23 research outputs found
Population genomics of the Viking world.
The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent
Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice
Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis
BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.
METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids.
RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)].
CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support
New Microbe Killers : Self-Assembled Silver(I) Coordination Polymers Driven by a Cagelike Aminophosphine
New Ag(I) coordination polymers, formulated as [Ag(μ-PTAH)(NO3)2]n (1) and [Ag(μ-PTA)(NO2)]n (2), were self-assembled as light- and air-stable microcrystalline solids and fully characterized by NMR and IR spectroscopy, electrospray ionization mass spectrometry (ESI-MS(±), elemental analysis, powder (PXRD) and single-crystal X-ray diffraction. Their crystal structures reveal resembling 1D metal-ligand chains that are driven by the 1,3,5-triaza-7-phospaadamantane (PTA) linkers and supported by terminal nitrate or nitrite ligands; these chains were classified within a 2C1 topological type. Additionally, the structure of 1 features a 1D!2D network extension through intermolecular hydrogen bonds, forming a two-dimensional hydrogen-bonded network with fes topology. Furthermore, both products 1 and 2 exhibit remarkable antimicrobial activity against different human pathogen bacteria (S. aureus, E. coli, and P. aeruginosa) and yeast (C. albicans), which is significantly superior to the activity of silver(I) nitrate as a reference topical antimicrobial.peerReviewe
New Microbe Killers: Self-Assembled Silver(I) Coordination Polymers Driven by a Cagelike Aminophosphine
New Ag(I) coordination polymers, formulated as [Ag(µ-PTAH)(NO3)2]n (1) and [Ag(µ-PTA)(NO2)]n (2), were self-assembled as light- and air-stable microcrystalline solids and fully characterized by NMR and IR spectroscopy, electrospray ionization mass spectrometry (ESI-MS(±), elemental analysis, powder (PXRD) and single-crystal X-ray diffraction. Their crystal structures reveal resembling 1D metal-ligand chains that are driven by the 1,3,5-triaza-7-phospaadamantane (PTA) linkers and supported by terminal nitrate or nitrite ligands; these chains were classified within a 2C1 topological type. Additionally, the structure of 1 features a 1D→2D network extension through intermolecular hydrogen bonds, forming a two-dimensional hydrogen-bonded network with fes topology. Furthermore, both products 1 and 2 exhibit remarkable antimicrobial activity against different human pathogen bacteria (S. aureus, E. coli, and P. aeruginosa) and yeast (C. albicans), which is significantly superior to the activity of silver(I) nitrate as a reference topical antimicrobial
Impact of genetic polymorphisms of drug transporters ABCB1 and ABCG2 and regulators of xenobiotic transport and metabolism PXR and CAR on clinical efficacy of dasatinib in chronic myeloid leukemia
INTRODUCTION: Functional single-nucleotide polymorphisms (SNPs) in genes regulating cellular uptake, elimination, and metabolism of xenobiotics may potentially influence the outcome of chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKI). Dasatinib, a second-generation TKI, is a substrate of the ABC-superfamily xenobiotic transporters ABCB1 (MDR1, Pg-P) and ABCG2 (BCRP). Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are involved in the control of expression of ABCB1 and ABCG2. AIM OF THE STUDY: In this study, we assessed the impact of inherited variants in ABCB1, ABCG2, PXR, and CAR genes on dasatinib efficacy and toxicity in CML. MATERIALS AND METHODS: Sixty-one tagging SNPs in ABCB1, ABCG2, PXR, and CAR genes were analyzed by real-time quantitative PCR with specific probes in 86 CML patients who failed imatinib therapy. RESULTS: We found the associations between SNPs rs7787082 (ABCB1, OR = 0.2; 95% CI = 0.06-0.66, p = 0.008), rs12505410 (ABCG2, OR = 3.82; 95% CI = 1.38-10.55; p = 0.010), and rs3114018 (ABCG2, OR = 0.24; 95% CI = 0.08-0.71; p = 0.010) and the probability of achieving CCyR. Furthermore, progression-free survival (PFS) was significantly influenced by SNPs rs3732357 (HR = 0.2, 95% CI = 0.26-0.70; p = 0.001), rs3732360 (HR = 0.59; 95% CI = 0.38-0.93; p = 0.020), rs11917714 (HR = 0.58; 95% CI = 0.36-0.92; p = 0.020), and rs3732359 (HR = 0.57; 95% CI = 0.36-0.91; p = 0.024) in PXR; rs2307418 (HR = 2.02; 95% CI = 1.19-3.43; p = 0.048) in CAR; and rs2235023 (HR = 2.49; 95% CI = 1.13-5.50; p = 0.011) and rs22114102 (HR = 1.90; 95% CI = 1.00-3.63; p = 0.028) in ABCB1. Moreover, overall survival (OS) was impacted by rs3842 (HR = 1.84; 95% CI = 1.01-3.33; p = 0.012) and rs2235023 (HR = 2.28; 95% CI = 1.03 = 5.02; p = 0.027) in ABCB1, rs11265571 (HR = 1.59; 95% CI = 0.82-3.08; p = 0.037) and rs2307418 (HR = 73.68; 95% CI = 4.47-1215.31; p = 0.003) in CAR, and rs3732360 (HR = 0.64; 95% CI = 0.40 = 1.04; p = 0.049) in PXR. Taking into account the influence of the tested SNPs on treatment toxicity, we found a significant relationship between allele G of polymorphism in the ABCB1 rs7787082 (OR = 4.46; 95% CI = 1.38-14.39 p = 0.012) and hematological complications assuming the codominant gene inheritance model as well as a significant correlation between the presence of minor allele (G) of SNP rs2725256 in the ABCG2 gene (OR = 4.71; 95% CI = 1.20-18.47; p = 0.026) and the occurrence of non-hematological complications assuming a recessive gene inheritance model. CONCLUSION: Our data suggest that inherited variants in the genes encoding for proteins involved in the transport of xenobiotics may modify the toxicity and efficacy of dasatinib therapy in CML patients
Silver(I) 1,3,5-Triaza-7-phosphaadamantane Coordination Polymers Driven by Substituted Glutarate and Malonate Building Blocks: Self-Assembly Synthesis, Structural Features, and Antimicrobial Properties
Three
new bioactive silver(I) coordination polymers formulated as [Ag<sub>2</sub>(μ<sub>2</sub>-PTA)(μ<sub>3</sub>-PTA)(μ<sub>2</sub>-pga)(H<sub>2</sub>O)]<sub><i>n</i></sub>·6H<sub>2</sub>O (<b>1</b>), [Ag<sub>2</sub>(μ<sub>2</sub>-PTA)(μ<sub>3</sub>-PTA)<i>(</i>Hpmal)<sub>2</sub>]<i><i><sub>n</sub></i></i>·2H<sub>2</sub>O (<b>2</b>), and [Ag(μ<sub>3</sub>-PTA) (Hdmga)]<i><sub>n</sub></i> (<b>3</b>) were self-assembled from Ag<sub>2</sub>O, 1,3,5-triaza-7-phosphaadamantane
(PTA), and a substituted dicarboxylic acid (3-phenylglutaric acid
(H<sub>2</sub>pga), phenylmalonic acid (H<sub>2</sub>pmal), or 3,3-dimethylglutaric
acid (H<sub>2</sub>dmga)) as an ancillary ligand. Compounds <b>1</b>–<b>3</b> were fully characterized by IR and
NMR spectroscopy, ESI-MS(±), elemental analysis, and single-crystal
X-ray diffraction, revealing that their architectural and topological
diversity is governed by structural modulation of a dicarboxylate
building block. The structures vary from a 1D cyclic chain with the
SP 1-periodic net (4,4)(0,2) topology in <b>2</b> to distinct
2D metal–organic layers with the <b>cem-d</b> and <b>hcb</b> topologies in <b>1</b> and <b>3</b>, respectively.
In addition, compounds <b>1</b>–<b>3</b> exhibit
a notable antimicrobial efficiency against a panel of common Gram-negative
(E. coli and P. aeruginosa) and Gram-positive (S. aureus) bacteria
and yeast (C. albicans). The best normalized
minimum inhibitory concentrations (normalized MIC) of 11–23
nmol mL<sup>–1</sup> (for bacterial strains) or 68 nmol mL<sup>–1</sup> (for a yeast strain) are shown by compound <b>2</b>, and the eventual structure–bioactivity correlations
are discussed
New Microbe Killers: Self-Assembled Silver(I) Coordination Polymers Driven by a Cagelike Aminophosphine
Aliphatic Dicarboxylate Directed Assembly of Silver(I) 1,3,5-Triaza-7-phosphaadamantane Coordination Networks: Topological Versatility and Antimicrobial Activity
The
present work describes the facile synthesis, full characterization,
and architectural diversity of three new bioactive silver-organic
networks, namely 1D [Ag<sub>2</sub>(μ-PTA)<sub>2</sub>(<i>μ-</i>suc)]<sub><i>n</i></sub>·2<i>n</i>H<sub>2</sub>O (<b>1</b>), 2D [Ag<sub>2</sub>(μ-PTA)<sub>2</sub>(μ<sub>4</sub><i>-</i>adip)]<sub><i>n</i></sub>·2<i>n</i>H<sub>2</sub>O (<b>2</b>), and
3D [Ag<sub>2</sub>(μ<sub>4</sub>-PTA)(μ<sub>4</sub><i>-</i>mal)]<sub><i>n</i></sub> (<b>3</b>) coordination
polymers, generated via a mixed-ligand strategy using PTA (1,3,5-triaza-7-phosphaadamantane)
as a main building block and flexible aliphatic dicarboxylic acids
(succinic (H<sub>2</sub>suc), adipic (H<sub>2</sub>adip), or malonic
(H<sub>2</sub>mal) acids) as an ancillary ligand source. The compounds <b>1</b>–<b>3</b> were isolated as moderately air and
light stable crystalline solids and were fully characterized by IR
and <sup>1</sup>H and <sup>31</sup>P{<sup>1</sup>H} NMR spectroscopy,
elemental analysis, ESI(±)-MS spectrometry, and single-crystal
X-ray crystallography. The type of aliphatic dicarboxylate plays a
key role in defining the dimensionality and structural and topological
features of the resulting networks, which are also driven by the PTA
blocks that adopt unconventional N,P- or N<sub>3</sub>,P-coordination
modes. The topological analysis of simplified underlying nets revealed
that <b>1</b> possesses uninodal 3-connected chains with the
SP 1-periodic net (4,4)(0,2) topology, <b>2</b> features a uninodal
4-connected layer with the skl topology, and <b>3</b> reveals
a uninodal 4-connected metal–organic framework with the dia
topology. The presence of the crystallization water molecules in polymers <b>1</b> and <b>2</b> gives rise to the extension of their
metal–organic structures into 3D (<b>1</b>) or 2D (<b>2</b>) H-bonded networks that disclose rather rare topologies.
All of the obtained silver(I) coordination polymers feature solubility
in water (<i>S</i><sub>25 °C</sub> ≈ 3–5
mg mL<sup>–1</sup>) and show significant antibacterial and
antifungal activity against the selected strains of Gram-negative
(Escherichia coli, Pseudomonas
aeruginosa) and Gram-positive (Staphylococcus
aureus) bacteria and yeast (Candida
albicans)