- Last 7 days
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www.dcceew.gov.au www.dcceew.gov.au
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a means of controlling pest beetles in the sugar cane industry in 1935, before the use of agricultural chemicals became widespread.
Why they were introduced
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voracious predators of insects and other small prey
They are known to be very effective predators
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“heightened tensions between the United States and Russia have manifestedanew in the Council, leading to concerns that the body may be less able to defuse crises”.[
The ongoing gridlock among the P-5 members is identified as a primary cause of the UNSC’s inaction.
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“half a million Syrians [being]killed, most by pro-regime forces, and more than half of the country’s prewar population of some twenty-two million[being] displaced”.[24]
Such a large amount of people killed.
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, terrorism has significantly contributed to not only compounding the complexity of the overall conflict,
Stopped the UN and Security Council’s ability to facilitate a ceasefire and peace agreement.
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led to increased military
Islamic State (Daesh) has further complicated the war.
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Shiite-backed troops of President Bashar al-Assad and the predominantly Sunni Gulfstates.
Two main proxy conflicts.
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As more than four competing networks vie to achieve their respective geopolitical objectives inthe country, the fundamental humanitarian necessity of protecting civilian lives from heinous atrocities has becomediluted as a result of the struggles presented by the ever-intensifying war.
The conflict between Proxy wars and the humanitarian crisis.
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Following the initial 2011 Arab Spring uprisings, Syria emerged at the center of what has now deteriorated into nearlya decade of complex civil unrest that has challenged the international community and its ability to intervene in thewar.
The international community's struggle to intervene effectively.
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“weighed and balanced against individual sovereignty, asrecognized in the international human rights instruments”
Shows the complexities of legal intervention in internal conflicts.
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Thelack of international mechanisms with the jurisdiction and capacity to hold non-state actors accountable has limitedthe UN’s success in intervening in civil unrest.
Shows a challenge with Non-State Actors.
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demands to civil war parties [becoming] more numerousand increasingly oriented toward post-conflict peace building between 1989 and 2006”.
A Shift in UNSC Focus.
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In the past decade, civil unrest has grown increasingly prevalent throughout the world and has subsequentlychallenged the international community in pressuring non-state and state actors to comply by the demands of theSecurity Council.[
Civil Unrest and Accountability.
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proxy strategies
Rise of Proxy Wars.
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Evidently, there is a disconnect between presentthreats to international security and the capacity for entities such as the UNSC to effectively mediate and mitigateconflict.
Changing Nature of Conflicts.
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With the determination of the P-5having been structured in the aftermath of World War II, critics note that the current authority of the bodydisproportionately favors the positions of the permanent members, thus hindering the UNSC’s ability to distance itselffrom the sovereign interests of states when attempting to combat international security risks.
Power Dynamics.
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“its efficacy and authority as a mediator on matters of international security” is ongoingand increasingly prevalent in light of presently deteriorating modern conflicts.
Efficacy and Authority of the UN.
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The UN and its contemporary challenges
Challenges of Sovereignty too.
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A plethora of contemporary challenges have exposed the UN to criticism in its ability to evolve with changes ingeopolitics, most notably the organization’s responsive rather than reactive approach to confronting internationalcrises and the rise in nations disinterested in international consensus building.
A more proactive approach might mitigate crises before they escalate.
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the denial of human security to the citizens in one ormore states as a result of civil conflict and strife”.
The organization’s capacity to intervene in internal conflicts without infringing on state sovereignty.
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geopolitic
Shifting power dynamics.
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United Nations Security Council (UNSC
Almost limitless power.
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“a guardian of international peace and security, as a promoter of human rights, as a protectorof international law, and as an engineer of socioeconomic advancement”
Complexities of politics .
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www.gutenberg.org www.gutenberg.org
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Sometimes from out the folded paper the pale clerk takes a ring:—the finger it was meant for, perhaps, moulders in the grave; a bank-note sent in swiftest charity:—he whom it would relieve, nor eats nor hungers any more; pardon for those who died despairing; hope for those who died unhoping; good tidings for those who died stifled by unrelieved calamities. On errands of life, these letters speed to death. Ah Bartleby! Ah humanity!
Melville ends the book with the lawyer feeling pity and sadness for bartleby, but also for humanity as a whole.
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The round face of the grub-man peered upon me now. “His dinner is ready. Won’t he dine to-day, either? Or does he live without dining?” “Lives without dining,” said I, and closed his eyes. “Eh!—He’s asleep, aint he?” “With kings and counselors,” murmured I
I personally wanted to highlight this section because I love the way it is written. I got chills. I just imagined the quiet, cold tombs and the mysterious nature of bartleby alongside the warmth, curiosity, and compassion of the lawyer. The lawyer realizes that bartleby isn't just drunk and asleep, but has passed away.
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I now recalled all the quiet mysteries which I had noted in the man.
In the story, one can see the dark and gloomy tone as well as the mystery and uncertainty throughout. Here, the lawyer talks about the "quiet mysteries" of Bartleby. He is somewhat intrigued but cautious too.
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I am a rather elderly man. The nature of my avocations for the last thirty years has brought me into more than ordinary contact with what would seem an interesting and somewhat singular set of men, of whom as yet nothing that I know of has ever been written:—I mean the law-copyists or scriveners
The story's first person narrator is the lawyer.
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hermitage
hermitage: "the dwelling of a hermit, especially when small and remote"
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thewasteland.info thewasteland.info
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One must be so careful these days.
Informal annotation: There is another way to interpret the role of prophecy in "The Waste Land." Perhaps Eliot has intentionally characterized the prophets as creators instead of foretellers of the future. This is certainly true in the case of Huxley's Mme. Sesostris (Mr. Scogan), from which Eliot's clairvoyante takes her name -- his predictions are only true because he renders them true (i.e., he will hit his client with a hammer; he will ask the village girl about heaven outside the local church). In the context of Eliot's poem, it could be argued that it is exactly Mme. Sosostris' vision of the Phoenician Sailor that drowns him in later sections of the work.
Having established this, the final line of this stanza could be directed at prophets and interpreted in another way. It warns them of their reality-morphing powers in the modern world.
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'Speak to me. Why do you never speak. Speak. 'What are you thinking of? What thinking? What?
In the first part of The Game of Chess, the female character is isolated and defined by the lifeless objects surrounding her—perfumes, glass, candle flames, lacquer, and more. Only through these objects, do we get a chance to become acquainted with her. These inanimate items symbolize suffocation and entrapment in her loneliness. The readers can only speculate if it’s the notion of rape that Eliot continuoulsy references that led to this isolation. No matter the cause of it, however, the character strives to get herself out of this situation. She strives for human connection. Her plea, “Speak to me,” reflects this need, but the absence of a question mark in “Why do you never speak to me” suggests that the character already knows the answer. The reader, however, is left to speculate: does she see herself as undesirable because of her trauma? Or is it simply the years of a relationship that deteriorate this connection referencing Eliot’s own troubled marriage? In either case, this emotional disconnect is further demonstrated by the subsequent question, “What are you thinking of?” This time, the question is marked by a question mark, suggesting an actual attempt to break through this emotional barrier. These attempts, however, are ineffective, as the desperation rises and the questions shorten to “what thinking” and “what.” This fragmented monologue mirrors the fragmentation of her emotional state.
In contrast, the second character suffers from the destructive excess of human connection. Shamed for her appearance, she faces the reality of her partner’s potential infidelity, reflected in the statement, “And if you don’t give it to him, there’s others.” The references to abortion intensify this degradation. She justifies her loss of beauty and confidence with the line, “It’s them pills I took, to bring it off.” Instead of finding fulfillment in connection, this character’s relationships strip her of her self-worth.
In these two cases, Eliot presents women trapped at the opposite extremes of human connection: one suffers from its absence, the other from its destructive abundance. Yet, in both cases, external forces define and entrap them. The first woman is reduced to the objects around her, while the second is judged by an external voice—the pronoun “I” suggesting our, as readers, own judgment projected onto the character. We become not simply the judges, but also the victimes of this broken connection. The poem’s fragmented language, which severely affects our understanding of it, mirrors the emotional chaos, invoking feelings rather than rationality, similarly to Ophelia’s “mad” song in Hamlet.
This pattern mirrors the nature of chess, where a single wrong move can drastically alter the entire game. Just as in chess, life’s unpredictability is highlighted in these women’s lives, as one extreme of human connection can quickly shift to another, with equally devastating outcomes. The title of the section, The Game of Chess, thus, reflects this instability —one wrong move leads to extremes of connection. In this case, these characters and we, as readers, are not simply entrapped in this game. Instead, we are playing with an unwinnable position from the very outset: each move only brings the inevitability of loss closer.
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www.terrestres.org www.terrestres.org
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surmonter l’opposition entre travail intellectuel et travail physique, et celle entre villes et campagnes.
C'est le cas de Cargonomia qui délivre en vélo-cargo des légumes produits dans une micro-ferme. https://cargonomia.hu/fr/
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Par exemple, il serait possible de remplacer l’approvisionnement électrique d’un fournisseur qui utilise l’énergie atomique par un approvisionnement qui utilise des énergies renouvelables produites localement.
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en dehors du temps de travail
du temps de travail rémunéré ? Je clarifie, car on pourrait aussi appeler "travail" une création non rémunérée
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eliterature.org eliterature.org
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In this sense electronic literature is a "hopeful monster" (as geneticists call adaptive mutations) composed of parts taken from diverse traditions
Electronic Literature has to be a “hopeful monster” in todays’ developing world. It adapts to the needs of reality and seeks to pique the curiosity of people. That is why, literature went through a series of ‘mutations’ and turned into electronic one. Now it makes it possible not only to grasp the attention of readers by captivating plot. It gives them the opportunity to partake in the process of content creation, to immerse in the ‘new world’ and to influence its ‘line of development’.
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Electronic literature, generally considered to exclude print literature that has been digitized, is by contrast "digital born," a first-generation digital object created on a computer and (usually) meant to be read on a computer. The Electronic Literature Organization, whose mission is to "promote the writing, publishing, and reading of literature in electronic media," convened a committee headed by Noah Wardrip-Fruin, himself a creator and critic of electronic literature, to come up with a definition appropriate to this new field. The committee's choice was framed to include both work performed in digital media and work created on a computer but published in print (as, for example, was Brian Kim Stefans's computer-generated poem "Stops and Rebels"). The committee's formulation: "work with an important literary aspect that takes advantage of the capabilities and contexts provided by the stand-alone or networked computer."
This definition provides a useful framework for understanding and appreciating electronic literature. It successfully balances the emphasis on technological innovation with the core values of literature, acknowledging its inherent dynamism and potential for future evolution. The inclusion of computer-generated works published in print adds to its comprehensiveness, but further discussion and refinement may be needed to address potential ambiguities in classification.
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www.historyisaweapon.com www.historyisaweapon.com
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In 1982 corporate growers gave Deukmejian one million dollars to run for governor of California. Since he took office, Deukmejian has paid back his debt to the growers with the blood and sweat of California farm workers. Instead of enforcing the law as it was written against those who break it, Deukmejian invites growers who break the law to seek relief from the governors appointees. What does all this mean for farm workers? It means that the right to vote in free elections is a sham! It means that the right to talk freely about the union among your fellow workers on the job is a cruel hoax! It means the right to be free from threats and intimidation by growers is an empty promise! It means the right to sit down and negotiate with your employer as equals across the bargaining table—and not as peons in the field—is a fraud! It means that thousands of farm workers—who are owed millions of dollars in back pay because their employers broke the law—are still waiting for their checks. It means that 36,000 farm workers—who voted to be represented by the United Farm Workers in free elections—are still waiting for contracts from growers who refuse to bargain in good faith. It means that, for farm workers, child labor will continue. It means that infant mortality will continue. It means malnutrition among our children will continue. It means the short life expectancy and the inhuman living and working conditions will continue.
Taking away human rights from farmers and becasue of this child labor, malnutrition, and the life expectancey decline will still happen.
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better off today because of what the farm workers taught people about organization, about pride and strength, about seizing control over their own lives.
The farmers tought the people to take control over their own life.
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Malnutrition among migrant worker children is 10 times higher than the national rate. Farm workers' average life expectancy is still 49 years—compared to 73 years for the average American.
The famers died faster because malnutrition
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www.jstor.org www.jstor.org
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a baselinefor specific locations, we can reexamine aviancommunities at the same locations in the future as
always important to revisit and reexamine data in years to come!
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However, withoutpre-colonization data, we canno
limited data before bird colonization, likely because the colonization was unanticipated
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we found few relationships betweenpotential food competitors and the parakeets.Population numbers for those species were similarbetween MOPA and Non-MOPA site
parakeets are not displacing any native birds for food
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of more bird feeders in thoseareas because Monk Parakeets appear entirelydependent upon them during the Chicago wint
this made me chuckle-- Chicago winters are brutal and generally any animal will eat whatever food available, no matter if it's a tropical bird and it's -40 degrees
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avian communities they invade. Our data suggesthat presence of Monk Parakeets does notsignificantly affect avian communities in theChicago a
monk parakeets (again) are more subtle nuisance than direct disturbance (as of now)
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Spearman correlati
important for statisticians, they can also learn how to use this data
-
five more sites (T
thorough research
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nly Rock Pigeons had a significant (negative)correlation with Monk Parakeets based on meanrelative abundance at s
this makes sense-- pigeons are abundant in most cities
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species
important to note-- this research is well conducted and notes any/all possible (in)consistencies
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On average, these species accounted for themajority of birds observed at MOPA sites andnearly half the birds observed at Non-MOPA sites(Table 2
key data point, which is matched in graphs and charts
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We also tested for correlations (Spearman rank) between parakeets andthose same competitor species when we had atleast 40 observation
purpose: to compare habitat and lifestyle of parakeets and competitors
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"food competitor community" by onlyusing species observed with diets that mightoverlap significantly with Monk Parakeets (i.e., alarge portion of their diet includes plant materialssuch as seeds, fruits, leaf buds, and grasses) basedon their species accounts in Birds of NorthAmerica Online
again, looking for the most similar birds that are not monk parakeets (great scientific practice!)
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measured avian diversity,evenness, and richness.
in-depth search, also good scientific practice
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. A preliminary analysis of woody plants at asubsample of the transect sites found no significantdifference in abundance, richness, diversity, andevenness bet
making conditions as comparable as possible-- good scientific practice
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, interviews with residents, mediareleases requesting information, and searches bythe authors upon initiation of the stud
such an important part of research-- communication with eyewitnesses!
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ood. We looked for broad relationships that could generate future hypotheses andmore focused future resear
difficult to build on much previous research because not much exists
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008). Since then, theparakeets have expanded out of their putativeorigin in Hyde Park (Pruett-Jones and Tarvin1998) and have become particularly abundant inthe south and southwestern portions of the greaterChicago area (Marcisz 2005, Pruett-J
habitat expansion could cause a greater magnitude of problems for a greater magnitude of people
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for other species that usetheir nests as breeding platforms or use chambersas cavities
nests could be used for other birds-- would parakeets get territorial, though?
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vectors for disease
birds could spread infections, but few reports of this actually happening (though also could be lack of research)
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Anecdotal accounts suggestMonk Parakeets are aggressive and behaviorallydominant over other avian speci
could possibly compete with other birds for food
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ir popularity as pets (i.e., propagulepressure) help make them excellent colonizers andpotential invad
adds to the theory that they were pets first and released into the environment
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010). Invasive species mayaffect native species directly through prédation,competition, and disease or indirectly throughprocesses like habitat disruption (Gurevitch and
examples of how invasive species may harm an environment. So far no examples of how parakeets have harmed the urban environment through these methods
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ets likely are not having a strong influence on urban avian communities, but we cannot rule out effescale
again, parakeets are more of just a nuisance, rather than causing significant harm
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out Monk Parakeets and hypothesized that observed differences between t
this study explored differences in communities with and without monk parakeets
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docdrop.org docdrop.orgUntitled32
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In this regard, both pursue the same goal; scientific thought is only a moreperfected form of religious thought. Hence it seems natural that religionshould lose ground as science becomes better at performing its task.
science often perceived as a perfected form of religion
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In short, the former gods are growing old or dying, and others have notbeen born.
need to make new Gods
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Its pity forthe downcast seems to us too platonic. We would like one that is more vig-orous but do not yet see clearly what it should be or how it might be realizedin fact.
religion is kind of dead and we need a revival of morals
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uitenaturally, the corresponding mythological personages are of the same charac-ter; their sphere of influence is not definite; they hover above the individualtribes and above the land. These are the great international gods
even among tribes are religions shared
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Except by reachingoutside himself, how could the individual add to the energies he possesses
not true religion because not beyond oneself
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have shown that precisely this is often true of ritual activityand mythological thought.
not just reflection of history and growth of knowledge?
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It rests on conditions that can be uncovered through observa-tion. It is a natural product of social life.
religion is scientific in its patterns that can be observed
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In short, upon the real world where pro-fane life is lived, he superimposes another that, in a sense, exists only in histhought, but one to which he ascribes a higher kind of dignity than he as-cribes to the real world of profane life.
sacred is just an imposed reality
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since what defines the sacred is that thesacred is added to the real.
this is a bar
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his persistent idealization is a fundamental fea-ture of religions.
religion is idealization of the world in its hyperbolic notions of goodness, justice, a vision for the future alongside evil, trickery, and bad intentions.
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n the end, the point is not to exerta kind of physical constraint upon blind and, more than that, imaginaryforces but to reach, fortify, and discipline consciousnesses.
no physical or even divine aspect of religion beyond moral fortification on a broad scale
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religion
in conversation with current(for him) ideas of everything stemming from religion- replacing religion with society
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hus it is action that dominates religious life, for the very rea-son that society is its source.
action is fuel source to religion
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have shown what moralforces it develops and how it awakens that feeling of support, safety, and pro-tective guidance which binds the man of faith to his cult.
society makes religion
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properties
distinct separation of science and religion- fundamentally different purposes
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Thecultisnotmerelyasystemof signsbywhichthefaithisoutwardlyexpressed;itisthesumtotalofmeansbywhichthat faithiscreated andrecreatedperiodically
the collective creates the greater source from which an power that is beyond oneself stems from
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he is a man who is stronger.
Knowing God isn't about gaining knowledge it's about receiving fuel or gaining resilience
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Indeed, they sense that thetrue function of religion is not to make us think, enrich our knowledge, or addrepresentations of a different sort and source to those we owe to science. Itstrue function is to make us act and to help us live.
Religion and Science have fundamentally different purposes WE LOVE TO SEE ITTTT
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hether there is room alongside scientific knowledge for another form ofthought held to be specifically religious.
basis of science and religion is not within some far off natural truth-
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single idea cannot express one reality here and a dif-ferent one there unless this duality is merely apparent.
if it wasn't true it wouldn't make itself apparent and if something contrasts there is a duality
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the truths thus obtained would be applicable to allliving things, including the most advanced, even if this case was the simplestprotoplasmic being imaginable.
a little too confident in his concept nonsense theory but ok
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But it is noless true that when a law has been proved by a single well-made experiment,this proof is universally valid.
ummmm no
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ollective consciousness is the highest form of psychic life, forit is a consciousness of consciousnesses. Being outside and above individualand local contingencies, collective consciousness sees things only in theirpermanent and fundamental aspect,* which it crystallizes in ideas that can becommunicated.
consciousness of consciousness- understand the world outside of ourselves too see something more fundamental and with stronger continuity across human experience
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single causal relation
common collective goals bring people together
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time
time is a commonly established concept
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other
need for classifications to form groups with similar needs
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Thesewould be sufficient for man as well if his movements had to satisfy individualneeds alone. In order to recognize that one thing resembles others withwhich we are already acquainted, we need not arrange them in genera andspecies.
need to understand what others need and see is why concepts were born- proof of social beings
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way
history is a collective memory based in events impact on society
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For the same reason, the rhythm of collective life governs and con-tains the various rhythms of all the elementary lives of which it is the result;consequently, the time that expresses it governs and contains all the individ-ual times. It is time as a whole.
conceptualization exists only alongside collective- does not exist in one persons mind
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The concept of totality is but the concept ofsociety in abstract form.
society is in a sense totality- all things
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Since the universe exists only insofar as it is thought of and since it isthought of in its totality only by society, it takes its place within society; itbecomes an element of society’s inner life, and thus is itself the total genusoutside which nothing exists.
universe is our concept of it- grounds in society - don't think he actually means the universe as a a physical object with limitations is only in our heads, but the only way we understand and know it is through our societal concepts, confining it to the social space. Do we know the universe outside of our collective conceptualization?
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But that state of personal expectancy can-not be assimilated to the conception of a universal order of succession thatimposes itself on all minds and all events.
understands existence and changing of world beyond himself but still sees through own experience.
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www.youtube.com www.youtube.com
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44:30 sagt dir ja niemals ein arzt "weniger gluten, weniger milch, weniger rauchen"<br /> weil "die leute" haben keine lust auf "zu radikale" lösungen<br /> und wollen um jeden preis ihren lifestyle behalten... und nur symptome verdrängen
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... alles nur symptome von pazifismus und übervölkerung.<br /> aktuell depopulation, danach werden die lügen nicht mehr gebraucht.
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AI and ML can enhance the efficiency and accuracy of AML monitoring processes
Have there been any fintech companies that have tried to implement AI & ML in AML?
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mlpp.pressbooks.pub mlpp.pressbooks.pub
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In the second half of the nineteenth century, Chicago became a symbol of the triumph of American industrialization. Its meatpacking industry represented many of the troubling changes occurring in American life. In the last decades of the century Chicago became America’s butcher.
Meat Packing was on the rise and Chicago being the center, I think helped many get jobs and change big corporations to not just objects but to food.
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Addams decided to start her own in Chicago. She returned home and opened Hull House in 1889
I also think that it's amazing how she used the influence and stayed with a humane theme to help others.
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In addition to engineers and city planners addressing growing cities’ needs for drinking water and sanitation, idealistic nineteenth-century reformers began working to improving social conditions in American cities.
Along size with technologic advances there are still social issues. It starts with personal relation between the people. I think if it smelled terrible and cities you lived in were disgusting then people wouldn't be extremely happy and cause hate and unnecessary conflict.
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Addams’ approach to solving problems of urban poverty included equal parts of direct aid to poor city people, scientific study into the roots of poverty and dependency, and political activism to bring this information to the public and government officials and to advocate change.
Her views on poverty and how to combat was very humane. It started with how and why this is such a problem and what can be done as a government and a people to make a change.
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By 1911, six western states had passed suffrage amendments to their constitutions. Women’s suffrage was typically part of a package of reform efforts. Many suffragists argued that women’s votes were necessary to clean up politics and combat social evils.
Women suffrage movements were finally getting attention form state. Not only was voting a need for women's rights but it created avenues for working class women as well.
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oosevelt believed there were good and bad trusts, necessary monopolies and corrupt ones. Although his reputation as a trust buster was wildly exaggerated, he was the first major national politician to at least speak against the trusts.
Roosevelt seemed to be for the people which is why I believe that he was exaggerated greatly because of his reputation. I think he used his reputation to shape financial politics.
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That meant they were immigrants or the children of immigrants, overwhelmingly from either Irish or German-speaking families. Descendants of German immigrants, who arrived in great numbers just as the Midwest was opening for settlement in the mid-nineteenth century, still make up the majority ethnicity of a wide swath of middle America.
Again, we talk about immigrants who arrived. What would America be if no immigrants were never allowed to come here? I wonder
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population historians discovered that the most mobile city-dwellers were often wage-workers and the poor. People who owned businesses and valuable real estate were much more “persistent,” in demographic terms, because they were in a sense anchored by their possessions. Over time, though, the greater persistence of more prosperous residents often allowed them to gain greater political power than poorer people who in many cases did not stick around long enough to organize; or often even to vote
I think once ppl moved to Boston, they felt like they could receive better opportunities somewhere else. It really was for the wealthy that owed possessions and the poor had no reason to stay.
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Much of the U.S. population growth of the first half of the nineteenth century was due to the extremely high birth rates of the generations just before and after the American Revolution, when the average family had well over four children and the population actually doubled every generation. After the War of 1812, many more were immigrants from foreign countries. Some of the first migrations of large groups followed the Irish Famine in 1845 and a series of failed socialist revolutions in the German states in 1848.
It seems like Immigrants help grow the population, and we are fighting to keep them out now.
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By 1850, Boston had 137,000 residents, New York 515,000, Chicago 30,000, San Francisco 21,000, and Los Angeles 1,600. By 1900, although only forty percent of Americans lived in cities or large towns, Boston had grown to 561,000, New York to 3.4 million, Chicago to 1.7 million, San Francisco to 343,000, and Los Angeles had 102,000.
It,s amazing how Chicago and some of the other cities hadn't been established yet. The growth by 1850 was amazing.
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www.americanyawp.com www.americanyawp.com
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In my opinion, the Spanish-American and Philippine-American Wars marked a turning point in American history by illuminating the complexity of the country's principles and identity. While there was a sincere desire to uphold the rights of the downtrodden and promote democracy, the strategies used—such as colonialism and military intervention—contradicted the fundamental ideals of liberty and self-determination.
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neuroyoganyc.thrivecart.com neuroyoganyc.thrivecart.com
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Access to all presentations by top researchers studying the neuroscience of yoga ($5000+ value)
Put price and value higher up the page
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empowering knowledge about how yoga affects the brain
Higher up
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scientifically-backed benefits of yoga
Add higher up in description of how this is different
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the Neuroscience and Yoga Online Conference
Update to be about subscription
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misinformation
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My mission is to bridge the yoga world and the neuroscience world by connecting scientists and yogis, replicating hands-on neuroscience experiments for learners, and sharing resources.
Why? Structure: I am a x who does y I discovered a So, I'm offering this product
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making this an incredible library of knowledge. All presentations with down-to-earth scientists, yoga classes with top teachers, recordings of Q&A sessions, workbooks, experiments, and quizzes are available.
Shorten: a library/archive of x that will enable you to y
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Build your library over time or apply your subscription fees toward Lifetime-Access Passes for continuing education credits.
Confusing to me. Do I get everything now or just a section, then I upgrade?
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WITH EXPERTS FEATURED IN
Great idea
First: a section about the problem/frustration your target audience is facing, what they really want, then how this subscription solves that
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improve
This might be the main result
Focus on improve first - this is the 'what' Learn is the 'how'
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Neuroscience and Yoga Online Conference Subscription
Better layout than previous sales page.
Add: the tangible result people get from having this subscription (look at testimonials). What can I do that I couldn't do before? Who is it for Also see language at beginning of video: treasure trove, wide range
Move line under, edit sub headline
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Workbooks and quizzes to guide your learning, and turn passive listening into active learning
This kind of sentence for each feature. i.e. what does each feature enable me to do/give me that I didn't have before.
Remove underlines (we think we'll click somewhere)
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the
from
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This subscription is
Delete. Make font bigger
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ecampusontario.pressbooks.pub ecampusontario.pressbooks.pub
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One faculty member
is there a reason this is anonymized?
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open assignment
could we include examples of open assignments?
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student-created content
expand to include permission form and link out
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retained, reused, revised, remixed, and redistributed
link to 5Rs
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accessible online
brief explanation of copyright/creative commons would be helpful. possibly a link to the guide to making OER with students?
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renewable assignments
link to more info about this
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pressbooks.senecapolytechnic.ca pressbooks.senecapolytechnic.ca
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wheat from the chaff
去粗取精
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www.aphis.usda.gov www.aphis.usda.gov
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heir status at the Statelevel varies considerably─from no regulation to completeprotection.
Should establish a working group that identifies their actual threatened status in different areas so that scientists can work together
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To date, widespread crop damage in the U.S. by monkparakeets has not materialized as originally anticipated.
again, not a life threatening species to citizens, more of a nuisance
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n general, movements to feeding sites are short, within 3to 5 km (1.8 to 3.1 miles) of the nest colony.
stay in concentrated areas
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Nesting usually occurs in colonies. The colony includessingle and compound nest structures closely spacedamong a few trees, or on a cell tower, transmission linetower, or electric utility substation. A given compound neststructure may contain several chambers, each used by adifferent pair of birds. Massive nests in Argentinareportedly contained more than 200 nest chambers andweighed hundreds of pounds. Compound nests aremaintained by all birds using the structure, including non-breeders
nests would be very hard to remove
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he monk parakeet first appeared inNew York in 1968, and was first recorded breeding inFlorida in 1969. Today, thriving populations of monkparakeets occur in several states, particularly New York,Connecticut, Illinois, Texas, Louisiana, and Florida
Mostly concentrated in either tropical or urban areas-- prime spots for the exotic pet trade
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(3 to 4 ounces body mass,approximately 11 inches total length).
fairly large, could possibly be aggressive if provoked by humans
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Monk parakeets nest seasonally, and nestremovals can often be timed to avoid accidentallydestroying eggs or nestlings
some sort of solution, but will not fix the more permanent problem. I think the fertility drug would be the best option with the smallest amount of labor
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“well-trained personnel whoare regularly monitored to ensure proficiency.”
definitely too resource intensive to be effecive
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Manystates prohibit the release of non-native species; severalstates prohibit possession, transport, sale or release ofmonk parakeets.
Likely won't help, the birds can just fly to a different area
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or now, this method remains experimentalas diazacon is not registered with the U.S. EnvironmentalProtection Agency
I think this might work the most: not harmful, does not require too much manual human labor, and does not brutally kill the birds. The EPA should reconsider this method
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n south Florida, one utility companyremoved hundreds of birds at several substations by hiringa private contractor to implement this approach.Figure 6. Special long-handled nets have been developed for parakeetremoval at nests.Page 4Figures 7 (left) and 8. Remotely triggered spring-loaded trap installed atmonk parakeet feeding platform. After the observer confirms non-targetspecies are not present, the trap is activated and parakeets are captured.WDM Technical Series—Monk Parakeets
most success with trapping, and poses least danger to humans
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None are registered.
could also be dangerous to people (specifically in residential areas)
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The feasibilityof applying this approach is unknown
this sounds difficult and may not be worth intensive work
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Thisapproach would not be cost-effective or practical on a largescale
This is the key difficulty with all of the solutions: none are practical or cost-effective
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south Florida from 349 in 2001 to142 in 2006.
relatively successful strategy, could continue to be implemented
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The tubular construction creates few flat surfaces andangles thereby greatly reducing preferred nestingsubstrates
further economic consideration: build more of these towers that are difficult to nest on, thereby attempting to alleviate this problem
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sometimes removed with long-handled nets or live traps
difficult and does not solve the larger problem of too many birds, but a start
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Anymanagement actions associated with electric utilityfacilities should be carried out by trained utility employeesor their authorized agents
Economic concerns of environmental problems, reflective of people and nature idea
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The frequency of power outages due toparakeet nests increases during wet weather.
again, still mostly just nuisance and not life-threatening damage, though with increasing bird populations, this could escalate
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he high-voltage, energized environment around substations makesthe removal of nests very dangerous unless the substationis taken offline─an unlikely occurrence given theassociated expense and disruption of service to the localcommunity
difficult for humans to remove bird nests, and gives further explanation as to why this method is ineffective
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Reproductivecontrol through contraception showspromise for long-term, nonlethalpopulation management.
solution, though likely difficult to implement, costly, and may backfire if it goes wrong
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Monk parakeets often construct nests onman-made structures, such as electricutility facilities and cell phone towers.
Nuisance, but also could be dangerous
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population to be increasing exponentially
sudden population change... I wonder why?
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www.eapoe.org www.eapoe.org
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The{a} mental features discoursed of as the analytical{a′} are, in themselves, but little, susceptible of analysis.
still found it hard to fully understand this, but Edgar put it in the beginning of the story, it should be an important or inspiring idea.
Tags
Annotators
URL
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www.liberation.fr www.liberation.fr
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archimash.com archimash.com
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Cut – Involves removing soil from higher areas to lower areas to create level building pads. It can also be used when building is dug into the ground such as a basement. Fill – Entails adding soil to lower areas to raise elevations and create level platforms.
how would you display these on a topographic map?
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Are you looking at a larger, regional, macro map?
What are these?
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Relief Levels
why do you need special types of levels? cant you just use qa regular level?
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wol.jw.org wol.jw.org
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¿Por qué debemos obedecer a los que nos dirigen?
Es verdad que los hermanos que nos dirigen, son tan imperfectos como nosotros, tal cómo también lo eran Pablo y Timoteo. Pero al igual que ellos, los ancianos se esfuerzan por aplicar y enseñar, todo lo que él esclavo fiel y prudente les comunica. Son humildes trabajadores y se rigen por las instrucciones los programas de enseñanza que la organización decide, basando toda su enseñanza en la palabra de Dios, la Biblia. Por éso es que Seguír su consejo y dirección, fortalece y hace crecer nuestra fé personal en Jehová y su Organización. Y por añadidura crece y se fortalece toda la congregación.
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Cómo se beneficiaron las congregaciones?
Su fe creció y se hizo más fuerte, y la predicación daba sus frutos porque el número de creyentes también creció.
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¿Por qué se había ganado Timoteo una reputación tan buena?
Por sus cualidades, que se hicieron tan evidentes, que se reflejaban en su comportamiento, de manera que todos se sentían impulsados a hablar muy bien de él. Y Jehová que ve los corazones, lo bendijo con una hermosa responsabilidad, porque vió su motivación sincera, basada en el amor por lo que aprendía y predicaba.
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www.regiedesecrivains.com www.regiedesecrivains.com
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Une question ? Une demande de prix ?
image qui change du style générale de la page, peu être mettre des feuilles pour que ce soit en accord couleur ?
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metarationality.com metarationality.com
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Everyday reasonableness is the foundation of technical, formal, and systematic rationality.
yep
the real is reasonable not rational
and only the reasonable can be real
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metarationality.com metarationality.com
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rationality as a particular application of reasonableness—not an overall-better version, but a specialization—and therefore only correctly understandable if reasonableness is understood.
rationaility narrowly understood is sheer unreasonableness
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This is not cognitive science
good
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viewer.athenadocs.nl viewer.athenadocs.nl
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Without the pressure of the competitive market, above-normal profits (from monopolist for example) will not be reduced by moving resources, resulting in too little output.
????
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daily.bandcamp.com daily.bandcamp.com
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“We really were left to our own devices, for the most part, for 300 years,” he says, “and the accents developed quite a bit in that time. It’s not uncommon for me to this day to go to Moncton and talk to someone in my regular accent and they don’t quite understand me. They have to have me repeat stuff.”
Geographic isolation can lead to the development of distinct dialects, like chiac and acadjonne, even in close regions, which emphasizes the diversity within Acadian linguistic traditions
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or so full of the joy of chiac’s musical language. Bubbling over with synths and funky guitar lines, shimmering with rhinestones and polyester, LeBlanc’s original concept of “trash folk” is warped into another century.
Lisa's blend of Acadian culture and humor in her music highlights how local, everyday details, like Tim Horton's gossip, can become part of a larger artistic expression, turning regional quirks into something universally joyful and relatable."
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The origins of chiac are murky. Some say it originates in the 17th century, others that it was created in the 20th. But everyone agrees on where it comes from: Southeastern New Brunswick alongside the hypnotic tides and rivers of the Bay of Fundy.
This draws attention to the interplay between language, geography, and cultural identity, emphasizing the uniqueness of chiac's evolution.
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meaningness.substack.com meaningness.substack.com
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Purposes are the currency of reasonableness
Like that association very much
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Understanding purposes meta-rationally
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www.ietf.org www.ietf.org
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logging in a portal, VPN
Just to keep the definition open for further use cases?
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Since the address changes only when a new session is established, there is no disconnection/reconnection involved.
It is, but it's done already anyway.
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the probability of address duplication in a network is negligible
Duplicate Address Detection
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iii) provide means for the device not to use MAC addresses it is not authorized to use or that are currently in use
Duplicate Address Detection
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study demonstrates a mechanism underlying the sex-dependent regulation of the susceptibility to gut colonization by Methicillin-resistant Staphylococcus aureus (MRSA). The evidence supporting the conclusion is solid, but additional experiments would strengthen the findings. The work will interest biologists who are working on intestinal infection and immunity.
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Reviewer #1 (Public review):
Summary:
Lejeune et al. demonstrated sex-dependent differences in the susceptibility to MRSA infection. The authors demonstrated the role of the microbiota and sex hormones as potential determinants of susceptibility. Moreover, the authors showed that Th17 cells and neutrophils contribute to sex hormone-dependent protection in female mice.
Strengths:
The role of microbiota was examined in various models (gnotobiotic, co-housing, microbiota transplantation). The identification of responsible immune cells was achieved using several genetic knockouts and cell-specific depletion models. The involvement of sex hormones was clarified using ovariectomy and the FCG model.
Weaknesses:
The mechanisms by which specific microbiota confer female-specific protection remain unclear.
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Reviewer #2 (Public review):
The current study by Lejeune et al. investigates factors that allow for persistent MRSA infection in the GI tract. They developed an intriguing model of intestinal MRSA infection that does not use the traditional antibiotic approach, thereby allowing for a more natural infection that includes the normal intestinal microbiota. This model is more akin to what might be expected to be observed in a healthy human host. They find that biological sex plays a clear role in bacterial persistence during infection but only in mice bred at an NYU Facility and not those acquired from Jackson Labs. This clearly indicates a role for the intestinal microbiome in affecting female bacterial persistence but not male persistence which was unaffected by the origin of the mice and thus the microbiome. Through a series of clever microbiome-specific transfer experiments, they determine that the NYU-specific microbiome plays a role in this sexual dimorphism but is not solely responsible. Additional experiments indicate that Th17 cells, estrogen, and neutrophils also participate in the resistance to persistent infection. Notably, they assess the role of sex chromosomes (X/Y) using the established four core genotype model and find that these chromosomes appear to play little role in bacterial persistence.
Overall, the paper nicely adds to the growing body of literature investigating how biological sex impacts the immune system and the burden of infectious disease. The conclusions are mostly supported by the data although there are some aspects of the data that could be better addressed and clarified.
(1) There is something of a disconnect between the initial microbiome data and the later data that analyzes sex hormones and chromosomes. While there are clearly differences in microbial species across the two sites (NYU and JAX) how these bacterial species might directly interact with immune cells to induce female-specific responses is left unexplored. At the very least it would help to try and link these two distinct pieces of data to try and inform the reader how the microbiome is regulating the sex-specific response. Indeed, the reader is left with no clear exploration of the microbiota's role in the persistence of the infection and thus is left wanting.
(2) While the authors make a reasonable case that Th17 T cells are important for controlling infection (using RORgt knockout mice that cannot produce Th17 cells), it is not clear how these cells even arise during infection since the authors make most of the observations 2 days post-infection which is longer before a normal adaptive immune response would be expected to arise. The authors acknowledge this, but their explanation is incomplete. The increase in Th17 cells they observe is predicated on mitogenic stimulation, so they are not specific (at least in this study) for MRSA. It would be helpful to see a specific restimulation of these cells with MRSA antigens to determine if there are pre-existing, cross-reactive Th17 cells specific for MRSA and microbiota species which could then link these two as mentioned above.
(3) The ovariectomy experiment demonstrates a role for ovarian hormones; however, it lacks a control of adding back ovarian hormones (or at least estrogen) so it is not entirely obvious what is causing the persistence in this experiment. This is especially important considering the experiments demonstrating no role for sex chromosomes thus demonstrating that hormonal effects are highly important. Here it leaves the reader without a conclusive outcome as to the exact hormonal mechanism.
(4) The discussion is underdeveloped and is mostly a rehash of the results. It would greatly enhance the manuscript if the authors would more carefully place the results in the context of the current state of the field including a more enhanced discussion of the role of estrogen, microbiome, and T cells and how the field might predict these all interact and how they might be interacting in the current study as well.
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Reviewer #3 (Public review):
Summary:
Using a mouse model of Staphylococcus aureus gut colonization, Lejeune et al. demonstrate that the microbiome, immune system, and sex are important contributing factors for whether this important human pathogen persists in the gut. The work begins by describing differential gut clearance of S. aureus in female B6 mice bred at NYU compared to those from Jackson Laboratories (JAX). NYU female mice cleared S. aureus from the gut but NYU male mice and mice of both sexes from JAX exhibited persistent gut colonization. Further experimentation demonstrated that differences between staphylococcal gut clearance in NYU and JAX female mice were attributed to the microbiome. However, NYU male and female mice harbor similar microbiomes, supporting the conclusion that the microbiome cannot account for the observed sex-dependent clearance of S. aureus gut colonization. To identify factors responsible for female clearance of S. aureus, the authors performed RNAseq on intestinal epithelial cells and cells enriched within the lamina propria. This analysis revealed sex-dependent transcriptional responses in both tissues. Genes associated with immune cell function and migration were distinctly expressed between the sexes. To determine which immune cell types contribute to S. aureus clearance Lejeune et al employed genetic and antibody-mediated immune cell depletion. This experiment demonstrated that CD4+ IL17+ cells and neutrophils promote the elimination of S. aureus from the gut. Subsequent experiments, including the use of the 'four core genotype model' were conducted to discern between the roles of sex chromosomes and sex hormones. This work demonstrated that sex-chromosome-linked genes are not responsible for clearance, increasing the likelihood that hormones play a dominant role in controlling S. aureus gut colonization.
Strengths:
A strength of the work is the rigorous experimental design. Appropriate controls were executed and, in most cases, multiple approaches were conducted to strengthen the authors' conclusions. The conclusions are supported by the data.
The following suggestions are offered to improve an already strong piece of scholarship.
Weaknesses:
The correlation between female sex hormones and the elimination of S. aureus from the gut could be further validated by quantifying sex hormones produced in the four core genotype mice in response to colonization. Additionally, and this may not be feasible, but according to the proposed model administering female sex hormones to male mice should decrease colonization. Finally, knowing whether the quantity of IL-17a CD4+ cells change in the OVX mice has the potential to discern whether abundance/migration of the cells or their activation is promoted by female sex hormones.
In the Discussion, the authors highlight previous work establishing a link between immune cells and sex hormone receptors, but whether the estrogen (and progesterone) receptor is differentially expressed in response to S. aureus colonization could be assessed in the RNAseq dataset. Differential expression of known X and Y chromosome-linked genes were discussed but specific sex hormones or sex hormone receptors, like the estrogen receptor, were not. This potential result could be highlighted.
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Author response:
Reviewer #1 (Public review):
Summary:
Lejeune et al. demonstrated sex-dependent differences in the susceptibility to MRSA infection. The authors demonstrated the role of the microbiota and sex hormones as potential determinants of susceptibility. Moreover, the authors showed that Th17 cells and neutrophils contribute to sex hormone-dependent protection in female mice.
Strengths:
The role of microbiota was examined in various models (gnotobiotic, co-housing, microbiota transplantation). The identification of responsible immune cells was achieved using several genetic knockouts and cell-specific depletion models. The involvement of sex hormones was clarified using ovariectomy and the FCG model.
Weaknesses:
The mechanisms by which specific microbiota confer female-specific protection remain unclear.
We thank the reviewer for highlighting the strength of the manuscript including the models and techniques we employ. We agree that the relationship between the microbiota and sex-dependent protection is less developed compared with other aspects of the study. In preparation of a revised manuscript, we intend on performing a more thorough comparison of male vs. female microbiota, along with quantification of sex hormones and downstream Th17 function (neutrophil recruitment and activation).
Reviewer #2 (Public review):
Overall, the paper nicely adds to the growing body of literature investigating how biological sex impacts the immune system and the burden of infectious disease. The conclusions are mostly supported by the data although there are some aspects of the data that could be better addressed and clarified.
We thank the reviewer for appreciating our contribution. We intend on performing experiments to fill-in gaps and text revisions to increase clarity and acknowledge limitations.
(1) There is something of a disconnect between the initial microbiome data and the later data that analyzes sex hormones and chromosomes. While there are clearly differences in microbial species across the two sites (NYU and JAX) how these bacterial species might directly interact with immune cells to induce female-specific responses is left unexplored. At the very least it would help to try and link these two distinct pieces of data to try and inform the reader how the microbiome is regulating the sex-specific response. Indeed, the reader is left with no clear exploration of the microbiota's role in the persistence of the infection and thus is left wanting.
We agree. This comment is similar to Reviewer #1’s feedback. As mentioned above, we anticipate clarifying the association between sex differences and the microbiota. We will attempt to investigate specific bacteria, although some aspects of microbiota characterization may be outside the timeframe of the revision.
(2) While the authors make a reasonable case that Th17 T cells are important for controlling infection (using RORgt knockout mice that cannot produce Th17 cells), it is not clear how these cells even arise during infection since the authors make most of the observations 2 days post-infection which is longer before a normal adaptive immune response would be expected to arise. The authors acknowledge this, but their explanation is incomplete. The increase in Th17 cells they observe is predicated on mitogenic stimulation, so they are not specific (at least in this study) for MRSA. It would be helpful to see a specific restimulation of these cells with MRSA antigens to determine if there are pre-existing, cross-reactive Th17 cells specific for MRSA and microbiota species which could then link these two as mentioned above.
We acknowledge that this is a major limitation of our study. Although an experiment demonstrating pre-existing, cross-reactive T cells would help support our conclusion, aspects of MRSA biology may make the results of this experiment difficult to interpret. We have consulted with an expert on MRSA virulence factors, co-lead author Dr. Victor Torres, about the feasibility of this experiment. MRSA possess superantigens, such as Staphylococcal enterotoxin B, which bind directly to specific Vβ regions of T-cell receptors (TCR) and major histocompatibility complex (MHC) class II on antigen-presenting cells, resulting in hyperactivation of T lymphocytes and monocytes/macrophages. Additionally, other MRSA virulence factors, such as α-hemolysin and LukED, can induce cell death of lymphocytes. MRSA’s enterotoxins are heat stable, so heat-inactivation of the bacterium may not help in this matter. For these reasons, restimulation of lymphocytes with MRSA antigens may be difficult to interpret. We humbly suggest that addressing this aspect of the mechanism is outside the scope of this manuscript.
A study by Shao et al. provides an example of a host commensal species inducing Th17 cells with cross-reactivity against MRSA. Upon intestinal colonization, the intestinal fungus Candida albicans influences T cell polarization towards a Th17 phenotype in the spleen and peripheral lymph nodes which provided protection to the host against systemic candidemia. Interestingly, this induction of protective Th17 cells, increased IL-17 and responsiveness in circulating Ly6G+ neutrophils also protected mice from intravenous infection with MRSA, indicating that T cell activation and polarization by intestinal C. albicans leads to non-specific protective responses against extracellular pathogens.
Shao TY, Ang WXG, Jiang TT, Huang FS, Andersen H, Kinder JM, Pham G, Burg AR, Ruff B, Gonzalez T, Khurana Hershey GK, Haslam DB, Way SS. Commensal Candida albicans Positively Calibrates Systemic Th17 Immunological Responses. Cell Host & Microbe. 2019 Mar 13;25(3):404-417.e6. doi: 10.1016/j.chom.2019.02.004. PMID: 30870622; PMCID: PMC6419754.
Reviewer #3 (Public review):
Strengths:
A strength of the work is the rigorous experimental design. Appropriate controls were executed and, in most cases, multiple approaches were conducted to strengthen the authors' conclusions. The conclusions are supported by the data.
The following suggestions are offered to improve an already strong piece of scholarship.
Weaknesses:
The correlation between female sex hormones and the elimination of S. aureus from the gut could be further validated by quantifying sex hormones produced in the four core genotype mice in response to colonization. Additionally, and this may not be feasible, but according to the proposed model administering female sex hormones to male mice should decrease colonization. Finally, knowing whether the quantity of IL-17a CD4+ cells change in the OVX mice has the potential to discern whether abundance/migration of the cells or their activation is promoted by female sex hormones.
In the Discussion, the authors highlight previous work establishing a link between immune cells and sex hormone receptors, but whether the estrogen (and progesterone) receptor is differentially expressed in response to S. aureus colonization could be assessed in the RNAseq dataset. Differential expression of known X and Y chromosome-linked genes were discussed but specific sex hormones or sex hormone receptors, like the estrogen receptor, were not. This potential result could be highlighted.
We appreciate the comment on the scholarship and thank the Reviewer for the insightful suggestions to improve this manuscript. We intend on measuring hormone levels and performing the recommended (or similar) experiments based on availability of reagents and mice during the revision period. We also apologize for not including references that address some of the Reviewer’s questions. Other research groups have compared the levels of hormones between XX and XY males and females in the four core genotypes model and have found similar levels of circulating testosterone in adult XX and XY males. No difference was found in circulating estradiol levels in XX vs XY- females when tested at 4-6 or 7-9 months of age.
Karen M. Palaszynski, Deborah L. Smith, Shana Kamrava, Paul S. Burgoyne, Arthur P. Arnold, Rhonda R. Voskuhl, A Yin-Yang Effect between Sex Chromosome Complement and Sex Hormones on the Immune Response. Endocrinology, Volume 146, Issue 8, 1 August 2005, Pages 3280–3285, https://doi.org/10.1210/en.2005-0284
Sasidhar MV, Itoh N, Gold SM, Lawson GW, Voskuhl RR. The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY. Ann Rheum Dis. 2012 Aug;71(8):1418-22. doi: 10.1136/annrheumdis-2011-201246. Epub 2012 May 12. PMID: 22580585; PMCID: PMC4452281.
Examination of the levels of estrogen, progesterone, and androgen receptors in our cecal-colonic lamina propria RNA-seq dataset is an excellent idea. We will add these analyses to the revised manuscript. We are planning additional experiments to better understand the contributions of hormones or their receptors and anticipate including such data in either a response letter or revised manuscript.
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¿Por qué podemos confiar en las normas morales de Jehová?
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¿Por qué no debemos confiar en las normas morales de este mundo?
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¿Está usted realmente convencido de que seguir las normas de Jehová siempre es lo mejor?
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Las normas de Jehová son las mejores
.H1
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source.android.com source.android.com
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config_wifiAllowEnhancedMacRandomizationOnOpenSsids
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable manuscript investigated the role of glutamate signaling in the dorsomedial striatum of rats in a treadmill-based task and reported that it differs in goal-trackers compared to sign-trackers in a way that corresponds to differences in behaviour. The evidence supporting these claims is solid but could be further strengthened by adding more analyses and more detailed descriptions of current analyses. These findings will primarily be of interest to behavioural neuroscientists.
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Reviewer #1 (Public review):
Summary:
The authors measured glutamate transients in the DMS of rats as they performed an action selection task. They identified diverse patterns of behavior and glutamate dynamics depending on the pre-existing behavioral phenotype of the rat (sign tracker or goal tracker). Using pathway-specific DREADDs, they showed that these behavioral phenotypes and their corresponding glutamate transients were differentially dependent on input from the prelimbic cortex to the DMS.
Strengths:
Overall there are some very interesting results that make an important contribution to the field. Notably, the results seem to point to differential recruitment of the PL-DMS pathway in goal-tracking vs sign-tracking behaviors.
Weaknesses:
There is a lot of missing information and data that should be reported/presented to allow a complete understanding of the findings and what was done. The writing of the manuscript was mostly quite clear, however, there are some specific leaps in logic that require more elaboration, and the focus at the start and end on cholinergic neurons and Parkinson's disease are, at the moment, confusing and require more justification.
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Reviewer #2 (Public review):
Summary:
The authors aimed to determine whether goal-directed and cue-driven attentional strategies (goal- and sign-tracking phenotypes) were associated with variation in cued motor responses and dorsomedial striatal (DMS) glutamate transmission. They used a treadmill task in which cues indicated whether rats should turn or stop to receive a reward. They collected and analyzed several behavioral measures related to task performance with a focus on turns (performance, latency, duration) for which there are more measures than for stops. First, they established that goal-trackers perform better than sign-trackers in post-criterion turn performance (cued turns completed) and turn initiation. They used glutamate sensors to measure glutamate transmission in DMS. They performed analyses on glutamate traces that suggest phasic glutamate DMS dynamics to cues were primarily associated with successful turn performance and were more characteristic of goal-trackers (ie. rats with "goal-directed" attentional strategy). Smaller and more frequent DMS glutamate peaks were associated with other task events, cued misses (missed turns), cued stops, and reward delivery and were more characteristic of sign-trackers (i.e. rats with "cue-driven" attentional strategies). Consistent with the reported glutamate findings, chemogenetic inhibition of prelimbic-DMS glutamate transmission had an effect on goal-trackers' turn performance without affecting sign-trackers' performance in the treadmill task.
