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The identification of disease-causing mutations or strong risk factors for Parkinson’s disease in genes encoding proteins such as α-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2), or glucocerebrosidase (GBA1) has led to a better understanding of the different components of disease pathogenesis. Many gene and mutation-specific targeted disease-modifying treatments are under development and several studies are under way. It is, therefore, important to raise awareness among patients and their families and to offer genetic testing, at least to those patients who are considering to participate in innovative trials.

Over the past few years, genetic findings have changed our views on the molecular pathogenesis of Parkinson disease (PD), as mutations in a growing number of genes have been found to cause monogenic forms of the disorder. These mutations cause neuronal dysfunction and neurodegeneration either by a toxic gain of function, as in the case of the dominant forms of monogenic PD caused by mutations in the genes for α-synuclein or LRRK2, or by a loss of an intrinsic protective function, as is likely for the recessive PD genes parkin (PRKN), PINK1 and DJ-1. Evidence is emerging that at least some of the pathways uncovered in the rare monogenic forms of PD may play a direct role in the aetiology of the common sporadic disorder and that variants of the respective genes contribute to the risk of developing the disease. These findings will allow the search for new treatment strategies that focus on the underlying molecular pathophysiology, rather than simply on ameliorating symptoms.

The etiology of Parkinson’s disease (PD) is complex and most likely involves numerous environmental and heritable risk factors. Interestingly, many genetic variants, which have been linked to familial forms of PD or identified as strong risk factors, also play a critical role in modulating inflammatory responses. There has been considerable debate in the field as to whether inflammation is a driving force in neurodegeneration or simply represents a response to neuronal death. One emerging hypothesis is that inflammation plays a critical role in the early phases of neurodegeneration. In this review, we will discuss emerging aspects of both innate and adaptive immunity in the context of the pathogenesis of PD. We will highlight recent data from genetic and functional studies that strongly support the theory that genetic susceptibility plays an important role in modulating immune pathways and inflammatory reactions, which may precede and initiate neuronal dysfunction and subsequent neurodegeneration. A detailed understanding of such cellular and molecular inflammatory pathways is crucial to uncover pathogenic mechanisms linking sporadic and hereditary PD and devise tailored neuroprotective interventions.

The dystonias are a heterogeneous group of hyperkinetic movement disorders characterised by involuntary sustained muscle contractions that lead to abnormal postures and repetitive movements. Dystonia syndromes represent common movement disorders and yet are often misdiagnosed or unrecognised. In recent years, there have been substantial advances in the understanding of the spectrum of clinical features that encompass dystonia syndromes, from severe generalised childhood dystonia that is often genetic in origin, to adult-onset focal dystonias and rarer forms of secondary dystonias, to dystonia as a feature of other types of CNS dysfunction. There has also been a rationalisation of the classification of dystonia and a greater understanding of the causes of dystonic movements from the study of genetics, neurophysiology, and functional imaging in the most prevalent form of dystonia syndrome, primary dystonia.

Prasinezumab is a monoclonal antibody to α-synuclein, a protein involved in the pathogenesis of Parkinson’s disease. In a placebo-controlled trial, prasinezumab did not slow the progression of disease over a period of 52 weeks.

China’s commitment to carbon neutrality by 2060 relies on the Land Use, Land-Use Change, and Forestry (LULUCF) sector, with forestation targets designed to enhance carbon removal. However, the exact sequestration potential of these initiatives remains uncertain due to differing accounting conventions between national inventories and scientific assessments. Here, we reconcile both estimates and reassess LULUCF carbon fluxes up to 2100, using a spatially explicit bookkeeping model, state-of-the-art historical data, and national forestation targets. We simulate a carbon sink of −0.24 ± 0.03 Gt C yr −1 over 1994–2018 from past forestation efforts, aligned well with the national inventory. Should the official forestation targets be followed and extended, this could reach −0.35 ± 0.04 Gt C yr −1 in 2060, offsetting 43 ± 4% of anticipated residual fossil CO 2 emissions. Our findings confirm the key role of LULUCF in carbon sequestration, but its potential will decline if forestation efforts cease, highlighting the necessity for emission reductions in other sectors to achieve carbon neutrality. China’s 2060 carbon neutrality goal relies on forestation to enhance carbon removal. This study reconciles national and scientific LULUCF carbon flux estimates, projecting that continued forestation could offset 43% of CO 2 emissions by 2060.

