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Is it better for the people that are using it? No.
for - progress trap - example - cell phone usage
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for - human cell - resonant frequency
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there are no genes for any of those membranes all the lipids that form the membranes and the complicated 00:07:27 structures that you can see in a typical cell none of that is coded for in the genome all of that is inherited
for - key insight - decision-making structures are in the cell membrane, not the genes
key insight - The codes that enable us to make choices are located in - the membranes of our cells and - their protein channels - There are no genes for - any of those membranes - all the lipids that form the membranes and the complicated structures that you can see in a typical cell - None of that is coded for in the genome - All of that is inherited
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a bit of size comparison
for - size comparison - genome to cell
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it's easy for us to look at us and think okay we're 30 trillion human cells give or take we're about 39 trillion bacterial cells at what point do we consider ourselves bacteria or at what point do we consider ourselves 00:07:46 human
for - question - identity - individual cell vs multicellular organism
question - identity - individual cell vs multicellular organism - This is a fascinating question as it looks at our evolutionarily composite nature - as a multi-scale competency architecture - Certainly our ordinary consciousness operates as the governance system for the entire population of collaborating cells and microbes - but can we actually directly identify with each individual cell or microbe in this vast integrated collection? - how does Levin's computational boundary of self help to shed light on this question?
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Fluorescence Activated Cell Sorting (FACS). From sorting cells for single cell genomics to identifying the host range of a plasmid; from detecting metabolically active cells in an environmental sample to studying colitogenic-driving intestinal bacteria, FACS can be used in a multitude of applications to study microbial communities (Rinke et al. 2014, Klumper et al. 2015, Kalyuzhnaya et al. 2008, Hatzenpichler et al. 2016, Palm et al. 2014).
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article-summarizer.scholarcy.com article-summarizer.scholarcy.com
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Komórki Purkinjego i móżdżekJak stwierdzono, komputery PC wmóżdżekmają istotne prognozy dotyczące LC ( Schwarz i in., 2015 ). Warto zauważyć, że niższa całkowita liczba komputerów PC lub zmniejszona gęstość komputerów PC to jedne z najbardziej powtarzalnych odkryć neurobiologicznych w ASD (około 75% osób z ASD wykazuje dysfunkcję/zmniejszoną liczbę komputerów PC ; Fatemi i in., 2002 ; Whitney i in., 2009 ;Passarelli i in., 2013 ;Hampson i Blatt, 2015 ). Niektóre dowody wskazują, że liczba komputerów PC zmniejsza się również w przypadku ADHD , ale konieczne są dalsze badania (Rout i in., 2012 ;Passarelli i in., 2013 ). Jak zauważają Rout i in. (2012 ),zmniejszoną liczbę PC można zaobserwować jedynie w podtypie ADHD z dysfunkcją móżdżku, jak wykazano w bardziej globalnej ocenie neuroobrazowania(patrz Durston i in., 2011 ). Obecnie wciąż nie można zrozumieć genetycznych podstaw PC w ASD (Hampson i Blatt, 2015 ). W jednym badaniu przeprowadzonym przez Rout i wsp. (2012 ) wykazano zwiększony poziom przeciwciał przeciwko dekarboksylazie kwasu glutaminowego 65 ( GAD65 ) w surowicy w grupach ASD i ADHD w porównaniu z osobami z grupy kontrolnej (przeciwciała GAD65 nie były obecne u żadnej zdrowej osoby). GAD65 jest ważny w syntezie kwasu γ-aminomasłowego ( GABA ). Następnie myszom nałożono surowicę z grup ASD i ADHDmóżdżek, gdzie przeciwciała reagowały z komputerami PC . Zastosowanie tych przeciwciał ostatecznie doprowadziło do śmierci PC ( Mitoma i in., 2003 ;Rout i in., 2012 ). Zwiększone przeciwciała przeciwko GAD65 mogą zatem przyczyniać się do dysfunkcji PC w ASD i ADHD , ale wymagane są badania na większych próbach. Nieprawidłowe projekcje doprowadzające PC w ASD i być może ADHD do LC mogą prowadzić do dysfunkcji LC -NE. Jednak możliwa jest także sytuacja odwrotna. Jak stwierdzono, LC moduluje asocjacyjną plastyczność synaptyczną móżdżku, co wpływa na odpalanie PC ( Carey i Regehr, 2009 ). Dlatego nieprawidłowe działanie LC -NE może prowadzić do zakłóceń w działaniu komputera .Ostatnią opcją jest to, że wzajemne projekcje między LC i móżdżkiem w obu kierunkach są nieprawidłowe, co również wskazywałoby na dysfunkcję LC-NE i PC/móżdżku
Komurki Purkinego bardziej związane z ASD, ale możliwe że LC NE zaburza działanie komurek purkinjego
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Jaka jest behawioralna konsekwencja tej synchronizacji? Prawdopodobieństwo synchronizacji było największe dla sakkad, które znajdowały się w kierunku, który pokrywał się z najmniejszym prawdopodobieństwem CS (CS+180). W przypadku wielu rodzajów zachowań, w tym kondycjonowania powiek oczu, sakkad i ruchów kończyn, strojenie CS komórki P jest prawdopodobnie dostosowane do kierunku działania neuronu jądra [19, 46, 47]. Na przykład w sakkadowych ruchach gałek ocznych analiza wpływu CS na SS i zachowanie sugeruje, że komórki P, które mają dostrojenie CS do błędów punktu końcowego w lewo, rzutują na neurony jądra, które mają dalszy kierunek działania, który pośrednio promuje wytwarzanie sił w lewo [19], korygując w ten sposób te błędy. Oznacza to, że podczas sakkady w kierunku CS+180 zwiększona synchronizacja łączy się z odhamowaniem (pauzą szczytową), aby porwać neurony jądra podczas zwalniania [9], wytwarzając siły w dół, które są wyrównane z CS-on macierzystych komórek P. W rezultacie, efekt synchronizacji limfocytów P, w połączeniu z odhamowaniem jądra, prawdopodobnie wytworzy siły, które sprzeciwiają się kierunkowi ruchu, powodując jego zatrzymanie.
Hamowanie za pomocą Komurek Purkinjego
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Tu Skupiliśmy się na wychylnych ruchach gałek ocznych, ponieważ są one tak krótkie, że wykluczają możliwość sensorycznego sprzężenia zwrotnego, co wymaga od mózgu polegania wyłącznie na swoich wewnętrznych przewidywaniach [13,14,15]. Przewidywania te zależą w dużej mierze od móżdżku [16, 17]. Na przykład szybkość wypalania populacji komórek P, ale nie pojedynczych komórek, przewiduje kierunek i prędkość trwającej sakkady [18, 19]. Jednak, aby sprawdzić synchronizację, musieliśmy jednocześnie rejestrować z wielu komórek P podczas sakkad, coś, co, według naszej wiedzy, nie zostało osiągnięte u żadnego gatunku naczelnych.Informacje, które jeden obszar mózgu przekazuje drugiemu, są zwykle postrzegane przez pryzmat szybkości wypalania. Gdyby jednak neurony wyjściowe mogły zmieniać czas swoich skoków, to poprzez synchronizację zwracałyby uwagę na informacje, które mogą mieć kluczowe znaczenie dla kontroli zachowania. Tutaj donosimy, że w móżdżku populacje komórek Purkinjego, które podzielają preferencję błędu, przekazują do jądra, kiedy spowolnić ruch, zmniejszając szybkość wypalania i tymczasowo synchronizując pozostałe kolce.
Działanie komórek Purkinjego
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- Nov 2023
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you can train them it has memory you can train it you can take a a trained one and a naive one and fuse them they 00:39:24 they'll fuse together and then the memory sort of propagates and the naive one will now remember you know have the memory that that the other one had um no nerves no no brain um single cell
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for: Michael Levin - slime mold experiment, question - new theory of consciousness from a single cell
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question
- is it possible that a theory can be constructed to explain consciousness from the behavior of a single cell organism such as a slime mold?
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typically between 1010 and 1011 microbial cells per wet-weight gram of faeces7,8,9.
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www.frontiersin.org www.frontiersin.org
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Eukaryotic single-celled organisms appear in the fossil record perhaps by 1.6 BYA (Knoll et al., 2006). Yet for a “boring billion” years of evolutionary history, they remain minor components in bacterial-dominated ecosystems before explosively radiating as large, multicellular species in an Ediacaran and Cambrian MST. Eukaryotes are obviously essential for this MST, as all animals, plants and fungi are eukaryotes. However, the initial appearance of eukaryotic cells seems insufficient for a MST.
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for: example, example - MET and FET insufficient for MST
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example: MET and FET insufficient for MST
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paraphrase
- Eukaryotic single-celled organisms appear in the fossil record by approx. 1.6 BYA (Knoll et al., 2006).
- Yet for a “boring billion” years of evolutionary history, they remain minor components in bacterial-dominated ecosystems
- before explosively radiating as large, multicellular species in
- an Ediacaran and
- Cambrian MST.
- before explosively radiating as large, multicellular species in
- Eukaryotes are obviously essential for this MST, as all
- animals,
- plants and
- fungi
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are eukaryotes.
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However, the initial appearance of eukaryotic cells seems insufficient for a MST
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tinlizzie.org tinlizzie.org
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Imagine having your own self-contained knowledge manipulator in a portable package the size andshape of an ordinary notebook. How would you use it if it had enough power to outrace yoursenses of sight and hearing, enough capacity to store for later retrieval thousands of page-equivalentsof reference materials, poems, letters, recipes, drawings, animations, musical scores, waveforms,dynamic simulations, and anything else you would like to create, remember, and change?
Fascinating how Even though we did realized some of this with the mobile phone we still have a system that's so fragmented that it's fundamentally getting in the way of progress
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- Sep 2023
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for: superorganism, multi-level superorganism, collective intelligence, individual-collective gestalt, Michael Levin,
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title: Cell Intelligence in Physiological and Morphological Spaces
- author: Michael Levin
- date 2022
- comment
- This is a talk on collective intelligence in unconventional spaces
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Rickshaw Bags, Traveler's Notebook Case $59.00
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the big discovery of the 21st century is that actually just because someone's died and I've given them a Death Note as a physician as an intensive care physician the cells inside the body 00:02:15 have not yet died
- (cell) life after death
- cells within the body still remain alive after what a physician would normally deem a person dead.
- cells (including brain cells) go into a hibernation state for many hours after death.
- (cell) life after death
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Review coordinated by Life Science Editors.
Reviewed by: Dr. Helen Pickersgill, Life Science Editors
Potential Conflicts of Interest: None
Main point of the paper: By combining multiple stains and antibodies with ultrastructural expansion (light) microscopy in Plasmodium falciparum during the course of mitosis within red blood cells (the asexual blood stage), when it causes the symptoms of malaria, the authors identified new structural features of cell division in this important human parasite.
Why this is interesting: Imaging the dramatic physical events that occur when cells divide tells us a lot about the biology of the process and is insightful to compare between different eukaryotes, but many organisms are too small to visualise by light microscopy, which is the most versatile imaging technique. So, they used an existing preparation technique to enlarge the parasites, a wide array of dyes and antibodies, and sampled at multiple timepoints so that more intracellular structures could be visualised and their behaviour and potential functions in cell division revealed.
Background: Expansion microscopy (ExM) has been around since 2015 (doi: 10.1126/science.1260088) and is a fairly simple and affordable technique. It involves physically magnifying a specimen by embedding it in a polyelectrolyte gel that swells up in water enabling super-resolution imaging. It has been previously applied to Plasmodium and other Apicomplexa, but not with so many different labels across different timepoints at this important life-stage.
Results: • They imaged 13 subcellular structures (including microtubules, microtubule organising centres, apicoplasts, Golgi and the ER) at multiple timepoints covering the entire asexual blood stage. • Among many results were the following: • They found a central role for the nuclear MTOC in coordinating mitosis and likely in establishing apical-basal polarity early during the asexual cycle. o the MTOC is tethered to the parasite plasma membrane (via cytoplasmic extensions) throughout mitosis. o the cytoplasmic extensions of the MTOC were closely associated (in numbers and positions) with several apical structures including the Golgi and the basal complex. o the MTOC is tethered to the mitochondria and apicoplast during fission and may also regulate their copy numbers. • They performed the first detailed characterization of the short-lived interpolar spindles, previously difficult to visualize, which consist of microtubules connecting duplicated MTOCs as they move to opposite sides of the cell. They found a large variation in their size, which may be how they enable the MTOCs to move without detaching from the plasma membrane. • They were able to study the biogenesis of rhoptries, which secrete proteins required for the parasite to invade host red blood cells, and discovered that: o biogenesis begins earlier than thought and that they associate with MTOCs during the remaining rounds of mitosis. o Rhoptry pairs are likely synthesized independently because over 95% are different sizes and densities.
Remaining thoughts: • Clearly written and easy to read paper with stunning images. • Comprehensive (including descriptions of when things didn’t work), but remains largely descriptive (of course). • Could be shortened/sharpened to make it more manageable to read without losing the main messages, which are somewhat lost in the text. • A top-level, specialised paper that opens the door for more targeted studies of organelle functions during mitosis and comparisons of these functions with other (higher) eukaryotes. • By identifying key players in mitosis during the asexual blood stage it may reveal candidate therapeutic targets for treating malaria.
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- Feb 2023
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Review coordinated by Life Science Editors
Reviewed by: Dr. Helen Pickersgill, Life Science Editors
Potential Conflicts of Interest: None
Impact Point: Transcription factors may mediate the release of specific genes in extracellular vesicles that could be taken up by other cells and directly influence their behaviour.
Background: Extracellular vesicles (EVs) are nanoscale, membrane-bound vesicles containing proteins, nucleic acids and lipids that are released by most cell types. Originally thought of as a cell waste disposal mechanism, they have since been rebranded as a means of intercellular communication, both short and long range, (like a cellular postal service), and can, for example, modify gene expression and function in recipient cells via the transfer of specific RNAs (DOI: 10.1038/s41580-020-0251-y). One interesting function for EVs was the recent discovery that antigen presenting cells (APCs) could donate telomeres via EVs to recipient T cells and rescue them from senescence (DOI: 10.1038/s41556-022-00991-z).
Given EVs contain a wide variety of cargos derived from the secreting cells, which have been extensively profiled (e.g., DOI: 10.1016/j.cell.2020.07.009) they are particularly interesting as sources of biomarkers for diagnosing diseases such as cancer (e.g., DOI: 10.1038/s12276-019-0219-1). We might also be able to use them as stable delivery mechanisms for controlling cell behaviour or targeting therapeutics/diagnostics.
We know quite a bit about how RNAs and proteins are selected for secretion by EVs (mediated by the autophagy protein LC3: e.g., DOIs: 10.1080/15548627.2020.1756557; 10.1038/s41556-019-0450-y). But little is known about DNA. DNA presents a particular challenge as it is packed up into the nucleus. This is also particularly important to understand in the context of horizontal gene transfer, i.e., passing functional genes between cells.
Main question: How does a cell ‘select’ specific DNA cargo from the nucleus and enable it to be released by EVs?
The advance: They discover that a transcription factor (FOXM1) plays a central role in mediating DNA release in EVs.
Results: • FOXM1 and LC3 (autophagy protein) colocalize and interact in cultured cells (coIP endogenous and exogenous, EMSA, immunostaining and identify an FOXM1-binding domain mutant). • FOXM1, LC3 and DNA colocalise in the cytoplasm in cultured cells, which increases upon starvation-induced autophagy (immunofluorescence). • FOXM1 and LC3 are found in EVs released from cultured cells (Western blot). • 15,544 DNA identified in EVs released from cultured cells (evDNA sequencing), of which 25 overlapped with DNA loci binding FOXM1 (ChIP). • FOXM1-bound nuclear DNA is transported to the cytoplasm upon induction of autophagy and is released in EVs in cultured cells (knock-in tagged chromatin with CRISPR-cas9, IF and PCR). This is dependent on FOXM1 (knock-out in cultured cells).
Significance: Transcription factors display strong DNA binding specificity and so are ideal candidates for directing specific genes into EVs for potential transfer to recipient cells.
Remaining questions/points: Care needs to be taken with regard to purification of EVs. Are the FOXM1-DNAs in the EVs functional in recipient cells? Is the DNA being actively ‘selected’ for an intercellular signalling purpose or is this just random degradation? Is it all FOXM1 bound DNA that has the potential to be trafficked to EVs or just a subset? Do other transcription factors have the same function or is it specific to this protein/family? Does this mechanism occur in other contexts (e.g., in vivo, under disease conditions).
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Transparent Peer Review
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Transparent Peer Review
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Transparent Peer Review
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Review coordinated by Life Science Editors.
Reviewed by: Dr. Angela Andersen, Life Science Editors
Potential Conflicts of Interest: Dr. Mill has worked with Life Science Editors on other manuscripts.
Background: Retinitis pigmentosa (RP) is a group of rare eye diseases that cause vision loss. Symptoms usually start in childhood, and most people eventually lose most of their sight. There is no cure for RP. Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause RP and compromise the renewal of light-sensitive “disc” membranes (specialized cilia) at the outer segment of photoreceptors, resulting in the loss of these cells over time. Evidence suggests that disc formation is similar to the release of ectosomes (small extracellular vesicles) and that both rely on the actin cytoskeleton. Knockdown of RPGR in retinal pigmented epithelium cells showed stronger actin filaments and reduced cilia suggesting that it may regulate nascent photoreceptor disc formation by regulating actin-mediated membrane extension in the retina (Gakovic et al., Human Molecular Genetics, 2011). In addition, RPGR patient iPSC-retinal models displayed phenotypes consistent with abnormal actin regulation (Megaw et al., Nature Communications, 2017; Karam et al., J Personalized Medicine, 2022).
Question: What function of RPGR is compromised in photoreceptors to cause RP?
Advance: The authors generated novel Rpgr mutant mice harboring human disease-causing mutations that recapitulate human disease phenotypes: aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. RPGR is located at the site of disc formation – to test if it plays a role in disc genesis, they engineered a novel reporter mouse to track outer segment turnover. Rhodopsin was tagged with the self-labelling peptide SNAP- Rhodopsin is the major protein component of outer segment discs, and so incubating RhodSNAP retinal slice cultures with SNAP fluorophores results in outer segment labelling. Perturbation of RPGR resulted in a slowed rate of disc formation, leading to shortened outer segments and increased vesicle shedding. To me, the breakthrough is in the last figure: the actin depolymerizing drug Cytochalasin D in PBS was injected intravitreally, and fixed retinas were analyzed 6 hours later by electron microscopy. Cytochalasin D treatment significantly reduced the number of shed vesicles from the base of the outer segment in Rpgr-mutant mice (they now look like wild-type).
Significance: Nails down the disease-relevant function of RPGR and a molecular mechanism of RP in photoreceptor cells, in vivo, in mice. Pharmacological rescue not only demonstrates the importance of the mechanism to disease but also sheds light on a potential therapeutic avenue for RP.
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- Jan 2023
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Transparent Peer Review
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- Dec 2022
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There are a number of ways in which a cell can move from one point in space to another.
- Axoneme
- Cell crawling via the remodelling of the actin cytoskeleton.
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APC: anaphase promoting complex; active APC drives cell out of mitosis with its E3 ubiquitin ligase activity, modifying cyclin and targeting it for proteolysis;
APC/C targets S-CDK and M-CDK. Degradation of M-cylin.
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- Nov 2022
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