023 QHPs (10.0%) in 2018 to 3466 of 7401 QHPs (46.8%) in 2020. QHPs with exclusive PA requirement for emtricitabine/tenofovir disoproxil fumarate were higher in EHE jurisdictions than non-EHE jurisdictions (difference: 2018, 0.9 percentage points; 2019, 3.5 percentage points; 2020, 29.1 percentage points). QHPs were more likely to place emtricitabine/tenofovir disoproxil fumarate on a specialty tier compared with emtricitabine/tenofovir alafenamide (difference: 2018, 1.8 percentage points; 2019, 3.7 percentage points; 2020, 4.1 percentage points). Conclusions and Relevance: In this cross-sectional study, despite similar indications for biomedical prevention, QHPs were more likely to cover emtricitabine/tenofovir disoproxil fumarate than emtricitabine/tenofovir alafenamide, and QHPs were also more likely to subject emtricitabine/tenofovir disoproxil fumarate to PA or place it on a specialty tier despite the broader clinical indication. QHP PA requirements of emtricitabine/tenofovir disoproxil fumarate following emtricitabine/tenofovir alafenamide approval does not reflect clinical guidelines. The requirements could reflect differences in clinical indication, manufacturer discounts, or anticipation of a changing regulations and emerging generics. High rates of exclusive PA for emtricitabine/tenofovir disoproxil fumarate in areas where rates of HIV diagnoses are highest and PrEP is most needed (eg, the South and EHE priority jurisdictions) is concerning; policy solutions to address the growing PrEP health equity crisis could include regulator actions and a national PrEP program.

Pre-Younger Dryas megafaunal extirpation at Rancho La Brea linked to fire-driven state shift.

The cause, or causes, of the Pleistocene megafaunal extinctions have been difficult to establish, in part because poor spatiotemporal resolution in the fossil record hinders alignment of species disappearances with archeological and environmental data. We obtained 172 new radiocarbon dates on megafauna from Rancho La Brea in California spanning 15.6 to 10.0 thousand calendar years before present (ka). Seven species of extinct megafauna disappeared by 12.9 ka, before the onset of the Younger Dryas. Comparison with high-resolution regional datasets revealed that these disappearances coincided with an ecological state shift that followed aridification and vegetation changes during the Bølling-Allerød (14.69 to 12.89 ka). Time-series modeling implicates large-scale fires as the primary cause of the extirpations, and the catalyst of this state shift may have been mounting human impacts in a drying, warming, and increasingly fire-prone ecosystem.

A dietary perspective of cat-human interactions in two medieval harbors in Iran and Oman revealed through stable isotope analysis.

Cats are hypercarnivorous, opportunistic animals that have adjusted to anthropogenic environments since the Neolithic period. Through humans, either by direct feeding and/or scavenging on food scraps, the diet of cats has been enriched with animals that they cannot kill themselves (e.g., large mammals, fish). Here, we conducted carbon and nitrogen stable isotope ratio analysis to reconstruct the diet of medieval cats and investigate cat-human interactions in two medieval harbor sites (Qalhât, Oman and Siraf, Iran). The analysis included 28 cat individuals and 100 associated marine and terrestrial faunal samples pertaining to > 30 taxa. The isotopic results indicate a high marine protein-based diet for the cats from Qalhât and a mixed marine-terrestrial (C4) diet for the cats from Siraf. Cats at these sites most likely scavenged on both human food scraps and refuse related to fishing activities, with differences in the two sites most likely associated with the availability of marine resources and/or the living conditions of the cats. By shedding light on the dietary habits of cats from two medieval harbors in the Arabian Gulf and Gulf of Oman, this study illustrates the potential of stable isotope analysis in reconstructing human-cat interactions in the past.

Using SXRF and LA-ICP-TOFMS to Explore Evidence of Treatment and Physiological Responses to Leprosy in Medieval Denmark.

