Phylogenetic trees provide insight into the evolutionary trajectories of species and molecules. However, because (2n-5)! Phylogenetic trees can be constructed from a dataset containing n sequences, but this method of phylogenetic tree construction is not ideal from the viewpoint of a combinatorial explosion to determine the optimal tree using brute force. Therefore, we developed a method for constructing a phylogenetic tree using a Fujitsu Digital Annealer, a quantum-inspired computer that solves combinatorial optimization problems at a high speed.
View Article and Find Full Text PDFPhylogenetic trees are essential tools in evolutionary biology that present information on evolutionary events among organisms and molecules. From a dataset of n sequences, a phylogenetic tree of (2n-5)!! possible topologies exists, and determining the optimum topology using brute force is infeasible. Recently, a recursive graph cut on a graph-represented-similarity matrix has proven accurate in reconstructing a phylogenetic tree containing distantly related sequences.
View Article and Find Full Text PDFRecently, cultured meat obtained from livestock-derived cells is being considered as a sustainable food source that reduces the use of natural resources. This study aimed to show that nutrients extracted from Chlorella vulgaris were beneficial in the culture of primary bovine myoblasts (PBMs), a major cell source for cultured meat production. Nutrients (glucose, amino acids, and vitamins) present in the animal-cell culture media were effectively recovered from C.
View Article and Find Full Text PDFAmyloid precursor protein (APP) family members are involved in essential neuronal development including neurite outgrowth, neuronal migration and maturation of synapse and neuromuscular junction. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expressed in neurons and has specialized functions during synaptogenesis. Although a potential role for APLP1 in neuronal evolution has been indicated, its precise evolutionary and functional contributions are unknown.
View Article and Find Full Text PDFBiochem Biophys Res Commun
March 2020
Cereblon (CRBN) was identified as a gene that causes intellectual disabilities. The encoded CRBN protein, containing 442 amino acids, is located in several organs. Cytosolic CRBN was reported to mainly act as a component of the E3 ubiquitin ligase complex.
View Article and Find Full Text PDFMammalian cells have been used in various research fields. More recently, cultured cells have been used as the cell source of "cultured meat." Cell cultivation requires media containing nutrients, of which glucose and amino acids are the essential ones.
View Article and Find Full Text PDFCereblon (CRBN) is a substrate recognition subunit of the CRL4 E3 ubiquitin ligase complex, directly binding to specific substrates for poly-ubiquitination followed by proteasome-dependent degradation of proteins. Cellular CRBN is responsible for energy metabolism, ion-channel activation, and cellular stress response through binding to proteins related to the respective pathways. As CRBN binds to various proteins, the selective pressure at the interacting surface is expected to result in functional divergence.
View Article and Find Full Text PDFCereblon (CRBN) is a substrate receptor for an E3 ubiquitin ligase that directly binds to target proteins resulting in cellular activities, such as energy metabolism, membrane potential regulation, and transcription factor degradation. Genetic mutations in human CRBN lead to intellectual disabilities. In addition, it draws pathological attention because direct binding with immunomodulatory drugs can cure multiple myeloma (MM) and lymphocytic leukemia.
View Article and Find Full Text PDFGe-132 is a synthetic organic germanium that is used as a dietary supplement. The antioxidant activity of Ge-132 on cultured mammalian cells was investigated in this study. First, Ge-132 cytotoxicity on mammalian cultured cells was determined by measuring lactate dehydrogenase (LDH) levels.
View Article and Find Full Text PDFThalidomide was originally used as a sedative and found to be a teratogen, but now thalidomide and its derivatives are widely used to treat haematologic malignancies. Accumulated evidence suggests that thalidomide suppresses nerve cell death in neurologic model mice. However, detailed molecular mechanisms are unknown.
View Article and Find Full Text PDFAmyloid β protein (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Point mutations in the Aβ sequence, which cluster around the central hydrophobic core of the peptide, are associated with familial AD (FAD). Several mutations have been identified, with the Arctic mutation exhibiting a purely cognitive phenotype that is typical of AD.
View Article and Find Full Text PDFCereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity.
View Article and Find Full Text PDFLon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix, and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual disability-associated and thalidomide-binding protein cereblon (CRBN) contains a large, highly conserved Lon domain.
View Article and Find Full Text PDFThe gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown.
View Article and Find Full Text PDFCereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear.
View Article and Find Full Text PDFAmyloid β protein (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Point mutations within the Aβ sequence associated with familial AD (FAD) are clustered around the central hydrophobic core of Aβ. Several types of mutations within the Aβ sequence have been identified, and the 'Arctic' mutation (E22G) has a purely cognitive phenotype typical of AD.
View Article and Find Full Text PDFWe propose, as an alternative to conventional spectroscopic assays, a simple method for discriminating fibrous amyloid proteins by using a label-free semiconductor-based biosensor. The highly sensitive assay is expected to be useful for accelerating amyloid related research.
View Article and Find Full Text PDFThe proton motive force (PMF) is bio-energetically important for various cellular reactions to occur. We developed PMF-photogenerating mitochondria in cultured mammalian cells. An archaebacterial rhodopsin, delta-rhodopsin, which is a light-driven proton pump derived from Haloterrigena turkmenica, was expressed in the mitochondria of CHO-K1 cells.
View Article and Find Full Text PDFAnn N Y Acad Sci
November 2006
Here we overview Disrupted-in-Schizophrenia-1 (DISC1), a promising lead in studying the pathophysiology of major mental conditions. Genetic association studies reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar disorder in several ethnic groups. Different from several other susceptibility genes for schizophrenia, such as neuregulin-1 and dysbindin, there are two independent pedigrees in which genetic variations of DISC1 directly segregate with major mental conditions.
View Article and Find Full Text PDFHere we analyze the species conservation of disrupted-in-schizophrenia-1 (DISC1) gene, a susceptibility gene for schizophrenia. We cloned cDNA of DISC1 and characterized DISC1 protein in monkey brains and compared their features with those in a variety of species, including humans, rodents and lower vertebrates. Sequences of human and monkey DISC1 are very similar for both nucleotides and amino acids, in sharp contrast to those of rodents; this is reminiscent of G72, another gene involved in major mental illnesses.
View Article and Find Full Text PDFDisrupted-In-Schizophrenia-1 (DISC1), originally identified at the breakpoint of a chromosomal translocation that is linked to a rare familial schizophrenia, has been genetically implicated in schizophrenia in other populations. Schizophrenia involves subtle cytoarchitectural abnormalities that arise during neurodevelopment, but the underlying molecular mechanisms are unclear. Here, we demonstrate that DISC1 is a component of the microtubule-associated dynein motor complex and is essential for maintaining the complex at the centrosome, hence contributing to normal microtubular dynamics.
View Article and Find Full Text PDFDisrupted-In-Schizophrenia 1 (DISC1) was identified as the sole gene whose ORF is truncated and cosegregates with major mental illnesses in a Scottish family. DISC1 has also been suggested, by association and linkage studies, to be a susceptibility gene for schizophrenia (SZ) in independent populations. However, no analysis of DISC1 protein in human brains, especially those of patients with SZ, has yet been conducted.
View Article and Find Full Text PDFLipid rafts and their component, cholesterol, modulate the processing of beta-amyloid precursor protein (APP). However, the role of sphingolipids, another major component of lipid rafts, in APP processing remains undetermined. Here we report the effect of sphingolipid deficiency on APP processing in Chinese hamster ovary cells treated with a specific inhibitor of serine palmitoyltransferase, which catalyzes the first step of sphingolipid biosynthesis, and in a mutant LY-B strain defective in the LCB1 subunit of serine palmitoyltransferase.
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