ObjectivesThis study aimed to retrospectively evaluate clinical and radiographic outcomes of partial pulpotomy performed in permanent teeth with carious pulp exposure.Materials and methodsRecords of patients undergoing treatment at an undergraduate dental clinic between 2010 and 2019 were screened for partial pulpotomies in teeth with a presumptive diagnosis of normal pulp or reversible pulpitis. The follow-up had to be ≥ 1 year. Patient data were retrieved and analyzed using Mantel-Cox chi square tests and Kaplan–Meier statistics. The level of significance was set at α = 0.05.ResultsPartial pulpotomy was performed in 111 cases, of which 64 (58%) fulfilled the eligibility criteria. At the time of partial pulpotomy, the mean age was 37.3 (± 13.5) years (age range 18–85). The mean observation period was 3.1 (± 2.0) years. Two early failures (3.1%) and five late failures (7.7%) were recorded. The overall success rate of maintaining pulp vitality was 89.1%, with 98.4% tooth survival. The cumulative pulp survival rates of partial pulpotomy in patients aged < 30 years, between 30 and 40 years, and > 40 years were 100%, 75.5%, and 90.5%, respectively, with no significant difference between the age groups (p = 0.225). At follow-up, narrowing of the pulp canal space and tooth discoloration were observed in 10.9% and 3.1% of cases, respectively.ConclusionsAcross age groups, partial pulpotomy achieved favorable short and medium-term outcomes in teeth with carious pulp exposure.Clinical relevanceAdequate case selection provided, partial pulpotomy is a viable operative approach to treat permanent teeth with deep carious lesions irrespective of patients’ age.

Anthropogenic emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) have made significant contributions to global warming since the pre-industrial period and are therefore targeted in international climate policy. There is substantial interest in tracking and apportioning national contributions to climate change and informing equitable commitments to decarbonisation. Here, we introduce a new dataset of national contributions to global warming caused by historical emissions of carbon dioxide, methane, and nitrous oxide during the years 1851–2021, which are consistent with the latest findings of the IPCC. We calculate the global mean surface temperature response to historical emissions of the three gases, including recent refinements which account for the short atmospheric lifetime of CH4. We report national contributions to global warming resulting from emissions of each gas, including a disaggregation to fossil and land use sectors. This dataset will be updated annually as national emissions datasets are updated.

Grasslands absorb and release carbon dioxide (CO 2 ), emit methane (CH 4 ) from grazing livestock, and emit nitrous oxide (N 2 O) from soils. Little is known about how the fluxes of these three greenhouse gases, from managed and natural grasslands worldwide, have contributed to past climate change, or the roles of managed pastures versus natural grasslands. Here, global trends and regional patterns of the full greenhouse gas balance of grasslands are estimated for the period 1750 to 2012. A new spatially explicit land surface model is applied, to separate the direct effects of human activities from land management and the indirect effects from climate change, increasing CO 2 and regional changes in nitrogen deposition. Direct human management activities are simulated to have caused grasslands to switch from a sink to a source of greenhouse gas, because of increased livestock numbers and accelerated conversion of natural lands to pasture. However, climate change drivers contributed a net carbon sink in soil organic matter, mainly from the increased productivity of grasslands due to increased CO 2 and nitrogen deposition. The net radiative forcing of all grasslands is currently close to neutral, but has been increasing since the 1960s. Here, we show that the net global climate warming caused by managed grassland cancels the net climate cooling from carbon sinks in sparsely grazed and natural grasslands. In the face of future climate change and increased demand for livestock products, these findings highlight the need to use sustainable management to preserve and enhance soil carbon storage in grasslands and to reduce greenhouse gas emissions from managed grasslands. Grasslands, and the livestock that live there, are dynamic sources and sinks of greenhouse gases, but what controls these fluxes remains poorly characterized. Here the authors show that on the global level, grasslands are climate neutral owing to the cancelling effects of managed vs. natural systems.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values >0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials. Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.