Climate change scenarios predict increases in temperature, changes in precipitation patterns, and longer drought periods in most semi-arid regions of the world. Ecosystems in these regions are prone ...to land degradation, which may be aggravated by climate change. Soil respiration is one of the main processes responsible for organic carbon losses from arid and semi-arid ecosystems. We measured soil respiration over one year in two steppe ecosystems having different degrees of land degradation under three ground-covers: with vegetation, bare soil, and an intermediate situation between plants and bare soil.
The largest differences in soil respiration rates between the sites were observed in spring, coinciding with the highest level of plant activity. The degraded site had drier and hotter soils with less soil water availability and a longer drought period. As a result, vegetation on the degraded site did not respond to spring rainfall events. Soil respiration showed a strong seasonal variability, with average annual rates of 1.1 and 0.8 μmol CO2 m−2 s−1 in the natural and degraded sites, respectively. We did not observe significant differences in soil respiration rates associated with ground-cover i.e., the temporal variation was much larger than the spatial variation. At both sites, soil moisture was the controlling driver of soil respiration for most of the year, when temperatures were above 20 °C and constrained the response to temperature for the few months when the temperature was below 20 °C. An empirical model based on soil temperature and soil moisture explained 90% and 72% of the seasonal variability of soil respiration on the natural and degraded sites, respectively. For the first time, this study suggests that land degradation may alter the carbon balance of these ecosystems through changes in the temporal dynamics of soil respiration and plant productivity, which have important negative consequences for ecosystem functioning and sustainability.
► The seasonal and spatial variation of soil respiration in a semi-arid grassland ecosystem. ► The importance of soil temperature and moisture controlling soil respiration in these regions. ► The impact of land degradation by comparing the dynamics of soil respiration in two steppe ecosystems with different degree of vegetation cover.
Objective
To continue evaluation of the long‐term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy ...(DMD). Three‐year progression of eteplirsen‐treated patients was compared to matched historical controls (HC).
Methods
Ambulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open‐label basis. The primary functional assessment in this study was the 6‐Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.
Results
At 36 months, eteplirsen‐treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen‐treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.
Interpretation
Over 3 years of follow‐up, eteplirsen‐treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. Ann Neurol 2016;79:257–271
Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient-patient variability in disease onset and progression and response to glucocorticoids is seen, ...suggesting genetic or environmental modifiers.
Two DMD cohorts were used as test and validation groups to define genetic modifiers: a Padova longitudinal cohort (n = 106) and the Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history cohort (n = 156). Single nucleotide polymorphisms to be genotyped were selected from mRNA profiling in patients with severe vs mild DMD, and genome-wide association studies in metabolism and polymorphisms influencing muscle phenotypes in normal volunteers were studied.
Effects on both disease progression and response to glucocorticoids were observed with polymorphism rs28357094 in the gene promoter of SPP1 (osteopontin). The G allele (dominant model; 35% of subjects) was associated with more rapid progression (Padova cohort log rank p = 0.003), and 12%-19% less grip strength (CINRG cohort p = 0.0003).
Osteopontin genotype is a genetic modifier of disease severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in inclusion criteria in DMD clinical trials would reduce intersubject variance, and increase sensitivity of the trials, particularly in older subjects.
Rapid Arctic warming is causing permafrost to thaw and exposing large quantities of soil organic carbon (C) to potential decomposition. In dry upland tundra systems, subsidence from thawing ...permafrost can increase surface soil moisture resulting in higher methane (CH4) emissions from newly waterlogged soils. The proportion of C released as carbon dioxide (CO2) and CH4 remains uncertain as previously dry landscapes transition to a thawed state, resulting in both wetter and drier microsites. To address how thaw and moisture interact to affect total C emissions, we measured CH4 and CO2 emissions from paired chambers across thaw and moisture gradients created by nine years of experimental soil warming in interior Alaska. Cumulative growing season (May–September) CH4 emissions were elevated at both wetter (216.1–1,099.4 mg CH4‐C m−2) and drier (129.7–392.3 mg CH4‐C m−2) deeply thawed microsites relative to shallow thaw (55.6–215.7 mg CH4‐C m−2) and increased with higher deep soil temperatures and permafrost thaw depth. Interannual variability in CH4 emissions was driven by wet conditions in graminoid‐dominated plots that generated >70% of emissions in a wet year. Shoulder season emissions were equivalent to growing season CH4 emissions rates in the deeply thawed, warmed soils, highlighting the importance of non‐growing season CH4 emissions. Net C sink potential was reduced in deeply thawed wet plots by 4%–42%, and by 3.5%–8% in deeply thawed drier plots due to anaerobic respiration, suggesting that some dry upland tundra landscapes may transition into stronger CH4 sources in a warming Arctic.
Plain Language Summary
The Arctic is warming twice as fast as the global average. This is causing permafrost to thaw and subside. Soil carbon decomposition under these conditions can be released as carbon dioxide in dry soils, or as methane in newly waterlogged soils, which has a stronger global warming potential. We artificially warmed permafrost soils to measure how thaw and moisture affect total carbon emissions in a dry, upland tundra ecosystem. Methane emissions were higher with deeper thaw and wetter soils, especially in plots with sedge tussocks. Permafrost thaw increased soil moisture and we expect that this will lead to increased methane emissions from even dry landscapes in the future.
Key Points
Hotspots accounted for 72% of growing season methane emissions in a wet year in patches where sedges dominated the plant community
Thawed soil volume was a strong driver of increased methane emissions, even in the absence of high surface moisture
Increased methane emissions with deep thaw reduced net growing season carbon uptake by 18% in wet areas, and 4% in drier areas
Abstract Background and Purpose The aim was to investigate whether neurofilament light chain (NfL) and profilin‐1 (PFN‐1) might qualify as surrogate disease and treatment‐response biomarkers by ...correlating their concentrations dynamic with clinical status in a cohort of 30 adult spinal muscular atrophy type 3 patients during nusinersen therapy up to 34 months. Methods Neurofilament light chain was measured in cerebrospinal fluid at each drug administration with a commercial enzyme‐linked immunosorbent assay (ELISA); PFN‐1 concentrations were tested in serum sampled at the same time points with commercial ELISA assays. Functional motor scores were evaluated at baseline, at the end of the loading phase and at each maintenance dose and correlated to biomarker levels. The concurrent effect of age and clinical phenotype was studied. Results Neurofilament light chain levels were included in the reference ranges at baseline; a significant increase was measured during loading phase until 1 month. PFN‐1 was higher at baseline than in controls and then decreased during therapy until reaching control levels. Age had an effect on NfL but not on PFN‐1. NfL was partially correlated to functional scores at baseline and at last time point, whilst no correlation was found for PFN‐1. Conclusion Cerebrospinal fluid NfL levels did not qualify as an optimal surrogate treatment biomarker in adult spinal muscular atrophy patients with a long disease duration, whilst PFN‐1 might to a greater extent represent lower motor neuron pathological processes. The observed biomarker level variation during the first 2 months of nusinersen treatment might suggest a limited effect on axonal remodeling or rearrangement.
Background and purpose
Literature data on spinal and bulbar muscular atrophy (SBMA) epidemiology are limited and restricted to specific populations. The aim of our study was to accurately collect ...information about SBMA patients living in the Veneto region in Italy to compute reliable epidemiological data. Androgen receptor (AR) lineages were genotyped to evaluate the presence of a founder effect.
Methods
A prevalence survey considering all SBMA patients diagnosed in the Italian Veneto region on 31 January 2018 was carried out. The presence of different haplotypes obtained genotyping 15 polymorphic markers (single nucleotide polymorphisms and short tandem repeats) around the AR gene was evaluated.
Results
Based on 68 patients, the punctual prevalence of the disease on 31 January 2018 was 2.58/100 000 (95% confidence interval 1.65–3.35) in the male population. Five different haplotypes were identified, confirming the existence of multiple founder effects. It was also observed that, within the same haplotype, patients had a similar CAG repeat number (P‐value < 0.001).
Conclusions
A reliable estimation of SBMA prevalence in the Italian Veneto region was calculated which does not seem to be affected by a strong founder effect. Moreover, our data suggest that the length of the CAG expansion could be preserved in patients harbouring the same haplotype.
Peculiar cognitive profile of patients with SBMA has been described by fragmented literature. Our retrospective study reports the neuropsychological evaluations of a large cohort of patients in order ...to contribute towards the understanding of this field. We consider 64 neuropsychological evaluations assessing mnesic, linguistic and executive functions collected from 2013 to 2015 in patients attending at Motor Neuron Disease Centre of University of Padova. The battery consisted in: Digit Span forwards and backwards, Prose Memory test, Phonemic Verbal fluency and Trail making tests. ANCOVA statistics were employed to compare tests scores results with those obtained from a sample of healthy control subjects. Multiple linear regressions were used to study the effect on cognitive performance of CAG-repeat expansion, the degree of androgen insensitivity and their interaction to cognitive performance. Statistical analyses did not reveal altered scores in any neuropsychological tests among those adopted. Interestingly, patients performed significantly better in the Prose Memory test's score. No relevant associations were found with genetic, hormonal or clinical patients' profile. Results inconsistent with previous studies have been interpreted according to the phenomenon of somatic mosaicism. We suggest a testosterone-related and the mood state-dependant perspectives as two possible interpretations of the enhanced performances in the Prose Memory test. Further studies employing more datailed tests batteries are encouraged.
New FIG4 gene mutations causing aggressive ALS Bertolin, C.; Querin, G.; Bozzoni, V. ...
European journal of neurology,
March 2018, 2018-Mar, 20180301, Letnik:
25, Številka:
3
Journal Article
The aim of the study was to assess different outcome measures in a cohort of ambulant boys with Duchenne muscular dystrophy (DMD) over 12 months in order to establish the spectrum of possible changes ...in relation to age and steroid treatment.
The study is a longitudinal multicentric cohort study. A total of 106 ambulant patients with DMD were assessed using the 6-minute walk test (6MWT) and North Star Ambulatory Assessment (NSAA) at baseline and 12 months. Clinical data including age and steroid treatment were collected.
During the 12 months of the study, we observed a mean decline of 25.8 meters in the 6MWT with a SD of 74.3 meters. On NSAA, the mean decline was 2.2 points with a SD of 3.7. Not all the boys with DMD in our cohort showed a decline over the 12 months, with young boys showing some improvement in their 6MWT and NSAA scores up to the age of 7. NSAA and the 6MWT had the highest correlation (r = 0.52, p < 0.001).
This study provides longitudinal data of NSAA and 6MWT over a 12-month period. These data can be useful when designing a clinical trial.
Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (alpha-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or ...putative glycosyltransferases.
The aim of the study was to establish the prevalence of mutations in the six genes in the Italian population and the spectrum of clinical and brain MRI findings.
As part of a multicentric study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and alpha-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of alpha-dystroglycanopathy but in whom a muscle biopsy was not available for alpha-DG immunostaining (n = 5).
Homozygous and compound heterozygous mutations were detected in a total of 43/81 patients (53%), and included seven novel variants. Mutations in POMT1 were the most prevalent in our cohort (21%), followed by POMT2 (11%), POMGnT1 (10%), and FKRP (9%). One patient carried two heterozygous mutations in fukutin and one case harbored a new homozygous variant in LARGE. No clear-cut genotype-phenotype correlation could be observed with each gene, resulting in a wide spectrum of clinical phenotypes. The more severe phenotypes, however, appeared to be consistently associated with mutations predicted to result in a severe disruption of the respective genes.
Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.
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