Could the Last Interglacial Constrain Projections of Future Antarctic Ice Mass Loss and Sea‐Level Rise?

Previous studies have interpreted Last Interglacial (LIG; ∼129–116 ka) sea-level estimates in multiple different ways to calibrate projections of future Antarctic ice-sheet (AIS) mass loss and associated sea-level rise. This study systematically explores the extent to which LIG constraints could inform future Antarctic contributions to sea-level rise. We develop a Gaussian process emulator of an ice-sheet model to produce continuous probabilistic projections of Antarctic sea-level contributions over the LIG and a future high-emissions scenario. We use a Bayesian approach conditioning emulator projections on a set of LIG constraints to find associated likelihoods of model parameterizations. LIG estimates inform both the probability of past and future ice-sheet instabilities and projections of future sea-level rise through 2150. Although best-available LIG estimates do not meaningfully constrain Antarctic mass loss projections or physical processes until 2060, they become increasingly informative over the next 130 years. Uncertainties of up to 50 cm remain in future projections even if LIG Antarctic mass loss is precisely known (±5 cm), indicating that there is a limit to how informative the LIG could be for ice-sheet model future projections. The efficacy of LIG constraints on Antarctic mass loss also depends on assumptions about the Greenland ice sheet and LIG sea-level chronology. However, improved field measurements and understanding of LIG sea levels still have potential to improve future sea-level projections, highlighting the importance of continued observational efforts

Ribonucleolytic resection is required for repair of strand displaced nonhomologous end-joining intermediates

Nonhomologous end-joining (NHEJ) pathways repair DNA double-strand breaks (DSBs) in eukaryotes and many prokaryotes, although it is not reported to operate in the third domain of life, archaea. Here, we describe a complete NHEJ complex, consisting of DNA ligase (Lig), polymerase (Pol), phosphoesterase (PE), and Ku from a mesophillic archaeon, Methanocella paludicola (Mpa). Mpa Lig has limited DNA nick-sealing activity but is efficient in ligating nicks containing a 3′ ribonucleotide. Mpa Pol preferentially incorporates nucleoside triphosphates onto a DNA primer strand, filling DNA gaps in annealed breaks. Mpa PE sequentially removes 3′ phosphates and ribonucleotides from primer strands, leaving a ligatable terminal 3′ monoribonucleotide. These proteins, together with the DNA end-binding protein Ku, form a functional NHEJ break-repair apparatus that is highly homologous to the bacterial complex. Although the major roles of Pol and Lig in break repair have been reported, PE’s function in NHEJ has remained obscure. We establish that PE is required for ribonucleolytic resection of RNA intermediates at annealed DSBs. Polymerase-catalyzed strand-displacement synthesis on DNA gaps can result in the formation of nonligatable NHEJ intermediates. The function of PE in NHEJ repair is to detect and remove inappropriately incorporated ribonucleotides or phosphates from 3′ ends of annealed DSBs to configure the termini for ligation. Thus, PE prevents the accumulation of abortive genotoxic DNA intermediates arising from strand displacement synthesis that otherwise would be refractory to repair

Could the Last Interglacial Constrain Projections of Future Antartic Ice Mass Loss and Sea-Level Rise?

Previous studies have interpreted Last Interglacial (LIG; ∼129–116 ka) sea‐level estimates in multiple different ways to calibrate projections of future Antarctic ice‐sheet (AIS) mass loss and associated sea‐level rise. This study systematically explores the extent to which LIG constraints could inform future Antarctic contributions to sea‐level rise. We develop a Gaussian process emulator of an ice‐sheet model to produce continuous probabilistic projections of Antarctic sea‐level contributions over the LIG and a future high‐emissions scenario. We use a Bayesian approach conditioning emulator projections on a set of LIG constraints to find associated likelihoods of model parameterizations. LIG estimates inform both the probability of past and future ice‐sheet instabilities and projections of future sea‐level rise through 2150. Although best‐available LIG estimates do not meaningfully constrain Antarctic mass loss projections or physical processes until 2060, they become increasingly informative over the next 130 years. Uncertainties of up to 50 cm remain in future projections even if LIG Antarctic mass loss is precisely known (±5 cm), indicating that there is a limit to how informative the LIG could be for ice‐sheet model future projections. The efficacy of LIG constraints on Antarctic mass loss also depends on assumptions about the Greenland ice sheet and LIG sea‐level chronology. However, improved field measurements and understanding of LIG sea levels still have potential to improve future sea‐level projections, highlighting the importance of continued observational efforts

Complexation of Z-ligustilide with hydroxypropyl-β-cyclodextrin to improve stability and oral bioavailability

To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-β-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG

Stretchable and Skin-Conformable Conductors Based on Polyurethane/Laser-Induced Graphene

The conversion of various polymer substrates into laser-induced graphene (LIG) with a CO2 laser in ambient condition is recently emerging as a simple method for obtaining patterned porous graphene conductors, with a myriad of applications in sensing, actuation, and energy. In this paper, a method is presented for embedding porous LIG (LIG-P) or LIG fibers (LIG-F) into a thin (about 50 μm) and soft medical grade polyurethane (MPU) providing excellent conformal adhesion on skin, stretchability, and maximum breathability to boost the development of various unperceivable monitoring systems on skin. The effect of varying laser fluence and geometry of the laser scribing on the LIG micro-nanostructure morphology and on the electrical and electromechanical properties of LIG/MPU composites is investigated. A peculiar and distinct behavior is observed for either LIG-P or LIG-F. Excellent stretchability without permanent impairment of conductive properties is revealed up to 100% strain and retained after hundreds of cycles of stretching tests. A distinct piezoresistive behavior, with an average gauge factor of 40, opens the way to various potential strain/pressure sensing applications. A novel method based on laser scribing is then introduced for providing vertical interconnect access (VIA) into LIG/MPU conformable epidermal sensors. Such VIA enables stable connections to an external measurement device, as this represents a typical weakness of many epidermal devices so far. Three examples of minimally invasive LIG/MPU epidermal sensing proof of concepts are presented: as electrodes for electromyographic recording on limb and as piezoresistive sensors for touch and respiration detection on skin. Long-term wearability and functioning up to several days and under repeated stretching tests is demonstrated

Sea-ice-free Arctic during the Last Interglacial supports fast future loss

The Last Interglacial (LIG), a warmer period 130-116 ka before present, is a potential analog for future climate change. Stronger LIG summertime insolation at high northern latitudes drove Arctic land summer temperatures 4-5 °C higher than the preindustrial era. Climate model simulations have previously failed to capture these elevated temperatures, possibly because they were unable to correctly capture LIG sea-ice changes. Here, we show the latest version of the fully-coupled UK Hadley Center climate model (HadGEM3) simulates a more accurate Arctic LIG climate, including elevated temperatures. Improved model physics, including a sophisticated sea-ice melt-pond scheme, result in a complete simulated loss of Arctic sea ice in summer during the LIG, which has yet to be simulated in past generations of models. This ice-free Arctic yields a compelling solution to the longstanding puzzle of what drove LIG Arctic warmth and supports a fast retreat of future Arctic summer sea ice

Agreement between reconstructed and modeled boreal precipitation of the Last Interglacial

The last extended time period when climate may have been warmer than today was during the Last Interglacial (LIG; ca. 129 to 120 thousand years ago). However, a global view of LIG precipitation is lacking. Here, seven new LIG climate models are compared to the first global database of proxies for LIG precipitation. In this way, models are assessed in their ability to capture important hydroclimatic processes during a different climate. The models can reproduce the proxy-based positive precipitation anomalies from the preindustrial period over much of the boreal continents. Over the Southern Hemisphere, proxy-model agreement is partial. In models, LIG boreal monsoons have 42% wider area than in the preindustrial and produce 55% more precipitation and 50% more extreme precipitation. Austral monsoons are weaker. The mechanisms behind these changes are consistent with stronger summer radiative forcing over boreal high latitudes and with the associated higher temperatures during the LIG

Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways

Purpose: To investigate the effect of Z-ligustilide (Z-lig) on cisplatin-induced nephrotoxicity and examine whether NRF2 signaling mediates the underlying mechanism of action.Methods: Human proximal tubular epithelial cells (HK-2) were pretreated with 20 or 100 μM Z-lig for 2 h, followed by 10 μM cisplatin treatment for 24 h. Cell viability was measured using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A commercial kit was used todetermine lactate dehydrogenase (LDH) release. Apoptosis was determined by flow cytometry while Western blotting was used to evaluate protein levels. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) were assessed by enzymelinked immunosorbent assay (ELISA).Results: Cisplatin decreased HK-2 cell viability and increased LDH release, while Z-lig increased cell viability and decreased LDH release in a dose-dependent manner (p < 0.05). Moreover, Z-lig reduced cisplatin-induced apoptosis (p < 0.01), and alleviated cellular oxidative stress caused by cisplatin (p < 0.05). Furthermore, Z-lig activated NRF2/HO-1 signaling in cells treated with cisplatin (p < 0.05).Conclusion: Z-lig reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling. Thus, Z-lig is a potential drug for the treatment of nephrotoxicity caused by cisplatin. Keywords: Z-ligustilide, Cisplatin, Nephrotoxicity, Oxidative stress, Apoptosis, Nuclear factor erythroid 2-related factor 2, Heme oxygenase-

Low-income housing layouts under socio-architectural complexities: A parametric study for sustainable slum rehabilitation

Lack of sustainable slum redevelopment guidelines in India is a policy gap that needs immediate attention. A rational design and planning route is necessary to ensure sustainability of the upcoming low-income (LIG) housing stocks. In this study, we performed a cross-sectional evaluation of LIG housing layouts through a socio-architectural and site-based wind-flow analysis route. We hypothesise that a better indoor environment in the LIG housing can be achieved through a better wind driven natural-ventilation in the living spaces, which is a function of the housing layout. Specific objectives of this study were: i) to investigate the influence of socio-architectural and geometric parameters on the LIG housing layouts; ii) to examine the effect of site-wind flow on LIG housing layouts using CFD simulations. BDD chawls of Mumbai were adopted as the case study. Results show that the current form of the LIG houses had a poor indoor environment and social interaction spaces, while the hypothesised iterated layout ‘Form A’ performed better in all the socio-architectural and wind-flow metrics that can promote relatively better quality of life. This study is a first-step approach for the development of regulatory guidelines in LIG housing design that is coherent to the context of the space.Ministry of Human Resource Development, Government of India Commonwealth Scholarship Commission Cambridge Trus