Measuring the Contributions of Motives and Perceived Barriers to Active Aging

General motivation to be active and general perceived barriers to activity may help to explain the overall activity patterns of older persons in the second half of the life course. We report on a project designed to develop and refine measures of motivation and perceived barriers that can be used to examine the relationships between activity motivation, activity barriers, and several forms of actual activities. Four specific activities were considered: working, volunteering, exercising, and taking classes. An opportunity sample of 192 middle-aged and older persons from eastern Massachusetts responded to a questionnaire concerned with motivation, perceived barriers, and activities. Reliable measures of both general and activity-specific motivation and perceived barriers to activity were developed. The measures were examined for construct validity purposes. This analysis demonstrates that general activity motivation and perceived barriers are helpful in understanding patterns of activity among older people

Elder Activities: Patterns, Motives, and Interpretation. Massachusetts Lifestyles Study III

We are engaged in a continuing effort to understand the scope of elder activity and the implications of activity for well-being. We are particularly interested in the forces that encourage or inhibit multiple forms of activity, the ways in which participation in some activities influences participation in other activities, and the cumulative implications of activities for well being. Our interest in multiple forms of activities sets us somewhat apart from Gerontologists who focus on single forms of activity such as volunteering, taking classes, caring for grandchildren, working, or exercising

Cytotoxicity and polyphenol diversity in selected parts of Mangifera pajang and Artocarpus odoratissimus fruits.

Purpose Research on cancer chemopreventive properties of fruits has increased in recent years. Polyphenols have been suggested to exert such effects. The purpose of this paper is to determine the cytotoxic activity of Mangifera pajang (bambangan) and Artocarpus odoratissimus (tarap) crude extracts against selected cancer cell lines (i.e. ovarian, liver and colon cancer) and to compare the amount of selected polyphenols (phenolic acids, flavanones, flavonols and flavones) in the kernel, peel and flesh of M. pajang; and the seed and flesh of A. odoratissimus. Design/methodology/approach Cytotoxicity activity of the extracts are investigated using MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay while polyphenols are determined using high performance liquid chromatography. Findings The results show that only the kernel and peel extracts from M. pajang display cytotoxic activity in liver and ovarian cancer cell lines with IC50 values ranging from 34.5 to 92.0  μg/ml. The proliferation of colon cancer cell line is inhibited only by the kernel of M. pajang with IC50 value of 63.0  μg/ml. The kernel and peel from M. pajang contains a broad range of polyphenol phytochemicals which might be responsible for the cytotoxicity activity against selected cancer cell lines. Originality/value Previous reports have indicated that both M. pajang and A. odoratissimus contain high antioxidant properties. This study further determines the phytochemicals profiling in both fruits, which might contribute to the antioxidant activity. Besides that, the result from this study shows that the waste of the fruits (i.e. kernel and peel) contain superior phenolic phytochemicals and display better anticancer potential compared to the flesh; suggests the use of them in health‐industry application. Utilization of all parts of the fruits (i.e. flesh, seed, kernel and peel) for the development of nutraceutical and functional food application is suggested

Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan).

An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5μg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24. h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72. h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36. h for MCF-7 cells and 24. h for MDA-MB-231cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines

Evolved Resistance to a Novel Cationic Peptide Antibiotic Requires High Mutation Supply

Background and Objectives A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 (also known as PLG0206) is a promising broad-spectrum antimicrobial compound that has completed Phase I clinical studies. It has activity against Gram-negative and Gram-positive bacteria including infections associated with biofilm. No definitive mechanisms of resistance to WLBU2 have been identified. Methodology Here, we used experimental evolution under different levels of mutation supply and whole genome sequencing (WGS) to detect the genetic pathways and probable mechanisms of resistance to this peptide. We propagated populations of wild-type and hypermutator Pseudomonas aeruginosa in the presence of WLBU2 and performed WGS of evolved populations and clones. Results Populations that survived WLBU2 treatment acquired a minimum of two mutations, making the acquisition of resistance more difficult than for most antibiotics, which can be tolerated by mutation of a single target. Major targets of resistance to WLBU2 included the orfN and pmrB genes, previously described to confer resistance to other cationic peptides. More surprisingly, mutations that increase aggregation such as the wsp pathway were also selected despite the ability of WLBU2 to kill cells growing in a biofilm. Conclusions and implications The results show how experimental evolution and WGS can identify genetic targets and actions of new antimicrobial compounds and predict pathways to resistance of new antibiotics in clinical practice

Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice

A critical event in ischemia-based cell death is the opening of the mitochondrial permeability transition pore (MPTP). However, the molecular identity of the components of the MPTP remains unknown. Here, we determined that the Bcl-2 family members Bax and Bak, which are central regulators of apoptotic cell death, are also required for mitochondrial pore-dependent necrotic cell death by facilitating outer membrane permeability of the MPTP. Loss of Bax/Bak reduced outer mitochondrial membrane permeability and conductance without altering inner membrane MPTP function, resulting in resistance to mitochondrial calcium overload and necrotic cell death. Reconstitution with mutants of Bax that cannot oligomerize and form apoptotic pores, but still enhance outer membrane permeability, permitted MPTP-dependent mitochondrial swelling and restored necrotic cell death. Our data predict that the MPTP is an inner membrane regulated process, although in the absence of Bax/Bak the outer membrane resists swelling and prevents organelle rupture to prevent cell death

Structural Features Underlying Raloxifene’s Biophysical Interaction with Bone Matrix

Raloxifene, a selective estrogen receptor modulator (SERM), reduces fracture risk at least in part by improving the mechanical properties of bone in a cell- and estrogen receptor-independent manner. In this study, we determined that raloxifene directly interacts with the bone tissue. Through the use of multiple and complementary biophysical techniques including nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR), we show that raloxifene interacts specifically with the organic component or the organic/mineral composite, and not with hydroxyapatite. Structure–activity studies reveal that the basic side chain of raloxifene is an instrumental determinant in the interaction with bone. Thus, truncation of portions of the side chain reduces bone binding and also diminishes the increase in mechanical properties. Our results support a model wherein the piperidine interacts with bone matrix through electrostatic interactions with the piperidine nitrogen and through hydrophobic interactions (van der Waals) with the aliphatic groups in the side chain and the benzothiophene core. Furthermore, in silico prediction of the potential binding sites on the surface of collagen revealed the presence of a groove with sufficient space to accommodate raloxifene analogs. The hydroxyl groups on the benzothiophene nucleus, which are necessary for binding of SERMs to the estrogen receptor, are not required for binding to the bone surface, but mediate a more robust binding of the compound to the bone powder. In conclusion, we report herein a novel property of raloxifene analogs that allows them to interact with the bone tissue through potential contacts with the organic matrix and in particular collagen

Role of fatty acid transporters in epidermis: Implications for health and disease

Skin epidermis is an active site of lipid synthesis. The intercellular lipids of human stratum corneum (SC) are unique in composition and quite different from the lipids found in most biological membranes. The three major lipids in the SC are free fatty acids, cholesterol and ceramides. Fatty acids can be synthesized by keratinocytes de novo and, in addition, need to be taken up from the circulation. The latter process has been shown to be protein mediated, and several fatty acid transporters are expressed in skin. Recent studies of transgenic and knockout animal models for fatty acid transporters and the identification of fatty acid transport protein 4 (FATP4 or SLC27A4) mutations as causative for Ichthyosis Prematurity Syndrome highlight the vital roles of fatty acid transport and metabolism in skin homeostasis. This review provides an overview of our current understanding of the role of fatty acids and their transporters in cutaneous biology, including their involvement in epidermal barrier generation and skin inflammation

Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching