A Concise Total Synthesis of (--)-Maoecrystal Z

The first total synthesis of (--)-maoecrystal Z is described. The key steps of the synthesis include a diastereoselective Ti^(III)-mediated reductive epoxide coupling reaction and a diastereoselective Sm^(II)-mediated reductive cascade cyclization reaction. These transformations enabled the preparation of (--)-maoecrystal Z in only 12 steps from (--)-γ-cyclogeraniol

Implementation, utilization and influence of a community-based participatory nutrition promotion programme in rural Ethiopia: programme impact pathway analysis.

OBJECTIVE: A community-based participatory nutrition promotion (CPNP) programme, involving a 2-week group nutrition session, attempted to improve child feeding and hygiene. The implementation, utilization and influence of the CPNP programme were examined by programme impact pathway (PIP) analysis. DESIGN: Five CPNP programme components were evaluated: (i) degree of implementation; (ii) participants' perception of the nutrition sessions; (iii) participants' message recall; (iv) utilization of feeding and hygiene practices at early programme stage; and (v) participants' engagement in other programmes. SETTING: Habro and Melka Bello districts, Ethiopia. SUBJECTS: Records of 372 nutrition sessions, as part of a cluster-randomized trial, among mothers (n 876 in intervention area, n 914 in control area) from a household survey and CPNP participants (n 197) from a recall survey. RESULTS: Overall, most activities related to nutrition sessions were successfully operated with high fidelity (>90 %), but a few elements of the protocol were only moderately achieved. The recall survey among participants showed a positive perception of the sessions (~90 %) and a moderate level of message recall (~65 %). The household survey found that the CPNP participants had higher minimum dietary diversity at the early stage (34·0 v. 19·9 %, P=0·01) and a higher involvement in the Essential Nutrition Action (ENA) programme over a year of follow-up (28·2 v. 18·3 %; P<0·0001) compared with non-participants within the intervention area. CONCLUSIONS: Our PIP analysis suggests that CPNP was feasibly implemented, promoted a sustained utilization of proper feeding behaviours, and enhanced participation in the existing ENA programme. These findings provide a possible explanation to understanding CPNP's effectiveness

Buy One Get One to Share: Preference Between Bonus Packs and Price Discounts For Experiential Versus Material Products

Four studies show that a bonus pack promotion is more preferred for experiential products than for material products. This effect is observed only when bonus pack promotions for experiential goods suggest shared consumption and is moderated by extraversion and experience of social exclusion

Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

BackgroundAlthough the contrast-enhancing (CE) lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden.MethodsFifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy.ResultsThe Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data.ConclusionsThe similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM

Loop dependence of the stability and dynamics of nucleic acid hairpins

Hairpin loops are critical to the formation of nucleic acid secondary structure, and to their function. Previous studies revealed a steep dependence of single-stranded DNA (ssDNA) hairpin stability with length of the loop (L) as ∼L8.5 ± 0.5, in 100 mM NaCl, which was attributed to intraloop stacking interactions. In this article, the loop-size dependence of RNA hairpin stabilities and their folding/unfolding kinetics were monitored with laser temperature-jump spectroscopy. Our results suggest that similar mechanisms stabilize small ssDNA and RNA loops, and show that salt contributes significantly to the dependence of hairpin stability on loop size. In 2.5 mM MgCl2, the stabilities of both ssDNA and RNA hairpins scale as ∼L4 ± 0.5, indicating that the intraloop interactions are weaker in the presence of Mg2+. Interestingly, the folding times for ssDNA hairpins (in 100 mM NaCl) and RNA hairpins (in 2.5 mM MgCl2) are similar despite differences in the salt conditions and the stem sequence, and increase similarly with loop size, ∼L2.2 ± 0.5 and ∼L2.6 ± 0.5, respectively. These results suggest that hairpins with small loops may be specifically stabilized by interactions of the Na+ ions with the loops. The results also reinforce the idea that folding times are dominated by an entropic search for the correct nucleating conformation

Optimising text messaging to improve adherence to web-based smoking cessation treatment: a randomised control trial protocol

Introduction Millions of smokers use the Internet for smoking cessation assistance each year; however, most smokers engage minimally with even the best designed websites. The ubiquity of mobile devices and their effectiveness in promoting adherence in other areas of health behaviour change make them a promising tool to address adherence in Internet smoking cessation interventions. Text messaging is used by most adults, and messages can proactively encourage use of a web-based intervention. Text messaging can also be integrated with an Internet intervention to facilitate the use of core Internet intervention components. Methods and analysis We identified four aspects of a text message intervention that may enhance its effectiveness in promoting adherence to a web-based smoking cessation programme: personalisation, integration, dynamic tailoring and message intensity. Phase I will use a two-level full factorial design to test the impact of these four experimental features on adherence to a web-based intervention. The primary outcome is a composite metric of adherence that incorporates general utilisation metrics (eg, logins, page views) and specific feature utilisation shown to predict abstinence. Participants will be N=860 adult smokers who register on an established Internet cessation programme and enrol in its text message programme. Phase II will be a two-arm randomised trial to compare the efficacy of the web-based cessation programme alone and in conjunction with the optimised text messaging intervention on 30-day point prevalence abstinence at 9 months. Phase II participants will be N=600 adult smokers who register to use an established Internet cessation programme and enrol in text messaging. Secondary analyses will explore whether adherence mediates the effect of treatment condition on outcome. Ethics and dissemination This protocol was approved by Chesapeake IRB. We will disseminate study results through peer-reviewed manuscripts and conference presentations related to the methods and design, outcomes and exploratory analyses. Trial registration number NCT02585206

Testing mood-activated psychological markers for suicidal ideation

To what extent are death- and life-oriented psychological processes among suicidal individuals activated by mood? According to Teasdale’s (1988) Differential Activation Hypothesis, we would expect that negative mood-activated psychological processes are maladaptive among suicide ideators (vs. non-ideators) and predictive of subsequent suicidal ideation. This, however, has never been prospectively studied. To address this knowledge gap, we conducted a prospective study assessing psychological risk factors via the Death/Life Implicit Association Test (IAT) and the Suicide Stroop task before and after a temporary negative mood induction. Suicidal ideation was assessed one and six months later. Results based on Death/Life IAT performance largely supported hypotheses, such that suicide ideators demonstrated significantly weaker implicit identification with life after (vs. before) the negative mood induction. Non-ideators demonstrated no significant change, maintaining strong identification with life irrespective of mood. Of note, this baseline interaction may have been accounted for by depressive symptoms. Identification with death (vs. life) predicted greater likelihood of suicidal ideation one month later, controlling for depressive symptoms and baseline suicidal ideation. Only negative mood-activated identification with death predicted suicidal ideation six months later. Suicide Stroop scores did not change as a function of mood or predict subsequent suicidal ideation. Death/Life IAT findings support the Differential Activation Hypothesis and suggest that suicide ideators’ identification with life is more variable and easily weakened by negative mood relative to non-ideators. We encourage future work to consider the potential role of transient mood and the importance of measuring psychological processes that pertain to both death and life

Increased cytotoxic efficacy of protocatechuic acid in A549 human lung cancer delivered via hydrophobically modified-chitosan nanoparticles as an anticancer modality

The growing incidence of global lung cancer cases against successful treatment modalities has increased the demand for the development of innovative strategies to complement conventional chemotherapy, radiation, and surgery. The substitution of chemotherapeutics by naturally occurring phenolic compounds has been touted as a promising research endeavor, as they sideline the side effects of current chemotherapy drugs. However, the therapeutic efficacy of these compounds is conventionally lower than that of chemotherapeutic agents due to their lower solubility and consequently poor intracellular uptake. Therefore, we report herein a hydrophobically modified chitosan nanoparticle (pCNP) system for the encapsulation of protocatechuic acid (PCA), a naturally occurring but poorly soluble phenolic compound, for increased efficacy and improved intracellular uptake in A549 lung cancer cells. The pCNP system was modified by the inclusion of a palmitoyl group and physico-chemically characterized to assess its particle size, Polydispersity Index (PDI) value, amine group quantification, functional group profiling, and morphological properties. The inclusion of hydrophobic palmitoyl in pCNP-PCA was found to increase the encapsulation of PCA by 54.5% compared to unmodified CNP-PCA samples whilst it only conferred a 23.4% larger particle size. The single-spherical like particles with uniformed dispersity pCNP-PCA exhibited IR bands, suggesting the successful incorporation of PCA within its core, and a hydrophobic layer was elucidated via electron micrographs. The cytotoxic efficacy was then assessed by using an MTT cytotoxicity assay towards A549 human lung cancer cell line and was compared with traditional chitosan nanoparticle system. Fascinatingly, a controlled release delivery and enhanced therapeutic efficacy were observed in pCNP-PCA compared to CNP, which is ascribed to lower IC50 values in the 72-h treatment in the pCNP system. Using the hydrophobic system, efficacy of PCA was significantly increased in 24-, 48-, and 72-h treatments compared to a single administration of the compound, and via the unmodified CNP system. Findings arising from this study exhibit the potential of using such modified nanoparticulate systems in increasing the efficacy of natural phenolic compounds by augmenting their delivery potential for better anti-cancer responses

A unified strategy for the synthesis of (−)-maoecrystal Z, (−)-trichorabdal A, and (−)-longikaurin E

Herein we describe in full our investigations that led to the completion of the first total syntheses of (−)-maoecrystal Z, (−)-trichorabdal A, and (−)-longikaurin E. The unified strategy employs a Ti^(III)-mediated reductive epoxide coupling to rapidly prepare a key spirolactone. Highly diastereoselective Sm^(II)-mediated reductive cyclizations and a Pd^(II)-mediated oxidative cyclization enable the construction of three architecturally distinct ent-kauranoid frameworks from this common intermediate

The Ras-ERK MAPK regulatory network controls dedifferentiation in Caenorhabditis elegans germline

Appendix A Supplementary data Supplementary materials. Download Appendix A Supplementary data Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.bbamcr.2012.07.006 . Abstract How a committed cell can be reverted to an undifferentiated state is a central question in stem cell biology. This process, called dedifferentiation, is likely to be important for replacing stem cells as they age or get damaged. Tremendous progress has been made in understanding this fundamental process, but its mechanisms are poorly understood. Here we demonstrate that the aberrant activation of Ras-ERK MAPK signaling promotes cellular dedifferentiation in the Caenorhabditis elegans germline. To activate signaling, we removed two negative regulators, the PUF-8 RNA-binding protein and LIP-1 dual specificity phosphatase. The removal of both of these two regulators caused secondary spermatocytes to dedifferentiate and begin mitotic divisions. Interestingly, reduction of Ras-ERK MAPK signaling, either by mutation or chemical inhibition, blocked the initiation of dedifferentiation. By RNAi screening, we identified RSKN-1/P90 RSK as a downstream effector of MPK-1/ERK that is critical for dedifferentiation: rskn-1 RNAi suppressed spermatocyte dedifferentiation and instead induced meiotic divisions. These regulators are broadly conserved, suggesting that similar molecular circuitry may control cellular dedifferentiation in other organisms, including humans