“Iglesia me llamo”: realidad y ficción en los alias criminales del Siglo de Oro

Este estudio tiene el propósito combinado de anunciar de nuevo un rico caudal de datos sobre los numerosos apodos criminales del siglo XVII y demostrar que la creatividad y hasta exageración patentes en los apodos reales no son menores que las de las creaciones literarias de los autores de la época. A veces, hasta la realidad es más extraña que la fi cción, como suele decirse en inglés. Será este artículo una invitación a volver a las fuentes para intentar librarnos de encadenamientos circulares de citas encontradas en ediciones modernas de comedias, poemas y novelas del Siglo de Oro. Estos encadenamientos pueden atraparnos sin que podamos averiguar si lo que leemos en una obra es pura fi cción, inspirada por algo real, o informe sobre una realidad indiscutible. Es importante notar que, como mis predecesores, no he intentado hacer una lista exhaustiva de apodos y su sentido, sino ofrecer unos ejemplos que pertenecen a unas tendencias particulares.This study has both the purpose of reintroducing scholars to a rich trove of information about many criminal nicknames from the seventeenth century and the purpose of demonstrating that the creativity, and even exaggeration, present in the real nicknames are no less than those of the era’s author’s literary creations. At times truth is stranger than fiction, as the old saying goes. This article will be an invitation to return to the source in order to free ourselves from circular chains of association based on citations found in modern editions of comedias, poems, and novels from the Golden Age. These associations can trap us and impede us from verifying if what we are reading in a work is pure fi ction, inspired by something real, or information from an undeniable reality. It is important to note that, as with my predecessors, I have not attempted to make an exhaustive list, but rather offer to some examples that belong to particular tendencies

Dispersed Activity during Passive Movement in the Globus Pallidus of the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Treated Primate

Parkinson's disease is a neurodegenerative disorder manifesting in debilitating motor symptoms. This disorder is characterized by abnormal activity throughout the cortico-basal ganglia loop at both the single neuron and network levels. Previous neurophysiological studies have suggested that the encoding of movement in the parkinsonian state involves correlated activity and synchronized firing patterns. In this study, we used multi-electrode recordings to directly explore the activity of neurons from the globus pallidus of parkinsonian primates during passive limb movements and to determine the extent to which they interact and synchronize. The vast majority (80/103) of the recorded pallidal neurons responded to periodic flexion-extension movements of the elbow. The response pattern was sinusoidal-like and the timing of the peak response of the neurons was uniformly distributed around the movement cycle. The interaction between the neuronal activities was analyzed for 123 simultaneously recorded pairs of neurons. Movement-based signal correlation values were diverse and their mean was not significantly different from zero, demonstrating that the neurons were not activated synchronously in response to movement. Additionally, the difference in the peak responses phase of pairs of neurons was uniformly distributed, showing their independent firing relative to the movement cycle. Our results indicate that despite the widely distributed activity in the globus pallidus of the parkinsonian primate, movement encoding is dispersed and independent rather than correlated and synchronized, thus contradicting current views that posit synchronous activation during Parkinson's disease

Rescuing Loading Induced Bone Formation at Senescence

The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential

Resistance to MPTP-Neurotoxicity in α-Synuclein Knockout Mice Is Complemented by Human α-Synuclein and Associated with Increased β-Synuclein and Akt Activation

Genetic and biochemical abnormalities of α-synuclein are associated with the pathogenesis of Parkinson's disease. In the present study we investigated the in vivo interaction of mouse and human α-synuclein with the potent parkinsonian neurotoxin, MPTP. We find that while lack of mouse α-synuclein in mice is associated with reduced vulnerability to MPTP, increased levels of human α-synuclein expression is not associated with obvious changes in the vulnerability of dopaminergic neurons to MPTP. However, expressing human α-synuclein variants (human wild type or A53T) in the α-synuclein null mice completely restores the vulnerability of nigral dopaminergic neurons to MPTP. These results indicate that human α-synuclein can functionally replace mouse α-synuclein in regard to vulnerability of dopaminergic neurons to MPTP-toxicity. Significantly, α-synuclein null mice and wild type mice were equally sensitive to neurodegeneration induced by 2′NH2-MPTP, a MPTP analog that is selective for serotoninergic and noradrenergic neurons. These results suggest that effects of α-synuclein on MPTP like compounds are selective for nigral dopaminergic neurons. Immunoblot analysis of β-synuclein and Akt levels in the mice reveals selective increases in β-synuclein and phosphorylated Akt levels in ventral midbrain, but not in other brain regions, of α-synuclein null mice, implicating the α-synuclein-level dependent regulation of β-synuclein expression in modulation of MPTP-toxicity by α-synuclein. Together these findings provide new mechanistic insights on the role α-synuclein in modulating neurodegenerative phenotypes by regulation of Akt-mediated cell survival signaling in vivo

“Iglesia me llamo”: realidad y ficción en los alias criminales del Siglo de Oro

Este estudio tiene el propósito combinado de anunciar de nuevo un rico caudal de datos sobre los numerosos apodos criminales del siglo XVII y demostrar que la creatividad y hasta exageración patentes en los apodos reales no son menores que las de las creaciones literarias de los autores de la época. A veces, hasta la realidad es más extraña que la fi cción, como suele decirse en inglés. Será este artículo una invitación a volver a las fuentes para intentar librarnos de encadenamientos circulares de citas encontradas en ediciones modernas de comedias, poemas y novelas del Siglo de Oro. Estos encadenamientos pueden atraparnos sin que podamos averiguar si lo que leemos en una obra es pura fi cción, inspirada por algo real, o informe sobre una realidad indiscutible. Es importante notar que, como mis predecesores, no he intentado hacer una lista exhaustiva de apodos y su sentido, sino ofrecer unos ejemplos que pertenecen a unas tendencias particulares.This study has both the purpose of reintroducing scholars to a rich trove of information about many criminal nicknames from the seventeenth century and the purpose of demonstrating that the creativity, and even exaggeration, present in the real nicknames are no less than those of the era’s author’s literary creations. At times truth is stranger than fiction, as the old saying goes. This article will be an invitation to return to the source in order to free ourselves from circular chains of association based on citations found in modern editions of comedias, poems, and novels from the Golden Age. These associations can trap us and impede us from verifying if what we are reading in a work is pure fi ction, inspired by something real, or information from an undeniable reality. It is important to note that, as with my predecessors, I have not attempted to make an exhaustive list, but rather offer to some examples that belong to particular tendencies

Expanding the medicinal chemistry synthetic toolbox

The key objectives of medicinal chemistry are to efficiently design and synthesize bioactive compounds that have the potential to become safe and efficacious drugs. Most medicinal chemistry programmes rely on screening compound collections populated by a range of molecules derived from a set of known and robust chemistry reactions. Analysis of the role of synthetic organic chemistry in subsequent hit and lead optimization efforts suggests that only a few reactions dominate. Thus, the uptake of new synthetic methodologies in drug discovery is limited. Starting from the known limitations of reaction parameters, synthesis design tools, synthetic strategies and innovative chemistries, here we highlight opportunities for the expansion of the medicinal chemists’ synthetic toolbox. More intense crosstalk between synthetic and medicinal chemists in industry and academia should enable enhanced impact of new methodologies in future drug discovery. © 2018 Springer Nature Limited. All rights reserved