Genetic Interaction between Mfrp and Adipor1 Mutations Affect Retinal Disease Phenotypes

Adipor1tm1Dgen and Mfrprd6 mutant mice share similar eye disease characteristics. Previously, studies established a functional relationship of ADIPOR1 and MFRP proteins in maintaining retinal lipidome homeostasis and visual function. However, the independent and/or interactive contribution of both genes to similar disease phenotypes, including fundus spots, decreased axial length, and photoreceptor degeneration has yet to be examined. We performed a gene-interaction study where homozygous Adipor1tm1Dgen and Mfrprd6 mice were bred together and the resulting doubly heterozygous F1 offspring were intercrossed to produce 210 F2 progeny. Four-month-old mice from all nine genotypic combinations obtained in the F2 generation were assessed for white spots by fundus photo documentation, for axial length by caliper measurements, and for photoreceptor degeneration by histology. Two-way factorial ANOVA was performed to study individual as well as gene interaction effects on each phenotype. Here, we report the first observation of reduced axial length in Adipor1tmlDgen homozygotes. We show that while Adipor1 and Mfrp interact to affect spotting and degeneration, they act independently to control axial length, highlighting the complex functional association between these two genes. Further examination of the molecular basis of this interaction may help in uncovering mechanisms by which these genes perturb ocular homeostasis

Increased Connexin36 Phosphorylation in AII Amacrine Cell Coupling of the Mouse Myopic Retina.

Myopia is a substantial public health problem worldwide. In the myopic retina, distant images are focused in front of the photoreceptors. The cells and mechanisms for retinal signaling that account either for emmetropization (i.e., normal refraction) or for refractive errors have remained elusive. Gap junctions play a key component in enhancement of signal transmission in visual pathways. AII amacrine cells (ACs), coupled by connexin36, segregate signals into ON and OFF pathways. Coupling between AII ACs is actively modulated through phosphorylation at serine 293 via dopamine in the mouse retina. In this study, form deprivation mouse myopia models were used to evaluate the expression patterns of connexin36-positive plaques (structural assay) and the state of connexin36 phosphorylation (functional assay) in AII ACs, which was green fluorescent protein-expressing in the Fam81a mouse line. Single-cell RNA sequencing showed dopaminergic synapse and gap junction pathways of AII ACs were downregulated in the myopic retina, although Gjd2 mRNA expression remained the same. Compared with the normal refractive eye, phosphorylation of connexin36 was increased in the myopic retina, but expression of connexin36 remained unchanged. This increased phosphorylation of Cx36 could indicate increased functional gap junction coupling of AII ACs in the myopic retina, a possible adaptation to adjust to the altered noisy signaling status

Elevational distribution and seasonal dynamics of alpine soil prokaryotic communities

The alpine grassland ecosystem is a biodiversity hotspot of plants on the Qinghai-Tibetan Plateau, where rapid climate change is altering the patterns of plant biodiversity along elevational and seasonal gradients of environments. However, how belowground microbial biodiversity changes along elevational gradient during the growing season is not well understood yet. Here, we investigated the elevational distribution of soil prokaryotic communities by using 16S rRNA amplicon sequencing along an elevational gradient between 3,200 and 4,200 m, and a seasonal gradient between June and September in the Qinghai-Tibetan alpine grasslands. First, we found soil prokaryotic diversity and community composition significantly shifted along the elevational gradient, mainly driven by soil temperature and moisture. Species richness did not show consistent elevational trends, while those of evenness declined with elevation. Copiotrophs and symbiotic diazotrophs declined with elevation, while oligotrophs and AOB increased, affected by temperature. Anaerobic or facultatively anaerobic bacteria and AOA were hump-shaped, mainly influenced by moisture. Second, seasonal patterns of community composition were mainly driven by aboveground biomass, precipitation, and soil temperature. The seasonal dynamics of community composition indicated that soil prokaryotic community, particularly Actinobacteria, was sensitive to short-term climate change, such as the monthly precipitation variation. At last, dispersal limitation consistently dominated the assembly process of soil prokaryotic communities along both elevational and seasonal gradients, especially for those of rare species, while the deterministic process of abundant species was relatively higher at drier sites and in drier July. The balance between deterministic and stochastic processes in abundant subcommunities might be strongly influenced by water conditions (precipitation/moisture). Our findings suggest that both elevation and season can alter the patterns of soil prokaryotic biodiversity in alpine grassland ecosystem of Qinghai-Tibetan Plateau, which is a biodiversity hotspot and is experiencing rapid climate change. This work provides new insights into the response of soil prokaryotic communities to changes in elevation and season, and helps us understand the temporal and spatial variations in such climate change-sensitive regions

Downregulation of Long Non-coding RNA FALEC Inhibits Gastric Cancer Cell Migration and Invasion Through Impairing ECM1 Expression by Exerting Its Enhancer-Like Function

Long non-coding RNAs (lncRNAs) have been shown to play important roles in many human diseases. However, their functions and mechanisms in tumorigenesis and development remain largely unknown. Here, we demonstrated that focally amplified lncRNA in epithelial cancer (FALEC) was upregulated and significantly correlated with lymph node metastasis, TNM stage in gastric cancer (GC). Further experiments revealed that FALEC knockdown significantly inhibited GC cells migration and invasion in vitro. Mechanistic investigations demonstrated that small interfering RNA-induced silencing of FALEC decreased expression of the nearby gene extracellular matrix protein 1 (ECM1) in cis. Additionally, ECM1 and FALEC expression were positively correlated, and high levels of ECM1 predicted shorter survival time in GC patients. Our results suggest that the downregulation of FALEC significantly inhibited the migration and invasion of GC cells through impairing ECM1 expression by exerting an enhancer-like function. Our work provides valuable information and a novel promising target for developing new therapeutic strategies in GC

Gray Matter Atrophy Is Associated With Cognitive Impairment in Patients With Presbycusis: A Comprehensive Morphometric Study

Presbycusis (PC) is characterized by bilateral sensorineural hearing loss at high frequencies and speech-perception difficulties in noisy environments and has a strikingly detrimental impact on cognitive function. As the neural consequences of PC may involve the whole brain, we hypothesized that patients with PC would show structural alterations not only in the auditory cortex but also in the cortexes involved in cognitive function. The purpose of this study was to use surface-based morphometry (SBM) analysis to elucidate whole-brain structural differences between patients with PC and age-matched normal hearing controls. Three-dimensional T1-weighted MR images of 26 patients with mild PC and 26 age-, sex- and education-matched healthy controls (HCs) were acquired. All participants underwent a battery of neuropsychological tests. Our results revealed gray matter atrophy in several auditory cortical areas, nodes of the default mode network (DMN), including the bilateral precuneus and inferior parietal lobule, the right posterior cingulate cortex (PCC), and the right insula of patients with PC compared to that in the HCs. Our findings also revealed that hearing loss was associated with reduced gray matter volume in the right primary auditory cortex of patients with PC. Moreover, structural alterations in the nodes of the DMN were associated with cognitive impairments in PC patients. Additionally, this study provides evidence that a thicker right insula is associated with better speech perception in patients with PC. Based on these findings, we argue that the onset of PC seems to trigger its own cascade of conditions, including a need for increased cognitive resources during speech comprehension, which might lead to auditory and cognition-related cortical reorganization

GBAS Ionospheric Anomaly Monitoring Based on a Two-Step Approach

As one significant component of space environmental weather, the ionosphere has to be monitored using Global Positioning System (GPS) receivers for the Ground-Based Augmentation System (GBAS). This is because an ionospheric anomaly can pose a potential threat for GBAS to support safety-critical services. The traditional code-carrier divergence (CCD) methods, which have been widely used to detect the variants of the ionospheric gradient for GBAS, adopt a linear time-invariant low-pass filter to suppress the effect of high frequency noise on the detection of the ionospheric anomaly. However, there is a counterbalance between response time and estimation accuracy due to the fixed time constants. In order to release the limitation, a two-step approach (TSA) is proposed by integrating the cascaded linear time-invariant low-pass filters with the adaptive Kalman filter to detect the ionospheric gradient anomaly. The performance of the proposed method is tested by using simulated and real-world data, respectively. The simulation results show that the TSA can detect ionospheric gradient anomalies quickly, even when the noise is severer. Compared to the traditional CCD methods, the experiments from real-world GPS data indicate that the average estimation accuracy of the ionospheric gradient improves by more than 31.3%, and the average response time to the ionospheric gradient at a rate of 0.018 m/s improves by more than 59.3%, which demonstrates the ability of TSA to detect a small ionospheric gradient more rapidly

Ionosphere-Constrained Triple-Frequency Cycle Slip Fixing Method for the Rapid Re-Initialization of PPP

The re-initialization of precise point positioning (PPP) can be avoided by cycle slip detection and correction. Ionospheric delay is critical for cycle slip detection and correction, especially for a long data gap. The frequency diversity from GNSS modernization provides the potential for mitigating the impact of ionospheric delay on cycle slip detection and correction. The proposed method constructs the extra-wide lane (EWL), the wide lane (WL), and the narrow lane (NL) epoch-differenced linear combinations based on the ionosphere constrain criterion, so as to determine the undifferenced cycle slips from the cascading ambiguity resolution. The experiment results show that the cycle slips can be fixed correctly even though cycle slips occur in all the available carrier phase observations, and the 3 min data gaps can be merged without high precision positioning continuity loss. The kinematic experiment shows that the instantaneous re-initialization can be achieved with the proposed method