Holocene vegetation, fire and land use dynamics at Lake Svityaz, an agriculturally marginal site in northwestern Ukraine

Observing natural vegetation dynamics over the entire Holocene is difficult in Central Europe, due to pervasive and increasing human disturbance since the Neolithic. One strategy to minimize this limitation is to select a study site in an area that is marginal for agricultural activity. Here, we present a new sediment record from Lake Svityaz in northwestern Ukraine. We have reconstructed regional and local vegetation and fire dynamics since the Late Glacial using pollen, spores, macrofossils and charcoal. Boreal forest composed of Pinus sylvestris and Betula with continental Larix decidua and Pinus cembra established in the region around 13,450 cal BP, replacing an open, steppic landscape. The first temperate tree to expand was Ulmus at 11,800 cal BP, followed by Quercus, Fraxinus excelsior, Tilia and Corylus ca. 1,000 years later. Fire activity was highest during the Early Holocene, when summer solar insolation reached its maximum. Carpinus betulus and Fagus sylvatica established at ca. 6,000 cal BP, coinciding with the first indicators of agricultural activity in the region and a transient climatic shift to cooler and moister conditions. Human impact on the vegetation remained initially very low, only increasing during the Bronze Age, at ca. 3,400 cal BP. Large-scale forest openings and the establishment of the present-day cultural landscape occurred only during the past 500 years. The persistence of highly diverse mixed forest under absent or low anthropogenic disturbance until the Early Middle Ages corroborates the role of human impact in the impoverishment of temperate forests elsewhere in Central Europe. The preservation or reestablishment of such diverse forests may mitigate future climate change impacts, specifically by lowering fire risk under warmer and drier conditions

Holocene vegetation and fire history of the mountains of Northern Sicily (Italy)

Knowledge about vegetation and fire history of the mountains of Northern Sicily is scanty. We analysed five sites to fill this gap and used terrestrial plant macrofossils to establish robust radiocarbon chronologies. Palynological records from Gorgo Tondo, Gorgo Lungo, Marcato Cixé, Urgo Pietra Giordano and Gorgo Pollicino show that under natural or near natural conditions, deciduous forests (Quercus pubescens, Q. cerris, Fraxinus ornus, Ulmus), that included a substantial portion of evergreen broadleaved species (Q. suber, Q. ilex, Hedera helix), prevailed in the upper meso- mediterranean belt. Mesophilous deciduous and evergreen broadleaved trees (Fagus sylvatica, Ilex aquifolium) dominated in the natural or quasi-natural forests of the oro- mediterranean belt. Forests were repeatedly opened for agricultural purposes. Fire activity was closely associated with farming, providing evidence that burning was a primary land use tool since Neolithic times. Land use and fire activity intensified during the Early Neolithic at 5000 bc, at the onset of the Bronze Age at 2500 bc and at the onset of the Iron Age at 800 bc. Our data and previous studies suggest that the large majority of open land communities in Sicily, from the coastal lowlands to the mountain areas below the thorny-cushion Astragalus belt (ca. 1,800 m a.s.l.), would rapidly develop into forests if land use ceased. Mesophilous Fagus-Ilex forests developed under warm mid Holocene conditions and were resilient to the combined impacts of humans and climate. The past ecology suggests a resilience of these summer-drought adapted communities to climate warming of about 2 °C. Hence, they may be particularly suited to provide heat and drought-adapted Fagus sylvatica ecotypes for maintaining drought-sensitive Central European beech forests under global warming conditions

Developmental Splicing Deregulation in Leukodystrophies Related to EIF2B Mutations

Leukodystrophies (LD) are rare inherited disorders that primarily affect the white matter (WM) of the central nervous system. The large heterogeneity of LD results from the diversity of the genetically determined defects that interfere with glial cells functions. Astrocytes have been identified as the primary target of LD with cystic myelin breakdown including those related to mutations in the ubiquitous translation initiation factor eIF2B. EIF2B is involved in global protein synthesis and its regulation under normal and stress conditions. Little is known about how eIF2B mutations have a major effect on WM. We performed a transcriptomic analysis using fibroblasts of 10 eIF2B-mutated patients with a severe phenotype and 10 age matched patients with other types of LD in comparison to control fibroblasts. ANOVA was used to identify genes that were statistically significantly differentially expressed at basal state and after ER-stress. The pattern of differentially expressed genes between basal state and ER-stress did not differ significantly among each of the three conditions. However, 70 genes were specifically differentially expressed in eIF2B-mutated fibroblasts whatever the stress conditions tested compared to controls, 96% being under-expressed. Most of these genes were involved in mRNA regulation and mitochondrial metabolism. The 13 most representative genes, including genes belonging to the Heterogeneous Nuclear Ribonucleoprotein (HNRNP) family, described as regulators of splicing events and stability of mRNA, were dysregulated during the development of eIF2B-mutated brains. HNRNPH1, F and C mRNA were over-expressed in foetus but under-expressed in children and adult brains. The abnormal regulation of HNRNP expression in the brain of eIF2B-mutated patients was concomitant with splicing dysregulation of the main genes involved in glial maturation such as PLP1 for oligodendrocytes and GFAP in astrocytes. These findings demonstrate a developmental deregulation of splicing events in glial cells that is related to abnormal production of HNRNP, in eIF2B-mutated brains

Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms

Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing. Knowledge on white matter physiology and pathology has also dramatically built up. This led to the recognition that only few leukodystrophies are due to mutations in myelin- or oligodendrocyte-specific genes, and many are rather caused by defects in other white matter structural components, including astrocytes, microglia, axons and blood vessels. We here propose a novel classification of leukodystrophies that takes into account the primary involvement of any white matter component. Categories in this classification are the myelin disorders due to a primary defect in oligodendrocytes or myelin (hypomyelinating and demyelinating leukodystrophies, leukodystrophies with myelin vacuolization); astrocytopathies; leuko-axonopathies; microgliopathies; and leuko-vasculopathies. Following this classification, we illustrate the neuropathology and disease mechanisms of some leukodystrophies taken as example for each category. Some leukodystrophies fall into more than one category. Given the complex molecular and cellular interplay underlying white matter pathology, recognition of the cellular pathology behind a disease becomes crucial in addressing possible treatment strategies

Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect

The creatine transporter (CRTR) defect is a recently discovered cause of X-linked intellectual disability for which treatment options have been explored. Creatine monotherapy has not proved effective, and the effect of treatment with L-arginine is still controversial. Nine boys between 8 months and 10 years old with molecularly confirmed CRTR defect were followed with repeated 1H-MRS and neuropsychological assessments during 4–6 years of combination treatment with creatine monohydrate, L-arginine, and glycine. Treatment did not lead to a significant increase in cerebral creatine content as observed with H1-MRS. After an initial improvement in locomotor and personal-social IQ subscales, no lasting clinical improvement was recorded. Additionally, we noticed an age-related decline in IQ subscales in boys affected with the CRTR defect

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Regional climate model simulations for Europe at 6 and 0.2 k BP : sensitivity to changes in anthropogenic deforestation

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Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe