Dairying enabled Early Bronze Age Yamnaya steppe expansions.

During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic-Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known as the Afanasievo) far to the east in the Altai Mountains1,2 and Mongolia3. Although some models hold that this expansion was the outcome of a newly mobile pastoral economy characterized by horse traction, bulk wagon transport4-6 and regular dietary dependence on meat and milk5, hard evidence for these economic features has not been found. Here we draw on proteomic analysis of dental calculus from individuals from the western Eurasian steppe to demonstrate a major transition in dairying at the start of the Bronze Age. The rapid onset of ubiquitous dairying at a point in time when steppe populations are known to have begun dispersing offers critical insight into a key catalyst of steppe mobility. The identification of horse milk proteins also indicates horse domestication by the Early Bronze Age, which provides support for its role in steppe dispersals. Our results point to a potential epicentre for horse domestication in the Pontic-Caspian steppe by the third millennium BC, and offer strong support for the notion that the novel exploitation of secondary animal products was a key driver of the expansions of Eurasian steppe pastoralists by the Early Bronze Age.

Perispinal injection of a TNF blocker directed to the brain of rats alleviates the sensory and affective components of chronic constriction injury-induced neuropathic pain.

Neuropathic pain is chronic pain that follows nerve injury, mediated in the brain by elevated levels of the inflammatory protein tumor necrosis factor-alpha (TNF). We have shown that peripheral nerve injury increases TNF in the hippocampus/pain perception region, which regulates neuropathic pain symptoms. In this study we assessed pain sensation and perception subsequent to specific targeting of brain-TNF (via TNF antibody) administered through a novel subcutaneous perispinal route. Neuropathic pain was induced in Sprague-Dawley rats via chronic constriction injury (CCI), and thermal hyperalgesia was monitored for 10 days post-surgery. On day 8 following CCI and sensory pain behavior testing, rats were randomized to receive perispinal injection of TNF antibody or control IgG isotype antibody. Pain perception was assessed using conditioned place preference (CPP) to the analgesic, amitriptyline. CCI-rats receiving the perispinal injection of TNF antibody had significantly decreased CCI-induced thermal hyperalgesia the following day, and did not form an amitriptyline-induced CPP, whereas CCI-rats receiving perispinal IgG antibody experienced pain alleviation only in conjunction with i.p. amitriptyline and did form an amitriptyline-induced CPP. The specific targeting of brain TNF via perispinal delivery alleviates thermal hyperalgesia and positively influences the affective component of pain. PERSPECTIVE: This study presents a novel route of drug administration to target central TNF for treatment of neuropathic pain. Targeting central TNF through perispinal drug delivery could potentially be a more efficient and sustained method to treat patients with neuropathic pain.

Early agriculture and crop transmission among Bronze Age mobile pastoralists of Central Eurasia.

Archaeological research in Central Eurasia is exposing unprecedented scales of trans-regional interaction and technology transfer between East Asia and southwest Asia deep into the prehistoric past. This article presents a new archaeobotanical analysis from pastoralist campsites in the mountain and desert regions of Central Eurasia that documents the oldest known evidence for domesticated grains and farming among seasonally mobile herders. Carbonized grains from the sites of Tasbas and Begash illustrate the first transmission of southwest Asian and East Asian domesticated grains into the mountains of Inner Asia in the early third millennium BC. By the middle second millennium BC, seasonal camps in the mountains and deserts illustrate that Eurasian herders incorporated the cultivation of millet, wheat, barley and legumes into their subsistence strategy. These findings push back the chronology for domesticated plant use among Central Eurasian pastoralists by approximately 2000 years. Given the geography, chronology and seed morphology of these data, we argue that mobile pastoralists were key agents in the spread of crop repertoires and the transformation of agricultural economies across Asia from the third to the second millennium BC.

Agricultural origins from the ground up: archaeological approaches to plant domestication.

The timing, geographical locations, causes, and consequences of crop domestication have long been major concerns of archaeologists, and agricultural origins and dispersals are currently more relevant than ever to scientists seeking solutions to elusive problems involving food insecurity and global health disparities. Perennial research issues that archaeologists continue to tackle include (1) thinking outside centers of origin that were based on limited and insufficient past knowledge; (2) distinguishing between single and multiple domestications of specific crops; (3) measuring the pace of domestication; and (4) decoupling domestication from agricultural economies. Paleoethnobotanists have expanded their toolkits to include analysis of ancient and modern DNA and have added increasingly sophisticated techniques in the field and the laboratory to derive precise chronological sequences to assess morphological changes in ancient and often fragmentary archaeobotanical remains and to correctly interpret taphonomy and context. Multiple lines of archaeological evidence are ideally brought together, and whenever possible, these are integrated with information from complementary sources. We discuss current perspectives and anthropological approaches to research that have as their goals the fuller and broader understanding of ancient farming societies, the plants that were domesticated, the landscapes that were created, and the culinary legacies that were passed on.

Agriculture along the upper part of the Middle Zarafshan River during the first millennium AD: A multi-site archaeobotanical analysis.

The Zarafshan River runs from the mountains of Tajikistan and terminates in the sands of the Kyzyl-Kum Desert in Uzbekistan; it served as a communication route and homeland for the Sogdians. The Sogdians are historically depicted as merchants existing from the end of the first millennium BC through the first millennium AD. While recent research has provided the first glimpse into cultivation, commerce, communication, and consumption in the Lower Zarafshan, the agricultural heartland of the Middle Zarafshan Basin has remained unstudied. This paper presents the results of archaeobotanical investigations conducted at five ancient urban sites/areas spanning the fifth to the twelfth centuries AD: Kainar (Penjikent citadel), Penjikent (shahristan), Sanjar-Shah, Kuk-Tosh (pre-Mongol Penjikent), and Afrasiab. Collectively, these data show that cereals, legumes, oil/fiber crops, fruits, and nuts were cultivated on the fertile Zarafshan floodplains. In this paper, we discuss evidence for the diversification of the agricultural assemblage over time, including the introduction of new staple crops and fruits into an already complex cultivation system. In addition, we contrast our data with previously published results from sites along the course of the Zarafshan to determine whether there is a dietary difference between pre-and post-Islamic conquest periods at settlements located along the river.

Biomolecular evidence for changing millet reliance in Late Bronze Age central Germany.

The Bronze Age of Central Europe was a period of major social, economic, political and ideological change. The arrival of millet is often seen as part of wider Bronze Age connectivity, yet understanding of the subsistence regimes underpinning this dynamic period remains poor for this region, in large part due to a dominance of cremation funerary rites, which hinder biomolecular studies. Here, we apply stable isotope analysis, radiocarbon dating and archaeobotanical analysis to two Late Bronze Age (LBA) sites, Esperstedt and Kuckenburg, in central Germany, where human remains were inhumed rather than cremated. We find that people buried at these sites did not consume millet before the Middle Bronze Age (MBA) (ca. 1600 BCE). However, by the early LBA (ca. 1300-1050 BCE) people consumed millet, often in substantial quantities. This consumption appears to have subsequently diminished or ceased around 1050-800 BCE, despite charred millet grains still being found in the archaeological deposits from this period. The arrival of millet in this region, followed by a surge in consumption spanning two centuries, indicates a complex interplay of cultural and economic factors, as well as a potential use of millet to buffer changes in aridity in a region increasingly prone to crop failure in the face of climate change today.

Archaeological and molecular evidence for ancient chickens in Central Asia.

The origins and dispersal of the chicken across the ancient world remains one of the most enigmatic questions regarding Eurasian domesticated animals. The lack of agreement concerning timing and centers of origin is due to issues with morphological identifications, a lack of direct dating, and poor preservation of thin, brittle bird bones. Here we show that chickens were widely raised across southern Central Asia from the fourth century BC through medieval periods, likely dispersing along the ancient Silk Road. We present archaeological and molecular evidence for the raising of chickens for egg production, based on material from 12 different archaeological sites spanning a millennium and a half. These eggshells were recovered in high abundance at all of these sites, suggesting that chickens may have been an important part of the overall diet and that chickens may have lost seasonal egg-laying.

Food globalization in southern Central Asia: archaeobotany at Bukhara between antiquity and the Middle Ages.

The Silk Road is a modern name for a globalization phenomenon that marked an extensive network of communication and exchange in the ancient world; by the turn of the second millennium AD, commercial trade linked Asia and supported the development of a string of large urban centers across Central Asia. One of the main arteries of the medieval trade routes followed the middle and lower Zarafshan River and was connected by mercantile cities, such as Samarkand and Bukhara. Bukhara developed into a flourishing urban center between the fourth and sixth centuries AD, served as the capital of the Samanid court between AD 893 and 999, and remained prosperous into the Qarakhanid period (AD 999-1220), until the Mongol invasion in AD 1220. We present the first archaeobotanical study from this ancient center of education, craft production, artistic development, and commerce. Radiocarbon dates and an archaeological chronology that has been developed for the site show that our samples cover a range between the third and eleventh centuries AD. These samples from Bukhara represent the richest systematically collected archaeobotanical assemblage thus far recovered in Central Asia. The assemblage includes spices and both annual and perennial crops, which allowed Sogdians and Samanids to feed large cities in river oases surrounded by desert and arid steppe and supported a far-reaching commercial market in the first millennium AD. Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-023-01827-z.

Bearing Fruit: Miocene Apes and Rosaceous Fruit Evolution.

Extinct megafaunal mammals in the Americas are often linked to seed-dispersal mutualisms with large-fruiting tree species, but large-fruiting species in Europe and Asia have received far less attention. Several species of arboreal Maloideae (apples and pears) and Prunoideae (plums and peaches) evolved large fruits starting around nine million years ago, primarily in Eurasia. As evolutionary adaptations for seed dispersal by animals, the size, high sugar content, and bright colorful visual displays of ripeness suggest that mutualism with megafaunal mammals facilitated the evolutionary change. There has been little discussion as to which animals were likely candidate(s) on the late Miocene landscape of Eurasia. We argue that several possible dispersers could have consumed the large fruits, with endozoochoric dispersal usually relying on guilds of species. During the Pleistocene and Holocene, the dispersal guild likely included ursids, equids, and elephantids. During the late Miocene, large primates were likely also among the members of this guild, and the potential of a long-held mutualism between the ape and apple clades merits further discussion. If primates were a driving factor in the evolution of this large-fruit seed-dispersal system, it would represent an example of seed-dispersal-based mutualism with hominids millions of years prior to crop domestication or the development of cultural practices, such as farming.

Paleoproteomic evidence reveals dairying supported prehistoric occupation of the highland Tibetan Plateau.

The extreme environments of the Tibetan Plateau offer considerable challenges to human survival, demanding novel adaptations. While the role of biological and agricultural adaptations in enabling early human colonization of the plateau has been widely discussed, the contribution of pastoralism is less well understood, especially the dairy pastoralism that has historically been central to Tibetan diets. Here, we analyze ancient proteins from the dental calculus (n = 40) of all human individuals with sufficient calculus preservation from the interior plateau. Our paleoproteomic results demonstrate that dairy pastoralism began on the highland plateau by ~3500 years ago. Patterns of milk protein recovery point to the importance of dairy for individuals who lived in agriculturally poor regions above 3700 m above sea level. Our study suggests that dairy was a critical cultural adaptation that supported expansion of early pastoralists into the region's vast, non-arable highlands, opening the Tibetan Plateau up to widespread, permanent human occupation.

Rapid improvement in severe long COVID following perispinal etanercept.

BACKGROUND: This study aimed to describe the neurological improvements in a patient with severe long COVID brain dysfunction following perispinal etanercept administration. Perispinal administration of etanercept, a novel method designed to enhance its brain delivery via carriage in the cerebrospinal venous system, has previously been shown to reduce chronic neurological dysfunction after stroke. Etanercept is a recombinant biologic that is capable of ameliorating two components of neuroinflammation: microglial activation and the excess bioactivity of tumor necrosis factor (TNF), a proinflammatory cytokine that is a key neuromodulator in the brain. Optimal synaptic and brain network function require physiological levels of TNF. Neuroinflammation, including brain microglial activation and excess central TNF, can be a consequence of stroke or peripheral infection, including infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. METHODS: Standardized, validated measures, including the Montreal Cognitive Assessment, Beck Depression Index-II (BDI-II), Fatigue Assessment Scale, Controlled Oral Word Association Test, Trail Making Tests, Timed Finger-to-Nose Test, 20 m Self-Paced Walk Test, 5 Times Sit-to-Stand Test and Grip Strength measured with a Jamar Dynamometer were used to quantitate changes in cognition, depression, fatigue and neurological function after a single 25 mg perispinal etanercept dose in a patient with severe long COVID of 12 months duration. RESULTS: Following perispinal etanercept administration there was immediate neurological improvement. At 24 h, there were remarkable reductions in chronic post-COVID-19 fatigue and depression, and significant measurable improvements in cognition, executive function, phonemic verbal fluency, balance, gait, upper limb coordination and grip strength. Cognition, depression and fatigue were examined at 29 days; each remained substantially improved. CONCLUSION: Perispinal etanercept is a promising treatment for the chronic neurologic dysfunction that may persist after resolution of acute COVID-19, including chronic cognitive dysfunction, fatigue, and depression. These results suggest that long COVID brain neuroinflammation is a potentially reversible pathology and viable treatment target. In view of the increasing unmet medical need, clinical trials of perispinal etanercept for long COVID are urgently necessary. The robust results of the present case suggest that perispinal etanercept clinical trials studying long COVID populations with severe fatigue, depression and cognitive dysfunction may have improved ability to detect a treatment effect. Positron emission tomographic methods that image brain microglial activation and measurements of cerebrospinal fluid proinflammatory cytokines may be useful for patient selection and correlation with treatment effects, as well as provide insight into the underlying pathophysiology.

Morphotype broadening of the grapevine (Vitis vinifera L.) from Oxus civilization 4000 BP, Central Asia.

The region of Transoxiana underwent an early agricultural-demographic transition leading to the earliest proto-urban centers in Central Asia. The agronomic details of this cultural shift are still poorly studied, especially regarding the role that long-generation perennials, such as grapes, played in the cultivation system. In this paper, we present directly dated remains of grape pips from the early urban centers of Sapalli and Djarkutan, in south Uzbekistan. We also present linear morphometric data, which illustrate a considerable range of variation under cultivation that we divide into four distinct morphotypes according to pip shape. While some of the pips in these two assemblages morphologically fall within the range of wild forms, others more closely resemble modern domesticated populations. Most of the specimens measure along a gradient between the two poles, showing a mixed combination of domesticated and wild features. We also point out that the seeds recovered from the Djarkutan temple were, on average, larger and contained more affinity towards domesticated forms than those from domestic contexts. The potential preference of morphotypes seems to suggest that there were recognized different varieties that local cultivators might aware and possibly propagating asexually.

Exaptation Traits for Megafaunal Mutualisms as a Factor in Plant Domestication.

Megafaunal extinctions are recurring events that cause evolutionary ripples, as cascades of secondary extinctions and shifting selective pressures reshape ecosystems. Megafaunal browsers and grazers are major ecosystem engineers, they: keep woody vegetation suppressed; are nitrogen cyclers; and serve as seed dispersers. Most angiosperms possess sets of physiological traits that allow for the fixation of mutualisms with megafauna; some of these traits appear to serve as exaptation (preadaptation) features for farming. As an easily recognized example, fleshy fruits are, an exaptation to agriculture, as they evolved to recruit a non-human disperser. We hypothesize that the traits of rapid annual growth, self-compatibility, heavy investment in reproduction, high plasticity (wide reaction norms), and rapid evolvability were part of an adaptive syndrome for megafaunal seed dispersal. We review the evolutionary importance that megafauna had for crop and weed progenitors and discuss possible ramifications of their extinction on: (1) seed dispersal; (2) population dynamics; and (3) habitat loss. Humans replaced some of the ecological services that had been lost as a result of late Quaternary extinctions and drove rapid evolutionary change resulting in domestication.

A Journey to the West: The Ancient Dispersal of Rice Out of East Asia.

Rice is one of the most culturally valued and widely grown crops in the world today, and extensive research over the past decade has clarified much of the narrative of its domestication and early spread across East and South Asia. However, the timing and routes of its dispersal into West Asia and Europe, through which rice eventually became an important ingredient in global cuisines, has remained less clear. In this article, we discuss the piecemeal, but growing, archaeobotanical data for rice in West Asia. We also integrate written sources, linguistic data, and ethnohistoric analogies, in order to better understand the adoption of rice outside its regions of origin. The human-mediated westward spread of rice proceeded gradually, while its social standing and culinary uses repeatedly changing over time and place. Rice was present in West Asia and Europe by the tail end of the first millennium BC, but did not become a significant crop in West Asia until the past few centuries. Complementary historical, linguistic, and archaeobotanical data illustrate two separate and roughly contemporaneous routes of westward dispersal, one along the South Asian coast and the other through Silk Road trade. By better understanding the adoption of this water-demanding crop in the arid regions of West Asia, we explore an important chapter in human adaptation and agricultural decision making.

Megadrought and cultural exchange along the proto-silk road.

