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Ophthalmology. Retina Apr 2024To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina.
OBJECTIVE
To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina.
DESIGN
Cross sectional descriptive study from December 2021 to December 2022.
PARTICIPANTS
Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis.
METHODS
Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA).
MAIN OUTCOME MEASURES
Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (μm) from OCT, foveal avascular zone (mm) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA.
RESULTS
A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 μm (range, 217-488 μm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes.
CONCLUSIONS
This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Male; Female; Cross-Sectional Studies; Tomography, Optical Coherence; Adult; Fluorescein Angiography; Visual Acuity; Electroretinography; Middle Aged; Multimodal Imaging; Leukoencephalopathies; Visual Fields; Retinal Diseases; Retinal Vessels; Young Adult; Fundus Oculi; Adolescent
PubMed: 38752998
DOI: 10.1016/j.oret.2023.10.013 -
Proceedings of the National Academy of... May 2024Congenital stationary night blindness (CSNB) is an inherited retinal disease that causes a profound loss of rod sensitivity without severe retinal degeneration. One...
Congenital stationary night blindness (CSNB) is an inherited retinal disease that causes a profound loss of rod sensitivity without severe retinal degeneration. One well-studied rhodopsin point mutant, G90D-Rho, is thought to cause CSNB because of its constitutive activity in darkness causing rod desensitization. However, the nature of this constitutive activity and its precise molecular source have not been resolved for almost 30 y. In this study, we made a knock-in (KI) mouse line with a very low expression of G90D-Rho (equal in amount to ~0.1% of normal rhodopsin, WT-Rho, in WT rods), with the remaining WT-Rho replaced by REY-Rho, a mutant with a very low efficiency of activating transducin due to a charge reversal of the highly conserved ERY motif to REY. We observed two kinds of constitutive noise: one being spontaneous isomerization (R*) of G90D-Rho at a molecular rate (R* s) 175-fold higher than WT-Rho and the other being G90D-Rho-generated dark continuous noise comprising low-amplitude unitary events occurring at a very high molecular rate equivalent in effect to ~40,000-fold of R* s from WT-Rho. Neither noise type originated from G90D-Opsin because exogenous 11--retinal had no effect. Extrapolating the above observations at low (0.1%) expression of G90D-Rho to normal disease exhibited by a KI mouse model with and genotypes predicts the disease condition very well quantitatively. Overall, the continuous noise from G90D-Rho therefore predominates, constituting the major equivalent background light causing rod desensitization in CSNB.
Topics: Animals; Night Blindness; Eye Diseases, Hereditary; Mice; Rhodopsin; Genetic Diseases, X-Linked; Myopia; Retinal Rod Photoreceptor Cells; Darkness; Transducin; Gene Knock-In Techniques; Disease Models, Animal
PubMed: 38743626
DOI: 10.1073/pnas.2404763121 -
Frontiers in Microbiology 2024Saline-alkaline lakes often shelter high biomasses despite challenging conditions, owing to the occurrence of highly adapted phototrophs. Dziani Dzaha (Mayotte) is one...
Saline-alkaline lakes often shelter high biomasses despite challenging conditions, owing to the occurrence of highly adapted phototrophs. Dziani Dzaha (Mayotte) is one such lake characterized by the stable co-dominance of the cyanobacterium and the picoeukaryote throughout its water column. Despite light penetrating only into the uppermost meter, the prevailing co-dominance of these species persists even in light- and oxygen-deprived zones. Here, a depth profile of phototrophs metatranscriptomes, annotated using genomic data from isolated strains, is employed to identify expression patterns of genes related to carbon processing pathways including photosynthesis, transporters and fermentation. The findings indicate a prominence of gene expression associated with photosynthesis, with a peak of expression around 1 m below the surface, although the light intensity is very low and only red and dark red wavelengths can reach it, given the very high turbidity linked to the high biomass of . Experiments on strains confirmed that both species do grow under these wavelengths, at rates comparable to those obtained under white light. A decrease in the expression of photosynthesis-related genes was observed in with increasing depth, whereas maintained a very high pool of A transcripts down to the deepest point as a possible adaptation against photodamage, in the absence and/or very low levels of expression of genes involved in protection. In the aphotic/anoxic zone, expression of genes involved in fermentation pathways suggests active metabolism of reserve or available dissolved carbon compounds. Overall, seems to be adapted to the uppermost water layer, where it is probably maintained thanks to gas vesicles, as evidenced by high expression of the A gene. In contrast, occurs at similar densities throughout the water column, with a peak in abundance and gene expression levels which suggests a better adaptation to lower light intensities. These slight differences may contribute to limited inter-specific competition, favoring stable co-dominance of these two phototrophs.
PubMed: 38741748
DOI: 10.3389/fmicb.2024.1368523 -
Physiological and Structural Changes in Leaves of Seedlings Exposed to Increasing Light Intensities.Plants (Basel, Switzerland) Apr 2024Understanding the light adaptation of plants is critical for conservation. , an endangered deciduous shrub endemic to East Asia, possesses high ornamental and...
Understanding the light adaptation of plants is critical for conservation. , an endangered deciduous shrub endemic to East Asia, possesses high ornamental and phylogeographic value. However, the weak environmental adaptability of species has limited its general growth and conservation. To obtain a deeper understanding of the growth conditions, we examined the leaf morphology and physiology via anatomical and chloroplast ultrastructural analyses following exposure to different natural light intensities (full light, 40%, and 10%). The findings indicated that seedings in the 10% light intensity had significantly improved leaf morphological characteristics and specific leaf area compared to those exposed to other intensities. The net photosynthetic rate, chlorophyll (Chl) content, photosynthetic nitrogen use efficiency (PNUE), and photosynthetic phosphorus use efficiency (PPUE) exhibited marked increases at a 10% light intensity compared to both 40% light and full light intensities, whereas the light compensation point and dark respiration levels reached their lowest values under the 10% light condition. With reduced light, leaf thickness, palisade tissue, spongy tissue, and stomatal density significantly decreased, whereas the stomatal length, stomatal width, and stomatal aperture were significantly elevated. When exposed to 10% light intensity, the ultrastructure of chloroplasts was well developed, chloroplasts and starch grain size, the number of grana, and thylakoids all increased significantly, while the number of plastoglobules was significantly reduced. Relative distance phenotypic plasticity index analysis exhibited that adapts to varying light environments predominantly by adjusting PPUE, Chl b, PNUE, chloroplast area, and the activity of PSII reaction centers. We proposed that efficiently utilizes low light to reconfigure its energy metabolism by regulating its leaf structure, photosynthetic capacity, nutrient use efficiency, and chloroplast development.
PubMed: 38732478
DOI: 10.3390/plants13091263 -
BMC Primary Care May 2024Medical assistants are essential for the healthcare system. However, they face several working demands every day, for which they need resources to cope. While several...
BACKGROUND
Medical assistants are essential for the healthcare system. However, they face several working demands every day, for which they need resources to cope. While several studies show that humour can be a resource for healthcare professionals, studies on humour styles/comic styles in healthcare are scarce. But, as humour styles (e.g., light vs. dark) may have varying - and even negative - effects on positive psychological functioning, it is important to investigate their individual potential for medical assistants. Thus, this study investigates the relationships between medical assistants' comic styles and their positive psychological functioning at work.
METHODS
Applying a cross-sectional design we assessed German medical assistants' eight comic styles (i.e., benevolent humour, fun, wit, nonsense, irony, satire, sarcasm, cynicism) and facets of positive psychological functioning (e.g., well-being, feeling of competence). We analysed relationships between the variables by means of Pearson correlations, ANCOVAs and hierarchical regressions. All analyses were conducted with the total sample (N = 608; completion rate 44%) as well as a large subsample of medical assistants working in general medicine (N = 263).
RESULTS
While most of the light styles (e.g., benevolent humour) relate positively to most facets, the dark style sarcasm relates negatively. The other dark styles showed coefficients around zero or even slightly positive ones (e.g., satire). Most relationships were also prevalent in the subgroup of medical assistants working in general medicine.
CONCLUSIONS
The eight comic styles might have varying potential for medical assistants' positive psychological functioning at work, with benevolent humour being most adaptive and sarcasm being maladaptive. This study points to the relevance of raising attention regarding the (mal-)adaptiveness of different comic styles of healthcare professionals. Trainings of professionals (e.g., vocational education and training of medical assistants) might integrate the topic of humour (i.e., foster benevolent vs. caution against sarcastic humour) to build and maintain this helpful resource which professionals can use as a tool to master various challenges of everyday work (e.g., cope with stressful situations).
Topics: Humans; Cross-Sectional Studies; Male; Adult; Wit and Humor as Topic; Female; Middle Aged; Germany; Surveys and Questionnaires; Adaptation, Psychological
PubMed: 38714938
DOI: 10.1186/s12875-024-02363-y -
Evolution; International Journal of... May 2024Urbanization presents a natural evolutionary experiment because selection pressures in cities can be strongly mismatched with those found in species' historic habitats....
Urbanization presents a natural evolutionary experiment because selection pressures in cities can be strongly mismatched with those found in species' historic habitats. However, some species have managed to adapt and even thrive in these novel conditions. When a species persists across multiple cities, a fundamental question arises: do we see similar traits evolve under similar novel environments? By testing if and how similar phenotypes emerge across multiple urban populations, we can begin to assess the predictability of population response to anthropogenic change. Here, we examine variation within and across multiple populations of a songbird, the dark-eyed junco (Junco hyemalis). We measured morphological variations in juncos across urban and non-urban populations in Southern California. We investigated whether the variations we observed are due to differences in environmental conditions across cities. Bill shape differed across urban populations; Los Angeles and Santa Barbara juncos had shorter, deeper bills than non-urban juncos, but San Diego juncos did not. On the other hand, wing length decreased with the built environment, regardless of the population. Southern Californian urban juncos exhibit both similarities and differences in morphological traits. Studying multiple urban populations can help us determine the predictability of phenotypic evolutionary response to novel environments.
PubMed: 38700135
DOI: 10.1093/evolut/qpae067 -
Developmental Cell Apr 2024Photomorphogenesis is a light-dependent plant growth and development program. As the core regulator of photomorphogenesis, ELONGATED HYPOCOTYL 5 (HY5) is affected by...
Photomorphogenesis is a light-dependent plant growth and development program. As the core regulator of photomorphogenesis, ELONGATED HYPOCOTYL 5 (HY5) is affected by dynamic changes in its transcriptional activity and protein stability; however, little is known about the mediators of these processes. Here, we identified PHOTOREGULATORY PROTEIN KINASE 1 (PPK1), which interacts with and phosphorylates HY5 in Arabidopsis, as one such mediator. The phosphorylation of HY5 by PPK1 is essential to establish high-affinity binding with B-BOX PROTEIN 24 (BBX24) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), which inhibit the transcriptional activity and promote the degradation of HY5, respectively. As such, PPKs regulate not only the binding of HY5 to its target genes under light conditions but also HY5 degradation when plants are transferred from light to dark. Our data identify a PPK-mediated phospho-code on HY5 that integrates the molecular mechanisms underlying the regulation of HY5 to precisely control plant photomorphogenesis.
PubMed: 38677285
DOI: 10.1016/j.devcel.2024.04.007 -
Cell Reports May 2024Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment...
Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.
Topics: Animals; Mice; Carrier Proteins; Ependymoglial Cells; Mice, Inbred C57BL; Mice, Knockout; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Pigments; Retinal Rod Photoreceptor Cells; Male; Female
PubMed: 38676924
DOI: 10.1016/j.celrep.2024.114143 -
Ecology and Evolution Apr 2024Cave-adapted animals evolve a suite of regressive and constructive traits that allow survival in the dark. Most studies aiming at understanding cave animal evolution... (Review)
Review
Cave-adapted animals evolve a suite of regressive and constructive traits that allow survival in the dark. Most studies aiming at understanding cave animal evolution have focused on the genetics and environmental underpinnings of regressive traits, with special emphasis on vision loss. Possibly as a result of vision loss, other non-visual sensory systems have expanded and compensated in cave species. For instance, in many cave-dwelling fish species, including the blind cavefish of the Mexican tetra, , a major non-visual mechanosensory system called the lateral line, compensated for vision loss through morphological expansions. While substantial work has shed light on constructive adaptation of this system, there are still many open questions regarding its developmental origin, synaptic plasticity, and overall adaptive value. This review provides a snapshot of the current state of knowledge of lateral line adaption in , with an emphasis on anatomy, synaptic plasticity, and behavior. Multiple open avenues for future research in this system, and how these can be leveraged as tools for both evolutionary biology and evolutionary medicine, are discussed.
PubMed: 38654714
DOI: 10.1002/ece3.11286 -
Frontiers in Behavioral Neuroscience 2024The purpose of this review extends beyond the traditional triune brain model, aiming to elucidate the evolutionary aspects of alpha rhythms in vertebrates. The... (Review)
Review
The purpose of this review extends beyond the traditional triune brain model, aiming to elucidate the evolutionary aspects of alpha rhythms in vertebrates. The forebrain, comprising the telencephalon (pallium) and diencephalon (thalamus, hypothalamus), is a common feature in the brains of all vertebrates. In mammals, evolution has prioritized the development of the forebrain, especially the neocortex, over the midbrain (mesencephalon) optic tectum, which serves as the prototype for the visual brain. This evolution enables mammals to process visual information in the retina-thalamus (lateral geniculate nucleus)-occipital cortex pathway. The origin of posterior-dominant alpha rhythms observed in mammals in quiet and dark environments is not solely attributed to cholinergic pontine nuclei cells functioning as a 10 Hz pacemaker in the brainstem. It also involves the ability of the neocortex's cortical layers to generate traveling waves of alpha rhythms with waxing and waning characteristics. The utilization of alpha rhythms might have facilitated the shift of attention from external visual inputs to internal cognitive processes as an adaptation to thrive in dark environments. The evolution of alpha rhythms might trace back to the dinosaur era, suggesting that enhanced cortical connectivity linked to alpha bands could have facilitated the development of nocturnal awakening in the ancestors of mammals. In fishes, reptiles, and birds, the pallium lacks a cortical layer. However, there is a lack of research clearly observing dominant alpha rhythms in the pallium or organized nuclear structures in fishes, reptiles, or birds. Through convergent evolution, the pallium of birds, which exhibits cortex-like fiber architecture, has not only acquired advanced cognitive and motor abilities but also the capability to generate low-frequency oscillations (4-25 Hz) resembling alpha rhythms. This suggests that the origins of alpha rhythms might lie in the pallium of a common ancestor of birds and mammals.
PubMed: 38651071
DOI: 10.3389/fnbeh.2024.1384340