Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus.

PURPOSE: TNR, encoding Tenascin-R, is an extracellular matrix glycoprotein involved in neurite outgrowth and neural cell adhesion, proliferation and migration, axonal guidance, myelination, and synaptic plasticity. Tenascin-R is exclusively expressed in the central nervous system with highest expression after birth. The protein is crucial in the formation of perineuronal nets that ensheath interneurons. However, the role of Tenascin-R in human pathology is largely unknown. We aimed to establish TNR as a human disease gene and unravel the associated clinical spectrum. METHODS: Exome sequencing and an online matchmaking tool were used to identify patients with biallelic variants in TNR. RESULTS: We identified 13 individuals from 8 unrelated families with biallelic variants in TNR sharing a phenotype consisting of spastic para- or tetraparesis, axial muscular hypotonia, developmental delay, and transient opisthotonus. Four homozygous loss-of-function and four different missense variants were identified. CONCLUSION: We establish TNR as a disease gene for an autosomal recessive nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus and highlight the role of central nervous system extracellular matrix proteins in the pathogenicity of spastic disorders

Compositional response of Amazon forests to climate change.

Most of the planet's diversity is concentrated in the tropics, which includes many regions undergoing rapid climate change. Yet, while climate-induced biodiversity changes are widely documented elsewhere, few studies have addressed this issue for lowland tropical ecosystems. Here we investigate whether the floristic and functional composition of intact lowland Amazonian forests have been changing by evaluating records from 106 long-term inventory plots spanning 30 years. We analyse three traits that have been hypothesized to respond to different environmental drivers (increase in moisture stress and atmospheric CO2 concentrations): maximum tree size, biogeographic water-deficit affiliation and wood density. Tree communities have become increasingly dominated by large-statured taxa, but to date there has been no detectable change in mean wood density or water deficit affiliation at the community level, despite most forest plots having experienced an intensification of the dry season. However, among newly recruited trees, dry-affiliated genera have become more abundant, while the mortality of wet-affiliated genera has increased in those plots where the dry season has intensified most. Thus, a slow shift to a more dry-affiliated Amazonia is underway, with changes in compositional dynamics (recruits and mortality) consistent with climate-change drivers, but yet to significantly impact whole-community composition. The Amazon observational record suggests that the increase in atmospheric CO2 is driving a shift within tree communities to large-statured species and that climate changes to date will impact forest composition, but long generation times of tropical trees mean that biodiversity change is lagging behind climate change

Comprehensive characterization of protein 4.1 expression in epithelium of large intestine

The protein 4.1 family consists of four members, 4.1R, 4.1N, 4.1B and 4.1G, each encoded by a distinct gene. All 4.1 mRNAs undergo extensive alternative splicing. Functionally, they usually serve as adapters that link actin-based cytoskeleton to plasma membrane proteins. It has been reported that 4.1 proteins are expressed in most animal cell types and tissues including epithelial cells and epithelial tissues. However, the expression of 4.1 proteins in large intestine has not been well characterized. In the present study, we performed RT-PCR, western blot and immunohistochemistry analysis to characterize the transcripts, the protein expression and cellular localization of 4.1 proteins in the epithelia of mouse large intestine. We show that multiple transcripts derive from each gene, including eight 4.1R isoforms, four 4.1N isoforms, four 4.1B isoforms and six 4.1G isoforms. However, at the protein level, only one or two major bands were detected, implying that not all transcripts are translated and/or the proteins do not accumulate at detectable levels. Immunohistochemistry revealed that 4.1R, 4.1N and 4.1B are all expressed at the lateral membrane as well as cytoplasm of epithelial cells, suggesting a potentially redundant role of these proteins. Our findings not only provide new insights into the structure of protein 4.1 genes but also lay the foundation for future functional studies

Water table depth modulates productivity and biomass across Amazonian forests

Aim Water availability is the major driver of tropical forest structure and dynamics. Most research has focused on the impacts of climatic water availability, whereas remarkably little is known about the influence of water table depth and excess soil water on forest processes. Nevertheless, given that plants take up water from the soil, the impacts of climatic water supply on plants are likely to be modulated by soil water conditions. Location Lowland Amazonian forests. Time period 1971–2019. Methods We used 344 long-term inventory plots distributed across Amazonia to analyse the effects of long-term climatic and edaphic water supply on forest functioning. We modelled forest structure and dynamics as a function of climatic, soil-water and edaphic properties. Results Water supplied by both precipitation and groundwater affects forest structure and dynamics, but in different ways. Forests with a shallow water table (depth <5 m) had 18% less above-ground woody productivity and 23% less biomass stock than forests with a deep water table. Forests in drier climates (maximum cumulative water deficit < −160 mm) had 21% less productivity and 24% less biomass than those in wetter climates. Productivity was affected by the interaction between climatic water deficit and water table depth. On average, in drier climates the forests with a shallow water table had lower productivity than those with a deep water table, with this difference decreasing within wet climates, where lower productivity was confined to a very shallow water table. Main conclusions We show that the two extremes of water availability (excess and deficit) both reduce productivity in Amazon upland (terra-firme) forests. Biomass and productivity across Amazonia respond not simply to regional climate, but rather to its interaction with water table conditions, exhibiting high local differentiation. Our study disentangles the relative contribution of those factors, helping to improve understanding of the functioning of tropical ecosystems and how they are likely to respond to climate change