The colonization of the land by plants, sometime before 470 million years ago, was accompanied by the evolution tissue systems 1–3. Specialized structures with diverse functions—from nutrient ...acquisition to reproduction—derived from single cells in the outermost layer (epidermis) were important sources of morphological innovation at this time 2, 4, 5. In extant plants, these structures may be unicellular extensions, such as root hairs or rhizoids 6–9, or multicellular structures, such as asexual propagules or secretory hairs (papillae) 10–12. Here, we show that a ROOTHAIR DEFECTIVE SIX-LIKE (RSL) class I basic helix-loop-helix transcription factor positively regulates the development of the unicellular and multicellular structures that develop from individual cells that expand out of the epidermal plane of the liverwort Marchantia polymorpha; mutants that lack MpRSL1 function do not develop rhizoids, slime papillae, mucilage papillae, or gemmae. Furthermore, we discovered that RSL class I genes are also required for the development of multicellular axillary hairs on the gametophyte of the moss Physcomitrella patens. Because class I RSL proteins also control the development of rhizoids in mosses and root hairs in angiosperms 13, 14, these data demonstrate that the function of RSL class I genes was to control the development of structures derived from single epidermal cells in the common ancestor of the land plants. Class I RSL genes therefore controlled the generation of adaptive morphological diversity as plants colonized the land from the water.
•Class I RSL genes control the development of structures derived from single cells•Class I RSL function is conserved among land plants•Class I RSL controlled epidermal development in the land plant common ancestor•These genes controlled the development of the first plant rooting systems
The colonization of the land by plants was accompanied by the evolution of specialized cells and structures that develop from single cells. Proust et al. show that RSL class I basic helix-loop-helix transcription factors controlled the development of specialized structures from single epidermal cells in the last common ancestor of the land plants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Alzheimer's disease (AD) genetics implies a causal role for innate immune genes, TREM2 and CD33, products that oppose each other in the downstream Syk tyrosine kinase pathway, activating microglial ...phagocytosis of amyloid (Aβ). We report effects of low (Curc-lo) and high (Curc-hi) doses of curcumin on neuroinflammation in APPsw transgenic mice. Results showed that Curc-lo decreased CD33 and increased TREM2 expression (predicted to decrease AD risk) and also increased TyroBP, which controls a neuroinflammatory gene network implicated in AD as well as phagocytosis markers CD68 and Arg1. Curc-lo coordinately restored tightly correlated relationships between these genes' expression levels, and decreased expression of genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL1β). In contrast, very high dose curcumin did not show these effects, failed to clear amyloid plaques, and dysregulated gene expression relationships. Curc-lo stimulated microglial migration to and phagocytosis of amyloid plaques both in vivo and in ex vivo assays of sections of human AD brain and of mouse brain. Curcumin also reduced levels of miR-155, a micro-RNA reported to drive a neurodegenerative microglial phenotype. In conditions without amyloid (human microglial cells in vitro, aged wild-type mice), Curc-lo similarly decreased CD33 and increased TREM2. Like curcumin, anti-Aβ antibody (also reported to engage the Syk pathway, increase CD68, and decrease amyloid burden in human and mouse brain) increased TREM2 in APPsw mice and decreased amyloid in human AD sections ex vivo. We conclude that curcumin is an immunomodulatory treatment capable of emulating anti-Aβ vaccine in stimulating phagocytic clearance of amyloid by reducing CD33 and increasing TREM2 and TyroBP, while restoring neuroinflammatory networks implicated in neurodegenerative diseases.
•Curcumin (Curc) restores innate immune gene expression in AD models.•Curc increased TREM2 and TYROBP, while decreasing CD33 expression.•Curc stimulates phagocytosis and increases CD68 and Arg1 expression.•Curc reduces pro-inflammatory microglia markers CD11b, iNOS, COX-2, IL1β.•These results support a novel mechanism for Curc, which emulates the Aβ vaccine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch. ...However, the same thermokarst lakes can also sequester carbon, and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 ± 10 grams of carbon per square metre per year; mean ± standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears, potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Singly ionized ytterbium, with ultranarrow optical clock transitions at 467 and 436 nm, is a convenient system for the realization of optical atomic clocks and tests of present-day variation of ...fundamental constants. We present the first direct measurement of the frequency ratio of these two clock transitions, without reference to a cesium primary standard, and using the same single ion of Yb+171. The absolute frequencies of both transitions are also presented, each with a relative standard uncertainty of 6x10-16. Combining our results with those from other experiments, we report a threefold improvement in the constraint on the time variation of the proton-to-electron mass ratio, mu super(.)/ mu =0.2(1.1)x10-16 yr-1, along with an improved constraint on time variation of the fine structure constant, alpha super(.)/ alpha =-0.7(2.1)x10-17 yr-1
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
The blood system is maintained by a small pool of haematopoietic stem cells (HSCs), which are required and sufficient for replenishing all human blood cell lineages at millions of cells per second ...throughout life. Megakaryocytes in the bone marrow are responsible for the continuous production of platelets in the blood, crucial for preventing bleeding--a common and life-threatening side effect of many cancer therapies--and major efforts are focused at identifying the most suitable cellular and molecular targets to enhance platelet production after bone marrow transplantation or chemotherapy. Although it has become clear that distinct HSC subsets exist that are stably biased towards the generation of lymphoid or myeloid blood cells, we are yet to learn whether other types of lineage-biased HSC exist or understand their inter-relationships and how differently lineage-biased HSCs are generated and maintained. The functional relevance of notable phenotypic and molecular similarities between megakaryocytes and bone marrow cells with an HSC cell-surface phenotype remains unclear. Here we identify and prospectively isolate a molecularly and functionally distinct mouse HSC subset primed for platelet-specific gene expression, with enhanced propensity for short- and long-term reconstitution of platelets. Maintenance of platelet-biased HSCs crucially depends on thrombopoietin, the primary extrinsic regulator of platelet development. Platelet-primed HSCs also frequently have a long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs. These findings show that HSC subtypes can be organized into a cellular hierarchy, with platelet-primed HSCs at the apex. They also demonstrate that molecular and functional priming for platelet development initiates already in a distinct HSC population. The identification of a platelet-primed HSC population should enable the rational design of therapies enhancing platelet output.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Commercial-scale mining for polymetallic nodules could have a major impact on the deep-sea environment, but the effects of these mining activities on deep-sea ecosystems are very poorly known. The ...first commercial test mining for polymetallic nodules was carried out in 1970. Since then a number of small-scale commercial test mining or scientific disturbance studies have been carried out. Here we evaluate changes in faunal densities and diversity of benthic communities measured in response to these 11 simulated or test nodule mining disturbances using meta-analysis techniques. We find that impacts are often severe immediately after mining, with major negative changes in density and diversity of most groups occurring. However, in some cases, the mobile fauna and small-sized fauna experienced less negative impacts over the longer term. At seven sites in the Pacific, multiple surveys assessed recovery in fauna over periods of up to 26 years. Almost all studies show some recovery in faunal density and diversity for meiofauna and mobile megafauna, often within one year. However, very few faunal groups return to baseline or control conditions after two decades. The effects of polymetallic nodule mining are likely to be long term. Our analyses show considerable negative biological effects of seafloor nodule mining, even at the small scale of test mining experiments, although there is variation in sensitivity amongst organisms of different sizes and functional groups, which have important implications for ecosystem responses. Unfortunately, many past studies have limitations that reduce their effectiveness in determining responses. We provide recommendations to improve future mining impact test studies. Further research to assess the effects of test-mining activities will inform ways to improve mining practices and guide effective environmental management of mining activities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dementia with Lewy bodies (DLB) is increasingly recognized as a common cause of dementia in older people. However, its true frequency remains unclear, with previous studies reporting a prevalence ...range from zero to 22.8% of all dementia cases. This review aimed to establish the population prevalence and incidence for DLB and to compare this to its prevalence in secondary care settings.
A literature review of all relevant population and clinical studies was conducted using PubMed. Additional references from papers found during that process were added to this.
DLB accounted for 4.2% of all diagnosed dementias in the community. In secondary care this increased to 7.5%. The incidence of DLB was 3.8% of new dementia cases. There was a significant increase in DLB diagnoses when using the revised (2005) International Consensus Criteria (ICC) for DLB compared to the original (1996) criteria.
DLB currently accounts for around one in 25 dementia cases diagnosed in the community and one in 13 cases in secondary care. The significantly higher rates of DLB in secondary care may reflect enhanced diagnostic accuracy in specialist settings and/or the increased morbidity and carer burden of the DLB syndrome compared to other dementias. However, the true prevalence is likely to be much higher because DLB diagnoses are often missed, although there is evidence that new criteria aid case identification.
More than 250 patients with uncomplicated, primary spontaneous pneumothorax were treated conservatively or by pleural intervention. In a complete-case analysis, reexpansion within 8 weeks occurred in ...98.5% of the patients in the intervention group and in 94.4% of those in the conservative-management group.
The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone ...on postoperative pain and explore adverse events associated with this treatment.
MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes.
Forty-five studies involving 5796 patients receiving dexamethasone 1.25–20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) −0.49 95% confidence interval (CI): −0.83, −0.15} and 24 h MD −0.48 (95% CI: −0.62, −0.35) after surgery. Dexamethasone-treated patients used less opioids at 2 h MD −0.87 mg morphine equivalents (95% CI: −1.40 to −0.33) and 24 h MD −2.33 mg morphine equivalents (95% CI: −4.39, −0.26), required less rescue analgesia for intolerable pain relative risk 0.80 (95% CI: 0.69, 0.93), had longer time to first dose of analgesic MD 12.06 min (95% CI: 0.80, 23.32), and shorter stays in the post-anaesthesia care unit MD −5.32 min (95% CI: −10.49 to −0.15). There was no dose–response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h MD 0.39 mmol litre−1 (95% CI: 0.04, 0.74).
A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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