199 research outputs found
Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice
Dogs accompanied humans during the Neolithic expansion into Europe
International audienceNear Eastern Neolithic farmers introduced several species of domestic plants and animals as they dispersed into Europe. Dogs were the only domestic species present in both Europe and the Near East prior to the Neolithic. Here, we assessed whether early Near Eastern dogs possessed a unique mitochondrial lineage that differentiated them from Mesolithic European populations. We then analysed mitochondrial DNA sequences from 99 ancient European and Near Eastern dogs spanning the Upper Palaeolithic to the Bronze Age to assess if incoming farmers brought Near Eastern dogs with them, or instead primarily adopted indigenous European dogs after they arrived. Our results show that European pre-Neolithic dogs all possessed the mitochondrial haplogroup C, and that the Neolithic and Post-Neolithic dogs associated with farmers from Southeastern Europe mainly possessed haplogroup D. Thus, the appearance of haplogroup D most probably resulted from the dissemination of dogs from the Near East into Europe. In Western and Northern Europe, the turnover is incomplete and haplogroup C persists well into the Chalcolithic at least. These results suggest that dogs were an integral component of the Neolithic farming package and a mitochondrial lineage associated with the Near East was introduced into Europe alongside pigs, cows, sheep and goats. It got diluted into the native dog population when reaching the Western and Northern margins of Europe
Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice
The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible
Postnatal PPARÎŽ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice
BACKGROUND: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice. METHODOLOGY/PRINCIPAL FINDINGS: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. CONCLUSIONS/SIGNIFICANCE: The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM
Redefining the timing and circumstances of the chicken's introduction to Europe and north-west Africa
This is the final version. Available on open access from Cambridge University Press via the DOI in this recordLittle is known about the early history of the chicken (Gallus gallus domesticus), including the timing and circumstances of its introduction into new cultural environments. To evaluate its spatio-temporal spread across Eurasia and north-west Africa, the authors radiocarbon dated 23 chicken bones from presumed early contexts. Three-quarters returned dates later than those suggested by stratigraphy, indicating the importance of direct dating. The results indicate that chickens did not arrive in Europe until the first millennium BC. Moreover, a consistent time-lag between the introduction of chickens and their consumption by humans suggests that these animals were initially regarded as exotica and only several centuries later recognised as a source of âfoodâ.Arts and Humanities Research Council (AHRC)Natural Environment Research Council (NERC)Chair of Palaeoanatomy, LMU Munic
Origins and genetic legacy of prehistoric dogs
Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry
Preparation of a Trp-BODIPY fluorogenic amino acid to label peptides for enhanced live-cell fluorescence imaging
Electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells
It has been reported previously that electric pulses of sufficiently high voltage and short duration can permeabilize the membranes of various organelles inside living cells. In this article, we describe electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. The cells were exposed to short, high-voltage electric pulses (from 1 to 20 pulses, 60Â ns, 50Â kV/cm, repetition frequency 1Â kHz). We observed that 10 and 20 such pulses induced permeabilization of membranes of endocytotic vesicles, detected by release of lucifer yellow from the vesicles into the cytosol. Simultaneously, we detected uptake of propidium iodide through plasma membrane in the same cells. With higher number of pulses permeabilization of the membranes of endocytotic vesicles by pulses of given parameters is accompanied by permeabilization of plasma membrane. However, with lower number of pulses only permeabilization of the plasma membrane was detected
Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets
Human-mediated biological exchange has had global social and ecological impacts. In subS-aharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation
Grey wolf genomic history reveals a dual ancestry of dogs
The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe
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