The Mediterranean diet has long been attributed to preventing or delaying the onset of cardiovascular disease, diabetes and various solid organ cancers. In this particular study, a rosemary extract ...standardized to carnosic acid was evaluated for its potential in disrupting the endoplasmic reticulum machinery to decrease the viability of prostate cancer cells and promote degradation of the androgen receptor. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two different patients undergoing radical prostatectomy were treated with standardized rosemary extract and evaluated by flow cytometry, MTT, BrdU, Western blot and fluorescent microscopy. A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress. This biphasic response suggests that standardized rosemary extract may preferentially target cancer cells as opposed to "normal" cells. Furthermore, we observed standardized rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153. Using a xenograft tumor model we observed standardized rosemary extract when given orally to significantly suppress tumor growth by 46% compared to mice not receiving standardized rosemary extract. In the last several years regulatory governing bodies (e.g. European Union) have approved standardized rosemary extracts as food preservatives. These results are especially significant as it is becoming more likely that individuals will be receiving standardized rosemary extracts that are a part of a natural preservative system in various food preparations. Taken a step further, it is possible that the potential benefits that are often associated with a "Mediterranean Diet" in the future may begin to extend beyond the Mediterranean diet as more of the population is consuming standardized rosemary extracts.
Abstract
Successful communication in daily life depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with ...a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, comprehension of acoustically degraded speech in these diseases has been little studied. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer’s disease and 30 patients representing the three canonical syndromes of primary progressive aphasia (non-fluent/agrammatic variant primary progressive aphasia; semantic variant primary progressive aphasia; logopenic variant primary progressive aphasia), compared to 25 healthy age-matched controls. As a paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility.
We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients’ brain images) were also assessed. Mean noise-vocoded speech intelligibility threshold was significantly higher in all patient groups than healthy controls, and significantly higher in Alzheimer’s disease and logopenic variant primary progressive aphasia than semantic variant primary progressive aphasia (all P < 0.05). In a receiver operating characteristic analysis, vocoded intelligibility threshold discriminated Alzheimer’s disease, non-fluent variant and logopenic variant primary progressive aphasia patients very well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in predefined regions of interest, impaired noise-vocoded speech comprehension across syndromes was significantly associated (P < 0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network that has previously been widely implicated in processing degraded speech signals.
Our findings suggest that the comprehension of acoustically altered speech captures an auditory brain process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications.
Jiang et al. show that people with Alzheimer’s disease and progressive aphasia are impaired versus healthy controls on a degraded speech comprehension task. Using voxel-based morphometry, they show that impaired task performance correlates with atrophy of a fronto-temporal cortical network previously implicated in degraded speech processing.
Purpose of Review
The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable ...challenges to clinicians and researchers.
Recent Findings
Here, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering ‘fragmentary’ syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed.
Summary
New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies.
In this paper, we address the question of how to automatically map computational kernels to highly efficient code for a wide range of computing platforms and establish the correctness of the ...synthesized code. More specifically, we focus on two fundamental problems that software developers are faced with: performance portability across the ever-changing landscape of parallel platforms and correctness guarantees for sophisticated floating-point code. The problem is approached as follows: We develop a formal framework to capture computational algorithms, computing platforms, and program transformations of interest, using a unifying mathematical formalism we call operator language (OL). Then we cast the problem of synthesizing highly optimized computational kernels for a given machine as a strongly constrained optimization problem that is solved by search and a multistage rewriting system. Since all rewrite steps are semantics preserving, our approach establishes equivalence between the kernel specification and the synthesized program. This approach is implemented in the SPIRAL system, and we demonstrate it with a selection of computational kernels from the signal and image processing domain, software-defined radio, and robotic vehicle control. Our target platforms range from mobile devices, desktops, and server multicore processors to large-scale high-performance and supercomputing systems, and we demonstrate performance comparable to expertly hand-tuned code across kernels and platforms.
Four new adjacent bis-tetrahydrofuran acetogenins, bullacin C (7), uvarirufin (9), and uvariasolins III (12) and IV (13), along with 11 known acetogenins, were isolated from the stem of Uvaria rufa. ...Their structures were elucidated based on spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and MALDI-MS/MS of the lithium adducts. Absolute configurations were assigned using Mosher ester analysis and ECD measurements. Uvarirufin (9) possesses a unique C-39 skeleton among acetogenins. Most tested acetogenins exhibited cytotoxicity against human cancer cell lines (HCT 116, 22Rv1, MDA-MB-435, OVCAR3). Squamocin (8) and uvarirufin (9) were found to be the most potent, with an IC50 value of 1.2 μM for both in HCT 116 colon cancer cells. Additionally, a new application of Dragendorff’s reagent is proposed herein for the TLC detection of acetogenins.
The three‐dimensional (3D) physical aspects of ecosystems are intrinsically linked to ecological processes. Here, we describe structural diversity as the volumetric capacity, physical arrangement, ...and identity/traits of biotic components in an ecosystem. Despite being recognized in earlier ecological studies, structural diversity has been largely overlooked due to an absence of not only a theoretical foundation but also effective measurement tools. We present a framework for conceptualizing structural diversity and suggest how to facilitate its broader incorporation into ecological theory and practice. We also discuss how the interplay of genetic and environmental factors underpin structural diversity, allowing for a potentially unique synthetic approach to explain ecosystem function. A practical approach is then proposed in which scientists can test the ecological role of structural diversity at biotic–environmental interfaces, along with examples of structural diversity research and future directions for integrating structural diversity into ecological theory and management across scales.
Scope: Resveratrol (3,5,4′‐trihydroxystilbene) is a phytoalexin shown to possess a multitude of health‐promoting properties in pre‐clinical studies. However, the poor in vivo bioavailability of ...resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination.
Methods and results: Employing a standardized LC/MS assay, we determined the effect of piperine co‐administration with resveratrol on serum levels resveratrol and resveratrol‐3‐O‐β‐D‐glucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg; oral gavage)+piperine (10 mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol‐3‐O‐β‐D‐glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (Cmax) was increased to 1544% with the addition of piperine.
Conclusion: Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.
Molecular nonlinear optical (NLO) crystals feature important advantages compared to inorganic counterparts, such as low dielectric constants, ultrafast response times, and large electro‐optic ...coefficients. Conjugated push–pull chromophores connecting electron‐donating with accepting groups are often employed in the design of these crystals. However, associated large molecular dipole moments induce antiparallel or centrosymmetric conformations in the solid‐state, which leads to NLO inactivity. The cation–anion hydrogen bond interactions of a hydroxy‐piperidino electron donor group are combined with increased van der Waals volume effects induced by an ethyl modification of the electron‐accepting moiety. This produces non‐centrosymmetric packing in the organic salt EHPSI‐4NBS ((E)‐1‐ethyl‐2‐(4‐(4‐(hydroxymethyl)piperidin‐1‐yl)styryl)‐3,3‐dimethyl‐3H‐indol‐1‐ium 4‐nitrobenzenesulfonate). Converting a methyl group into ethyl changes the packing symmetry in the molecular crystal to switch on NLO activity. This behavior is attributed to the increased size of the ethyl group, which pushes apart the van der Waals contacts of the cation that lead to centrosymmetric packing in the methyl derivative. To test the NLO properties of EHPSI‐4NBS, THz generation experiments are performed at 1200 nm pump wavelength. Spectral amplitude similar to DAST ((E)‐4‐(4‐(dimethylamino)styryl)‐1‐methylpyridin‐1‐ium tosylate) crystal is observed with generation profile from 0 to 3.8 THz.
The design of a new non‐centrosymmetric organic salt crystal (EHPSI‐4NBS) is achieved by adding one carbon to the methylated quaternary nitrogen of the cation in centrosymmetric HPSI‐4NBS. The additional carbon creates a cation conformational shifting effect that reduces the molecular interactions, causing a drastic change in molecular packing in EHPSI‐4NBS compared with HPSI‐4NBS.
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