Laser spectroscopy and dynamic of transient species

Work on sub-Doppler spectroscopy of thioformaldehyde is nearing completion; the sub-Doppler structure in the H[sub 2]CS spectrum correlates with previous observations of anomalously long fluorescence lifetimes and reduced quantum yields of fluorescence under collision-free conditions. Singlet-triplet perturbations are large and occur haphazardly when levels in the two states are near- coincidence. High-resolution FTIR spectra of many bands of HCOCl and DCOCl have been recorded. Laser fluorescence on formic acid is being studied. Reactive jet spectroscopy is being used to produce new reactive intermediates in F[sub 2]/Ar gas streams. Preliminary experiments are underway in S[sub 3] and S[sub 4] systems

Laser spectroscopy and dynamics of transient species. Progress report, June 1, 1993--May 31, 1994

Work was done on sub-Doppler spectroscopy of thioformaldehyde, electronic spectrum of FS{sub 2} radical, FTIR spectra of the transient molecule formyl chloride (HCOCl and DCOCl), and high-resolution FTIR spectra of the {nu}{sub 9} (CH{sub 2} wag) and {nu}{sub 5} (CSO symm. stretch) bands of sulfine (H{sub 2}CSO), a transient species formed in pyrolysis of dimethyl sulfoxide and oxidation of thioformaldehyde

An analysis of the methyl rotation dynamics in the S0 (X̃ 1A1) and T1 (ã 3A2) states of thioacetone, (CH3)2 CS and (CD 3)2 CS from pyrolysis jet spectra

Jet-cooled, laser-induced phosphorescence excitation spectra (LIP) of thioacetone (CH3)2CS/(CD3)2 CS have been recorded over the region 16 800-18 500 cm-1 using the pyrolysis jet spectroscopic technique. The responsible electronic transition, T 1 ←-S0, ã 3 A ″ ← X̃ 1A1, results from an n → π* electron promotion and gives rise to a pattern of vibronic bands that were attributed to activity of the methyl torsion and the sulphur out-of-plane wagging modes. The intensities of the torsional and wagging progressions in the excitation spectra were interpreted in terms of a C2υ-Cs molecular distortion of the triplet molecule from its singlet ground state equilibrium structure. A complete unrestricted Hartree-Fock (UHF) ab initio molecular orbital (MO) structural optimization of the T1 state predicted that the sulphur was displaced by 27.36° from the molecular plane and the methyl groups were rotated by 10.93° in clockwise-counterclockwise directions. Restricted Hartree-Fock (RHF) calculations were used to generate the F(θ1,θ2) potential surface governing methyl rotation for the S0 state. This was incorporated into a two-dimensional Hamiltonian, symmetrized for the G36 point group and solved variationally for the torsional frequencies. The calculated frequencies of 159.97/118.94 for the ν17 (b1) mode of S0 (CH3)2CS/(CD3)2 CS were found to agree with the experimental values, 153.2/114.7 cm-1. © 1991 American Institute of Physics.The authors are grateful to the Natural Sciences and Engineering Research Council of Canada for financial support of this work. D. J. C. acknowledges the support of the National Science Foundation through Grant No. CHE-8914403.Peer Reviewe

Evidence for the prepattern/cooption model of vertebrate jaw evolution

The appearance of jaws was a turning point in vertebrate evolution because it allowed primitive vertebrates to capture and process large, motile prey. The vertebrate jaw consists of separate dorsal and ventral skeletal elements connected by a joint. How this structure evolved from the unjointed gill bar of a jawless ancestor is an unresolved question in vertebrate evolution. To understand the developmental bases of this evolutionary transition, we examined the expression of 12 genes involved in vertebrate pharyngeal patterning in the modern jawless fish lamprey. We find nested expression of Dlx genes, as well as combinatorial expression of Msx, Hand and Gsc genes along the dorso-ventral (DV) axis of the lamprey pharynx, indicating gnathostome-type pharyngeal patterning evolved before the appearance of the jaw. In addition, we find that Bapx and Gdf5/6/7, key regulators of joint formation in gnathostomes, are not expressed in the lamprey first arch, whereas Barx, which is absent from the intermediate first arch in gnathostomes, marks this domain in lamprey. Taken together, these data support a new scenario for jaw evolution in which incorporation of Bapx and Gdf5/6/7 into a preexisting DV patterning program drove the evolution of the jaw by altering the identity of intermediate first-arch chondrocytes. We present this “Pre-pattern/Cooption” model as an alternative to current models linking the evolution of the jaw to the de novo appearance of sophisticated pharyngeal DV patterning

Elucidating the role of Agl in bladder carcinogenesis by generation and characterization of genetically engineered mice

