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It is shown that laminin-1 binds to alphaDG (alpha-dystroglycan) via LG4-5, causing syntrophin to become phosphorylated on a tyrosine and allowing Grb2 to bind via its SH2 domain. A model for how this phosphorylation may initiate downstream events, such as binding of Sos1/2 or syntrophin phosphorylation on tryosine, in laminin signaling is presented.

The synthesis of 3'-fluoro-2',3'-dideoxy-2',3'-didehydro-4'-ethynyl D- and L-furanosyl nucleosides, starting from 2,3-O-isopropylidene-D-glycer-aldehyde, is reported. The newly synthesized 4'-substituted nucleosides are tested for their activities against HIV, among which the D-adenine derivative showed moderate anti-HIV activity without significant cytotoxicity.

Simultaneous detection of cancer biomarkers holds great promise for the early diagnosis of cancer. In the present work, an ultrasensitive and reliable surface-enhanced Raman scattering (SERS) sensor has been developed for simultaneous detection of multiple liver cancer related microRNA (miRNA) biomarkers. We first proposed a novel strategy for the synthesis of nanogap-based SERS nanotags by modifying gold nanoparticles (AuNPs) with thiolated DNA and nonfluorescent small encoding molecules. We also explored a simple approach to a green synthesis of hollow silver microspheres (Ag-HMSs) with bacteria as templates. On the basis of the sandwich hybridization assay, probe DNA-conjugated SERS nanotags used as SERS nanoprobes and capture DNA-conjugated Ag-HMSs used as capture substrates were developed for the detection of target miRNA with a detection limit of 10 fM. Multiplexing capability for simultaneous detection of the three liver cancer related miRNAs with the high sensitivity and specificity was demonstrated using the proposed SERS sensor. Furthermore, the practicability of the SERS sensor was supported by the successful determination of target miRNA in cancer cells. The experimental results indicated that the proposed strategy holds significant potential for multiplex detection of cancer biomarkers and offers the opportunity for future applications in clinical diagnosis. [ABSTRACT FROM AUTHOR]

Hydrogen atom abstraction from allylic C-H bonds by molecular oxygen plays a very important role in determining the reactivity of fuel molecules having allylic hydrogen atoms. Rate constants for hydrogen atom abstraction by molecular oxygen from molecules with allylic sites have been calculated. A series of molecules with primary, secondary, tertiary, and super secondary allylic hydrogen atoms of alkene, furan, and alkylbenzene families are taken into consideration. Those molecules include propene, 2-butene, isobutene, 2-methylfuran, and toluene containing the primary allylic hydrogen atom; 1-butene, 1-pentene, 2-ethylfuran, ethylbenzene, and n-propylbenzene containing the secondary allylic hydrogen atom; 3-methyl-1-butene, 2-isopropylfuran, and isopropylbenzene containing tertiary allylic hydrogen atom; and 1-4-pentadiene containing super allylic secondary hydrogen atoms. The M06-2X/6-311++G(d,p) level of theory was used to optimize the geometries of all of the reactants, transition states, products and also the hinder rotation treatments for lower frequency modes. The G4 level of theory was used to calculate the electronic single point energies for those species to determine the 0 K barriers to reaction. Conventional transition state theory with Eckart tunnelling corrections was used to calculate the rate constants. The comparison between our calculated rate constants with the available experimental results from the literature shows good agreement for the reactions of propene and isobutene with molecular oxygen. The rate constant for toluene with O2 is about an order magnitude slower than that experimentally derived from a comprehensive model proposed by Oehlschlaeger and coauthors. The results clearly indicate the need for a more detailed investigation of the combustion kinetics of toluene oxidation and its key pyrolysis and oxidation intermediates. Despite this, our computed barriers and rate constants retain an important internal consistency. Rate constants calculated in this work have also been used in predicting the reactivity of the target fuels of 1-butene, 2-butene, isobutene, 2-methylfuran, 2,5-dimethylfuran, and toluene, and the results show that the ignition delay times for those fuels have been increased by a factor of 1.5-3. This work provides a first systematic study of one of the key initiation reaction for compounds containing allylic hydrogen atoms. [ABSTRACT FROM AUTHOR]

The development of highly sensitive, selective, nondestructive, and multiplexed imaging modalities is essential for latent fingerprint (LFP) identification and fingerprint residues detection. Herein, we present a versatile strategy to identify LFPs and to probe the multiple trace residues in a single LFP simultaneously. With the purpose of achieving high sensitivity, we for the first time introduced a polydopamine (PDA)-triggered Au growth method to prepare superbright and multiplex surface-enhanced Raman scattering (SERS) tags, which were endowed with high selectivity by conjugating with specific antibodies. In combination with a rapid Raman mapping technique, the sensitivity of the SERS probes was down to picogram scale and all the three levels of LFP features can be clearly seen. More significantly, the multiplexed imaging of diverse residues in a single LFP provides more accurate information than that using monochromatic imaging of individuals alone. The high analytical figures of merit enable this approach great promise for use in the fields ranging from chemical detection to molecular imaging. [ABSTRACT FROM AUTHOR]

Theoretical aspects of the development of a chemical kinetic model for the pyrolysis and combustion of a cyclic ketone, cyclopentanone, are considered. Calculated thermodynamic and kinetic data are presented for the first time for the principal species including 2- and 3-oxo-cyclopentyl radicals, which are in reasonable agreement with the literature. These radicals can be formed via H atom abstraction reactions by Ḣ and Ö atoms and ȮH, HȮ2, and ĊH3 radicals, the rate constants of which have been calculated. Abstraction from the β-hydrogen atom is the dominant process when ȮH is involved, but the reverse holds true for HȮ2 radicals. The subsequent β-scission of the radicals formed is also determined, and it is shown that recent tunable VUV photoionization mass spectrometry experiments can be interpreted in this light. The bulk of the calculations used the composite model chemistry G4, which was benchmarked in the simplest case with a coupled cluster treatment, CCSD(T), in the complete basis set limit. [ABSTRACT FROM AUTHOR]

A synergetic tert-butyl hydroperoxide/K3PO4-promoted oxidative cyclization has been developed for the facile synthesis of various functionalized quinazolin-4(3H)-ones from commercially available isatins and amidine hydrochlorides at room temperature. The synthetic utility of this strategy was illustrated by the convenient synthesis of tryptanthrin derivatives via a self-dimerization of isatins under the same conditions. [ABSTRACT FROM AUTHOR]

Herein we report an atom- and step-economic aromatic cyanoalkylation reaction that employs nitriles as building blocks and proceeds through Csp²--H and Csp³--H bond activation steps mediated by NiIII. In addition to cyanomethylation with MeCN, regioselective α-cyanoalkylation was observed with various nitrile substrates to generate secondary and tertiary nitriles. Importantly, to the best of our knowledge these are the first examples of C--H bond activation reactions occurring at a NiIII center, which may exhibit different reactivity and selectivity profiles than those corresponding to analogous NiII centers. These studies provide guiding principles to design catalytic C--H activation and functionalization reactions involving high-valent Ni species. [ABSTRACT FROM AUTHOR]

The article discusses research concerning the significant of in vitro diagnostic (IVF) diagnostic test on biological samples from a living body, such as urine, blood and tissue to determine or confirm the existence of disease in an individual. Topics include IVF's accessible diagnosis without invasive surgeries, prevent from biological safety problems in patients and quick valuable information concerning the healthcare conditions of patients.

A highly efficient Fe/Cu relay-catalyzeddomino protocol has beendeveloped for the synthesis of 2-phenylquinazolin-4-amines from commerciallyavailable ortho-halogenated benzonitriles, aldehydes,and sodium azide. This elegant domino process involved consecutiveiron-mediated [3 + 2] cycloaddition, copper-catalyzed SNAr, reduction, cyclization, oxidation, and copper-catalyzed denitrogenationsequences. The formed structure is the privileged core in drugs andbioactive molecules. [ABSTRACT FROM AUTHOR]

A one-electron reduced species of a cationic phosphorus(V) tetraazaporphyrin complex has been isolated as an air-stable solid. Cyclic voltammetry and magnetic measurements showed the species to be a neutral π radical, and the solid state structure was elucidated by single crystal X-ray diffraction analysis. Magnetic circular dichroism spectroscopy and theoretical calculations also support a 19π electron conjugated electronic circuit. [ABSTRACT FROM AUTHOR]

Herein we report the synthesis and reactivity of several organometallic NiIII complexes stabilized by a modified tetradentate pyridinophane ligand containing one phenyl group. A room temperature stable dicationic NiIII--disolvento complex was also isolated, and the presence of two available cis coordination sites in this complex offers an opportunity to probe the C-heteroatom bond formation reactivity of high-valent Ni centers. Interestingly, the NiIII-dihydroxide and NiIII-dimethoxide species can be synthesized, and they undergo aryl methoxylation and hydroxylation that is favored by addition of oxidant, which also limits the β-hydride elimination side reaction. Overall, these results provide strong evidence for the involvement of high-valent organometallic Ni species, possibly both NiIII and NiIV species, in oxidatively induced C-heteroatom bond formation reactions. [ABSTRACT FROM AUTHOR]

The phosphinoamide-linked Co/Hf complexes ICo(Ph2PNiPr)3HfCI (4), ICo(iPr2PNMes)3HfCI (5), and ICo(iPr2PNiPr)3HfCI (6) have been synthesized from the corresponding tris(phosphinoamide)HICI complexes (1-3) for comparison with the recently reported tris(phosphinoamide) Co/Zr complexes. Very minor structural and electronic differences between the Zr and Hf complexes were found when the N-iPr-substituted phosphinoamide ligands [Ph2PNiPr]- and [Pr2PNiPr]- were utilized. The reduction products [(THF)4Na-{(N2-Co(Ph2PNiPr)3HfCl}2]Na(THF)6 (7) and N2-Co(iPr2PNiPr)3Hf (9) are also remarkably similar to the corresponding Zr/Co analogues. In the case of Hf/Co and Zr/Co complexes linked by the N-Mes ligand [iPr2PNMes]- (Mes = 2,4,6-trimethylphenyl), however, more pronounced differences in structure, bonding, and reactivity are observed. While differences associated with S are still modest, larger variations are observed when comparing the two-electron reduction product [N2-Co(iPr2PNMes)3Hf-X] [Na(THF)5] (8) with its Zr congener. In addition to structural and spectroscopic differences, vastly different reactivity is observed, with 8 undergoing one-electron oxidation to form ClHf(MesNPiPr2)3CoN2 (II) in the presence of Mel, while a two-electron oxidative addition process occurs in a similar reaction with the Zr derivative. The activity of S toward Kumada coupling was investigated, finding significantly diminished activity in comparison to Co/Zr complexes. [ABSTRACT FROM AUTHOR]

The CrIIcomplexes CpCr[DppNC(Me)CHC(Me)NC6H4Y] (1; Dpp = 2,6-(Me2CH)2C6H3) were used to prepare the corresponding CrIIIiodo (2) and methyl (3) mixed-aryl β-diketiminate compounds with Y = OMe (a), CH3(b), H (c), CF3(d). Oxidation of the CrIIprecursors with iodine gave CpCr[DppNC(Me)CHC(Me)NC6H4Y](I) (2a−d). The CrIIImethyl compounds 3a−dwere prepared by reaction of the CrIIcomplexes with iodomethane followed by MeMgI. The CrIIIchloride complexes 4a−dwere synthesized by salt metathesis of isolated CpCrCl2(THF) with the appropriate deprotonated mixed-aryl β-diketiminate. The structures of the paramagnetic complexes 1b,c, 2a,b, 3a−d, and 4a−dwere determined by single-crystal X-ray diffraction. The rate constants for the single-electron oxidative addition of iodomethane with 1a−dwere determined by monitoring the reaction by UV−vis spectroscopy. The rate constants correlated well with the electronic parameters of the Y substituents (ρ = −0.36). The rate constants for 1a−dwere an order of magnitude greater than those previously obtained for the same reaction with CpCr[(DppNCMe)2CH] and related ortho-disubstituted symmetric β-diketiminate complexes. [ABSTRACT FROM AUTHOR]

4′-(4-{2-[4-(N,N-diphenylamino)phenyl]ethenyl}phenyl)-2,2′:6′,2′′-terpyridine is a highly conjugated compound, which is used to grow polymorphs. The results obtained suggest that polymorphs could appear as the Eu3+/Ag+-induced feature. Only three intermolecular C−H···π interactions stabilize the polymorph A in monoclinic space group C2/cwith Z= 8, while five intermolecular C−H···π interactions assume completely new pattern to arrange the Eu3+/Ag+-induced polymorph B in monoclinic space group P21/cwith Z= 4. The changes in patterns of the C−H···π interactions could impose on the molecular conformation, induced dipole, electronic delocalization and intra- and intermolecular electron transfer transition, and thus give rise to the very different photoelectric response for polymorphic forms. [ABSTRACT FROM AUTHOR]

The minimum capital cost/total annualized cost (MCC/MTAC) problem is investigated, within the infinite-dimensional state-space (IDEAS) framework, for homogeneous and isothermal reactor networks. The resulting mathematical formulation is an infinite-dimensional program with linear constraints and a separable concave objective function to be minimized. The global optimum of this infinite program is approximated through global solution of a series of finite-dimensional programs with concave separable objective functions and linear feasible regions. A branch-and-bound algorithm is used to solve globally each of these finite programs. The proposed methodology is illustrated with a reactor network synthesis case study aiming at capital cost minimization. [ABSTRACT FROM AUTHOR]

Previously, a signaling pathway was described [Oak, Zhou, and Jarrett (2003) J. Biol. Chem. 278, 39287-39295] that links matrix laminin binding on the outside of the sarcolemma to Grb2 binding to syntrophin on the inside surface of the sarcolemma and by way of Grb2-Sos1-Rac1-PAK1-JNK ultimately results in the phosphorylation of c-jun on Ser65. How this signaling is initiated was investigated. Grb2- binding to syntrophin is increased by the addition of either laminin-1 or the isolated laminin α1 globular domain modules LG4-5, a protein referred to as E3. This identifies the LG4-5 sequences as the region of laminin responsible for signaling. Since laminin α1 LG4 is known to bind α-dystroglycan, this directly implicates α-dystroglycan as the laminin-signaling receptor. E3 or laminin-1 increase Grb2-binding and Rac1 activation. In the presence of E3 or laminin-1, syntrophin is phosphorylated on a tyrosine residue, and this increases and alters Grb2 binding. The α-dystroglycan antibody, IIH6, which blocks binding of laminins to α-dystroglycan, blocks both the laminin-induced Sos1/2 recruitment and syntrophin phosphorylation, showing that it is α-dystroglycan binding the LG4-5 region of laminin that is responsible. The C-terminal SH3 domain of Grb2 (C-SH3) binds only to nonphosphorylated syntrophin, and phosphorylation causes the Grb2 SH2 domain to bind and prevents SH3 binding. Syntrophin, tyrosine phosphate, β-dystroglycan, and Rac1 all co-localize to the sarcolemma of rat muscle sections. A model for how this phosphorylation may initiate downstream events in laminin signaling is presented. [ABSTRACT FROM AUTHOR]

Shows that an acridine derivative incorporated within the sequence of an oligopyrimidine third strand strongly stabilizes the triple-helical complexes. Synthesis of the oligonucleotides and acridine-containing oligonucleotides; UV thermal denaturation; Static fluorescence measurements; Thermal denaturation experiments.

The reaction of 2,2'-bipyridine (bpy) with monomeric chromium(II) precursors was used to prepare the S = 1 complexes Cr(tBu-acac)2(bpy) (1) and (Ã5-Cp)(η¹-Cp)Cr(bpy) (3), as well as the S = 2 compound Cr[N(SiMe3)2]2(bpy) (4). The crystallographically determined bond lengths indicate that die bpy ligands in 1 and 3 are best regarded as radical anions, while 4 shows no structural evidence for electron transfer from Cr11 to the neutral bpy ligand. [ABSTRACT FROM AUTHOR]

Fucoxanthin, a natural carotenoid derived from algae, exhibits novel anticancer potential. However, fucoxanthin with high purity is hard to prepare, and the anticancer mechanism remains elusive. In the present study, fucoxanthin with high purity was prepared and purified from the marine microalgae Nitzschia sp. by silica-gel column chromatography (SGCC), and the underlying mechanism against human glioma cells was evaluated. The results showed that fucoxanthin time- and dose-dependently inhibited U251-human-glioma-cell growth by induction of apoptosis (64.4 ± 4.8, P < 0.01) accompanied by PARP cleavage and caspase activation (244 ± 14.2, P < 0.01). Mechanically, fucoxanthin time-dependently triggered reactive-oxygen-species (ROS)-mediated DNA damage (100 ± 7.38, P < 0.01), as evidenced by the phosphorylation activation of Ser1981-ATM, Ser428-ATR, Ser15-p53, and Ser139-histone. Moreover, fucoxanthin treatment also time-dependently caused dysfunction of MAPKs and PI3K-AKT pathways, as demonstrated by the phosphorylation activation of Thr183-JNK, Thr180-p38, and Thr202-ERK and the phosphorylation inactivation of Ser473-AKT. The addition of kinase inhibitors further confirmed the importance of MAPKs and PI3K-AKT pathways in fucoxanthin-induced cell-growth inhibition (32.5 ± 3.6, P < 0.01). However, ROS inhibition by the antioxidant glutathione (GSH) effectively inhibited fucoxanthin-induced DNA damage, attenuated the dysfunction of MAPKs and PI3K-AKT pathways, and eventually blocked fucoxanthin-induced cytotoxicity (54.3 ± 5.6, P < 0.05) and cell apoptosis (32.7 ± 2.5, P < 0.05), indicating that ROS production, an early apoptotic event, is involved in the fucoxanthin-mediated anticancer mechanism. Taken together, these results suggested that fucoxanthin induced U251-human-glioma-cell apoptosis by triggering ROS-mediated oxidative damage and dysfunction of MAPKs and PI3K-AKT pathways, which validated that fucoxanthin may be a candidate for potential applications in cancer chemotherapy and chemoprevention.