Leprosy can lead to blood depletion in Zn, Ca, Mg, and Fe and blood enrichment in Cu. In late medieval Europe, minerals were used to treat leprosy. Here, physiological responses to leprosy and possible evidence of treatment are investigated in enamel, dentine, and cementum of leprosy sufferers from medieval Denmark (n = 12) and early 20th century Romania (n = 2). Using SXRF and LA-ICP-TOFMS, 12 elements were mapped in 15 tooth thin sections, and the statistical covariation of paired elements was computed to assess their biological relevance. The results show marked covariations in the Zn, Ca, and Mg distributions, which are compatible with clinical studies but cannot be directly attributed to leprosy. Minerals used historically as a treatment for leprosy show no detectable intake (As, Hg) or a diffuse distribution (Pb) related to daily ingestion. Intense Pb enrichments indicate acute incorporations of Pb, potentially through the administration of Pb-enriched medication or the mobilization of Pb from bone stores to the bloodstream during intense physiological stress related to leprosy. However, comparisons with a healthy control group are needed to ascertain these interpretations. The positive correlations and the patterns observed between Pb and essential elements may indicate underlying pathophysiological conditions, demonstrating the potential of SXRF and LA-ICP-TOFMS for paleopathological investigations.

Infancy, childhood, and puberty on the Silk Road revealed with isotopic analysis of incremental dentine.

Childhood is a unique phase in human life history, in which newborns are breastfed and weaned, and are progressively familiarized to adult diets. By investigating dietary changes from infancy to adolescence, valuable information regarding past cultural behaviors and aspects of human lives can be explored and elucidated. Here, in conjunction with published isotopic results of serial dentine (n = 21) from Yingpan Man, new δ13C and δ15N results are obtained from 172 samples of incremental dentine from 8 teeth of 8 individuals of the Yingpan cemetery, located in Xinjiang, China. The δ13C values range from - 18.2 to - 14.6‰ with a mean ± SD value of - 16.3 ± 0.9‰, and the δ15N results range between 13.4 and 19.9‰ with a mean ± SD value of 16.0 ± 1.4‰. This indicates that the childhood diets were mixtures of C3 and C4 dietary resources and were clearly influenced by breastfeeding and weaning practices. In particular, the findings indicate that there were significant inter-individual differences in terms of the timing and duration of breastfeeding and weaning practices as well as childhood dietary practices at Yingpan. For instance, three individuals were exclusively breastfed after birth, while, two individuals and Yingpan Man were not. In addition, the post-weaning diets of most Yingpan individuals were relatively stable, but one individual and Yingpan Man displayed clear evidence of increased consumption of C4 foods, likely millet, during late and post-weaning periods. Further, 7 individuals had unique dietary changes between 9 to 14 years old. Potential factors related to this are presented from the perspective of changes in social roles that might be caused by their early participation in the social division of labor or puberty and marriage.

Directed cell migration towards softer environments.

How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.

Revealing lost secrets about Yingpan Man and the Silk Road.

Yingpan Man, is one of the most exquisitely preserved mummies found in the Xinjiang Uyghur Autonomous Region of China. Here links between Yingpan Man and the Silk Road are explored through a detailed isotopic and bioarchaeological investigation of his life history. Analytical techniques of carbon, nitrogen, and sulfur stable isotope ratio analysis on hair, teeth, muscle and bones as well as associated animal and plant remains, radiocarbon dating and starch grain analysis of dental calculus are presented to visualize never before seen aspects of Yingpan Man's life, including: environment, breastfeeding and weaning practices, adolescent and adult diet, disease and nutritional status as well as season of death. Furthermore, in combination with a detailed review of his associated grave goods, this research examines the social status and identity of Yingpan Man, and demonstrates the profound impact and cultural fusion that the Silk Road had upon the peoples of Xinjiang and Eurasia.

Isotopic investigation of skeletal remains at the Imdang tombs reveals high consumption of game birds and social stratification in ancient Korea.

Understanding the development of early states on the Korean Peninsula is an important topic in Korean archaeology. However, it is not clear how social structure was organized by these early states and what natural resources were utilized from their surrounding environments. To investigate dietary adaptation and social status in ancient Korea, stable isotope ratios and radiocarbon dates were measured from humans and animals from the Imdang cemetery, Gyeongsan city, South Korea. The results indicate that the Imdang diet was mainly based on C3 plants and terrestrial animals. Animal remains in the graves were directly consumed as daily food items as well as for ritual offerings. MixSIAR modeling results revealed that the dietary sources for the humans were: game birds > C3 plants > terrestrial herbivores > marine fish > C4 plants. The finding that the game birds represented the highest contribution to the whole diet, indicates that game birds must have been intensively hunted. Furthermore, elites consumed more game birds than their retainers and they also consumed seafood as a privileged dietary item in the Imdang society. This study demonstrates that the Apdok was a stratified society having high variations in the consumption of food items available to an individual and provides new insights about the subsistence and social status of the early ancient Apdok state on the Korean Peninsula.

Leprosy in medieval Denmark: Exploring life histories through a multi-tissue and multi-isotopic approach.

OBJECTIVES: By focusing on two Danish leprosaria (Naestved and Odense; 13th-16th c. CE) and using diet and origin as proxies, we follow a multi-isotopic approach to reconstruct life histories of patients and investigate how leprosy affected both institutionalized individuals and the medieval Danish community as a whole. MATERIALS AND METHODS: We combine archaeology, historical sources, biological anthropology, isotopic analyses (δ13 C, δ15 N, δ34 S, 87 Sr/86 Sr) and radiocarbon dating, and further analyze bones with different turnover rates (ribs and long bones). RESULTS: The δ13 C, δ15 N and δ34 S results indicate a C3 terrestrial diet with small contributions of marine protein for leprosy patients and individuals from other medieval Danish sites. A similar diet is seen through time, between males and females, and patients with and without changes on facial bones. The isotopic comparison between ribs and long bones reveals no significant dietary change. The δ34 S and 87 Sr/86 Sr results suggest that patients were local to the regions of the leprosaria. Moreover, the radiocarbon dates show a mere 50% agreement with the arm position dating method used in Denmark. CONCLUSIONS: A local origin for the leprosy patients is in line with historical evidence, unlike the small dietary contribution of marine protein. Although only 10% of the analyzed individuals have rib/long bone offsets that undoubtedly show a dietary shift, the data appear to reveal a pattern for 25 individuals (out of 50), with elevated δ13 C and/or δ15 N values in the ribs compared to the long bones, which points toward a communal type of diet and reveals organizational aspects of the institution.

Septic Shock Caused by Rahnella aquatilis Bacteremia in an Immunocompetent Adult.

BACKGROUND Rahnella aquatilis is a facultatively anaerobic, gram-negative rod bacterium commonly found in freshwater. There are few cases of bacteremia caused by Rahnella aquatilis in the literature and even fewer cases reported of it causing sepsis in immunocompetent individuals. In this case report, we present a rare case of an immunocompetent individual who developed sepsis secondary to bacteremia caused by Rahnella aquatilis. CASE REPORT A 37-year-old immunocompetent man with cerebral palsy and chronic enterocutaneous fistulas, with an indwelling peripherally inserted central catheter (PICC) line for total parenteral nutrition (TPN), presented to the emergency department with complaints of increased enteric drainage from his fistula, rigors, and subjective fevers following a mechanical fall, which occurred approximately 1 week before. The day following admission, the patient developed septic shock and was transferred to the intensive care unit for vasopressor support. He was given intravenous cefepime and metronidazole for empiric therapy. Blood cultures grew Rahnella aquatilis, and antibiotic therapy was de-escalated to monotherapy with intravenous ceftriaxone. The patient's condition stabilized, his PICC line was replaced, and he was successfully discharged, and continued on outpatient antibiotic therapy with ceftriaxone. CONCLUSIONS This case report represents a novel presentation of septic shock secondary to bacteremia caused by a gram-negative rod bacterium, Rahnella aquatilis, in an immunocompetent host dependent on TPN via a PICC line. This case also demonstrates that Rahnella aquatilis can be susceptible to and treated successfully with intravenous ceftriaxone. Bacteremia caused by Rahnella aquatilis can cause a swift, aggressive decompensation and should be treated with antibiotics immediately.

Successful transforaminal epidural blood patch in a patient with multilevel spinal fusion.

INTRODUCTION: Epidural blood patch (EBP) is a vital tool in treating postdural puncture headache (PDPH). Traditional interlaminar epidural needle insertion into the epidural space, however, may be challenging due to anatomical variations. As an alternative method, we successfully performed an EBP via transforaminal approach. CASE REPORT: A mid-50-year-old male patient with multilevel spinal fusion developed PDPH after a failed spinal cord stimulator electrode placement. A transforaminal EBP was carried out by injecting a total of 8 mL of autologous blood into the neuroforamen at the L1-L2 level bilaterally. Our patient's positional headache resolved immediately after the procedure. DISCUSSION: To our knowledge, this is the first case reported of a transforaminal EBP in a patient with diffuse epidural adhesive fibrosis secondary to multilevel laminectomies and spinal fusion. This case report highlights potential risks and benefits of this novel technique and also discusses its therapeutic mechanism of action. We believe that a transforaminal EBP should be considered in patients who are poor candidates for the traditional interlaminar EBP.

Multiproxy isotopic analyses of human skeletal material from Rapa Nui: Evaluating the evidence from carbonates, bulk collagen, and amino acids.

OBJECTIVES: Stable isotope ratio analysis of bulk bone collagen dominates research into past diet; however, bone carbonate and compound specific isotope analyses (CSIA) of amino acids provide alternative, yet complementary, lines of evidence toward that same research goal. Together they inform on different aspects of diet, allowing greater certainty in reconstructions. Here we present new data on carbonate isotopes for Rapa Nui and reevaluate prehistoric diet in the context of these new and previously published bulk collagen and CSIA data. MATERIALS AND METHODS: We analyzed carbon isotopes in bone carbonate from 28 prehistoric human teeth from Rapa Nui. These represent a subset of material examined previously for carbon and nitrogen isotope ratios in bulk collagen. We then reevaluate prehistoric diet in light of these and other published data. In addition, we analyzed carbon and nitrogen isotope ratios in 28 modern plant specimens from Rapa Nui to better approximate the isotopic value of the terrestrial endmember. RESULTS: Bulk data suggest a predominantly terrestrial diet, with the amount of marine sources incorporated varying though time. While previously argued to reveal greater amounts of marine consumption, reanalysis of recently published CSIA data suggests this result may relate to the proportion of carbon assimilated rather than consumed. Utilizing models incorporating concentration dependence for estimating dietary proportions results in much lower estimates of marine consumption, in line with findings of the bulk data. DISCUSSION: While these data indicate a larger focus on terrestrial resources, limitations in all forms of analysis make it difficult to determine exact dietary contributions in this mixed system. Better understanding of the complex physiological processes governing isotopic routing and fractionation, and knowledge of appropriate isotopic endmember values are needed to advance this research.

Dorset Pre-Inuit and Beothuk foodways in Newfoundland, ca. AD 500-1829.

Archaeological research on the Canadian island of Newfoundland increasingly demonstrates that the island's subarctic climate and paucity of terrestrial food resources did not restrict past Pre-Inuit (Dorset) and Native American (Beothuk) hunter-gatherer populations to a single subsistence pattern. This study first sought to characterize hunter-gatherer diets over the past 1500 years; and second, to assess the impact of European colonization on Beothuk lifeways by comparing the bone chemistry of Beothuk skeletal remains before and after the intensification of European settlement in the early 18th century. We employed radiocarbon dating and stable carbon and nitrogen isotope ratio analysis of bulk bone collagen from both Dorset (n = 9) and Beothuk (n = 13) cultures, including a naturally mummified 17th century Beothuk individual. Carbon and nitrogen isotope analysis of 108 faunal samples from Dorset and Beothuk archaeological sites around the island were used as a dietary baseline for the humans. We combined our results with previously published isotope data and radiocarbon dates from Dorset (n = 12) and Beothuk (n = 18) individuals and conducted a palaeodietary analysis using Bayesian modelling, cluster analysis and comparative statistical tests. Dorset diets featured more marine protein than those of the Beothuk, and the diets of Beothuk after the 18th century featured less high trophic level marine protein than those of individuals predating the 18th century. Despite inhabiting the same island, Dorset and Beothuk cultures employed markedly different dietary strategies, consistent with interpretations of other archaeological data. Significantly, European colonization had a profound effect on Beothuk lifeways, as in response to the increasing European presence on the coast, the Beothuk relied more extensively on the limited resources of the island's boreal forests and rivers.

Tianshanbeilu and the Isotopic Millet Road: reviewing the late Neolithic/Bronze Age radiation of human millet consumption from north China to Europe.

The westward expansion of human millet consumption from north China has important implications for understanding early interactions between the East and West. However, few studies have focused on the Xinjiang Uyghur Autonomous Region, the vast geographical area directly linking the ancient cultures of the Eurasian Steppe and the Gansu Corridor of China. In this study, we present the largest isotopic investigation of Bronze Age China (n = 110) on material from the key site of Tianshanbeilu, in eastern Xinjiang. The large range of δ13C values (-17.6‰ to -7.2‰; -15.5 ± 1.2‰) provides direct evidence of unique dietary diversity and consumption of significant C4 resources (millets). The high δ15N results (10.3‰ to 16.7‰; 14.7 ± 0.8‰) likely reflect sheep/goat and wild game consumption and the arid climate of the Taklamakan Desert. Radiocarbon dates from four individuals indicate Tianshanbeilu was in use between 1940 and 1215 cal bc. The Tianshanbeilu results are then analysed with respect to 52 Bronze Age sites from across Eurasia, to investigate the spread and chronology of significant human millet consumption and human migration. This isotopic survey finds novel evidence that the second millennium bc was a dynamic period, with significant dietary interconnectivity occurring between north China, Central Asia and Siberia. Further, we argue that this 'Isotopic Millet Road' extended all the way to the Mediterranean and Central Europe, and conclude that these C4 dietary signatures of millet consumption reflect early links (migration and/or resource transfer) between the Bronze Age inhabitants of modern-day China and Europe.

An exploration of the aversive properties of 2-deoxy-D-glucose in rats.

Hypoglycemia can alter arousal and negatively impact mood. This study tests the hypothesis that acute drops in glucose metabolism cause an aversive state mediated by monoamine activity. In experiment 1, male Sprague-Dawley rats were either food deprived (FD) or pre-fed (PF) and tested on conditioned place avoidance (CPA; biased place conditioning design; 3 pairings drug/vehicle, each 30 min-long) induced by the glucose antimetabolite 2-deoxy-D-glucose (2-DG; 0, 300 or 500 mg/kg, SC). Locomotion and blood glucose were also assessed. Experiment 2 examined whether clonidine (noradrenergic α2 agonist, 0, 10 or 40 µg/kg, SC) or bupropion (monoamine reuptake blocker, 0, 10 or 30 mg/kg, SC) could alter CPA induced by 500 mg/kg 2-DG. In experiment 3, blood corticosterone (CORT) was measured in response to 500 mg/kg 2-DG, alone or in combination with 40 µg/kg clonidine or 30 mg/kg bupropion. Finally, experiment 4 controlled for possible place conditioning induced by 10 or 40 µg/kg clonidine, or 10 or 30 mg/kg bupropion injected without 2-DG. It was found that 2-DG increased blood glucose and produced a robust CPA. The feeding status of the animals modulated these effects, including CORT levels. Both clonidine and bupropion attenuated the effects of 2-DG on CPA and CORT, but only bupropion reversed suppression of locomotion. Taken together, these results in rats suggest that impaired glucose metabolism can negatively impact arousal and mood via effects on HPA and monoamine systems.