Amylo-\u3b1-1,6-glucosidase,4-\u3b1-glucanotransferase (AGL) is an enzyme primarily responsible for glycogen debranching. Germline mutations lead to glycogen storage disease type III (GSDIII). We recently found AGL to be a tumor suppressor in xenograft models of human bladder cancer (BC) and low levels of AGL expression in BC are associated with poor patient prognosis. However, the impact of low AGL expression on the susceptibility of normal bladder to carcinogenesis is unknown. We address this gap by developing a germline Agl knockout (Agl-/-) mouse that recapitulates biochemical and histological features of GSDIII. Agl-/- mice exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) had a higher BC incidence compared with wild-type mice (Agl+/+). To determine if the increased BC incidence observed was due to decreased Agl expression in the urothelium specifically, we developed a urothelium-specific conditional Agl knockout (Aglcko) mouse using a Uroplakin II-Cre allele. BBN-induced carcinogenesis experiments repeated in Aglcko mice revealed that Aglcko mice had a higher BC incidence than control (Aglfl/fl) mice. RNA sequencing revealed that tumors from Agl-/- mice had 19 differentially expressed genes compared with control mice. An 'Agl Loss' gene signature was developed and found to successfully stratify normal and tumor samples in two BC patient datasets. These results support the role of AGL loss in promoting carcinogenesis and provide a rationale for evaluating Agl expression levels, or Agl Loss gene signature scores, in normal urothelium of populations at risk of BC development such as older male smokers

Contributions of Muscles and External Forces to Medial Knee Load Reduction Due to Osteoarthritis Braces

Background Braces for medial knee osteoarthritis can reduce medial joint loads through a combination of three mechanisms: application of an external brace abduction moment, alteration of gait dynamics, and reduced activation of antagonistic muscles. Although the effect of knee bracing has been reported independently for each of these parameters, no previous study has quantified their relative contributions to reducing medial knee loads. Methods In this study, we used a detailed musculoskeletal model to investigate immediate changes in medial and lateral loads caused by two different knee braces: OA Assist and OA Adjuster 3 (DJO Global). Seventeen osteoarthritis subjects and eighteen healthy controls performed overground gait trials in unbraced and braced conditions. Results Across all subjects, bracing reduced medial loads by 0.1 to 0.3 times bodyweight (BW), or roughly 10%, and increased lateral loads by 0.03 to 0.2 BW. Changes in gait kinematics due to bracing were subtle, and had little effect on medial and lateral joint loads. The knee adduction moment was unaltered unless the brace moment was included in its computation. Only one muscle, biceps femoris, showed a significant change in EMG with bracing, but this did not contribute to altered peak medial contact loads. Conclusions Knee braces reduced medial tibiofemoral loads primarily by applying a direct, and substantial, abduction moment to each subject's knee. To further enhance brace effectiveness, future brace designs should seek to enhance the magnitude of this unloader moment, and possibly exploit additional kinematic or neuromuscular gait modifications

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

MicroRNA93 regulates proliferation and differentiation of normal and malignant breast stem cells

MicroRNAs (miRNAs) play important roles in normal cellular differentiation and oncogenesis. microRNA93 (mir-93), a member of the mir106b-25 cluster, located in intron 13 of the MCM7 gene, although frequently overexpressed in human malignancies may also function as a tumor suppressor gene. Using a series of breast cancer cell lines representing different stages of differentiation and mouse xenograft models, we demonstrate that mir-93 modulates the fate of breast cancer stem cells (BCSCs) by regulating their proliferation and differentiation states. In "claudin low" SUM159 cells, expression of mir-93 induces Mesenchymal-Epithelial Transition (MET) associated with downregulation of TGFβ signaling and downregulates multiple stem cell regulatory genes, including JAK1, STAT3, AKT3, SOX4, EZH1, and HMGA2, resulting in cancer stem cell (CSC) depletion. Enforced expression of mir-93 completely blocks tumor development in mammary fat pads and development of metastases following intracardiac injection in mouse xenografts. The effect of mir-93 on the CSC population is dependent on the cellular differentiation state, with mir-93 expression increasing the CSC population in MCF7 cells that display a more differentiated "luminal" phenotype. mir-93 also regulates the proliferation and differentiation of normal breast stem cells isolated from reduction mammoplasties. These studies demonstrate that miRNAs can regulate the states and fates of normal and malignant mammary stem cells, findings which have important biological and clinical implications. © 2012 Liu et al

Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons

During development, sympathetic neurons extend axons along a myriad of distinct trajectories, often consisting of arteries, to innervate one of a large variety of distinct final target tissues. Whether or not subsets of neurons within complex sympathetic ganglia are predetermined to innervate select end-organs is unknown. Here we demonstrate in mouse embryos that the endothelin family member Edn3 (ref. 1), acting through the endothelin receptor EdnrA (refs 2, 3), directs extension of axons of a subset of sympathetic neurons from the superior cervical ganglion to a preferred intermediate target, the external carotid artery, which serves as the gateway to select targets, including the salivary glands. These findings establish a previously unknown mechanism of axonal pathfinding involving vascular-derived endothelins, and have broad implications for endothelins as general mediators of axonal growth and guidance in the developing nervous system. Moreover, they suggest a model in which newborn sympathetic neurons distinguish and choose between distinct vascular trajectories to innervate their appropriate end organs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62906/1/nature06859.pd