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 (Canis familiaris) lived1-8. 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 IFT88 40,000-30,000 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.

Dissipative three-dimensional topological optical solitons with crossed localization of polarization components.

We present a new, to the best of our knowledge, type of vector three-dimensional dissipative optical solitons with more extended degrees of freedom in a laser or laser medium with saturable absorption. These solitons are reconfigurable, include polarization singularities, and have various mutual orientations of nearly toroidal localization domains of polarization components. Numerical modeling confirms the stability of these solitons and breathers and reveals their symmetry and even "supersymmetry," as well as transformations when parameters leave the stability region. These solitons, which have no scalar analogs, are capable of carrying more than one bit of information. Our results expand the "alphabet" of solitons and can provide a route to breakthroughs in larger-capacity communication and information applications.

Solutocapillary transport of oxygen bubbles in a diffusion-bubbling membrane core.

Bubbles are extensively explored as gas and energy carriers. However, despite notable progress, the bubble transport mechanisms are still poorly understood. At the present time there is not sufficient understanding of whether the body or surface forces play a major role in bubble transport in liquid interfacial systems. This understanding is important to be able to drive oxygen bubble transport. Here, we show the crucial role of solutocapillary forces in oxygen bubble transport in the core of a diffusion-bubbling membrane with a high density of solid/liquid and gas/liquid interfaces that operates under the oxygen chemical potential gradient. In order to describe the transport of oxygen bubbles in the membrane core, we developed a mathematical model. Both the velocity of bubbles and oxygen flux through this membrane predicted by this model agree with experiments. An in-depth understanding of the bubble transport mechanism presented in this study could eventually lead the way to more efficient bubble membrane gas separation, bubble energy generation, and bubble-assisted therapy in the future.

Prediction-Retrodiction Measurements for Teleportation and Conditional State Transfer.

Regular measurements allow predicting the future and retrodicting the past of quantum systems. Time-nonlocal measurements can leave the future and the past uncertain, yet establish a relation between them. We show that continuous time-nonlocal measurements can be used to transfer a quantum state via teleportation or direct transmission. Considering two oscillators probed by traveling fields, we analytically identify strategies for performing the state transfer perfectly across a wide range of linear oscillator-field interactions beyond the pure beam-splitter and two-mode-squeezing types.

Investigation of the Information Possibilities of the Parameters of Vibroacoustic Signals Accompanying the Processing of Materials by Concentrated Energy Flows.

Creating systems for monitoring technology processes based on concentrated energy flows is an urgent and challenging task for automated production. Similar processes accompany such processing technologies: intensive thermal energy transfer to the substance, heating, development of the melting and evaporation or sublimation, ionization, and expansion of the released substance. It is accompanied by structural and phase rearrangements, local changes in volumes, chemical reactions that cause perturbations of the elastic medium, and the propagation of longitudinal and transverse waves in a wide frequency range. Vibrational energy propagates through the machine's elastic system, making it possible to register vibrations on surfaces remotely. Vibration parameters can be used in monitoring systems to prevent negative phenomena during processing and to be a tool for understanding the processes' kinetics. In some cases, it is the only source of information about the progress in the processing zone.

Frequency locking and alternation of topological indices of vortex laser solitons.

We analyze the effect of frequency locking for polarization components of a semiconductor laser with fast gain, saturating absorption, and weak anisotropy. A mode of alternation of topological indices when leaving the locking area was found.

Ancient RNA from Late Pleistocene permafrost and historical canids shows tissue-specific transcriptome survival.

While sequencing ancient DNA (aDNA) from archaeological material is now commonplace, very few attempts to sequence ancient transcriptomes have been made, even from typically stable deposition environments such as permafrost. This is presumably due to assumptions that RNA completely degrades relatively quickly, particularly when dealing with autolytic, nuclease-rich mammalian tissues. However, given the recent successes in sequencing ancient RNA (aRNA) from various sources including plants and animals, we suspect that these assumptions may be incorrect or exaggerated. To challenge the underlying dogma, we generated shotgun RNA data from sources that might normally be dismissed for such study. Here, we present aRNA data generated from two historical wolf skins, and permafrost-preserved liver tissue of a 14,300-year-old Pleistocene canid. Not only is the latter the oldest RNA ever to be sequenced, but it also shows evidence of biologically relevant tissue specificity and close similarity to equivalent data derived from modern-day control tissue. Other hallmarks of RNA sequencing (RNA-seq) data such as exon-exon junction presence and high endogenous ribosomal RNA (rRNA) content confirms our data's authenticity. By performing independent technical library replicates using two high-throughput sequencing platforms, we show not only that aRNA can survive for extended periods in mammalian tissues but also that it has potential for tissue identification. aRNA also has possible further potential, such as identifying in vivo genome activity and adaptation, when sequenced using this technology.

Toporosides A and B, Cyclopentenyl-Containing ω-Glycosylated Fatty Acid Amides, and Toporosides C and D from the Northwestern Pacific Marine Sponge Stelodoryx toporoki.

Toporosides A-D (1-4), new ω-glycosylated fatty acid amides, were isolated from the sponge Stelodoryx toporoki. The structures of these compounds, including absolute configurations of stereogenic centers, were established using analysis of 1D and 2D NMR, ECD, and HR mass spectra as well as chemical transformations. Toporosides A (1) and B (2) are the first lipids containing a cyclopentenyl α,ß-unsaturated carbonyl moiety in the polymethylene chain. Toporoside C (3) is likely a precursor, which undergoes intramolecular aldol condensation to produce 1 and 2. Toporosides A, C, and D showed protective effects against TNF-α-induced injury in H9c2 cardiomyocytes.

1-O-Alkylglycerol Ethers from the Marine Sponge Guitarra abbotti and Their Cytotoxic Activity.

The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge Guitarra abbotti, whose 1-O-alkyl-sn-glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using 1H and 13C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1-O-(Z-docos-15-enyl)-sn-glycerol (1), 1-O-(Z-docos-17-enyl)-sn-glycerol (2), 1-O-(Z-tricos-15-enyl)-sn-glycerol (3), 1-O-(Z-tricos-16-enyl)-sn-glycerol (4), 1-O-(Z-tricos-17-enyl)-sn-glycerol (5), and 1-O-(Z-tetracos-15-enyl)-sn-glycerol (6). The isolated AGEs show weak cytotoxic activity in THP-1, HL-60, HeLa, DLD-1, SNU C4, SK-MEL-28, and MDA-MB-231 human cancer cells. A further cytotoxicity analysis in JB6 P+ Cl41 cells bearing mutated MAP kinase genes revealed that ERK2 and JNK1 play a cytoprotective role in the cellular response to the AGE-induced cytotoxic effects.

Tubular laser solitons.

We analyze, to the best of our knowledge, a new type of topological optical solitons in lasers with fast saturable absorption, which is intermediate between 2D and 3D ones. Being generated by 2D laser solitons, such 3D dissipative solitons in a laser cavity of length L have a number of vortex lines, which are straight for under-critical values L and spiral for larger L. For supercritical L, a vortex with multiple topological charges m>1 in generating 2D solitons transforms into m separate vortex lines. Taking into account weak non-paraxiality reveals polarization singularities in the form of lines, on which the elliptical polarization turns into linear in the cross section of the structures.

Oxygen-Selective Diffusion-Bubbling Membranes with Core-Shell Structure: Bubble Dynamics and Unsteady Effects.

Oxygen is the second-largest-volume industrial gas that is mainly produced using cryogenic air separation. However, the state-of-the-art cryogenic technology thermodynamic efficiency has approached a theoretical limit as near as is practicable. Therefore, there is stimulus to develop an alternative technology for efficient oxygen separation from air. Mixed ionic electronic-conducting (MIEC) ceramic membrane-based oxygen separation technology could become this alternative, but commercialization aspects, including cost, have revealed inadequacies in ceramic membrane materials. Currently, diffusion-bubbling molten oxide membrane-based oxygen separation technology is being developed. It is a potentially disruptive technology that would propose an improvement in oxygen purity and a reduction in capital costs. Bubbles play an important role in ensuring the oxygen mass transfer in diffusion-bubbling membranes. However, there is not sufficient understanding of the bubble dynamics. This understanding is important to be able to control transport properties of these membranes and assess their potential for technological application. The aim of this feature article is to highlight the progress made in developing this understanding and specify the directions for future research.

Bubble nucleation in core-shell structured molten oxide-based membranes with combined diffusion-bubbling oxygen mass transfer: experiment and theory.

Oxygen-selective membranes are likely to play a leading part in the future separation processes relevant to energy engineering. A newly developed molten copper and vanadium oxide-based diffusion-bubbling membrane with core-shell structure and fast combined oxygen mass transfer is a promising candidate for efficient oxygen separation. In this work, the oxygen bubble nucleation and transport properties of the diffusion-bubbling membrane were experimentally and theoretically studied. Bubble size distribution and cumulative oxygen flux have been plotted as functions of oxygen partial pressure. The relationship between the bubble density, oxygen partial pressure, and oxygen permeation flux was established. The oxygen flux and bubble density vary in the ranges of 3.2 × 10-8-1.4 × 10-7 mol cm-2 s-1 and 1.3 × 1013-5.8 × 1013 m-3 at ΔPO2 = 0.1-0.75 atm, respectively. The mechanisms of homogeneous, heterogeneous, pseudo-classical and non-classical nucleation are reviewed within the framework of the Cahn-Hilliard model. It is shown that the homogeneous nucleation mechanism is most likely in the membrane core. The estimated values of the interfacial tension, energy barrier, and rate nucleation are 0.02 J m-2, 5 kT, and 4 × 1029 m-3 s-1, respectively.

Ancient DNA suggests modern wolves trace their origin to a Late Pleistocene expansion from Beringia.

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that have maintained a wide geographical distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the Late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single Late Pleistocene population. Both the geographical origin of this ancestral population and how it became widespread remain unknown. Here, we used a spatially and temporally explicit modelling framework to analyse a data set of 90 modern and 45 ancient mitochondrial wolf genomes from across the Northern Hemisphere, spanning the last 50,000 years. Our results suggest that contemporary wolf populations trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum, and that this process was most likely driven by Late Pleistocene ecological fluctuations that occurred across the Northern Hemisphere. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore, and provides insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because Late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.

Clamp-Tapering Increases the Quality Factor of Stressed Nanobeams.

Stressed nanomechanical resonators are known to have exceptionally high quality factors ( Q) due to the dilution of intrinsic dissipation by stress. Typically, the amount of dissipation dilution and thus the resonator Q is limited by the high mode curvature region near the clamps. Here we study the effect of clamp geometry on the Q of nanobeams made of high-stress Si3N4. We find that tapering the beam near the clamps, thus locally increasing the stress, leads to an increased Q of MHz-frequency low order modes due to enhanced dissipation dilution. Contrary to recent studies of tethered-membrane resonators, we find that widening the clamps leads to a decreased Q despite increased stress in the beam bulk. The tapered-clamping approach has practical advantages compared to the recently developed "soft-clamping" technique, as it enhances the Q of the fundamental mode and can be implemented without increasing the device size.

Quantum-Limited Measurements Using an Optical Cavity with Modulated Intrinsic Loss.

We analyze a cavity optomechanical setup, in which the position of an oscillator modulates the internal optical loss. We show that, in contrast to systems with a fixed internal loss, in such a setup, quantum-limited position measurements can be performed and formulate conditions under which it is possible. Additionally, under these conditions the setup exhibits a number of potential benefits for practical operation, including the complete absence of dynamical backaction and optomechanical instability, rejection of classical laser noise, and thermal fluctuations of cavity frequency from the measurement record. We address a few potential experimental implementations of this setup.

Guitarrins A-E and Aluminumguitarrin A: 5-Azaindoles from the Northwestern Pacific Marine Sponge Guitarra fimbriata.

Guitarrins A-E (1-5), the first natural 5-azaindoles, and aluminumguitarrin A (1a), the first aluminum-containing compound from marine invertebrates, were isolated from the sponge Guitarra fimbriata. The structures of these compounds were established using detailed analysis of 1D and 2D NMR data, mass spectra, and X-ray analysis of 1 and 1a. Compound 3 was proved to be a natural inhibitor of alkaline phosphatase.

Melonoside B and Melonosins A and B, Lipids Containing Multifunctionalized ω-Hydroxy Fatty Acid Amides from the Far Eastern Marine Sponge Melonanchora kobjakovae.

Melonoside B (1) and melonosins B (2) and A (3), new lipids based on polyoxygenated fatty acid amides, and known melonoside A (4) were isolated from two different collections of the marine sponge Melonanchora kobjakovae. The structures of these compounds, including their absolute configurations, were established using detailed analysis of 1D and 2D NMR, ECD, and mass spectra as well as chemical transformations. Melonosins 2 and 3 inhibit AP-1- and NF-kB-dependent transcriptional activities in JB6 Cl41 cells at noncytotoxic concentrations, demonstrating potential cancer preventive activity.

Anti-migratory activity of marine alkaloid monanchocidin A - proteomics-based discovery and confirmation.

Monanchocidin A (MonA) is a novel marine alkaloid with promising anti-cancer properties. We recently demonstrated its high efficacy in human urogenital cancers including germ cell tumors. Here, we applied a global proteome screening approach to investigate molecular targets and biological processes affected by MonA in the human cisplatin-resistant germ cell cancer cell line NCCIT-R. Bioinformatical analysis of the proteomics data predicted an effect of MonA on cancer cell migration. Thus, proteins known to be involved in cancer cell migration and invasion were chosen for further validation. The protein alterations identified by proteomics resulted from both, regulation of the total protein expression and post-transcriptional modifications. Among others, regulation of an isoform of vimentin, up-regulation of multiple apolipoprotein E isoforms, and inhibition of hypusination of eukaryotic translation initiation factor 5A-1 were found upon treatment with MonA. Further functional analyses were performed and revealed decreased cell migration and colony formation of cancer cells treated with MonA at non-cytotoxic and non-antiproliferative concentrations. This work provides further insights into the molecular mechanisms behind MonA bioactivity. Furthermore, our research is exemplary for the ability of proteomics to predict drug targets and mode of action of natural anti-cancer agents.

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo. FrA revealed high efficacy in human prostate cancer cells, while non-malignant cells were less sensitive. Remarkably, proliferation and colony formation of cells resistant to enzalutamide and abiraterone (due to the androgen receptor splice variant AR-V7) were also significantly inhibited by FrA. The marine compound caused cell type specific cell cycle arrest and induction of caspase-dependent or -independent apoptosis. Up-regulation or induction of several pro-apoptotic proteins (Bax, Bad, PTEN), cleavage of PARP and caspase-3 and down-regulation of anti-apoptotic proteins (survivin and Bcl-2) were detected in treated cells. Global proteome analysis revealed regulation of proteins involved in formation of metastases, tumor cell invasion, and apoptosis, like keratin 81, CrkII, IL-1ß and cathepsin B. Inhibition of pro-survival autophagy was observed following FrA exposure. In vivo, FrA inhibited tumor growth of PC-3 and DU145 cells with a notable reduction of lung metastasis, as well as circulating tumor cells in the peripheral blood. Increased lymphocyte counts of treated animals might indicate an immune modulating effect of FrA. In conclusion, our results suggest that FrA is a promising new drug for the treatment of mCRPC. Induction of apoptosis, inhibition of pro-survival autophagy, and immune modulatory effects are suspected modes of actions.

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro.

Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1-6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1-4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P⁺ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading.