Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles

Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene LGALS3BP, we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alterations in migratory dynamics. To investigate how extracellular vesicles affect neuronal specification and migration dynamics, we collected extracellular vesicles from ventral cerebral organoids carrying a mutation in LGALS3BP, previously identified in individuals with cortical malformations and neuropsychiatric disorders. These results revealed differences in protein composition and changes in dorsoventral patterning. Proteins associated with cell fate decision, neuronal migration, and extracellular matrix composition were altered in mutant extracellular vesicles. Moreover, we show that treatment with extracellular vesicles changes the transcriptomic profile in neural progenitor cells. Our results indicate that neuronal molecular differentiation can be influenced by extracellular vesicles

Constraining Non-Standard Interactions of the Neutrino with Borexino

We use the Borexino 153.6 ton.year data to place constraints on non-standard neutrino-electron interactions, taking into account the uncertainty in the 7Be solar neutrino flux, and backgrounds due to 85Kr and 210Bi beta-decay. We find that the bounds are comparable to existing bounds from all other experiments. Further improvement can be expected in Phase II of Borexino due to the reduction in the 85Kr background.Comment: 21 pages, 16 pdf figures, 2 tables. Analysis updated including the uncertainty in sin^2\theta_{23}. Accepted in JHE

DeadEasy Mito-Glia: Automatic Counting of Mitotic Cells and Glial Cells in Drosophila

Cell number changes during normal development, and in disease (e.g., neurodegeneration, cancer). Many genes affect cell number, thus functional genetic analysis frequently requires analysis of cell number alterations upon loss of function mutations or in gain of function experiments. Drosophila is a most powerful model organism to investigate the function of genes involved in development or disease in vivo. Image processing and pattern recognition techniques can be used to extract information from microscopy images to quantify automatically distinct cellular features, but these methods are still not very extended in this model organism. Thus cellular quantification is often carried out manually, which is laborious, tedious, error prone or humanly unfeasible. Here, we present DeadEasy Mito-Glia, an image processing method to count automatically the number of mitotic cells labelled with anti-phospho-histone H3 and of glial cells labelled with anti-Repo in Drosophila embryos. This programme belongs to the DeadEasy suite of which we have previously developed versions to count apoptotic cells and neuronal nuclei. Having separate programmes is paramount for accuracy. DeadEasy Mito-Glia is very easy to use, fast, objective and very accurate when counting dividing cells and glial cells labelled with a nuclear marker. Although this method has been validated for Drosophila embryos, we provide an interactive window for biologists to easily extend its application to other nuclear markers and other sample types. DeadEasy MitoGlia is freely available as an ImageJ plug-in, it increases the repertoire of tools for in vivo genetic analysis, and it will be of interest to a broad community of developmental, cancer and neuro-biologists

Minimal lepton flavor violating realizations of minimal seesaw models

We study the implications of the global U(1)R symmetry present in minimal lepton flavor violating implementations of the seesaw mechanism for neutrino masses. In the context of minimal type I seesaw scenarios with a slightly broken U(1)R, we show that, depending on the R-charge assignments, two classes of generic models can be identified. Models where the right-handed neutrino masses and the lepton number breaking scale are decoupled, and models where the parameters that slightly break the U(1)R induce a suppression in the light neutrino mass matrix. We show that within the first class of models, contributions of right-handed neutrinos to charged lepton flavor violating processes are severely suppressed. Within the second class of models we study the charged lepton flavor violating phenomenology in detail, focusing on mu to e gamma, mu to 3e and mu to e conversion in nuclei. We show that sizable contributions to these processes are naturally obtained for right-handed neutrino masses at the TeV scale. We then discuss the interplay with the effects of the right-handed neutrino interactions on primordial B - L asymmetries, finding that sizable right-handed neutrino contributions to charged lepton flavor violating processes are incompatible with the requirement of generating (or even preserving preexisting) B - L asymmetries consistent with the observed baryon asymmetry of the Universe.Comment: 21 pages, 4 figures; version 2: Discussion on possible generic models extended, typos corrected, references added. Version matches publication in JHE

