Regulatory Roles of the N-Terminal Intrinsically Disordered Region of Modular Src.

Src, the prototype of Src family kinases (SFKs), is a modular protein consisting of SH4 (SH4) and unique (UD) domains in an N-terminal intrinsically disordered region (IDR), and SH3, SH2, and kinase (KD) folded domains conserved among SFKs. Src functions as a pleiotropic signaling hub in proliferating and post-mitotic cells, and it is related to cancer and neurological diseases. However, its regulatory mechanism is unclear because the existing canonical model is derived from crystallographic analyses of folded constructs lacking the IDR.

Nonphosphorylatable Src Ser75 Mutation Increases Ethanol Preference and Consumption in Mice.

Src is highly expressed in CNS neurons and contributes not only to developmental proliferation and differentiation but also to high-order brain functions, such as those contributing to alcohol consumption. Src knock-out mice exhibit no CNS abnormalities, presumably due to compensation by other Src family kinases (SFKs), but have a shortened lifespan and osteopetrosis-associated defects, impeding investigations of the role of Src on behavior in adult mice. However, the Unique domain of Src differs from those in other SFKs and is phosphorylated by cyclin-dependent kinase 1 (Cdk1) and Cdk5 at Ser75, which influences its postmitotic function in neurons.

Individual differences in torpor expression in adult mice are related to relative birth mass.

Daily torpor is a physiological adaptation in small mammals and birds, characterised by drastic reductions in metabolism and body temperature. Energy-constraining conditions, such as cold and starvation, are known to cause the expression of daily torpor. However, the reason for high degrees of inter- and intra-individual variation in torpor expression (TE) in similar situations is not clear.

A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice.

Src knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA).

Sheaf theoretic formulation for consciousness and qualia and relationship to the idealism of non-dual philosophies.

Questions about the nature of reality, whether Consciousness is the fundamental reality in the universe, and what is Consciousness itself, have no answer in systems that assume an external reality independent of Consciousness. Ultimately, the ontological foundation of such systems is the absolute division of subject and object. We advocate instead what we consider to be an approach that is in agreement with the foundation of quantum reality, which is based on Rāmānuja's version of Vedanta philosophy and non-dual Kashmir Śaivism.

Protein restriction does not affect body temperature pattern in female mice.

Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression.

Susceptibility of muridae cell lines to ecotropic murine leukemia virus and the cationic amino acid transporter 1 viral receptor sequences: implications for evolution of the viral receptor.

Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV infection, and treatment of rat and hamster cells with a glycosylation inhibitor, tunicamycin, enhances Eco-MLV infection. Although the mouse CAT1 is also glycosylated, it does not inhibit Eco-MLV infection.

Production of mouse ES cells homozygous for Cdk5-phosphorylated site mutation in c-Src alleles.

c-Src-null mutants have not provided a full understanding of the cellular functions of c-Src, reflecting the functional redundancy among Src family members. c-Src is phosphorylated by cyclin-dependent kinase 1 (Cdk1) and Cdk5 at Ser75 in the unique amino terminal c-Src-specific domain. The specific roles of c-Src may be assessed by establishing mouse embryonic stem (ES) cells homozygous for a point mutation at Ser75.