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Provides a look into the world and the characters of A wrinkle in time, featuring unique perspectives in the characters' voices.

Current research into the FERONIA family of receptor kinases highlights both questions and opportunities for understanding signaling strategies in plant growth and survival.

Dietary guidelines recommend avoiding foods high in saturated fat. Yet, emerging evidence suggests cardiometabolic benefits of dairy products and dairy fat. Evidence on the role of butter, with high saturated dairy fat content, for total mortality, cardiovascular disease, and type 2 diabetes remains unclear. We aimed to systematically review and meta-analyze the association of butter consumption with all-cause mortality, cardiovascular disease, and diabetes in general populations. We searched 9 databases from inception to May 2015 without restriction on setting, or language, using keywords related to butter consumption and cardiometabolic outcomes. Prospective cohorts or randomized clinical trials providing estimates of effects of butter intake on mortality, cardiovascular disease including coronary heart disease and stroke, or diabetes in adult populations were included. One investigator screened titles and abstracts; and two reviewed full-text articles independently in duplicate, and extracted study and participant characteristics, exposure and outcome definitions and assessment methods, analysis methods, and adjusted effects and associated uncertainty, all independently in duplicate. Study quality was evaluated by a modified Newcastle-Ottawa score. Random and fixed effects meta-analysis pooled findings, with heterogeneity assessed using the I2 statistic and publication bias by Egger's test and visual inspection of funnel plots. We identified 9 publications including 15 country-specific cohorts, together reporting on 636,151 unique participants with 6.5 million person-years of follow-up and including 28,271 total deaths, 9,783 cases of incident cardiovascular disease, and 23,954 cases of incident diabetes. No RCTs were identified. Butter consumption was weakly associated with all-cause mortality (N = 9 country-specific cohorts; per 14g(1 tablespoon)/day: RR = 1.01, 95%CI = 1.00, 1.03, P = 0.045); was not significantly associated with any cardiovascular disease (N = 4; RR = 1.00, 95%CI = 0.98, 1.02; P = 0.704), coronary heart disease (N = 3; RR = 0.99, 95%CI = 0.96, 1.03; P = 0.537), or stroke (N = 3; RR = 1.01, 95%CI = 0.98, 1.03; P = 0.737), and was inversely associated with incidence of diabetes (N = 11; RR = 0.96, 95%CI = 0.93, 0.99; P = 0.021). We did not identify evidence for heterogeneity nor publication bias. This systematic review and meta-analysis suggests relatively small or neutral overall associations of butter with mortality, CVD, and diabetes. These findings do not support a need for major emphasis in dietary guidelines on either increasing or decreasing butter consumption, in comparison to other better established dietary priorities; while also highlighting the need for additional investigation of health and metabolic effects of butter and dairy fat.

Permeation through nanometer pores is important in the design of materials for filtration and separation techniques and because of unusual fundamental behavior arising at the molecular scale. We found that submicrometer-thick membranes made from graphene oxide can be completely impermeable to liquids, vapors, and gases, including helium, but these membranes allow unimpeded permeation of water (H₂0 permeates through the membranes at least 10¹⁰ times faster than He). We attribute these seemingly incompatible observations to a low-friction flow of a monolayer of water through two-dimensional capillaries formed by closely spaced graphene sheets. Diffusion of other molecules is blocked by reversible narrowing of the capillaries in low humidity and/or by their clogging with water.

Kinetic Alfvén waves (KAWs) are ubiquitous throughout the plasma universe. Although they are broadly believed to provide a potential approach for energy exchange between electromagnetic fields and plasma particles, neither the detail nor the efficiency of the interactions has been well-determined yet. The primary difficulty has been the paucity of knowledge of KAWs’ spatial structure in observation. Here, we apply a particle-sounding technique to Magnetospheric Multiscale mission data to quantitatively determine the perpendicular wavelength of KAWs from ion gyrophase-distribution observations. Our results show that KAWs’ perpendicular wavelength is statistically 2.4 ± 0.7 times proton thermal gyro-radius. This observation yields an upper bound of the energy the majority proton population can reach in coherent interactions with KAWs, that is, roughly 5.76 times proton perpendicular thermal energy. Therefore, the method and results shown here provide a basis for unraveling the effects of KAWs in dissipating energy and accelerating particles in a number of astrophysical systems, e.g., planetary magnetosphere, astrophysical shocks, stellar corona and wind, and the interstellar medium. Kinetic Alfven Waves (KAWs) are ubiquitous in space plasmas. Here, the authors show that application of particle sounding technique to Magnetospheric Multiscale Mission data enables measuring perpendicular wavelength of KAWs.

Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT–PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1–MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-β1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-β1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-β1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower ( P =0.006 and P =0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-β1–MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.

Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023–$28,800 US dollars (USD) in Japan to $14,513–$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.

The effect of dietary fats on cardiometabolic diseases, including cardiovascular diseases and type 2 diabetes mellitus, has generated tremendous interest. Many earlier investigations focused on total fat and conventional fat classes (such as saturated and unsaturated fats) and their influence on a limited number of risk factors. However, dietary fats comprise heterogeneous molecules with diverse structures, and growing research in the past two decades supports correspondingly complex health effects of individual dietary fats. Moreover, health effects of dietary fats might be modified by additional factors, such as accompanying nutrients and food-processing methods, emphasizing the importance of the food sources. Accordingly, the rapidly increasing scientific findings on dietary fats and cardiometabolic diseases have generated debate among scientists, caused confusion for the general public and present challenges for translation into dietary advice and policies. This Review summarizes the evidence on the effects of different dietary fats and their food sources on cell function and on risk factors and clinical events of cardiometabolic diseases. The aim is not to provide an exhaustive review but rather to focus on the most important evidence from randomized controlled trials and prospective cohort studies and to highlight current areas of controversy and the most relevant future research directions for understanding how to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.Dietary fats comprise heterogeneous molecules with diverse structures and complex health effects. This Review discusses the effects of different dietary fats on cell processes and cardiometabolic disease risk factors and clinical events, highlighting areas of controversy and future research directions to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.

Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis. We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias. This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.

Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The upregulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription but also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction had a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis.