Over 500 million people interact daily with Facebook. Yet, whether Facebook use influences subjective well-being over time is unknown. We addressed this issue using experience-sampling, the most reliable method for measuring in-vivo behavior and psychological experience. We text-messaged people five times per day for two-weeks to examine how Facebook use influences the two components of subjective well-being: how people feel moment-to-moment and how satisfied they are with their lives. Our results indicate that Facebook use predicts negative shifts on both of these variables over time. The more people used Facebook at one time point, the worse they felt the next time we text-messaged them; the more they used Facebook over two-weeks, the more their life satisfaction levels declined over time. Interacting with other people “directly” did not predict these negative outcomes. They were also not moderated by the size of people's Facebook networks, their perceived supportiveness, motivation for using Facebook, gender, loneliness, self-esteem, or depression. On the surface, Facebook provides an invaluable resource for fulfilling the basic human need for social connection. Rather than enhancing well-being, however, these findings suggest that Facebook may undermine it.

Prior research indicates that Facebook usage predicts declines in subjective well-being over time. How does this come about? We examined this issue in 2 studies using experimental and field methods. In Study 1, cueing people in the laboratory to use Facebook passively (rather than actively) led to declines in affective well-being over time. Study 2 replicated these findings in the field using experience-sampling techniques. It also demonstrated how passive Facebook usage leads to declines in affective well-being: by increasing envy. Critically, the relationship between passive Facebook usage and changes in affective well-being remained significant when controlling for active Facebook use, non-Facebook online social network usage, and direct social interactions, highlighting the specificity of this result. These findings demonstrate that passive Facebook usage undermines affective well-being.

Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment.

We examined rodent models with altered levels of mitoNEET, a protein residing in the mitochondrial outer membrane. Adipocyte-specific overexpression of mitoNEET enhances lipid-uptake and storage, leading to an expansion of adipose tissue mass. Despite the resulting massive obesity, benign aspects of adipose tissue expansion prevail and insulin sensitivity is preserved. MitoNEET inhibits mitochondrial iron transport into the matrix. Since iron is a rate-limiting component for electron transport, mitoNEET reduces β-oxidation rates. This is associated with reduced mitochondrial membrane potential and reduced reactive oxygen species damage, along with higher levels of adiponectin production. Conversely, the reduction of mitoNEET enhances mitochondrial respiratory capacity through enhanced iron content in the matrix, with reduced weight gain on a high fat diet. However, a reduction of mitoNEET also causes heightened oxidative-stress and glucose-intolerance. MitoNEET is therefore a potent regulator of mitochondrial function that profoundly impacts the dynamics of cellular and whole-body lipid homeostasis.

Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC-metal (loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]-PC 2 transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)-PC 2 transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs.ABC transporter | vacuolar sequestration | multidrug resistance-associated protein

ABC transporters constitute one of the largest protein families found in all living organisms. ABC transporters are driven by ATP hydrolysis and can act as exporters as well as importers. The plant genome encodes for more than 100 ABC transporters, largely exceeding that of other organisms. In Arabidopsis, only 22 out of 130 have been functionally analyzed. They are localized in most membranes of a plant cell such as the plasma membrane, the tonoplast, chloroplasts, mitochondria and peroxisomes and fulfill a multitude of functions. Originally identified as transporters involved in detoxification processes, they have later been shown to be required for organ growth, plant nutrition, plant development, response to abiotic stresses, pathogen resistance and the interaction of the plant with its environment. To fulfill these roles they exhibit different substrate specifies by e.g. depositing surface lipids, accumulating phytate in seeds, and transporting the phytohormones auxin and abscisic acid. The aim of this review is to give an insight into the functions of plant ABC transporters and to show their importance for plant development and survival.

Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The EPR effect (Enhanced Permeability and Retention) can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Further, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial anti-tumor efficacy and is in human trials. Here, we demonstrate that thermally sensitive liposomes release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream.

Adipocytes represent a major cell type in the mammary tumor microenvironment and are important for tumor growth. Collagen VI (COL6) is highly expressed in adipose tissue, upregulated in the obese state, and enriched in breast cancer lesions and is a stimulator of mammary tumor growth. Here, we have described a cleavage product of the COL6α3 chain, endotrophin (ETP), which serves as the major mediator of the COL6-mediated tumor effects. ETP augmented fibrosis, angiogenesis, and inflammation through recruitment of macrophages and endothelial cells. Moreover, ETP expression was associated with aggressive mammary tumor growth and high metastatic growth. These effects were partially mediated through enhanced TGF-β signaling, which contributes to tissue fibrosis and epithelial-mesenchymal transition (EMT) of tumor cells. Our results highlight the crucial role of ETP as an obesity-associated factor that promotes tumor growth in the context of adipocyte interactions with tumor and stromal cells.