Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy

15 p.Hypoglycosylation of α-dystroglycan (cx-DG) resulting from deficiency of protein O-mannosyltransferase 1 (POMT1) may cause severe neuromuscular dystrophies with brain and eye anomalies, named dystroglycanopathies. The retinal involvement of these disorders motivated us to generate a conditional knockout (cKO) mouse experiencing a Pomt1 intragenic deletion (exons 3–4) during the development of photoreceptors, mediated by the Cre recombinase expressed from the cone-rod homeobox (Crx) gene promoter. In this mouse, retinal α-DG was unglycosylated and incapable of binding laminin. Retinal POMT1 deficiency caused significant impairments in both electroretinographic recordings and optokinetic reflex in Pomt1 cKO mice, and immunohistochemical analyses revealed the absence of β-DG and of the α-DG-interacting protein, pikachurin, in the outer plexiform layer (OPL). At the ultrastructural level, noticeable alterations were observed in the ribbon synapses established between photoreceptors and bipolar cells. Therefore, O-mannosylation of α-DG in the retina carried out by POMT1 is crucial for the establishment of proper synapses at the OPL and transmission of visual information from cones and rods to their postsynaptic neurons

Spinal Manipulative Therapy Effects in Autonomic Regulation and Exercise Performance in Recreational Healthy Athletes : A Randomized Controlled Trial

7 p.Study design: A randomized, double blind, parallel groups, sham-controlled trial. Objective: The aim of this study was to analyze the acute effects of spinal manipulative therapy (SMT) on performance and autonomic modulation. Summary of background data: The use of SMT is progressively spreading from the clinical to the sporting context owing to its purported ergogenic effects. However, its effects remain unclear. Methods: Thirty-seven male recreational athletes (aged 37 ± 9 years) who had never received SMT were assigned to a sham (n = 19) or actual SMT group (n = 18). Study endpoints included autonomic modulation (heart rate variability), handgrip strength, jumping ability, and cycling performance [8-minute time trial (TT)]. Differences in custom effects between interventions were determined using magnitude-based inferences. Results: A significant and very likely lower value of a marker of sympathetic modulation, the stress score, was observed in response to actual compared with sham SMT [P = 0.007; effect size (ES) = -0.97]. A trend toward a significant and likely lower sympathetic:parasympathetic ratio (P = 0.055; ES = -0.96) and a likely higher natural logarithm of the root-mean-square differences of successive heartbeat intervals [(LnRMSSD), P = 0.12; ES = 0.36] was also found with actual SMT. Moreover, a significantly lower mean power output was observed during the TT with actual compared with sham SMT (P = 0.035; ES = -0.28). Nonsignificant (P > 0.05) and unclear or likely trivial differences (ES < 0.2) were found for the rest of endpoints, including handgrip strength, heart rate during the TT, and jump loss thereafter. Conclusion: A single pre-exercise SMT session induced an acute shift toward parasympathetic dominance and slightly impaired performance in recreational healthy athletes

Tools and Biomarkers for the Study of Retinal Ganglion Cell Degeneration

The retina is part of the central nervous system, its analysis may provide an idea of the health and functionality, not only of the retina, but also of the entire central nervous system, as has been shown in Alzheimer"s or Parkinson"s diseases. Within the retina, the ganglion cells (RGC) are the neurons in charge of processing and sending light information to higher brain centers. Diverse insults and pathological states cause degeneration of RGC, leading to irreversible blindness or impaired vision. RGCs are the measurable endpoints in current research into experimental therapies and diagnosis in multiple ocular pathologies, like glaucoma. RGC subtype classifications are based on morphological, functional, genetical, and immunohistochemical aspects. Although great efforts are being made, there is still no classification accepted by consensus. Moreover, it has been observed that each RGC subtype has a different susceptibility to injury. Characterizing these subtypes together with cell death pathway identification will help to understand the degenerative process in the different injury and pathological models, and therefore prevent it. Here we review the known RGC subtypes, as well as the diagnostic techniques, probes, and biomarkers for programmed and unprogrammed cell death in RGC

