Biology subjects

Turk, A.

Publications and source records attributed to Turk, A..

6 recordsLinked to original sources

bioRxiv2026

Omics-scale capture of electrophilic metabolites

The majority of metabolic pathways rely on the production of activated electrophilic intermediates, e.g., coenzyme-A esters, and their chemical structures and abundances are central to understanding enzyme function and biochemical mechanisms. However, most electrophilic metabolites are lost in traditional metabolomic analysis and thus remain poorly characterized. Here we introduce a biochemical probe, O-(trimethylammoniobutyl)-hydroxylamine (TAMOHA), that enables comprehensive profiling of electrophilic species such as coenzyme-A esters, ketones, and aldehydes. TAMOHA incorporates a highly nucleophilic hydroxyl amine that reacts quickly with electrophilic species upon tissue lysis, trapping them as stable derivatives that feature a tetraalkylammonium moiety whose constitutive charge and characteristic MS2 fragmentation fingerprint enable their highly sensitive detection. Using TAMOHA to survey the electrophilomes of E. coli, C. elegans, and mouse revealed several thousand electrophilic metabolites, most of which have not been characterized. We then demonstrate trapping of electrophilic metabolites with TAMOHA in the context of specific biochemical pathways, confirming previously proposed functions of two fatty acid metabolism enzymes, detecting formaldehyde production in mice, and providing new insights into the biosynthesis of ascaroside pheromones in C. elegans. We anticipate that use of TAMOHA for the profiling of electrophilic species will help clarify enzyme function and uncover previously elusive biochemical mechanisms in a wide range of biological systems. Table of Contents artwork O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/743530v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@79a416org.highwire.dtl.DTLVardef@3b937org.highwire.dtl.DTLVardef@74cae9org.highwire.dtl.DTLVardef@1b5a915_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Ancient human genomes from the Altai region reveal population continuity and shifts in the 4th-12th centuries

The Altai region is a crossroads of the Asian steppes. However, the population history of the region remains understudied. We analyse ancient human genomes from the Altai and Ob regions, creating a ca. 1400-year-long time transect with 91 new data. We demonstrate an Iron Age genetic variety that continued into the Medieval era, with additional large-scale spread of East Asian genetic ancestry coinciding with the rise and spread of the Turkic cultural customs. Furthermore, we find a unique lineage in the Early Medieval Altai with elevated Ancient North Eurasian ancestry, providing a missing link between the North Eurasian hunter-gatherers and modern North Asian people. We identify distinct genetic patterns and connections among populations of the Mountainous and the Forest-Steppe Altai in the 4th-8th centuries.

genetics↗

bioRxiv2026

Efficacy of SGLT2 Inhibitors in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Preclinical Studies

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease marked by vascular remodeling, elevated pulmonary pressures, and right ventricular failure. Current therapies are mainly vasodilatory, underscoring the need for treatments targeting additional pathways. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially used for diabetes, have demonstrated cardiovascular benefits. AimsThis systematic review and meta-analysis evaluated the effects of SGLT2 inhibitors in animal models of PAH, focusing on pulmonary hemodynamics and right ventricular function. MethodsPubMed, Embase, Web of Science, and Scopus were searched for preclinical studies reporting mean pulmonary artery pressure (mPAP), right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RV/LV+S), tricuspid annular plane systolic excursion (TAPSE), or pulmonary artery acceleration time (PAAT). Random-effects meta-analyses were performed using R. ResultsNine studies were included. SGLT2 inhibitors were significantly associated with lower mPAP (WMD -9.79 mmHg), RVSP (WMD -14.81 mmHg), and RV/LV+S (WMD -0.10). They were also associated with higher indices of right ventricular function, including TAPSE (WMD 0.53 mm) and PAAT (WMD 6.39 ms). ConclusionIn preclinical models of PAH, SGLT2 inhibitor treatment was associated with favorable hemodynamic and structural parameters. Further research is needed to clarify their translational potential and long-term safety.

pharmacology and toxicology↗

bioRxiv2024

Modeling speech adaptation to altered sensory feedback through continuous learning of internal sensory predictions

The paper presents a version of an optimization-based model of speech production that reproduces key acoustic and articulatory features of motorsensory adaptation to altered sensory feedback. In the presented approach, the mechanism of motorsensory adaptation is based on regular updates, based on the sensory feedback perceived by the speaker, of two of the speakers internal models used for computing (near)-optimal articulation. These internal models, modeled as separate Artificial Neural Networks, are 1) a model that predicts the acoustic consequences of motor (articulatory commands) and 2) a model that predicts the somatosensory sensations from given motor commands. The paper presents simulations of adaptation experiments that successfully reproduce key acoustic and articulatory features of motorsensory adaptation of speech to altered sensory feedback. These include gradual and incomplete motorsensory adaptation when the auditory (or the somatosensory) feedback is suddenly altered (F1-shifted for the altered auditory feedback, forced jaw movement for altered somatosensory feedback). The presented simulations also show that the rate and magnitude of adaptation behavior depend on a small number of parameters. Variation in the values of these parameters can potentially explain inter-speaker differences in terms of adaptation behavior, including sensory preference.

neuroscience↗

bioRxiv2022

Tracing genetic connections of ancient Hungarians to the 6-14th century populations of the Volga-Ural region

Most of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological, and archaeological data. We present here the uniparental genetic makeup of the medieval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originates from ancient proto-Ob-Ugric people from Western Siberia (6th-13th century), the pre-Conquest period, and subsisting Hungarians from the Volga-Ural region (6th-14th century) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework. We analysed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East-Eurasian uniparental lineages in their genepool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups. Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors maternal genepool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.

genetics↗

bioRxiv2020

Early Medieval Genetic Data from Ural Region Evaluated in the Light of Archaeological Evidence of Ancient Hungarians

The ancient Hungarians originated from the Ural region of Russia, and migrated through the Middle-Volga region and the Eastern European steppe into the Carpathian Basin during the 9th century AD. Their Homeland was probably in the southern Trans-Ural region, where the Kushnarenkovo culture disseminated. In the Cis-Ural region Lomovatovo and Nevolino cultures are archaeologically related to ancient Hungarians. In this study we describe maternal and paternal lineages of 36 individuals from these regions and nine Hungarian Conquest period individuals from todays Hungary, as well as shallow shotgun genome data from the Trans-Uralic Uyelgi cemetery. We point out the genetic continuity between the three chronological horizons of Uyelgi cemetery, which was a burial place of a rather endogamous population. Using phylogenetic and population genetic analyses we demonstrate the genetic connection between Trans-, Cis-Ural and the Carpathian Basin on various levels. The analyses of this new Uralic dataset fill a gap of population genetic research of Eurasia, and reshape the conclusions previously drawn from 10-11th century ancient mitogenomes and Y-chromosomes from Hungary.

genetics↗