Conserved pattern-based classification of human odorant receptor multigene family.

Conserved protein-coding sequences are critical for maintaining protein function across species. Odorant receptors (ORs), a large poorly understood multigene family responsible for odor detection, lack comprehensive classification methods that reflect their functional diversity. In this study, we propose a new approach called conserved motif-based classification (CMC) for classifying ORs based on amino acid sequence similarities within conserved motifs.

The effect of ceramides on skin absorption by Raman spectroscopy.

Introduction: Ceramides are essential epidermal constituents that play a critical role in skin moisturization treatment as a raw material in cosmetics formulation. Recently, ceramides have been known to be frequently applied in various cosmetic formulations. Despite ceramide's beneficial characteristics, academic research regarding ceramides and their skin absorption remains insufficient.

Computer-Assisted Rehabilitation Shows Greater Efficacy Than Traditional in Visuospatial Skills and Cognition in Neglect Patients.

This study is crucial for improving unilateral spatial neglect (USN) treatments, focusing on comparing the effectiveness of computer-assisted cognitive rehabilitation (CACR) against conventional rehabilitation (CR) methods. It aimed to address a significant research gap and improve patient outcomes by evaluating the impact of CACR versus CR on visuospatial perception, visual field and attention, and visual memory in patients with USN. This study was a randomized controlled trial.

Cullin-RING E3 ubiquitin ligase 4 regulates neurite morphogenesis during neurodevelopment.

Neuritogenesis is crucial for establishing proper neuronal connections during brain development; its failure causes neurodevelopmental defects. Cullin-RING E3 ubiquitin ligase complexes participate in various neurodevelopmental processes by regulating protein stability. We demonstrated the regulatory function of Cullin-RING E3 ubiquitin ligase 4 (CRL4) in neurite morphogenesis during early neurodevelopment.

The mediating effect of caregiver burden on the caregivers' quality of life.

[Purpose] Quality of life (QoL) can be closely related to caregiver burden, which may be a potential mediating effect on the relationships among stroke patient caregivers. This study investigated the predictors of caregiver's QoL based on patient and caregiver characteristics, with caregiver burden as a mediator. [Methods] This study was conducted using surveys, a literature review, and interviews.

Production of anteiso-branched fatty acids in Escherichia coli; next generation biofuels with improved cold-flow properties.

Microbial fermentation is emerging as an increasingly important resource for the production of fatty acids to serve as precursors for renewable diesel as well as detergents, lubricants and other industrial chemicals, as an alternative to traditional sources of reduced carbon such as petroleum. A major disadvantage of fuels derived from biological sources is their undesirable physical properties such as high cloud and pour points, and high viscosity. Here we report the development of an Escherichia coli strain that efficiently produces anteiso-branched fatty acids, which can be converted into downstream products with lower cloud and pour points than the mixtures of compounds produced via the native metabolism of the cell.

The Relationship between Rehabilitation and Changes in Depression in Stroke Patients.

[Purpose] This study investigated the primary factors behind changes in depressive symptoms among stroke patients after 8 weeks of rehabilitation (physical, occupational, and cognitive therapy). [Methods] This study was conducted using a literature review, and electronic medical records from January, 2008 to December, 2009. Data were collected for 120 subjects with chronic stroke.

Heterologous expression and manipulation of three tetracycline biosynthetic pathways.

A very accommodating host: Three tetracycline biosynthetic pathways were overexpressed and manipulated in the heterologous host Streptomyces lividans K4-114. Through the inactivation of various genes and characterization of the resulting biosynthetic intermediates, new tetracycline-modifying enzymes were identified (see scheme).

Heterologous production of polyketides by modular type I polyketide synthases in Escherichia coli.

Heterologous production of polyketide compounds, an important class of natural products with complex chemical structures, was first demonstrated with Streptomyces parvulus in 1984. Although Streptomyces strains are good first options for heterologous polyketide biosynthesis, their slow growth kinetics prompt other hosts to also be considered. Escherichia coli provides key elements of an ideal host in terms of the growth rate, culture conditions, and available recombinant DNA tools.

Identification of three positive regulators in the geldanamycin PKS gene cluster of Streptomyces hygroscopicus JCM4427.

In the Streptomyces hygroscopicus JCM4427 geldanamycin biosynthetic gene cluster, Five putative regulatory genes were identified by protein homology searching. Among three of those genes, gel14, gel17, and gel19, are located downstream of polyketide synthase genes. Gel14 and Gel17 are members of the LAL family of transcriptional regulators, including an ATP/GTP-binding domain at the N-terminus and a DNA binding helix-turn-helix domain at the C-terminus.

Biochemical analysis of the biosynthetic pathway of an anticancer tetracycline SF2575.

SF2575 1 is a tetracycline polyketide produced by Streptomyces sp. SF2575 and displays exceptionally potent anticancer activity toward a broad range of cancer cell lines. The structure of SF2575 is characterized by a highly substituted tetracycline aglycon.

Rational biosynthetic engineering for optimization of geldanamycin analogues.

Tailor made: We report the rational biosynthesis of C15 hydroxylated non-quinone geldanamycin analogues by site-directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post-PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound. A rational biosynthetic engineering approach was applied to the optimization of the pharmacological properties of the benzoquinone ansamycin, geldanamycin.

Characterization of tailoring genes involved in the modification of geldanamycin polyketide in Streptomyces hygroscopicus JCM4427.

Geldanamycin and its analogs are important anticancer agents that inhibit the newly targeted, heat-shock protein (Hsp) 90, which is a chaperone protein in eukaryotic cells. To resolve which geldanamycin biosynthetic genes are responsible for particular post-polyketide synthase (PKS) processing steps and in which order the reactions occur, we individually inactivated candidate genes in Streptomyces hygroscopicus subsp. duamyceticus JCM4427, and isolated and elucidated the structures of intermediates from each mutant.

Synthesis and anticancer activity of geldanamycin derivatives derived from biosynthetically generated metabolites.

A new series of geldanamycin derivatives were synthesized using a semi-synthetic approach involving genetically engineered biosynthetic intermediates. These analogues were then evaluated for anti-proliferation activity in human cancer cell lines, SK-Br3 and SK-Ov3. Most of the synthesized compounds exhibited potent in vitro anti-proliferation activity toward both cell lines.

Cytotoxic 6-alkylsalicylic acids from the endophytic Streptomyces laceyi.

Two new 6-alkylsalicylic acids, salaceyins A and B were isolated by bioassay-guided fractionation from the culture of the endophytic Streptomyces laceyi MS53 and their structures were determined on the basis of spectroscopic data. Salaceyins A and B exhibited modest cytotoxicity against a human breast cancer cell line (SKBR3) with IC50 values of 3.0 and 5.

Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin.

The post-polyketide synthase modification of geldanamycin (1) biosynthesis is of interest as a means of introducing structural diversity into the compound. From the inactivation of a gene encoding carbamoyltransferase, we demonstrated that the C-17 hydroxylation and the C-21 oxidation precede O-carbamoylation and that the hypothetical progeldanamycin does not possess a double bond at C-4 and C-5. More importantly, our result revealed new intermediates 4,5-dihydro-7-O-descarbamoyl-7-hydroxygeldanamycin (3) and 4,5-dihydrogeldanamycin (5), indicating that O-carbamoylation occurs prior to the C-4,5 cis double bond formation in geldanamycin biosynthesis.

Escherichia coli periplasmic thiol peroxidase acts as lipid hydroperoxide peroxidase and the principal antioxidative function during anaerobic growth.

To clarify the enzymatic property of Escherichia coli periplasmic thiol peroxidase (p20), the specific peroxidase activity toward peroxides was compared with other bacterial thiol peroxidases. p20 has the most substrate preference and peroxidase activity toward organic hydroperoxide. Furthermore, p20 exerted the most potent lipid peroxidase activity.

Nuclear thiol peroxidase as a functional alkyl-hydroperoxide reductase necessary for stationary phase growth of Saccharomyces cerevisiae.

Yeast nucleus-localized thiol peroxidase (nTPx) was characterized as a functional peroxidase. There are two cysteine residues in nTPx. Replacement of Cys-106 or Cys-111 with serine resulted in a complete loss of thioredoxin-linked peroxidase activity.

Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock).