Genes to Cells Cover Gallery

Ebisu (the god of fortune) is delighted to have obtained a mouse with a panda pattern through crossbreeding. In Japan, selective breeding of plants and animals became popular during the Edo period, and the method for producing mice with various patterns, including panda patterns, was described in Chin-Gan-Sodate-Gusa (1787). These fancy mice were likely exported to Europe and crossbred, and about 7% of the genome of the C57BL/6J strain is derived from the Japanese mouse subspecies Mus musculus molossinus. This cover illustration was created in reference to the meeting report published in the July 2024 issue of this journal (Abe et al. (2024) Genes Cells 29(7): 525-531, DOI: 10.1111/gtc.13131).

Kintsugi is a traditional Japanese technique for repairing broken ceramics using urushi lacquer and gold powder. What makes kintsugi unique from other restoration methods is the philosophy that the repair adds new value to the ceramics. This concept is very similar to modern genome editing (particularly knock-in techniques). We, too, have attempted a knock-in on a broken tea bowl using kintsugi.

Female mosquitoes suck blood to mature their eggs. It has been reported that fibrinopeptide A (FPA), which is cleaved from fibrinogen α chain during blood coagulation, makes mosquitoes feel 'full' and stop sucking blood (Sakuma et al. (2024) Cell Reports 43: 114354, DOI: 10.1016/j.celrep.2024.114354). The mother in this painting is trying to use a mosquito net imbued with the ability of FPA to override the child's nightmare of a blood-sucking mosquito with the image of a satiated mosquito. In addition to fibrinogen and FPA, the mother's kimono shows schematic images of fibrin that has just begun to coagulate.

In establishing the left-right axis of the body in Drosophila, a torsion-like deformation of the cell occurs (cell chirality). Two myosin Is, Myo1D and Myo1C, are thought to be involved in this process, producing right-handed and left-handed cell chirality, respectively. A paper published in the May issue of this journal (Utsunomiya et al. (2024) Genes Cells 29: 380-396, DOI: 10.1111/gtc.13110) reported that when these myosin Is were expressed in macrophages to observe their interactions with the membrane at the single-molecule level, Myo1D exhibited mobility consistent with free diffusion, whereas Myo1C showed notably lower mobility. This picture, depicting two vortices in a strait, aptly illustrates their differences. Compared to the fast currents that produce the right-handed vortex in the back, the currents of the left-handed vortex in the foreground are docile.

A puffed-up fugu is wrestling with a toad. The body of the fugu has numerous spots that look like insulin secretory granules and a nucleus-like pattern, just like the pancreatic β-cells. Perhaps triggered by the wrestling, the fugu's body releases insulin. Inspired by a review article in this journal (Izumi (2023). Multiple pathways and independent functional pools in insulin granule exocytosis. Genes Cells 28: 471-481, DOI: 10.1111/gtc.13029).

It has been demonstrated that in Arabidopsis thaliana, the accumulation of the plant hormone jasmonic acid at the base of flowering petals turns on a gene expression cascade there, resulting in the activation of autophagy and vacuolar development, which in turn causes petal shedding (Furuta et al. (2024) Nat. Commun. 15: 1098, DOI: 10.1038/s41467-024-45371-3). Perhaps in the future, we will be able to control the timing of the fall of the petals in other flowering plants, such as cherry blossoms, as we wish.

Son Goku (Sun Wukong), a god in monkey form, was brandishing a Nyoi-bo representing the TBXT gene. However, an AluY-marked dagger hit the Nyoi-bo and broke it off. Xia et al. showed that the loss of tails in hominoids, including humans and apes, was due in part to changes in splicing patterns caused by the insertion of an AluY element into the ancestral TBXT gene (Xia et al. (2024) Nature 626:1042-1048, DOI: 10.1038/s41586-024-07095-8). Son Goku cannot hide the look of impatience on his face as his tail begins to disappear, having impaired the function of the Nyoi-bo, which is necessary to maintain his tail, the source of Son Goku's magical power.

This is an ornamental tool called an 'inro' used to carry medicines in the Edo period. On the surface of this inro, the structure of N1-methyl-pseudouridine (N1mΨ), the key to the development of the mRNA vaccine against COVID-19, is schematically depicted with plum buds (oxygen atoms) and branches, using the maki-e lacquer decoration technique. Coronavirus particles are depicted on the toggle ('netsuke') used to secure the inro to the obi of the kimono. Perhaps one day, wherever we travel, we will enjoy our journey without fear of unknown viruses by swallowing a pill taken from our portable pill case like this inro.

A fishmonger skillfully cutting a planarian with a high regenerative capacity creates various forms of planarians, including two-headed and four-headed (the planarians are depicted enlarged).

The year 2024, the Year of the Dragon, was opened. Mt. Fuji was quickly enveloped by colorful clustered single-cell RNA-seq data-like clouds that rose from the dragon targeting the mountain.

A woman observes Danionella in a fishbowl (the fish depicted magnified). Danionella has the advantage of having all its organs transparent throughout its life, making it a promising new model organism for imaging and optogenetics.

Mouse sperm are immature immediately after production in the testis. Lumicrine factors (NELL2 and NICOL) secreted by the testis stimulate the differentiation of epididymal initial segment epithelial cells, and these epithelial cells are responsible for processing the ADAM3 protein on the sperm surface, resulting in sperm maturation. For details, see the review article in this issue (Kiyozumi (2023) Genes Cells 28: 757-763, DOI: 10.1111/gtc.13066). The boys with long hair in this drawing also have their hair cut at the barbershops at the approach to a bridge and go out into the world, crossing the bridge as mature men.

An awake mouse is pulling to move a soundly sleeping mouse by the tail. The tail of the awake mouse is coiled just like the 3D structure of orexin-A, a hormone that regulates arousal.

A full moon rises over the torii gate of Itsukushima Shrine in Miyajima (Hiroshima Prefecture), with countless reflections on the waves. Upon closer inspection, the numerous moon figures seen on the waves are actually cells of the fission yeast Schizosaccharomyces pombe. In addition to cells undergoing vegetative growth, cells in the process of sexual reproduction (conjugation, first and second meiosis) and asci containing spores are visible in the foreground. The Meeting Report of the 11th International Fission Yeast Meeting in Hiroshima (POMBE2023 Hiroshima) appears in this month's issue of this journal (Toda et al., Genes Cells 28: 642-645, DOI: 10.1111/gtc.13055).

Morning glories bloom on an August morning. The pattern of the flowers is reminiscent of paraspeckles, which are nonmembranous organelles formed by lncRNA Neat1. Also, the tendril extending right-upwards looks like Hero proteins, which are intrinsically disordered. A review article on nondomain biopolymers, including Neat1 and Hero proteins, appears in this issue of this journal (Arakawa et al. (2023) Genes Cells 28: 539-552, DOI: 10.1111/gtc.13050).

Finally, today is the deadline for abstract submission for the annual meeting of the Molecular Biology Society of Japan. As the deadline is approaching, the front of the building, where the registration desk is situated, is getting crowded with people having their abstracts to submit. In the next building, a few people are in a hurry as they have not yet completed their abstracts, and the woman at the far end of the cover illustration of the June issue is there too. The abstract submission deadline for this year's annual meeting (MBSJ2023) is July 31, 17:00 (JST). Your early submission is highly appreciated.

The abstract registration deadline for the annual meeting of the Molecular Biology Society of Japan on July 31 is 40 days ahead. Here is a scene in a laboratory. As is usual, the preparation of abstracts has begun. The degree of progress varies from person to person; some have already received corrections from the faculty members, while others, like the person at the far end of the room, are taking a slower pace. What will the deadline they will face be like!? (To be continued in the next issue; for a hint, see the meeting report on MBSJ2022 in this issue (Fukagawa (2023) Genes Cells 28: 403-410, DOI: 10.1111/gtc.13023).)

Stimulated to the leaves, the sensitive plant (Mimosa pudica) folds its leaves one after another. To elucidate the mechanism, a transgenic M. pudica was produced so that the cytosolic Ca²⁺ concentration can be observed as fluorescence by GCaMP6f (Hagihara et al. (2022) Nat. Commun. 13: 6412, DOI: 10.1038/s41467-022-34106-x). When a leaflet was wounded, the fluorescent signal caused by Ca²⁺ propagated through the veins to the tertiary pulvinus at the base of the leaflet, immediately followed by a movement of the pair of leaflets to fold inwards. And, Ca²⁺ signals were propagated to the adjacent tertiary pulvini sequentially, and the leaflets were also folded successively. At this time, electrical signals were transmitted simultaneously with the fluorescent signals. The authors also observed that the immotile M. pudica was more susceptible to feeding damage by insects, suggesting that the movement above protects the plant from feeding damage.

Wnt2022, an international conference on Wnt research, was held on November 15 to 19, 2022, in Awaji Island (Hyogo Prefecture). This memorable gathering was the first Wnt meeting in Japan and Asia, finally held in person after being postponed for two years due to COVID-19. The cover of this issue features Himeji Castle (Himeji, Hyogo Prefecture) (*CG fiction) with an exceptional decoration showing the name of the meeting and the names of important components of Wnt signaling, to commemorate this occasion. The Meeting Report in this issue detailed the discussion at the conference and its connection to Himeji Castle (Kikuchi et al. (2023) Genes Cells, 28: 249-257, DOI: 10.1111/gtc.13014).

