Project description:In this work we show that in genome-wide association studies (GWAS) there is a strong bias favoring of genes covered by larger numbers of SNPs. Thus, we state here that there is a need for correction for such bias when performing downstream gene-level analysis, e.g. pathway analysis and gene-set analysis. We investigate several methods of obtaining gene level statistical significance in GWAS, and compare their effectiveness in correcting such bias. We also propose a simple algorithm based on first order statistic that corrects such bias.
Project description:Since plant organs sense their environment locally, gradients of micro-climates in the plant shoot may induce spatial variability in the physiological state of the plant tissue and hence secondary metabolism. Therefore, plant architecture, which affects micro-climate in the shoot, may considerably affect the uniformity of cannabinoids in the Cannabis sativa plant, which has significant pharmaceutical and economic importance. Variability of micro-climates in plant shoots intensifies with the increase in plant size, largely due to an increase in inter-shoot shading. In this study, we therefore focused on the interplay between shoot architecture and the cannabinoid profile in large cannabis plants, ~2.5 m in height, with the goal to harness architecture modulation for the standardization of cannabinoid concentrations in large plants. We hypothesized that (i) a gradient of light intensity along the plants is accompanied by changes to the cannabinoid profile, and (ii) manipulations of plant architecture that increase light penetration to the plant increase cannabinoid uniformity and yield biomass. To test these hypotheses, we investigated effects of eight plant architecture manipulation treatments involving branch removals, defoliation, and pruning on plant morpho-physiology, inflorescence yield, cannabinoid profile, and uniformity. The results revealed that low cannabinoid concentrations in inflorescences at the bottom of the plants correlate with low light penetration, and that increasing light penetration by defoliation or removal of bottom branches and leaves increases cannabinoid concentrations locally and thereby through spatial uniformity, thus supporting the hypotheses. Taken together, the results reveal that shoot architectural modulation can be utilized to increase cannabinoid standardization in large cannabis plants, and that the cannabinoid profile in an inflorescence is an outcome of exogenous and endogenous factors.
Project description:This study explored whether there is a gender difference in letter-sound knowledge when children start at school. 485 children aged 5-6 years completed assessment of letter-sound knowledge, i.e., large letters; sound of large letters; small letters; sound of small letters. The findings indicate a significant difference between girls and boys in all four factors tested in this study in favor of the girls. There are still no clear explanations to the basis of a presumed gender difference in letter-sound knowledge. That the findings have origin in neuro-biological factors cannot be excluded, however, the fact that girls probably have been exposed to more language experience/stimulation compared to boys, lends support to explanations derived from environmental aspects.
Project description:Visual performance of human observers depends not only on the optics of the eye and early sensory encoding but also on subsequent cortical processing and representations. In two experiments, we demonstrated that motion adaptation can enhance as well as impair visual acuity. Observers who experienced an expanding motion aftereffect exhibited improved letter recognition, whereas observers who experienced a contracting motion aftereffect showed impaired letter recognition. We conclude that illusory enlargement and shrinkage of a visual stimulus can modulate visual acuity.
Project description:BackgroundIntracavernous injection (ICI) of adipose-derived stem cells (ADSCs) has been demonstrated promising for neurogenic erectile dysfunction (ED). However, due to the sponge-like structure of corpus cavernosum (CC) with abundant vessels, ICI was indeed like intravenous injection. Thus, the cell escaping may be a concern of safety and limited therapy, but the issue has not been clearly demonstrated yet.MethodsSuspensions of free ADSCs (FAs) and ADSCs-based spheroids (ASs) with suitable size were intracavernously injected at doses of 0.5, 1, 2, or 4 million cells. The cell loss and safety after ICI, erectile function and histopathologic change, etc. were analyzed with multimodality of methods.FindingsMost FAs escaped from sponge-like CC after ICI due to their small size, weakening stem-cell therapeutic efficacy. Worse still, the escaped cells were shown to cause widespread pulmonary embolism (PE), and even death in some animals. Further, it was founded that the therapeutic effect of FAs may be ascribed to the larger cell clusters which spontaneously aggregated before ICI and were trapped within CC after ICI. In comparison, cell loss and PE were significantly avoided by transplanting ASs. Importantly, better therapeutic outcomes were detected after ICI of ASs when compared to FAs with the same cell number.InterpretationTransplantation of size-specific ASs instead of single-cell suspension of FAs for neurogenic ED may be a wiser choice to achieve steady therapeutic outcome and to reduce risks for the future clinical application. FUND: This work was supported by the National Natural Science Foundation of China (81701432) (to Y. Xu). Youth Training Project for Medical science (16QNP129) and Beijing Nova Program of science and technology (Z171100001117115) (to Z. Liu).
Project description:Many hippocampal cell types are characterized by a progressive increase in scale along the dorsal-to-ventral axis, such as in the cases of head-direction, grid and place cells. Also located in the medial entorhinal cortex (MEC), border cells would be expected to benefit from such scale modulations. However, this phenomenon has not been experimentally observed. Grid cells in the MEC of mammals integrate velocity related signals to map the environment with characteristic hexagonal tessellation patterns. Due to the noisy nature of these input signals, path integration processes tend to accumulate errors as animals explore the environment, leading to a loss of grid-like activity. It has been suggested that border-to-grid cells' associations minimize the accumulated grid cells' error when rodents explore enclosures. Thus, the border-grid interaction for error minimization is a suitable scenario to study the effects of border cell scaling within the context of spatial representation. In this study, we computationally address the question of (i) border cells' scale from the perspective of their role in maintaining the regularity of grid cells' firing fields, as well as (ii) what are the underlying mechanisms of grid-border associations relative to the scales of both grid and border cells. Our results suggest that for optimal contribution to grid cells' error minimization, border cells should express smaller firing fields relative to those of the associated grid cells, which is consistent with the hypothesis of border cells functioning as spatial anchoring signals.
Project description:This study evaluated whether worsened outcomes in sex mismatch are related to mismatch of organ size in heart transplantation.Sizing for organ allocation in heart transplantation currently incorporates only body weight differences between the donor and recipient. Weight correlates poorly to cardiac size, and donor–recipient weight differences are not associated with differential survival. Heart size correlates with sex, and donor–recipient sex mismatch conveys worse-than-expected outcomes.We performed a retrospective cohort study of 31,634 donor–recipient adult heart transplant pairings from the United Network for Organ Sharing transplantation registry. We used predictive models to calculate the predicted total heart mass (pHM) for recipient and donor pairs. We assessed organ size mismatch by calculating the percent difference between the donor and recipient pHM as [(pHM(recipient) – pHM(donor))/(pHM(recipient))]*100.The most-undersized pHM septile demonstrated higher mortality during the first year post-transplantation (hazard ratio [HR]: 1.27; p < 0.001), which remained robust in adjusted models (HR: 1.25; p = 0.03). Survival did not vary across septiles of weight differences. On univariate analysis, sex mismatch was associated with higher mortality in male patients, but not in female patients. Controlling for differences in pHM reversed these associations. Adjusted models demonstrated worse survival associated with sex mismatch in female patients (1-year HR: 1.28; p = 0.02) but no difference in male patients (1-year HR, 1.00; p = 1.0).Differences in donor–recipient pHM modulated the survival associated with donor–recipient sex mismatch and identified donor heart undersizing as an otherwise occult and potentially preventable cause of mortality following orthotopic heart transplantation.
Project description:Microcystic and macrocystic lymphatic malformations are similar but clinically distinct infantile malformations, with distinct clinical responses and prognoses. In this study, we identify considerable differences in gene expression between the microcystic and macrocystic malformation subtypes with respect to healthy tissue.