Glial-cell-line-derived neurotrophic factor (GDNF), a recently cloned new member of the transforming growth factor-beta superfamily, promotes survival of cultured fetal mesencephalic dopamine neurons and is expressed in the developing striatum. There have, however, been no reports about effects of GDNF in situ. We have used the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces parkinsonian symptoms in man, to determine whether GDNF might exert protective or regenerative effects in vivo in the adult nigrostriatal dopamine system in C57/B1 mice. GDNF injected over the substantia nigra or in striatum before MPTP potently protects the dopamine system, as shown by numbers of mesencephalic dopamine nerve cell bodies, dopamine nerve terminal densities and dopamine levels. When GDNF is given after MPTP, dopamine levels and fibre densities are significantly restored. In both cases, motor behaviour is increased above normal levels. We conclude that intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease.

Drylands are home to more than 38% of the world's population and are one of the most sensitive areas to climate change and human activities. This review describes recent progress in dryland climate change research. Recent findings indicate that the long‐term trend of the aridity index (AI) is mainly attributable to increased greenhouse gas emissions, while anthropogenic aerosols exert small effects but alter its attributions. Atmosphere‐land interactions determine the intensity of regional response. The largest warming during the last 100 years was observed over drylands and accounted for more than half of the continental warming. The global pattern and interdecadal variability of aridity changes are modulated by oceanic oscillations. The different phases of those oceanic oscillations induce significant changes in land‐sea and north‐south thermal contrasts, which affect the intensity of the westerlies and planetary waves and the blocking frequency, thereby altering global changes in temperature and precipitation. During 1948–2008, the drylands in the Americas became wetter due to enhanced westerlies, whereas the drylands in the Eastern Hemisphere became drier because of the weakened East Asian summer monsoon. Drylands as defined by the AI have expanded over the last 60 years and are projected to expand in the 21st century. The largest expansion of drylands has occurred in semiarid regions since the early 1960s. Dryland expansion will lead to reduced carbon sequestration and enhanced regional warming. The increasing aridity, enhanced warming, and rapidly growing population will exacerbate the risk of land degradation and desertification in the near future in developing countries.

Abstract. The Paris Agreement of December 2015 stated a goal to pursue efforts to keep global temperatures below 1.5 • C above preindustrial levels and well below 2 • C. The IPCC was charged with assessing climate impacts at these temperature levels, but fully coupled equilibrium climate simulations do not currently exist to inform such assessments. In this study, we produce a set of scenarios using a simple model designed to achieve long-term 1.5 and 2 • C temperatures in a stable climate. These scenarios are then used to produce century-scale ensemble simulations using the Community Earth System Model, providing impact-relevant long-term climate data for stabilization pathways at 1.5 and 2 • C levels and an overshoot 1.5 • C case, which are realized (for the 21st century) in the coupled model and are freely available to the community. Here we describe the design of the simulations and a brief overview of their impact-relevant climate response. Exceedance of historical record temperature occurs with 60 % greater frequency in the 2 • C climate than in a 1.5 • C climate aggregated globally, and with twice the frequency in equatorial and arid regions. Extreme precipitation intensity is statistically significantly higher in a 2.0 • C climate than a 1.5 • C climate in some specific regions (but not all). The model exhibits large differences in the Arctic, which is ice-free with a frequency of 1 in 3 years in the 2.0 • C scenario, and 1 in 40 years in the 1.5 • C scenario. Significance of impact differences with respect to multi-model variability is not assessed.

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Greenhouse gases (GHGs) and aerosols are the two most important anthropogenic forcing agents in the 21st century. The expected declines of anthropogenic aerosols in the 21st century from present‐day levels would cause an additional warming of the Earth's climate system, which would aggravate the climate extremes caused by GHG warming. We examine the increased rate of precipitation extremes with global mean surface warming in the 21st century caused by anthropogenic GHGs and aerosols, using an Earth system model ensemble simulation. Similar to mean precipitation, the increased rate of precipitation extremes caused by aerosol forcing is significantly larger than that caused by GHG forcing. The aerosol forcing in the coming decades can play a critical role in inducing change in precipitation extremes if a lower GHG emission pathway is adopted. Our results have implications for policy‐making on climate adaptation to extreme precipitation events.

The 2015 Paris Agreement aims to limit global warming below 2 °C and pursue efforts to even limit it to 1.5 °C relative to pre-industrial levels. Decision makers need reliable information on the impacts caused by these warming levels for climate mitigation and adaptation measures. We explore the changes in climate extremes, which are closely tied to economic losses and casualties, under 1.5 °C and 2 °C global warming and their scenario dependence using three sets of ensemble global climate model simulations. A warming of 0.5 °C (from 1.5 °C to 2 °C) leads to significant increases in temperature and precipitation extremes in most regions. However, the projected changes in climate extremes under both warming levels highly depend on the pathways of emissions scenarios, with different greenhouse gas (GHG)/aerosol forcing ratio and GHG levels. Moreover, there are multifold differences in several heavily polluted regions, among the scenarios, in the changes in precipitation extremes due to an additional 0.5 °C warming from 1.5 °C to 2 °C. Our results demonstrate that the chemical compositions of emissions scenarios, not just the total radiative forcing and resultant warming level, must be considered when assessing the impacts of global 1.5/2 °C warming.

The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9. We discover that HDAC5 inhibits neurite extension both in differentiated P19 cells and primary neurons. We also show that the neuronal membrane glycoprotein GPM6A (M6a) is a direct target gene of HDAC5 regulated transcriptional factor MEF2C. HDAC5 inhibits neurite elongation, acting at least partially via a MEF2C/M6a signaling pathway. We also confirmed the miR-124/miR-9 regulated HDAC5-MEF2C-M6a pathway regulates neurite development in primary neurons. Thus, HDAC5 emerges as a cellular conductor of MEF2C and M6a activity and is regulated by miR-124 and miR-9 to control neurite development.

Anthropogenic aerosol (AA) forcing has been shown as a critical driver of climate change over Asia since the mid-20th century. Here we show that almost all Coupled Model Intercomparison Project Phase 6 (CMIP6) models fail to capture the observed dipole pattern of aerosol optical depth (AOD) trends over Asia during 2006–2014, last decade of CMIP6 historical simulation, due to an opposite trend over eastern China compared with observations. The incorrect AOD trend over China is attributed to problematic AA emissions adopted by CMIP6. There are obvious differences in simulated regional aerosol radiative forcing and temperature responses over Asia when using two different emissions inventories (one adopted by CMIP6; the other from Peking university, a more trustworthy inventory) to driving a global aerosol-climate model separately. We further show that some widely adopted CMIP6 pathways (after 2015) also significantly underestimate the more recent decline in AA emissions over China. These flaws may bring about errors to the CMIP6-based regional climate attribution over Asia for the last two decades and projection for the next few decades, previously anticipated to inform a wide range of impact analysis.