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Additional file 1: Fig. S1. Secondary structure prediction of GREB1L protein. The effect of the variant on secondary structure formation was examined using PSIPRED [1], a bioinformatic tool. Predicted secondary structures for the (A) wildtype and (B) mutant proteins. Blue rectangles were used to indicate the absence and presence of a helix at the mutation site of the wildtype and mutant proteins respectively. Red rectangles were used to highlight the sites where differences were observed...

In the context of a binary treatment, matching is a well-established approach in causal inference. However, in the context of a continuous treatment or exposure, matching is still underdeveloped. We propose an innovative matching approach to estimate an average causal exposure-response function under the setting of continuous exposures that relies on the generalized propensity score (GPS). Our approach maintains the following attractive features of matching: a) clear separation between the design and the analysis; b)...

A curvature detection method based on bogie attitude trajectory information fusion is proposed to improve the accuracy and real-time performance of track curvature detection. The running speed, yaw angular velocity, and roll angle of a bogie were measured to obtain horizontal running and roll attitude trajectories through curve fitting. Track superelevation and curvature were estimated from these trajectories, and the characteristics and mechanisms of the parameter estimation errors were analysed. Data fusion algorithms based on...

Additional file 2: Supplementary Fig. 2. Sanger sequencing of the PCDH15 gene. The sequence trace shows the PCDH15 variant, which is consistent with whole exome sequencing (WES) test results.

Additional file 1: Supplementary Fig. 1. Full-field electroretinography (ffERG) at presentation shows extinguished rod response, combined rod-cone response, cone response and 30 Hz flicker response in both eyes.

Abstract Background The assembly of the rhizomicrobiome, i.e., the microbiome in the soil adhering to the root, is influenced by soil conditions. Here, we investigated the core rhizomicrobiome of a wild plant species transplanted to an identical soil type with small differences in chemical factors and the impact of these soil chemistry differences on the core microbiome after long-term cultivation. We sampled three natural reserve populations of wild rice (i.e., in situ) and three populations...

The rarity of nitrogen (N)-fixing trees in frequently N-limited higher-latitude (here, > 35°) forests is a central biogeochemical paradox. One hypothesis for their rarity is that evolutionary constraints limit N-fixing tree diversity, preventing N-fixing species from filling available niches in higher-latitude forests. Here, we test this hypothesis using data from the USA and Mexico. N-fixing trees comprise only a slightly smaller fraction of taxa at higher vs. lower latitudes (8% vs. 11% of genera), despite...

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control spontaneous electrical activity in heart and brain. Binding of cAMP to the cyclic nucleotide-binding domain (CNBD) facilitates channel opening by relieving a tonic inhibition exerted by the CNBD. Despite high resolution structures of the HCN1 channel in the cAMP bound and unbound states, the structural mechanism coupling ligand binding to channel gating is unknown. Here we show that the recently identified helical HCN-domain (HCND) mechanically couples the CNBD and...

Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially...

There are two theories about how allocation of metabolic products occurs. The allometric biomass partitioning theory (APT) suggests that all plants follow common allometric scaling rules. The optimal partitioning theory (OPT) predicts that plants allocate more biomass to the organ capturing the most limiting resource. We used whole-plant harvests of mature and juvenile tropical deciduous trees, evergreen trees, and lianas and model simulations to address the following knowledge gaps: 1) Do mature lianas comply with...

Biodiversity is inherently multidimensional, encompassing taxonomic, functional, phylogenetic, genetic, landscape and many other elements of variability of life on the Earth. However, this fundamental principle of multidimensionality is rarely applied in research aimed at understanding biodiversity's value to ecosystem functions and the services they provide. This oversight means that our current understanding of the ecological and environmental consequences of biodiversity loss is limited primarily to what unidimensional studies have revealed. To address this issue, we...

