Development of functional ectopic compound eyes in scarabaeid beetles by knockdown of orthodenticle

Complex traits like limbs, brains, or eyes form through coordinated integration of diverse cell fates across developmental space and time, yet understanding how complexity and integration emerge from uniform, undifferentiated precursor tissues remains limited. Here, we use ectopic eye formation as a paradigm to investigate the emergence and integration of novel complex structures following massive ontogenetic perturbation. We show that down-regulation via RNAi of a single head patterning gene—orthodenticle—induces ectopic structures externally resembling compound eyes at the middorsal adult head of both basal and derived scarabaeid beetle species (Onthophagini and Oniticellini). Scanning electron microscopy documents ommatidial organization of these induced structures, while immunohistochemistry reveals the presence of rudimentary ommatidial lenses, crystalline cones, and associated neural-like tissue within them. Further, RNA-sequencing experiments show that after orthodenticle down-regulation, the transcriptional signature of the middorsal head—the location of ectopic eye induction—converges onto that of regular compound eyes, including up-regulation of several retina-specific genes. Finally, a light-aversion behavioral assay to assess functionality reveals that ectopic compound eyes can rescue the ability to respond to visual stimuli when wild-type eyes are surgically removed. Combined, our results show that knockdown of a single gene is sufficient for the middorsal head to acquire the competence to ectopically generate a functional compound eye-like structure. These findings highlight the buffering capacity of developmental systems, allowing massive genetic perturbations to be channeled toward orderly and functional developmental outcomes, and render ectopic eye formation a widely accessible paradigm to study the evolution of complex systems.Fil: Zattara, Eduardo Enrique. Indiana University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Macagno, Anna L. M.. Indiana University; Estados UnidosFil: Busey, Hannah A.. Indiana University; Estados UnidosFil: Moczek, Armin P.. Indiana University; Estados Unido

Adaptive maternal behavioral plasticity and developmental programming mitigate the transgenerational effects of temperature in dung beetles

Phenotypic plasticity allows organisms to cope with rapid environmental change. Yet exactly when during ontogeny plastic responses are elicited, whether plastic responses produced in one generation influence phenotypic variation and fitness in subsequent generations, and the role of plasticity in shaping population divergences, remains overall poorly understood. Here, we use the dung beetle Onthophagus taurus to assess plastic responses to temperature at several life stages bridging three generations and compare these responses across three recently diverged populations. We find that beetles reared at hotter temperatures grow less than those reared at mild temperatures, and that this attenuated growth has transgenerational consequences by reducing offspring size and survival in subsequent generations. However, we also find evidence that plasticity may mitigate these consequences in two ways: 1) mothers modify the temperature of their offspring's developmental environment via behavioral plasticity and 2) in one population, offspring exhibit accelerated growth when exposed to hot temperatures during very early development (‘developmental programming’). Lastly, our study reveals that offspring responses to temperature diverged among populations in fewer than 100 generations, possibly in response to range-specific changes in climatic or social conditions.Fil: Macagno, Anna L. M.. Indiana University; Estados UnidosFil: Zattara, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Indiana University; Estados UnidosFil: Ezeakudo, Onye. Homestead High School; Estados UnidosFil: Moczek, Armin P.. Indiana University; Estados UnidosFil: Ledón Rettig, Cristina. Indiana University; Estados Unido

The impact of fixed triple therapy with beclometasone/formoterol/glycopyrronium on health status and adherence in chronic obstructive pulmonary disease (COPD) in an italian context of real life: The TRITRIAL study protocol

Background: The fixed triple combination Beclometasone dipropionate/Formoterol fuma- rate/Glycopyrronium (BDP/FF/G, Trimbow\uae), an extrafine formulation in a unique pressur- ized metered dose inhaler, is indicated for the maintenance treatment in adult patients with moderate to severe COPD, not adequately treated by ICS/LABA or LABA/LAMA. Besides the evidence from three randomized controlled trials, the impact of fixed triple therapy has not been extensively evaluated in a real-world population of COPD patients. TRITRIAL (TRIple Therapy in Real life: Impact on Adherence and HeaLth status) is a non- interventional study to assess the effect of BDP/FF/G in a real world setting in Italy. Design: TRITRIAL is a 12-month, multicenter, cohort, prospective, longitudinal observational study. Two follow-up visits will be performed at 6 and 12 months, respectively. The study includes the collection of anamnestic clinical and functional data before the start of BDP/FF/G. The study is built for digital conduction, from signature of the informed consent on a dedicated web platform, to the collection of questionnaires and clinical data on the eCRF. Population: A total of 800 patients with COPD ranging from Global Initiative for Obstructive Lung Disease (GOLD) stages 2 to 4, receiving therapy with BDP/FF/G accord- ing to the Summary of Product Characteristics and local clinical practice, will be recruited. All concomitant therapies will be permitted for the duration of the study. Evaluations: The primary endpoint is the change of CAT score at 12 months versus baseline. Secondary endpoints are adherence, health-related quality of life, sleep quality, disease-related outcomes (lung function and COPD exacerbations), device usability, eco- nomic resources consumption, and safety. Conclusion: TRITRIAL study is expected to give relevant information about effectiveness of BDP/FF/G fixed triple therapy in a real-life setting of patients with COPD, where adherence, usability of inhalers and patient\u2019s preference of the device are crucial factors for the success of the therapy

Correlation between SERS of Pyridine and Electrochemical Response of Silver Electrodes in Halide-Free Alkaline Solutions

Surface-enhanced Raman scattering (SERS) of pyridine (Py) on Ag electrodes in alkaline solutions free of halide ions was obtained at 25°C as a function of the applied potential. The Ag surface was activated for SERS through repetitive oxidation-reduction cycles (ORC), the effect being dependent on the electrochemical electrode history. The SERS effect was correlated to the activation for the hydrogen evolution reaction (HER), which can be obtained by means of potentiodynamic as well as potentiostatic procedures. The maximum SERS activity was achieved at potentials near the potential of zero charge (pzc) of polycrystalline Ag and appeared to be related to the maximum observed in the roughness factor vs potential curve. These results can be interpreted through the formation of a new uniform globular overlayer structure on the electroreduced Ag surface, which apparently exhibits a certain degree of preferred crystallographic orientation. Three well-defined potential regions can be distinguished for the complex competitive interactions between H2O, OH- ion, and Py with the new Ag electrode surface.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Individual differences in level of wisdom are associated with brain activation during a moral decision-making task.

IntroductionWisdom is reportedly associated with better health and quality of life. However, our knowledge of the neurobiology of wisdom is still in the early stages of development. We aimed to improve our understanding by correlating a psychometric measure of the trait with patterns of brain activation produced by a cognitive task theorized to be relevant to wisdom: moral decision-making. In particular, we aimed to determine whether individual differences in wisdom interact with moral task complexity in relation to brain activation.MethodsParticipants were 39 community-dwelling men and women aged 27-76 years, who completed moral and nonmoral decision-making tasks while undergoing functional magnetic resonance imaging. Brain activation in select regions of interest was correlated with participants' scores on the San Diego Wisdom Scale (SD-WISE).ResultsIndividual differences in wisdom were found to interact with brain response to moral versus nonmoral and moral personal versus impersonal dilemmas, particularly in regions in or near the default mode network. Persons with higher scores on the SD-WISE had less contrast between moral and nonmoral dilemmas and greater contrast between moral-personal and moral-impersonal dilemmas than individuals with lower SD-WISE scores.ConclusionsResults confirmed our hypothesis that individual differences in level of wisdom would interact with moral condition in relation to brain activation, and may underscore the relevance of considering one's own and others' actions and experiences in the context of wise thinking. Future studies are needed to replicate these findings and to examine specific neurocircuits