Novel <em>GFM2</em> variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits

Mitochondrial diseases are characterised by clinical, molecular and functional heterogeneity, reflecting their bi-genomic control. The nuclear gene GFM2 encodes mtEFG2, a protein with an essential role during the termination stage of mitochondrial translation. We present here two unrelated patients harbouring different and previously unreported compound heterozygous (c.569G&gt;A, p.(Arg190Gln); c.636delA, p.(Glu213Argfs*3)) and homozygous (c.275A&gt;C, p.(Tyr92Ser)) recessive variants in GFM2 identified by whole exome sequencing (WES) together with histochemical and biochemical findings to support the diagnoses of pathological GFM2 variants in each case. Both patients presented similarly in early childhood with global developmental delay, raised CSF lactate and abnormalities on cranial MRI. Sanger sequencing of familial samples confirmed the segregation of bi-allelic GFM2 variants with disease, while investigations into steady-state mitochondrial protein levels revealed respiratory chain subunit defects and loss of mtEFG2 protein in muscle. These data demonstrate the effects of defective mtEFG2 function, caused by previously unreported variants, confirming pathogenicity and expanding the clinical phenotypes associated with GFM2 variants

Factors influencing epiphytic bryophyte and lichen species richness at different spatial scales in managed temperate forests

The effect of management related factors on species richness of epiphytic bryophytes and lichens was studied in managed deciduous-coniferous mixed forests in Western-Hungary. At the stand level, the potential explanatory variables were tree species composition, stand structure, microclimate and light conditions, landscape and historical variables; while at tree level host tree species, tree size and light were studied. Species richness of the two epiphyte groups was positively correlated. Both for lichen and bryophyte plot level richness, the composition and diversity of tree species and the abundance of shrub layer were the most influential positive factors. Besides, for bryophytes the presence of large trees, while for lichens amount and heterogeneity of light were important. Tree level richness was mainly determined by host tree species for both groups. For bryophytes oaks, while for lichens oaks and hornbeam turned out the most favourable hosts. Tree size generally increased tree level species richness, except on pine for bryophytes and on hornbeam for lichens. The key variables for epiphytic diversity of the region were directly influenced by recent forest management; historical and landscape variables were not influential. Forest management oriented to the conservation of epiphyte s should focus on: (i) the maintenance of tree species diversity in mixed stands; (ii) increment the proportion of deciduous trees (mainly oaks); (iii) conserving large trees within the stands; (iv) providing the presence of shrub and regeneration layer; (v) creating heterogeneous light conditions. For these purposes tree selection and selective cutting management seem more appropriate than shelterwood system

Development of Secondary Woodland in Oak Wood Pastures Reduces the Richness of Rare Epiphytic Lichens

Wooded pastures with ancient trees were formerly abundant throughout Europe, but during the last century, grazing has largely been abandoned often resulting in dense forests. Ancient trees constitute habitat for many declining and threatened species, but the effects of secondary woodland on the biodiversity associated with these trees are largely unknown. We tested for difference in species richness, occurrence, and abundance of a set of nationally and regionally red-listed epiphytic lichens between ancient oaks located in secondary woodland and ancient oaks located in open conditions. We refined the test of the effect of secondary woodland by also including other explanatory variables. Species occurrence and abundance were modelled jointly using overdispersed zero-inflated Poisson models. The richness of the red-listed lichens on ancient oaks in secondary woodland was half of that compared with oaks growing in open conditions. The species-level analyses revealed that this was mainly the result of lower occupancy of two of the study species. The tree-level abundance of one species was also lower in secondary woodland. Potential explanations for this pattern are that the study lichens are adapted to desiccating conditions enhancing their population persistence by low competition or that open, windy conditions enhance their colonisation rate. This means that the development of secondary woodland is a threat to red-listed epiphytic lichens. We therefore suggest that woody vegetation is cleared and grazing resumed in abandoned oak pastures. Importantly, this will also benefit the vitality of the oaks

Local Abundance Patterns of Noctuid Moths in Olive Orchards: Life-History Traits, Distribution Type and Habitat Interactions

Local species abundance is related to range size, habitat characteristics, distribution type, body size, and life-history variables. In general, habitat generalists and polyphagous species are more abundant in broad geographical areas. Underlying this, local abundance may be explained from the interactions between life-history traits, chorological pattern, and the local habitat characteristics. The relationship within taxa between life-history traits, distribution area, habitat characteristics, and local abundance of the noctuid moth (Lepidoptera: Noctuidae) assemblage in an olive orchard, one of the most important agro-ecosystems in the Mediterranean basin, was analyzed. A total of 66 species were detected over three years of year-round weekly samplings using the light-trap method. The life-history traits examined and the distribution type were found to be related to the habitat-species association, but none of the biological strategies defined from the association to the different habitats were linked with abundance. In contrast to general patterns, dispersal ability and number of generations per year explained differences in abundance. The relationships were positive, with opportunistic taxa that have high mobility and several generations being locally more abundant. In addition, when the effect of migrant species was removed, the distribution type explained abundance differences, with Mediterranean taxa (whose baricenter is closer to the studied area) being more abundant

GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands

GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board

The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics, and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals: the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%), and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%), and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%), and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P=0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%); motor delay with non-ambulance (64%); and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P=0.003), non-ambulance (P=0.035), ongoing enteral feeds (P<0.001), and cortical visual impairment (P=0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs; provide insights into their neurological basis; and, vitally, enable meaningful genetic counselling for affected individuals and their families

Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty

This study explores how researchers’ analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers’ expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team’s workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers’ results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings