| 1. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 2. |
- Szucs, Edina, et al.
(författare)
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Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
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| 3. |
- Agalave, Nilesh M., et al.
(författare)
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Sex-dependent role of microglia in disulfide high mobility group box 1 protein-mediated mechanical hypersensitivity
- 2021
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Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 162:2, s. 446-458
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Tidskriftsartikel (refereegranskat)abstract
- High mobility group box 1 protein (HMGB1) is increasingly regarded as an important player in the spinal regulation of chronic pain. Although it has been reported that HMGB1 induces spinal glial activation in a Toll-like receptor (TLR)4-dependent fashion, the aspect of sexual dimorphisms has not been thoroughly addressed. Here, we examined whether the action of TLR4-activating, partially reduced disulfide HMGB1 on microglia induces nociceptive behaviors in a sex-dependent manner. We found disulfide HMGB1 to equally increase microglial Iba1 immunoreactivity in lumbar spinal dorsal horn in male and female mice, but evoke higher cytokine and chemokine expression in primary microglial culture derived from males compared to females. Interestingly, TLR4 ablation in myeloid-derived cells, which include microglia, only protected male mice from developing HMGB1-induced mechanical hypersensitivity. Spinal administration of the glial inhibitor, minocycline, with disulfide HMGB1 also prevented pain-like behavior in male mice. To further explore sex difference, we examined the global spinal protein expression using liquid chromatography-mass spectrometry and found several antinociceptive and anti-inflammatory proteins to be upregulated in only male mice subjected to minocycline. One of the proteins elevated, alpha-1-antitrypsin, partially protected males but not females from developing HMGB1-induced pain. Targeting downstream proteins of alpha-1-antitrypsin failed to produce robust sex differences in pain-like behavior, suggesting that several proteins identified by liquid chromatography-mass spectrometry are required to modulate the effects. Taken together, the current study highlights the importance of mapping sex dimorphisms in pain mechanisms and point to processes potentially involved in the spinal antinociceptive effect of microglial inhibition in male mice.
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| 4. |
- Hegedus, Csaba, et al.
(författare)
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Redox control of cancer cell destruction
- 2018
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 16, s. 59-74
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Tidskriftsartikel (refereegranskat)abstract
- Redox regulation has been proposed to control various aspects of carcinogenesis, cancer cell growth, metabolism, migration, invasion, metastasis and cancer vascularization. As cancer has many faces, the role of redox control in different cancers and in the numerous cancer-related processes often point in different directions. In this review, we focus on the redox control mechanisms of tumor cell destruction. The review covers the tumor intrinsic role of oxidants derived from the reduction of oxygen and nitrogen in the control of tumor cell proliferation as well as the roles of oxidants and antioxidant systems in cancer cell death caused by traditional anticancer weapons (chemotherapeutic agents, radiotherapy, photodynamic therapy). Emphasis is also put on the role of oxidants and redox status in the outcome following interactions between cancer cells, cytotoxic lymphocytes and tumor infiltrating macrophages.
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| 5. |
- Herdean, Andrei, 1984, et al.
(författare)
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A voltage-dependent chloride channel fine-tunes photosynthesis in plants
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7:artikel nr 11654
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Tidskriftsartikel (refereegranskat)abstract
- n natural habitats, plants frequently experience rapid changes in the intensity of sunlight. To cope with these changes and maximize growth, plants adjust photosynthetic light utilization in electron transport and photoprotective mechanisms. This involves a proton motive force (PMF) across the thylakoid membrane, postulated to be affected by unknown anion (Cl−) channels. Here we report that a bestrophin-like protein from Arabidopsis thaliana functions as a voltage-dependent Cl− channel in electrophysiological experiments. AtVCCN1 localizes to the thylakoid membrane, and fine-tunes PMF by anion influx into the lumen during illumination, adjusting electron transport and the photoprotective mechanisms. The activity of AtVCCN1 accelerates the activation of photoprotective mechanisms on sudden shifts to high light. Our results reveal that AtVCCN1, a member of a conserved anion channel family, acts as an early component in the rapid adjustment of photosynthesis in variable light environments.
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| 6. |
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| 7. |
- Szabó, Katalin É., et al.
(författare)
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Sequential colonization of river periphyton analysed by microscopy and molecular fingerprinting
- 2008
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 53:7, s. 1359-1371
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Tidskriftsartikel (refereegranskat)abstract
- 1. An artificial glass substratum was incubated in the River Danube for a period of 28 days in order to detect the sequential colonization of microorganisms.2. Light and fluorescent microscopy showed that microalgae and the picoalgal fraction on the slides increased rapidly over the first 2 weeks of colonization. Diatoms were numerically the most abundant component of the periphyton and their species richness and diversity increased rapidly in the early phase of colonization whereas diversity subsequently increased moderately.3. Evenness of the diatom community was initially high, lower in the intermediate phase and again higher later on. Succession involving early, intermediate and late colonizer species was observed. Community composition during the first 5 days of colonization was very different from later stages whereas there were only minor changes subsequently.4. Molecular community analysis by means of terminal restriction fragment length polymorphism analysis of PCR amplified 16S rRNA and 18S rRNA genes pointed to even larger differences between the composition of samples obtained early and late in the period.5. The number of 18S rRNA and 16S rRNA terminal restriction fragments (T-RF-s) was variable over the colonization period and the fragment patterns of both the bacterial and eukaryotic portion of the microbial community were variable, with most T-RF-s unique to a single sample, suggesting a wide diversity and dynamic properties of periphytic organisms.
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| 8. |
- Szabó, Katalin, et al.
(författare)
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Importance of rare and abundant populations for the structure and functional potential of freshwater bacterial communities
- 2007
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Ingår i: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 47:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Lakewater microcosms were inoculated with freshwater bacterioplankton, to determine how the elimination of less abundant populations affects the structure and basic functional features (growth) of microbial communities. The number of bacteria added to individual microcosms varied from <1 to 2.6 × 10 7 cells. Cultures amended with 11 mg C l_1 of either isolated humic substances or phenol, as well as unamended controls, were studied in parallel. All cultures inoculated with 260 cells or more showed vigorous growth, whereas an inoculum size of 2.6 to 26 cells resulted in growth in the control and humic enrichment cultures only. All cultures were harvested at steady state within 14 d of inoculation. The biomass yield was only slightly affected by the dilution factor. The catechol 2,3-dioxygenase gene (encoding the enzyme responsible for starting the meta pathway of aromatic compound degradation) was detected in all phenol and in the least diluted humic enrichment cultures. Dominant members of the emerging bacterial communities were detected by terminal restriction fragment length polymorphism (T-RFLP) of PCR-amplified 16S rRNA genes. The number of detected community members was much higher in the humic treatment than in the phenol and control treatments. Based on the T-RFLP data, dilution of the inoculum significantly affected the resulting community composition (p < 0.0001). Rare, opportunistic populations were apparently able to exploit the humic enrichment cultures. Phenol appeared to be detrimental to the most abundant members of the original inoculum, but promoted the growth of relatively rare species carrying the catechol 2,3-dioxygenase gene. Thus, community functioning following an environmental perturbation can depend on the presence of rare as well as abundant species.
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| 9. |
- Szabó-Taylor, Katalin É., et al.
(författare)
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Composition and dynamics of microeukaryote communities in the River Danube
- 2010
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Ingår i: Fottea. - 1802-5439. ; 10:1, s. 99-113
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Tidskriftsartikel (refereegranskat)abstract
- The diversity of microeukaryote communities inhabiting rivers is still poorly known. Here, we have analyzed the periphytic and planktonic microeukaryote communities present in one section of the River Danube by two different methods: 18S rRNA-based terminal restriction fragment length polymorphism with fragment sequencing and microscopical analysis of the phytoplankton and periphyton. Both data sets were then related to environmental variables. Molecular fingerprinting revealed diverse communities with fluctuating composition, with the majority of sequences affiliated to the groups Bacillariophyta, Synurophyceae and Chlorophyceae. This was in accordance with microscopical data. The total number of detected T-RFs during the study period was 145, with more than half of the T-RFs being restricted to either plankton or periphyton. This suggests that the likely different natural selection regimes experienced by microeukaryotes in these two environments may promote the presence of different lineages in each of them. Significant correlations were found between phytoplankton chlorophyll a content, phosphorus content, temperature, and the T RFLP pattern of the planktonic microeukaryotic community, suggesting that the former environmental factors are especially important in structuring the planktonic microeukaryote communities in the River Danube. These data, together with earlier studies suggest that molecular methods are an invaluable addition in pursuit of the better understanding of the diversity and fluctuation of freshwater microeukaryotic communities.
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| 10. |
- Ötvös, Ferenc, et al.
(författare)
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Synthesis and biochemical evaluation of 17-N-beta-aminoalkyl-4,5α-epoxynormorphinans
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17-N-substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure–activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [3H]DAMGO, [3H]Ile5,6-deltorphin II and [3H]HS665, respectively. Pharmacological characterization of the compounds in G-protein signaling was determined by [35S]GTPγS binding assays. The normorphine analogues showed higher affinity to KOR compared to MOR and DOR, while most of the noroxymorphone derivatives did not bind to KOR. The presence of 14-OH substituent resulted in a shift in the pharmacological profiles in the agonist > partial agonist > antagonist direction compared to the parent compounds. A molecular docking-based in silico method was also applied to estimate the pharmacological profile of the compounds. Docking energies and the patterns of the interacting receptor atoms, obtained with experimentally determined active and inactive states of MOR, were used to explain the observed pharmacological features of the compounds.
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