184 research outputs found
The p53 Tumor Suppressor-Like Protein nvp63 Mediates Selective Germ Cell Death in the Sea Anemone Nematostella vectensis
Here we report the identification and molecular function of the p53 tumor suppressor-like protein nvp63 in a non-bilaterian animal, the starlet sea anemone Nematostella vectensis. So far, p53-like proteins had been found in bilaterians only. The evolutionary origin of p53-like proteins is highly disputed and primordial p53-like proteins are variably thought to protect somatic cells from genotoxic stress. Here we show that ultraviolet (UV) irradiation at low levels selectively induces programmed cell death in early gametes but not somatic cells of adult N. vectensis polyps. We demonstrate with RNA interference that nvp63 mediates this cell death in vivo. Nvp63 is the most archaic member of three p53-like proteins found in N. vectensis and in congruence with all known p53-like proteins, nvp63 binds to the vertebrate p53 DNA recognition sequence and activates target gene transcription in vitro. A transactivation inhibitory domain at its C-terminus with high homology to the vertebrate p63 may regulate nvp63 on a molecular level. The genotoxic stress induced and nvp63 mediated apoptosis in N. vectensis gametes reveals an evolutionary ancient germ cell protective pathway which relies on p63-like proteins and is conserved from cnidarians to vertebrates
Distinct Molecular Evolutionary Mechanisms Underlie the Functional Diversification of the Wnt and TGFβ Signaling Pathways
The canonical Wnt pathway is one of the oldest and most functionally diverse of animal intercellular signaling pathways. Though much is known about loss-of-function phenotypes for Wnt pathway components in several model organisms, the question of how this pathway achieved its current repertoire of functions has not been addressed. Our phylogenetic analyses of 11 multigene families from five species belonging to distinct phyla, as well as additional analyses employing the 12 Drosophila genomes, suggest frequent gene duplications affecting ligands and receptors as well as co-evolution of new ligand–receptor pairs likely facilitated the expansion of this pathway’s capabilities. Further, several examples of recent gene loss are visible in Drosophila when compared to family members in other phyla. By comparison the TGFβ signaling pathway is characterized by ancient gene duplications of ligands, receptors, and signal transducers with recent duplication events restricted to the vertebrate lineage. Overall, the data suggest that two distinct molecular evolutionary mechanisms can create a functionally diverse developmental signaling pathway. These are the recent dynamic generation of new genes and ligand–receptor interactions as seen in the Wnt pathway and the conservative adaptation of ancient pre-existing genes to new roles as seen in the TGFβ pathway. From a practical perspective, the former mechanism limits the investigator’s ability to transfer knowledge of specific pathway functions across species while the latter facilitates knowledge transfer
Identification and In Vivo Characterization of NvFP-7R, a Developmentally Regulated Red Fluorescent Protein of Nematostella vectensis
In recent years, the sea anemone Nematostella vectensis has emerged as a critical model organism for comparative genomics and developmental biology. Although Nematostella is a member of the anthozoan cnidarians (known for producing an abundance of diverse fluorescent proteins (FPs)), endogenous patterns of Nematostella fluorescence have not been described and putative FPs encoded by the genome have not been characterized.We described the spatiotemporal expression of endogenous red fluorescence during Nematostella development. Spatially, there are two patterns of red fluorescence, both restricted to the oral endoderm in developing polyps. One pattern is found in long fluorescent domains associated with the eight mesenteries and the other is found in short fluorescent domains situated between tentacles. Temporally, the long domains appear simultaneously at the 12-tentacle stage. In contrast, the short domains arise progressively between the 12- and 16-tentacle stage. To determine the source of the red fluorescence, we used bioinformatic approaches to identify all possible putative Nematostella FPs and a Drosophila S2 cell culture assay to validate NvFP-7R, a novel red fluorescent protein. We report that both the mRNA expression pattern and spectral signature of purified NvFP-7R closely match that of the endogenous red fluorescence. Strikingly, the red fluorescent pattern of NvFP-7R exhibits asymmetric expression along the directive axis, indicating that the nvfp-7r locus senses the positional information of the body plan. At the tissue level, NvFP-7R exhibits an unexpected subcellular localization and a complex complementary expression pattern in apposed epithelia sheets comprising each endodermal mesentery.These experiments not only identify NvFP-7R as a novel red fluorescent protein that could be employed as a research tool; they also uncover an unexpected spatio-temporal complexity of gene expression in an adult cnidarian. Perhaps most importantly, our results define Nematostella as a new model organism for understanding the biological function of fluorescent proteins in vivo
Ambulatory assessment of psychophysiological stress among police officers: A proof-of-concept study.
Occupational stress has been widely recognized as a global challenge and has received increased attention by the academic community. Ambulatory Assessment methodologies, combining psychophysiological measures of stress, offer a promising avenue for future prevention and/or rehabilitation stress research. Considering that policing is well known for being a particularly stressful occupation, Emergency Responders Officers (EROs) stress levels were investigated. Particularly, this study analyzed: (i) physiological stress data obtained during shifts and compared these data with baseline levels (days off), as well as (ii) with normative values for healthy populations; (iii) stress symptoms differences from beginning to end of shift; (iv) stress events and events intensity and (v) the acceptability and feasibility of this proof-of-concept study in a highly stressful occupation. A Geo-location event system was used to help retrospective accounts of psychological stress, combined with electrocardiogram (ECG) data and mobile self-reports, that include stress symptoms, event types and event intensity. Results suggest that EROs experience high levels of stress (both on-duty and off duty) when compared to healthy populations. Stress symptoms increase from the beginning to end of the shift. However, the mean events intensity was very low. It can be concluded that stress may not always be diagnosed when using merely self-reports. These findings highlight the importance of combining both self-report and physiological stress measures in occupational health contexts. Finally, results confirm the acceptability and feasibility of the multi-method used. Key implications for policy makers and applied practitioners in the area of occupational health and future research directions are discussed
“A Massive Long Way”: Interconnecting Histories, a “Special Child,” ADHD, and Everyday Family Life
Focusing on one family from a study of dual-earner middle-class families carried out in Los Angeles, California, this article draws on interview and video-recorded data of everyday interactions to explore illness and healing as embedded in the microcultural context of the Morris family. For this family, an important aspect of what is at stake for them in their daily lives is best understood by focusing on 9-year-old Mark, who has been diagnosed with attention-deficit/hyperactivity disorder (ADHD). In this article, we grapple with the complexity of conveying some sense of how Mark’s condition is experienced and relationally enacted in everyday contexts. Through illuminating connections between lives as lived and lives as told, we explore the narrative structuring of healing in relation to Mark’s local moral world with the family at its center. We examine how his parents understand the moral consequences of the child’s past for his present and future, and work to encourage others to give due weight to his troubled beginnings before this child joined the Morris family. At the same time, we see how the Morris parents act to structure Mark’s moral experience and orient to a desired future in which Mark’s “success” includes an appreciation of how he is accountable to others for his actions. Through our analyses, we also seek to contribute to discussions on what is at stake in everyday life contexts for children with ADHD and their families, through illuminating aspects of the cultural, moral and relational terrain that U.S. families navigate in contending with a child’s diagnosis of ADHD. Further, given that ADHD is often construed as a “disorder of volition,” we seek to advance anthropological theorizing about the will in situations where volitional control over behavior is seen to be disordered
Exceptionally Preserved Jellyfishes from the Middle Cambrian
Cnidarians represent an early diverging animal group and thus insight into their origin and diversification is key to understanding metazoan evolution. Further, cnidarian jellyfish comprise an important component of modern marine planktonic ecosystems. Here we report on exceptionally preserved cnidarian jellyfish fossils from the Middle Cambrian (∼505 million years old) Marjum Formation of Utah. These are the first described Cambrian jellyfish fossils to display exquisite preservation of soft part anatomy including detailed features of structures interpreted as trailing tentacles and subumbrellar and exumbrellar surfaces. If the interpretation of these preserved characters is correct, their presence is diagnostic of modern jellyfish taxa. These new discoveries may provide insight into the scope of cnidarian diversity shortly after the Cambrian radiation, and would reinforce the notion that important taxonomic components of the modern planktonic realm were in place by the Cambrian period