Allele-specific expression (ASE) analysis, which quantifies the relative expression of two alleles in a diploid individual, is a powerful tool for identifying cis-regulated gene expression variations that underlie phenotypic differences among individuals. Existing methods for gene-level ASE detection analyze one individual at a time, therefore failing to account for shared information across individuals. Failure to accommodate such shared information not only reduces power, but also makes it difficult to interpret results across individuals. However, when...

Urban Norway rats (Rattus norvegicus) carry several pathogens transmissible to people. However, pathogen prevalence can vary across fine spatial scales (i.e., by city block). Using a population genomics approach, we sought to describe rat movement patterns across an urban landscape, and to evaluate whether these patterns align with pathogen distributions. We genotyped 605 rats from a single neighborhood in Vancouver, Canada and used 1,495 genome-wide single nucleotide polymorphisms to identify parent-offspring and sibling relationships using...

We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ∼5-fold and ∼7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity.

1. Sexual signals may be acquired or lost over evolutionary time, and are tempered in their exaggeration by natural selection. 2. In the Pacific field cricket, Teleogryllus oceanicus, a mutation (“flatwing”) causing loss of the sexual signal, the song, spread in < 20 generations in two of three Hawaiian islands where the crickets have been introduced. Flatwing (as well as some normal-wing) males behave as satellites, moving towards and settling near calling males to intercept...

Background: Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials. Methods: This prospective...

The study of pollen morphology has historically allowed evolutionary biologists to assess phylogenetic relationships among Angiosperms, as well as to better understand the fossil record. During this process, pollen has mainly been studied by discretizing some of its main characteristics such as size, shape, and exine ornamentation. One large plant clade in which pollen has been used this way for phylogenetic inference and character mapping is the order Myrtales, composed by the small families Alzateaceae,...

Microglia are a major cellular component of gliomas, and abundant in the centre of the tumour and at the infiltrative margins. While glioma is a notoriously infiltrative disease, the dynamics of microglia and glioma migratory patterns have not been well characterized. To investigate the migratory behaviour of microglia and glioma cells at the infiltrative edge, we performed two-colour time-lapse fluorescence microscopy of brain slices generated from a platelet-derived growth factor-B (PDGFB)-driven rat model of glioma,...

Tackling the conceptual grounds of how maps have been deployed as tools of imperial capitalist extraction, this essay critiques how the two-dimensional visualization of land has traditionally flattened the racial entanglement of the Caribbean archipelago. It explores how born-digital cartography can be used to open up a new sensory possibility for understanding space amplified by sonic and video technologies. The author embarked on the digital project *Unmapping the Caribbean* with her students and a team...

Real-time optical reflection of incident p-polarized light near Brewster’s angle shows that after drop-casting iron oxide nanoparticles (NPs) in heptane on top of a diethylene glycol (DEG) liquid substrate, an iron oxide NP layer forms at the DEG/heptane interface, and it self-limits to a monolayer even when there are excess NPs dispersed in the upper heptane phase. Most modes of NP self-assembly do not self-limit growth after the formation of a single monolayer. Observations are...

Objective: To develop, replicate, and validate an MRI-based quantitative measure of both cerebrovascular and neurodegeneration in Alzheimer’s disease for clinical and potentially research purposes. Methods. We used data from a cross-sectional and longitudinal community-based study of Medicare-eligible residents in northern Manhattan followed every 18-24 months (N=1,175, mean age=78 years). White matter hyperintensities, infarcts, hippocampal volumes, and cortical thicknesses were quantified from MRI and combined to generate an MRI measure associated with episodic memory. The combined...

Ammonites have disparate adult morphologies indicative of diverse ecological niches, but ammonite hatchlings are small (~1 mm diameter), which raises questions about the similarity of egg incubation and hatchling life mode in ammonites. Modern Nautilus is sometimes used as a model organism for understanding ammonites, but despite their outward similarities, the groups are only distantly related. Trends in ammonite diversity and extinction vulnerability in the fossil record contrast starkly with those of nautilids, and embryonic...

The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen (N)-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest-inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area...

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers....