Nucleus-independent transgenerational small RNA inheritance in Caenorhabditis elegans.

In Caenorhabditis elegans worms, epigenetic information transmits transgenerationally. Still, it is unknown whether the effects transfer to the next generation inside or outside of the nucleus. Here, we use the tractability of gene-specific double-stranded RNA-induced silencing to demonstrate that RNA interference can be inherited independently of any nuclear factors via mothers that are genetically engineered to transmit only their ooplasm but not the oocytes' nuclei to the next generation. We characterize the mechanisms and, using RNA sequencing, chimeric worms, and sequence polymorphism between different isolates, identify endogenous small RNAs which, similarly to exogenous siRNAs, are inherited in a nucleus-independent manner. From a historical perspective, these results might be regarded as partial vindication of discredited cytoplasmic inheritance theories from the 19th century, such as Darwin's "pangenesis" theory.

Functional and anatomical outcomes of fovea on, fovea off and fovea-splitting rhegmatogenous retinal detachment.

PURPOSE: To compare the anatomical and functional outcomes of fovea-on, fovea-off, and fovea-split rhegmatogenous retinal detachment (RRD). METHODS: Retrospective case series of consecutive patients diagnosed with RRD and treated with only pars plana vitrectomy (PPV). Preoperative and postoperative optical coherence tomography (OCT) and functional outcomes were obtained prior to and 6 months after surgery. RRD extending to the edge of the fovea on OCT was termed fovea-split RRD. RESULTS: A total of 152 eyes were included, out of which 89 eyes presented with a fovea-off, 36 with a fovea-on, and 27 with a fovea-split RRD. The mean visual acuity (VA) preoperatively was 1.32 ± 0.58 logMAR (20/400 equivalent on Snellen chart), 0.19 ± 0.20 (20/30), and 0.71 ± 0.56 (20/100) for the fovea-off, fovea-on, and fovea-split groups, respectively (p < 0.001). The mean VA at 6 months of follow-up significantly improved for the fovea-split and fovea-off groups to 0.54 ± 0.79 (20/70) (p < 0.001) and 0.45 ± 0.29 (20/50) (p = 0.01), respectively, and remained stable for the fovea-on group 0.24 ± 0.20 (20/30) (p = 0.25). Differences in alterations of the outer retinal layers (p < 0.001) and in the in-segment/outer-segment ratio (p < 0.001) were found between the groups. CONCLUSION: Eyes with fovea-split RRD had both a preoperative and a final postoperative VA between those of fovea-on and fovea-off eyes and different anatomical changes on OCT. This new entity warrants different patient expectations for postoperative outcomes.

Additive Value of a Face-to-Face Visit to Virtual Remote Decision in Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The increasing high prevalence of neovascular age-related macular degeneration (nvAMD) in the aging population combined with the need for frequent monitoring and treatment for many years, especially in the COVID-19 era, raises the need to establish an effective, reliable, and safe follow-up and treatment model. This study evaluates the difference in treatment decisions comparing between the gold standard face-to-face clinical examination and virtual evaluation approach based only on visual acuity (VA) and optical coherence tomography (OCT) scans without clinical fundoscopic examination in nvAMD patients. METHODS: A single-center retrospective cohort study was conducted that compared an original "face-to-face" visit treatment decision regarding the need for anti-vascular endothelial growth factor drug, interval, and treatment regimen based on routine VA, spectral domain OCT imaging, and dilated fundus examination to two "virtual" treatment decisions based on evaluation of OCT scans and previous medical records before and after revealing VA data on the same nvAMD patients eyes. RESULTS: About 169 eyes of 114 patients were included in the study. Forty-nine patients (43%) suffered from bilateral nvAMD and had both eyes included in the study. Agreement between the "face-to-face visit treatment decision" and "virtual treatment decision" was noted in 74.6% and 71.6% eyes before and after revealing the patient's VA in the study visit, respectively. CONCLUSIONS: Virtual evaluation results in similar treatment decisions for nvAMD patients compared to standard face-to-face clinical examination.

Phosphorylation of Serine 114 of the transcription factor ABSCISIC ACID INSENSITIVE 4 is essential for activity.

The transcription factor ABA-INSENSITIVE(ABI)4 has diverse roles in regulating plant growth, including inhibiting germination and reserve mobilization in response to ABA and high salinity, inhibiting seedling growth in response to high sugars, inhibiting lateral root growth, and repressing light-induced gene expression. ABI4 activity is regulated at multiple levels, including gene expression, protein stability, and activation by phosphorylation. Although ABI4 can be phosphorylated at multiple residues by MAPKs, we found that S114 is the preferred site of MPK3. To examine the possible biological role of S114 phosphorylation, we transformed abi4-1 mutant plants with ABI4pro::ABI4 constructs encoding wild type (114S), phosphorylation-null (S114A) or phosphomimetic (S114E) forms of ABI4. Phosphorylation of S114 is necessary for the response to ABA, glucose, salt stress, and lateral root development, where the abi4 phenotype could be complemented by expressing ABI4 (114S) or ABI4 (S114E) but not ABI4 (S114A). Comparison of root transcriptomes in ABA-treated roots of abi4-1 mutant plants transformed with constructs encoding the different phosphorylation-forms of S114 of ABI4 revealed that 85 % of the ABI4-regulated genes whose expression pattern could be restored by expressing ABI4 (114S) are down-regulated by ABI4. Phosphorylation of S114 was required for regulation of 35 % of repressed genes, but only 17 % of induced genes. The genes whose repression requires the phosphorylation of S114 are mainly involved in embryo and seedling development, growth and differentiation, and regulation of gene expression.

Heterosis as a consequence of regulatory incompatibility.

BACKGROUND: The merging of genomes in inter-specific hybrids can result in novel phenotypes, including increased growth rate and biomass yield, a phenomenon known as heterosis. Heterosis is typically viewed as the opposite of hybrid incompatibility. In this view, the superior performance of the hybrid is attributed to heterozygote combinations that compensate for deleterious mutations accumulating in each individual genome, or lead to new, over-dominating interactions with improved performance. Still, only fragmented knowledge is available on genes and processes contributing to heterosis. RESULTS: We describe a budding yeast hybrid that grows faster than both its parents under different environments. Phenotypically, the hybrid progresses more rapidly through cell cycle checkpoints, relieves the repression of respiration in fast growing conditions, does not slow down its growth when presented with ethanol stress, and shows increased signs of DNA damage. A systematic genetic screen identified hundreds of S. cerevisiae alleles whose deletion reduced growth of the hybrid. These growth-affecting alleles were condition-dependent, and differed greatly from alleles that reduced the growth of the S. cerevisiae parent. CONCLUSIONS: Our results define a budding yeast hybrid that is perturbed in multiple regulatory processes but still shows a clear growth heterosis. We propose that heterosis results from incompatibilities that perturb regulatory mechanisms, which evolved to protect cells against damage or prepare them for future challenges by limiting cell growth.

Individual olfactory perception reveals meaningful nonolfactory genetic information.

Each person expresses a potentially unique subset of ∼ 400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10(-10)), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10(-4)), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10(-6)). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.