Role of ON and OFF Visual Pathways in Rod- and Cone-Driven Flicker Responses

Purpose: To evaluate the effects of various retinal neurotransmitters on temporal resolution, particularly, on the Critical Flicker Fusion Frequency (CFF), which has been previously applied in ophthalmic pathophysiologic research. Methods: A binocular physiologic electroretinogram was performed on adult mice. Animals in the control group were injected in the right eye with 1 & mu;L of phosphate-buffered saline (PBS). Animals in the experimental group were injected in the left eye with 1 & mu;L of PBS and in the right eye with 1 & mu;L of PBS to which different molecules were added: 2-amino-4-phosphonobutyric hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). Initially, rod response was recorded and later the cone response. Results: APB suppressed the rod-driven, but not the cone-driven flicker response. The other agents severely affected the lower flickering frequency response amplitude, in particular, at 3 Hz. The threshold of CFF was lowered from 50 Hz to 40 Hz after applying APB, Glycine, and HEPES. GABA remarkably enhanced rod-driven and cone-driven flicker response at 3 Hz, whereas Glutamate and GABA/Glutamate only did in rod-driven flicker response. Conclusions: Both ON and OFF visual pathways were implied in cone-driven response, but only the ON visual pathway appears to play a relevant role in rod-driven flicker response. Flicker response seems to be enhanced by horizontal cells both in roddriven and cone-driven response. In addition, due to the greater sensitivity of the flicker at low frequencies, it is suggested that pathophysiological studies should be carried out at said frequencies

Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.This work was supported by project grants from Spanish Ministerio de Economía y Competitividad-FEDER (http://www.mineco.gob.es) #BFU2012‐36845, Instituto de Salud Carlos III RETICS (http://www.oftared.com) #RD12/0034/0010 and Organización Nacional de Ciegos Españoles (http://www.once.es) to NC; Ministerio de Ciencia e Innovación #JCI‐2009‐05224 to VGV; Universidad de Alicante (http://www.ua.es) #2010-48536273 to GE; Instituto de Salud Carlos III (http://www.isciii.es) #PI13/02098 and RETICS #RD12/0034/0006 to PdV; and FUNDALUCE

Deleterious Effect of NMDA Plus Kainate on the Inner Retinal Cells and Ganglion Cell Projection of the Mouse

Combined administration of N-Methyl-D-Aspartate (NMDA) and kainic acid (KA) on the inner retina was studied as a model of excitotoxicity. The right eye of C57BL6J mice was injected with 1 µL of PBS containing NMDA 30 mM and KA 10 mM. Only PBS was injected in the left eye. One week after intraocular injection, electroretinogram recordings and immunohistochemistry were performed on both eyes. Retinal ganglion cell (RGC) projections were studied by fluorescent-cholerotoxin anterograde labeling. A clear decrease of the retinal “b” wave amplitude, both in scotopic and photopic conditions, was observed in the eyes injected with NMDA/KA. No significant effect on the “a” wave amplitude was observed, indicating the preservation of photoreceptors. Immunocytochemical labeling showed no effects on the outer nuclear layer, but a significant thinning on the inner retinal layers, thus indicating that NMDA and KA induce a deleterious effect on bipolar, amacrine and ganglion cells. Anterograde tracing of the visual pathway after NMDA and KA injection showed the absence of RGC projections to the contralateral superior colliculus and lateral geniculate nucleus. We conclude that glutamate receptor agonists, NMDA and KA, induce a deleterious effect of the inner retina when injected together into the vitreous chamber.This research was funded by the Instituto de Salud Carlos III and co‐funded by the European Regional Development Fund (ERDF) within the “Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020” (grant numbers #RD16/0008/0016; #RD16/0008/0020; #FIS/PI 18‐00754)

Ensamble de aves en zonas con diferente grado de urbanización en la ciudad de Bahía

La fragmentación y cambios en la vegetación se encuentran entre los procesos relacionados a la urbanización con mayor incidencia sobre las aves. El objetivo del trabajo es analizar las variaciones en el ensamble de aves según el grado de urbanización en la ciudad de Bahía Blanca, Buenos Aires. Se definieron 20 transectas de 100m de longitud (ambas veredas) en el micro-centro, macro-centro y periferia de la ciudad. Se realizaron dos muestreos semanales de octubre a diciembre de 2007. Se registró la riqueza y abundancia de aves, las perchas utilizadas y el número de automóviles/personas transitando por minuto. Se observaron 25 especies de aves, de las cuales las más comunes fueron Columba livia, Zenaida auriculata y Passer domesticus. Las transectas con mayor tránsito vehicular y peatonal mostraron las menores riquezas específicas. La mayoría de las aves observadas utilizaron árboles como perchas para posarse. Los gremios más representados fueron los granívoros, omnívoros e insectívoros. Nuestros resultados indican que el impacto de la urbanización sobre los ambientes naturales podría provocar la retracción de algunas especies y favorecer la expansión de otras ampliamente distribuidas.Fragmentation and vegetation changes are processes related to urbanization with an important incidence on birds. In this work we analize the bird assemblage variations along an urban gradient in Bahía Blanca city, Buenos Aires. Twenty transects were established, 100 metres long and 12 metres wide, in the micro-centre, macro-centre and the periphery of the city. Two samples a week were taken from october to december. We registered richness, bird abundance, perche-sites and number of vehicles/people per minute. Twenty five species were observed and Columba livia, Zenaida auriculata and Passer domesticus were the most common species. The transects with more vehicular and pedestrian traffic showed the minor specific richnesses. The most observed birds used trees as perche-sites. Granivores, omnivores and insectivores were the most represented guilds. Our results indicate that the impact of urbanization on natural environments could provoke the retraction of some species and promote the expansion of other of them widely distributed.Fil: Germain, Paola. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Grupo de Estudios en Conservación y Manejo; ArgentinaFil: Cuevas, Yannina Andrea. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Grupo de Estudios en Conservación y Manejo; ArgentinaFil: Sanhueza, Cristina del Carmen. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Grupo de Estudios en Conservación y Manejo; ArgentinaFil: Tizón, Francisco Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Loydi, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: de Villalobos, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Zapperi, Georgina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Vazquez, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Pompozzi, Gabriel Alejandro. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Zoología de Invertebrados II; ArgentinaFil: Piovan, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentin

The role of entrepreneurship and green innovation intention on sustainable development: moderating impact of inclusive leadership

Today, sustainable development (SD) is a worldwide requirement due to the numerous environmental challenges that require the attention of academics. Consequently, the current study explores the effect of entrepreneurial and green innovation aims on SD in Peru. In addition, the study examines the moderating effect of inclusive leadership on entrepreneurship, green innovation intention, and sustainable development in Peru. The study utilized primary data collection instruments such as questionnaires to collect information from the selected respondents. The paper also used smart-PLS to examine the data's dependability and the correlation between factors. In Peru, entrepreneurship and green innovation intentions were found to have a good relationship with sustainable development. In addition, the data demonstrated that inclusive leadership moderates the relationship between entrepreneurship, green innovation intention, and SD in Peru. The essay supports policy-making authorities in formulating SD-related policies by refocusing entrepreneurs' attention on green innovation.Wilson Cruz Mamani (Universidad Peruana Unión Juliaca), Germain Marcos Lagos Manrique (Universidad Nacional Federico Villarreal), Soraya del Pilar Carranco Madrid (Universidad Central del Ecuador), Edward Espinoza Herrera (Universidad Nacional Federico Villarreal), David Barrial Acosta (Universidad Nacional Micaela Bastidas de Apurímac), Rolando Remy Rivas-Diaz (Universidad Nacional de San Agustín), José Luis Arias-Gonzáles (University of British Columbia), Yuselino Maquera Maquera (Universidad Nacional del Altiplano Puno), Francisco Samael Saravia Ramos (Universidad Nacional De San Agustín)Includes bibliographical references

A virtual imaging platform for multi-modality medical image simulation.

International audienceThis paper presents the Virtual Imaging Platform (VIP), a platform accessible at http://vip.creatis.insa-lyon.fr to facilitate the sharing of object models and medical image simulators, and to provide access to distributed computing and storage resources. A complete overview is presented, describing the ontologies designed to share models in a common repository, the workflow template used to integrate simulators, and the tools and strategies used to exploit computing and storage resources. Simulation results obtained in four image modalities and with different models show that VIP is versatile and robust enough to support large simulations. The platform currently has 200 registered users who consumed 33 years of CPU time in 2011

Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor-associated macrophages

Tumor-associated macrophages (TAMs), a class of immune cells that play a key role in tumor immunosuppression, are recognized as important targets to improve cancer prognosis and treatment. Consequently, the engineering of drug delivery nanocarriers that can reach TAMs has acquired special relevance. This work describes the development and biological evaluation of a panel of hyaluronic acid (HA) nanocapsules (NCs), with different compositions and prepared by different techniques, designed to target macrophages. The results showed that plain HA NCs did not significantly influence the polarization of M0 and M2-like macrophages towards an M1-like pro-inflammatory phenotype; however, the chemical functionalization of HA with mannose (HA-Man) led to a significant increase of NCs uptake by M2 macrophages in vitro and to an improved biodistribution in a MN/MNCA1 fibrosarcoma mouse model with high infiltration of TAMs. These functionalized HA-Man NCs showed a higher accumulation in the tumor compared to non-modified HA NCs. Finally, the pre-administration of the liposomal liver occupying agent Nanoprimer™ further increased the accumulation of the HA-Man NCs in the tumor. This work highlights the promise shown by the HA-Man NCs to target TAMs and thus provides new options for the development of nanomedicine and immunotherapy-based cancer treatmentsOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the 2^2-INTRATARGET project (A20/00028) funded by the ISCIII under the umbrella of the ERA NET EuroNanoMed GA N 723770 of the EU Horizon 2020 Research and Innovation Programme. This work was also supported by the Xunta de Galicia (ED431C 2018/30, and “Centro singular de investigación de Galicia” accreditation 2019 − 2022, ED431G2019/03), and the European Union (European Regional Development Fund-ERDF)S