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The co-emergence of a six-layered cerebral neocortex and its corticospinal output system is one of the evolutionary hallmarks of mammals. However, the genetic programs that underlie their development and evolution remain poorly understood. Here we identify a conserved non-exonic element (E4) that acts as a cortex-specific enhancer for the nearby gene Fezf2 (also known as Fezl and Zfp312 ), which is required for the specification of corticospinal neuron identity and connectivity. We find that SOX4 and SOX11 functionally compete with the repressor SOX5 in the transactivation of E4. Cortex-specific double deletion of Sox4 and Sox11 leads to the loss of Fezf2 expression, failed specification of corticospinal neurons and, independent of Fezf2 , a reeler -like inversion of layers. We show evidence supporting the emergence of functional SOX-binding sites in E4 during tetrapod evolution, and their subsequent stabilization in mammals and possibly amniotes. These findings reveal that SOX transcription factors converge onto a cis -acting element of Fezf2 and form critical components of a regulatory network controlling the identity and connectivity of corticospinal neurons. SOX transcription factors converge on a cortex-specific enhancer to regulate the dynamic, cell-type-specific expression of Fezf2 , a gene necessary for the formation of corticospinal system. Control of neocortical development The emergence and expansion of the neocortex has been crucial to the evolution of higher brain function in mammals. Neocortical layers differ in their projection patterns, with upper layers connecting to other cortical neurons and deeper layers projecting long distances to other brain areas and the spinal cord, but the genetic programs underlying these anatomical differences are unknown. Here, Shim et al . identify a conserved, cortex-specific enhancer that drives the Fezf2 -initiated specification program required for the production of the deep-layer, long-range projection neurons in the corticospinal tract. SOX transcription factors influence this enhancer through sites found to have emerged with tetrapods, modulating the regulatory network responsible for the corticospinal output system, an evolutionary hallmark of mammals.

We analyse historical (1850–2014) atmospheric hydroxyl (OH) and methane lifetime data from Coupled Model Intercomparison Project Phase 6 (CMIP6)/Aerosols and Chemistry Model Intercomparison Project (AerChemMIP) simulations. Tropospheric OH changed little from 1850 up to around 1980, then increased by around 9 % up to 2014, with an associated reduction in methane lifetime. The model-derived OH trends from 1980 to 2005 are broadly consistent with trends estimated by several studies that infer OH from inversions of methyl chloroform and associated measurements; most inversion studies indicate decreases in OH since 2005. However, the model results fall within observational uncertainty ranges. The upward trend in modelled OH since 1980 was mainly driven by changes in anthropogenic near-term climate forcer emissions (increases in anthropogenic nitrogen oxides and decreases in CO). Increases in halocarbon emissions since 1950 have made a small contribution to the increase in OH, whilst increases in aerosol-related emissions have slightly reduced OH. Halocarbon emissions have dramatically reduced the stratospheric methane lifetime by about 15 %–40 %; most previous studies assumed a fixed stratospheric lifetime. Whilst the main driver of atmospheric methane increases since 1850 is emissions of methane itself, increased ozone precursor emissions have significantly modulated (in general reduced) methane trends. Halocarbon and aerosol emissions are found to have relatively small contributions to methane trends. These experiments do not isolate the effects of climate change on OH and methane evolution; however, we calculate residual terms that are due to the combined effects of climate change and non-linear interactions between drivers. These residual terms indicate that non-linear interactions are important and differ between the two methodologies we use for quantifying OH and methane drivers. All these factors need to be considered in order to fully explain OH and methane trends since 1850; these factors will also be important for future trends.

In this study, diurnal characteristics and long-term changes in extreme precipitation (PR) in the Republic of Korea (KR) are investigated. Hourly PR data from 59 ASOS stations across the country over a 50-year period (1973–2022) are used. The focus is on the summer season (June to September), during which extreme PR frequently occurs. During the period 1973–1997 (FP), both the amount and frequency of extreme PR events peak between 01 and 09 LST. In contrast, during the period 1998–2022 (LP), a notable increase in extreme PR and its frequency is observed between 04 and 12 LST, with the peak occurrence hours shifting to this time frame. An analysis of atmospheric variables related to extreme PR is conducted for the 04–12 LST time frame. Compared to all PR events during the summer season, a low-level low-pressure anomaly is found west of the KR, leading to southerly winds and positive specific humidity anomalies over the south of the KR. Relative to the FP period, both the amplitude and frequency of high water vapor content have increased during the LP period. This intensified moisture may be associated with the observed increase in extreme PR during 04–12 LST. However, no significant changes are found in the strength and frequency of the southerly wind.

The East Asian summer monsoon (EASM) is an influential monsoon system that provides two-thirds of the annual precipitation in the Asian region. Therefore, considerable attention has been paid to the changes in future climate. Thus far, studies on EASM characteristics have not been conducted considering specific global warming level (GWL) using Coupled Model Inter-comparison Project 6 (CMIP6) simulations. We analyze the EASM characteristics in present-day (PD) and the changes in EASM corresponding to the projections at 1.5, 2.0, and 3.0°C GWLs. The newly released 30 CMIP6 models effectively captured the migration of the monsoon in PD with a pattern correlation coefficient of 0.91, which is an improvement over that reported in previous studies. As a result of the separate analysis of the P1 (first primary peak; 33–41 pentad) and P2 (from P1 to the withdrawal; 42–50 pentad) periods, a higher frequency of weak to moderate precipitation in P2 and a smaller amount of moderate to extreme precipitation in P1 are mainly occurred. The CMIP6 models project increasing precipitation of approximately 5.7%°C −1 , 4.0%°C −1 , and 3.9%°C −1 for the three GWLs, respectively, with longer durations (earlier onset and delayed termination). Under the three GWLs, the projected precipitation frequency decreases below 6 mm d −1 (76th percentile) and significant increases above 29 mm d −1 (97th percentile). These changes in precipitation frequency are associated with an increasing distribution of precipitation amount above 97th percentile. Additionally, these tendencies in P1 and P2 are similar to that of the total period, while the maximum changes occur in 3.0°C GWL. In particular, future changes in EASM accelerate with continuous warming and are mainly affected by enhanced extreme precipitation (above 97th percentile). Our findings are expected to provide information for the implementation of sustainable water management programs as a part of national climate policy.

Astrocytes, the most abundant glial cell type in the central nervous system (CNS), are essential for maintaining neural homeostasis, forming gliovascular unit, and modulating synaptic function. However, commonly used astrocytic markers often display regional variability or lack strict specificity, limiting their reliability for consistently identifying astrocytes across brain regions. To address this limitation, we generated a novel transgenic mouse line (AldoC BAC-GFP) that expresses green fluorescent protein (GFP) under the control of the aldolase C (AldoC) promoter using modified bacterial artificial chromosome (BAC) technology. AldoC is an enzyme abundantly expressed in astrocytes. We confirmed that GFP-expressing cells in these mice co-express endogenous AldoC and are co-labeled with established astrocytic markers, thereby validating their astrocytic identity. Importantly, GFP expression was largely restricted to astrocytes throughout diverse brain regions. Moreover, GFP-positive astrocytes in brain slices exhibited the characteristic linear-shaped passive conductance of mature astrocytes. Collectively, these findings demonstrate that AldoC BAC-GFP transgenic mice represent a reliable and broadly applicable model for functional studies of astrocytes in the CNS.

The corticospinal (CS) tract is involved in controlling discrete voluntary skilled movements in mammals. The CS tract arises exclusively from layer (L) 5 projection neurons of the cerebral cortex, and its formation requires L5 activity of Fezf2 (Fezl, Zfp312). How this L5-specific pattern of Fezf2 expression and CS axonal connectivity is established with such remarkable fidelity had remained elusive. Here we show that the transcription factor TBR1 directly binds the Fezf2 locus and represses its activity in L6 corticothalamic projection neurons to restrict the origin of the CS tract to L5. In Tbr1 null mutants, CS axons ectopically originate from L6 neurons in a Fezf2-dependent manner. Consistently, misexpression of Tbr1 in L5 CS neurons suppresses Fezf2 expression and effectively abolishes the CS tract. Taken together, our findings show that TBR1 is a direct transcriptional repressor of Fezf2 and a negative regulator of CS tract formation that restricts the laminar origin of CS axons specifically to L5.

Quantifying forcings from anthropogenic perturbations to the Earth system (ES) is important for understanding changes in climate since the pre-industrial (PI) period. Here, we quantify and analyse a wide range of present-day (PD) anthropogenic effective radiative forcings (ERFs) with the UK's Earth System Model (ESM), UKESM1, following the protocols defined by the Radiative Forcing Model Intercomparison Project (RFMIP) and the Aerosol and Chemistry Model Intercomparison Project (AerChemMIP). In particular, quantifying ERFs that include rapid adjustments within a full ESM enables the role of various chemistry–aerosol–cloud interactions to be investigated. Global mean ERFs for the PD (year 2014) relative to the PI (year 1850) period for carbon dioxide (CO2), nitrous oxide (N2O), ozone-depleting substances (ODSs), and methane (CH4) are 1.89 ± 0.04, 0.25 ± 0.04, −0.18 ± 0.04, and 0.97 ±  0.04 W m−2, respectively. The total greenhouse gas (GHG) ERF is 2.92 ± 0.04 W m−2. UKESM1 has an aerosol ERF of −1.09 ± 0.04 W m−2. A relatively strong negative forcing from aerosol–cloud interactions (ACI) and a small negative instantaneous forcing from aerosol–radiation interactions (ARI) from sulfate and organic carbon (OC) are partially offset by a substantial forcing from black carbon (BC) absorption. Internal mixing and chemical interactions imply that neither the forcing from ARI nor ACI is linear, making the aerosol ERF less than the sum of the individual speciated aerosol ERFs. Ozone (O3) precursor gases consisting of volatile organic compounds (VOCs), carbon monoxide (CO), and nitrogen oxides (NOx), but excluding CH4, exert a positive radiative forcing due to increases in O3. However, they also lead to oxidant changes, which in turn cause an indirect aerosol ERF. The net effect is that the ERF from PD–PI changes in NOx emissions is negligible at 0.03 ± 0.04 W m−2, while the ERF from changes in VOC and CO emissions is 0.33 ± 0.04 W m−2. Together, aerosol and O3 precursors (called near-term climate forcers (NTCFs) in the context of AerChemMIP) exert an ERF of −1.03 ± 0.04 W m−2, mainly due to changes in the cloud radiative effect (CRE). There is also a negative ERF from land use change (−0.17 ± 0.04 W m−2). When adjusted from year 1850 to 1700, it is more negative than the range of previous estimates, and is most likely due to too strong an albedo response. In combination, the net anthropogenic ERF (1.76 ± 0.04 W m−2) is consistent with other estimates. By including interactions between GHGs, stratospheric and tropospheric O3, aerosols, and clouds, this work demonstrates the importance of ES interactions when quantifying ERFs. It also suggests that rapid adjustments need to include chemical as well as physical adjustments to fully account for complex ES interactions.

Preeclampsia is caused by placental hypoxia and systemic inflammation and is associated with reduced placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS) levels. The molecular signaling axes involved in this process may play a role in the pathogenesis of preeclampsia. Here, we found that hypoxic exposure increased hypoxia-inducible factor-1α (HIF-1α)/Twist1-mediated miR-214-3p biogenesis in trophoblasts, suppressing PlGF production and trophoblast invasion. TNF-α stimulation increased NF-κB-dependent miR-214-3p expression in endothelial cells, impairing eNOS expression and causing endothelial dysfunction. Synthetic miR-214-3p administration to pregnant mice decreased PlGF and eNOS expression, resulting in preeclampsia-like symptoms, including hypertension, proteinuria, and fetal growth restriction. Conversely, miR-214-3p deletion maintained the PlGF and eNOS levels in hypoxic pregnant mice, alleviating preeclampsia-like symptoms and signs. These findings provide new insights into the role of HIF-1/Twist1- and NF-κB-responsive miR-214-3p-dependent PlGF and eNOS downregulation in the pathogenesis of preeclampsia and establish miR-214-3p as a therapeutic or preventive target for preeclampsia and its complications. Hypoxia-induced miR-214-3p: key player in preeclampsia pathogenesis This research investigates how a molecule, miR-214-3p, impacts the occurrence of preeclampsia - a pregnancy issue marked by high blood pressure and organ damage. Scientists discovered that miR-214-3p produced more when oxygen levels are low, suppresses two other molecules, PlGF and eNOS, essential for a healthy pregnancy. In mouse experiments, artificially increasing miR-214-3p led to preeclampsia-like symptoms, while mice without miR-214-3p alleviated these symptoms in low oxygen. This suggests miR-214-3p could be a focus for preeclampsia prevention or treatment. Further studies are required to confirm this. “This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.”

Cerebellar deficits with Purkinje cell (PCs) loss are observed in several neurologic disorders. However, the underlying mechanisms as to how the cerebellum is affected during development remain unclear. Here we demonstrated that specific inactivation of murine Ebp1 in the central nervous system causes a profound neuropathology characterized by reduced cerebellar volume and PCs loss with abnormal dendritic development, leading to phenotypes including motor defects and schizophrenia (SZ)-like behaviors. Loss of Ebp1 leads to untimely gene expression of Fbxw7, an E3 ubiquitin ligase, resulting in aberrant protein degradation of PTF1A, thereby eliciting cerebellar defects. Reinstatement of Ebp1, but not the Ebp1-E183Ter mutant found in SZ patients, reconstituted cerebellar architecture with increased PCs numbers and improved behavioral phenotypes. Thus, our findings indicate a crucial role for EBP1 in cerebellar development, and define a molecular basis for the cerebellar contribution to neurologic disorders such as SZ.

Near-term climate forcers (NTCFs), including aerosols and chemically reactive gases such as tropospheric ozone and methane, offer a potential way to mitigate climate change and improve air quality-so called 'win-win' mitigation policies. Prior studies support improved air quality under NTCF mitigation, but with conflicting climate impacts that range from a significant reduction in the rate of global warming to only a modest impact. Here, we use state-of-the-art chemistry-climate model simulations conducted as part of the Aerosol and Chemistry Model Intercomparison Project (AerChemMIP) to quantify the 21st-century impact of NTCF reductions, using a realistic future emission scenario with a consistent air quality policy. Non-methane NTCF (NMNTCF; aerosols and ozone precursors) mitigation improves air quality, but leads to significant increases in global mean precipitation of 1.3% by mid-century and 1.4% by end-of-the-century, and corresponding surface warming of 0.23 and 0.21 K. NTCF (all-NTCF; including methane) mitigation further improves air quality, with larger reductions of up to 45% for ozone pollution, while offsetting half of the wetting by mid-century (0.7% increase) and all the wetting by end-of-the-century (non-significant 0.1% increase) and leading to surface cooling of −0.15 K by mid-century and −0.50 K by end-of-the-century. This suggests that methane mitigation offsets warming induced from reductions in NMNTCFs, while also leading to net improvements in air quality.