Can this new probiotic reduce lactose intolerance? by [[Terence Eden]]

reply to michaljjwilk at https://hypothes.is/a/rwiI4rJYEe62aaN50r2zzQ to ensure it's properly indexed:

Most following my argument will have likely read The Two Definitions of Zettelkasten which may cover some of your initial question, or at least from my perspective. (Others certainly have different views.)

Some of your questions relate to what Robert Hutchins calls "The Great Conversation" (1952) and efforts over time to create Summa or compilations of all knowledge.

Variations of your remark about Plato can be seen in later Greeks' aphorism that "Everywhere I go in my head, I meet Plato coming back." or more recently in A.N. Whitehead's statement that everything is "a footnote to Plato".

Review coordinated by Life Science Editors Foundation

Reviewed by: Dr. Angela Andersen, Life Science Editors Foundation & Life Science Editors. *Assisted substantially by NotebookLM.

Potential Conflicts of Interest: Angela thinks Olivia Rissland is everything a scientist should be.

What is an N-degron? N-degrons are short amino acid sequences located at the N-terminus of a protein that signal for the protein's degradation. This process is an essential part of protein quality control and regulation within cells. N-degrons are recognized by specific E3 ubiquitin ligases, also known as N-recognins, which help target the protein for degradation by the ubiquitin-proteasome system.

How was this new Arg/N-degron pathway discovered? The authors were initially studying how N-terminal sequences affect gene expression using a reporter gene assay. They found that a specific tripeptide motif (KIH) inserted at the N-terminus of a reporter protein led to a dramatic decrease in protein expression. Further investigation revealed that this decrease was due to rapid protein degradation, indicating the presence of a novel N-degron.

What are the key features of this new N-degron pathway? This newly discovered N-degron pathway targets proteins with a lysine (K) or arginine (R) residue at the third position (position 3) from the N-terminus. Importantly, this pathway requires: * • Methionine Removal: The initiator methionine (M) at position 1 must be removed by the enzyme methionine aminopeptidase 2 (MetAP2) for the degron to be active. * • UBR4 Recognition: The E3 ligase UBR4, but not UBR1 or UBR2, recognizes this specific degron and initiates the degradation process.

Why is the identity of the second amino acid important? The second amino acid plays a crucial role in determining whether MetAP2 can cleave the initiator methionine. This study found that the degron is only active when the second amino acid is threonine (T) or valine (V). These amino acids allow MetAP2 to remove the methionine, exposing the lysine or arginine at position 3 for recognition by UBR4. In contrast, if the second amino acid is alanine (A) or serine (S), MetAP1 removes the methionine. The researchers hypothesize that these N-termini are then acetylated, preventing UBR4 recognition.

Is there evidence that this pathway affects endogenous proteins? Yes, analysis of previously published data and additional experiments by the researchers suggest that this MetAP2-UBR4 pathway is not limited to artificial reporter systems. They found that endogenous proteins with MTK or MVK N-termini were less stable than those with other amino acids at position.

Does UBR4 work alone in this pathway? UBR4 appears to function as part of a complex with the protein KCMF1 to degrade proteins containing this new degron. Experiments showed that disrupting the UBR4-KCMF1 complex stabilized the degradation of reporter proteins containing the KIH degron.

What is the broader significance of this discovery? The identification of this new Arg/N-degron pathway expands our understanding of the N-end rule, a fundamental mechanism for protein degradation in cells. It highlights the complexity of this system and reveals how the interplay between different enzymes like MetAP2 and E3 ligases like UBR4 can fine-tune protein stability. Additionally, it suggests that there may be other undiscovered N-degron pathways that remain to be characterized.

What questions still need to be answered about this new pathway? This study raises several new questions, including: * • Substrate Specificity: What are the precise rules governing UBR4 recognition of position 3 lysine and arginine degrons? Do other amino acids in the protein sequence affect degron recognition? * • Physiological Roles: What are the specific cellular processes and pathways regulated by this MetAP2-UBR4 N-degron pathway? * • Evolutionary Conservation: Is this pathway conserved in other organisms, or is it unique to mammals? * • Therapeutic Potential: Could this pathway be targeted for therapeutic purposes? For example, could stabilizing proteins involved in disease by manipulating this pathway be beneficial?

What was not known: * • Whether a lysine or arginine residue at position 3 of a protein could act as an N-degron. * • Whether MetAP2 could play a role in initiating N-degron-mediated degradation.

What this preprint reveals: * • A new family of N-degrons: The study identified a new class of N-degrons characterized by a lysine or arginine residue at position 3, following a methionine at position 1 and a MetAP2-cleavable residue (threonine or valine) at position * • MetAP2-dependent initiation of the Arg/N-degron pathway: The study found that MetAP2-mediated removal of the initiator methionine is essential for the recognition and degradation of these position 3 lysine/arginine degrons. This is the first demonstration of MetAP2's involvement in this pathway * • UBR4 as the primary E3 ligase: UBR4, rather than UBR1 or UBR2, was identified as the primary E3 ligase responsible for recognizing and targeting proteins with the newly identified position 3 degrons for degradation. * • Role of downstream residues: The study showed that amino acid residues downstream of the position 3 lysine/arginine can influence both methionine cleavage by MetAP2 and recognition by UBR4, highlighting the complexity of the N-degron pathway. * • Endogenous protein regulation: The study provided evidence suggesting that this MetAP2-dependent, UBR4-mediated Arg/N-degron pathway regulates the stability of endogenous proteins, highlighting its broader biological significance.

Ang's take- somewhat specialized and 'ectopic' but important, thorough, and unambiguous. Satisfying. Very likely to be physiologically relevant even though most of the assays were done with reporters. Regardless, showing that this rule 'is' true is useful for technological applications.

for - more meaningful lives from connecting to the greater whole of the human species - n other words - experience the sacred

Der britische Premierminister Sunak hat in n Wales an Protesten von militanten Vertreter:innen der konventionellen Landwirtschaft teilgenommen, die eine Abkehr von der Net-Zero-Politik fordern.

The intellectual historian in me: 😱

for - major evolutionary transitions in individuality - MET in individuality - https://hyp.is/3CqphlpHEe6yUmfDjm_p5A/www.pnas.org/doi/full/10.1073/pnas.1421402112

• for: MET, MST, MCT, FET, MET - information, MST - information, Amanda N. Robin, major evolutionary transition, major system transition, facilitating evolutionary transition

• Title:Major Evolutionary Transitions and the Roles of Facilitation and Information in Ecosystem Transformations

• Author: Robin et al.

• Date: 2021

• Abstract

  • A small number of extraordinary “Major Evolutionary Transitions” (METs) have attracted attention among biologists.
  • They comprise novel forms of
    • individuality and
    • information,

  • and are defined in relation to organismal complexity, irrespective of broader ecosystem-level effects.

  • This divorce between

    • evolutionary and
    • ecological consequences

  • qualifies unicellular eukaryotes, for example, as a MET although they alone failed to significantly alter ecosystems.

  • Additionally, this definition excludes revolutionary innovations not fitting into either MET type

    • (e.g., photosynthesis).
  • We recombine
    • evolution with
    • ecology
  • to explore how and why entire ecosystems were
    • newly created or
    • radically altered

  • as Major System Transitions (MSTs).

  • In doing so, we highlight important morphological adaptations that spread through populations because of

    • their immediate, direct-fitness advantages for individuals.

  • These are Major Competitive Transitions, or MCTs.

  • We argue that often
    • multiple
      • METs and
      • MCTs

  • must be present to produce MSTs.

  • For example, sexually-reproducing, multicellular eukaryotes (METs) with

    • anisogamy and
    • exoskeletons (MCTs)

  • significantly altered ecosystems during the Cambrian.

  • Therefore, we introduce the concepts of Facilitating Evolutionary Transitions (FETs) and Catalysts as

    • key events or agents that are insufficient themselves to set a MST into motion,
    • but are essential parts of synergies that do.

  • We further elucidate the role of information in MSTs as transitions across five levels:

    • (I) Encoded (Genetic);
    • (II) Epigenomic;
    • (III) Learned;
    • (IV) Inscribed; and
    • (V) Dark Information.

  • The latter is ‘authored’ by abiotic entities rather than biological organisms.

  • Level

    • IV has arguably allowed humans to produce a MST, and
    • V perhaps makes us a FET for a future transition that melds
      • biotic and
      • abiotic life
    • into one entity.
  • Understanding the interactive processes involved in past major transitions will illuminate both
    • current events and
    • the surprising possibilities that abiotically-created information may produce.

Indyweb / Indranet citations - Michael Levin, Roy Baumeister, Adam Omary youtube conversation - specifically, the question about whether a social superorganism of global human civilization / society / culture constitutes a new Major Evolutionary Transition of Individuality - https://hyp.is/rQgvZn2hEe6-TF8HFSS9mg/docdrop.org/video/UfoVTA0ilsY/

"Surrendering" by Ocean Vuong

1. He moved into United State when he was age of five. He first came to United State when he started kindergarten. Seven of them live in the apartment one bedroom and bathroom to share the whole. He learned ABC song and alphabet. He knows the ABC that he forgot the letter is M comes before N.

2. He went to the library since he was on the recess. He was in the library hiding from the bully. The bully just came in the library doing the slight frame and soft voice in front of the kid where he sit. He left the library, he walked to the middle of the schoolyard started calling him the pansy and fairy. He knows the American flag that he recognize on the microphone against the backdrop.

How might one use quirky algorithms in interestingly destructive or even generative ways to combinatorially create new things?

• Title
  • Visualizing a Field of Research With Scientometrics: Climate Change Associated With Major Aquatic Species Production in the World
• Authors
  • Mohamad N. Azra
  • Mohn Iqbal Mohd Noor
  • Yeong Yik Sung
  • Mazlan Abd Ghaffar
• Date July 13, 2022
• Source
  • https://www.frontiersin.org/articles/10.3389/fenvs.2022.905428/full
• Abstract
  • Climate change research on major aquatic species assists various stakeholders (e.g. policymakers, farmers, funders) in better managing its aquaculture activities and productivity for future food sustainability.
  • However, there has been little research on the impact of climate change on aquatic production, particularly in terms of scientometric analyses.
  • Thus, using the
    • bibliometric and
    • scientometric analysis methods,
  • this study was carried out to determine what research exists on the impact of climate change on aquatic production groups.
  • We focused on
    • finfish,
    • crustaceans, and
    • molluscs.
  • Data retrieved from Web of Science was
    • mapped with CiteSpace and
    • used to assess
      • the trends and
      • current status of research topics
    • on climate change associated with worldwide aquatic production.
  • We identified ocean acidification as an important research topic for managing the future production of aquatic species.
  • We also provided a comprehensive perspective and delineated the need for:
    • i) more international collaboration for research activity focusing on climate change and aquatic production in order to achieve the United Nations Sustainable Development Goal by 2030;
    • ii) the incorporation of work from molecular biology, economics, and sustainability.

Five core layers: 1. Presentation Layer 2. Application Layer 3. Domain Layer 4. Persistence Layer 5. Database Layer

https://www.amazon.com/Snap-N-Store-Index-Card-Black-SNS01577/dp/B002VCVCKW/

Boris Vladimirovich Gnedenko https://en.wikipedia.org/wiki/Boris_Vladimirovich_Gnedenko

He wrote with/worked with Khinchin and Kolmogorov.

Cathy N. Davidson. Now You See It: How the Brain Science of Attention Will Transform the Way We Live, Work, and Learn

https://www.amazon.com/Now-You-See-Attention-Transform/dp/0670022829/

This can be interpreted as an instantiation of the hero's journey, in the context of research that combines evolution with ecology as in the research paper: Major Evolutionary Transitions and the Roles of Facilitation and Information in Ecosystem Transformations (Robin et al., 2021).From this lens, cumulative cultural evolution (CCE) was first made possible through spoken language, then accelerated through written language. The authors claim that another Major System Transition (MST).is emerging, which they posit to be abiotic in nature involving Artificial Intelligence.

Faced with a self-induced civilization-scale threat, we may ask whether a major cultural evolution may be necessary to avoid catastrophe and whether it may constitute another MST. Could a rapid higher level global understanding of the epistemological dualism of self and other which undergirds normative alienation, othering and conflict, both with others of our own species, of other species and with the planetary system itself play a major role in the transition?

https://www.hastac.org/blogs/cathy-davidson/2011/12/18/relaxing-digital-garden-how-thrive-21st-century

An early reference to the idea of digital gardens with respect to not only the digital space but gardening within education.

Could this have potentially influenced Mike Caulfield's Garden and the Stream essay?

gene name: DICER 1 PMID (PubMed ID): 33570641 HGNCID: n/a Inheritance Pattern: autosomal dominant Disease Entity: benign and malignant tumor mutation Mutation: somatic Zygosity: heterozygous Variant: n/a Family Information: n/a Case: people of all sexes, ages, ethnicities and races participated CasePresentingHPOs: individuals with DICER1-associated tumors or pathogenic germline DICER1 variants were recruited to participate CasePreviousTesting: n/a gnomAD: n/a

Hello Everyone!

Some discussion of doing research on zettelkasten methods and workflows.

What do note taking methods and processes look like for individual people?

What questions would one ask for this sort of research in an interview setting (compared to how one would look at extant physical examples in document-based research)? #openquestions

Link this to the work of Earle Havens on commonplace books through portions of history.

Not like I will be late, but how long are usually the extensions given or accepted?

It seems at odds to use Charles W. Eliot as an example here as his writings described by Cathy Davidson in The New Education indicates that Eliot was specifically attempting to create standards in education that are counter to Menand's argument here.

Is it simply the stratification of power and roles that is causing these problems? Is it that some of this has changed and that communication between people of different power levels is the difficulty in these cases?

I have noticed a movement in pedagogy spaces that puts the teacher as a participant rather than as a leader thus erasing the power structures that previously existed. This exists within Cathy Davidson's The New Education where teachers indicate that they're learning as much as their students.

http://www.pasadenastarnews.com/2021/08/10/in-n-out-could-replace-camerons-seafood-in-pasadena-but-theres-a-catch

Zur diskontinuierlichen Klimapolitik der USA unter den letzten Administrationen https://www.nytimes.com/2021/04/19/climate/biden-climate-change.html

A vat is a large barrel or tank in which liquids can be stored. 大桶; 缸

N-VAR A misapprehension is a wrong idea or impression that you have about something. 误解; 误会

捐赠者；供者；赠送人

活组织检查；活组织切片检查；切片检查法

空想主义者；愿景者；远见者（visionary的复数）

N-COUNT Rodents are small mammals which have sharp front teeth. Rats, mice, and squirrels are rodents. 啮齿动物

N-COUNT If you are in a quandary, you have to make a decision but cannot decide what to do. 不知所措

n. a strict vegetarian; someone who eats no animal or dairy products at all

N-COUNT A vegetarian is someone who is vegetarian. 素食者

古时的高官

沸石

直径

n. 毫米；千分之一米

原料，组成部分

n. a product of your creative thinking and work 脑力劳动的产物

the process of purifying a liquid by boiling it and condensing its vapors蒸馏

液化

n. [化学] 氩

药物

IZA – Institute of Labor Economics. ‘COVID-19 and the Labor Market’. Accessed 6 October 2020. https://covid-19.iza.org/publications/dp13664/.

Original post is here.

This explanation should be combined with 24 Days of GHC Extensions: Rank N Types (see related hypothes.is note).

One of the best rock bands, ever.

See this video to understand their potential.

A national currency is a legal tender issued by a country's central bank or monetary authority.

Geosesarma dennerle

gilmanhernandez already linked to the video I was considering, but (according to a cursory search of YouTube at least) videos of turtle sounds are also likely to be videos of turtles mating or attempting to mate, so how 'mournful' they are is perhaps up to interpretation... 😂

Doreen Massey has an interesting book that touches on this (Space, Place, and Gender), where she points out that time and space are treated as binaries, where time is typically masculine and dynamic and space is feminine and static. Nature (gendered feminine) is spatial, a place, and therefore not a time ("ahistorical and timeless"). Culture, on the other hand, is temporal, dynamic, masculine. It's a very particular rhetoric which begs the "which one?" question.

(While Massey points out this common way of conceiving of time/space and binaries in general [A vs. Not A], she argues that the concept of space needs to be defined on its own merit, distinct from its binary opposite.)

I'm curious about what we would find by tracking the word "too" across the entire Mansfield short story corpus, mainly with word counts, word collocations, and n-grams. My hypothesis would be that the word "too" appears most frequently (perhaps exclusively) in stories with thematics of excess, both material and immaterial.

The story begins with the additive conjunction "and," which already suggests accumulation (and perhaps even festive excess) on a syntactical level. Some part-of-speech tagging and n-grams would allow us to see how often the speaker uses additive conjunctions, and to what effects.

not many care for his return from war but for those who celebrated his return were not that excited to see him only one man showed his appreciation toward the guy with no legs. he thanks the man in the wheel chair for sacrificing his life for the people. he also gave out fruits to him showing his appreciation.

Should titles ever be used for directions? Don't they override (or are overridden) by labels in some assistive techgnologies?

1. Dai-Riki 135 size 14
2. 140 denier yellow thread
3. Mop tenticles
4. Clown egg material

Does this mean wrapping an edit field with a label is not sufficient? Do such labels need a for attribute pointing to the id of the field?

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Para instruções detalhadas, veja o tutorial [NO ROOT] How to Install TWRP & custom ROM without root on Galaxy S5 G900.

Wms hsqr bml'r ilmu ufcl rm osgr, fsf Qfybmu-Egpj-uyllyzc-wmspqcjd?

Nmr, wms pcyjjw lccb rm kccr rfyr icrrjc~

Qm ufw lmr pcnspnmqc rfc "yaacqqmpgcq" glrm yarsyj mlcq jgic zmuq? Kcrfgliq rfcw'b yr jcyqr zc md sqc rfcl... Qglac wms'pc yjj ynnypclrjw kmpc zjglb rfyl kwqcjd ^.^

Very true. If people note that they were debunked.

Attention / Rock n roll

rock and roll / attention

no