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Our research activities would be better served if they were communicated in a manner that is openly accessible to the public and all researchers. The research we share is often limited to representative data included in research papers—science would be much more efficient if all reproducible research data were shared alongside detailed methods and protocols, in the paradigm called Open Science. On the other hand, one primary function of research journals is to select manuscripts of good quality, verify the authenticity of the data and its impact, and deliver to the appropriate audience for critical evaluation and verification. In the current paradigm, where publication in a subset of journals is intimately linked to research evaluation, a hypercompetitive "market" has emerged where authors compete to access a limited number of top‐tier journals, leading to high rejection rates. Competition among publishers and scientific journals for market dominance resulted in an increase in both the number of journals and the cost of publishing and accessing scientific papers. Here we summarize the current problems and potential solutions from the development of AI technology discussed in the seminar at the 46th Annual Meeting of the Molecular Biology Society of Japan. [ABSTRACT FROM AUTHOR]

The 36th International Mammalian Genome Conference (IMGC) was held in a hybrid format at the Tsukuba International Congress Center in Tsukuba, Ibaraki, Japan, for 4 days from March 28 to 31, 2023. This international conference on functional genomics of mouse, human, and other mammalian species attracted 246 participants in total, of which 129 were from outside Japan, including Europe, the United States and Asia, and 117 participants were from Japan. The conference included three technical workshops, keynote lectures by domestic researchers, commemorative lectures for the conference awards, 57 oral presentations, and 97 poster presentations. The event was a great success. Topics included the establishment and analysis of disease models using genetically engineered or spontaneous mutant mice, systems genetic analysis using mouse strains such as wild‐derived mice and recombinant inbred mouse strains, infectious diseases, immunology, and epigenetics. In addition, as a joint program, a two‐day RIKEN Symposium was held, and active discussions continued over the four‐day period. Also, there was a trainee symposium, in which young researchers were encouraged to participate, and excellent papers were selected as oral presentations in the main session. [ABSTRACT FROM AUTHOR]

Front cover: 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. Designed by TRAIS Co., Ltd. (Kobe, Japan). [ABSTRACT FROM AUTHOR]

B Front cover: b 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. Now, what kind of cells will they make? What these women are enjoying is a fukuwarai with cell organelles likened to facial parts. [Extracted from the article]

B Front cover: b People are fl eeing from a tornado that has suddenly appeared. Designed by TRAIS Co., Ltd. (Kobe, Japan). 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. [Extracted from the article]

A letter to the editor is presented in response to an article on a report from the Working Group of the Molecular Biology Society of Japan that was published in one of the previous issues.

Cellular signaling regulates various cellular functions via protein phosphorylation. Phosphoproteomic data potentially include information for a global regulatory network from signaling to cellular functions, but a procedure to reconstruct this network using such data has yet to be established. In this paper, we provide a procedure to reconstruct a global regulatory network from signaling to cellular functions from phosphoproteomic data by integrating prior knowledge of cellular functions and inference of the kinase–substrate relationships (KSRs). We used phosphoproteomic data from insulin‐stimulated Fao hepatoma cells and identified protein phosphorylation regulated by insulin specifically over‐represented in cellular functions in the KEGG database. We inferred kinases for protein phosphorylation by KSRs, and connected the kinases in the insulin signaling layer to the phosphorylated proteins in the cellular functions, revealing that the insulin signal is selectively transmitted via the Pi3k‐Akt and Erk signaling pathways to cellular adhesions and RNA maturation, respectively. Thus, we provide a method to reconstruct global regulatory network from signaling to cellular functions based on phosphoproteomic data. In this study, we reconstruct global regulatory network from insulin signaling to the cellular functions via protein phosphorylation based on phosphoproteomic data. The arrows indicate phosphorylation of the quantitatively changed phosphopeptides by the protein kinases. [ABSTRACT FROM AUTHOR]

Front cover: 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. Designed by TRAIS Co., Ltd. (Kobe, Japan). [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV) have attracted attention as circulating biomarkers for many diseases, particularly cancer. Conventional immunofluorescence staining has been used for the detection of target antigens on EV by flow cytometry. However, the staining intensity depends on the amount of antigen expressed on the vesicles and is often only around the noise level. Instead of immunofluorescence, we combined immunomagnetic separation using nanosize MACS® MicroBeads with phospholipid staining of EV (IMS‐PS method). EpCAM‐positive EV were prepared from the culture supernatants of OVCAR3 (EpCAM‐high), A431 (EpCAM‐low) or Colon‐26 (non‐human control) cells as cancer models and were examined by the IMS‐PS method using EpCAM mAb‐coated MicroBeads. By employing Polaric‐500c6F as the dye for staining EV phospholipids and using appropriate flow cytometry settings, autofluorescence was excluded, whereas pretreatment of the MicroBeads with conventional blocking agents reduced nonspecific binding to non‐target vesicles. These modifications resulted in a linear relation between the number of EV detected and the sample volume, regardless of the level of EpCAM expression on the vesicles. A431 EV spiked into healthy volunteer plasma were enumerated with good accuracy. The IMS‐PS method may be useful for clinical evaluation of EV with low levels of antigen expression that are difficult to detect by conventional immunofluorescence. Extracellular vesicles (EV) in cultured cell supernatant are quantitated by immunomagnetic separation and phospholipid staining (IMS‐PS) method developed in the paper. Several improvements are made (A), appropriate amount of the bead is determined (B), and titrations of OVCAR3 EV and A431 EV show linear response between input EV sample volume and output counts (C). Colon‐26 EV are non‐human control. [ABSTRACT FROM AUTHOR]

Front cover: The position of the hindlimb, or the length of the trunk, of tetrapods is highly diversified. Very recently, it was revealed that the timing of expression of Gdf11 gene in tetrapods' embryonic development plays an important role in determining the eventual position of the sacral vertebrae and the hindlimb beyond species. In some species that has a short trunk, such as frog, Gdf11 is expressed relatively earlier; in contrast, it is expressed much later in snakes' embryo. On the cover of this issue, we drew tetrapods with various lengths of the vertebrae, imitating Choju‐jinbutsu‐giga, one of Japan's national treasures, on a photograph of bamboos, which remind us of somites. For drawing this image, we referred to a website https://nagoyaumb5.wixsite.com/morphogenesis/takayuki-suzuki and a research paper by Matsubara et al. (2017) Nature Ecology and Evolution, vol. 1, pp.1392–1399, DOI: 10.1038/s41559-017-0247-y. Designed by TRAIS Co., Ltd. (Kobe, Japan). [ABSTRACT FROM AUTHOR]

RNA sequencing (RNA-seq) provides information not only about the level of expression of individual genes but also about genomic sequences of host cells. When we use transcriptome data with whole-genome single nucleotide polymorphism (SNP) variant information, the allele frequency can show the genetic composition of the cell population and/or chromosomal aberrations. Here, I show how SNPs in mRNAs can be used to evaluate RNA-seq experiments by focusing on RNA-seq data based on a recently retracted paper on stimulus-triggered acquisition of pluripotency (STAP) cells. The analysis indicated that different types of cells and chromosomal abnormalities might have been erroneously included in the dataset. This re-evaluation showed that observing allele frequencies could help in assessing the quality of samples during a study and with retrospective evaluation of experimental quality. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are endogenous single-stranded, 22-nt (nucleotide) RNAs which complement mRNA to initiate post-transcriptional regulation. This review presents updates and evaluations of the public domain resources available for miRNA identification and target prediction toward their utilization in the biomedical research approach. This study discusses the basic principles of miRNA computational studies based on the nature and mechanism of action of miRNAs. Furthermore, we have explored fifty-nine current online miRNA tools that can be categorized into three classes in this paper: (i) miRNA identification; (ii) miRNA target prediction; and (iii) specialized miRNA tools. [ABSTRACT FROM AUTHOR]

Various conditions for differentiating embryonic stem (ES) cells or induced pluripotent stem (iPS) cells into specific kinds of cell lines are under intensive investigation. However, the production of a functional organ with a three-dimensional structure from ES or iPS cells is difficult to achieve in vitro. In the present paper, we describe the establishment of a green fluorescent protein-expressing rat ES cell line and production of mouse↔rat ES chimera by injecting rat ES cells into mouse blastocysts. The rat ES cells contributed to various organs in the chimera, including germ cells. When we injected ES cells into blastocysts of nu/nu mice lacking a thymus, the resultant chimeras produced thymus derived from rat ES cells in their bodies. The chimeric animals may provide a method for the derivation of various organs from ES or iPS cells. [ABSTRACT FROM AUTHOR]

The transcription factor IRF-3 is activated by microbial invasions and produces a variety of cytokines including type-I interferon. Upon microbial infection, IRF-3 is phosphorylated at its C-terminal regulatory domain, then oligomerized, translocated into the nucleus, and here it binds to CBP/p300. Although a number of studies have been reported investigating the activation mechanism of IRF-3, there are a number of unresolved issues, especially on the phosphorylation sites, the oligomerization process and the binding mechanism with CBP/p300. In this report, the phosphorylated IRF-3 regulatory domain (IRF-3 RD) was prepared using the kinase IKK-i, and the active form of phosphorylated IRF-3 RD was identified. The paper also reports the crystal structure of the active form of the phosphorylated IRF-3 RD. Furthermore, the phosphorylation of Ser386 was found to be essential for its dimerization and binding with CBP/p300 using mutational analysis and mass spectrometry. Thus, we conclude that the phosphorylation of Ser386 is essential for activation of IRF-3. [ABSTRACT FROM AUTHOR]

A recent paper ( Hayashi et al. 2007 ) in this issue of Genes to Cells shows that the fission yeast Schizosaccharomyces pombe Tel2, a homologue of mammalian/worm CLK2/Clk-2/Rad-5, physically interacts with all the phosphoinositide 3-kinase-related kinases (PIKKs) that include Rad3/Tel1 (ATR/ATM homologues), Tor1/Tor2 (TOR kinases) and Tra1/Tra2 (TRRAP homologues), raising the possibility that Tel2 family proteins link various PIKK-related cellular processes by interacting with PIKK family proteins. In this minireview, implications and impact of the findings, and a possibility that PIKKs are functionally related through Tel2, are discussed. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) has a characteristic polygonal structure with hallmark three-way junctions. In a previous paper, we reconstituted the disruption of the pre-existing ER network using mitotic cytosol from HeLa cells in streptolysin O (SLO)-permeabilized CHO-HSP cells (stably expressing GFP-HSP47). In addition, we found that interphase cytosol induced reformation of the disrupted ER network into a continuous network structure. Here, we show that the reformation of the ER network is accomplished through two sequential fusion reactions. The first process is mediated by NSF/α and γ-SNAPs, and involves the generation of typical membranous intermediate structures that connect the disrupted ER tubules. A subsequent fusion is mediated by p97/p47/VCIP135, which has been shown to be required for homotypic fusion events in Golgi cisternae regrowth after mitosis. In addition, we also found that both fusion processes involve the t-SNARE, syntaxin 18. [ABSTRACT FROM AUTHOR]

Amyloid-like protein aggregates have been implicated in various diseases and in the protein-based inheritance of yeast prions. The molecular chaperone Hsp104 has been shown to be necessary for the aggregate formation of polyglutamine in yeast, and for the maintenance of several yeast prion phenotypes through the formation of self-propagating aggregates. In this paper, we show that the polyglutamine aggregates that are formed independently of Hsp104, are required for Hsp104 to efficiently produce more aggregates. Similarly, in the yeast prion [ PSI+] system, Hsp104-dependent epigenetic changes to the [ PSI+] prion phenotype require the presence of prion aggregates in the normal [ psi−] state. We also show that the co-localization of different prion aggregates suggests that cross-seeding by different yeast prions increases the probability of Hsp104-dependent epigenetic change. These findings highlight the role of pre-existing aggregates in chaperone-dependent establishment of the epigenetic trait in yeast prions, and possibly in the pathology of several neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Lung alveolar epithelial cells are comprised of type I (ATI) and type II (ATII) cells. AΤΙ cells are polarized, although they have very flat morphology. The identification of marker proteins for apical and basolateral membranes of ATI cells is important to investigate into the differentiation of ATI cells. In this paper, we characterized receptor for advanced glycation end-products (RAGE) as a marker for ATI cells. RAGE was localized on basolateral membranes of ATI cells in the immunoelectron microscopy and its expression was enhanced in a parallel manner to the differentiation of ATI cells in vivo and in primary cultures of ATII cells. RAGE and T1α, a well-known ATI marker protein, were targeted to basolateral and apical membranes, respectively, when expressed in polarized Madine Darby canine kidney cells. Moreover, RAGE was expressed in ATI cells after T1α in vivo and in ex in vivo organ cultures. In conclusion, RAGE is a marker for basolateral membranes of well-differentiated ATI cells. ATI cells require some signal provided by the in vivo environment to express RAGE. [ABSTRACT FROM AUTHOR]

BackgroundEukaryotic DNA replication is initiated from distinct regions on the chromosome. However, the mechanism for recognition of replication origins is not known for most eukaryotes. In fission yeast, replication origins are isolated as autonomously replicating sequences (ARSs). Multiple adenine/thymine clusters are essential for replication, but no short consensus sequences are found. In this paper, we examined the interaction of adenine/thymine clusters with the replication initiation factor ORC. ResultsThe SpOrc1 or SpOrc2 immunoprecipitates (IPs) containing at least four subunits of SpORC, interacted with the ars2004 fragment, which is derived from a predominant replication origin on the chromosome. SpORC-IPs preferentially interacted with two regions of the ars2004, which consist of consecutive adenines and AAAAT repeats and are essential for ARS activity. The nucleotide sequences required for the interaction with SpORC-IPs correspond closely to those necessary for in vivo ARS activity. ConclusionOur results suggest that the SpORC interacts with adenine/thymine stretches, which have been shown to be the most important component in the fission yeast replication origin. The presence of multiple SpORC-binding sites, with certain sequence variations, is characteristic for the fission yeast replication origins. [ABSTRACT FROM AUTHOR]

Abstract Background: The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described. Results: We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK. Conclusion: In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK... [ABSTRACT FROM AUTHOR]

BackgroundProkaryotic translational release factors, RF1 and RF2, catalyse protein release at UAG/UAA and UGA/UAA stop codons, respectively. Mutations in RF1 and RF2 are known to cause non-sense suppression for UAG (amber) and UGA (opal) codons, respectively, and they do not exert a reciprocal (‘cross’) suppression phenotype. We aimed to isolate RF mutants of such cross-suppression activity, which we designated ‘Csu’ phenotype in this paper. ResultsUsing a lacZ (UAG) reporter, we selected amber suppressor alleles occurring in the plasmid-bearing RF2 gene of Salmonella typhimurium. Of nine such RF2 csu alleles, five were mis-sense mutations and four were non-sense mutations. The former mis-sense mutants retained the RF2 activity and catalysed UGA termination both in vivo and in vitro. RF2 C-terminal deletions equivalent to the non-sense alleles exerted amber suppression as well as opal suppression activity. Moreover, the equivalent RF1 segments also showed both the suppression phenotypes. ConclusionsAll the csu mutations were mapped at the C-terminal half of RF2 and are strikingly coincident with the highly conservative amino acids, suggesting that they affect the conserved function of bacterial RFs. We propose here that there should be an ‘initial binding’ step of RFs to the ribosome, preceding stop codon recognition (‘initial binding’ hypothesis) and that the N-terminal RF domain(s), that are truncated or affected by the csu mutations, are responsible for this step and interfere with the proper functioning of cognate release factors on the ribosome. [ABSTRACT FROM AUTHOR]

The article introduces the international journal "Genes to Cells." The journal aimed to provide an international forum for the publication of papers describing important aspects of molecular and cellular biology with the particular emphasis on conceptual advance in the field and understanding the basic mechanisms underlying biological events. "Genes to Cell" has received an outstanding reputation on its rigorous high standard.

Presents corrections to the paper dealing with a molecular mechanism for autoinhibition of the regulatory subunit of the phagocyte NADPH oxidase by Yuzawa et al.