The node forming transiently in mammalian embryos plays a key role in left-right axis determination. The node is a cavity, in which crown cells with immotile cilia surround pit cells that rotate their motile cilia to generate a leftward fluid flow (nodal flow). Experiments using GCaMP6, which emits green fluorescence in response to Ca²⁺, and optical tweezers revealed that immotile cilia sense mechanical force generated by nodal flow (Katoh et al. (2023) Science 379: 66-71, DOI: 10.1126/science.abq8148). A similar mechanism was shown to exist in zebrafish (Djenoune et al. (2023) Science 379: 71-78, DOI: 10.1126/science.abq7317). This picture shows the application of this mechanism to 'hiburi-ryo' (fishing by using flames to drive fish). The fishermen in the pond are creating a leftward current to be sensed by the men on the left bank, who are activated, and their torch flames intensify.

Urashima Taro, the protagonist of a Japanese fairy tale, returned from his undersea utopia with his youth intact after hundreds of years, but as soon as he was exposed to the smoke from the souvenir Tamatebako (jeweled box), he turned into an old man. This painting depicts how the smoke causes Urashima Taro to lose not only his youth but also the Y chromosome in a part of his cells. Mosaic loss of chromosome Y (mLOY) is commonly observed in older men and has been linked to ageing and cancer, and has also been found to increase the risk of heart disease (Sano et al. (2022) Science 377: 292-297, DOI: 10.1126/science.abn3100). We referred to Fukami & Miyado (2022) Reprod. Med. Biol. 21: e12445, DOI: 10.1002/rmb2.12445 for the depiction of chromosomes.

Fukuwarai is a traditional Japanese New Year's game in which blindfolded players compete on how well or strangely they can create faces by placing cut-out facial parts (eyes, nose, etc.) on paper with an outline of a face. What these women are enjoying is a fukuwarai with cell organelles likened to facial parts. Now, what kind of cells will they make?

Two pairs of “look-alikes” that match SNPs. Comparisons of multi-omics and lifestyle were made between look-alikes who were not genetically related but had similar faces (Joshi et al. (2022) Cell Reports 40: 111257, DOI: 10.1016/j.celrep.2022.111257). The results showed that among pairs of “look-alike,” the rate of matching SNPs related to facial features was high. In addition, height, weight, smoking habits, and education also had correlations. On the other hand, DNA methylome and microbiome were not similar. This study may provide clues as to how much the extent to which the genome sequence and environmental factors contribute to physical and behavioral traits.

People are fleeing from a tornado that has suddenly appeared. The tornado swallows a bundle of rope with shide (paper ornaments attached to ropes at Japanese shrines) as it unravels and tears the rope into small pieces to spit them out, just like the 26S proteasome that recognizes and degrades ubiquitinated target proteins. Inspired by https://www.janlabmgh.org/.

A frog and a lizard rush ahead in the race to live out their lifespan, while a turtle walks slowly at its own pace. Based on a large amount of data from long-term observations of the aging and longevity of various tetrapod ectotherms in the wild, Reinke et al. attributed the longevity of turtles to the physical protection of their bony shells and their relatively slow pace of life (Reinke et al. (2022) Science, 376: 1459-1466, DOI: 10.1126/science.abm0151). The evolutionary process of turtles never ceases to fascinate us. For drawing the phylogenetic tree, we referred to the genome decoding (https://www.riken.jp/en/news_pubs/research_news/pr/2013/20130429_1/index.html) by Dr. Shigeru Kuratani (RIKEN) et al.

A general-purpose humanoid karakuri ningyo (puppet) robot that accurately dispenses reagents. Saving labor is not the only thing such general-purpose robots for laboratories can do. The reproducibility of research could be dramatically improved by quantifying human skills and experience and setting them to robots. It will also facilitate scaling up of research. Sharing of programs (protocols) could make it easier for everyone to try highly challenging experiments.

Sugashima Island in Toba City, Mie Prefecture, was depicted in Hiroshige Utagawa's ukiyoe (below 'Cells' in this painting). A report on yeasts and filamentous fungi collected around the Sugashima Marine Laboratory, Graduate School of Science, Nagoya University (NU-MBL) on this island has been published in the February 2022 issue of this journal (Goshima (2022) Genes to Cells 27: 124-137, DOI: 10.1111/gtc.12916). It was the first article in this journal to explore new marine microorganism species. In this article, the author also observed that three species of marine black yeasts changed their mode of growth and division in response to cell density. We are reminded once again that the seas are a treasure trove of biodiversity. We thank Prof. Gohta Goshima (Director, NU-MBL) for providing the data.

Dyed cloths are hung out to dry and flutter coolly. Those cloths represent human 22 autosomes and X chromosome. Although it has been a long time since most of the human genome was sequenced, there were still many unresolved parts (the colored parts of the cloths in this drawing), such as telomere, centromere, ribosomal DNA, and segmental duplications. Thanks to the efforts of researchers and advances in technology, the sequencing of all bases except the Y chromosome has been finally achieved (Nurk et al. (2022) Science 376: 44-53, DOI: 10.1126/science.abj6987).

Barbour et al. created an experimental food web, as depicted in this drawing, consisting of four species, Arabidopsis thaliana, two species of aphids, and a parasitoid wasp parasitizing the aphids, and examined the effects of alleles of three genes in the aliphatic glucosinolate biosynthesis pathway in A. thaliana on the survival of the four species (Barbour et al. (2022) Science 376: 70-73, DOI: 10.1126/science.abf2232). Their finding was that the null allele of one gene (AOP2) significantly reduced the extinction rate of the four. They call AOP2 a 'keystone gene,' in analogy to a keystone species. We would like to thank Dr. Toshiyuki Harumoto (Hakubi Center for Advanced Research, Kyoto University) for his advice on the drawing.

Numerous rafts and small boats float in the river, which flows in the shape of a cup, surrounding a pond with an islet. They look as if they are part of the cells of the green alga Chlamydomonas. In the chloroplasts surrounding the nucleus, thylakoids overlap each other to form the grana. The long rafts in particular look like lamellae interconnecting the grana. The central sandbar with the rafts moored to it resemble a pyrenoid (a structure found in the chloroplasts of algae) with thylakoid membranes penetrating the pyrenoid itself. We referred to Figure 1(A) of Engel et al. (2015) eLife 4:e04889, DOI: 10.7554/eLife.04889.001. We would like to thank Dr. Takashi Yamano (Graduate School of Biostudies, Kyoto University) for his advice.

One Japanese bullfinch (Pyrrhula pyrrhula griseiventris), which likes to eat cherry blossoms, perches on a drooping cherry branch. This cherry tree has particularly well-shaped branches, and if we compare its flowers to five- or six-membered rings and the buds to sulfur atoms, the form of the flowers, buds and branches around the bird resemble the structure of methionine (left) and its metabolites, S-adenosylmethionine (SAM; top) and S-adenosylhomocysteine (SAH; right). It has been reported that restricting methionine intake extends lifespan in a variety of species. Hopefully this bullfinch doesn't eat too many flowers.

The Hi-C method (a method to examine genomic regions that are close to each other in the nucleus by fragmenting and ligating cross-linked nuclear chromatin and then reading the paired-end sequences by NGS) has revealed the existence of structural units called topologically associating domains (TADs) that are separated by insulators in the genome. When the results of the Hi-C method are drawn as a heatmap, TADs appear as characteristic diamond-shaped signals, with deeper colors indicating the higher probability that regions of the genome are closer to each other. We drew them on Hishimochi rice cakes (diamond-shaped rice cakes), an essential decoration for the Japanese Doll's Festival on March 3. We thank Drs. Ichiro Hiratani and Hisashi Miura (RIKEN BDR) for providing the data.

When translation by the ribosome is stalled, the subsequent ribosome collides with the stalled ribosome, resulting in the accumulation of abnormal proteins. To prevent this occurring, the cell recognizes the specific structures caused by the ribosome collisions, and marks the stalled ribosome for removal. In budding yeast, collisions are detected by the E3 ubiquitin ligase Hel2, and the uS10 of the 40S subunit of the stalled ribosome is marked with a K63-branched ubiquitin chain. The two ribosome-like Yukidarumas (snowmen) in this picture also collide, and the male watcher is marking the one to be removed with tags that mimic a ubiquitin chain. For drawing this image, we referred to a website http://www.inada-lab.ims.u-tokyo.ac.jp/research/.

At a New Year’s banquet, an entertainer is performing a juggling trick in which a DNA-like string is temporarily cleaved and another string passes through it using a eukaryotic topoisomerase II-mimicking ‘top.’ This trick requires ATP. In humans, topoisomerase IIα is highly expressed in proliferating cells and is essential for DNA replication, transcription, and structural maintenance and proper segregation of mitotic chromosomes, resulting in an important target for anticancer drugs.

This year's Annual Meeting of the Molecular Biology Society of Japan (MBSJ2021) is going to be held in Yokohama from December 1 to 3. This is the tenth Annual Meeting in Yokohama, but this will be the last. Online participation is also possible if preferred. We would like to express our sincere respect to all the people involved in the preparation of the event despite the difficulties in the COVID-19 pandemic. The participants are arriving at the train station one after another. Let's meet in Yokohama (or online)!

A woman enduring the heat of moxibustion, using a box with chili peppers on top as a pillow. The nonselective cation channel TRPV1 (schematically depicted on her kimono and the side of the box below her) is a receptor that responds to capsaicin, the pungent component of chili pepper, and heat above 43°C, making us feel heat and pain. Prof. David Julius, who discovered TRPV1, will be awarded the Nobel Prize in Physiology or Medicine in 2021 (jointly with Prof. Ardem Patapoutian for the discovery of receptors for mechanical stimuli).

A competition of protein 3D structure prediction. It is about how similar the predictions are to the correct answer (the actual experimental result), which is slightly to the right of the center. The prediction placed on the left of the correct answer was done by an AI, and won the first prize. AI has made remarkable progress in recent years, and in a contest held in 2020 (CASP14), the predictions made by AlphaFold 2, an AI developed by DeepMind, finally reached a level comparable to actual experimental results. The 3D structures shown here were drawn with PyMOL based on the PDB files of target ID T1053 and its prediction models downloaded from CASP14 website (https://www.predictioncenter.org/casp14/index.cgi).

Advances in optogenetic techniques, in which light-activated proteins that respond to specific wavelengths are expressed in specific cells, have made it possible to manipulate the activity of specific nerves in many animal species including mammals with high temporal and spatial precision. The method of using optical fiber for light irradiation (right) is highly invasive and restricts behavior of animal. However, new methods to overcome this problem have emerged. Some examples are a method of using implantable wireless light-emitting devices (top left), and a method of injecting upconversion nanoparticles that emit visible light in response to near-infrared (NIR) lights that reach deep into the body (center; the light emitted from Uchide-no-kozuchi (magic mallet) of Daikokuten is NIR).

Kikkoden is an event that used to be held on July 7th of the old lunisolar calendar, and is the prototype of Tanabata (Star Festival). On that day, people offered fruits and threads in hopes of improving their handicraft skills. We will follow the same practice and offer serial and coronal sections of the brain and watermelon rinds sliced in the hope of improving our skill of making paraffin-embedded serial sections with a microtome. In drawing the serial and coronal sections of the brain, we referred to G. Paxinos and C. Watson (1998) The Rat Brain in Stereotaxic Coordinates, 4th ed., Academic Press.

The night of Tanabata (Star Festival) on July 7th. A heat map of metabolic reactions in each tissue of C. elegans, derived from single-cell transcriptome analysis, illuminates the surface of the sea. And the metabolic networks of each tissue drawn based on the heat map decorate the night sky like constellations floating in the Milky Way. For drawing this image, we referred to Yilmaz et al. (2020) Mol. Syst. Biol. 16:e9649, DOI: 10.15252/msb.20209649.
The heat map: Adapted from Figure 3(C) of © Yilmaz et al. (2020) Mol. Syst. Biol. 16:e9649, DOI: 10.15252/msb.20209649. Licensed under CC BY 4.0.

Even in the same mammal, the time it takes for development is very different between humans and mice. The period of the segmentation clock in humans is about 5 hours, whereas that in mice is about 2 hours. The key regulator of the segmentation clock is the transcription factor HES7, whose expression level periodically increases or decreases by self-repression. Experiments in which human and mouse HES7 loci were swapped showed that differences in the speeds of intracellular biochemical reactions, such as gene expression and protein degradation, between species, rather than the sequences of HES7 loci themselves, produce the period difference. This finding suggests that the period difference of the segmentation clock may also be related to the difference in time scales in development between elephants and mice. We thank Dr. Miki Ebisuya (EMBL Barcelona) for her advice.

This “Daruma Otoshi” game imitates the VDJ recombination of the T cell receptor β (TCRβ) locus. In the first step, the DNA sequence between one D and one J is removed, and in the second step, the DNA sequence between one V and the said D is removed. The series of reactions is catalyzed by RAG1/RAG2. The current situation is that the first stage has been successfully completed and we are in the middle of the second step, that is, the DNA sequence between V_β3-1 and D_β1 is being knocked out with a hammer marked with RAG1 and RAG2. Since there are two alleles, there are two chances, but if both fail, the cell will undergo apoptosis.

Several laser beams shot from heaven onto the mountain, and a part of the mountain body was scattered. It is just like a laser ionization of a mixture of matrix and sample in a mass spectrometer using the MALDI (Matrix Assisted Laser Desorption/Ionization).

A woman washing two woven cloths in the river. The cloths are intertwined with each other like a double helix of DNA. What she is using to unwind them is a ring-shaped tool that imitates the hexamer of MCM (minichromosome maintenance) 2-7, a DNA helicase.

As with brown adipocytes, beige adipocytes are rich in mitochondria expressing Uncoupling Protein 1 (UCP1) and produce heat. However, their origin is white adipocytes, and their differentiation is induced by exposure to cold environments or stimulation with certain antidiabetic drugs. Now, in the cold snow scene where the induction of beige adipocytes is likely to progress, the snowball made by the children seems to have been changing into a beige adipocyte-like ball perhaps due to some stimulus.

The first sun of the year is rising above the ocean. Several lines of shadows that are emerging between the waves look like a ladder of a multicolored molecular weight marker for SDS-PAGE. It is very auspicious that they appear to be running horizontally and straight without smiling. We hope that this year will be a happy one for you all.

Many academic societies, including MBSJ, hold their annual meetings online this year. This woman is one of the participants, taking part in an online session via a tablet device behind the bamboo blinds. Guessing from her headset with microphone, she might be one of the presenters.

The involvement of liquid droplets formed by liquid-liquid phase separation (LLPS) in various life phenomena has attracted attention. What is depicted in this picture is the Naruto Strait between Shikoku and Awaji Island. In this strait, extremely strong tidal currents occur several times a day, forming huge whirlpools. Now, triggered by the change in the "phase" of the ocean current, enormous liquid droplets formed by LLPS have appeared in the strait along with the whirlpools.

Two drawings in which Hotei dolls with sumo umpire's fans (gunbai) are lined up. The dolls, the gunbais, and the difference of colors of the dolls' clothes represent cells, cadherins, and the difference of subtypes of cadherins, respectively. The drawing on the left depicts the state in which cadherin haven't been concentrated anywhere on the cell membrane yet, and it is reflected in the random arrangement of the dolls. On the other hand, in the drawing on the right, cadherins are concentrated at intercellular junctions, those of the same subtype are bound to each other, and as a result, dolls expressing the same subtype of cadherin are next to each other.

Goldfish (Carassius auratus) with the telescope-eye, dorsal-fin-loss or long-tail phenotype are swimming calmly in a large fishbowl followed by chromosomes. Goldfish experienced a whole-genome duplication 8-14 million years ago, making it difficult to analyze its genome, but finally the genome sequences of various varieties were sequenced and the causative genes (candidates) of these traits were also found. Among these, the causative gene (candidate) for long-tail, kcnk5bS, encodes a K⁺ channel as depicted on the side of the bowl. This research is expected to be applicable to the study of vertebrate morphogenesis and human disorders. See Chen et al. (2019) Science Advances 5: eaav0547 and Kon et al. (2020) Current Biology 30: 2260-2274 for further detail. We thank Prof. Yoshihiro Omori (Nagahama Institute of Bio-science and Technology) for his advice on drawing.

A scene of Yoiyama (the eve of 'Yamahoko Junko' (decorated floats' parade)) of Gion Matsuri in Kyoto. The float in front of us imitates the structure of the compound eye of Drosophila. Each paper lantern resembles an ommatidium, and thorn-shaped ornaments looking like sensory hair are projected from between them. Also, the decoration on the roof of the float also imitates the giant fiber neurons. It was a pity that many summer festivals, including Gion Matsuri, have been canceled or drastically reduced this year, but we hope that they will be splendidly held next year.

Organoids are miniaturized organs cultured in vitro. There are great expectations for its potential, including understanding of the mechanism of organ development, construction of disease models, search for new drugs, and application to regenerative medicine. Now, balloons imitating organoids are flying over the city one after another to announce the advent of a new era. The row of the buildings on the lower right looks like intestinal absorptive cells and Paneth cells lined up. For drawing the balloons, we referred to the following papers: From left, cerebral neocortex (Seto and Eiraku (2019) Neurosci. Res. 138, 33-42), intestine (Lancaster and Knoblich (2014) Science 345, 1247125), and optic cup (Sasai et al. (2012) Development 139, 4111-4121).

A kingfisher holding an aluminum ion flies toward hydrangea (Hydrangea macrophylla). Hydrangea flowers have a wide variety of colors, but the pigment is the same, delphinidin 3-glucoside, in both red and blue flowers. One of the keys that makes flowers blue is aluminum ions, and it is believed that the formation of a complex between delphinidin 3-glucoside, aluminum ion and copigment (e.g. 5-O-caffeoylquinic acid) results in blue flowers (Ito et al., (2018) Molecules 23, 1424). Three aluminum transporters have been identified in hydrangea so far, one of which was reported in Genes to Cells (Negishi et al., (2013) Genes to Cells 18, 341-352).

Each picture in the pattern on this woman's kimono is a cryo-electron microscopy image of E. coli chaperonin GroEL trapped in a thin film of amorphous ice. The method for reconstructing a three-dimensional structure as depicted in this fan from the average of a large number of such images of particles in various orientations (single-particle analysis) continues to improve. We referred a paper by Xu et al. (2016) PLOS ONE, 11(12): e0167765, DOI: 10.1371/journal.pone.0167765 in drawing the patterns on kimono.

The cherry blossom season has come. The latest product of this potted plants selling man is a potted cherry tree in full bloom of unusual design. The pots and trees seem to mimic magnetic beads and antibodies, respectively. They look just like immunoprecipitated cherry blossoms.

In Japan, there is a custom of displaying Hina Dolls on stair-shaped stages at the Doll's Festival on March 3. This year, our dolls are a bit unusual, with the three court lady dolls imitating a trimeric G protein. The current arrangement shows the situation where the α subunit has taken GTP form and has been dissociated from the βγ complex by receiving a signal from the upstream seven, not five, court musician dolls (seven-pass transmembrane receptor).

Attention has been focused on a phenomenon in which the properties of cells are changed by receiving extracellular vesicles containing miRNA and so on. Now, clouds like extracellular vesicles containing miRNA are released from the body of the dragon and flow towards Mt. Fuji. The dragon aims to change the nature of Mt. Fuji. How will Mt. Fuji change by receiving extracellular vesicles?

A demon is cornered by a mouse, the Chinese zodiac symbol of this year, on a neuron-like pole. Serotonin is one of the neurotransmitters that are known to regulate aggressive behavior in animals. According to the classical hypothesis, decreased serotonin levels are associated with increased aggression. However, it is not so simple because there have been opposite reports of increased aggression despite of increased serotonin levels. Further research into the mechanism is underway, and new discoveries are being made.

At a poster session. A crowd is gathering around one presenter who is playing a movie on a tablet. Everybody stares at the movie. I wonder what he is showing. Something hard to resist. If only the tablet were facing this way.

Several types of super-resolution fluorescence microscopies have been invented and begun to spread. One of them is the stimulated emission depletion (STED) microscopy, and its principle is illustrated in this drawing. In the traditional fluorescence microscopy, it is difficult to observe in sub-diffraction limit resolution, since there is a limit to reducing the spot size of excitation beam due to the diffraction limit. On the other hand, a STED microscope can narrow the excited area enough by overlapping the excitation beam and doughnut-shape STED beam. In this drawing, the woman's two umbrellas emit the excitation beam (cyan) and STED beam (orange) overlapping each other, and the fluorescence (green) is emitted from the area much narrower than the excitation beam spot.

Variously colored maple leaves decorate the autumn season in the mountains overlooking a village. Oh, no, wait a minute, actually they are neurons (red leaves) and astrocytes (yellow leaves) of the central nervous system. What look like branches seem to be blood vessels. In addition, oligodendrocytes and microglia can be seen.

A cluster of butterflies with eyespots on their wings fly away in the sky with concentric circles. Looking carefully, they consist of individuals with wild-type eyespots and mutants with different patterns than the wild-type. There are various theories about the mechanism of forming eyespots. One of them is that it involves the concentric diffusion of a morphogen from the center, but it has recently begun to be questioned. We thank Dr. Shigeyuki Koshikawa (Graduate School of Environmental Science, Hokkaido University) for providing us an idea of drawing and the current status of research in this field.

People have long loved ghost stories which send a chill down their spine in the hot summer season. What is illustrated here is the Chromatin Monster. As a result of tails of histones that form the neck being acetylated, the neck was extended, and it was expressed, scratch that, appeared from an old well while exhaling a spooky breath like mRNA from the mouth.

A method has been spreading for analyzing DNA fragments from organisms in the environment such as water or soil (environmental DNA or eDNA) to identify species being present there and to estimate their population. In this drawing, men are collecting the river water and amplifying certain DNA sequences using a handheld real-time PCR machine to estimate the population of a certain species of fish.

A woman wearing an ornamental hairpin, or kanzashi, likened to L-serine, is looking at the mirror. A D-serine kanzashi on her hair can be seen in the mirror. Since it has been revealed that at least some D-amino acids play physiological roles, focusing only on L-amino acids might be 'out of fashion.'

Many people come and go across a bridge in Kyoto. Two mountains, or actually histograms can be seen at the back. These graphs are the distribution of sleep amount for male (front, 'XY') and female (back, 'XX') flies of a large number of strains in a Drosophila mutant library, and the horizontal and vertical axes represent sleep amount and frequency (the number of strains), respectively. Since many strains showed longer sleep in male than in female in this experiment, a divergence can be observed between the peaks of the histograms. For drawing this image, we referred to Cirelli et al. (2005) Nature 434, 1087-1092.

The single-cell RNA-sequencing technology has a possibility of changing biological studies completely. This is a schematic image of the technology. As with petals of the cherry blossoms, for example, even a number of early embryonic cells indistinguishable from each other can be clustered and visualized based on gene expression data, just as the image is projected on the water surface, and then further analysis can be progressed. Data: Dr. Takefumi Kondo and Mr. Shunta Sakaguchi (Kyoto University).

This is the 'Spindle Checkpoint' placed at the important point 'Metaphase-Anaphase Transition' in the post town 'M Phase' on the 'Cell Cycle Highway.' The mitotic spindles and chromosomes carried by the travelers are carefully inspected, and the travelers must be arrested until all the chromosomes have been aligned at the equator and all the pairs of sister kinetochores have been properly attached to the microtubules from both poles of the spindle to achieve bi-orientation. Only those who safely pass the checkpoint can enter the 'anaphase' of their trips.

One winter day when the snow covered the trees and the ground, a woman is taking out racks, in which frozen samples are orderly stored, from a liquid nitrogen cryogenic storage vessel with a dipper. There might not have been any satisfactory safety gloves at that time. Patterns of snow crystals are printed on her kimono sash.

Kagami-mochi (mirror rice cake) is a representative of Japanese New Year decorations. It usually consists of a couple of stacked large round-shaped mochi that resemble ancient bronze mirrors with one daidai (Japanese bitter orange) on top. This year, however, our kagami-mochi is somewhat different from the usual; it is a so-called ribosome-like kagami-mochi. Two stacked mochi likened the ribosome's large and small subunits bind to a gohei (a folded ribbon of paper) that resembles an mRNA encoding (DAIDAI)_n amino acid sequence, and a chain of daidais extends upward from the mochi likened the large subunit. It looks like a polypeptide chain itself.

Mochi (rice cake) is indispensable to welcome the New Year in Japan. To use mochi for various purposes such as for food and for ornament, people firstly pound a large mochi and then divide it into small pieces according to the purposes. This process may be similar to that of producing various types of cells from fertilized eggs by asymmetric cell divisions. The woman in the front is dividing a large mochi asymmetrically such that beans that look like Sara (Smad anchor for receptor activation) endosomes and a crescent that looks like Numb (a cell fate-determining factor) are gathered only into the left half. The other woman on the back is preparing a decoration called mochi-bana (rice-cake flower). Note that she is trying to schematize a linage of stem cells and progeny. For drawing this image, we referred to Gonzalez (2015) Nature 528, 196-197, DOI: 10.1038/528196a.

When drawing a saturation binding curve of two proteins, there is a way of plotting the concentration of the free form of one of the pair on X axis, and the ratio of the other that is forming complex on Y axis. In this case, the slope of the curve is small if their affinity is low (i.e. large dissociation constant (K_d)); however, the slope is large if the affinity is high (i.e. small K_d). In this drawing, two flocks of wild geese are flying along two line-shaped clouds that are likened to saturation binding curves. The geese along the lower, gentle-slope cloud are flying apart as if their affinity is low. On the other hand, the ones flying along the steep-slope cloud in front of the moon are gathering together as if their affinity is high. For drawing this image, we referred to the research paper by Sadaie et al. (2014) Mol. Cell. Biol., 34:3272-3290, DOI: 10.1128/MCB.00087-14 that reports in vivo K_d values.

There is a pedestrian suspended bridge without side guards over a ravine surrounded by deer on the mountains and birds in the sky. The bridge bent by the weight of two persons, and its fork just look like the replication fork of DNA. The couple is walking across the bridge at the very point of the fork as if they were the replication machinery.

Katsushika Hokusai published not only ukiyo-e pictures, but also Hokusai Manga (Hokusai's Sketches) in which he presented how to draw assorted geometric patterns in addition to various examples of landscapes and figures of humans, animals, plants and so on. We drew Seigaiha (blue ocean wave) with auxiliary lines on the background of this drawing, and found it astonishingly close to the patterns of fish scales. Hokusai might have known it. For drawing this image, we referred to the research paper by Aman et al. (2018) eLife, 7:e37001, DOI: 10.7554/eLife.37001 that reported development of scales.

Fireworks likened to newly generated neurons have been launched from the brain. In recent years, it has been shown that neurons are continually generated in the brain of adult mammalians. At the very moment when these pyrotechnic 'stars' are engraved on your brain as an unforgettable memory of the summer, your new neurons should be working. We thank Dr. Itaru Imayoshi (Kyoto University) for providing the data.

A row of houses and a mountain can be seen behind rafts for cultivation of laver lined up in parallel. It just looks like a visualization of RNA-seq data mapped to a reference genome in order to see the depth of coverages (mountain) of reads (rafts) around a certain exon (row of houses) . We thank Dr. Fumiki Katsuoka (Tohoku Medical Megabank Organization, Tohoku University) for providing such a splendid idea for us.

At first glance, it might seem to be a Japanese rock garden (karesansui) with wavy lines in the sand (samon); however, it is actually an electron microscopic photograph of Drosophila midgut epithelium taken with the freeze-fracture method. The lines that look like samon are smooth septate junctions, which are a kind of occluding junction seen in invertebrates. We thank Prof. Mikio Furuse and Ms. Kyoko Furuse (National Institute for Physiological Sciences) for providing the data and sharing the idea of karesansui.

This is an acrobatic performance imitating immunoprecipitation using a phosphorylated protein-specific antibody. Two boys are acting two forms of a substrate protein. The boy on the left who wears red trousers, that represent the phosphorylation site of the substrate protein, is showing an opened fan and striking a pose that looks like the active form of the substrate protein. The other one who wears blue trousers is squatting on the ground to play the role of the dephosphorylated, inactive form of the substrate protein. The man who is suspended upside down in the midair is acting a phospho-specific antibody, and grasping the red trousers only, i.e. the site of phosphorylation.

A female weaver at the loom is dexterously managing a shuttle likened the condensin complex and a heddle with a weight likened to the cohesin complex as if they were parts of her own body to weave a metaphase chromosome-patterned fabric.

Researchers measured the concentration of various metabolites in plasma or red blood cells taken from volunteers, and found metabolites whose concentration was specifically higher or lower in elderly individuals. In this picture, two researchers are spreading these compound structure formulae beside them, and discussing correlations of concentration between two metabolites by plotting scatter charts using a lattice of a shoji door. A bamboo fence that is likened to a clustered heatmap of metabolites can be seen over there. For drawing this image, we referred to a research paper by Chaleckis et al. (2016) Proc. Natl Acad. Sci. USA, vol. 113, pp. 4252-4259. DOI: 10.1073/pnas.1603023113.

In Japan, people cerebrate Setsubun, the day before the lunar calendrical beginning of spring, around 3rd of February every year. People decorate sardine heads and holly leaves, put soy beans in a square wooden measuring box ('masu'), and scatter the beans to expel the bad spirits. Putting not only ordinary soybeans, but also other kinds of beans, we expressed a scene of the inside of a cell in the masu just like a bonsai. The real inside of the cells isn't sparse, but very much crowded, like this masu, with cellular organelles such as the nucleus, mitochondria, secretory vesicles and Golgi apparatus and cytoskeletons as well. For drawing this image, we referred to an essay by Shoichiro Tsukita https://www.brh.co.jp/seimeishi/journal/009/ss_4.html.

At Japanese shrines during New Year's holidays, you can find such dedicatory barrels of sake as in this picture. Looking closely at their labels, you will see the 3D structure, drawn on them, of green fluorescent protein ('緑乃光'), chaperonin ('寫丙論' and '界添'), proteasome ('蛋白ごろし'), aquaporin ('水之路') and sucrose porin ('満久淡泊'), all of which have barrel-like tertiary or quaternary structure.

A woman is dispensing reagents using a motorized pipettor. She is in a stylish kimono (hogusome) with a pattern like letters written with a brush. The text on her kimono is not only for fashion but also actually the recipe for the reagents (NaCl, glucose, amino acids, acetic acid, etc.); that is exactly to kill two birds with one stone. It will help her do experiments precisely at the busy end of the year.

It is known that an increase of cytosolic concentration of calcium ion (Ca²⁺) like a wave is initiated from the point of sperm entry and propagates throughout the egg after fertilization in many animal species. This calcium wave is caused by a kind of chain reaction; activated phospholipase C (PLC) produces inositol 1,4,5-triphosphate (IP₃) that induces release of Ca²⁺ from the endoplasmic reticulum (ER) near the egg surface, and released Ca²⁺ induces further release of Ca²⁺ from nearby ER. The leaves on the round-shape mountain are turning red like a wave coming down from the top of the mountain as if mimicking the calcium wave.

Site-specific DNA recombination technologies such as FLP-FRP and Cre-lox systems have been applied to various purposes including mosaic analysis or conditional knockout. We applied the mechanism to pruning a pine tree. When we gave a signal to the pine tree, a branch was circularized and was cut automatically at the specific site marked with the darker green pine needles.

Soba (buckwheat, Fagopyrum esculentum) is a pseudocereal with rich aroma and flavor, which is mainly eaten as noodles after Edo era in Japan. Yet there still remain many problems to overcome: its lower yield than the wheat or rice mainly caused by heteromorphic self-incompatibility (SI), its allergenic property that sometimes causes severe allergic reactions, and so on. Also, SI has been preventing us from producing good cultivars using genetic approaches. Finally, the buckwheat's whole genome has just been sequenced with next-generation sequencing (NGS), and it shows us a solution for those problems. We may have low-allergenic soba noodles in the foreseeable future.

An infant and his mother are playing with a small fish in a tub. The tub has a knothole from which water is pouring out, so the infant is carefully holding the small fish not to let it out from the hole. In the plasma membrane in various species, from bacteria to higher eukaryotes, there are such water channels called aquaporins that selectively allow water molecules to traverse the membrane. The schematized secondary and tertiary structures of the aquaporin's monomer are drawn on his mother's kimono and sash, respectively. And, aquaporins form tetramers to function in the plasma membrane just like the pattern drawn on the infant's kimono.

Naruto Strait, a strait between Shikoku and Awaji-shima Island, is famous for the huge Naruto-no-uzushio (Naruto whirlpools) that is generated by Japan's fastest current of sea water caused by the tide. It is thanks to the function of our inner ears that we can hear the roaring sound from and feel the acceleration of the rotation of the whirlpools. We saw an illusion of the structure of the inner ear (the semicircular canals, vestibule and cochlea) in a huge whirlpool that shook us by the inner ears.

Among phenotypes, quantitative traits are usually caused by many chromosomal loci (quantitative trait locus, QOL) in a complex manner, and researches using dogs have been fruitful. A number of dog breeds have been produced by human beings. The morphological character is highly variable among breeds, but uniformed within the same breed. Genome-wide association studies that coupled craniometric data obtained from various dog breeds have been conducted, and QTLs in which SNPs that might affect the skull shape existed concentratively were identified. One of the QTLs was mapped near BMP3 gene on Ch. 32, and it was shown that most breeds with shortened head had a common missense mutation in BMP3. Data on the background: Figure 3 of Schoenebeck et al. (2012) PLoS Genet. 8, e1002849 (DOI: 10.1371/journal.pgen.1002849). Upper panel: SNP distribution around BMP3 locus among various dog breeds. Lower panel: Plots of important SNPs (conserved, exonic, etc.) extracted from the upper panel.

Flow cytometry is a technology that allows high throughput analysis of the characteristics of cell populations by optically and rapidly measuring the morphological characteristics and fluorescent signals of the cells suspended in a narrow stream of fluid in equipment (flow cytometer). In addition, the equipment with a cell sorter can collect a certain type of cells from a heterogeneous population by charging droplets containing such cells identified by the optical data and attracting them by an electrostatic deflector. In this post town in this drawing, 'Positive' inn on the right and 'Negative' inn on the left are finding and attracting potential customers from passersby. They just look like a cell sorter. There is seen above them a cluster of clouds that resembles flow cytometric data.

Kiyomizu-dera temple in Kyoto is famous for its 12-meter high Butai ('stage'). In Edo era, there was a popular superstition that if one survived a jump from the Butai, one's wish would come true. In this drawing, one woman holding an umbrella as a parachute has jumped from the Butai over the fully blossomed cherry trees. In the Drosophila wing imaginal discs drawn on her kimono, the spatial expression patterns of genes involved in pattern formation can be discerned. May the Drosophila wing imaginal discs differentiate into wings before she crashes to the ground. Drosophila adults have gathered from nowhere as if they escorted her in a cherry blossom snowstorm.

Spring, that is the season of arousal for many living creatures. Even among mammals, some squirrels, bears and bats hibernate. This woman is researching hibernation of an individual of the Siberian chipmunk. The body temperature of hibernating chipmunk firstly drops to near ambient temperature, and reciprocally repeats the state of less than 10 °C (sustained hibernation) and the state of almost 37 °C (inter-bout arousal) like the chart on this drawing. We hope that life science will shed light on the mechanisms of various environmental adaptations of life. We thank Dr. Yoshifumi Yamaguchi (Graduate School of Pharmaceutical Sciences, The University of Tokyo) for his valuable suggestions for our drawing. Inspired by Figure 1 in Epperson & Martin (2002) Physiol. Genomics 10, 93-102.

In the most popular type of next-generation DNA sequencer, DNA fragments are PCR-amplified in the slide's channel coated by a lawn of PCR primers to form myriads of clone DNA clusters. After that, the DNA sequence of each cluster is determined by taking photographs of fluorescent signals on the slide with the image sensor again and again after each single-nucleotide extension step of a novel dye-terminator method. Thus, the reaction proceeding in the next-generation sequencer is massively parallel sequencing. In this drawing, we schematically expressed this mechanism with a flying hawk (image sensor) viewing clusters of pine trees (DNA) on the channel-shaped reclaimed land divided by embankments.

Worship the first sunrise of the new year from two rocks ‘Meoto-iwa’ (the wedded rocks, Mie, Japan) under double-helical DNA-like contrails in the sky. From left to right, there is the big rock, the sacred straw rope, the smaller rock, and the multi-exposed chain of suns. They just look like an RNA polymerase transcribing DNA into mRNA, its resultant mRNA, a ribosome translating the mRNA, and the new polypeptide chain growing upward from the ribosome, respectively.

Researchers in a lab at the very last moment on the night before a scientific meeting they are supposed to give their presentation. One is elated that her poster has been already done, while the other three are obviously fretting. The two people in the front are preparing for oral presentations. One on the left front is rehearsing with his slideshow, and the other is still revising her manuscript. Most of all, one on the left back is still collecting data for her slides, yet. Do not leave anything behind you, and good luck on your presentation tomorrow! Inspired by Figures 1(A) and 4(E) in Öst et al. (2014) Cell 159, 1352-1364.

The normal white (w⁺) gene in Drosophila is required for production of red pigment in the eyes. In some mutants in which the w⁺ gene has been moved to a region near the centrosomal heterochromatin due to an inversion in the X chromosome, the eyes are mottled with red and white patches; the w⁺ gene in the white cells has been silenced due to spreading heterochromatin, while w⁺ gene in the red cells is active. This phenomenon is called PEV (position-effect variegation), and a number of factors that control epigenetics, such as histone methyltransferases, have been identified by measuring the extent of variegation. Now, in this sliding screen, maple leaves in autumn were drawn with Japanese ink on gold foil background except some in the central oval with a red paint as an accent. A shadow that looks like Drosophila happened to be cast on it, emerging a figure of the w mutant with a mottled eye.

Kappa, a mischievous monster found in Japanese folklore, supposedly lives in a stream or pond, and has webbed hands and feet so that it's good at swimming. Human hands also have an interdigital web in the early embryo, but it disappears by apoptotic programmed cell death like a tadpole's tail. The intracellular signaling pathway that triggers apoptosis has been studied well; the signal flows down the 'cascade' that consists of multiple caspases (Cysteine-ASPartic proteASE) such as caspase 9 or 3 encoded by CASP9 or CASP3, respectively. This poor Kappa in this drawing has been saturated with the water flowing down the caspase cascade, and its vaunted web is in danger of disappearing by apoptosis.

Shoki (Zhong Kui in Chinese), derived from Chinese Taoism, is a god for warding off diseases. According to a legend, one night when Emperor Genso (Xuanzong) of the Tang Dynasty had a high fever, Shoki appeared to him in a dream, killed a monster, and saved the Emperor at last. In tribute to the legend, Shoki has been worshipped as a god who protects people from illness for hundreds of years in China and Japan. The role of Shoki in the legend is that of the immune system itself. In this drawing, Shoki holds a sasumata (spear fork) with an IgG-like spearhead in the right hand and wears a cloth with a crest of IgM and a pattern of a dendritic cell; they are weapons of mammalian adaptive immunity. In contrast, his left hand contains a monster (pathogen) by melanization, which is one of the weapons of the innate immunity of insects. We thank Prof. Hirotaka Kanuka's lab (The Jikei University School of Medicine) for their valuable suggestions for our drawing.

Transposons (transposable elements), discovered in maize by Barbara McClintock in 1948, are DNA sequences that can change their positions within the genome. Transposition of transposons can introduce mutations in the host genome. Actually, there was a close and astonishing relationship between transposons and the culture of the Edo era. In late Edo, a large number of mutant Asagaos (Japanese morning glory) were isolated, and it became popular to cultivate them; in fact, many mutations were caused by transposons. These mutant Asagaos have been collected by researchers and are currently maintained by a group led mainly by Kyushu University. See the website of National BioResource Project (NBRP) “Asagao” (http://www.shigen.nig.ac.jp/asagao/) for further details.

One of the highlights of the month of July in Japan is Tanabata (Star Festival). Tanabata, a festival to pray to the stars in the Milky Way in summer, was imported from ancient China. People in Edo era started to decorate bamboo branches with ‘tanzaku’ (small pieces of paper) on which they wrote their wishes, and to pray the wishes would come true. The bamboo branches in this drawing are likened to histone tails (H2A, H2B, H4 and H3 from the left). The tanzakus represent epigenetic modifications (acetylation, methylation and phosphorylation) of amino acid residues in histone tails. If you use this histone bamboo, mind that you have to phrase your wishes with the types, positions and combinations of decorations (or modifications). You need a textbook to perform modifications correctly.

It was in 1936 when the existence of ‘florigen’ was initially predicted as a plant hormone that transmits information on daylight length at their leaves to the tip of the stem and stimulates flower initiation. In 2007, it was finally identified as a protein, which is coded by the FT gene in Arabidopsis thaliana. FT protein is produced in the leaves and transmitted to the growing tip at the shoot apical meristem via the phloem, and interacts with a transcription factor (the product of the FD gene in Arabidopsis) to induce genes involved in flower initiation. In this drawing, an actor performing FT is contacting another actor performing FD, and trying to stimulate flower initiation with him in front of hydrangea flowers that represent the month of June in Japan.

There is a Japanese legend of an extraordinary strong child ‘Kintaro’, who caught a carp, taller than himself, only with his arms. Carp are familiar to people all over Japan as Koinobori (carp streamer) that is put up in May for their children's healthy growth. In this drawing, Kintaro is showing his extraordinary grip that acts as an external force to drive cellular convergent extension (a process in which a tissue is elongated along a certain axis by cell intercalation in animal development) to elongate the carp's body. The progression status of the convergent extension can be observed by the pattern of the carp's colored scales.

Genome editing technologies have been invented and improved in recent years, and there is a growing expectation that the technologies can be utilized as a tool not only for molecular biological studies, but also for genetic therapies. Among them, CRISPR-Cas9 system that was originally found as a part of the bacterial adaptive immune system gets noticed for its easy introduction. Here, users are only required to design a guide RNA with a 20-nt sequence that is complementary to the target DNA sequence and co-express Cas9 with the RNA in vivo, then Cas9 protein will cleave the target DNA in site-specific manner. This is a portrait of a kabuki actor who plays Cas9 as indicated by the crest “ku” (‘nine’) on kimono he is wearing. The “actor” definitely has a promising future ahead of him.

The fragrance of Japanese plum blossoms is the essence of early spring in Japan. This well-kept plum garden has a unique feature that it is a copy of a landscape of the outer side of animal plasma membrane. The ground represents hydrophilic head domains of the lipid molecules, while the trimmed trunks and branches in the front and the garden stones in the back look like glycosylated membrane proteins. There are a lot of plum trees that look like glycans far off in the distance. A mound on the ground under a basket and a pond in the back express lipid raft (a microdomain that has a different lipid composition) and endocytosis in process, respectively.

An atmospheric ghost light that is called Kitsunebi ('fox light') is described in Japanese folklore. The most famous one is the one in the Oji Inari shrine (Kita-ku, Tokyo). Every New Year's Eve in the old lunar calendar, foxes from all of the Kanto area, all suited up, gather to this shrine, light Kitsunebi under a big tree, and then stand in line. In this drawing, while the line of Kitsunebi in a standard single color is ahead of the rest, the rest of the foxes gathering under the tree are holding up 'new generation Kitsunebi' in various colors and about to join the line. This scene is reminiscent of the green fluorescent protein (GFP; here are three spatial structure models) genetically engineered so as to be available in different emission peaks.

Some dioecious plants determine sex by sex chromosomes (XY or ZW) like mammals or birds. A pair of birds on branches of a pine tree, which is a symbol of a new year in Japan, is a couple of Eclectus parrots (Eclectus roratus) having extreme sexual dimorphism (left: ZZ male; right: ZW female). What they hold in their beaks are flowers of 'Suiba' (common sorrel or Rumex acetosa; left: XY₁Y₂ male; right: XX female). Suiba is one of the first species among the seed plants whose existence of sex chromosomes was reported (H. Kimura & T. Ono (1923) Bot. Mag. (Tokyo) 37(438), 147-149. DOI: 10.15281/jplantres1887.37.438_147). It is known that Suiba's sex determination system is similar to that of Drosophila and depends on the ratio of X chromosomes to autosomes.

Genpaku Sugita (1733-1817) is well-known for his translation of 'Kaitai Shinsho' (New Text on Anatomy, in 1774) compiled based on a book of anatomy written in Dutch. This Japanese first full-blown translation from a Western language contributed to the development of medical science in Japan. The masterpiece has been accomplished while many translated terms such as "shinkei" (= nerve) were coined. Over the past 240 years since then, anatomical methods have dramatically improved. Various optical clearing agents have been invented to clear organs including the brain without difficulty. Now, those agents can make brains transparent without damaging any of the fine structures, and enable researchers to observe neurons deep inside the brain. With our great respect to Genpaku Sugita, let us give him components of the optical clearing agents: urea, detergents and aminoalcohol. Behind him stands a vase of a soapberry tree bearing fruit that used to be raw material for detergents in Edo era.

An experimental procedure in behavioral neuroscience known as the Morris water maze is a method to assess the animals' ability of spatial learning and memory. In the experiment, test animals are placed in a pool filled with a pool of clouded water where they are supposed to swim, and scientists record the process how the animals find an invisible platform under the water. In this picture, two scientists are recording behavior of mice in an experiment using the Morris water maze. It rains reminding us of dendrites of neurons. One woman puts up an umbrella over the other to prevent the recorder from being wet.

This wooden stand called "Marudai" is used for braiding a Kumihimo, a decorative belt used for tying on a kimono sash. This particular Marudai has the top surface engraved with a part of the codon table in order to translate nucleotide sequences of genes into the pattern of Kumihimo (polypeptide chain). The Marudai and bobbins actually play the role of ribosomes and tRNAs that synthesize proteins by translating mRNA sequences into amino acid sequences. The color of threads had changed depending on amino acids. The pattern of Kumihimo being braided in this drawing was obtained from the sequence of human insulin. Nothing can be as cool as gene sequences, which design the pattern of brilliantly colored Kumihimo.

F_oF₁ ATPase (also known as ATP synthase) exists in mitochondrial inner membranes and bacterial plasma membranes to synthesize ATP (adenosine triphosphate) by using electrochemical gradient of protons (H⁺) between inside and outside of the membranes. F_o is integrated in the membranes and thought to have a rotor ring that rotates horizontally. F₁ has a dome-like structure comprised of three α and three β subunits that are alternately arranged, which is anchored to the membranes to prevent rotation. Shaft-like γ subunit connects the center of the rotor ring of F_o and F₁. As protons flow down the gradient across the membranes through F_o, the rotor ring of F_o and γ rotate, and the spin force of γ against αβ complex is used to synthesize ATP molecules. In this drawing, a waterwheel (F_o) is rotated by the gradient of water (represents proton gradient), and series of three coins (which represent ATP) are generated from the 'apparatus' (αβ of F₁), which is made from six boards being attached to the front side of the waterwheel. A man in the back takes a role to transport protons to the outside of membranes to produce proton gradient.

Tsushima Tenno Festival has been held every summer in Tsushima city, Aichi prefecture, Japan, for the past 500 years. One of the highlights of the festival is the evening festival called Yoi-matsuri when five boats decorated hemispherically with a lot of illuminated lanterns come down the river. The distinctive shape of the hemispherical decoration reminds us of partially formed clathrin-coated vesicles (CCV). So this summer, we dare to replace the decorations with the one which looks exactly like spherical CCV after completion. On the front side of the river, we place Y-shaped structures modeled on the LDL (low-density lipoproteins) receptor that mediates CCV's capturing LDL. The reflection of the light from the lanterns which represent CCV sparkles on the water surface of the river, and creates a fantastic summer night view.

A scene of Yuzen Nagashi (a process of washing kimono silks) at a pontoon bridge over a river. This bridge actually illustrates the way a number of ribosomes (boats) are attached in a row along a single mRNA chain (a bridge) to translate in parallel, and then form a polysome. There is a grove, which is like a poly-A tail, extending from the bridge to the opposite bank of the river. The pieces of fabric form polypeptide chains synthesized by ribosomes with their edges trimmed in the shape of 'M' that is the abbreviation of methionine. Now, the translation processes probably have just terminated at the boats on the far end. The fabric is being folded while it is released from those boats.

A parade of “Kappore”, a dance with “nigaigasa” or double layer umbrellas. A decorative piece of cloth modeled after DNA wraps around each umbrella approximately 2 times to link one umbrella to the adjacent umbrellas. This seems to be a replication of the “beads-on-a-string” structure consisting of a DNA strand and nucleosome cores. Those who hold the “nigaigasa” are men representing the four families of core histones. If you look closely, you can find a towel printed “a-ce” on its tail hanging from one of the men's waist. This looks like the acetylation of a tail of one of the core histones. It has been found that the initiation of transcription is related to histone acetylation. If that is the case, this towel may be a sign to start dancing.

Two artisans are heaping up lumber in the form of layers. The process where the lumber is going to be piled up perfectly in six horizontal layers reminds us of the cerebral cortex in corticogenesis. One of the artisans below, on whose back a Chinese character ‘kan’ (‘stem’) can be seen, may play the role of the neural stem cell (radial glia cell), the source of new lumbers (newly created neurons), and extends a rope (radial glia fibers) upward so as to carry the lumber properly to the top layer. The other artisan above is considered to play a role similar to the cells that secrete reelin. The reelin is a protein that regulates correct migration and positioning of neurons.

“Yaedatami” or an eightfold straw mat is a tatami specially prepared for use in religious services. A craftsman folds “tatamiomote” or woven soft rush straws with edging of specially designed Nishijin brocade several times over so as to perfectly align patterns of creases of the folded edgings. We use the design to schematically illustrate the somitogenesis in vertebrates. As the U-shaped presomitic mesoderm moves tailward, periodic waves of gene expression form pairs of somites one after another from the anterior end. “Oshitone” or the top cushion has a mark of an embryo woven into it. If you carefully look at the edging of “oshitone”, you can find it bears the process of segmentation in Drosophila, a species which forms all of its segments simultaneously. Cooperated by Isogaki Tatami (Kyoto, Japan).

FRET (Fluorescence Resonance Energy Transfer), which is a phenomenon of energy transfer between two adjacent fluorescent molecules, has been applied to visualization of interaction between proteins in living cells and so on. To carry out high-efficiency FRET, not only the distance between two molecules must be very close (less than about 10 nm) but the relative orientation of two chromophores must also be optimized. One of the women in this picture carries the other with attention paid on how they are oriented to each other, and successfully lightens the plum blossoms just like FRET.

Mt. Fuji glows with the red tint of the rising sun. A bank of clouds is lying behind the mountain and presenting its characteristic appearance. There are lying clouds in shapes like, from the bottom, rough endoplasmic reticulum, smooth endoplasmic reticulum, and transport vesicles. There is seen above it a bank of clouds well-formed like a Golgi apparatus, and further above it smaller clouds like secretory vesicles. There may also be seen clouds like mitochondria. Wonder if it's just an illusion.

Wishing a prosperous new year, two horses, which carry a red and white twisted rope resembling F-actin, are galloping. This reminds us of pseudopodia that are strongly growing by the power generated from G-actin polymerization.

Following last month's issue, let's imagine what an international academic meeting was like in Edo era. No better place can be found than a Kabuki stage for the oral presentation! The presentation is full house. A presenter (probably the president of this meeting?) stands at the center of the stage, and on his left hand, the chairperson of this session is sitting on the stage. Each paper lantern hanging from the ceiling has a picture of crest imitating model organisms. There is a poster for the 36th Annual Meeting of the Molecular Biology Society of Japan (MBSJ) (3-6 December, 2013, Kobe) behind the presenter.

What if there had been an international academic meeting held in Edo era? It must be like this. This picture illustrates how successfully a poster session was being held. A student-like young man on the far left is performing a presentation on a poster titled “idenshi-kara-saibou-made” (in English, “from Genes to Cells”). Another poster on the right end is the one for the 36th Annual Meeting of the Molecular Biology Society of Japan (MBSJ) (3-6 December, 2013, Kobe). Inside the floor, in the back on the right of the picture, attendees from inside and outside the country are having a discussion over snacks.

Protruding from each side of the mountain (represented as cells) like classical cadherin cell adhesion molecules, bridge girders are mutually bound so as to link two summits (cells). This month's cover art represents the mountain surfaces as plasma membranes, the bridge girders and trails as classical cadherins (where each of the bridge girders shows five extracellular cadherin (EC) domains and a transmembrane domain, while the trails show intracellular domains), huts along the trails as catenins, groves of trees as actin filaments, and cliffs as an intercellular space. Sealed with a word “adhesion” at lower right.

Tadataka Inou (1745-1818) was over 50 when he retired from the family business and started to learn Western astronomy. At the age of 55, he led a surveying team to travel throughout Japan islands (40,000 kilometers in total) spending 17 years, and accomplished the first Japanese actual measured map, Dai Nihon Enkai Yochi Zenzu, based on the data collected during the survey. The map created about 200 years ago was so accurate that it later amazed the western surveying teams visiting the country. This month's cover art illustrates Tadataka Inou and his team working together to accomplish a metabolic map. Inspired by Figure 2-35 in The Molecular Biology of the Cell, 5th ed. (Alberts et al. 2008).

All the traditional Japanese sweets replicate the development of an early embryo from the first cleavage. Each confectionery expresses, from the back, a fertilized egg undergoing the first cleavage (made from “konashi” or kneaded sweet bean paste, coated with “kudzu” starch), a 2-cell-stage embryo (“aoume” or a green plum), an 8-cell-stage embryo (modified from “kiku” or chrysanthemum), a morula (“domyoji” or a sweet pink mochi), and a tailbud (modified from “magatama” or a claw-shaped bead). So, which one would you like to start with? Confectionery Coordination: Gion Narumiya, Kyoto, Japan.

Soma Nomaoi, Soma horse chasing festival, which used to be a religious ceremony, is now an event held in Soso District (north-eastern part of Fukushima prefecture) every July. In ancient times, Samurais captured wild horses roaming around fields, and dedicated them to Kami. Although wild horses were extinct early in Meiji era, later, the ceremony has been revived as an event in which hundreds of horsemen scramble for holy flags. In this cover art, we let warriors on horsebacks carry flags with arms of model organisms, the strongest tools for our research, to join this event. It is Arabidopsis thaliana (right foreground) what colors the field, the stage for the festival, and streamers of double helix are fluttering in the far background.

kaiA, kaiB and kaiC genes and their products constitute a core circadian oscillator in the cyanobacterium S. elongates (derived from a Japanese term “kai”, which means rotation or cycle number). KaiA stimulates autophosphorylation of KaiC, whereas KaiB promotes autodephosphorylation of KaiC. It is the particular characteristics of system of cyanobacteria that the three purified Kai proteins and ATP can reconstitute a circadian oscillation in a test tube. We overlay a diagram of this feedback loop on an armillary sphere in an Ukiyoe, which was installed at an astronomical observatory in Edo era. The pattern of roof tiles in the foreground depicts a circadian oscillation.

Speaking of Japanese seasonal tradition in May, you may think of carp streamers flying high over roofs of houses. People fly the carps, wishing for healthy growth of their children. This month, we have painted each scale of a carp streamer, mimicking a mechanism known as lateral inhibition. So, how would you grade the work?

This month's feature is molecular chaperones which support correct protein folding. A child represents a protein (or a polypeptide) trying to fold correctly, while a woman represents a chaperone teaching calligraphy. Pieces of paper scattered on the floor are misfolded polypeptides. In reality, accumulation of misfolded polypeptides will cause various kinds of diseases. Chaperones are essential to life.

A piece inspired by a fusion of traditional Japanese beauty and life sciences. There are a Japanese cosmetic brush and a hand mirror on a black board. An embryo fantastically reflected in the mirror suddenly reminds you of something: the brush is a very micropipette, and the embryo must be a subject of an experiment with it. How cleavage of a fertilized egg occurs is drawn like a family crest on a vanity bag, as if it indicates whom these cosmetic tools belong to. In the embryo, a lacZ marker transgene was driven by a connexin43 (Cx43) promoter in neural crest cells. Courtesy of Osamu Chisaka.

Kites are flying in the early spring in a town with the backdrop of Mt. Fuji. Being steered into the wind and skillfully manipulated via string, the kites look like metaphase chromosomes aligned on the equator of the cell.

Phages have greatly contributed to flourishing of molecular biology, and even today, they remain useful tools for scientists. In this illustration, a “hikeshi” (a firefighter in Edo) is carrying a “matoi” (a standard of his firefighter team as its symbol), which is likened to a phage. Meanwhile lanterns held by firefighters in the back look like bacteria.

The cover art of this month is the second part of the series from the November issue. It describes how cellular slime molds assemble into a dragon. The cellular slime molds normally are individual of an amoeba-like unicellular organism. However, when they starve, tens of thousands of cells aggregate in one place to form a cluster. The cluster hugs the ground like a slug, searches for the right place for making spores, and forms a fluting body (lower part of the ground). When placed in starvation conditions, the cellular slime molds begin to secrete cAMP, which stimulates nearby slime molds to secrete pulses of cAMP. Once they secrete cAMP, they become inactive for a while. As the result, waves of cAMP propagate as they swing in a spiral form (upper part of the sky).

The principle mechanism of skin pattern formation in vertebrates can be explained with a mathematical model proposed by Alan Turing (reaction-diffusion system, 1952). In this month's cover art, wild-type and mutant tigers are glaring to the right (at a dragon coming up in December issue). In the front of the wild-type tiger, a rock is illustrated with three peaks representing waves of activator and inhibitor that are observed in the reaction-diffusion system. Furthermore, two bamboos having four internodes represent transmembrane domains in a certain variant of connexin (a subunit of the gap junctions), which is a four-span transmembrande protein and one of the responsible genes for morphological mutation in a vertebrate.

Cilia of eukaryotic cells undulate in a well-balanced motion and play a variety of roles essential to life. The cover art for this month's issue presents movements of ciliated cells of respiratory epithelium in an analogy to Susuki glasses, a feature of autumn in Japan. The cilia beat in a given direction is defined by the direction of basal feet (red) that protrude from basal bodies (gray). In the picture, waves to the right are generating a current. There is a goblet cell that secretes mucus, slightly right of the center on the near side of the picture. The moon and geese are also arranged in the picture so as to evoke another feature of autumn in Japan.

The theme of this month is “translation”. The information in DNA is first transcribed into mRNA, which is further converted into a chain of amino acids. This conversion process is called translation and a stop codon marks the end of translation in each mRNA molecule. In the illustration, a fictitious translator on completion of his translation seals the letter with a Chinese character “stop” and amber (which is a nickname for UAG, one of the stop codons). The face of the seal depicts letters of “translation”.

Coloring the summer night sky of Japan, this firework has a theme of the half spindle of animal mitotic cells. A centrosome containing a pair of centrioles is located in the center, and astral microtubules extend to the up to the left, while polar microtubules extend to the opposite direction. Japanese technology currently produces cutting-edge fireworks, and it should not be difficult to produce such fireworks in reality.

This cover depicts The Bridge in the NGS Rain where people are being exposed to torrents of genomic information, that is, fruits of next generation sequencing. The man standing in the middle of the bridge is pictured deep in thought, considering how to utilize this sequence data set of the ALDH2 gene. Another man, shown to the right with a sake bottle, is eager to know whether he is genetically predisposed with a high tolerance for alcohol or not.

The Epigenetic landscape, which was firstly depicted by C. H. Waddington in 1950's, has often been used to illustrate cellular differentiation in the process of biological development. Presented on our cover is a timeless representation of the landscape where we see worshippers of Mt. Fuji are being reprogrammed on the slope. Some are climbing high to acquire pluripotency, while others are traversing the foot, and being directly reprogrammed.

Regulated cell adhesion and cellular motility underlies dynamic cell rearrangement, which is essential for morphogenesis of various organs. We expressed this process using a picture of a stone levee along a canal.

Branched waterfalls are reminiscent of the cell lineage of the nematode Caenorhabditis elegans from a zygote to a newly hatched larva.

A woman with a hanagasa (a traditional hat decorated with ornamental flowers) is performing a Japanese classical dance. The ornaments on the hat actually are gap junctions, and some of them are opened and allowing small molecules to pass through.

A fisherman on a cliff is pulling nets as if synchronizing circadian rhythms with the help of light shining down from the sky.

Set against the backdrop of Mt. Fuji, a skilled craftsman is fixing a broken wooden barrel by excising damaged bases and then introducing new ones. We liken this to the process of DNA repair thereby recovering hydrogen bonds between each pair of bases.

Since nerves of higher animals have myelin sheaths, an action potential is propagated rapidly (phenomenon called a saltatory conduction) like the swift wind. The wind god is likened to an action potential that conduct bounces to be propagated.

The Thunder God is generating the action potential, which is not lightning, in a neural network. The illustration is paired with that of December Issue.

Harvest time. Toreutics on a guard of a Japanese sword has a design of ears of rice and a butterfly landing on them. No, they actually are DNA winding around nucleosome.

A huge and prestigious shrine that looks like Izumo-Taisha shrine at a glance. White zigzag paper streamers like a leucine zipper-type transcription factor are tucked in a giant sacred rope (dextrorotatory double-helix). The paper streamers probably bind to specific sequences of dsDNA expressed as a sacred rope.

Being inspired by the similarity in the appearance, KOKESHIs are portrayed as metaphase chromosomes, which pair KOKESHIs. It deserves attention that each pair of KOKESHI is designed the same and tied with a thread at their necks (kinetochores) each other.

Importance of bidirectional transportation between TOHOKU and surrounding districts. The “Kaido” expressed as a stone-pave street is designed to look like microtubules. Carts going left and pulled by bulls and messengers going right are expressions of motor proteins with cargos in eukaryote cells.

A scene from a Chinese-inspired vigorous dragon dance in a festival in Kyushu, Japan. The dragon is likened to a messenger RNA (mRNA), expressing transcription with DNA template.

A beautiful woman of the Heian period is pulled by a dog and peeks out from behind a bamboo blind, which is likened to experimental data of DNase I footprint. Data:Akita et al. Genes to Cells 15(5) pp537-552 (2010).

Grand Sumo showing a YOKOZUNA or grand champion and “hands” of supporters are pulling the horizontal rope of the kesho-mawashi. They want to tie the kesho-mawashi, but simultaneously, they are making a new horizontal rope from an older vertical rope, using Holliday junction-like structure.

A designed family emblem of cell division blends well with traditional Japanese patterns of auspicious omens motifs as pine and bamboo, on the artwork of tiered food boxes in silver lacquer.

Two sets of segregated chromatids during telophase are depicted as cats cuddled up comfortably beside spindle poles.

Overlooking Mount Fuji in the distance through the arching wooden bridge, reflected on the water surface, forming complete circles to resemble a pair of spectacles or a ‘double helix.’