Untargeted/Targeted 2D Gas Chromatography/Mass Spectrometry Detection of the Total Volatile Tea Metabolome

Identifying all analytes in a natural product is a daunting challenge, even if fractionated by volatility. In this study, comprehensive two-dimensional gas chromatography/mass spectrometry (GC×GC-MS) was used to investigate relative distribution of volatiles in green, pu-erh tea from leaves collected at two different elevations (1162 m and 1651 m). A total of 317 high and 280 low elevation compounds were detected, many of them known to have sensory and health beneficial properties. The samples were evaluated by two different software. The first, GC Image, used feature-based detection algorithms to identify spectral patterns and peak-regions, leading to tentative identification of 107 compounds. The software produced a composite map illustrating differences in the samples. The second, Ion Analytics, employed spectral deconvolution algorithms to detect target compounds, then subtracted their spectra from the total ion current chromatogram to reveal untargeted compounds. Compound identities were more easily assigned, since chromatogram complexities were reduced. Of the 317 compounds, for example, 34% were positively identified and 42% were tentatively identified, leaving 24% as unknowns. This study demonstrated the targeted/untargeted approach taken simplifies the analysis time for large data sets, leading to a better understanding of the chemistry behind biological phenomena

Reductive Elimination from Cyclometalated Platinum(IV) Complexes To Form Csp2−Csp3 Bonds and Subsequent Competition between Csp2−H and Csp3−H Bond Activation

Reductive elimination reactions of the cyclometalated platinum(IV) compounds [PtMe2Br{C6H4CH NCH2(4-ClC6H4)}L] (L = SMe2, PPh3) to form Csp3−Csp2 bonds, followed by either exclusive Csp2−H bond activation (L = SMe2) or competition between Csp2−H and Csp3−H bond activation (L = PPh3) are reported. Reductive elimination to form a C−Br bond is also reported.</p

Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine astrocytes, as well as patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we further show that sex differences in p21-induced senescence are patterned during early development by gonadal sex. These data provide a rationale for the further study of sex differences in radiation response and how senescence might be enhanced for radiation sensitization. The determination that p21 and gonadal sex are required for sex differences in radiation response will serve as a foundation for these future mechanistic studies

Reductive Elimination From Cyclometalated Platinum Complexes with Chelate Ligands to Form New Cyclometalated Species that Contain an SP3-SP2 Coupling

Imine ligands are stirred at room temperature in acetone for an extended amount of time to produce cyclometalated Pt(IV) compounds [PtMe2X1{4-X2C6H3CH=NCH2(4-X3C6H4)}L] (L= SMe2 or PPh3) (X1, X2, X3 = Br, Cl, Me, or H). These compounds are subjected to thermolysis reactions where Csp3-Csp2 reductive elimination occurs and subsequently activation of either exclusive Csp2-H bonds (L = SMe2) or competition between Csp2-H and Csp3-H bonds (L = PPh3). A side reaction with Csp2-X (X = Br or Cl) reductive elimination is also reported

Direct Contact Sorptive Extraction: A Robust Method for Sampling Plant Volatiles in the Field

Plants produce volatile organic compounds (VOCs) with diverse structures and functions, which change in response to environmental stimuli and have important consequences for interactions with other organisms. To understand these changes, <i>in situ</i> sampling is necessary. In contrast to dynamic headspace (DHS), which is the most often employed method, direct contact sampling employing a magnetic stir bar held in place by a magnet eliminates artifacts produced by enclosing plant materials in glass or plastic chambers. Direct-contact sorptive extraction (DCSE) using polydimethylsiloxane coated stir bars (Twisters) coated stir bars is more sensitive than DHS, captures a wider range of compounds, minimizes VOC collection from neighboring plants, and distinguishes the effects of herbivory in controlled and field conditions. Because DCSE is relatively inexpensive and simple to employ, scalability of field trials can be expanded concomitant with increased sample replication. The sensitivity of DCSE combined with the spectral deconvolution data analysis software makes the two ideal for comprehensive, <i>in situ</i> profiling of plant volatiles

Regioselective C–H Activation Preceded by C_sp²–C_sp³ Reductive Elimination from Cyclometalated Platinum(IV) Complexes

Reductive elimination reactions of the cyclometalated platinum­(IV) compounds [PtMe₂Cl­{C₆H₄CHNCH₂(4-ClC₆H₄)}­L] and [PtMe₂Br­{C₆H₄CHNCH₂(C₆H₅)}­L] (L = SMe₂, PPh₃) to form C_sp³–C_sp² bonds, followed by either exclusive C_sp²–H bond activation (L = SMe₂) or competition between C_sp²–H and C_sp³–H bond activation (L = PPh₃), are reported. Isomerization to give <i>endo</i> products instead of the expected <i>exo</i> complex was observed for the ligand C₆H₄CHNCH₂(2-BrC₆H₅), and formation of an <i>endo</i> six-membered platinacycle occurs for the ligand 2,4,6-Me₃C₆H₂CHNCH₂(2-BrC₆H₄)

Cooperative p16 and p21 action protects female astrocytes from transformation

Abstract Mechanisms underlying sex differences in cancer incidence are not defined but likely involve dimorphism (s) in tumor suppressor function at the cellular and organismal levels. As an example, sexual dimorphism in retinoblastoma protein (Rb) activity was shown to block transformation of female, but not male, murine astrocytes in which neurofibromin and p53 function was abrogated (GBM astrocytes). Correlated sex differences in gene expression in the murine GBM astrocytes were found to be highly concordant with sex differences in gene expression in male and female GBM patients, including in the expression of components of the Rb and p53 pathways. To define the basis of this phenomenon, we examined the functions of the cyclin dependent kinase (CDK) inhibitors, p16, p21 and p27 in murine GBM astrocytes under conditions that promote Rb-dependent growth arrest. We found that upon serum deprivation or etoposide-induced DNA damage, female, but not male GBM astrocytes, respond with increased p16 and p21 activity, and cell cycle arrest. In contrast, male GBM astrocytes continue to proliferate, accumulate chromosomal aberrations, exhibit enhanced clonogenic cell activity and in vivo tumorigenesis; all manifestations of broad sex differences in cell cycle regulation and DNA repair. Differences in tumorigenesis disappeared when female GBM astrocytes are also rendered null for p16 and p21. These data elucidate mechanisms underlying sex differences in cancer incidence and demonstrate sex-specific effects of cytotoxic and targeted therapeutics. This has critical implications for lab and clinical research