Articles

Language Keepers: The Struggle for Indigenous Language Survival in California

• Revitalisation efforts for indigenous (often oral) languages of California— if lost, languages take ecological, historical, cultural knowledge with them. Akin to revitalisation of Maori, Hawaiian languages earlier in century
• Wukchumni: Marie Wilcox = last speaker, creating dictionary, teaching family
• Karuk: from region of gold rush, people experienced genocide from this.
• Nuwä: from southern end of Sierra Nevadas
• Tolowa Deeni’: Pacific Coast, near redwoods

Arrows of Time (Quanta)

• Cool timeline on cultural, biological, physics-al, and timekeeping events in the history of... time. Also, a really fucking cool method of visualization, use of color— keep in mind for future work!

Inside Deep Undersea Rocks, Life Thrives Without the Sun

• Recent discoveries and exploration of the deep subsurface microbial landscape — volcanic rock, Earth’s crust beneath the deep sea
• Ecosystems not reliant on the sun! Microbes powered by chemicals and minerals released by hydrothermal vents; populations of microbes an order of magnitude larger than those on land or in the sea
• Zombie cells buried deep in sediment layers (very slow exchange of nutrients)— alive, but living on extremely slow time scales (divide every 100-1000 years!)
• In harder rock like basalt, seawater circulates more rapidly— better environment for microbial life? Younger basalt studied a bit, but not looking at ancient basalt further from vents
• Use radiolysis: radiation released by rocks produces hydrogen, which can be used as fuel by cells
• Implications for origins of life?

What Happens to Them Happens to Us

• An Indigenous poet reflects on how releasing a captive killer whale could mean our own redemption.
• Orcinus = kingdom of the dead (Latin)
• In Lummi language, called Qwe lhol mech ten, “Our relations under the waves.”

Et alia

• Seven Sketches in Compositionality: An Invitation to Applied Category Theory
• A supernova in 1604 may have occurred close enough to Earth to affect the climate... Evidence for the event comes from the trace amounts of iron isotopes in the ferromanganese crust that grows on the ocean floor. The timing of the nova coincides with the drying up of Africa, which may have induced our hominid ancestors to descend from trees, thus enabling the course of human evolution.
• The pandemic is revealing the weaknesses in the US food supply chain and culture: namely, the industrial system based on commodities like soy and corn; reliance on a few mega-meat producers; and the nutritional deficits from the typical diet (which makes people more vulnerable to infection and serious symptoms). Conversely, decentralised (local) and diversified farmers have responded resiliently, highlighting the advantages of such systems in the modern works. Thanks, Michael Pollan.
• A cool peek behind the scenes of a collection of coronavirus illustrations.
• Microglia, the brain’s immune cells, respond to different frequencies of electrical activity that can be induced by external stimuli, like flashing lights or pulsing sounds. “Programming” immune cells in this way could potentially be used to treat Alzheimer’s and other neurological diseases.
• Scientific culture is at its most powerful and most dangerous. What ethical or value-based guidelines can we enact as a society to harness its power and avoid its potential threats?
• The counterintuitive reality of sea level rise due to melting ice sheets— the loss of gravitational attraction of water to the ice actually causes levels to drop within a radius of 2000 km, and disproportionately rise further away.
• We may be hardwired for selfishness for self-preservation, but we also have an innate human capacity for otherishness— a sustainable mentality of considering the impact of our actions on other people.

Research readings

DNA Methylation Atlas of the Mouse Brain at Single-Cell Resolution

Background

• Cytosine DNA methylation = 5mC, stable covalent modification in post-mitotic cells, usually occurs at CpG sites; critical for regulation
• Unique to neurons, also methylation at non-CpG sites = mCH(anti-correlated with gene expression)

Results

• Epigenome profiling by single-nucleus DNA methylation seq from 45 regions of mouse brain -> 161 cell clusters (distinct spatial location & projection targets); annotated with signature genes, reg elements, TFs
• Insights on how reg landscape affects cell fate, repetitive usage of regulators in excitatory and inhibitory cells to determine subtypes
• Methylation landscape in excitatory cells = continuous spatial gradient, used to build ANN to predict neuron identity and location
• Integrated methylome data with open chromatin, chromatin contact -> enhancer-gene cx, validated by chromatin confirmation capture experiments

The spatial distributions of pre-mRNAs suggest post-transcriptional splicing of specific introns within endogenous genes

(Arjun Raj, Stirling Churchman)

• When does splicing occur? Thought to be during transcription, but some evidence for after
• Single molecule RNA FISH (diff proves binding to introns and exons) + expansion microscopy -> visualise spatial distribution of nascent & partially-spliced RNA
• Showed that all 4 genes studied undergo post-transcriptional splicing; introns can be spliced in any order
• Patterns of localisation -> “regulation of the timing and localization of splicing is specific to individual introns“

Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism

• Transcriptionally upregulated (ex. HIF targets) genes and genes under selection in high altitude pop’ns not selectively essential in low oxygen

Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage

• How do cells protect their genome vs mechanical stress? Healthy epithelial tissue can withstand deformation without damage, while cancer cells usually undergo DNA damage.
• Nucleus connected to extracellular envt with various adapter proteins, cytoskeleton; heterochromatin organized into lamina-associated regions (enriched with histone modificafions)
• Mechanical stress shown to affect gene expression (and changes to methyl transferases affect chromatin positioning), but how?
• Stretch -> immediate nucleus deformation -> Piezo1-mediated Ca++ release from ER -> reduces laminar heterochromatin -> nucleus softens

Tools and Concepts for Interrogating and Defining Cellular Identity

• Can classify cells by feature or function: tightly linked, but also context-dependent (feature can lead diff functions in diff env’ts; extracellular heterogeneity can make identical cells abefunction differently); plasticity -> transitions in cell state over time... What does a given cell type do in steady state, vs what is it capable of in a given environment?

Tools for assessing cell features & functions

1. Detecting features associated with a cell type from pre-defined list of candidates: microscopy (immunohistochemistry, in situ hybridisation, fluorescent labelling of proteins, flow cytometry, etc. — current efforts to increase resolution, multiplex); mass cytometry (conjugate antibodies to metal jobs instead of fluorophores, can detect proteins or mRNA or both— CyTOF, EpiTOF, etc.); mRNA population methods like qRT-PCR, microarrays; single mRNA molecule methods like MERFISH, amplification via RNAscope, in situ with INSTA-seq, FISSEQ
2. Identifying new features and types with unbiased approaches: scRNA-seq; snRNA-seq (reduces dissociation bias); add spatial context with things like ZipSeq and multiplexing of aforementioned in situ methods (note that ISH is not unbiased as relies on predetermined oligos); other sc-omics like mass spec (still very new); profiling of chromatin structure and organization (scDNase-seq, scATAC-seq); beginning to layer molecular profiles with new techniques (literally profile same cells) or algorithms
3. Defining cellular relationships: live microscopy (ground truth for lineage tracing, dynamic assessment of cell behavior— tradeoff between complexity of physiological system you’re studying and complexity of tech needed); lineage tracing (all the usual); trajectories with scRNA-seq (diff time points, RNA velocity, etc.)

Assessing cell function: modulation of cellular contributions by tissue content

• Epithelial stem cells: now known that can undergo symmetric and asymmetric division (lost ones replaced by neighbors);give rise to diff cell fates depending on microenvironment cues, niche, neighboring cells
• Functional tests for stemness -> repopulation potential depends on context, assay: transplantation (big effect of microenvironment!); in vitro culture (organoids, important to consider additives)
• Stem cell behavior in response to damage: both factors can increase potential of existing stem cells, induce stemness in other cells
• Competitive intx with neighboring cells can increase or decrease potential of stem cells

Guidelines and definitions for research on epithelial–mesenchymal transition

Expansion Sequencing: Spatially Precise In Situ Transcriptomics in Intact Biological Systems

• First method for multiplexed RNA imaging in situ with nanoscale resolution of cellular morphology — untargeted library for hybridisation with expansion microscopy (had to neutralise charges generated by usual method)
• Use in situ sequencing followed by ex situ sequencing to get longer reads, better capture complexity
• Could characterize nanoscale transcriptional compartments in neurons (ex. specific transcripts in spines)
• Maps cell types and state in cancer tissue

Putative cell type discovery from single-cell gene expression data

• Identify groups of cells and weighted list of feature genes for each

Massively multiplex single-molecule oligonucleosome footprinting

• SAMOSA— single-molecule adenine methylated oligonucleosome sequencing assay— a high-throughput single-molecule sequencing method that combines adenine methyltransferase footprinting and single-molecule real-time DNA sequencing to natively and nondestructively measure nucleosome positions on individual chromatin fibres
• Allows unbiased classification of single-molecular 'states' of nucleosome occupancy on individual chromatin fibres

Podcasts

Ezra Klein with Jenny Odell on nature, art, and burnout in quarantine

• The weird duality of interdependence and independence (isolation?) emphasised by this situation
• The compulsion for productivity, and how it really just depends on your situation what this looks like for you right now— and that maybe your “idle” time now will fuel production later

Ezra Klein with Madeline Miller

• Lovely conversation on the Greek epics, language & translation, stories, and universal human nature

Linguists Hear an Accent Begin

• ... in Antarctica! (60 second science from Scientific American)

Wind of Change

• The fucking CIA, man