Biology subjects

Yamada, M.

Publications and source records attributed to Yamada, M..

47 records · Page 3Linked to original sources

bioRxiv2020

The Superior Frontal Longitudinal Tract: Connection between the Dorsal Premotor and the Dorsolateral Prefrontal Cortices

The structural connection between the dorsal premotor (PMd) and the lateral prefrontal cortices (DLPFC) has been revealed, in a few studies, as the frontal longitudinal system (FLS). This study conducted a tractography analysis and a limited, postmortem, white-fiber dissection to investigate the superior FLS tract (SFLT) and analyze both its symmetry and termination point patterns. An analysis of spatial location, termination points, laterality, and correlation with the subjects gender or handedness was performed. SFLT was constructed in 100% of right and 88% of left hemispheres. The tracts exhibited variable patterns in different subjects in their posterior terminations. Additionally, the SFLT was found to possess a complex spatial relationship with the adjacent bundles. The SFLT was revealed successfully in two right hemispheres, where the posterior terminations were found to originate in the PMd, and its posterior terminations being totally separate from the superior longitudinal fasciculus.

neuroscience↗

bioRxiv2019

AUTS2 regulation of synapses for proper synaptic inputs and social communication.

Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.

neuroscience↗

bioRxiv2019

Novel roles of Kinesin-13 and Kinesin-8 during cell growth and division in the moss Physcomitrella patens

Kinesin-13 and -8 are well-known microtubule (MT) depolymerases that regulate MT length and chromosome movement in animal mitosis. While much is unknown about plant Kinesin-8, Arabidopsis and rice Kinesin-13 have been shown to depolymerise MTs in vitro. However, mitotic function of both kinesins has yet to be understood in plants. Here, we generated the complete null mutants in plants of Kinesin-13 and -8 in the moss Physcomitrella patens. Both kinesins were found to be non-essential for viability, but the Kinesin-13 knockout (KO) line had increased mitotic duration and reduced spindle length, whereas the Kinesin-8 KO line did not display obvious mitotic defects. Surprisingly, spindle MT poleward flux, for which Kinesin-13 is responsible for in animals, was retained in the absence of Kinesin-13. Concurrently, MT depolymerase activity of either moss kinesins could not be observed, with MT catastrophe inducing (Kinesin-13) or MT gliding (Kinesin-8) activity observed in vitro. Interestingly, both KO lines showed waviness in their protonema filaments, which correlated with positional instability of the MT foci in their tip cells. Taken together, the results suggest that plant Kinesin-13 and -8 have diverged in both mitotic function and molecular activity, acquiring new roles in regulating MT foci positioning for directed tip-growth.\n\nOne sentence summaryThis study uncovered the roles of Kinesin-13 and Kinesin-8 in regulating microtubule dynamics for mitotic spindle formation and straight tip cell growth in the moss Physcomitrella patens

cell biology↗

bioRxiv2019

Critical domains of moss KCBP kinesin for cargo transport

KCBP is a microtubule (MT) minus-end-directed kinesin widely conserved in plants. It was shown in Arabidopsis that KCBP controls trichome cell shape by orchestrating MT and actin cytoskeletons using its tail and motor domains. In contrast, the KCBP knockout (KO) line in the moss Physcomitrella patens showed a defect in nuclear and organelle positioning in apical stem cells. Moss KCBP is postulated to transport the nucleus and chloroplast via direct binding to their membranes, since it binds to and transports liposomes composed of phospholipids in vitro. However, domains required for cargo transport in vivo have not been mapped. Here, we performed a structure-function analysis of moss KCBP. We found that the FERM domain in the tail region, which is known to bind to lipids as well as other proteins, is essential for both nuclear and chloroplast positioning, whereas the proximal MyTH4 domain plays a supporting role in chloroplast transport. After anaphase but prior to nuclear envelope re-formation, KCBP accumulates on the chromosomes, in particular at the centromeric region in a FERM-dependent manner. In the KCBP knockout line, poleward chromosome motility in anaphase was reduced and lagging chromosomes occasionally appeared. These results suggest that KCBP binds to non-membranous naked chromosomes via an unidentified protein(s) for their transport. Finally, the liverwort orthologue of KCBP rescued the chromosome/chloroplast mis-positioning of the moss KCBP KO line, suggesting that the cargo transport function is conserved at least in bryophytes.

plant biology↗

bioRxiv2019

Phospho-tuning immunity through Denisovan, modern human, and mouse TNFAIP3 gene variants

Resisting or tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here, genomic analyses of anatomically modern humans, extinct Denisovan hominins, and mice revealed a series of missense variants in the immune response inhibitor A20 (encoded by TNFAIP3), substituting non-catalytic residues of the ubiquitin protease domain to diminish I{kappa}B-dependent phosphorylation and activation of A20. Two A20 variants with partial phosphorylation deficits appeared beneficial: one originating in Denisovans and introgressed in modern humans throughout Oceania, and another in a mouse strain resistant to Coxsackievirus. By contrast, a variant with 95% loss of phosphorylation caused spontaneous inflammatory disease in humans and mice. Analysis of the partial phosphorylation variant in mice revealed diminished tolerance of bacterial lipopolysaccharide or to poxvirus inoculation as trade-offs for enhanced immunity.\n\nOne Sentence SummaryModern and ancient variants reveal a genetically tunable element for balancing immunity and microbial tolerance.

immunology↗

bioRxiv2019

Block HSIC Lasso: model-free biomarker detection for ultra-high dimensional data

MotivationFinding nonlinear relationships between biomolecules and a biological outcome is computationally expensive and statistically challenging. Existing methods have crucial drawbacks, among others lack of parsimony, non-convexity, and computational overhead. Here we present the block HSIC Lasso, a nonlinear feature selector that does not present the previous drawbacks. ResultsWe compare the block HSIC Lasso to other state-of-the-art feature selection techniques in synthetic data and real data, including experiments over three common types of genomic data: gene-expression microarrays, single-cell RNA-seq, and GWAS. In all the cases, we observe that features selected by block HSIC Lasso retain more information about the underlying biology than features of other techniques. As a proof of concept, we applied the block HSIC Lasso to a single-cell RNA-seq experiment on mouse hippocampus. We discovered that many genes linked in the past to brain development and function are involved in the biological differences between the types of neurons. AvailabilityBlock HSIC Lasso is implemented in the Python 2/3 package pyHSICLasso, available in Github (https://github.com/riken-aip/pyHSICLasso) and PyPi (https://pypi.org/project/pyHSICLasso). Contactmyamada@i.kyoto-u.ac.jp Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2018

Age of onset in genetic prion disease and the design of preventive clinical trials

Regulatory agencies worldwide have adopted programs to facilitate drug development for diseases where the traditional approach of a randomized trial with a clinical endpoint is expected to be prohibitively lengthy or difficult. Here we provide quantitative evidence that this criterion is met for the prevention of genetic prion disease. We assemble age of onset or death data from N=1,094 individuals with high penetrance mutations in the prion protein gene (PRNP), generate survival and hazard curves, and estimate statistical power for clinical trials. We show that, due to dramatic and unexplained variability in age of onset, randomized preventive trials would require hundreds or thousands of at-risk individuals in order to be statistically powered for an endpoint of clinical onset, posing prohibitive cost and delay and likely exceeding the number of individuals available for such trials. Instead, the characterization of biomarkers suitable to serve as surrogate endpoints will be essential for the prevention of genetic prion disease. Biomarker-based trials may require post-marketing studies to confirm clinical benefit. Parameters such as longer trial duration, increased enrollment, and the use of historical controls in a post-marketing study could provide opportunities for subsequent determination of clinical benefit.

neuroscience↗

bioRxiv2018

Antibacterial effects of nanoimprinted moth-eye film in practical settings

Recent studies report that surfaces displaying micrometer-or nanometer-sized undulating structures exhibit antibacterial effects. In previous work, we described the use of an advanced nanofabrication technique to generate an artificial biomimetic moth-eye film by coating a polyethylene terephthalate (PET) film with nanoscale moth-eye protrusions made from a hydrophilic resin. This moth-eye film exhibited enhanced antibacterial effects in in vitro experiments. The aim of the present study was to verify the antibacterial efficacy of the Moth-eye film in practical environments. Three types of films (Moth-eye film, Flat film, and PET film) were used to compare antibacterial effects. Sample films were pasted onto hand-wash sinks at the testing locations. After several hours of elapsed time, bacteria from the surface of sample films were collected using one of three kinds of culture media stampers (to permit identification of bacterial species). The stampers were incubated for 48 hours at 35 {degrees}C, and the numbers of colonies were counted.\n\nThe number of common bacteria including E. coli and S. aureus from the Moth-eye film was significantly lower than that from the PET film (p<0.05) and that from the Flat film at 1 hour (p<0.05). This study found that the Moth-eye film had durability of antibacterial effect and the Moth-eye structure (PET coated with nanoscale cone-shaped pillars) had a physical antibacterial effect from the earlier time points. Therefore, the Moth-eye film might be useful for general-purpose applications in practical environments.

microbiology↗

bioRxiv2018

KCH kinesin drives nuclear transport and cytoskeletal coalescence for tip cell growth

Long-distance transport along microtubules (MTs) is critical for intracellular organisation. In animals, antagonistic motor proteins kinesin (plus end-directed) and dynein (minus end-directed) drive cargo transport. In land plants, however, the identity of motors responsible for transport is poorly understood, as genes encoding cytoplasmic dynein are missing. How other functions of dynein are brought about in plants also remains unknown. Here, we show that a subclass of the kinesin-14 family, KCH--which can also bind actin--drives MT minus end-directed nuclear transport in the moss Physcomitrella patens. When all four KCH genes were deleted, the nucleus was not maintained in the cell centre but was translocated to the apical end of protonemal cells. In the knockout (KO) line, apical cell tip growth was also severely suppressed. KCH was localised on MTs, including at the MT focal point near the tip where MT plus ends coalesced with actin filaments. MT focus was not persistent in KCH KO lines, whereas actin destabilisation also disrupted the focus despite KCH remaining on unfocused MTs. Functions of nuclear transport and tip growth were distinct, as a truncated KCH construct restored nuclear transport activity but not tip growth retardation of the KO line. Thus, our study identified KCH as a long-distance retrograde transporter as well as a cytoskeletal crosslinker, reminiscent of the versatile animal dynein.

cell biology↗

bioRxiv2018

Root meristem growth factor 1 controls root meristem size through reactive oxygen species signaling

Stem cell niche and root meristem size are maintained by intercellular interactions and signaling networks of a plant peptide hormone, Root Meristem Growth Factor 1 (RGF1). How RGF1 regulates root meristem development is an essential question to understand stem cell function. Although five receptors of RGF1 have recently been identified, the downstream signaling mechanism remains unknown. Here, we report a series of signaling events following RGF1 action. The RGF1-receptor pathway controls distribution of reactive oxygen species (ROS) along the developmental zones of the Arabidopsis root. We identify a novel transcription factor, RGF1 INDUCIBLE TRANSCRIPTION FACTOR 1 (RITF1), which plays a central role in mediating RGF1 signaling. Manipulating RITF1 expression leads to redistribution of ROS along the root developmental zones. Changes in ROS distribution, in turn, enhance the stability of the PLETHORA2 (PLT2) protein, a master regulator of root stem cells. Taken together, our study clearly depicts a signaling cascade initiated by RGF1 and links the RGF1 peptide to ROS regulatory mechanisms.

plant biology↗

bioRxiv2017

Multiple kinesin-14 family members drive microtubule minus-end-directed transport in plant cells

Minus-end-directed cargo transport along microtubules (MTs) is exclusively driven by the molecular motor dynein in a wide variety of cell types. Interestingly, plants have lost the genes encoding dynein during evolution; the MT motors that compensate for dynein function are unknown. Here, we show that two members of the kinesin-14 family drive minus-end-directed transport in plants. Gene knockout analyses of the moss Physcomitrella patens revealed that the plant-specific class-VI kinesin-14, KCBP, is required for minus-end-directed transport of the nucleus and chloroplasts. Purified KCBP directly bound to acidic phospholipids (PLs) and unidirectionally transported PL liposomes along MTs in vitro. Thus, minus-end-directed transport of membranous cargoes might be driven by their direct interaction with this motor protein. Newly nucleated cytoplasmic MTs represent another known cargo exhibiting minus-end-directed motility, and we identified the conserved class-I kinesin-14 (ATK) as the motor involved. These results suggest that kinesin-14 motors were duplicated and developed as alternative MT-based minus-end-directed transporters in land plants.

cell biology↗