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.

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.

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.

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.

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.

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.

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.

Author Correction: Early Pastoral Economies and Herding Transitions in Eastern Eurasia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Early Pastoral Economies and Herding Transitions in Eastern Eurasia.

While classic models for the emergence of pastoral groups in Inner Asia describe mounted, horse-borne herders sweeping across the Eurasian Steppes during the Early or Middle Bronze Age (ca. 3000-1500 BCE), the actual economic basis of many early pastoral societies in the region is poorly characterized. In this paper, we use collagen mass fingerprinting and ancient DNA analysis of some of the first stratified and directly dated archaeofaunal assemblages from Mongolia's early pastoral cultures to undertake species identifications of this rare and highly fragmented material. Our results provide evidence for livestock-based, herding subsistence in Mongolia during the late 3rd and early 2nd millennia BCE. We observe no evidence for dietary exploitation of horses prior to the late Bronze Age, ca. 1200 BCE - at which point horses come to dominate ritual assemblages, play a key role in pastoral diets, and greatly influence pastoral mobility. In combination with the broader archaeofaunal record of Inner Asia, our analysis supports models for widespread changes in herding ecology linked to the innovation of horseback riding in Central Asia in the final 2nd millennium BCE. Such a framework can explain key broad-scale patterns in the movement of people, ideas, and material culture in Eurasian prehistory.

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.

Grazing animals drove domestication of grain crops.

In addition to large-seeded cereals, humans around the world during the mid-Holocene started to cultivate small-seeded species of herbaceous annuals for grain, including quinoa, amaranth, buckwheat, the millets and several lost crops domesticated in North America. The wild ancestors of these crops have small seeds with indigestible defences and do not germinate readily. Today, these wild plants exist in small fragmentary stands that are not appealing targets for foragers. This combination of traits has led many to argue that they must have been a food of last resort. We propose a new explanation: the domestication of small-seeded annuals involved a switch from endozoochoric dispersal (through animal ingestion) to human dispersal. Humans encountered these plants in dense stands created by grazing megafauna, making them easy to harvest. As humans began to cultivate these plants they took on the functional role of seed dispersers, and traits associated with endozoochory were lost or reduced. The earliest traits of domestication-thinning or loss of indigestible seed protections, loss of dormancy and increased seed size-can all be explained by the loss of the ruminant dispersal process and concomitant human management of wild stands. We demonstrate, by looking at rangeland ecology and herd animal herbivory patterns, that the progenitors of all of these species evolved to be dispersed by megafaunal ruminants and that heavy herbivory leads to dense homogenous clusters of endozoochoric plants. Hence, easily harvested stands on nitrogen hot spots near water sources would have existed in regions where these plants were domesticated. Future experimental and ecological studies could enhance our understanding of the relationships between specific crops and their possible ruminant dispersers.

Correction: Arboreal crops on the medieval Silk Road: Archaeobotanical studies at Tashbulak.

[This corrects the article DOI: 10.1371/journal.pone.0201409.].

Arboreal crops on the medieval Silk Road: Archaeobotanical studies at Tashbulak.

During the first millennium A.D., Central Asia was marked by broad networks of exchange and interaction, what many historians collectively refer to as the "Silk Road". Much of this contact relied on high-elevation mountain valleys, often linking towns and caravanserais through alpine territories. This cultural exchange is thought to have reached a peak in the late first millennium A.D., and these exchange networks fostered the spread of domesticated plants and animals across Eurasia. However, few systematic studies have investigated the cultivated plants that spread along the trans-Eurasian exchange during this time. New archaeobotanical data from the archaeological site of Tashbulak (800-1100 A.D.) in the mountains of Uzbekistan is shedding some light on what crops were being grown and consumed in Central Asia during the medieval period. The archaeobotanical assemblage contains grains and legumes, as well as a wide variety of fruits and nuts, which were likely cultivated at lower elevations and transported to the site. In addition, a number of arboreal fruits may have been collected from the wild or represent cultivated version of species that once grew in the wild shrubby forests of the foothills of southern Central Asia in prehistory. This study examines the spread of crops, notably arboreal crops, across Eurasia and ties together several data sets in order to add to discussions of what plant cultivation looked like in the central region of the Silk Road.

Barley (Hordeum vulgare) in the Okhotsk culture (5th-10th century AD) of northern Japan and the role of cultivated plants in hunter-gatherer economies.

This paper discusses archaeobotanical remains of naked barley recovered from the Okhotsk cultural layers of the Hamanaka 2 archaeological site on Rebun Island, northern Japan. Calibrated ages (68% confidence interval) of the directly dated barley remains suggest that the crop was used at the site ca. 440-890 cal yr AD. Together with the finds from the Oumu site (north-eastern Hokkaido Island), the recovered seed assemblage marks the oldest well-documented evidence for the use of barley in the Hokkaido Region. The archaeobotanical data together with the results of a detailed pollen analysis of contemporaneous sediment layers from the bottom of nearby Lake Kushu point to low-level food production, including cultivation of barley and possible management of wild plants that complemented a wide range of foods derived from hunting, fishing, and gathering. This qualifies the people of the Okhotsk culture as one element of the long-term and spatially broader Holocene hunter-gatherer cultural complex (including also Jomon, Epi-Jomon, Satsumon, and Ainu cultures) of the Japanese archipelago, which may be placed somewhere between the traditionally accepted boundaries between foraging and agriculture. To our knowledge, the archaeobotanical assemblages from the Hokkaido Okhotsk culture sites highlight the north-eastern limit of prehistoric barley dispersal. Seed morphological characteristics identify two different barley phenotypes in the Hokkaido Region. One compact type (naked barley) associated with the Okhotsk culture and a less compact type (hulled barley) associated with Early-Middle Satsumon culture sites. This supports earlier suggestions that the "Satsumon type" barley was likely propagated by the expansion of the Yayoi culture via south-western Japan, while the "Okhotsk type" spread from the continental Russian Far East region, across the Sea of Japan. After the two phenotypes were independently introduced to Hokkaido, the boundary between both barley domains possibly existed ca. 600-1000 cal yr AD across the island region. Despite a large body of studies and numerous theoretical and conceptual debates, the question of how to differentiate between hunter-gatherer and farming economies persists reflecting the wide range of dynamic subsistence strategies used by humans through the Holocene. Our current study contributes to the ongoing discussion of this important issue.

The hippocampus and TNF: Common links between chronic pain and depression.

Major depression and chronic pain are significant health problems that seriously impact the quality of life of affected individuals. These diseases that individually are difficult to treat often co-exist, thereby compounding the patient's disability and impairment as well as the challenge of successful treatment. The development of efficacious treatments for these comorbid disorders requires a more comprehensive understanding of their linked associations through common neuromodulators, such as tumor necrosis factor-α (TNFα), and various neurotransmitters, as well as common neuroanatomical pathways and structures, including the hippocampal brain region. This review discusses the interaction between depression and chronic pain, emphasizing the fundamental role of the hippocampus in the development and maintenance of both disorders. The focus of this review addresses the hypothesis that hippocampal expressed TNFα serves as a therapeutic target for management of chronic pain and major depressive disorder (MDD).

Chronic constriction injury-induced nociception is relieved by nanomedicine-mediated decrease of rat hippocampal tumor necrosis factor.

Neuropathic pain is a chronic pain syndrome that arises from nerve injury. Current treatments only offer limited relief, clearly indicating the need for more effective therapeutic strategies. Previously, we demonstrated that proinflammatory tumor necrosis factor-alpha (TNF) is a key mediator of neuropathic pain pathogenesis; TNF is elevated at sites of neuronal injury, in the spinal cord, and supraspinally during the initial development of pain. The inhibition of TNF action along pain pathways outside higher brain centers results in transient decreases in pain perception. The objective of this study was to determine whether specific blockade of TNF in the hippocampus, a site of pain integration, could prove efficacious in reducing sciatic nerve chronic constriction injury (CCI)-induced pain behavior. Small inhibitory RNA directed against TNF mRNA was complexed to gold nanorods (GNR-TNF siRNA; TNF nanoplexes) and injected into the contralateral hippocampus of rats 4 days after unilateral CCI. Withdrawal latencies to a noxious thermal stimulus (hyperalgesia) and withdrawal to innocuous forces (allodynia) were recorded up to 10 days and compared with baseline values and sham-operated rats. Thermal hyperalgesia was dramatically decreased in CCI rats receiving hippocampal TNF nanoplexes; and mechanical allodynia was transiently relieved. TNF levels (bioactive protein, TNF immunoreactivity) in hippocampal tissue were decreased. The observation that TNF nanoplex injection into the hippocampus alleviated neuropathic pain-like behavior advances our previous findings that hippocampal TNF levels modulate pain perception. These data provide evidence that targeting TNF in the brain using nanoparticle-protected siRNA may be an effective strategy for treatment of neuropathic pain.