Chemoselective reduction and oxidation of ketones in water through control of the electron transfer pathway

The selective synthesis of different products from the same starting materials in water, which is the most abundant solvent in nature, is a crucial issue as it maximizes the utilization of materials. Realizing such reactions for ketones is of considerable importance because numerous organic functionalities can be obtained via nucleophilic addition reactions. Herein, we report chemoselective reduction and oxidation reactions of 1,2-diketones in water, which initiates anionic electron transfer from the inorganic electride [Ca24Al28O64](4+)center dot 4e(-), through controlling the pathway of the electrons to substrates. The generation of different radical species for transient intermediates was the key process required to control the reaction selectivity, which was achieved by reacting the anionic electrons with either diketones or O-2, leading to the formation of ketyl dianion and superoxide radicals in the reduction and oxidation reactions, respectively. This methodology that utilizes electrides may provide an alternative to the pulse radiolysis of water in synthetic chemistry1441sciescopu

Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

Dysbindin and DISC1 are schizophrenia susceptibility factors playing roles in neuronal development. Here we show that the physical interaction between dysbindin and DISCI is critical for the stability of dysbindin and for the process of neurite outgrowth. We found that DISCI forms a complex with dysbindin and increases its stability in association with a reduction in ubiquitylation. Furthermore, knockdown of DISCI or expression of a deletion mutant, DISCI lacking amino acid residues 403-504 of DISC1 (DISC1(Delta 403-504)), effectively decreased levels of endogenous dysbindin. Finally, the neurite outgrowth defect induced by knockdown of DISCI was partially reversed by coexpression of dysbindin. Taken together, these results indicate that dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth.X111211Ysciescopu

Placental Growth Factor-1 and -2 Induce Hyperplasia and Invasiveness of Primary Rheumatoid Synoviocytes

Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have promigratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. In this study, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with small interfering RNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and neuropilin-1, and upregulating the expression of antiapoptotic molecules, pErk and Bcl2. Knockdown of PlGF transcripts reduced RA-FLS proliferation in a xenotransplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy.1177Ysciescopu

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Prevalence of neck pain in subjects with metabolic syndrome - a cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is increasingly common. Obesity has been suggested to associate with neck pain but prevalence of neck pain in subjects with MetS has not been studied. Aim of this study was to analyse the association between MetS and neck pain.</p> <p>Methods</p> <p>The study population consisted of 1294 middle-aged subjects in Pieksämäki, Finland. A total of 399 males and 500 females participated (69%). The mean age of both males and females was 46 years. Clinical and biochemical measurements were taken. The participants filled out a standard questionnaire. Psychological distress was assessed with the 12-item General Health Questionnaire (GHQ-12). Neck pain was defined as neck pain perceived daily. MetS was defined using National Cholesterol Education Program (NCEP) criteria. Statistical comparisons between the groups were performed using a bootstrap-type t-test or Chi-Square test. Risk ratios of having neck pain were calculated using generalised linear models with age, smoking, alcohol use, exercise and GHQ-12 score as covariates.</p> <p>Results</p> <p>The prevalence of MetS was 33% in males and 29% in females. Neck pain was present in 11% (N = 42) of males and 19% (N = 93) of females (P < 0.001). The prevalence of neck pain was 7.9% (95% CI, 4.9% to 12%) among male subjects without MetS and 16% (95% CI, 10% to 23%) among those with MetS. The respective proportions among females were 16% (95% CI, 12% to 20%) and 25% (95% CI, 18% to 33%). The multivariate analysis showed an increased risk of neck pain in males with MetS (RR 2.1, 95% CI, 1.2 to 3.7, P = 0.010) and in females with MetS (RR 1.5, 95% CI, 1.0 to 2.1, P = 0.040).</p> <p>Conclusions</p> <p>MetS was associated with neck pain. This association was stronger in males, but the prevalence of neck pain was higher in females. Prospective studies should explore the potential causal association between neck pain and MetS and the potential common background factors of neck pain and MetS.</p

Attention deficit hyperactivity symptoms predict problematic mobile phone use

Attention-deficit-hyperactivity disorder (ADHD) is the most commonly diagnosed childhood disorder characterised by inattention, hyperactivity/impulsivity, or both. Some of the key traits of ADHD have previously been linked to addictive and problematic behaviours. The aim of the present study was to examine the relationship between problematic mobile phone use, smartphone addiction risk and ADHD symptoms in an adult population. A sample of 273 healthy adult volunteers completed the Adult ADHD Self-Report Scale (ASRS), the Mobile Phone Problem Usage Scale (MPPUS), and the Smartphone Addiction Scale (SAS). A significant positive correlation was found between the ASRS and both scales. More specifically, inattention symptoms and age predicted smartphone addiction risk and problematic mobile phone use. Our results suggest that there is a positive relationship between ADHD traits and problematic mobile phone use. In particular, younger adults with higher level of inattention symptoms could be at higher risk of developing smartphone addiction. The implication of our findings for theoretical frameworks of problematic mobile phone use and clinical practice are discussed

Antisense DNA parameters derived from next-nearest-neighbor analysis of experimental data

<p>Abstract</p> <p>Background</p> <p>The enumeration of tetrameric and other sequence motifs that are positively or negatively correlated with <it>in vivo </it>antisense DNA effects has been a useful addition to the arsenal of information needed to predict effective targets for antisense DNA control of gene expression. Such retrospective information derived from <it>in vivo </it>cellular experiments characterizes aspects of the sequence dependence of antisense inhibition that are not predicted by nearest-neighbor (NN) thermodynamic parameters derived from <it>in vitro </it>experiments. However, quantitation of the antisense contributions of motifs is problematic, since individual motifs are not isolated from the effects of neighboring nucleotides, and motifs may be overlapping. These problems are circumvented by a next-nearest-neighbor (NNN) analysis of antisense DNA effects in which the overlapping nature of nearest-neighbors is taken into account.</p> <p>Results</p> <p>Next-nearest-neighbor triplet combinations of nucleotides are the simplest that include overlapping sequence effects and therefore can encompass interactions beyond those of nearest neighbors. We used singular value decomposition (SVD) to fit experimental data from our laboratory in which phosphorothioate-modified antisense DNAs (S-DNAs) 20 nucleotides long were used to inhibit cellular protein expression in 112 experiments involving four gene targets and two cell lines. Data were fitted using a NNN model, neglecting end effects, to derive NNN inhibition parameters that could be combined to give parameters for a set of 49 sequences that represents the inhibitory effects of all possible overlapping triplet interactions in the cellular targets of these antisense S-DNAs. We also show that parameters to describe subsets of the data, such as the mRNAs being targeted and the cell lines used, can be included in such a derivation. While NNN triplet parameters provided an adequate model to fit our data, NN doublet parameters did not.</p> <p>Conclusions</p> <p>The methodology presented illustrates how NNN antisense inhibitory information can be derived from <it>in vivo </it>cellular experiments. Subsequent calculations of the antisense inhibitory parameters for any mRNA target sequence automatically take into account the effects of all possible overlapping combinations of nearest-neighbors in the sequence. This procedure is more robust than the tallying of tetrameric motifs that have positive or negative antisense effects. The specific parameters derived in this work are limited in their applicability by the relatively small database of experiments that was used in their derivation.</p

Ethylene supports colonization of plant roots by the mutualistic fungus Piriformospora indica

The mutualistic basidiomycete Piriformospora indica colonizes roots of mono- and dicotyledonous plants, and thereby improves plant health and yield. Given the capability of P. indica to colonize a broad range of hosts, it must be anticipated that the fungus has evolved efficient strategies to overcome plant immunity and to establish a proper environment for nutrient acquisition and reproduction. Global gene expression studies in barley identified various ethylene synthesis and signaling components that were differentially regulated in P. indica-colonized roots. Based on these findings we examined the impact of ethylene in the symbiotic association. The data presented here suggest that P. indica induces ethylene synthesis in barley and Arabidopsis roots during colonization. Moreover, impaired ethylene signaling resulted in reduced root colonization, Arabidopsis mutants exhibiting constitutive ethylene signaling, -synthesis or ethylene-related defense were hyper-susceptible to P. indica. Our data suggest that ethylene signaling is required for symbiotic root colonization by P. indica

Number crunching in the cancer stem cell market

Like their normal counterparts, many tumours are thought to have a hierarchical organization, albeit a disorganized one. Accordingly, the concept of cancer stem cells has emerged, and that these cells are responsible for perpetuating tumour existence. Operationally, cancer stem cells are regarded as prospectively purified cells that are the most effective at tumour initiation in an in vivo assay, usually after xenotransplantation to NOD/SCID mice. The conventional wisdom is that such tumour-initiating cells are rare based upon having to xenotransplant large numbers of human tumour cells into immunodeficient mice to propagate the tumour, but new evidence indicates that perhaps these cells are not so rare, at least in malignant melanoma, if a supportive soil is provided for the transplanted cells along with further restriction of the murine host's immune response