Posttranslational modifications (PTMs) are known to constitute a key step in protein biosynthesis and in the regulation of protein functions. Recent breakthroughs in protein purification strategies ...and current proteome technologies make it possible to identify the proteomics of healthy and diseased retinas. Despite these advantages, the research field identifying sets of posttranslationally modified proteins (PTMomes) related to diseased retinas is significantly lagging, despite knowledge of the major retina PTMome being critical to drug development. In this review, we highlight current updates regarding the PTMomes in three retinal degenerative diseases-namely, diabetic retinopathy (DR), glaucoma, and retinitis pigmentosa (RP). A literature search reveals the necessity to expedite investigations into essential PTMomes in the diseased retina and validate their physiological roles. This knowledge would accelerate the development of treatments for retinal degenerative disorders and the prevention of blindness in affected populations.
Depressive rumination has been strongly linked to the development and maintenance of depression; however, less attention has been paid to ruminative processes in response to positive affect, and ...fewer have examined these processes in daily life. The current study sought to address these gaps by exploring depressive rumination and two forms of responses to positive affect,
dampening
and
positive rumination
, under ecologically valid conditions using daily diary methodology. One hundred fifty-seven young adults completed 14-day end-of-day diaries assessing positive affect and depressive symptoms in relation to depressive rumination, responses to positive affect, and daily positive and negative events. Daily depressive rumination predicted stronger associations between negative events and daily depressive symptoms. Higher daily dampening was associated with higher daily depressive symptoms and decreased positive affect and predicted lower associations between daily positive events and improvements in mood (including reduced daily positive affect and increased daily depressive symptoms). Higher daily positive rumination was negatively associated with daily depressive symptoms and interacted with daily positive events such that positive rumination had a greater impact on depressed mood on days when positive experiences were low. Results indicate that both depressive rumination and responses to positive affect play a role in influencing daily mood and depressive symptoms.
Each cell comprising an intact, healthy, confluent epithelial layer ordinarily remains sedentary, firmly adherent to and caged by its neighbors, and thus defines an elemental constituent of a ...solid-like cellular collective 1,2. After malignant transformation, however, the cellular collective can become fluid-like and migratory, as evidenced by collective motions that arise in characteristic swirls, strands, ducts, sheets, or clusters 3,4. To transition from a solid-like to a fluid-like phase and thereafter to migrate collectively, it has been recently argued that cells comprising the disordered but confluent epithelial collective can undergo changes of cell shape so as to overcome geometric constraints attributable to the newly discovered phenomenon of cell jamming and the associated unjamming transition (UJT) 1,2,5–9. Relevance of the jamming concept to carcinoma cells lines of graded degrees of invasive potential has never been investigated, however. Using classical in vitro cultures of six breast cancer model systems, here we investigate structural and dynamical signatures of cell jamming, and the relationship between them 1,2,10,11. In order of roughly increasing invasive potential as previously reported, model systems examined included MCF10A, MCF10A.Vector; MCF10A.14-3-3ζ; MCF10.ErbB2, MCF10AT; and MCF10CA1a 12–15. Migratory speed depended on the particular cell line. Unsurprisingly, for example, the MCF10CA1a cell line exhibited much faster migratory speed relative to the others. But unexpectedly, across different cell lines higher speeds were associated with enhanced size of cooperative cell packs in a manner reminiscent of a peloton 9. Nevertheless, within each of the cell lines evaluated, cell shape and shape variability from cell-to-cell conformed with predicted structural signatures of cell layer unjamming 1. Moreover, both structure and migratory dynamics were compatible with previous theoretical descriptions of the cell jamming mechanism 2,10,11,16,17. As such, these findings demonstrate the richness of the cell jamming mechanism, which is now seen to apply across these cancer cell lines but remains poorly understood.
•In each of 6 cancer cell lines, cell shape and its variability conformed with predicted structural signatures of unjamming.•Across these different cell lines, cell shape information alone was not sufficient to predict migratory dynamics.•Across cell lines, higher speeds were associated with enhanced cooperative pack sizes in a manner reminiscent of a peloton.
In this study, the authors aimed to identify the demographics of retinal detachment in children in the United States and to report the treatment modalities chosen by vitreoretinal surgeons and ...associated outcomes.
This was a multicenter cohort analysis of the Vestrum Health LLC Database (Naperville, IL). Children (1-17 years) with rhegmatogenous retinal detachment, as identified by ICD10 and CPT codes, between January 2015 and August 2021 were enrolled. Demographic, comorbidity, visual acuity, and treatment modality data were analyzed.
A total of 168,152 RRDs were identified, of which 2,200 (1.3%) were aged 1 to 17 years. The mean age was 12.7 years, and 821 (37%) were women. The prevalence of rhegmatogenous retinal detachment increased with age ( P = 0.009). Associated comorbidities included myopia (17.3%), ocular trauma (7.5%), and history of prematurity (5.7%). Laser retinopexy alone was used as the initial treatment modality in 19%, primary vitrectomy in 23%, primary scleral buckle in 25%, and vitrectomy with scleral buckle in 33%. The single surgery success rate for all procedures was 73.3%. Of the incisional surgical modalities, primary scleral buckling had the best single surgery success rate (79.0%) compared with vitrectomy alone (64.5%) and vitrectomy with scleral buckle (67.2%) ( P < 0.001 and P = 0.004, respectively). Younger age resulted in worse SSSR overall (coefficient = 0.151, R 2 = 0.746, P = 0.027).
