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And most medical procedures rely at least partly on the faith and hope of the patient. ‘Those that believe are healed’, said Sabina. Sadly, she felt the mushrooms lost some of their power once the hippies had desecrated the secret ritual. She became something of a pariah in Huautla, although once she was dead she was almost canonized, and is now celebrated in a large statue of her standing on a mushroom as you enter the town. Florencio likewise laments: ‘The arrival of the hippies swept away the old ways, and the mysticism and magic of Huautla.’

It’s interesting to wonder if the same will happen with Western psychedelic medicine, as it goes from being the latest new wonder drug to something familiar, standardized and commodified. Even as rational a therapy as CBT no longer works as well as it did in the 1960s, when it was the new wonder therapy. Will the miracle results of psilocybin therapy level off in a decade or two?

Today, Huautla has mushroom regalia festooned all over the town in a bid to bring the tourists back, but we hardly saw any – the town is too far away from Mexico City or Oaxaca City. Instead, the new mushroom Mecca is San Jose del Pacifico, a tiny town of 700 people conveniently located on the main highway from Oaxaca City to the beaches of Puerto Escondido.

The first hippies arrived here in the early 70s, perhaps after having been booted out from Huautla – the locals say they arrived after a solar eclipse. They bought huts in the hills, and found a local curandero to sell them mushrooms. Gradually the village became a New Age hot-spot, offering tourists a menu of therapies like Reiki, hydrotherapy, sweat lodges and mushrooms. ‘The gringos mainly take them in the day, and wander in the forest or by the river’, says a local young woman. ‘Sometimes they laugh, sometimes they cry, sometimes they stare at trees. They don’t bother anyone.’ I asked her if the locals in San Jose ever take them. ‘Oh no’, she said. ‘Only the gringos.’

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Posted on April 10, 2018 by Jules Evans

Here is part 2 of my interview with pioneering researcher Milan Scheidegger, who works in the psychedelics lab at University of Zurich. You can read part 1 here . In this half of the interview, we discuss how to translate aspects of indigenous ayahuasca rituals – such as the shaman or sacred plant songs – into the context of western healthcare. We also discuss Milan’s plans to establish a psychedelic healing clinic in Switzerland.

In terms of translating the elements of indigenous psychedelic rituals into a western context, the role of the shaman is taken by a therapist. The therapist becomes a spiritual guide, not just someone you talk to. They acquire a sort of vatic standing. What do you think of the scientist as shaman?

2) Results section–be more explicit about how the various cell states are defined.

3) Results section–how exactly were these efficiencies calculated? Do they take into account cell proliferation and loss at various stages?

4) Results section–is the intermediate DP state a necessary stage on the journey? Maybe it represents a default (early anterior stages) induced by growth factor depletion that then gets overtaken by the reprogramming factors.

5) Discussion section– because the MN endpoint is not characterised at a functional level by the authors in this study, the conclusions rely on comparison to historical controls, and therefore depend on the degree to which the authors' protocol mimics earlier efforts. Direct comparison of the two endpoints is only possible at the transcriptional level.

Reviewer #2:

Briggs, Li and coworkers aim to investigate if the developmental path taken by differentiating cells determines the final cellular state or if two alternative trajectories are able to produce a similar terminal fate. To do so, the collect single cell RNA-seq data from differentiating motor neurons induced by extracellular signals or by forced expression of transcription factors. An important difference between these samples rests on the fact that direct differentiation by forced transcription factor expression bypasses the canonical motor neuron progenitor stages. The results show that direct programming and standard differentiating cells diverge at early progenitor like state to take different path and converge on a final similar cell state. Although this was postulated before, these results test the hypothesis with the appropriate and up to date technology.

There are some important points that in my opinion should be addressed;

1) A better description of the criteria used to assign cell types will be useful. For example, motor neuron progenitors (MNP) are characterized by Olig2 expression, low or no Isl1, Mnx1 and Lhx3. In Figure 1E , MNP have an average Olig2 and high Mnx1, Isl1 and Lhx3. Thus, some of the cells in this cluster might be early MNs than progenitors. Are the markers in Figure 1D-E some of the genes driving the clustering?

2) The percentage of MNs in the SP protocol is surprisingly low. The culture conditions, crucial for this conclusion, should be clearly described in methods. Recapitulating development, SD protocol produces oligodendrocytes after MNs, thus efficiency as percentage of total cells it is expected to decrease. Where there antimitotic added to both (DP and SP) conditions to restrict the generation of mitotic byproducts?

3) It is my opinion that belted tailored trousers White Guild Prime eS6CxIA
should be divided into two figures. The first two panels are intrinsically linked to the goal of this manuscript, the characterization of DP MNs is less relevant and novel. The three-way comparison of SP, DP and PM is extremely valuable and on topic. Thus, I believe I deserves to be expanded and explained better. The supplementary figures associate with this figure should be in the main figure. On that note, it will be useful to color Figure 5—figure supplement 2A based on DP, SP and pMN to understand where cells "land" in these dimensions. Describe what is gene set that take DP closer to pMN than SP for example? Is it possible to add pMN and remake here low top laceup sneakers Black Car Shoe hCCBK8FSm


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