10/24
Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment (Science 2022 MPI Melina Schuh)
Mammalian oocytes stop transcription during later stages of growth and do not turn it back on until the embryonic genome is activated after fertilization - Thus, oocyte development into a mature egg occurs without transcription.
During this process, the oocyte must rely on previously stored mRNA to translate the new protein
Previous studies have identified various types of mRNA-storing membraneless compartments in non-mammalian oocytes. However, it is unclear where and how mRNA is stored in mammalian oocytes.
This paper finds that mammalian oocytes store mRNA in a mitochondria-associated membraneless compartment
The researchers identified RNA-binding proteins highly expressed in the cytoplasm of mouse oocytes by mass spectrometry and analyzed the localization of these proteins by immunostaining. These proteins were found to aggregate near mitochondria and form clusters with mitochondria.
In contrast, these RNA-binding proteins did not co-localize with other organelles, or only partially co-localized. RNA in situ hybridization (RNA-FISH) experiments revealed that mRNA was also localized in this structure, suggesting that it is an mRNA reservoir. Because this structure is significantly different from previously discovered RNA storage compartments, the researchers named the structure the mitochondria-associated ribonucleoprotein domain, or MARDO for short.

10/24
Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels (2022 Cell Rockefeller University Leslie B. Vosshall)
The paper found that some people are more attractive to mosquitoes due to different skin odors.
These people have higher levels of carboxylic acids on their skin, and mosquitoes with deficient sense of smell will show a decrease in preference, but they still can distinguish people with highly attracted odor and non-attractive odor.

10/24
An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice (2022 Science Holly A. Ingraham Ajay Chawla)
Compared with premenopausal women, men are more likely to suffer from abnormal accumulation of liver fat, non-alcoholic fatty liver disease, liver fibrosis and liver tumors
Sex differences in hepatic gene expression are regulated by transient secretion patterns of pituitary growth hormone
BCL6 is a class of sex-dependent, growth hormone-regulated hepatocyte transcription factors.
The paper found that BCL6 played a role in promoting the phenotype that male mice are more susceptible to high-fat diet-induced nonalcoholic fatty liver disease
In the case of bacterial infection, BCL6 can increase male survival rate, which is an evolutionary trade-off.

10/25
Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development (2022 Molecular Cell Upenn Marisa S. Bartolomei)
Diploid organisms have two sets of chromosomes, one from each parent.
In mammals, there are about 200 genes called imprinted genes that express genes from only one parent. These imprinted genes in the germline carry DNA methylation memory from the parent.
These imprinted genes in the germline carry DNA methylation memories from their parents.
DNA methylation-marked regions are also known as imprinting control regions (ICRs)
In addition to being a marker of parental memory, ICRs also control the expression of imprinted genes by coordinating, for example, noncoding RNAs and enhancers.
This paper identifies an unconventional differentially methylated region (DMRs) as a specific mechanism by which Grb10 and Ddc imprinted gene insulators regulate cardiac and muscle development.

10/26
Time-restricted feeding mitigates obesity through adipocyte thermogenesis (2022 Science Joseph Bass Northwest University)
Excessive consumption of food is also associated with disturbances in the meal timing and metabolic cycle of one's own biological clock, that is, eating at inappropriate times is more likely to lead to fat accumulation.
Genetically induced disruption of the circadian clock can cause nocturnal animals to consume more food in the day time (dormancy period) and produce more severe obesity problems
Eating at the wrong time worsens food-induced obesity. But limiting high-calorie food to periods of activity can improve metabolism and support health.
This paper reports that the circadian rhythm negatively regulates the transcription factor, ZFP423, through thermogenesis. ZFP423 regulates creatine content in adipose tissue, and creatine content promotes ineffective creatine cycle to further regulate thermogenesis; ultimately regulates energy metabolism under a high-fat diet.

10/27
CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo (2022 Nucleic Acids Research 胡家志/徐墨 Peking/Tsinghua)
CRISPR-Cas gene editing tools are widely used in scientific research and clinical practice. However, in addition to on-target products and off-target editing, CRISPR-Cas also produces chromosomal structural variations (SVs) such as chromosomal translocations and large deletions, as well as massive viral DNA insertion
This paper uses the high-throughput sequencing method PEM-seq (primer-extension-mediated sequencing) to sensitively track chromosomal structural abnormalities and the fate of viral DNA insertions in CRISPR-Cas9 edited T cells after infusion into mice.
Among 16 mice infused with edited T-cells, two of them were found with significant expansion of T-cell monoclonals.

11/1
Substrate-driven assembly of a translocon for multipass membrane proteins (Nature 2022 Robert J. Keenan University of Chicago)
Mechanism of an intramembrane chaperone for multipass membrane proteins (Nature 2022 MRC Ramanujan S. Hegde)
Most membrane proteins are synthesized on the rough endoplasmic reticulum, ribosomes are docked on the translocon, and the nascent peptide chain in the scope of the heterogeneity factor complex
The endoplasmic reticulum multi-channel translocon is a dynamic assemblage, and its different subunit compositions can be adjusted with the co-translational process to suit the needs of different substrate biosynthesis.

11/1
Ancient homomorphy of molluscan sex chromosomes sustained by reversible sex-biased genes and sex determiner translocation (Nature Ecology & Evolution 2022 中国海洋大学)

Traditional evolution review believe that sex chromosomes originate from autosomes, and the emergence of sex-determining genes will cause recombination inhibition between sex chromosomes and gradually degenerate to form heteromorphic sex chromosomes
Heteromorphic sex chromosomes are considered to be the "final fate" of the sex chromosome evolutionary pathway. However, contrary to this prediction, more and more evidences show that there are species with homomorphic sex chromosomes (two sex chromosomes without obvious differentiation) in the animal kingdom. According to statistics, about 90% of shellfish, fish and 96 The sex chromosomes of % of reptiles are not differentiated.

This paper reveals that the maintenance of homomorphic sex chromosomes is the "regular" of sex chromosome evolution, and the differentiation of heteromorphic sex chromosomes requires additional evolutionary power, which is a branch of the entire evolutionary pathway rather than "final destiny".

Microtubule nucleation: beyond the template
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621832/

11/1
Importin α Partitioning to the Plasma Membrane Regulates Intracellular Scaling (Cell 2019 Rebecca Heald UCB)
importin α: a conserved surface area-to-volume sensor that scales intracellular structures to cell size / a highly conserved and abundant nuclear transport factor that binds nuclear localization sequence (NLS)-containing proteins
palmitoylation-dependent importin α membrane association regulates mitotic spindle and nuclear scaling during Xenopus embryogenesis by providing a measure of the cell surface area-to-volume ratio
One technique - PEGylated surfactant
adding 2 μL of the extract reaction mixture on ice to 50 μL of the appropriate surfactant/lipid mixture
Cithrol DPHS resuspended in squalene at 50 mg/mL served as the surfactant to form inert membrane droplets, while total bovine liver extracts (preparation detailed above) were used as the physiological membrane surfactant
The extract/surfactant mixture was then pipetted up and down with a 20 μL pipette tip set to maximum volume approximately 10-20 times, depending on the desired size range of droplets desired.
The emulsified mixture was then added to a custom-built chamber composed of vacuum grease (Dow Corning) on a coverslip

11/2
Phenotypic plasticity and genetic control in colorectal cancer evolution (Nature 2022 British Andrea Sottoriva & Trevor A. Graham)
The article found a common phenomenon in CRC tumors (colorectal cancer), that tumors can acquire phenotypic plasticity without genetic factors (epigenetic or genetic) changes.

11/2
The gut-to-brain axis for toxin-induced defensive responses (Cell 2022 北京生命科学研究所 曹鹏)
After food poisoning, the brain initiates a series of defense responses such as nausea and vomiting. Through vomiting, the human body excretes the ingested toxic food out of the digestive tract, preventing the pathogen from further invading the body.
Through the disgusting emotion of nausea, the brain can form a long-term memory of the characteristics of a poisonous food, so as to avoid eating the poisonous food again in the future.
Studying the "nausea-vomiting" response is difficult because rodents commonly used in the laboratory, such as mice and rats, do not exhibit vomiting behavior. Rodents are unable to spit food out of their stomachs, thought to be due to underdeveloped smooth muscles in the digestive tract
Past research has only been able to use animals that exhibit vomiting behavior, such as dogs and ferrets. They found that cutting the subphrenic vagus nerve can effectively block the vomiting response, indicating that vomiting depends on the "gut-to-brain" axis between the gastrointestinal tract and the brain.
Brain regions involved in the vomiting response identified by means of damage and electrical stimulation
Through pharmacological methods, it was found that antagonists of 5-HT3R and NK1R can effectively inhibit the emesis response
To elucidate the mechanism by which the brain initiates the "nausea-vomiting" response, in addition to appropriate animal models and research paradigms, three long-standing mysteries need to be solved.
First, after the gastrointestinal tract was invaded by pathogens, which type of intestinal cells gave this important information to the vagus nerve?
Second, what is the identity and characteristics of the sensory neurons in the vagus nerve responsible for interfacing with the gut "intelligence"?
Third, when the brain receives the information of pathogen invasion from the vagus nerve, how does it quickly and synchronously initiate a series of defense responses such as nausea and vomiting?
This study established a new paradigm for studying the "nausea-vomiting" response using mice as an animal model, and initially revealed the molecular, cellular and neural circuit mechanisms that trigger the "nausea-vomiting" response by the brain's perception of pathogen invasion.

chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.pnas.org/doi/pdf/10.1073/pnas.2121147119

11/4
Emergent properties of mitotic chromosomes (Current Opinion in Cell Biology 2020 Rebecca Heald UCB)
How to connect the molecular-level activities to large-scale changes in whole-chromosome architecture that determine mitotic chromosome size, shape, and function.
In conclusion, multiple biochemical activities at the molecular level come together to mediate the large-scale chromosome organization and dynamics observed during mitosis.
Two major challenges:
integrating the many sources of structural information (imaging, sequencing, biochemistry) into a comprehensive, multiscale model for mitotic chromosome architecture
relating the structure and mechanics of mitotic chromosomes to their functions in cell division and epigenetic inheritance.

11/4
The power of amphibians to elucidate mechanisms of size control and scaling (Experimental Cell Research 2020 Rebecca Heald UCB)
Study scaling
study molecular links between genome, cell, and organism size and physiology

11/4
Rapid image deconvolution and multiview fusion for optical microscopy (Nature Biotechnology 2020)
Incorporating the image formation process into deep learning improves network performance (Nature Methods 2022)
Two optimization methods are proposed to improve the image resolution. One is to optimize the backprojection operator in the Richardson-Lucy deconvolution algorithm, which can improve the efficiency of deconvolution. The other is to use a deep learning network to learn the deconvolution mapping relationship.
In recent years, deep learning networks have performed well in various research fields, but its inexplicable "black box" characteristics and its high dependence on the quality of training data have led to the use of a content-based data training method. Models are difficult to apply directly to other types of data.
In this study, the Richardson-Lucy deconvolution model commonly used in post-processing of fluorescence microscopy images was explicitly introduced into the fully convolutional deep learning framework, and a Richardson-Lucy Network (RLN) was proposed to establish an iterative optimization method and a deep learning method. It can better realize the optimization of fluorescence microscopy image resolution, improve network interpretability and generalization ability, and build new intelligent modalities.

11/7
Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotype (Nature 2022 Makoto Nakanishi university of tokyo)
The researchers found that senescent cells heterogenously express the immune checkpoint PD-L1 (Programmed death-ligand 1), and PD-L1+ senescent cells accumulate in vivo with age.
This study demonstrates that eliminating PD-L1+ senescent cells by blocking PD-L1-PD-1 is a promising anti-aging therapeutic strategy.
Senescent hepatocytes induced by oncogenes and senescent stellate cells induced by injury could be eliminated by activated T cells and natural killer cells, respectively, suggesting a potential role of the immune system in the accumulation of senescent cells.

11/7
Histone H2B.8 compacts flowering plant sperm via chromatin phase separation (Nature 2022)
In eukaryotic cells, transposon-enriched heterochromatin is usually highly condensed, forming nuclear speckles and distributed at the edge of the nucleus, while gene-enriched euchromatin is loosely distributed in the nucleus and occupies nuclear space. This loosely distributed structure facilitates the binding of transcriptional complexes and promotes gene expression.
Condensed chromatin usually involves the repression of transcription, such as the condensed heterochromatin, which inhibits the activity of transposons and ensures the stability of the genome.
This paper discovers a novel mechanism for chromatin condensation that does not affect transcription. The authors discovered a histone H2B variant, H2B.8, expressed specifically in flowering plant sperm cells, which specifically binds to euchromatic transposons and intergenic regions. It condenses sperm cells by phase separation non-transcribed regions in the gene, thereby condensing sperm cell chromatin without affecting gene expression
This novel enrichment acts only on non-expressed euchromatin, thereby delicately reducing the size of the nucleus without affecting transcription.

11/9
Disassembly of Actin and Keratin Networks by Aurora B Kinase at the Midplane of Cleaving Xenopus laevis Eggs (Current Biology 2019 Tim Mitchison)

Aurora B kinase activity between asters disassembles actin and keratin networks
Cytoskeleton disassembly results in reduced cytoplasmic stiffness between asters
Aurora B kinase bound to beads causes local disassembly of cytoskeleton networks
Microtubule binding locally amplifies Aurora B kinase activity
CPC - mitotic kinase Aurora B / three additional subunits (INCENP, Survivin, and Borealin) that localize and activate the kinase
Centralspindlin - kinesin-6, MKLP1, and two molecules of MgcRacGAP, which contains a GTPase-activating protein (GAP) domain for Rho family GTPases.
CPC - the boundary between asters.
Aurora B kinase (AURKB) (subunit of the CPC) - caused disassembly of F-actin and keratin between asters
cytokinesis signaling protein complexes: chromosomal passenger complex (CPC) and Centralspindlin
A requirement for CPC activity for cytokinesis was shown in several large cell types, including zebrafish [4], sea urchin [5], and Xenopus [6].
CPC is activated by auto-phosphorylation, which is enhanced by binding to microtubules [7]
a CPC-positive state from anaphase chromatin to the egg cortex is spread via microtubule bundles between asters [1][2]
F-actin and keratin networks - impede centrosome movement and furrow ingression
A plausible model is that CDK1 promotes global network disassembly at mitotic entry, whereas AURKB adds a focused disassembly activity that prevents re-formation at the midplane, which might impede furrow ingression.
CDK1
Actin-intact interphase egg extract containing fluorescent probes was spread between passivated coverslips and imaged.
AURKB and Prc1/Kif4A activities together block plus-end growth and generate sharp boundaries between asters, as previously reported [6, 19]
an AURKB kinase inhibitor - inhibit actin’s disassembly
Keratin networks were also disrupted at aster boundaries when CPC was recruited (slower than f-actin)
To examine these phenomena in vivo, we analyzed intact zygotes using fixation, clearing, and laser-scanning confocal imaging
The mechanism of local disassembly of F-actin by AURKB is not known.
How AURKB destabilizes keratin filaments is also unknown