Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways

<p>Abstract</p> <p>Background</p> <p>Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways.</p> <p>Methods</p> <p>To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot.</p> <p>Results</p> <p>OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21.</p> <p>Conclusion</p> <p>The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways.</p

Generalized boson algebra and its entangled bipartite coherent states

Starting with a given generalized boson algebra U_(h(1)) known as the bosonized version of the quantum super-Hopf U_q[osp(1/2)] algebra, we employ the Hopf duality arguments to provide the dually conjugate function algebra Fun_(H(1)). Both the Hopf algebras being finitely generated, we produce a closed form expression of the universal T matrix that caps the duality and generalizes the familiar exponential map relating a Lie algebra with its corresponding group. Subsequently, using an inverse Mellin transform approach, the coherent states of single-node systems subject to the U_(h(1)) symmetry are found to be complete with a positive-definite integration measure. Nonclassical coalgebraic structure of the U_(h(1)) algebra is found to generate naturally entangled coherent states in bipartite composite systems.Comment: 15pages, no figur

Accelerated and interpretable oblique random survival forests

The oblique random survival forest (RSF) is an ensemble supervised learning method for right-censored outcomes. Trees in the oblique RSF are grown using linear combinations of predictors to create branches, whereas in the standard RSF, a single predictor is used. Oblique RSF ensembles often have higher prediction accuracy than standard RSF ensembles. However, assessing all possible linear combinations of predictors induces significant computational overhead that limits applications to large-scale data sets. In addition, few methods have been developed for interpretation of oblique RSF ensembles, and they remain more difficult to interpret compared to their axis-based counterparts. We introduce a method to increase computational efficiency of the oblique RSF and a method to estimate importance of individual predictor variables with the oblique RSF. Our strategy to reduce computational overhead makes use of Newton-Raphson scoring, a classical optimization technique that we apply to the Cox partial likelihood function within each non-leaf node of decision trees. We estimate the importance of individual predictors for the oblique RSF by negating each coefficient used for the given predictor in linear combinations, and then computing the reduction in out-of-bag accuracy. In general benchmarking experiments, we find that our implementation of the oblique RSF is approximately 450 times faster with equivalent discrimination and superior Brier score compared to existing software for oblique RSFs. We find in simulation studies that 'negation importance' discriminates between relevant and irrelevant predictors more reliably than permutation importance, Shapley additive explanations, and a previously introduced technique to measure variable importance with oblique RSFs based on analysis of variance. Methods introduced in the current study are available in the aorsf R package.Comment: 40 pages, 6 figure

Strangeness, charm and bottom in a chiral quark-meson model

In this paper we investigate an SU(3) extension of the chiral quark-meson model. The spectra of baryons with strangeness, charm and bottom are considered within a "rigid oscillator" version of this model. The similarity between the quark part of the Lagrangian in the model and the Wess-Zumino term in the Skyrme model is noted. The binding energies of baryonic systems with baryon number B=2 and 3 possessing strangeness or heavy flavor are estimated. The results obtained are in good qualitative agreement with those obtained previously in the topological soliton (Skyrme) model.Comment: 12 pages, no figures. Journal ref: submitted to Nucl.Phys.

Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat

INTRODUCTION: Of the more than one million global cases of breast cancer diagnosed each year, approximately fifteen percent are characterized as triple-negative, lacking the estrogen, progesterone, and Her2/neu receptors. Lack of effective therapies, younger age at onset, and early metastatic spread have contributed to the poor prognoses and outcomes associated with these malignancies. Here, we investigate the ability of the histone deacetylase inhibitor panobinostat (LBH589) to selectively target triple-negative breast cancer (TNBC) cell proliferation and survival in vitro and tumorigenesis in vivo. METHODS: TNBC cell lines MDA-MB-157, MDA-MB-231, MDA-MB-468, and BT-549 were treated with nanomolar (nM) quantities of panobinostat. Relevant histone acetylation was verified by flow cytometry and immunofluorescent imaging. Assays for trypan blue viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation, and DNA fragmentation were used to evaluate overall cellular toxicity. Changes in cell cycle progression were assessed with propidium iodide flow cytometry. Additionally, qPCR arrays were used to probe MDA-MB-231 cells for panobinostat-induced changes in cancer biomarkers and signaling pathways. Orthotopic MDA-MB-231 and BT-549 mouse xenograft models were used to assess the effects of panobinostat on tumorigenesis. Lastly, flow cytometry, ELISA, and immunohistochemical staining were applied to detect changes in cadherin-1, E-cadherin (CDH1) protein expression and the results paired with confocal microscopy in order to examine changes in cell morphology. RESULTS: Panobinostat treatment increased histone acetylation, decreased cell proliferation and survival, and blocked cell cycle progression at G2/M with a concurrent decrease in S phase in all TNBC cell lines. Treatment also resulted in apoptosis induction at 24 hours in all lines except the MDA-MB-468 cell line. MDA-MB-231 and BT-549 tumor formation was significantly inhibited by panobinostat (10 mg/kg/day) in mice. Additionally, panobinostat up-regulated CDH1 protein in vitro and in vivo and induced cell morphology changes in MDA-MB-231 cells consistent with reversal of the mesenchymal phenotype. CONCLUSIONS: This study revealed that panobinostat is overtly toxic to TNBC cells in vitro and decreases tumorigenesis in vivo. Additionally, treatment up-regulated anti-proliferative, tumor suppressor, and epithelial marker genes in MDA-MB-231 cells and initiated a partial reversal of the epithelial-to-mesenchymal transition. Our results demonstrate a potential therapeutic role of panobinostat in targeting aggressive triple-negative breast cancer cell types

Rethinking physical activity communication: using focus groups to understand women’s goals, values, and beliefs to improve public health

Abstract Background Communication about physical activity (PA) frames PA and influences what it means to people, including the role it plays in their lives. To the extent that PA messages can be designed to reflect outcomes that are relevant to what people most value experiencing and achieving in their daily lives, the more compelling and effective they will be. Aligned with self-determination theory, this study investigated proximal goals and values that are salient in everyday life and how they could be leveraged through new messaging to better support PA participation among women. The present study was designed to examine the nature of women’s daily goals and priorities and investigate women’s PA beliefs, feelings, and experiences, in order to identify how PA may compete with or facilitate women’s daily goals and priorities. Preliminary recommendations are proposed for designing new PA messages that align PA with women’s daily goals and desired experiences to better motivate participation. Methods Eight focus groups were conducted with White, Black, and Hispanic/Latina women aged 22–49, stratified by amount of self-reported PA (29 low active participants, 11 high active participants). Respondents discussed their goals, values, and daily priorities along with beliefs, feelings about and experiences being physically active. Data were collected, coded, and analyzed using a thematic analysis strategy to identify emergent themes. Results Many of the goals and values that both low and high active participants discussed as desiring and valuing map on to key principles of self-determination theory. However, the discussions among low active participants suggested that their beliefs, feelings, experiences, and definitions of PA were in conflict with their proximal goals, values, and priorities, also undermining their psychological needs for autonomy, competence, and relatedness. Conclusions Findings from this study can be used to inform and evaluate new physical activity communication strategies that leverage more proximal goals, values, and experiences of happiness and success to better motivate PA among ethnically diverse low active women. Specifically, this research suggests a need to address how women’s daily goals and desired experiences may undermine PA participation, in addition to framing PA as facilitating rather than competing with their daily priorities and desired leisure-time experiences.https://deepblue.lib.umich.edu/bitstream/2027.42/136775/1/12889_2017_Article_4361.pd

Insect herbivory and herbivores of Ficus species along a rain forest elevational gradient in Papua New Guinea

Classic research on elevational gradients in plant–herbivore interactions holds that insect herbivore pressure is stronger under warmer climates of low elevations. However, recent work has questioned this paradigm, arguing that it oversimplifies the ecological complexity in which plant–insect herbivore interactions are embedded. Knowledge of antagonistic networks of plants and herbivores is however crucial for understanding the mechanisms that govern ecosystem functioning. We examined herbivore damage and insect herbivores of eight species of genus Ficus (105 saplings) and plant constitutive defensive traits of two of these species, along a rain forest elevational gradient of Mt. Wilhelm (200–2,700 m a.s.l.), in tropical Papua New Guinea. We report overall herbivore damage 2.4% of leaf area, ranging from 0.03% in Ficus endochaete at 1,700 m a.s.l. to 6.1% in F. hombroniana at 700 m a.s.l. Herbivore damage and herbivore abundances varied significantly with elevation, as well as among the tree species, and between the wet and dry season. Community‐wide herbivore damage followed a hump‐shaped pattern with the peak between 700 and 1,200 m a.s.l. and this pattern corresponded with abundance of herbivores. For two tree species surveyed in detail, we observed decreasing and hump‐shaped patterns in herbivory, in general matching the trends found in the set of plant defenses measured here. Our results imply that vegetation growing at mid‐elevations of the elevational gradient, that is at the climatically most favorable elevations where water is abundant, and temperatures still relatively warm, suffers the maximum amount of herbivorous damage which changes seasonally, reflecting the water availability

Conserved community structure and simultaneous divergence events in the fig wasps associated with Ficus benjamina in Australia and China

Localised patterns of species diversity can be influenced by many factors, including regional species pools, biogeographic features and interspecific interactions. Despite recognition of these issues, we still know surprisingly little about how invertebrate biodiversity is structured across geographic scales. In particular, there have been few studies of how insect communities vary geographically while using the same plant host. We compared the composition (species, genera) and functional structure (guilds) of the chalcid wasp communities associated with the widespread fig tree, Ficus benjamina, towards the northern (Hainan province, China) and southern (Queensland, Australia) edges of its natural range. Sequence data were generated for nuclear and mtDNA markers and used to delimit species, and Bayesian divergence analyses were used to test patterns of community cohesion through evolutionary time. Both communities host at least 14 fig wasp species, but no species are shared across continents. Community composition is similar at the genus level, with six genera shared although some differ in species diversity between China and Australia; a further three genera occur in only China or Australia. Community functional structure remains very similar in terms of numbers of species in each ecological guild despite community composition differing a little (genera) or a lot (species), depending on taxonomic level. Bayesian clustering analyses favour a single community divergence event across continents over multiple events for different ecological guilds. Molecular dating estimates of lineage splits between nearest inter-continental species pairs are broadly consistent with a scenario of synchronous community divergence from a shared "ancestral community". Fig wasp community structure and genus-level composition are largely conserved in a wide geographic comparison between China and Australia. Moreover, dating analyses suggest that the functional community structure has remained stable for long periods during historic range expansions. This suggests that ecological interactions between species may play a persistent role in shaping these communities, in contrast to findings in some comparable temperate systems

Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP

An experimental study of the normalized three-jet rate of b quark events with respect to light quarks events (light= \ell \equiv u,d,s) has been performed using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are found to agree with theoretical predictions treating mass corrections at next-to-leading order. Measurements of the b quark mass have also been performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data are found to be better described when using the running mass. The measurement yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12 (theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise measurement of the b mass derived from a high energy process. When compared to other b mass determinations by experiments at lower energy scales, this value agrees with the prediction of Quantum Chromodynamics for the energy evolution of the running mass. The mass measurement is equivalent to a test of the flavour independence of the strong coupling constant with an accuracy of 7 permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.