Arid Central Asia (ACA), with its diverse landscapes of high mountains, oases, and deserts, hosted the central routes of the Silk Roads that linked trade centers from East Asia to the eastern Mediterranean. Ecological pockets and ecoclines in ACA are largely determined by local precipitation. However, little research has gone into the effects of hydroclimatic changes on trans-Eurasian cultural exchange. Here, we reconstruct precipitation changes in ACA, covering the mid-late Holocene with a U-Th dated, ~3 a resolution, multi-proxy time series of replicated stalagmites from the southeastern Fergana Valley, Kyrgyzstan. Our data reveal a 640-a megadrought between 5820 and 5180 a BP, which likely impacted cultural development in ACA and impeded the expansion of cultural traits along oasis routes. Instead, it may have diverted the earliest transcontinental exchange along the Eurasian steppe during the 5th millennium BP. With gradually increasing precipitation after the megadrought, settlement of peoples in the oases and river valleys may have facilitated the opening of the oasis routes, "prehistoric Silk Roads", of trans-Eurasian exchange. By the 4th millennium BP, this process may have reshaped cultures across the two continents, laying the foundation for the organized Silk Roads.

Evidence for early dispersal of domestic sheep into Central Asia.

The development and dispersal of agropastoralism transformed the cultural and ecological landscapes of the Old World, but little is known about when or how this process first impacted Central Asia. Here, we present archaeological and biomolecular evidence from Obishir V in southern Kyrgyzstan, establishing the presence of domesticated sheep by ca. 6,000 BCE. Zooarchaeological and collagen peptide mass fingerprinting show exploitation of Ovis and Capra, while cementum analysis of intact teeth implicates possible pastoral slaughter during the fall season. Most significantly, ancient DNA reveals these directly dated specimens as the domestic O. aries, within the genetic diversity of domesticated sheep lineages. Together, these results provide the earliest evidence for the use of livestock in the mountains of the Ferghana Valley, predating previous evidence by 3,000 years and suggesting that domestic animal economies reached the mountains of interior Central Asia far earlier than previously recognized.

Anthropogenic Seed Dispersal: Rethinking the Origins of Plant Domestication.

It is well documented that ancient sickle harvesting led to tough rachises, but the other seed dispersal properties in crop progenitors are rarely discussed. The first steps toward domestication are evolutionary responses for the recruitment of humans as dispersers. Seed dispersal-based mutualism evolved from heavy human herbivory or seed predation. Plants that evolved traits to support human-mediated seed dispersal express greater fitness in increasingly anthropogenic ecosystems. The loss of dormancy, reduction in seed coat thickness, increased seed size, pericarp density, and sugar concentration all led to more-focused seed dispersal through seed saving and sowing. Some of the earliest plants to evolve domestication traits had weak seed dispersal processes in the wild, often due to the extinction of animal dispersers or short-distance mechanical dispersal.

Prehistoric agriculture and social structure in the southwestern Tarim Basin: multiproxy analyses at Wupaer.

The oasis villages of the Tarim Basin served as hubs along the ancient Silk Road, and they played an important role in facilitating communication between the imperial centers of Asia. These villages were supported by an irrigated form of cereal farming that was specifically adapted to these early oasis settlements. In this manuscript, we present the results from new archaeobotanical analyses, radiocarbon dating, and organic carbon isotopic studies directly from carbonized seeds at the Wupaer site (1500-400 BC) in the Kashgar Oasis of the western Tarim Basin. Our results showed that early farming in the oasis relied on a mixed wheat and barley system, but after 1200 BC was intensified through more elaborate irrigation, the introduction of more water-demanding legumes, and possibly a greater reliance on free-threshing wheat. These crops and the knowledge of irrigated farming likely dispersed into the Tarim Basin through the mountains from southern Central Asia. Improved agricultural productivity in the Tarim Basin may also have led to demographic and socio-political shifts and fed into the increased exchange that is colloquially referred to as the Silk Road.

Economic Diversification Supported the Growth of Mongolia's Nomadic Empires.

Populations in Mongolia from the late second millennium B.C.E. through the Mongol Empire are traditionally assumed, by archaeologists and historians, to have maintained a highly specialized horse-facilitated form of mobile pastoralism. Until recently, a dearth of direct evidence for prehistoric human diet and subsistence economies in Mongolia has rendered systematic testing of this view impossible. Here, we present stable carbon and nitrogen isotope measurements of human bone collagen, and stable carbon isotope analysis of human enamel bioapatite, from 137 well-dated ancient Mongolian individuals spanning the period c. 4400 B.C.E. to 1300 C.E. Our results demonstrate an increase in consumption of C4 plants beginning at c. 800 B.C.E., almost certainly indicative of millet consumption, an interpretation supported by archaeological evidence. The escalating scale of millet consumption on the eastern Eurasian steppe over time, and an expansion of isotopic niche widths, indicate that historic Mongolian empires were supported by a diversification of economic strategies rather than uniform, specialized pastoralism.