Biology subjects

Ivanova, S.

Publications and source records attributed to Ivanova, S..

5 recordsLinked to original sources

bioRxiv2026

Tracing mobility among Eneolithic-Bronze Age Kurgan populations in the North Pontic steppe

Five millennia ago, nomadic people from the North Pontic steppe left a profound impact on the course of Eurasian prehistory. However, little is known about their mobility patterns within their home region. To address this knowledge gap, we conducted a survey of the strontium isotope landscape of people interred in the 4th-3rd millennium BCE burial mounds (kurgans) of the western part of the North Pontic steppe. By analyzing the strontium signature in human bone and dentin, we established strontium baseline values for the region. We subsequently correlated enamel strontium ratios from 25 selected individuals with the baseline obtained and with published strontium data across the North Pontic steppe. Enamel strontium ratios show that some individuals interred in the northwest North Pontic fall within the regional baseline range, whereas others overlap with values reported for the eastern North Pontic steppe. In conjunction with carbon ({delta}13C) and nitrogen ({delta}15N) stable isotope data, we further determined that some individuals interred in the western Pontic steppe either spent the later part of life in the west Caspian steppe or were affected by physiological stress during lifetime. By integrating our data with published isotopic datasets, we produced a first baseline heatmap of the North Pontic steppe for the c. 4000-2000 BCE chronological period.

evolutionary biology↗

bioRxiv2024

A genomic history of the North Pontic Region from the Neolithic to the Bronze Age

The north Black Sea (Pontic) Region was the nexus of the farmers of Old Europe and the foragers and pastoralists of the Eurasian steppe1,2, and the source of waves of migrants that expanded deep into Europe3-5. We report genome-wide data from 78 prehistoric North Pontic individuals to understand the genetic makeup of the people involved in these migrations and discover the reasons for their success. First, we show that native North Pontic foragers had ancestry not only from Balkan and Eastern hunter-gatherers6 but also from European farmers and, occasionally, Caucasus hunter-gatherers. More dramatic inflows ensued during the Eneolithic, when migrants from the Caucasus-Lower Volga area7 moved westward, bypassing the local foragers to mix with Trypillian farmers advancing eastward. People of the Usatove archaeological group in the Northwest Pontic were formed ca. 4500 BCE with an equal measure of ancestry from the two expanding groups. A different Caucasus-Lower Volga group, moving westward in a distinct but temporally overlapping wave, avoided the farmers altogether, and blended with the foragers instead to form the people of the Serednii Stih archaeological complex7. A third wave of expansion occurred when Yamna descendants of the Serednii Stih forming ca. 4000 BCE expanded during the Early Bronze Age (3300 BCE). The temporal gap between Serednii Stih and the Yamna expansion is bridged by a genetically Yamna individual from Mykhailivka in Ukraine (3635-3383 BCE), a site of uninterrupted archaeological continuity across the Eneolithic-Bronze Age transition, and the likely epicenter of Yamna formation. Each of these three waves propagated distinctive ancestries while also incorporating outsiders during its advance, a flexible strategy forged in the North Pontic region that may explain its peoples outsized success in spreading their genes and culture across Eurasia3-5,8-10.

genetics↗

bioRxiv2023

The new signaling pathway ERK5/TP53INP2 sensitizes cancer cells to death-receptor agonists and Natural Killer cells

Death receptor ligand TRAIL is a promising cancer therapy due to its ability to selectively trigger extrinsic apoptosis in cancer cells. However, TRAIL-based therapies in humans have shown limitations, mainly due inherent or acquired resistance of tumor cells. To address this issue, current efforts are focussed on dissecting the intracellular signaling pathways involved in resistance to TRAIL, to identify strategies that sensitize cancer cells to TRAIL-induced cytotoxicity. In this work, we describe the oncogenic MEK5-ERK5 pathway as a critical regulator of cancer cell resistance to the apoptosis induced by death receptor ligands. Using 2D and 3D cell cultures and transcriptomic analyses, we show that ERK5 controls the proteostasis of TP53INP2, a protein necessary for full activation of caspase-8 activation in response to TNF, FasL or TRAIL. Mechanistically, ERK5 phosphorylates and induces ubiquitylation and proteasomal degradation of TP53INP2, resulting in cancer cell resistance to TRAIL. Concordantly, ERK5 inhibition or genetic deletion, by stabilizing TP53INP2, sensitizes cancer cells to the apoptosis induced by recombinant TRAIL and TRAIL/FasL expressed by Natural Killer cells. The MEK5-ERK5 pathway regulates cancer cell proliferation and survival, and ERK5 inhibitors have shown anticancer activity in preclinical models of solid tumors. Using endometrial cancer patient-derived xenograft organoids, we propose ERK5 inhibition as an effective strategy to sensitize cancer cells to TRAIL-based therapies and Natural Killer cells.

cancer biology↗

bioRxiv2020

Feeding dihydroquercetin and vitamin E to broiler chickens reared at standard and high ambient temperatures

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition have recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitamin E and standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract development (GIT), jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets were fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at a constant 35 {degrees}C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27 {degrees}C at 7d of age to 22 {degrees}C at 20d of age (standard temperature; ST). Rearing birds at HT reduced: feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin E increased spleen and liver weights. When fed together, DHQ and vitamin E reduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under a range of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates.

physiology↗

bioRxiv2020

HIV-1 Vpr-induced Proinflammatory Response and Apoptosis are Mediated through the Sur1-Trpm4 Channel in Astrocytes

There are about 38 million people currently living with HIV/AIDS worldwide. Successful treatment with combinational antiretroviral therapies (cART) can eliminate active replicating viruses and prolong lives to nearly normal lifespans. However, the new challenge faced by more than half of those HIV-infected and aging patients is chronic CNS neuroinflammation, which leads to HIV-associated neurocognitive disorders (HAND). While severe and progressive HAND has decreased significantly due to cART, chronic HAND often persists, resulting in high rates of delirium, dementia and depression that could lead to suicide. Indeed, the risk of suicide mortality in HIV-infected persons is significantly higher than in HIV-uninfected counterparts. Nevertheless, the mechanism of neuropathogenesis underlying HAND is not well understood. HAND is typically characterized by HIV-mediated glial neuroinflammation and neurotoxicity. Interestingly, the severity of some HAND does not always correlate with the levels of HIV, but rather with glial activation, suggesting other HIV-associated factors, not the whole virus per se, contribute to those HAND. HIV-1 viral protein R (Vpr) might be one of those viral factors, because Vpr induces neuroinflammation and causes neuronal apoptosis. The objective of this study was to delineate the specific role(s) of Vpr in activation of host neuroinflammation and neurotoxicity, as well as its contribution to HAND. In this report, we show correlations between HIV expression and activation of proinflammatory markers (TLR4, TNF, and NF{kappa}B) and the Sur1-Trpm4 channel in astrocytes of HIV-infected postmortem human and transgenic mouse brain tissues. We further show that Vpr alone activate the same set of proinflammatory markers in an astrocytic cell line SNB19. Vpr-induced host cell proinflammatory responses result in apoptotic cell death. Together, our data suggest that HIV-1 Vpr-induced proinflammatory response and apoptotic cell death are mediated through the Sur1-Trpm4 channel in astrocytes.

neuroscience↗