Metalloradical complex Co-C˙Ph3 catalyzes the CO2 reduction in gas phase: a theoretical study.

Metal-stabilized radicals have been increasingly exploited in modern organic synthesis. Here, we theoretically designed a metalloradical complex Co-C˙Ph3 with the triplet characters through the transition metal cobalt (Co0) coordinating a triphenylmethyl radical. The potential catalytic role of this novel metalloradical in the CO2 reduction with H2/CH4 in the gas phase was explored via density functional theory (DFT) calculations. For the CO2 reduction reaction with H2, there are two possible pathways: one (path A) is the activation of CO2 by Co-C˙Ph3, followed by the hydrogenation of CO2. The other (path B) starts from the splitting of the H-H bond by Co-C˙Ph3, leading to the transition-metal hydride complex CoH-H, which can reduce CO2. DFT computations show that path B is more favorable than path A as their rate-determining free energy barriers are 18.3 and 27.2 kcal mol-1, respectively. However, for the reduction of CO2 by CH4 two different products, CH3COOH and HCOOCH3, can be generated following different reaction routes. Both routes begin with one CH4 molecule approaching the metalloradical Co-C˙Ph3 to form the intermediate CoH-CH3. This intermediate can evolve following two different pathways, depending on whether the H bonded to Co is transferred to the O (pathway PO) or the C (pathway PC) of CO2. Comparing their rate-determining steps, we identified that the PO route is more favorable for the reduction of CO2 by CH4 to CH3COOH with the reaction barrier 24.5 kcal mol-1. Thus, the present Co0-based metalloradical system represents a viable catalytic protocol that can contribute to the effective utilization of small molecules (H2 and CH4) to reduce CO2, and provides an alternative strategy for the exploration of CO2 conversion.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

Design of a catalyst through Fe doping of the boron cage B10H14 for CO2 hydrogenation and investigation of the catalytic character of iron hydride (Fe-H).

The innovative catalyst Fe@B10H14 is designed through Fe doping of the boron cage B10H14 and is employed to catalyze CO2 hydrogenation using a quantum mechanical method. First, the structure of the Fe@B10H14 complex is characterized through calculated 11B NMR chemical shifts and Raman spectra, and the interactions between Fe and the four H atoms of the opening in the cage are analyzed, which show that various iron hydride (Fe-H) characteristics exist. Subsequently, the potential of Fe@B10H14 as a catalyst for the hydrogenative reduction of CO2 in the gas phase is computationally evaluated. We find that an equivalent of Fe@B10H14 can consecutively reduce double CO2 to obtain the double product HCOOH through a two-step reduction, and Fe@B10H12 and Fe@B10H10 are successively obtained. The Fe presents single-atom character in the reduction of CO2, which is different from the common iron(ii) catalyzed CO2 reduction. The calculated total free energy barrier of the first CO2 reduction is only 8.79 kcal mol-1, and that of the second CO2 reduction is 25.71 kcal mol-1. Every reduction reaction undergoes two key transition states TSC-H and TSO-H. Moreover, the transition state of the C-H bond formation TSC-H is the rate-determining step, where the interaction between πC[double bond, length as m-dash]O* and the weak σFe-H bond plays an important role. Furthermore, the hydrogenations of Fe@B10H12 and Fe@B10H10 are investigated, which aim at determining the ability of Fe-H circulation in the Fe doped decaborane complex. We find that the hydrogenation of Fe@B10H10 undergoes a one-step H2-adsorbed transition state TSH-adsorb with an energy barrier of 6.42 kcal mol-1 from Fe@B10H12. Comparing with the hydrogenation of Fe@B10H10, it is slightly more difficult for the hydrogenation of Fe@B10H12, where the rate-determining step is the H2-cleaved transition state TS2H-H with an energy barrier of 17.38 kcal mol-1.

Electric field effects on the intermolecular interactions in water whiskers: insight from structures, energetics, and properties.

Modulation of intermolecular interactions in response to external electric fields could be fundamental to the formation of unusual forms of water, such as water whiskers. However, a detailed understanding of the nature of intermolecular interactions in such systems is lacking. In this paper, we present novel theoretical results based on electron correlation calculations regarding the nature of H-bonds in water whiskers, which is revealed by studying their evolution under external electric fields with various field strengths. We find that the water whiskers consisting of 2-7 water molecules all have a chain-length dependent critical electric field. Under the critical electric field, the most compact chain structures are obtained, featuring very strong H-bonds, herein referred to as covalent H-bonds. In the case of a water dimer whisker, the bond length of the novel covalent H-bond shortens by 25%, the covalent bond order increases by 9 times, and accordingly the H-bond energy is strengthened by 5 times compared to the normal H-bond in a (H2O)2 cluster. Below the critical electric field, it is observed that, with increasing field strength, H-bonding orbitals display gradual evolutions in the orbital energy, orbital ordering, and orbital nature (i.e., from typical π-style orbital to unusual σ-style double H-bonding orbital). We also show that, beyond the critical electric field, a single water whisker may disintegrate to form a loosely bound zwitterionic chain due to a relay-style proton transfer, whereas two water whiskers may undergo intermolecular cross-linking to form a quasi-two-dimensional water network. Overall, these results help shed new insight on the effects of electric fields on water whisker formation.

New acceptor-bridge-donor strategy for enhancing NLO response with long-range excess electron transfer from the NH2...M/M3O donor (M = Li, Na, K) to inside the electron hole cage C20F19 acceptor through the unusual σ chain bridge (CH2)4.

Using the strong electron hole cage C20F19 acceptor, the NH2...M/M3O (M = Li, Na, and K) complicated donors with excess electron, and the unusual σ chain (CH2)4 bridge, we construct a new kind of electride molecular salt e(-)@C20F19-(CH2)4-NH2...M(+)/M3O(+) (M = Li, Na, and K) with excess electron anion inside the hole cage (to be encapsulated excess electron-hole pair) serving as a new A-B-D strategy for enhancing nonlinear optical (NLO) response. An interesting push-pull mechanism of excess electron generation and its long-range transfer is exhibited. The excess electron is pushed out from the (super)alkali atom M/M3O by the lone pair of NH2 in the donor and further pulled inside the hole cage C20F19 acceptor through the efficient long σ chain (CH2)4 bridge. Owing to the long-range electron transfer, the new designed electride molecular salts with the excess electron-hole pair exhibit large NLO response. For the e(-)@C20F19-(CH2)4-NH2...Na(+), its large first hyperpolarizability (ß0) reaches up to 9.5 × 10(6) au, which is about 2.4 × 10(4) times the 400 au for the relative e(-)@C20F20...Na(+) without the extended chain (CH2)4-NH2. It is shown that the new strategy is considerably efficient in enhancing the NLO response for the salts. In addition, the effects of different bridges and alkali atomic number on ß0 are also exhibited. Further, three modulating factors are found for enhancing NLO response. They are the σ chain bridge, bridge-end group with lone pair, and (super)alkali atom. The new knowledge may be significant for designing new NLO materials and electronic devices with electrons inside the cages. They may also be the basis of establishing potential organic chemistry with electron-hole pair.

Li2 trapped inside tubiform [n] boron nitride clusters (n=4-8): structures and first hyperpolarizability.

The geometries and electronic properties of tubiform [n] boron nitride clusters entrapping Li(2) (Li(2)@BN-cluster(n,0); n=4-8), obtained by doping BN-cluster(n,0) with Li(2) molecules, are investigated by means of DFT. The effects of tube diameter n on the dipole moment µ(0), static polarizability α(0), and first hyperpolarizability ß(0) are elucidated. Both the dipole moment and polarizability increase with increasing tube diameter, whereas variation of the static first hyperpolarizability with tube diameter is not monotonic; ß(0) follows the order 1612 (n=4)<3112 (n=5)<5534 (n=7)<8244 (n=6)<12,282 a.u. (n=8). In addition, the natural bond orbital (NBO) charges show that charge transfer takes place from the Li(2) molecule to the BN cluster, except for BN-cluster(8,0) with larger tube diameter. Since the large-diameter tubular BN-cluster(8,0) can trap the excess electrons of the Li(2) molecule, Li(2)@BN-cluster(8,0) can be considered to be a novel electride compound.

Intercage electron transfer driven by electric field in Robin-Day-type molecules.

A new class of isomers, namely, intercage electron-transfer isomers, is reported for fluorinated double-cage molecular anion e(-)@C(20)F(18)(NH)(2)C(20)F(18) with C(20)F(18) cages: 1 with the excess electron inside the left cage, 2 with the excess electron inside both cages, and 3 with the excess electron inside the right cage. Interestingly, the C(20)F(18) cages may be considered as two redox sites existing in a rare nonmetal mixed-valent (0 and -1) molecular anion. The three isomers with two redox sites may be the founding members of a new class of mixed-valent compounds, namely, nonmetal Robin-Day Class II with localized redox centers for 1 and 3, and Class III with delocalized redox centers for 2. Two intercage electron-transfers pathways involving transfer of one or half an excess electron from one cage to the other are found: 1) Manipulating the external electric field (-0.001 a.u. for 1→3 and -0.0005 a.u. for 1→2) and 2) Exciting the transition from ground to first excited state and subsequent radiationless transition from the excited state to another ground state for 1 and 3. For the exhibited microscopic electron-transfer process 1→3, 2 may be the transition state, and the electron-transfer barrier of 6.021 kcal mol(-1) is close to the electric field work of 8.04 kcal mol(-1).

The association of a single nucleotide polymorphism in the promoter region of the LAMA1 gene with susceptibility to Chinese high myopia.

PURPOSE: High myopia is a severe hereditary ocular disease leading to blindness. LAMA1 (alpha subunit of laminin) is a promising candidate gene for high myopia present in the MYP2 (myopia 2) region. The purpose of this study was to determine if high myopia is associated with single nucleotide polymorphism (SNP) variants in LAMA1 in Chinese subjects. METHODS: Ninety-seven Chinese subjects with high myopia and ethnically and sexually matched 103 normal controls were enrolled. Genomic DNA was prepared from peripheral blood. The 5 SNPs of LAMA1 were analyzed using PCR and SNaPshot. Allele frequencies were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using the χ(2) tests or the Fisher exact tests. RESULTS: One of the 5 SNPs showed a significant difference between patients and control subjects (rs2089760: p(genotype)=0.005, p(allel)=0.003). There were no statistically significant differences between patients and control subjects for the other four SNPs: rs566655, rs11664063, rs607230, and rs3810046. CONCLUSIONS: Our results indicate that the polymorphism of rs2089760, located in the promoter region of LAMA1, may be associated with high myopia in the Chinese population and should be investigated further.

Exceptionally large second-order nonlinear optical response in donor-graphene nanoribbon-acceptor systems.

Graphene nanoribbon (GNR) has been used, for the first time, as an excellent conjugated bridge in a donor-conjugated bridge-acceptor (D-B-A) framework to design high-performance second-order nonlinear optical materials. Owing to the unique diradical planar conjugated bridge of GNR, D(NH(2))-GNR-A(NO(2)) exhibits exceptionally large static first hyperpolarizability (ß(0)) up to 2.5×10(6) a.u. (22000×10(-30) esu) for H(2)N-(7,3)ZGNR-NO(2) (ZGNR=zigzag-edged GNR), which is about 15 times larger than the recorded value of ß(0) (1470×10(-30) esu) for the D-A polyene reported by Blanchard-Desce et al. [Chem. Eur. J. 1997, 3, 1091]. Interestingly, we have found that the size effect of GNR plays a key role in increasing ß(0) for the H(2)N-GNR-NO(2) system, in which the width effect of GNR perpendicular to the D-A direction is superior to the length effect along the D-A direction.

Electric field-driven acid-base chemistry: proton transfer from acid (HCl) to base (NH3/H2O).

It is well-known that single H3N-HCl and H2O-HCl acid-base pairs do not react to form the ion pairs, H4N(+)Cl(-) and H3O(+)Cl(-), in isolation. On the basis of ab initio method, we propose a physical method of external electric field (Eext) to drive the proton transfer from acid (HCl) to base (NH3/H2O). Our results show that when Eext along the proton-transfer direction achieves or exceeds the critical electric field (Ec), the proton transfer occurs, such as, the Ec values of proton transfer for H3N-HCl and H2O-HCl are 54 × 10(-4) and 210 × 10(-4) au, respectively. And the degree of the proton transfer can be controlled by modulating the strength of Eext. Furthermore, we estimate the inductive strength of an excess electron (Ee) equivalent to the Eext = 125 × 10(-4) au, which is greater than the Ec (54 × 10(-4) au) of NH3-HCl but less than the Ec (210 × 10(-4) au) of H2O-HCl. This explains well the anion photoelectron spectroscopy [Eustis et al. Science 2008, 319, 936] that an excess electron can trigger the proton transfer for H3N-HCl but not for H2O-HCl. On the basis of the above estimation, we also predict that two excess electrons can induce H2O-HCl to undergo the proton transfer and form the ion pair H3O(+)Cl(-).

Push-pull electron effects of the complexant in a Li atom doped molecule with electride character: a new strategy to enhance the first hyperpolarizability.

Differing from the reported strategy of push or pull electron effects of the complexant, a new strategy of the combination effects of both push and pull electrons of the complexant to enhance the first hyperpolarizability is performed with two Li atom doped complexants with a pair of difluorophenyl subunit rings. Large variance of the static first hyperpolarizabilities (beta(0)) are exhibited at the MP2/6-311++G(d,p) level. The order of the beta(0) values is 2.9 x10(2) (complexant UD) << 5.9 x 10(3) (LL) < 1.9 x 10(4) (H-L) < 2.3 x 10(4) (H(F)-L) < 3.2 x 10(4) (L-L) < 7.8 x 10(5) a.u. (H(F)-L(F)). It is found that H(F)-L(F) with the edge-type push-pull electronic effect of the complexant has the largest beta(0). The edge-type push-pull electronic effect brings a 2700 times increase in the beta(0) from the UD to H(F)-L(F) structure. It shows that the push-pull electronic effect is a highly effective strategy to enhance the beta(0) value. The beta(0) (7.8 x 10(5) a.u.) of the H(F)-L(F) is considerable, due to the small DeltaE and the very large Delta mu (18.085 a.u.), which comes from the corresponding long-range charge transfer transition. It is interesting that a pair of subunit rings of the complexant may have different electronic effects. In H-L and H(F)-L(F), the left ring with a longer distance between Li and the subunit ring exhibits a push electronic effect, while the right ring with the shorter distance exhibits a pull electronic effect. This work may contribute to the development of potential high-performance nonlinear optical materials.

Reaction mechanism of CH + C(3)H(6): a theoretical study.

A detailed theoretical study is performed at the B3LYP/6-311G(d,p) and G3B3 (single-point) levels as an attempt to explore the reaction mechanism of CH with C(3)H(6). It is shown that the barrierless association of CH with C(3)H(6) forms two energy-rich isomers CH(3)-cCHCHCH(2) (1), and CH(2)CH(2)CHCH(2) (4). Isomers 1 and 4 are predicted to undergo subsequent isomerization and dissociation steps leading to ten dissociation products P(1) (CH(3)-cCHCHCH + H), P(2) (CH(3)-cCCHCH(2) + H), P(3) (cCHCHCH(2) + CH(3)), P(4) (CH(3)CHCCH(2) + H), P(5) (cis-CH(2)CHCHCH(2) + H), P(6) (trans-CH(2)CHCHCH(2) + H), P(7) (C(2)H(4) + C(2)H(3)), P(8) (CH(3)CCH + CH(3)), P(9) (CH(3)CCCH(3) + H) and P(12) (CH(2)CCH(2) + CH(3)), which are thermodynamically and kinetically possible. Among these products, P(5), P(6), and P(7) may be the most favorable products with comparable yields; P(1), P(2), and P(3) may be the much less competitive products, followed by the almost negligible P(4), P(8), P(9), and P(12). Since the isomers and transition states involved in the CH + C(3)H(6) reaction all lie lower than the reactant, the title reaction is expected to be fast, which is consistent with the measured large rate constant in experiment. The present study may lead us to a deep understanding of the CH radical chemistry.

[Research progress in A-type lamins].

A-type lamins are encoded by LMNA and a major component of the nuclear lamina, a dynamic meshwork located just under the nuclear envelope, providing essential mechanical support. In addition, A-type lamins associate with chromatin both directly and indirectly and have been suggested to play important roles in chromatin organization, transcription, DNA replication, and apoptosis. Mutations of LMNA or its encoding proteins can cause a series of human hereditary diseases which are collectively referred to as laminopathies. To approach functions of A-type lamins and their roles in laminopathies, this review summarizes several parts of A-type lamins, including its structure, type, modification, assembly, dynamics, interaction proteins and laminopathies.

Double-stranded break can be repaired by single-stranded oligonucleotides via the ATM/ATR pathway in mammalian cells.

Single-stranded oligonucleotide (SSO)-mediated gene modification is a newly developed tool for site-specific gene repair in mammalian cells; however, the corrected cells always show G2/M arrest and cannot divide to form colonies. This phenomenon and the unclear mechanism seriously challenge the future application of this technique. In this study, we developed an efficient SSO-mediated DNA repair system based on double-stranded break (DSB) induction. We generated a mutant EGFP gene with insertions of 24 bp to 1.6 kb in length as a reporter integrated in mammalian cell lines. SSOs were successfully used to delete the insertion fragments upon DSB induction at a site near the insertion. We demonstrated that this process is dependent on the ATM/ATR pathway. Importantly, repaired cell clones were viable. Effects of deletion length, SSO length, strand bias, and SSO modification on gene repair frequency were also investigated.

CTT1 overexpression increases the replicative lifespan of MMS-sensitive Saccharomyces cerevisiae deficient in KSP1.

Ksplp is a nuclear-localized Ser/Thr kinase that is not essential for the vegetative growth of yeast. A global gene function analysis in yeast suggested that Ksplp was involved in the oxidative stress response; however, the underlying mechanism remains unclear. Here, we showed that KSP1-deficient yeast cells exhibit hypersensitivity to the DNA alkylating agent methyl methanesulphonate (MMS), and treatment of the KSP1-deficient strain with MMS could trigger abnormal mitochondrial membrane potential and up-regulate reactive oxygen species (ROS) production. In addition, the mRNA expression level of the catalase gene CTT1 (which encodes cytosolic catalase) and total catalase activity were strongly down-regulated in the KSP1-deleted strain compared with those in wild-type cells. Moreover, the KSP1 deficiency also leads to a shortened replicative lifespan, which could be restored by the increased expression of CTT1. On the other hand, KSP1-overexpressed (KSP1OX) yeast cells exhibited increased resistance towards MMS, an effect that was, at least in part, CTT1 independent. Collectively, these findings highlight the involvement of Ksplp in the DNA damage response and implicate Ksplp as a modulator of the replicative lifespan.

Identification of lesion images from gastrointestinal endoscope based on feature extraction of combinational methods with and without learning process.

The gastrointestinal endoscopy in this study refers to conventional gastroscopy and wireless capsule endoscopy (WCE). Both of these techniques produce a large number of images in each diagnosis. The lesion detection done by hand from the images above is time consuming and inaccurate. This study designed a new computer-aided method to detect lesion images. We initially designed an algorithm named joint diagonalisation principal component analysis (JDPCA), in which there are no approximation, iteration or inverting procedures. Thus, JDPCA has a low computational complexity and is suitable for dimension reduction of the gastrointestinal endoscopic images. Then, a novel image feature extraction method was established through combining the algorithm of machine learning based on JDPCA and conventional feature extraction algorithm without learning. Finally, a new computer-aided method is proposed to identify the gastrointestinal endoscopic images containing lesions. The clinical data of gastroscopic images and WCE images containing the lesions of early upper digestive tract cancer and small intestinal bleeding, which consist of 1330 images from 291 patients totally, were used to confirm the validation of the proposed method. The experimental results shows that, for the detection of early oesophageal cancer images, early gastric cancer images and small intestinal bleeding images, the mean values of accuracy of the proposed method were 90.75%, 90.75% and 94.34%, with the standard deviations (SDs) of 0.0426, 0.0334 and 0.0235, respectively. The areas under the curves (AUCs) were 0.9471, 0.9532 and 0.9776, with the SDs of 0.0296, 0.0285 and 0.0172, respectively. Compared with the traditional related methods, our method showed a better performance. It may therefore provide worthwhile guidance for improving the efficiency and accuracy of gastrointestinal disease diagnosis and is a good prospect for clinical application.

All-metal electride molecules CuAg@Ca7M (M = Be, Mg, and Ca) with multi-excess electrons and all-metal polyanions: molecular structures and bonding modes as well as large infrared nonlinear optical responses.

All-metal electride molecules, CuAg@Ca7M (M = Be, Mg and Ca), have been designed and researched in theory for the first time. In these molecules, a pull-push electron relay occurs. Unusually, the all-metal polyanions of fourfold negatively charged [Cu-Ag-Be/Mg](4-) and [Cu-Ag](4-) with 4 extra electrons gained from Ca atoms push the remaining valence electrons of the Ca atoms forming the multi-excess electrons (Ne = 10/12). Therefore, these molecules can be described as salt-like [(Ca(2+))7(CuAgM)(4-)] + 10e(-) (M = Be and Mg) and [(Ca(2+))8(CuAg)(4-)] + 12e(-). In these salt-like molecules, there are extraordinary covalent bonding modes, which include 2c-2e/3c-2e σ-bonding in the polyanions and the Ca(2+) cations sharing the diffuse multi-excess electrons. For an intriguing nonlinear optical (NLO) response, these all-metal electride molecules display large electronic first hyperpolarizabilities (ß0), thus a new class of NLO molecules, all-metal electride NLO molecules, emerge. Moreover, it is also found that manipulating the atomic number and position of M is a new strategy to enhance ß0. As a result, CuAg@Ca7Mg(1) exhibits a considerable ß0 (1.43 × 10(4) au), which is 16 times the ß0 sum of two isolated CuAg and Ca7Mg(1) subunits, and this deeply reveals the fundamental origin of the considerable ß0, namely, the multi-excess electrons generated by the subunit interaction. These all-metal electride molecules have the infrared (IR) transparent region of 1.3-6 µm, and hence are new IR NLO molecules. In addition the electronic contribution, ß0, the large effects of vibrations on the static first hyperpolarizabilities of these all-metal electride molecules are also estimated. Thus, this study opens the new research field of all-metal electride IR NLO molecules.

A new strategy for simultaneously enhancing nonlinear optical response and electron stability in novel cup-saucer⁺-cage⁻-shaped sandwich electride molecules with an excess electron protected inside the cage.

Novel cup-saucer-cage-shaped sandwich electride molecules calix[4]pyrrole···K3O(+)···e@C(n)F(n)(-), (n = 8, 10, 14, 20, and 36) with an excess electron protected inside the C(n)F(n) cage are constructed theoretically. In the sandwich structures, the below calix[4]pyrrole cup pushes the valence electron of the sandwiched superalkali atom K3O saucer, forming an excess electron, which is further pulled and protected inside the above C(n)F(n) cage, thus an electron-transfer relay occurs. In particular, owing to the unusual electron transfer, an unusual and fortunate phenomenon is discovered that increasing the C(n)F(n) cage size enhances not only the nonlinear optical response (ß0), but also the electron stability (VIP). Thus, a new strategy of simultaneously enhancing ß0 and VIP values is found for the first time, namely by increasing the C(n)F(n) cage size in novel cup-saucer-cage-shaped sandwich electride molecules, with the excess electron protected inside the cage.

CIA2 deficiency results in impaired oxidative stress response and enhanced intracellular basal UPR activity in Saccharomyces cerevisiae.

Yeast Cia2p is a component of the cytosolic Fe/S protein assembly (CIA) machinery. Initial studies of the CIA machinery were performed in yeast, but the precise role of Cia2p in this eukaryote is still unknown. We report that CIA2 deficiency results in impaired oxidative stress response, as evidenced by increased sensitivity to the oxidant cumene hydroperoxide (CHP), impaired activities of superoxide dismutases and aconitase and decreased replicative lifespan in the mutants. Moreover, intracellular reactive oxygen species levels were significantly increased in CIA2-deficient cells after treatment with CHP. We also show that CIA2-deficient cells display an increased resistance to tunicamycin-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulated splicing of the mRNA of HAC1, which encodes a functional transcription factor that regulates the transcription of unfolded protein response (UPR) target genes, suggesting enhanced intracellular UPR activity. Furthermore, the transcription of several canonical UPR target genes is strongly induced in CIA2-deficient cells as compared with wild-type controls. Taken together, these results suggest the involvement of Cia2p in oxidative and ER stress responses in yeast.

PMT1 deficiency enhances basal UPR activity and extends replicative lifespan of Saccharomyces cerevisiae.

Pmt1p is an important member of the protein O-mannosyltransferase (PMT) family of enzymes, which participates in the endoplasmic reticulum (ER) unfolded protein response (UPR), an important pathway for alleviating ER stress. ER stress and the UPR have been implicated in aging and age-related diseases in several organisms; however, a possible role for PMT1 in determining lifespan has not been previously described. In this study, we report that deletion of PMT1 increases replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae, while overexpression of PMT1 (PMT1-OX) reduces RLS. Relative to wild-type and PMT1-OX strains, the pmt1Δ strain had enhanced HAC1 mRNA splicing and elevated expression levels of UPR target genes. Furthermore, the increased RLS of the pmt1Δ strain could be completely abolished by deletion of either IRE1 or HAC1, two upstream modulators of the UPR. The double deletion strains pmt1Δhac1Δ and pmt1Δire1Δ also displayed generally reduced transcription of UPR target genes. Collectively, our results suggest that PMT1 deficiency enhances basal activity of the ER UPR and extends the RLS of yeast mother cells through a mechanism that requires both IRE1 and HAC1.