Rhegmatogenous retinal detachments in children increased with age. Myopia, trauma, and history of retinopathy of prematurity were common risk factors. Treatment techniques varied, but primary scleral buckling had the best anatomical and visual outcomes.
We report maps of the concentrations of H, Si, Cl, K, Fe, and Th as determined by the Gamma Ray Spectrometer (GRS) on board the 2001 Mars Odyssey Mission for ±∼45° latitudes. The procedures by which ...the spectra are processed to yield quantitative concentrations are described in detail. The concentrations of elements determined over the locations of the various Mars landers generally agree well with the lander values except for Fe, although the mean of the GRS Fe data agrees well with that of Martian meteorites. The water‐equivalent concentration of hydrogen by mass varies from about 1.5% to 7.5% (by mass) with the most enriched areas being near Apollinaris Patera and Arabia Terra. Cl shows a distribution similar to H over the surface except that the Cl content over Medusae Fossae is much greater than elsewhere. The map of Fe shows enrichment in the northern lowlands versus the southern highlands. Silicon shows only very modest variation over the surface with mass fractions ranging from 19% to 22% over most of the planet, though a significant depletion in Si is noted in a region west of Tharsis Montes and Olympus Mons where the Si content is as low as 18%. K and Th show a very similar pattern with depletions associated with young volcanic deposits and enrichments associated with the TES Surface Type‐2 material. It is noted that there appears to be no evidence of significant globally distributed thick dust deposits of uniform composition.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr and Margiotta, 2016). At neuronal ...synapses where transmission is mediated by nicotinic acetylcholine receptors (nAChRs) transient PACAP exposure increases the frequency and amplitude (FS and AS) of spontaneous excitatory postsynaptic currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high-affinity PACAP receptor (PAC1R) signaling via adenylate cyclase (AC), cyclic AMP (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release (Pugh et al., 2010; Jayakar et al., 2014). Remarkably, synaptic changes persist 48h after transient PACAP exposure, featuring a similar increase in FS and an even larger increase in AS. Pharmacological studies reveal that this long-term (LT) plasticity requires PACAP/PAC1R signaling via AC and cAMP, but unlike ST plasticity, Phospholipase-C and new gene transcription are also necessary, whereas PKA, nAChR, impulse and NO synthase (NOS1) activities are dispensable. In accord with the increases in FS and AS characterizing LT plasticity, miniature EPSC (mEPSC) frequency, ACh release (quantal content), and mEPSC amplitude (quantal size) all increased in parallel. Consistent with these functional changes, imaging studies reveal that LT, but not ST, PACAP-induced plasticity is accompanied by increases in presynaptic terminal size, postsynaptic nAChR cluster size and density, and the size and density of co-localized pre- and post-synpatic sites. Thus PACAP/PAC1R signaling induces mechanistically distinct forms of synaptic plasticity, with a ST form arising from acute, membrane-delimited processes, and a LT form arising from transcription-dependent alterations in the function and structural arrangement of pre- and post-synaptic components.
•PACAP induces short- & long-term (ST & LT) plasticity at nAChR-mediated synapses.•ST and LT forms of synaptic plasticity are mechanistically distinct and independent.•The LT plasticity requires cAMP signaling but not protein kinase A activity.•The LT synaptic plasticity requires new gene transcription.•Functional and structural synaptic modifications accompany LT synaptic plasticity.
Summary Maternal depression serves as a potent source of stress among offspring, greatly enhancing the risk of numerous adverse outcomes including youth depression. Several factors moderate the ...transmission of depression from mothers to offspring. However, the role of genetic characteristics in this process merits further exploration. Consistent with an interpersonal perspective on depression, the present study focused on a genetic polymorphism that has been shown to be relevant to social functioning, the rs53576 polymorphism of the oxytocin receptor gene ( OXTR ). In a community sample of 441 youth, OXTR genotype moderated the association between maternal depression in early childhood and youth depressive symptoms in adolescence, such that youth possessing at least one A allele of OXTR who also had a history of maternal depression exhibited the highest levels of depressive symptoms at age 15. In order to explore possible interpersonal mediators of this effect, conditional process analyses examined the role of youth social functioning in adolescence. Results suggest that OXTR genotype may partially account for the transmission of maternal depression to youth and support the role of dysfunctional social processes as a mechanism through which OXTR influences the development of depressive symptoms.
We examine a sample of 2301 gamma-ray bursts, detected by Konus-Wind in the triggered mode between 1994 and 2017 and localized by the interplanetary network (IPN), for evidence of gravitational ...lensing. We utilize all the available gamma-ray burst (GRB) data: time histories, localizations, and energy spectra. We employ common IPN techniques to find and quantify similarities in the light curves of 2,646,150 burst pairs, and for the pairs with significant similarities, we examine their IPN localizations to determine whether they are consistent with a common origin. For pairs that are consistent, we derive and compare energy spectra, and compute a figure of merit that allows us to compare and rank burst pairs. We conduct both a blind search, between all possible burst pairs, and a targeted search, between pairs in which one burst has both a spectroscopic redshift and an identification of an intervening system, as measured by one or more lower spectroscopic redshifts. We identify six pairs in the blind search that could be taken as evidence for lensing, but none are compelling enough to claim a detection with good confidence. No candidates were detected in the targeted search. For our GRB sample, we set an upper limit to the optical depth to lensing of 0.0033, which is comparable to that of optical sources. We conclude that proposed scenarios in which a large fraction of the GRB population is lensed are extremely unlikely.
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