Strengths:
The power of the sign- and goal-tracking model to account for neurobiological and behavioral variability is critically important to the field's understanding of the heterogeneity of the brain in health and disease. The approach and methodology are sound in their contribution to this important effort.
The authors establish behavioral differences, measure a neurobiological correlate of relevance, and then manipulate that correlate in a broader circuitry and show a causal role in behavior that is consistent with neurobiological measurements and phenotypic differences.
Sophisticated analyses provide a compelling description of the authors' observations.
Weaknesses:
It is challenging to assess what is considered the "n" in each analysis (trial, session, rat, trace (averaged across a session or single trial)). Representative glutamate traces (n = 5 traces (out of hundreds of recorded traces)) are used to illustrate a central finding, while more conventional trial-averaged population activity traces are not presented or analyzed. The latter would provide much-needed support for the reported findings and conclusions. Digging deeper into the methods, results, and figure legends, provides some answers to the reader, but much can be done to clarify what each data point represents and, in particular, how each rat contributes to a reported finding (ie. single trial-averaged trace per session for multiple sessions, or dozens of single traces across multiple sessions).
Representative traces should in theory be consistent with population averages within phenotype, and if not, discussion of such inconsistencies would enrich the conclusions drawn from the study. In particular, population traces of the phasic cue response in GT may resemble the representative peak examples, while smaller irregular peaks of ST may be missed in a population average (averaged prolonged elevation) and could serve as a rationale for more sophisticated analyses of peak probability presented subsequently.
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Reviewer #3 (Public review):
Summary:
Avila and colleagues investigate the role of glutamate signaling in the dorsomedial striatum in a treadmill-based task where rats learn to turn or stop their walking based on learning cue-associations that allow them to acquire rewards. Phenotypic variation in Pavlovian conditioned sign and goal-tracking behavior was examined, where behavioral differences in stopping and turning were observed. Glutamate signals in the DMS were recorded during the treadmill task and were related to features of cue-controlled movement, with a stronger relationship seen for goal trackers. Finally, chemogenic inhibition of prelimbic neurons projecting to the DMS (the predicted source of those glutamate signals), preferentially affected cued movement in goal trackers. The authors couch these experiments in the context of cognitive control-attentional mechanisms, movement disorders, and individual differences in cue reactivity.
Strengths:
Overall these studies are interesting and are of general relevance to a number of research questions in neurology and psychiatry. The assessment of the intersection of individual differences in cue-related learning strategies with movement-related questions - in this case, cued turning behavior - is an interesting and understudied question. The link between this work and growing notions of corticostriatal control of action selection makes it timely.
Weaknesses:
The clarity of the manuscript could be improved in several places, including in the graphical visualization of data. It is sometimes difficult to interpret the glutamate results, as presented, in the context of specific behavior, for example.
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Author response:
Reviewer #1 (Public Review):
Strengths:
Overall there are some very interesting results that make an important contribution to the field. Notably, the results seem to point to differential recruitment of the PL-DMS pathway in goal-tracking vs sign-tracking behaviors.
Thank you.
Weaknesses:
There is a lot of missing information and data that should be reported/presented to allow a complete understanding of the findings and what was done. The writing of the manuscript was mostly quite clear, however, there are some specific leaps in logic that require more elaboration, and the focus at the start and end on cholinergic neurons and Parkinson's disease are, at the moment, confusing and require more justification.
In the revised paper, we provide additional information in support of results and clarify procedures and findings. Furthermore, we expand the discussion of the proposed interpretational framework that suggests that the contrasts between the cortical-striatal processing of movement cues in sign- versus goal trackers are related to previously established, parallel contrasts in the cortical cholinergic detection of attention-demanding cues.
Reviewer #2 (Public review):
Strengths:
The power of the sign- and goal-tracking model to account for neurobiological and behavioral variability is critically important to the field's understanding of the heterogeneity of the brain in health and disease. The approach and methodology are sound in their contribution to this important effort.
The authors establish behavioral differences, measure a neurobiological correlate of relevance, and then manipulate that correlate in a broader circuitry and show a causal role in behavior that is consistent with neurobiological measurements and phenotypic differences.
Sophisticated analyses provide a compelling description of the authors' observations.
Thank you.
Weaknesses:
It is challenging to assess what is considered the "n" in each analysis (trial, session, rat, trace (averaged across a session or single trial)). Representative glutamate traces (n = 5 traces (out of hundreds of recorded traces)) are used to illustrate a central finding, while more conventional trial-averaged population activity traces are not presented or analyzed. The latter would provide much-needed support for the reported findings and conclusions. Digging deeper into the methods, results, and figure legends, provides some answers to the reader, but much can be done to clarify what each data point represents and, in particular, how each rat contributes to a reported finding (ie. single trial-averaged trace per session for multiple sessions, or dozens of single traces across multiple sessions).
Representative traces should in theory be consistent with population averages within phenotype, and if not, discussion of such inconsistencies would enrich the conclusions drawn from the study. In particular, population traces of the phasic cue response in GT may resemble the representative peak examples, while smaller irregular peaks of ST may be missed in a population average (averaged prolonged elevation) and could serve as a rationale for more sophisticated analyses of peak probability presented subsequently.
Figures 5c-f depict individual data from all rats and trials. For all major analyses, the revised manuscript consolidates information about the number of rats per phenotype and sex, and the number of trials contributed by individual rats, in the result section.
As detailed in the section on statistical methods, and as mentioned by the reviewer under Strengths, we used advanced statistical methods to assure that data from individual animals contribute equally to the overall result, and to minimize the possibility that an inordinate number of trials obtained from just one or a couple of rats biased the overall analysis.
As the reviewer correctly pointed out, we have chosen not to show trial- or subject-averaged traces to illustrate glutamate release dynamics across trials. The present analyses focus on peak glutamate concentrations, the number of peaks, and the timing of peaks relative to a task cue or a behavioral event. Within a response bin, such as the 2-s period following turn cues, glutamate peaks – as defined in Methods - occur at variable times relative to cue onset. Averaging traces over a population of rats or trials would “wash-out” the phenotype- and task event-dependent patterns of glutamate peaks, yielding, for example, a single, nearly 2-s long plateau for cue-locked glutamate recordings from STs (Figure 5b). Thus, subject- or trial-averaged traces would not illustrate the major findings described in this paper and would rather be uninformative. As already mentioned, individual data from all subjects and trials are shown in Figs 5c-f.
Reviewer #3 (Public review):
Strengths:
Overall these studies are interesting and are of general relevance to a number of research questions in neurology and psychiatry. The assessment of the intersection of individual differences in cue-related learning strategies with movement-related questions - in this case, cued turning behavior - is an interesting and understudied question. The link between this work and growing notions of corticostriatal control of action selection makes it timely.
Thank you.
Weaknesses:
The clarity of the manuscript could be improved in several places, including in the graphical visualization of data. It is sometimes difficult to interpret the glutamate results, as presented, in the context of specific behavior, for example.
We appreciate the reviewer’s concerns about the complexity of some of the graphics, particularly the results from the arguably innovative analysis illustrated in Figure 6. Figure 6 illustrates that the likelihood of a cued turn can be predicted based on single and combined glutamate peak characteristics. The revised legend for this figure provides additional information and examples to ease the readers’ access to this figure.
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