110 research outputs found
La imagen del Gran Ducado de Lituania en el relato de viaje de Pedro Cubero Sebastián
No full textThis paper analyzes the image of the Grand Duchy of Lithuania pre-sented in the chapter XXI of Peregrinación del mundo del doctor Pedro Cubero Se-bastián (1682). Starting from the premise of the documentary value of the work, we carry out a comparative analysis of it with the other testimonies of the epoch. Likewise, we determine the nuclei around which the author organizes the narrative material: the political and the religious one, and we focus on investigating the inten-tional selection of the data that he provides to specify the condition of the recipients of his story, as well as its real purposeEn el presente artículo se analiza la imagen del Gran Ducado de Li-tuania presentada en el capítulo XXI de la Peregrinación del mundo del doctor Pe-dro Cubero Sebastián (1682). Partiendo de la premisa del valor documental de la obra, efectuamos un análisis comparativo de la misma con los demás testimonios de la época. Asimismo, determinamos los núcleos en torno a los cuales el autor organiza el material narrativo: el político y el religioso, y nos centramos en indagar en la intencionada selección de los datos que aporta para precisar la condición de los destinatarios de su relato, así como su verdadera finalida
La imagen del Gran Ducado de Lituania en el relato de viaje de Pedro Cubero Sebastián
No full textThis paper analyzes the image of the Grand Duchy of Lithuania presented in the chapter XXI of Peregrinación del mundo del doctor Pedro Cubero Sebastián (1682). Starting from the premise of the documentary value of the work, we carry out a comparative analysis of it with the other testimonies of the epoch. Likewise, we determine the nuclei around which the author organizes the narrative material: the political and the religious one, and we focus on investigating the intentional selection of the data that he provides to specify the condition of the recipients of his story, as well as its real purpose.
En el presente artículo se analiza la imagen del Gran Ducado de Lituania presentada en el capítulo XXI de la Peregrinación del mundo del doctor Pedro Cubero Sebastián (1682). Partiendo de la premisa del valor documental de la obra, efectuamos un análisis comparativo de la misma con los demás testimonios de la época. Asimismo, determinamos los núcleos en torno a los cuales el autor organiza el material narrativo: el político y el religioso, y nos centramos en indagar en la intencionada selección de los datos que aporta para precisar la condición de los destinatarios de su relato, así como su verdadera finalidad
PREreview of "The synapsin-dependent vesicle cluster is crucial for presynaptic plasticity at a glutamatergic synapse in male mice"
No full textThis Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/8376891.
This review reflects comments and contributions from Alberto J. Gonzalez-Hernandez, Ryan Cubero & Femi Arogundade. Review synthesized by Ryan Cubero.
The study builds up on a previous study (Owe et al., 2009) that observed impaired frequency facilitation and reduced distal vesicle density in symptomatic synapsin I/II double knockout mice, and fills the gap by unraveling the role of synapsins in the presynaptic mediated plasticity by evaluating the effects of the total loss of synapsins using a triple KO for synapsin I, II and III (SynTKO) in a region of the brain which expresses synapsin III isoform in adult male mice (hippocampal mossy fibers - CA3 glutamatergic synapses). The study follows rigorous ethical and methodological guidelines, utilizing various experimental techniques, including electrophysiological recordings and transmission electron microscopy, to comprehensively analyze synaptic properties in synapsin triple knockout mice. The study reveals that the absence of all synapsin isoforms leads to altered excitability, vesicle organization, and plasticity in mossy fiber boutons, providing insights into the critical role of synapsins in synaptic function and plasticity.
Positive aspects of the paper:
The findings offer valuable insights into how the absence of all synapsin isoforms affects synaptic properties, potentially advancing our knowledge of neurological conditions related to synaptic dysfunction.
The study employs a well-structured study design, utilizing two age groups (presymptomatic and symptomatic) and comparing C57BL/6J control mice with SynTKO mice. This design allows for the investigation of changes before and after the onset of epileptic seizures in SynTKO animals.
The study rigorously examines synaptic function and structure, employing various assays and statistical analyses. This scientific rigor strengthens the validity of the results.
The use of blinding during data analysis is a positive aspect of the study. The experimenter was blinded to the treatment of slices, ensuring that the analysis is objective and not influenced by prior knowledge.
The authors reported the study in accordance with the SAGER guidelines and ARRIVE guidelines 2.0. Such practices should be recognized and highly commended.
Aspects that need to be addressed:
The measurements of Paired Pulse Ratio need to be improved. In Figure 1-2 panels b and c, the SynTKO condition has a replicate out of the range (which could be a potential outlier). This can be potentially addressed by increasing the number of replicates to really depict a better representation of the data dispersion. Furthermore, for panel c, the representative traces should be replaced to ones that represent the median. Ideally, the point of the condition selected for the trace can be highlighted in the graph (e.g. clear fill and same color outline).
In Figure 3c, the authors find a peculiar normalized fEPSP dynamics in SynTKO mice where the fEPSP slowly reaches a peak and slowly decreases, compared to control mice where the peak is reached immediately and decreases abruptly. Perhaps, the authors can discuss what could cause this altered LTP maintenance, given that there is reduced facilitation and PTP, but unimpaired paired-pulse ratio.
Minor comments:
In Figure 1c, the related text says "In SynTKO the amplitudes reached a plateau after 15 stimuli, whereas in WT animals, the amplitudes increased until the end of the 1 Hz stimulation". However, in the plot, there is a plateau for the WT condition around 20-25 stimuli. This sentence needs to be clarified or omitted if the data did not clearly depict this continuous increase.
As a general but minor comment, the representative traces of individual experiments should represent points close to the median (or average) and the point where the trace comes from can be highlighted in the plot.
The TEM images seem to show altered structural abnormalities in mossy fiber boutons in SynTKO mice compared to controls. Were there observed differences in synaptic bouton density?
Comments on reporting:
The statistical analyses are reported correctly in the methods section and table 5. Excluded recordings were also properly justified and detailed in table 6.
Suggestions for future studies:
In this mossy fiber-CA3 synapse, which has been reported to be highly plastic, it would be interesting to also explore what happens in the SynTKO model in presynaptic long term depression (caused by a low frequency stimulation protocol).
Inspecting potential differences in glutamate receptors in mossy fiber presynaptic boutons between SynTKO and control mice could help elucidate the observed differences in synaptic physiology.
Future experiments aiming to understand the role of synapsins (or the lack thereof) in inhibitory neurons will give us a clearer picture of the role of synapsins in synaptic function. It will also be interesting to explore how network connectivity is altered due to total loss of synapsins.
Competing interests
The author declares that they have no competing interests
El misionero aragonés Pedro Cubero Sebastián en Polonia: un relato del viaje realizado en 1674
No full textThe present article analyzes the chapters XVII and XVIII of the Breve relación de la peregrinación que ha hecho de la mayor parte del mundo don Pedro Cubero Sebastián, concerning the Aragonese missionary´s visit to Poland, in the light of the travel narrative theory. Taking into consideration the fundamental characteristics of the genre we focus on the documentary value of the book, as well as on the organization of its discourse. Paying attention to the geographic coordinates and descriptions of the places visited by the traveler, we present the detailed map of his route. We also concentrate on the country’s and its inhabitants’ image, that spreads throughout the book, in order to compare it with testimonies of the epoch and historical documents concerning the political situation in the Kingdom of Poland in the second half of the seventeenth century. Additionaly, we note the nuclei around which the author organizes the narrative material and clarify the role of these episodes in his relationEn el presente artículo se analizan los capítulos XVII y XVIII de la Breve relación de la peregrinación que ha hecho de la mayor parte del mundo don Pedro Cubero Sebastián, relativos a la visita del misionero aragonés a Polonia, a la luz de la teoría del relato de viajes. Teniendo en cuenta las características fundamentales del género nos fijamos en el valor documental de la obra, así como en la organización de su discurso. Atendiendo a las coordenadas geográficas y las descripciones de lugares visitados por el viajero, presentamos el detallado mapa de su ruta. Nos centramos también en la imagen del país y sus habitantes que difunde el libro, a fin de comparala con los testimonios de la época y documentos históricos concernientes a la situación política del Reino de Polonia en la segunda mitad del siglo XVII. Asimismo, señalamos los núcleos alrededor de los cuales el autor organiza el material narrativo y aclaramos la función que cumplen estos episodios dentro de su relació
PREreview of "The circadian clock is a pacemaker of the axonal regenerative ability"
No full text<p><strong>This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at <a href="https://prereview.org/reviews/10079230">https://prereview.org/reviews/10079230</a>.</strong></p>
<p><i>This review reflects comments and contributions by Bhargy Sharma, Ryan Cubero & Anna Oliveras. Review synthesized by Ryan Cubero.</i></p><p>In this preprint, De Virgiliis and colleagues use a murine model of sciatic injury to provide functional evidence that peripheral nerve regeneration is affected by circadian rhythm. The authors show that regenerative capacity of mice DRG neurons is time-of-day dependent and that the disruption of the intrinsic neuronal circadian rhythm via knockdown or deletion of Bmal1, a non-redundant core clock gene, decreases regeneration capability after injury. They found that injuries performed at ZT20 induce a transcriptional program that enhances regeneration and targets long-lasting re-innervation. Also, lithium, a chono-active compound, is pinpointed as a new therapeutic avenue for nerve repair. Although the role of the circadian clock has already been shown for other wound healing processes, these novel findings describe for the first time the regenerative potential in the PNS is controlled by neuronal intrinsic circadian clock and is time-of-day dependent. </p><p>Positive aspects of the study:</p><ul><li><p>The preprint starts with a meta-analysis of previously published transcriptomes, which allowed them to establish "circadian rhythms" as a potential common pathway. Studies like this that make use of the vast published transcriptomes should be highly encouraged and commended.</p></li><li><p>Overall, the experiments are well designed and well explained with images. The supplementary material provides extensive control experiments that help to draw and strengthen the conclusions.</p></li><li><p>The conclusions suggest a careful re-evaluation of previous data interpretation taking in account the time dependency of data acquisition. This might help to solve previous controversial data. As well, the conclusions highlight important considerations for future experimental designs. We believe that the findings provided by the authors are remarkably relevant for the scientific community, specially those in the field of axonal regeneration research.</p></li><li><p>The implications of the study for future therapeutic strategies:</p><ul><li><p>Focusing current neurorehabilitation therapies to time-of-day effects</p></li><li><p>Using chrono-active compounds for axon regeneration therapies</p></li><li><p>Potential gene therapy targeting circadian clock molecular machinery</p></li></ul></li></ul><p>Major aspects to be addressed:</p><ul><li><p>Although authors found transcriptional differences in ZT20 vs ZT8 after injury, we wonder if there is already a background regeneration machinery that is highly active at ZT20 in unchallenged DRGs that allows for increased regenerative capacity.</p></li><li><p>Although authors clearly show that the regeneration ability depends on Baml1, they miss proving that Baml1 is directly binding regulatory gene sequences and actually orchestrating the transcriptional response. If not Baml1, who is the main orchestrator?</p></li><li><p>While the authors denote lithium as a chrono-active drug, the way it affects circadian rhythm-dependent enhancement of regenerative ability is unclear. We suggest a thorough characterization of the effect of lithium treatment across all ZT during 24h.</p></li><li><p>The authors should discuss the results of the recent publication <a href="https://www.nature.com/articles/s41467-023-40816-7">https://www.nature.com/articles/s41467-023-40816-7</a> were they found that Baml1 controls axon regeneration via Tet3 epigenetics</p></li><li><p>The authors show that the role of inflammation triggered by non-neuronal cells in nerve regeneration is not clock-dependent. Nevertheless, neutrophin, BDNF and NFG levels were measured in naive DRG neurons. The authors should specify if "naive" means uninjured neurons. In this case, we recommend comparing these data with post-injury levels.</p></li></ul><p>Minor comments:</p><ul><li><p>In the introduction, we would suggest to include more background information (more details on the different mechanisms of PNS regeneration or evolutionary perspective on why regeneration might be controlled by circadian rhythms) and limit the description of the results to a very short summary.</p></li><li><p>We consider that Figure 1 can gain some clarity by reworking the following aspects:</p><ul><li><p>The heatmap shows biological processes instead of genes. Caption of the figure legend should be corrected accordingly.</p></li><li><p>Mention abbreviation of "DE genes" in figure legend</p></li><li><p>In the comparative GO analysis, we wonder how much overlap there is in the differentially expressed circadian rhythm genes across the regenerative models?</p></li><li><p>Mention abbreviation of SGC10 in the main text. A reference for this marker would be helpful as well.</p></li><li><p>We suggest having the fluorescence intensity distribution plotted beneath the representative image so readers can get a better sense of the regeneration index.</p></li><li><p>Legend for 1F is incorrect. Should be modified for G and H accordingly.</p></li></ul></li><li><p>We would like to encourage the authors to give some reason why they chose a sciatic nerve crush over sciatic nerve axotomy</p></li><li><p>Supplementary figure 1 shows representative images ZT0, 4, 8, 12, 16 and 20 instead of only ZT8 and 20. Caption should be revised. In the same figure legend, authors explain that "Fluorescence intensity was measured in one series of tissue sections for each nerve". We suggest providing more details on the average size of each tissue section, and how many sections in one series.</p></li><li><p>Edit y-axis label of supplementary figure 2B to 'CTB+ DRG neurons' </p></li><li><p>In supplementary figures 3 and 4, describing abbreviations for LY6G and CD68 will help the reader. As well, we suggest to mark on the images the site of the injury and double-check consistency between the number of replicates shown in the plots and the figure legend.</p></li><li><p>How many hours post-injury refers to the data shown in supplementary figure 5?</p></li><li><p>The text of supplementary figure 7 legend should be checked for clarity, "mRNA levels of Bmal1 mRNA levels" is confusing and also the references to other figures.</p></li><li><p>Also, why in supplementary figure 7B, 5 replicates are chosen instead of 6 that were included in figure 1D?</p></li><li><p>Figure 2B and supplementary Figure 8A should be consistently labeled using the same labels (ZT8_1, ZT8_2, and so on) in the heatmap and the PCA analysis of the clustered differentially expressed genes.</p></li><li><p>Regarding the data presented in Supplementary Figure 8B, we wonder if there could be any reason why the ZT20 transcriptome is more likely to resemble IF than EE, if both non-injury models promote regeneration? Also, when comparing their data with previously published dataset, we find important to comment at which ZT the samples were collected, if available</p></li><li><p>Clarify in Figure 2C how to interpret dot-plot data regarding size and color code of the dots</p></li><li><p>In Figure 2D, we wonder whether there could be RAGs that are already upregulated in ZT20 even without the SNC? On that figure the y-label states -log12FC, while the figure legend states -log2 Fold Change.</p></li><li><p>In Table 2, we recommend to add indications for green colored fold changes and specify whether are these log2(FC) or log10(FC)</p></li><li><p>In Figure 3B the x-labels don't match between the histogram and the legend. The so</p></li></ul><p>Comments on reporting:</p><ul><li><p>As the number of biologically independent groups varies from 3 to 6 for different experiments for similar samples throughout this study, an explanation for these differences in discussion would be good.</p></li></ul>
<h2>Competing interests</h2>
<p>
The author declares that they have no competing interests.
</p>
PREreview of "Dynein and dynactin move long-range but are delivered separately to the axon tip"
No full textThis Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/8362691.
This review reflects comments and contributions from Kamaldeep Singh, Prithviraj Rajebhosale, Luciana Gallo, Ryan Cubero & Femi Arogundade. Review synthesized by Kamaldeep Singh.
In this study, Fellows et al. investigated the motility of endogenously-tagged dynein motors and its regulators along the length of the axons using live imaging of neuron-inducible human-stem cell lines (iNeurons) as a model system. Using highly inclined and laminated optical sheet (HILO) imaging of iNeurons, they show that dynein and dynactin are transported at different speeds to the distal tip of the axon. Further, use of SNAP and Halo-tag conjugated with highly stable fluorophores also allowed them to show that single molecules of dynein and dynactin can traverse the entire length of the axon (>500 um). In summary, this study has contributed in advancing the cell biological understanding of dynein and its regulators in mammalian axons.
We believe that the following positive aspects make the findings of the study strong and convincing:
Use of neuron-inducible human stem cell-derived iNeurons as a model system is a significant advantage as it provides a better understanding of mammalian cell biology for studying axonal transport compared to traditional cancer cell lines.
Use of microfluidic devices to separate axons from the somatodendritic compartments allows a convincing and clear demonstration of retrograde and anterograde transport in the axons and dynamics thereof.
Use of CRISPR to endogenously tag the dynein heavy chain and the ARP11 subunit of dynactin with a SNAP and HaloTag allowed the authors to selectively label the motos with high spatio-temporal resolution. This not only aided in imaging dynein/dynactin at a near single-molecule level but also allowed them to figure that single molecules of dynein and dynactin can traverse the entire length of the axon (>500um).
The photobleaching analysis on dynein spots in iNeurons provides valuable insights into the possible number of dynein molecules per cargo (which also agrees well with recent measurements of dynein number on endosomes in literature) and supports the claim of detecting single molecules under the given experimental conditions.
We also noted several points regarding the study and the manuscript (as major or minor comments) which if addressed, could possibly make the study better:
Major comments:
The authors observed mostly 1 and 2 step bleaching for dynein (Figure 2). Here, while they commented on the two step events being predominant and representative of the cytoplasmic dynein dimer, an explanation for the single bleaching events is lacking. Is it possible that these could be Halo-tagged dynein molecules dimerized with endogenous, untagged dynein from monoallelic targeting by CRISPR? It would therefore be nice to clarify and show the data that validates their CRISPR knock-in efficiency.
The authors mention: "We saw many distinct dynein spots in the axonal compartment, most of which were diffusing, often along microtubules (Fig S2A, Video 4)." How did the authors determine that these events were diffusive and that they occured along microtubules?
Minor comments:
Figure 3 is incorrectly labeled as Figure 2 in the legend. Kindly correct this.
"Thought" is misspelled as "thught" in the last paragraph of Introudction section.
Fig 3C is incorrectly addressed as "Fig 3B" under the results section "Dynein moves long range".
In the videos attached along with the manuscript: It would be nice if there could be additional markers - for instance arrows tracking the particles (just like box on the spot where photobleaching was performed) - to help readers focus on the main point the authors are trying to make with respect to a given video.
While the microfluidic devices utilized in the study might be standard in the trafficking field, it would be nice if the authors could provide a detailed description such as the devices' exact dimensions and manufacturer/supplier details.
Authors have already hinted towards many unanswered questions, possible experiments and also listed anticipated outcomes for many such questions. Here are a few suggestions for lines of investigation that one could undertake in the future research:
As it has already been emphasized by authors, LIS1 is an important regulator of dynein activation. Therefore, simultaneous imaging of LIS1 and dynein might allow authors to identify whether the pausing of dynein is due to exchange of LIS1 within the complexes. Similar studies conducted with dynein together with other dynein cofactors, activators, or even kinesins will be useful to address many unanswered questions in the field.
Given that the authors can compartmentalize the somatodendrites and axons, it would also be interesting to know whether supply of dynein at the distal tip is regulated in response to different stimuli for e.g. in response to perturbations in neuronal activity.
We wish the authors best of luck for all of their future research endeavours!
Competing interests
The author declares that they have no competing interests
Ye hualtemo in iztacoatl (Ya viene bajando la serpiente blanca).: Ritualidad en los cerros sagrados de la sierra norte de Puebla
No full textTesis para obtener el grado de Doctor en Historia y Etnohistori
Devoción, reciprocidad y compromiso al Señor Santiago en el pueblo de Tecozautla
No full textTesis para obtener el grado de Maestro en Historia y Etnohistori
Ma kualli: la noción de lo no bueno entre los nahuas de Chiconcuautla de la Sierra Norte de Puebla
No full textTesis para obtener el grado de Maestro en Historia y Etnohistori
El calor humano y economía de afectos entre los nahuas de Xolotla.: Un acercamiento etnohistórico y etnográfico
No full textTesis para obtener el grado de Maestro en Historia y Etnohistori
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