Silicon photonics fiber-to-the-home transceiver array based on transfer-printing-based integration of III-V photodetectors
An international collaborative evaluation of central serous chorioretinopathy: different therapeutic approaches and review of literature. The European Vitreoretinal Society central serous chorioretinopathy study
Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11 months but was extended in a minority of cases up to 7 years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1 month) was favoured by age <60 years (p < 0.005), no previous observation (p < 0.0002), duration less than 3 months (p < 0.0001), absence of CSCR in the fellow eye (p = 0.04), leakage outside of the arcade (p = 0.05) and fluid height >500 \u3bcm (p = 0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1 month was favoured by first episode (p = 0.04), height of subretinal fluid >500 \u3bcm (p < 0.0001) and short duration of observation (p = 0.02). Finally, there was no statistically significant difference among the treatments at 12 months. Conclusion: Spontaneous resolution has been described in a high percentage of patients. Laser (micropulse and thermal) and PDT seem to lead to significant early anatomical improvement; however, there is little change beyond the first month of treatment. The real visual benefit needs further clarification
Enhanced prefrontal serotonin 5-HT1A currents in a mouse model of Williams-Beuren syndrome with low innate anxiety
Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the hemizygous deletion of 28 genes on chromosome 7, including the general transcription factor GTF2IRD1. Mice either hemizygously (Gtf2ird1+/−) or homozygously (Gtf2ird1−/−) deleted for this transcription factor exhibit low innate anxiety, low aggression and increased social interaction, a phenotype that shares similarities to the high sociability and disinhibition seen in individuals with WBS. Here, we investigated the inhibitory effects of serotonin (5-HT) on the major output neurons of the prefrontal cortex in Gtf2ird1−/− mice and their wildtype (WT) siblings. Prefrontal 5-HT receptors are known to modulate anxiety-like behaviors, and the Gtf2ird1−/− mice have altered 5-HT metabolism in prefrontal cortex. Using whole cell recording from layer V neurons in acute brain slices of prefrontal cortex, we found that 5-HT elicited significantly larger inhibitory, outward currents in Gtf2ird1−/− mice than in WT controls. In both genotypes, these currents were resistant to action potential blockade with TTX and were suppressed by the selective 5-HT1A receptor antagonist WAY-100635, suggesting that they are mediated directly by 5-HT1A receptors on the recorded neurons. Control experiments suggest a degree of layer and receptor specificity in this enhancement since 5-HT1A receptor-mediated responses in layer II/III pyramidal neurons were unchanged as were responses mediated by two other inhibitory receptors in layer V pyramidal neurons. Furthermore, we demonstrate GTF2IRD1 protein expression by neurons in layer V of the prefrontal cortex. Our finding that 5-HT1A-mediated responses are selectively enhanced in layer V pyramidal neurons of Gtf2ird1−/− mice gives insight into the cellular mechanisms that underlie reduced innate anxiety and increased sociability in these mice, and may be relevant to the low social anxiety and disinhibition in patients with WBS and their sensitivity to serotonergic medicines
Ancient Origin of the New Developmental Superfamily DANGER
Developmental proteins play a pivotal role in the origin of animal complexity and diversity. We report here the identification of a highly divergent developmental protein superfamily (DANGER), which originated before the emergence of animals (∼850 million years ago) and experienced major expansion-contraction events during metazoan evolution. Sequence analysis demonstrates that DANGER proteins diverged via multiple mechanisms, including amino acid substitution, intron gain and/or loss, and recombination. Divergence for DANGER proteins is substantially greater than for the prototypic member of the superfamily (Mab-21 family) and other developmental protein families (e.g., WNT proteins). DANGER proteins are widely expressed and display species-dependent tissue expression patterns, with many members having roles in development. DANGER1A, which regulates the inositol trisphosphate receptor, promotes the differentiation and outgrowth of neuronal processes. Regulation of development may be a universal function of DANGER family members. This family provides a model system to investigate how rapid protein divergence contributes to morphological complexity
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