Intra-familial transmission of Streptococcus dysgalactiae subsp. equisimilis (SDSE): A first case report and review of the literature.

BACKGROUND: Concern about Streptococcus dysgalactiae infections has been increasing worldwide, and many cases of invasive infections have been reported. Streptococcus dysgalactiae has two main subspecies: S. dysgalactiae subsp. equisimilis (SDSE) and S. dysgalactiae subsp. dysgalactiae (SDSD). The epidemiology of invasive SDSE infections is not well understood, and the exact numbers of human SDSE infections are not known because standard laboratories are not able to identify Lancefield group C streptococci (GCS) or group G streptococci (GGS) to the species level. SDSE is often present in skin lesions, and sites of SDSE colonization and focal SDSE infections serve as the principal reservoirs for the transmission of skin and soft-tissue infections. Although the person-to-person transmission of S. pyogenes infections has been reported, the intra-familial transmission of SDSE has not been reported. CASE PRESENTATION: We report two cases of cellulitis with bacteremia in a family. A 72-year-old female with cellulitis in her right lower extremity was hospitalized, and a 104-year-old male relative was hospitalized with cellulitis 2 days later. Two strains of Streptococcus dysgalactiae subsp. equisimilis were isolated from the blood of the patients. Single nucleotide polymorphism analysis of the bacterial genomes suggested that the two strains had the same origin. This is the first case report about the intra-familial transmission of Streptococcus dysgalactiae subsp. equisimilis. CONCLUSIONS: This is the first case report about the intra-familial transmission of Streptococcus dysgalactiae subsp. equisimilis.

Total Synthesis of (-)-Lepadiformine A via Radical Translocation-Cyclization Reaction.

Total synthesis of (-)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation-cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol. After the radical translocation-cyclization reaction, a hydroxymethyl group at the C-13 position was stereoselectively introduced by a one-pot partial reduction-allylation protocol of the unprotected lactam derivative. Finally, the total synthesis is completed by formation of a C ring.

Catalytic C(sp3)-H bond activation in tertiary alkylamines.

The development of robust catalytic methods to assemble tertiary alkylamines provides a continual challenge to chemical synthesis. In this regard, transformation of a traditionally unreactive C-H bond, proximal to the nitrogen atom, into a versatile chemical entity would be a powerful strategy for introducing functional complexity to tertiary alkylamines. A practical and selective metal-catalysed C(sp3)-H activation facilitated by the tertiary alkylamine functionality, however, remains an unsolved problem. Here, we report a Pd(II)-catalysed protocol that appends arene feedstocks to tertiary alkylamines via C(sp3)-H functionalization. A simple ligand for Pd(II) orchestrates the C-H activation step in favour of deleterious pathways. The reaction can use both simple and complex starting materials to produce a range of multifaceted γ-aryl tertiary alkylamines and can be rendered enantioselective. The enabling features of this transformation should be attractive to practitioners of synthetic and medicinal chemistry as well as in other areas that use biologically active alkylamines.

Total Synthesis of (-)-Histrionicotoxin through a Stereoselective Radical Translocation-Cyclization Reaction.

Stereoselective total syntheses of (-)-histrionicotoxin and (-)-histrionicotoxin 235A are described. The 1-azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation-cyclization reaction involving a chiral cyclic acetal; the use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity. The cyclization product was converted into (-)-histrionicotoxin 235A through a one-pot partial-reduction-allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (-)-histrionicotoxin.

Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression.

Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. Circadian variations in DNA synthesis and proliferation have been identified in tumor cells, but their relationship with intracellular iron levels is unclear. In this study, we identified a 24-h rhythm in iron regulatory protein 2 (IRP2) levels in colon-26 tumors implanted in mice. Our findings suggest that IRP2 regulates the 24-h rhythm of transferrin receptor 1 (Tfr1) mRNA expression post-transcriptionally, by binding to RNA stem-loop structures known as iron-response elements. We also found thatIrp2mRNA transcription is promoted by circadian clock genes, including brain and muscle Arnt-like 1 (BMAL1) and the circadian locomotor output cycles kaput (CLOCK) heterodimer. Moreover, growth in colon-26(Δ19) tumors expressing the clock-mutant protein (CLOCK(Δ19)) was low compared with that in wild-type colon-26 tumor. The time-dependent variation of cellular iron levels, and the proliferation rate in wild-type colon-26 tumor was decreased by CLOCK(Δ19)expression. Our findings suggest that circadian organization contributes to tumor cell proliferation by regulating iron metabolism in the tumor.

A disruption mechanism of the molecular clock in a MPTP mouse model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in the substantia nigra and dopamine depletion in the striatum. Although the motor symptoms are still regarded as the main problem, non-motor symptoms in PD also markedly impair the quality of life. Several non-motor symptoms, such as sleep disturbances and depression, are suggested to be implicated in the alteration in circadian clock function. In this study, we investigated circadian disruption and the mechanism in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP-treated mice exhibited altered 24-h rhythms in body temperature and locomotor activity. In addition, MPTP treatment also affected the circadian clock system at the genetic level. The exposure of human neuroblastoma cells (SH-SY5Y) to 1-metyl-4-phenylpyridinium (MPP(+)) increased or decreased the mRNA levels of several clock genes in a dose-dependent manner. MPP(+)-induced changes in clock genes expression were reversed by Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Most importantly, addition of ATP to the drinking water of MPTP-treated mice attenuated neurodegeneration in dopaminergic neurons, suppressed AMPK activation and prevented circadian disruption. The present findings suggest that the activation of AMPK caused circadian dysfunction, and ATP may be a novel therapeutic strategy based on the molecular clock in PD.

Novel display technique for reference images for visibility of temporal change on radiographs--color digital summation radiography.

PURPOSE: The present study investigated color digital summation radiography (CDSR) as a novel display technique for reference images for the visibility of temporal change on radiographs. In CDSR, only the parts with temporal differences are displayed in color. Moreover, all other parts are displayed in gray scale. MATERIALS AND METHODS: CDSR was defined as "radiographs combined by the additive color mixture method". The visibility of simulated nodules located in the lung fields and mediastinum was evaluated by 12 radiologists (mean experience, 9.8 years; range, 1-26 years) for 24 conventional radiographs and CDSR for 6 color patterns. A five-point rating system (5, very good; 4, good; 3, adequate; 2, poor; 1, very poor) was used. RESULTS: The mean scores (average +/- standard deviation) for the visibility of simulated nodules were as follows: magenta, 3.88 +/- 0.90; blue, 3.08 +/- 0.72; green, 3.04 +/- 0.86; red, 3.00 +/- 0.98; cyan, 2.71 +/- 0.86; and yellow, 2.50 +/- 0.72. Compared to conventional radiography in gray scale, at 1.21 +/- 0.41, all six color patterns for CDSR displayed significantly improved scores (p<0.001). CONCLUSION: CDSR might represent a useful technique for reference images from chest digital radiography.