The Glial Regenerative Response to Central Nervous System Injury Is Enabled by Pros-Notch and Pros-NFκB Feedback

Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces proliferation of enwrapping glia, leading to axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, and may reflect a common underlying genetic mechanism. Here, we show that injury to the Drosophila larval CNS induces glial proliferation, and we uncover a gene network controlling this response. It consists of the mutual maintenance between the cell cycle inhibitor Prospero (Pros) and the cell cycle activators Notch and NFκB. Together they maintain glia in the brink of dividing, they enable glial proliferation following injury, and subsequently they exert negative feedback on cell division restoring cell cycle arrest. Pros also promotes glial differentiation, resolving vacuolization, enabling debris clearance and axonal enwrapment. Disruption of this gene network prevents repair and induces tumourigenesis. Using wound area measurements across genotypes and time-lapse recordings we show that when glial proliferation and glial differentiation are abolished, both the size of the glial wound and neuropile vacuolization increase. When glial proliferation and differentiation are enabled, glial wound size decreases and injury-induced apoptosis and vacuolization are prevented. The uncovered gene network promotes regeneration of the glial lesion and neuropile repair. In the unharmed animal, it is most likely a homeostatic mechanism for structural robustness. This gene network may be of relevance to mammalian glia to promote repair upon CNS injury or disease

Tratamiento de Flegmasía Cerúlea Dolens con Trombólisis; Reporte de Caso

La Flegmasía Cerúlea Dolens es una complicación rara y severa de la trombosis venosa profunda, que se manifiesta clínicamente con edema profuso, dolor y cianosis del miembro inferior afectado. La obstrucción masiva del sistema venoso determina un aumento de la presión de los compartimentos de la extremidad, que finalmente compromete la circulación arterial. Su tratamiento debe ser agresivo para evitar la gangrena y/o la muerte. Presentamos el caso de una paciente atendida en la Clínica La Sagrada Familia, Armenia – Colombia, quien consultó por cuadro clínico de edema progresivo en miembro inferior izquierdo, encontrando cambios isquémicos en falanges distales y edema grado III en miembro inferior izquierdo, con reporte de dúplex venoso con trombosis venosa profunda iliofemoral extensa izquierda y dúplex arterial con reducción de los flujos arteriales secundario a edema severo de tejidos blandos, se indica flebografía con trombólisis venosa por catéter regional en miembro inferior izquierdo con infusión continua de trombolítico. Con respectivos controles angiográficos a las 24 y 48 horas con recanalización del 80% de las venas iliaca, femoral y poplítea, se suspendió infusión y se retiró catéter, continuó anticoagulación con heparina no fraccionada hasta lograr paso a anticoagulación oral con posterior egreso hospitalario dado su evolución satisfactoria

Repressing Anarchy in Neutrino Mass Textures

The recent results that $\theta_{13}$ is relatively large, of the order of the previous upper bound, and the indications of a sizable deviation of $\theta_{23}$ from the maximal value are in agreement with the predictions of Anarchy in the lepton sector. The quark and charged lepton hierarchies can then be reproduced in a SU(5) GUT context by attributing non-vanishing $U(1)_{FN}$ charges, different for each family, only to the SU(5) tenplet states. The fact that the observed mass hierarchies are stronger for up quarks than for down quarks and charged leptons supports this idea. As discussed in the past, in the flexible context of $SU(5)\otimes U(1)_{FN}$, different patterns of charges can be adopted going from Anarchy to various types of hierarchy. We revisit this approach by also considering new models and we compare all versions to the present data. As a result we confirm that, by relaxing the extreme ansatz of equal $U(1)_{FN}$ charges for all SU(5) pentaplets and singlets, better agreement with the data than for Anarchy is obtained without increasing the model complexity. We also present the distributions obtained in the different models for the Dirac CP-violating phase. Finally we discuss the relative merits of these simple models.Comment: v1: 12 pages, 3 figures; v2: 13 pages, 3 figures, text improved, matches version accepted for publication; v3: submitted to add an acknowledgment to a networ