Usual energy intake mediates the relationship between food reinforcement and BMI

The relative reinforcing value of food (RRV(food)) is positively associated with energy consumed and overweight status. One hypothesis relating these variables is that food reinforcement is related to BMI through usual energy intake. Using a sample of two hundred fifty-two adults of varying weight and BMI levels, results showed that usual energy intake mediated the relationship between RRV(food) and BMI (estimated indirect effect = 0.0027, bootstrapped 95% confidence intervals (CIs) 0.0002-0.0068, effect ratio = 0.34), controlling for age, sex, minority status, education, and reinforcing value of reading (RRV(reading)). Laboratory and usual energy intake were correlated (r = 0.24, P < 0.001), indicating that laboratory energy intake could provide an index of eating behavior in the natural environment. The mediational relationship observed suggests that increasing or decreasing food reinforcement could influence body weight by altering food consumption. Research is needed to develop methods of modifying RRV(food) to determine experimentally whether manipulating food reinforcement would result in changes in body weight.     

Are filarial nematode Wolbachia obligate mutualist symbionts?

The intracellular symbiotic bacteria of filarial nematodes have inspired new ideas for the control of disease using antibacterial drugs. For effective, long-term control, this requires that the bacteria are essential to their nematode hosts. Two recent studies offer conflicting evidence: long, close coevolution between most filarial nematodes and their symbionts contrasts with many species having naturally lost them. An attempt to transfer symbionts to an uninfected host found that the bacteria did not thrive, suggesting they are adapted to one host.     

Immortalized Human Schwann Cell Lines Derived From Tumors of Schwannomatosis Patients

Schwannomatosis, a rare form of neurofibromatosis, is characterized predominantly by multiple, often painful, schwannomas throughout the peripheral nervous system. The current standard of care for schwannomatosis is surgical resection. A major obstacle to schwannomatosis research is the lack of robust tumor cell lines. There is a great need for mechanistic and drug discovery studies of schwannomatosis, yet appropriate tools are not currently available. Schwannomatosis tumors are difficult to grow in culture as they survive only a few passages before senescence. Our lab has extensive experience in establishing primary and immortalized human Schwann cell cultures from normal tissue that retain their phenotypes after immortalization. Therefore we took on the challenge of creating immortalized human Schwann cell lines derived from tumors from schwannomatosis patients. We have established and fully characterized 2 schwannomatosis cell lines from 2 separate patients using SV40 virus large T antigen. One patient reported pain and the other did not. The schwannomatosis cell lines were stained with S100B antibodies to confirm Schwann cell identity. The schwannomatosis cells also expressed the Schwann cell markers, p75NTR, S100B, and NGF after multiple passages. Cell morphology was retained following multiple passaging and freeze/ thaw cycles. Gene expression microarray analysis was used to compare the cell lines with their respective parent tumors. No differences in key genes were detected, with the exception that several cell cycle regulators were upregulated in the schwannomatosis cell lines when compared to their parent tumors. This upregulation was apparently a product of cell culturing, as the schwannomatosis cells exhibited the same expression pattern of cell cycle regulatory genes as normal primary human Schwann cells. Cell growth was also similar between normal primary and immortalized tumor cells in culture. Accurate cell lines derived directly from human tumors will serve as invaluable tools for advancing schwannomatosis research, including drug screening.     

A global metagenomic map of urban microbiomes and antimicrobial resistance

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Novel Lys63-linked ubiquitination of IKKβ induces STAT3 signaling

NFκB signaling plays a significant role in human disease, including breast and ovarian carcinoma, insulin resistance, embryonic lethality and liver degeneration, rheumatoid arthritis, aging and Multiple Myeloma (MM). Inhibitor of κB (IκB) kinase β (IKKβ) regulates canonical Nuclear Factor κB (NFκB) signaling in response to inflammation and cellular stresses. NFκB activation requires Lys63-linked (K63-linked) ubiquitination of upstream proteins such as NEMO or TAK1, forming molecular complexes with membrane-bound receptors. We demonstrate that IKKβ itself undergoes K63-linked ubiquitination. Mutations in IKKβ at Lys171, identified in Multiple Myeloma and other cancers, lead to a dramatic increase in kinase activation and K63-linked ubiquitination. These mutations also result in persistent activation of STAT3 signaling. Liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS) analysis identified Lys147, Lys418, Lys555 and Lys703 as predominant ubiquitination sites in IKKβ. Specific inhibition of the UBC13-UEV1A complex responsible for K63-linked ubiquitination establishes Lys147 as the predominant site of K63-ubiquitin conjugation and responsible for STAT3 activation. Thus, IKKβ activation leads to ubiquitination within the kinase domain and assemblage of a K63-ubiquitin conjugated signaling platform. These results are discussed with respect to the importance of upregulated NFκB signaling known to occur frequently in MM and other cancers.