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We use a global array of ~120 sea-surface temperature (SST) records based on Mg/Ca, alkenone, and faunal proxies to reconstruct global and regional temperature change over the last 5 Myr. All records are placed on the LR04 age model. Here we report the reconstructions and discuss their implications for characterizing global climate evolution (frequency, variance, transitions) over this interval and its relationship to changes in CO2, orbital forcing, and mean ocean temperature. Average global temperature has cooled by ~6.5oC since 5 Ma, with significant breakpoints tentatively identified at ~3.38 Ma, 1.34 Ma, and 0.88 Ma. We also invert the global reconstruction to reconstruct global sea level for the last 5 Myr.

High obliquity excursions on Mars are hypothesised to have redistributed water from the poles to nourish mid-latitude glaciers. Evidence of this process is provided by a variety of viscous flow features—ice-rich deposits buried beneath sediment mantle—located there today, including ‘lobate debris aprons’, or LDAs. During high obliquity extremes, ice may have persisted even nearer the equator, as indicated by numerous enigmatic moat-like depressions in the tropical Kasei Valles region. Numerous depressions surround isolated mesas and demarcate the past interaction between flowing lava and what were presumably ice-rich radial flows resembling today’s LDAs, but which have long since disappeared. Little is known about ‘ghost lobate debris aprons’ (ghost LDAs), besides their spatial extent as recorded by these depressions. This collection of ghost LDAs implies tropical ice loss over an area ~100,000 km2. To constrain their history in Kasei Valles we derive model ages of different terrain types from crater counts. To constrain the volume of ice loss, we use a 2D perfect-plasticity model of ice flow to reconstruct the ghost LDA surfaces. Parametrised by the present surface topography and the range of yield stresses derived from radar interrogation of mid-latitude ice masses, the model reconstructs former ice surfaces along multiple flowlines orientated normal to ghost LDA boundaries. This reconstruction indicates between 1,300–3,300 km3 of ice—similar to that present in Iceland on Earth—was lost since lava emplacement ~1.4 Ga. Dating of these depressions shows that the ghost LDAs survived for ~800 million years following lava emplacement in the Kasei Valles region before their final demise.

Pigeonpea and Soybean are closely related agronomically important legumes that diverged ∼23 million years ago followed by a whole genome duplication event in Soybean. However, the impact of divergence on their epigenomes is not known. Comparative epigenomics is a powerful tool to understand shaping of epigenomes and its functional consequences during evolution. In this study, we investigated the conservation and divergence of Gene body methylation (GbM) and gene-expression patterns between the two species. We compared their genome-wide DNA methylation landscape at single-base resolution and studied the influence of GbM on duplicate gene retention. Our results indicate that during the divergence of Pigeonpea and Soybean, the effects of methylation on gene expression evolved in a heterogeneous manner. GbM features-slow evolution rate and increased length remained conserved in Pigeonpea and Soybean. We also found that contrary to high CG-methylation conservation, non-CG methylated genes remained diverged during evolution due to transposons insertion in adjacent sequences. The methylation differences in paralogs were associated with expression divergence. Notably, we found that variably methylated marks are less likely to target evolutionary conserved sequences. Finally, our findings identify conservation of nitrogen-related genes during evolution, which are promising candidates for epi-alleles for crop improvement.

Atypical TCRδ found in sharks, amphibians, birds, and monotremes and TCRμ found in monotremes and marsupials are TCR chains that use Ig or BCR-like variable domains (VHδ/Vμ) rather than conventional TCR V domains. These unconventional TCR are consistent with a scenario in which TCR and BCR, although having diverged from each other more than 400 million years ago, continue to exchange variable gene segments in generating diversity for Ag recognition. However, the process underlying this exchange and leading to the evolution of these atypical TCR receptor genes remains elusive. In this study, we identified two TCRα/δ gene loci in the Chinese alligator (Alligator sinensis). In total, there were 144 V, 154 Jα, nine Jδ, eight Dδ, two Cα, and five Cδ gene segments in the TCRα/δ loci of the Chinese alligator, representing the most complicated TCRα/δ gene system in both genomic structure and gene content in any tetrapod examined so far. A pool of 32 VHδ genes divided into 18 subfamilies was found to be scattered over the two loci. Phylogenetic analyses revealed that these VHδ genes could be related to bird VHδ genes, VHδ/Vμ genes in platypus or opossum, or alligator VH genes. Based on these findings, a model explaining the evolutionary pattern of atypical TCRδ/TCRμ genes in tetrapods is proposed. This study sheds new light on the evolution of TCR and BCR genes, two of the most essential components of adaptive immunity.

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic &beta, cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes&mdash, fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-&alpha, levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.

The springtail, Megaphorura arctica, is freeze-avoiding and survives sub-zero temperatures by cryoprotective dehydration. At the onset of dehydration there is some supercooling of body fluids, and the danger of inoculative freezing, which would be lethal. To see if the springtails are protected by antifreeze proteins in this pre-equilibrium phase, we examined extracts from cold-acclimated M. arctica and recorded over 3 °C of freezing point depression. Proteins responsible for this antifreeze activity were isolated by ice affinity. They comprise isoforms ranging from 6.5 to 16.9 kDa, with an amino acid composition dominated by glycine (>35 mol%). Tryptic peptide sequences were used to identify the mRNA sequence coding for the smallest isoform. This antifreeze protein sequence has high similarity to one characterized in Hypogastrura harveyi, from a different springtail order. If these two antifreeze proteins are true homologs, we suggest their origin dates back to the Permian glaciations some 300 million years ago.

The flavonoid pathway is one of the best characterized specialized metabolite pathways of plants. In angiosperms, the flavonoids have varied roles in assisting with tolerance to abiotic stress and are also key for signaling to pollinators and seed dispersal agents. The pathway is thought to be specific to land plants and to have arisen during the period of land colonization around 550–470 million years ago. In this review we consider current knowledge of the flavonoid pathway in the bryophytes, consisting of the liverworts, hornworts, and mosses. The pathway is less characterized for bryophytes than angiosperms, and the first genetic and molecular studies on bryophytes are finding both commonalities and significant differences in flavonoid biosynthesis and pathway regulation between angiosperms and bryophytes. This includes biosynthetic pathway branches specific to each plant group and the apparent complete absence of flavonoids from the hornworts.

BackgroundCarrot (Daucus carota subsp. carotaL.) is an important root crop with an available high-quality genome. The carrot genome is thought to have undergone recursive paleo-polyploidization, but the extent, occurrences, and nature of these events are not clearly defined.ResultsUsing a previously published comparative genomics pipeline, we reanalysed the carrot genome and characterized genomic fractionation, as well as gene loss and retention, after each of the two tetraploidization events and inferred a dominant and sensitive subgenome for each event. In particular, we found strong evidence of two sequential tetraploidization events, with one (Dc-α) approximately 46–52 million years ago (Mya) and the other (Dc-β) approximately 77–87 Mya, both likely allotetraploidization in nature. The Dc-β event was likely common to all Apiales plants, occurring around the divergence of Apiales-Bruniales and after the divergence of Apiales-Asterales, likely playing an important role in the derivation and divergence of Apiales species. Furthermore, we found that rounds of polyploidy events contributed to the expansion of gene families responsible for plastidial methylerythritol phosphate (MEP), the precursor of carotenoid accumulation, and shaped underlying regulatory pathways. The alignment of orthologous and paralogous genes related to different events of polyploidization and speciation constitutes a comparative genomics platform for studying Apiales, Asterales, and many other related species.ConclusionsHierarchical inference of homology revealed two tetraploidization events that shaped the carrot genome, which likely contributed to the successful establishment of Apiales plants and the expansion of MEP, upstream of the carotenoid accumulation pathway.

We provide an evaluation of the paleolatitudinal dependence of the paleosecular variation throughout the Paleozoic-Mesozoic transition - linked to the high geomagnetic reversal frequency interval Illawarra Hyperzone of Mixed Polarity (IHMP; ~266.7-228.7 Myr). Our findings were compared with those for intervals of distinctive geomagnetic reversal frequencies within the Phanerozoic. Our results for the IHMP were conducted through estimates of angular dispersion (S

Comparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from noncoding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure of goddard, a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus. Previous studies found that goddard is required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and circular dichroism (CD) data, we show that Goddard protein contains a large central α-helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years., Previous work identified goddard as a putative de novo evolved gene in Drosophila melanogaster. Here, the authors characterize the structure and function of the Goddard protein in D. melanogaster, and they infer its ancestral and extant structures across the Drosophila genus.

Rapporten utforsker i hvilken grad forbudet mot nydyrking av myr vil virke etter hensikten og dermed hvilket potensial forbudet har som klimapolitisk virkemiddel. Rapporten utforsker bakgrunnen til lovforslaget og ulike aktørers syn uttrykt gjennom høringssvar og intervjuer. Det er også beregnet sannsynlige konsekvenser av forbudet på matproduksjon, økonomiske effekter for næringen og klimagassutslipp. Analysene viser at forbudet har et stort potensial som klimapolitisk virkemiddel. Potensialet underbygges av at konsekvenser for matproduksjon og økonomiske konsekvenser for bruk er relativt lave og håndterbare. Derimot viser rapporten at det er relativt høy risiko for at dette potensialet uthules i implementeringsfasen, for eksempel ved at det gis mange dispensasjoner fra forbudet. Det er derfor viktig å understreke at forbudet har et stort potensial som klimapolitisk virkemiddel som ikke nødvendigvis vil utløses. Funnene i denne rapporten kan bidra til å utløse dette potensialet.

The stick-insect genus Pijnackeria includes four diploid bisexual and two polyploid (3n, 4n) parthenogenetic species. Earlier analyses of the tetraploid parthenogen P. hispanica using mitochondrial markers allowed tracing its maternal ancestry to Pijnackeria originis, while no maternal nuclear contribution was found, thus suggesting an androgenetic and hybrid origin. The recently described Pijnackeria recondita—showing, among other features, a specific antennal structure linking it to the tetraploid parthenogen—prompted us to check whether the new species could be theunknown paternal ancestorof P. hispanica. In this work, we use karyology and molecular analysis of the mitochondrial gene cytochrome c oxidase subunit 2 (cox2) and the nuclear gene elongation factor 1 subunit α (ef1-α) to investigate the origin of such a complex tetraploid hybrid parthenogen. The molecular analysis supported P. recondita as being a paternal ancestor of P. hispanica, but also suggested that two more fathering species have to be taken into account: P. barbarae and the unknown paternal ancestor of the triploid hybrid P. masettii. Therefore, P. hispanica is apparently a polyphyletic chimeric androgen, which we propose to indicate as an androgenetic complex. Our data also revealed that P. hispanica is between 1.96 Myr and 3.31 Myr old, making it the oldest parthenogenetic taxon discovered among insects.

Jokerud, M., Breistøl, A., Blaalid, R. & Ihlen, P.G. 2020. Konsekvenser for naturmangfold i forbindelse med ny kabeltrasé på Nyhamna. NINA Rapport 1865. Norsk institutt for naturforskning. Norske Shell A/S ønsker å etablere en ny kabeltrasé for to strømkabler på land samt et nytt frekvensomformeranlegg rett utenfor prosessanlegget på Nyhamna i Aukra, Møre og Romsdal. Vi har utredet hvilke konsekvenser dette utbyggingsalternativet kan få for naturmangfold. Fokus i oppdraget har vært viktige naturtyper, rødlistearter og økologiske funksjonsområder for arter som fugl, oter og hjortevilt. Rapporten er basert på tilgjengelig kunnskap og nye feltbefaringer. Vurderinger av verdi, omfang og konsekvens har blitt gjort basert på Vegvesenets håndbok for konsekvensanalyser i tillegg til relevante nasjonale håndbøker og standarder. Kystlynghei er både en sterkt truet (EN) og en utvalgt naturtype. En stor del av kabeltraséen går igjennom kystlynghei med store verdier og siden kabeltraséen er 10-12 meter bred vil tiltaket (Alternativ 1) gi en middels negativ konsekvens for naturtypen. Området som er berørt av tiltaket brukes til hekking og for næringssøk av vanlige arter, men det er gjort observasjon av storspove som er en truet fugleart (VU). Oter som også er en truet art (VU) er kjent fra området men de oppholder seg mest nær sjøen. For økologiske funksjonsområder for fugl og pattedyr vil tiltaket gi noe negativ konsekvens. Kystlyngheia og myrområdene tillegges størst vekt i sammenstillingen fordi de har middels til store verdier og siden tiltakene påvirker disse delområdene mest negativt. Samlet konsekvensvurdering av tiltaket er derfor her oppsummert som middels negativ konsekvens. Det er knyttet liten usikkerhet til datagrunnlaget fordi det bygger på både eksisterende kunnskap og registreringer fra eget feltarbeid. Det er liten til middels usikkerhet knyttet til vurderingene av tiltakets påvirkning på naturområdene.

Detailed cyclostratigraphic analyses have been made from seven Tithonian–Hauterivian sections of the Vaca Muerta and Agrio Formations, exposed in southern Mendoza area of the Neuquen Basin. Both lithostratigraphic units are characterized by decimeter-scale rhythmic alternations of marlstones and limestones, showing a well-ordered hierarchy of cycles, including elementary cycles, bundles, and superbundles. According to biostratigraphic data, elementary cycles have a periodicity of ~18–21 ky, which correlates with the precessional cycle of the Earth’s axis. Spectral analysis based on time series of elementary cycle thicknesses allowed us to identify frequencies of ~400 ky, and ~90–120 ky, which we interpret as the modulation of the precessional cycle by the Earth’s orbital eccentricity. A third band frequency of ~40 ky was also identified that can be assigned to the obliquity cycle. Cyclostratigraphy enabled the construction of almost continuous floating astronomical time scale for the Tithonian–Hauterivian, for which a minimum duration of 5.67 myr for the Tithonian, 5.27 myr for the Berriasian, >3.45 myr for the Valanginian, and 5.96 myr for the Hauterivian have been assessed. Additionally, the likely transference mechanisms of the orbital signal to the sedimentary record are analyzed, proposing the coexistence of carbonate exportation and dilution as the dominant mechanisms.

As part of our search for new low-mass members of nearby young moving groups (YMG), we discovered three low-mass, spectroscopic binaries, two of which are not kinematically associated with any known YMG. Using high-resolution optical spectroscopy, we measure the component and systemic radial velocities of the systems, as well as their lithium absorption and H$\alpha$ emission, both spectroscopic indicators of youth. One system (2MASS J02543316-5108313, M2.0+M3.0) we confirm as a member of the 40 Myr old Tuc-Hor moving group, but whose binarity was previously undetected. The second young binary (2MASS J08355977-3042306, K5.5+M1.5) is not a kinematic match to any known YMG, but each component exhibits lithium absorption and strong and wide H$\alpha$ emission indicative of active accretion, setting an upper age limit of 15 Myr. The third system (2MASS J10260210-4105537, M1.0+M3.0) has been hypothesized in the literature to be a member of the 10 Myr old TW Hya Association (TWA), but with our measured systemic velocity, shows the binary is in fact not part of any known YMG. This last system also has lithium absorption in each component, and has strong and variable H$\alpha$ emission, setting an upper age limit of 15 Myr based on the lithium detection., Comment: published in ApJ

Bjerke, J.W. & Tømmervik, H. 2020. Våtmark som hovedøkosystem i Naturindeks for Norge. Vurdering av tilhørighet og referansetilstand for eksisterende og potensielt nye indikatorer. NINA Rapport 1688. Norsk institutt for naturforskning. På oppdrag for Miljødirektoratet har vi vurdert muligheten for utvikling av nye indikatorer for ho-vedøkosystemet våtmark i Naturindeks for Norge. Bakgrunnen for oppdraget var at det eksiste-rende indikatorsettet for våtmark er svært mangelfullt og skjevt fordelt mellom trofiske grupper, samt at det er svært lite overvåking i våtmark, spesielt av det bakkeboende artsinventaret. Definisjon og avgrensning av våtmark varierer betydelig mellom ulike studier. Vi startet derfor oppdraget med å utrede hvordan hovedøkosystemet våtmark skal avgrenses i forhold til andre hovedøkosystemer i Naturindeks, da med spesielt fokus på hvilke natursystemer fra det nasjo-nale type- og beskrivelsessystemet «Natur i Norge» (NiN) som faller inn under våtmark. Ram-meverket for Naturindeks sier at våtmark omfatter myr og kilde både ovenfor og nedenfor skog-grensa. Ut fra dette tolker vi det slik at våtmark i Naturindeks omfatter NiN-typene V1 åpen jord-vannsmyr, V3 nedbørsmyr, V4 kaldkilde og V6 våtsnøleie og snøleiekilde. Hevdpregede natur-typer slik som V9 seminaturlig myr og V10 seminaturlig våteng er definert utenfor, og vi foreslår at disse i stedet innlemmes i hovedøkosystemet åpent lavland i Naturindeks slik at hovedøko-systemet våtmark ikke består av en blanding av indikatorer som skal vurderes utfra to helt for-skjellige referansetilstander, dvs. god hevd kontra menneskelig aktivitet som er eller har vært så begrenset at den har minimal påvirkning på det biologiske mangfoldet. Med bakgrunn i den om-fattende tradisjonelle og moderne naturbruken i Norge diskuterer vi hvorvidt den enkelte overvå-kingslokalitet og den enkelte indikator er representanter for seminaturlige (V9, V10) eller natur-lige (V1, V3, V4, V6) våtmarker. Vi viser at det eksisterende datasettet for våtmark i stor grad er representanter for V9 eller representerer andre hovedøkosystemer. Vår gjennomgang av eksisterende norske tidsserier fra naturovervåkinger som inkluderer fukt-krevende arter viser at de fleste av disse ikke representerer våtmark, dvs. V1, V3, V4 eller V6. I stedet representerer de seminaturlig våtmark, åpent lavland eller skog. Molte kan benyttes som eksempel. Den inngår i en rekke overvåkinger. Til tross for at den er et norsk ikon for myr, så har den også en rekke andre voksesteder. Vår analyse viser at nesten alle tidsserier for molte er fra andre hovedøkosystemer enn våtmark. Vi foreslår flere tiltak som kan forbedre indikatorsettet for hovedøkosystemet våtmark. I Naturin-deks har alle indikatorer tilhørighet til ett eller flere hovedøkosystemer. Vi viser at flere indikatorer fra andre hovedøkosystemer bør ha en viss deltilhørighet i våtmark. Dette gjelder for eksempel villrein som per i dag har 100 % tilhørighet i hovedøkosystemet fjell. Vi foreslår videre at tamrein også bør innlemmes i Naturindeks. Vi viser at våtmark er en viktig næringskilde for all norsk rein. Dette vil gi en eller flere indikatorer for rein som dekker over halvparten av norsk landareal, og som bør ha 30 % deltilhørighet til våtmark. Det vil imidlertid være ei utfordring å avgjøre om dette er seminaturlig våtmark eller naturlig, spesielt i lys av at reindriftlandskapet også er en integrert del av det norske kulturlandskapet. Videre foreslår vi en tilstandsindikator for myr basert på inngrepsfrekvens, som i oppbygging ligner på to eksisterende tilstandsindikatorer for åpent lavland. Våtsnøleie og snøleiekilde er mangelfullt representert i Naturindeks. Vi beskriver her hvordan en ny indikator kan etableres med bakgrunn i rødlistevurderinger av arter fra disse naturtypene. Indikatorens viktigste påvirk-ningsfaktor er klimaendringer. Vi beskriver også en potensielt ny indikator for mikrovåtmarks-habitater i skoglandskapet basert på overvåkinger av torvmoser i forsenkinger i skog. Vi viser at mengde av disse kan endres raskt over korte tidsrom. Disse og andre tiltak summeres til slutt opp i ni anbefalinger. Disse retter seg mot videre utvikling av både Naturindeks og NiN til det best for norsk miljøforvaltning.

International audience; Because of their relatively reduced tectonic influence, post-rift sedimentary successions have a propensity to preserve climatically-driven cyclicity over long durations. Here we present an integrated cyclostratigraphic and sequence stratigraphic study of the post-rift Limoeiro sedimentary Formation (Fm) of the Foz do Amazonas Basin (offshore Brazil), which spans the entire Late Cretaceous epoch (almost 35 Myr long). The principal goal of the present study is to decipher very long (multi-Myr) sedimentary cyclicities and their potential origin(s) in order to delineate the main controlling factors of post-rift sediment sequences and packages.We used gamma-ray (GR) well-log data for cyclostratigarphy, and seismic data for sequence stratigraphy. Time-series analysis of GR data shows a rich series of Milankovitch frequency bands. In particular, long-period cyclicities (405 kyr, 2.4 Myr, 4.7 Myr and 9.5 Myr) are detected with high fidelity. Seismic and sequence stratigraphic interpretation shows a striking sea-level (SL) depositional sequence order, matching the 4.7 Myr orbital cyclicity inferred from cyclostratigraphy. Longer SL sequences interpreted in previous studies from the Limoeiro Fm closely match the 9.5 Myr GR related orbital cycles.Thus, we infer that the post-rift Limoeiro Fm was deposited continuously under astronomical forcing over the Late Cretaceous epoch, resulting in an extraordinary record of direct base- and sea-level responses to Milankovitch climatic forcing, including longer (multi-Myr) periodicities. The 4.7 Myr orbital component is recorded for the first time in SL sedimentary proxies, thus allowing here to update SL hierarchical orders. We suggest that third-order, and second-order and suborders SL sequences were most likely paced by long-period astronomical cycles (2.4 Myr eccentricity, and 4.7 and 9.5 Myr orbital cycles, respectively.

Aims. We present a new technique to estimate the relative ages of multiple stellar populations hosted by five globular clusters: NGC 104 (47 Tuc), NGC 6121 (M4), NGC 6352, NGC 6362 and NGC 6723. Methods. We used the catalogs of the database "HST UV Globular cluster Survey (HUGS)" to create color-magnitude and two-color diagrams of the Globular Clusters. We identified the multiple populations within each globular cluster, and we divided them into two main stellar populations: POPa or first generation (1G) and POPb, composed of all the successive generations of stars. The new technique allows us to obtain an accurate estimate of the relative ages between POPa and POPb. Results. The multiple populations of NGC 104 and NGC 6121 are coeval within 220 Myr and 214 Myr, while those of NGC 6352, NGC 6362 and NGC 6723 are coeval within 336 Myr, 474 Myr and 634 Myr, respectively. These results were obtained combining all the sources of uncertainties., Comment: 11 pages, 10 figures, 3 tables. Accepted for publication in A&A on December 9, 2020

Hydroxynitrile lyases (HNL’s) belonging to the α/β-hydrolase-fold superfamily evolved from esterases approximately 100 million years ago. Reconstruction of an ancestral hydroxynitrile lyase in the α/β-hydrolase fold superfamily yielded a catalytically active hydroxynitrile lyase, HNL1. Several properties of HNL1 differ from the modern HNL from rubber tree (HbHNL). HNL1 favors larger substrates as compared to HbHNL, is two-fold more catalytically promiscuous for ester hydrolysis (p-nitrophenyl acetate) as compared to mandelonitrile cleavage, and resists irreversible heat inactivation to 35 °C higher than for HbHNL. We hypothesized that the x-ray crystal structure of HNL1 may reveal the molecular basis for the differences in these properties. The x-ray crystal structure solved to 1.96-Å resolution shows the expected α/β-hydrolase fold, but a 60% larger active site as compared to HbHNL. This larger active site echoes its evolution from esterases since related esterase SABP2 from tobacco also has a 38% larger active site than HbHNL. The larger active site in HNL1 likely accounts for its ability to accept larger hydroxynitrile substrates. Site-directed mutagenesis of HbHNL to expand the active site increased its promiscuous esterase activity 50-fold, consistent with the larger active site in HNL1 being the primary cause of its promiscuous esterase activity. Urea-induced unfolding of HNL1 indicates that it unfolds less completely than HbHNL (m-value = 0.63 for HNL1 vs 0.93 kcal/ mol·M for HbHNL), which may account for the ability of HNL1 to better resist irreversible inactivation upon heating. The structure of HNL1 shows changes in hydrogen bond networks that may stabilize regions of the folded structure.

Oppdragsgiver: Statens Vegvesen Resultater fra naturvitenskapelig undersøkelse av to myrområder på Laupland, gnr. 15, Bokn kommune presenteres. Dette er en del av de arkeologiske undersøkelsene av ID 180670, 180673, 180561, 180564 og 216618 som lå inntil myrområdene og ble utgravd i 2016 og 2017. Bakgrunnen er den planlagte og nå påbegynte vegforbindelsen E39-Rogfast fra Harestad i Randaberg via Kvitsøy til Vestre og Austre Bokn i Rogaland, der traséen på Vestre Bokn går over Laupland. Hensikten med den naturvitenskapelige undersøkelsen var å gi kunnskap om lokal vegetasjons- og landskapsutvikling. Det ble tatt en boreprøve fra en myr som lå 18 moh., like nedenfor lokal marin grense. Resultatene viser at det opprinnelig var et lite vann der bunnsedimenter er C14-datert til senglasial og preboreal (tidligmesolitikum) og som etter hvert vokste igjen og i atlantisk tid (senmesolitikum) var bevokst med or. I myr som lå 4 moh., nedenfor Tapes transgresjonsnivå, ble det sjaktet fra tørt land ut mot midten av myra og tatt prøver fra sjaktveggen ved tre prøvepunkter. Begynnende myrdanning i sentral del er C14-datert til subboreal tid (yngre bronsealder), men også denne myra startet opp som et lite tjern og ble etter hvert bevokst med kratt, særlig av or og vier. Det er røsslynghei og beitemark i området omkring. Myrtypen og vegetasjonsbildet ellers vedvarer inn i romertid da området vest for myra blir tatt i bruk til åker. Det er spor etter avsviing og bestanden av or reduseres sterkt. Jordbruket intensiveres ytterligere i middelalder, og det er tydelige spor etter kornåker ned mot vestre kant av myra. Pollenanalysen viser til bygg, hvete og havre. Yngre steinalder og eldre bronsealder er ikke dekket av analysene som er utført i denne undersøkelsen.

Dipeptidyl peptidase-4 (DPP-4) is a proteolytic enzyme responsible for the rapid degradation of Glucagon-like peptide 1 (GLP-1) that is required for the secretion of insulin. DPP-4 also influences activation of node like receptor family, pyrin domain containing 3 (NLRP3) inflammasome under diabetic conditions. Although several polyphenols are reported for various bioactivities, they are consumed as part of the food matrix and not in isolation. Horsegram (Macrotyloma uniflorum) is a rich source of myricetin (Myr) (35 μg/g flour), reported for its anti-hyperglycemic effect. In this investigation, we aimed to study the effect of Myr, singly, and in the presence of co-nutrient horsegram protein (HP) on DPP-4 activity and its consequential impact on GLP-1, insulin, and NLRP3 inflammasome in high-fat diet and single low dose streptozotocin (STZ)-induced diabetic male Wistar rats. In diabetic control (DC), the activity of DPP-4 and its expression were higher compared to treated groups. The consequential decrease in the circulating GLP-1 levels in the DC group, but not treated groups, further indicated the effectiveness of our test molecules under diabetic conditions. Specifically, Myr decreased DPP-4 activity and its expression levels with enhanced circulating GLP-1 and insulin levels. Myr administration also resulted in a lessening of diabetes-induced NLRP3 inflammasome activation and enhanced antioxidant enzyme activities. HP also proved to be efficient in reducing elevated blood glucose levels and enhancing antioxidant enzyme activities. However, Myr, in the presence of HP as a co-nutrient, had diminished capacity to inhibit DPP-4 and, consequently, reduced potential in ameliorating diabetic conditions. Myr proved to be a potent inhibitor of DPP-4 in vitro and in vivo, resulting in enhanced circulating GLP-1 and insulin levels, thereby improving diabetic conditions. Though Myr and HP, individually ameliorate diabetic conditions, their dietary combination had reduced efficiency.

Studying the accretion process in very low-mass objects has important implications for understanding their formation mechanism. Many nearby late-M dwarfs that have previously been identified in the field are in fact young brown dwarf members of nearby young associations. Some of them are still accreting. They are therefore excellent targets for further studies of the accretion process in the very low-mass regime at different stages. We aim to search for accreting young brown dwarf candidates in a sample of 85 nearby late-M dwarfs. Using photometric data from DENIS, 2MASS, and WISE, we constructed the spectral energy distribution of the late-M dwarfs based on BT-Settl models to detect infrared excesses. We then searched for lithium and H$\alpha$ emission in candidates that exhibit infrared excesses to confirm their youth and the presence of accretion. Among the 85 late-M dwarfs, only DENIS-P J1538317$-$103850 (M5.5) shows strong infrared excesses in WISE bands. The detection of lithium absorption in the M5.5 dwarf and its Gaia trigonometric parallax indicate an age of $\sim$1 Myr and a mass of 47 $M_{\rm J}$. The H$\alpha$ emission line in the brown dwarf shows significant variability that indicates sporadic accretion. This 1 Myr-old brown dwarf also exhibits intense accretion bursts with accretion rates of up to $10^{-7.9}$$M_{\odot}$ yr$^{-1}$. Our detection of sporadic accretion in one of the youngest brown dwarfs might imply that sporadic accretion at early stages could play an important role in the formation of brown dwarfs. Very low-mass cores would not be able to accrete enough material to become stars, and thus they end up as brown dwarfs., Comment: 17 pages, 11 figures, accepted for publication in Astronomy and Astrophysics

In order to further explore the role that hydroxyl plays in synthesizing and improving physicochemical properties of pharmaceutical cocrystals of flavonoids, an unreported pharmaceutical cocrystal (MYR•BPY•EtOH) of myricetin (MYR) with 4,4′-bipyridine (BPY) has been synthesized and characterized. However, something unexpected happened. MYR•BPY•EtOH is a cocrystal with supramolecular helical structure which is different from the supramolecular layered structure of MYR•BPY•H2O that we have reported on. This may be due to the O9-H9•••O6 hydrogen bond, which was formed by the hydroxyl of the ethanol molecule and the 6-oxygen atoms of the MYR, maintains the cocrystal helical structure. Additionally, MYR•BPY•EtOH shows better solubility in comparison to pure MYR and MYR•BPY•H2O. but the hygroscopic stability of MYR•BPY•EtOH and MYR•BPY•H2O are lower than that of pure MYR. It may be compared with planar MYR and layered-structured MYR•BPY•H2O, helically-structured MYR•BPY•EtOH is more likely to allow water molecules to enter. This study implies that we should not ignore the influential that hydroxyl groups of solvent molecules have on the structures and properties of flavonoid pharmaceutical cocrystals when considering the influence of hydroxyl groups of the A, B, and C rings of flavonoid on the cocrystal structure of flavonoids.

We use the Bayesian approach to write the posterior probability density for the three-dimensional velocity of a pulsar and for its kinematic age. As a prior, we use the bimodal velocity distribution found in a recent article by Verbunt, Igoshev & Cator (2017). When we compare the kinematic ages with spin-down ages, we find that in general, they agree with each other. In particular, maximum likelihood analysis sets the lower limit for the exponential magnetic field decay timescale at $8$ Myr with a slight preference of $t_\mathrm{dec} \approx 12$ Myr and compatible with no decay at all. One of the objects in the study, pulsar B0950+08 has kinematic and cooling ages $\approx 2$ Myr which is in strong contradiction with its spin-down age $��\approx 17$ Myr. The 68 per cent credible range for the kinematic age is 1.2--8.0 Myr. We conclude that the most probable explanation for this contradiction is a combination of magnetic field decay and long initial period. Further timing, UV and X-ray observations of B0950+08 are required to constrain its origin and evolution better., Accepted for publication in MNRAS on 29 October 2018 . 11 pages, 11 figures

In Drosophila, large variations in rearrangement rate have been reported among different lineages and among Muller’s elements. Nevertheless, the mechanisms that are involved in the generation of inversions, their increase in frequency, as well as their impact on the genome are not completely understood. This is in part due to the lack of comparative studies on species distantly related to Drosophila melanogaster. Therefore, we sequenced and assembled the genomes of two species of the virilis phylad (Drosophila novamexicana [15010-1031.00] and Drosophila americana [SF12]), which are diverging from D. melanogaster for more than 40 Myr. Based on these data, we identified the precise location of six novel inversion breakpoints. A molecular characterization provided clear evidence that DAIBAM (a miniature inverted–repeat transposable element) was involved in the generation of eight out of the nine inversions identified. In contrast to what has been previously reported for D. melanogaster and close relatives, ectopic recombination is thus the prevalent mechanism of generating inversions in species of the virilis phylad. Using pool-sequencing data for three populations of D. americana, we also show that common polymorphic inversions create a high degree of genetic differentiation between populations for chromosomes X, 4, and 5 over large physical distances. We did not find statistically significant differences in expression levels between D. americana (SF12) and D. novamexicana (15010-1031.00) strains for the three genes surveyed (CG9588, Fig 4, and fab1) flanking three inversion breakpoints. This article is a result of the project Norte-01-0145-FEDER-000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). N.P. and M.R. are funded by the Emmy Noether Programme of the Deutsche Forschungsgemeinschaft (Grant Number: PO 1648/3-1 to N.P.). We would like to thank the Transcriptome Analysis Lab (TAL) (University Medical Center Göttingen, UMG) in Göttingen for the Illumina sequencing.

As the world's largest water diversion project, the South-to-North Water Diversion Project in China will have potential environmental effects on the Miyun Reservoir (MYR). However, Cu is a toxic pollutant, and the potential risk of Cu remobilization in MYR soils after water impoundment remains unknown. Riparian soils (five land use types and three vertical elevations) were collected from the MYR before water impoundment. Soil properties, total concentrations of Cu in soils (Ctotal-Cu) and pore water (Csol-Cu), and chemical fractions were measured. Diffusive gradients in thin films (DGT) and the DGT-induced fluxes in soils (DIFS) model were applied to investigate Cu availability. The average Ctotal-Cu was higher than the Chinese background values, indicating potential anthropogenic input of Cu. No significant influences of land use types/vertical elevations on DGT-labile Cu (CDGT-Cu) and Ctotal-Cu were observed. A significant positive relationship between CDGT-Cu and Csol-Cu showed that CDGT-Cu can effectively predict bioavailable Cu fraction in MYR soils, whereas CDGT-Cu had no correlation with different chemical fractions measured by European Community Bureau of Reference (BCR) geochemical fractionation, suggesting that BCR chemical fractions cannot reflect Cu mobility in MYR soils. Risk assessment code showed a low risk of Cu remobilization in MYR soils, but a reducing environment would cause higher mobilization of Cu associated with Fe/Mn oxides after water impoundment. Moreover, the DIFS model reported a deficient soil resupply capacity; this agreed with low R values, which were mostly attributed to the limited available pool of Cu in the soil solid phase.

DS Tuc Ab is a Neptune-sized planet that orbits around a member of the 45 Myr old Tucana-Horologium moving group. Here, we report the measurement of the sky-projected angle between the stellar spin axis and the planet's orbital axis, based on the observation of the Rossiter-McLaughlin effect during three separate planetary transits. The orbit appears to be well aligned with the equator of the host star, with a projected obliquity of lambda = 2.5 +1.0/-0.9 deg. In addition to the distortions in the stellar absorption lines due to the transiting planet, we observed variations that we attribute to large starspots, with angular sizes of tens of degrees. The technique we have developed for simultaneous modeling of starspots and the planet-induced distortions may be useful in other observations of planets around active stars., Accepted by ApJL

Phased, secondary siRNAs (phasiRNAs) represent a class of small RNAs in plants generated via distinct biogenesis pathways, predominantly dependent on the activity of 22-nt miRNAs. Most 22-nt miRNAs are processed by DCL1 from miRNA precursors containing an asymmetric bulge, yielding a 22/21-nt miRNA/miRNA* duplex. Here we show that miR1510, a soybean miRNA capable of triggering phasiRNA production from numerous nucleotide-binding leucine-rich repeat (NB-LRRs), previously described as 21 nt in its mature form, primarily accumulates as a 22-nt isoform via monouridylation. We demonstrate that, in Arabidopsis, this uridylation is performed by HESO1. Biochemical experiments showed that the 3' terminus of miR1510 is only partially 2'-O-methylated because of the terminal mispairing in the miR1510/miR1510* duplex that inhibits HEN1 activity in soybean. miR1510 emerged in the Phaseoleae ∼41-42 million years ago with a conserved precursor structure yielding a 22-nt monouridylated form, yet a variant in mung bean is processed directly in a 22-nt mature form. This analysis of miR1510 yields two observations: (i) plants can utilize postprocessing modification to generate abundant 22-nt miRNA isoforms to more efficiently regulate target mRNA abundances; and (ii) comparative analysis demonstrates an example of selective optimization of precursor processing of a young plant miRNA.

In grasses, two pathways that generate diverse and numerous 21-nt (premeiotic) and 24-nt (meiotic) phased siRNAs are highly enriched in anthers, the male reproductive organs. These “phasiRNAs” are analogous to mammalian piRNAs, yet their functions and evolutionary origins remain largely unknown. The 24-nt meiotic phasiRNAs have only been described in grasses, wherein their biogenesis is dependent on a specialized Dicer (DCL5). To assess how evolution gave rise to this pathway, we examined reproductive phasiRNA pathways in nongrass monocots: garden asparagus, daylily, and lily. The common ancestors of these species diverged approximately 115–117 million years ago (MYA). We found that premeiotic 21-nt and meiotic 24-nt phasiRNAs were abundant in all three species and displayed spatial localization and temporal dynamics similar to grasses. The miR2275-triggered pathway was also present, yielding 24-nt reproductive phasiRNAs, and thus originated more than 117 MYA. In asparagus, unlike in grasses, these siRNAs are largely derived from inverted repeats (IRs); analyses in lily identified thousands of precursor loci, and many were also predicted to form foldback substrates for Dicer processing. Additionally, reproductive phasiRNAs were present in female reproductive organs and thus may function in both male and female germinal development. These data describe several distinct mechanisms of production for 24-nt meiotic phasiRNAs and provide new insights into the evolution of reproductive phasiRNA pathways in monocots.

Auxin homeostasis is tightly regulated by several mechanisms, including conjugation of the hormone to specific moieties, such as amino acids or sugar. The inactive phytohormone conjugate is stored in large pools in plants and hydrolyzed to regain full activity. Many conjugate hydrolases (M20D metallopeptidases) have been identified and characterized throughout the plant kingdom. We have traced this regulatory gene family back to liverwort (Marchantia polymorpha), a member of the most ancient extant land plant lineage, which emerged approximately 475 million years ago. We have isolated and characterized a single hydrolase homologue, dubbed M. polymorpha IAA-Leucine Resistant1 (MpILR1), from liverwort. MpILR1 can hydrolyze two auxin (indole acetic acid [IAA]) substrates (IAA-Leucine and IPA-Alanine) at very low levels of activity, but it cannot hydrolyze the two native auxin conjugates of liverwort (IAA-Glycine and IAA-Valine). We conclude from these results that liverwort likely does not employ active auxin conjugate hydrolysis as a regulatory mechanism and that conjugate homeostasis likely takes place in liverwort by passive background degradation. Furthermore, we present evidence that MpILR1 was probably exapted by tracheophytes over evolutionary time into the auxin regulatory pathway.

Essentials Tissue factor (TF) enhances factor VIIa (FVIIa) activity through structural and dynamic changes. We analyzed conservation of TF-activated FVIIa allosteric networks in extant vertebrate lamprey. Lamprey Tf/FVIIa molecular dynamics show conserved Tf-induced structural/dynamic FVIIa changes. Lamprey Tf activation of FVIIa allosteric networks follows molecular pathways similar to human. SUMMARY Background Previous studies have provided insight into the molecular basis of human tissue factor (TF) activation of activated factor VII (FVIIa). TF-induced allosteric networks of FVIIa activation have been rationalized through analysis of the dynamic changes and residue connectivities in the human soluble TF (sTF)/FVIIa complex structure during molecular dynamics (MD) simulation. Evolutionary conservation of the molecular mechanisms for TF-induced allosteric FVIIa activation between humans and extant vertebrate jawless fish (lampreys), where blood coagulation emerged more than 500 million years ago, is unknown and of considerable interest. Objective To model the sTf/FVIIa complex from cloned Petromyzon marinus lamprey sequences, and with comparisons to human sTF/FVlla investigate conservation of allosteric mechanisms of FVIIa activity enhancement by soluble TF using MD simulations. Methods Full-length cDNAs of lamprey tf and f7 were cloned and characterized. Comparative models of lamprey sTf/FVIIa complex and free FVIIa were determined based on constructed human sTF/FVIIa complex and free FVIIa models, used in full-atomic MD simulations, and characterized using dynamic network analysis approaches. Results Allosteric paths of correlated motion from Tf contact points in lamprey sTf/FVIIa to the FVIIa active site were determined and quantified, and were found to encompass residue-residue interactions along significantly similar paths compared with human. Conclusions Despite low conservation of residues between lamprey and human proteins, 30% TF and 39% FVII, the structural and protein dynamic effects of TF activation of FVIIa appear conserved and, moreover, present in extant vertebrate proteins from 500 million years ago when TF/FVIIa-initiated extrinsic pathway blood coagulation emerged.

We studied the effects of the major long-chain fatty acids accumulating in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, namely cis-5-tetradecenoic acid (Cis-5) and myristic acid (Myr), on important mitochondrial functions in isolated mitochondria from cardiac fibers and cardiomyocytes of juvenile rats. Cis-5 and Myr at pathological concentrations markedly reduced mitochondrial membrane potential (ΔΨm ), matrix NAD(P)H pool, Ca2+ retention capacity, ADP- (state 3) and carbonyl cyanide 3-chlorophenyl hydrazine-stimulated (uncoupled) respiration, and ATP generation. By contrast, these fatty acids increased resting (state 4) respiration (uncoupling effect) with the involvement of the adenine nucleotide translocator because carboxyatractyloside significantly attenuated the increased state 4 respiration provoked by Cis-5 and Myr. Furthermore, the classical inhibitors of mitochondrial permeability transition (MPT) pore cyclosporin A plus ADP, as well as the Ca2+ uptake blocker ruthenium red, fully prevented the Cis-5- and Myr-induced decrease in ΔΨm in Ca2+ -loaded mitochondria, suggesting, respectively, the induction of MPT pore opening and the contribution of Ca2+ toward these effects. The findings of the present study indicate that the major long-chain fatty acids that accumulate in VLCAD deficiency disrupt mitochondrial bioenergetics and Ca2+ homeostasis, acting as uncouplers and metabolic inhibitors of oxidative phosphorylation, as well as inducers of MPT pore opening, in the heart at pathological relevant concentrations. It is therefore presumed that a disturbance of bioenergetics and Ca2+ homeostasis may contribute to the cardiac manifestations observed in VLCAD deficiency.

N-terminal myristoylation, a major eukaryotic protein lipid modification, is difficult to detect in vivo and challenging to predict in silico. We developed a proteomics strategy involving subfractionation of cellular membranes, combined with separation of hydrophobic peptides by mass spectrometry-coupled liquid chromatography to identify the Arabidopsis thaliana myristoylated proteome. This approach identified a starting pool of 8837 proteins in all analyzed cellular fractions, comprising 32% of the Arabidopsis proteome. Of these, 906 proteins contain an N-terminal Gly at position 2, a prerequisite for myristoylation, and 214 belong to the predicted myristoylome (comprising 51% of the predicted myristoylome of 421 proteins). We further show direct evidence of myristoylation in 72 proteins; 18 of these myristoylated proteins were not previously predicted. We found one myristoylation site downstream of a predicted initiation codon, indicating that posttranslational myristoylation occurs in plants. Over half of the identified proteins could be quantified and assigned to a subcellular compartment. Hierarchical clustering of protein accumulation combined with myristoylation and S-acylation data revealed that N-terminal double acylation influences redirection to the plasma membrane. In a few cases, MYR function extended beyond simple membrane association. This study identified hundreds of N-acylated proteins for which lipid modifications could control protein localization and expand protein function.

This study investigated the protective effects of myricetin (MYR) and myricetrin (MYRR) in dextran sodium sulfate (DSS) induced liver and colon damage in mice. The results showed that MYR and MYRR alleviate liver damage of colitis mice via tumor necrosis factor-α (TNF-α)/nuclear factor kappa-B (NF-κB) pathway. After dexamethasone acetate (DXMS) and MYR treatment, the expressions of myosin light chain kinase (MLCK) were increased in mice colon. The expression of occludin was increased after MYR treatment, while MYRR significantly increased tight junction protein 1 (ZO1) expression compared to colitis mice. MYR significantly reduced the abundance of intestinal Proteobacteria and Cyanobacteria to alleviate colitis. At the species level, treatment with MYR and MYRR reduced the abundance of Helicobacter-sp-MIT and Lachnospiraceae bacterium, and increased the abundance of Lactobacillus gasseri. The protective role of MYR and MYRR in DSS induced colitis mice may attribute to their intestinal microbiota and tight junction proteins modulation activities.

Despite various pharmacological effects, myricetin (Myr) shows low oral bioavailability (

X-ray microcomputed tomography was used to reveal putative trematode metacercariae (Platyhelminthes: Digenea) located in cysts positioned at the base of the femora in a 100 myr agamid lizard preserved in Myanmar amber. The cysts are characterized and compared with encysted metacercariae recovered from a similar location in an extant Anolis lizard. This discovery provides evidence that lizards were serving as intermediate hosts of trematodes some 100 Ma.

We present $Spitzer$ IRS 5--14 $\mu$m spectra and 16 $\mu$m and 22 $\mu$m photometry of the T2.5 companion to the $\sim$300 Myr-old G0V star HN Peg. We incorporate previous 0.8--5 $\mu$m observations to obtain the most comprehensive spectral energy distribution of an intermediate-gravity L/T-transition dwarf which, together with an accurate Gaia EDR3 parallax of the primary, enable us to derive precise fundamental parameters. We find that young ($\approx$0.1--0.3 Gyr) early-T dwarfs on average have $\approx$140 K lower effective temperatures, $\approx$20% larger radii, and similar bolometric luminosities compared to $\gtrsim$1 Gyr-old field dwarfs with similar spectral types. Our accurate infrared spectrophotometry offers new detail at wavelengths where the dominant carbon-bearing molecules have their strongest transitions: at 3.4 $\mu$m for methane and at 4.6 $\mu$m for carbon monoxide. We assess the performance of various widely available photospheric models and find that models with condensates and/or clouds better reproduce the full SED of this moderately young early-T dwarf. However, cloud-free models incorporating a more general convective instability treatment reproduce at least the low-resolution near-IR spectrum similarly well. Our analysis of $R\approx2300$ $J$-band spectra shows that the near-infrared potassium absorption lines in HN Peg B have similar strengths to those seen in both younger and older T2-T3 dwarfs. We conclude that while alkali lines are well-established as surface gravity indicators for L-type or warmer stars, they are insensitive to surface gravity in early-T dwarfs, Comment: Accepted for publication in ApJ

Myricetin (MYR) shows a lot of pharmacological activity such as antioxidant capacity and antitumor activity. However, the poor aqueous solubility of MYR (2 μg/mL) limits its pharmaceutical applications. To improve the dissolution rate of MYR, microparticles and inclusion complexes of MYR were successfully prepared by supercritical antisolvent (SAS) technology. The effects of the drug concentration, temperature, pressure, CO2 and solution volumetric feeding rate on the formation of MYR microparticles and the MYR/hydroxypropyl-β-cyclodextrin (HP-β-CD) complex microparticles were investigated systematically. The physical and chemical properties of the MYR microparticles were characterized by SEM, DSC, FTIR and XRD. After SAS processed, the particle size of MYR microparticles decreased and the crystal form of MYR changed due to the complexation with HP-β-CD, which lead to enhanced solubility, dissolution rate and further improve the antioxidant activity and antitumor activity.

Blastoids possess characteristic internal structures called hydrospires through which seawater flowed in life. Hydrospire walls are very thin and extensive, composed of a fine meshwork of calcite and functioned in respiratory gas exchange. Hydrospire-bearing blastoids survived from the early Late Ordovician to the Late Permian, about 200 Myr, significantly longer than any other blastozoan taxon, (e.g., Dichoporita c. 105 Myr) perhaps because their hydrospires functioned more efficiently. Hydrospires differ from all other types of respiratory pore structures in Palaeozoic echinoderms in that as they grew, they increased their surface area perpendicular to the experimentally demonstrated internal current direction. This is six times more efficient at increasing the rate of respiratory gas exchange than increasing the area of the exchange surface parallel to the current direction. The latter method is how all other blastozoan respiratory structures grew. Thus, as respiratory requirements increased with growth, blastoids were better able to meet these requirements than other blastozoans. It seems likely that this advantage contributed to the greater evolutionary success and survivorship of the blastoids compared with other blastozoan groups. The greater diversity of Permian fissiculate blastoid genera suggests that fissiculates benefited more than spiraculates from this inherent advantage, which is unexpected.

Parkinson’s disease (PD) is a proteinopathy associated with the aggregation of α-synuclein and the formation of lipid–protein cellular inclusions, named Lewy bodies (LBs). LB formation results in impaired neurotransmitter release and uptake, which involve membrane traffic and require lipid synthesis and metabolism. Lipids, particularly ceramides, are accumulated in postmortem PD brains and altered in the plasma of PD patients. Autophagy is impaired in PD, reducing the ability of neurons to clear protein aggregates, thus worsening stress conditions and inducing neuronal death. The inhibition of ceramide synthesis by myriocin (Myr) in SH-SY5Y neuronal cells treated with preformed α-synuclein fibrils reduced intracellular aggregates, favoring their sequestration into lysosomes. This was associated with TFEB activation, increased expression of TFEB and LAMP2, and the cytosolic accumulation of LC3II, indicating that Myr promotes autophagy. Myr significantly reduces the fibril-related production of inflammatory mediators and lipid peroxidation and activates NRF2, which is downregulated in PD. Finally, Myr enhances the expression of genes that control neurotransmitter transport (SNARE complex, VMAT2, and DAT), whose progressive deficiency occurs in PD neurodegeneration. The present study suggests that counteracting the accumulation of inflammatory lipids could represent a possible therapeutic strategy for PD.

The six largest known impact craters of the last 250 Myr (≥70 km in diameter), which are capable of causing significant environmental damage, coincide with four times of recognized extinction events at 36 (with 2 craters), 66, and 145 Myr ago, and possibly with two provisional extinction events at 168 and 215 Myr ago. These impact cratering events are accompanied by layers in the geologic record interpreted as impact ejecta. Chance occurrences of impacts and extinctions can be rejected at confidence levels of 99.96% (for 4 impact/extinctions) to 99.99% (for 6 impact/extinctions). These results argue that several extinction events over the last 250 Myr may be related to the effects of large-body impacts.

Variability of the East Asian winter monsoon (EAWM), stronger during glacials and weaker during interglacials, has been tightly linked to the wax and wane of the Northern Hemisphere ice sheets (NHIS) via the Siberian High over the last 2.8 million years (Myr). However, the long eccentricity cycle (ca. 400 kyr) in the EAWM record from the late Pliocene to early-Pleistocene (2.8–1.2 Ma) could not be linked to NHIS changes, which lacked the long eccentricity cycle in the Pleistocene. Here, we present the first low latitude EAWM record of the last 2.8 Myr using surface and subsurface temperature difference from the northern South China Sea to evaluate interactions between tropical ocean and EAWM changes. The results show that the EAWM variability displayed significant 400 kyr cycle between 2.8 Ma and 1.2 Ma, with weak (strong) EAWM during high (low) earth orbital eccentricity state. A super El Nino–Southern Oscillation (ENSO) proxy record, calculated using west-east equatorial Pacific sea surface temperature differences, revealed 400 kyr cycles throughout the last 2.8 Myr with warm phase during high eccentricity state. Thus, we propose that super ENSO mean state strongly modulated the EAWM strength through remote forcing to generate the 400 kyr cycle between 2.8 Ma and 1.2 Ma, while low NHIS volume was not sufficient to dominate the EAWM variation as it did over the last 0.9 Myr with 100 kyr cycles in dominance.

Many studies have linked mass extinction events with the catastrophic effects of large-body impacts and flood-basalt eruptions, sometimes as competing explanations. We find that the ages of at least 10 out of a total of 11 documented extinction events over the last 260 Myr (12 out of 13 if we include two lesser extinction events) coincide, within errors, with the best-known ages of either a large impact crater (≥70 km diameter) or a continental flood-basalt eruption. The null hypothesis that this could occur by chance can be rejected with very high confidence (>99.999%). The ages of large impact craters correlate with recognized extinction events at ~36 (two impacts), 66, 145 and 215 Myr ago (and possibly an event at ~168 Myr ago), and the ages of continental flood basalts correlate with extinctions at 66, ~94, ~116, 183, 201, 252 and 259 Myr ago (and possibly at ~133 Myr ago). Furthermore, at least 7 periods of widespread anoxia in the oceans of the last 260 Myr coincide with the ages of flood-basalt eruptions (with 99.999% confidence), and are coeval with extinctions, suggesting causal connections. These statistical relationships argue that most mass extinction events are related to climatic catastrophes produced by the largest impacts and large-volume continental flood-basalt eruptions.