Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays;mild to severe intellectual disability;autistic features;seizures;behavioral and movement abnormalities;hypotonia;and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system

Carbon-sensitive pedotransfer functions for plant available water

Currently accepted pedotransfer functions show negligible effect of management-induced changes to soil organic carbon (SOC) on plant available water holding capacity (θAWHC), while some studies show the ability to substantially increase θAWHC through management. The Soil Health Institute\u27s North America Project to Evaluate Soil Health Measurements measured water content at field capacity using intact soil cores across 124 long-term research sites that contained increases in SOC as a result of management treatments such as reduced tillage and cover cropping. Pedotransfer functions were created for volumetric water content at field capacity (θFC) and permanent wilting point (θPWP). New pedotransfer functions had predictions of θAWHC that were similarly accurate compared with Saxton and Rawls when tested on samples from the National Soil Characterization database. Further, the new pedotransfer functions showed substantial effects of soil calcareousness and SOC on θAWHC. For an increase in SOC of 10 g kg–1 (1%) in noncalcareous soils, an average increase in θAWHC of 3.0 mm 100 mm–1 soil (0.03 m3 m–3) on average across all soil texture classes was found. This SOC related increase in θAWHC is about double previous estimates. Calcareous soils had an increase in θAWHC of 1.2 mm 100 mm–1 soil associated with a 10 g kg–1 increase in SOC, across all soil texture classes. New equations can aid in quantifying benefits of soil management practices that increase SOC and can be used to model the effect of changes in management on drought resilience

Linking soil microbial community structure to potential carbon mineralization: A continental scale assessment of reduced tillage

Potential carbon mineralization (Cmin) is a commonly used indicator of soil health, with greater Cmin values interpreted as healthier soil. While Cmin values are typically greater in agricultural soils managed with minimal physical disturbance, the mechanisms driving the increases remain poorly understood. This study assessed bacterial and archaeal community structure and potential microbial drivers of Cmin in soils maintained under various degrees of physical disturbance. Potential carbon mineralization, 16S rRNA sequences, and soil characterization data were collected as part of the North American Project to Evaluate Soil Health Measurements (NAPESHM). Results showed that type of cropping system, intensity of physical disturbance, and soil pH influenced microbial sensitivity to physical disturbance. Furthermore, 28% of amplicon sequence variants (ASVs), which were important in modeling Cmin, were enriched under soils managed with minimal physical disturbance. Sequences identified as enriched under minimal disturbance and important for modeling Cmin, were linked to organisms which could produce extracellular polymeric substances and contained metabolic strategies suited for tolerating environmental stressors. Understanding how physical disturbance shapes microbial communities across climates and inherent soil properties and drives changes in Cmin provides the context necessary to evaluate management impacts on standardized measures of soil microbial activity

USING THE COMPREHENSIVE ASSESSMENT OF SOIL HEALTH TO ASSESS REMNANT TALLGRASS PRAIRIE SOILS AS A TARGET FOR FUTURE SOIL RESTORATION

50 pagesThe planet’s arable soils are rapidly degrading, primarily through mismanagement, erosion, and pollution. In contrast, some of the most fertile soils in the world lie under grasslands, such as in the Central Plains region of the United States. These soils were developed over thousands of years through wind depositions and through the deep roots of native grasses and forbs, each year depositing the organic matter and carbon of old roots under the surface. The eastern edge of US grasslands is occupied by Tallgrass Prairie, 98% of which has been converted to row crops and human use. There remains, among these soils, small remnants which have remained uncultivated or plowed, and which are likely the best remaining examples of grassland soils from before modern agriculture. To improve and preserve the agricultural soils throughout the Midwest, it is essential to thoroughly understand the soil properties of these remnant soils. Currently the most widely recognized and comprehensive suite of soil tests available for analyzing chemical, physical, and biological aspects of soil is the Comprehensive Assessment of Soil Health offered by the Cornell Soil Health Laboratory (CSHL). Multiple government and research groups use this testing service for the quantification of soil health properties. The goals of this study are to use Cornell University’s Comprehensive Assessment of Soil Health tools to: 1) evaluate the soil health of remnant tallgrass prairies in Nebraska, by quantifying a suite of relevant physical, chemical, and biological soil properties collected at multiple remnant sites; 2) compare the data from these remnant grasslands with comparable data collected in nearby agricultural fields to determine the degree and type of soil degradation which may have occurred there; and 3) use the profile characteristics of the remnant soils as a benchmark for evaluating soil health of samples derived from a region-wide data base for agricultural soils of collected from former prairies throughout the Great Plains. In the Nebraska Tallgrass Prairie region, nine research sites were identified. Five remnant sites were paired with one of four nearby agricultures sites that had a similar soil type, slope, and elevation. At each site, five subsamples were collected at 0-15 cm and at 15-30 cm soil depths. The samples were analyzed for soil texture, available water capacity, organic matter percentage, soil protein, soil respiration, active carbon, pH, total carbon, total nitrogen macro and micronutrients. The data analyses were conducted using R Studio, and the results of the remnant sites and of the agricultural sites were compared: 1) with each other, and 2) with selected samples from the CSHL Prairie State Database (PSD). There were significant differences between the remnant soils and the agricultural soils at 0-15 cm. Differences were most pronounced in the biological soil properties, with remnant soils exhibiting higher values among soil health properties that measure soil functional capacity. This pattern was also evident in the physical soil properties, although the differences were not as pronounced. In the chemical analyses, higher nutrient concentrations were found in the remnant sites than in the agricultural sites, apart from phosphorous, which was significantly higher in the agricultural sites. Similar patterns were found in the samples from 15-30 cm depth, although less pronounced. Pearson’s Correlation revealed significant correlations among the biological indicators, particularly among carbon-related soil properties. In addition, a Principal Component Analysis identified associations among indicators strongly associated with microbial activity and organic matter quality. Comparison of the Nebraska samples with the Prairie Soils from the broader CSHL data base was especially insightful as soils from the remnant sites had higher soil health indicators for every property measured, except phosphorous, iron and zinc. In general, this study indicated serious degradation in the agricultural soils as compared with the remnants, with total nitrogen showing the highest difference, followed by various forms of carbon. The comparison of remnant prairie sites with agricultural sites in eastern Nebraska quantified what is apparently a breakdown of healthy soil functions in active agricultural land, as a result of long-term agricultural practices. The remnant soil health profiles presented here can therefore serve as a reference for guiding management and restoration of agricultural systems throughout the Tallgrass Prairie Region. This study also highlights the powerful approach of using the CSHL comprehensive soil analyses in combination with remnant grasslands as a diagnostic tool for other types of grasslands across the Great Plains and globally

Immune defence, dispersal and local adaptation

To determine the influence of dispersal on the expression of immune traits, we conducted a reciprocal transfer experiment. Chorthippus biguttulus grasshoppers from two populations were released as juveniles into their native and transfer environments. After recapture as adults, we found that an immune trait, the amount of phagocytically active cells, was significantly reduced in the transfer environments. In contrast, adult body mass differed between the two habitats, but was not reduced in the transfer environments. The results suggest that dispersal to a new environment can reduce the expression of immune traits, while otherwise not influencing body condition. One reason for such an effect could be that the parasite community in the foreign environment might be relatively maladapted, which would lead to reduced demands for resource allocation to immune traits

Ecological insights into soil health according to the genomic traits and environment-wide associations of bacteria in agricultural soils

Abstract Soil microbiomes are sensitive to current and previous soil conditions, and bacterial ‘bioindicators’ of biological, physical, and chemical soil properties have considerable potential for soil health assessment. However, the lack of ecological or physiological information for most soil microorganisms limits our ability to interpret the associations of bioindicators and, thus, their utility for guiding management. We identified bioindicators of tillage intensity and twelve soil properties used to rate soil health using a 16S rRNA gene-based survey of farmland across North America. We then inferred the genomic traits of bioindicators and evaluated their environment-wide associations (EWAS) with respect to agricultural management practice, disturbance, and plant associations with 89 studies from agroecosystems. Most bioindicators were either positively correlated with biological properties (e.g., organic matter) or negatively correlated with physical and chemical properties. Higher soil health ratings corresponded with smaller genome size and higher coding density, while lower ratings corresponded with larger genomes and higher rrn copy number. Community-weighted genome size explained most variation in health ratings. EWAS linked prominent bioindicators with the impacts of environmental disturbances. Our findings provide ecological insights into bioindicators of soil properties relevant to soil health management, illustrating the tight coupling of microbiome and soil function

TRansfusion strategies in Acute brain INjured patients (TRAIN): a prospective multicenter randomized interventional trial protocol

Background: Although blood transfusions can be lifesaving in severe hemorrhage, they can also have potential complications. As anemia has also been associated with poor outcomes in critically ill patients, determining an optimal transfusion trigger is a real challenge for clinicians. This is even more important in patients with acute brain injury who were not specifically evaluated in previous large randomized clinical trials. Neurological patients may be particularly sensitive to anemic brain hypoxia because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue oxygen demand. Methods: We described herein the methodology of a prospective, multicenter, randomized, pragmatic trial comparing two different strategies for red blood cell transfusion in patients with acute brain injury: a “liberal” strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL and a “restrictive” approach in which the aim is to maintain Hb concentrations greater than 7 g/dL. The target population is patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH). The primary outcome is the unfavorable neurological outcome, evaluated using the extended Glasgow Outcome Scale (eGOS) of 1–5 at 180 days after the initial injury. Secondary outcomes include, among others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the occurrence of extra-cerebral organ dysfunction/failure, and the development of any infection or thromboembolic events. The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome from 50 to 39% between groups (397 patients in each arm). The study was initiated in 2016 in several ICUs and will be completed in December 2022. Discussion: This trial will assess the impact of a liberal versus conservative strategy of blood transfusion in a large cohort of critically ill patients with a primary acute brain injury. The results of this trial will help to improve blood product and transfusion use in this specific patient population and will provide additional data in some subgroups of patients at high risk of brain ischemia, such as those with intracranial hypertension or cerebral vasospasm. Trial registration: ClinicalTrials.gov NCT02968654

Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct.

Macrophages adopt an alternatively activated phenotype (AAMs) when activated by the interleukin-4receptor(R)α. AAMs can be derived either from proliferation of tissue resident macrophages or recruited inflammatory monocytes, but it is not known whether these different sources generate AAMs that are phenotypically and functionally distinct. By transcriptional profiling analysis, we show here that, although both monocyte and tissue-derived AAMs expressed high levels of Arg1, Chi3l3, and Retnla, only monocyte-derived AAMs up-regulated Raldh2 and PD-L2. Monocyte-derived AAMs were also CX3CR1-green fluorescent protein (GFP)(high) and expressed CD206, whereas tissue-derived AAMs were CX3CR1-GFP and CD206 negative. Monocyte-derived AAMs had high levels of aldehyde dehydrogenase activity and promoted the differentiation of FoxP3(+) cells from naïve CD4(+) cells via production of retinoic acid. In contrast, tissue-derived AAMs expressed high levels of uncoupling protein 1. Hence monocyte-derived AAM have properties associated with immune regulation, and the different physiological properties associated with AAM function may depend on the distinct lineage of these cells