Phorbol myristate acetate stimulates microtubule and 10-nm filament extension and lysosome redistribution in mouse macrophages

Phorbol myristate acetate (PMA) stimulates cell spreading and fluid-phase pinocytosis in mouse peritoneal macrophages. Colchicine (10(-5) M) and cytochalasin B (10(-5) M) abolish PMA stimulated pinocytosis but have little effect on cellular spreading (Phaire-Washington et al., 1980, J. Cell Biol., 86:634-640). We report here that PMA also alters the organization of the cytoskeleton and the distrubution of organelles in these cells. Neither control nor PMA-treated macrophages contain actin cables. PMA-treated resident thioglycolate-elicited macrophages exhibit beneath their substrate-adherent membranes many randomly distributed punctate foci that stain brightly for actin. The appearance and distribution of these actin-containing foci are not altered by colchicine (10(-5) M) or cytochalasin B (10(-5) M). In thioglycolate-elicited macrophages PMA causes the extension and radial organization of microtubules and 10-nm filaments and promotes the movement of secondary lysosomes from their perinuclear location to the peripheral cytoplasm. Depending upon the concentration of PMA used, 45-71% of thioglycolate-elicited macrophages and 32-44% of proteose-peptone-elicited macrophages and numerous lysosomes, radiating from the centrosphere region, arranged linearly along microtubule and 10-nm filament bundles. Colchicine (10(-5) M) and podophyllotoxin (10(-5) M) prevent the radial redistribution of microtubules, 10-nm filaments, and lysosomes in these cells. Cytochalasins B and D (10(-5) M) have no inhibitory effects on these processes. These findings indicate that microtubules and 10-nm filaments respond in a coordinated fashion to PMA and to agents that inhibit microtubule function; they suggest that these cytoskeletal elements regulate the movement and distribution of lysosomes in the macrophage cytoplasm

A youth empowerment intervention to prevent childhood obesity: design and methods for a cluster randomized trial of the H2GO! program

BACKGROUND: Reducing sugar-sweetened beverage (SSB) consumption is a promising dietary target for childhood obesity prevention. This paper describes the design and methods of a cluster randomized trial of H2GO!, a youth empowerment intervention to prevent childhood obesity through reducing SSB consumption among a low-income, ethnically diverse sample of youth. METHODS: This cluster randomized controlled trial is an academic-community partnership with the Massachusetts Alliance of Boys and Girls Clubs (BGC). Ten BGC sites will be randomly assigned to the H2GO! intervention or a wait-list, usual care control. Eligible study participants will be N = 450 parent-child pairs (youth ages 9-12 years and their parents/caregivers) recruited from participating BGCs. The 6-week in-person H2GO! intervention consists of 12 group-based sessions delivered by BGC staff and youth-led activities. An innovative feature of the intervention is the development of youth-produced narratives as a strategy to facilitate youth empowerment and parental engagement. Child outcomes include measured body mass index z scores (zBMI), beverage intake, and youth empowerment. Parent outcomes include beverage intake and availability of SSBs at home. Outcomes will be measured at baseline and at 2, 6, and 12 months. With a 75% retention rate, the study is powered to detect a minimum group difference of 0.1 zBMI units over 12 months. DISCUSSION: Empowering youth may be a promising intervention approach to prevent childhood obesity through reducing SSB consumption. This intervention was designed to be delivered through BGCs and is hypothesized to be efficacious, relevant, and acceptable for the target population of low-income and ethnically diverse youth. TRIAL REGISTRATION: ClinicalTrials.gov NCT04265794 . Registered 11 February 2020

Guest Induced Transformations of Assembled Pyridyl Bis-Urea Macrocycles

Pyridine macrocycles with no cavities assembled into close packed columns yet absorbed guests including hydrogen, carbon dioxide, and iodine

Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis.

Obesity and extracellular matrix (ECM) density are considered independent risk and prognostic factors for breast cancer. Whether they are functionally linked is uncertain. We investigated the hypothesis that obesity enhances local myofibroblast content in mammary adipose tissue and that these stromal changes increase malignant potential by enhancing interstitial ECM stiffness. Indeed, mammary fat of both diet- and genetically induced mouse models of obesity were enriched for myofibroblasts and stiffness-promoting ECM components. These differences were related to varied adipose stromal cell (ASC) characteristics because ASCs isolated from obese mice contained more myofibroblasts and deposited denser and stiffer ECMs relative to ASCs from lean control mice. Accordingly, decellularized matrices from obese ASCs stimulated mechanosignaling and thereby the malignant potential of breast cancer cells. Finally, the clinical relevance and translational potential of our findings were supported by analysis of patient specimens and the observation that caloric restriction in a mouse model reduces myofibroblast content in mammary fat. Collectively, these findings suggest that obesity-induced interstitial fibrosis promotes breast tumorigenesis by altering mammary ECM mechanics with important potential implications for anticancer therapies

Hydrographic observations from the US/PRC Cooperative Program in the Western Equatorial Pacific Ocean, cruises 5-8

In support of the Tropical Ocean and Global Atmosphere (TOGA) program, investigators from the Woods Hole Oceanographic Institution (WHOI), NOAA Pacific Marine Environmental Laboratory (PMEL), and the State Oceanic Administration (SOA) from both Qingdao (First Institute) and Guangzhou (South China Sea Branch) conducted hydrographic observations aboard the Chinese R/V Xiang Yang Hong 14 in the western equatorial Pacific Ocean. The objective of this component of the TOGA program was to document the water mass property distributions of the western equatorial Pacific and describe the oceanic velocity field. The four cruises summarized here were conducted during the period November 1988 to July 1990 and are the final half of an eight cruise repeated survey of the region begun in 1985. Conductivity-Temperature-Depth-Oxygen (CTD/O2) stations were collected to a minimum cast depth of 2500m or the bottom when shallower. The cruises reoccupied the same stations to provide temporal information. Summarized listings of CTD/02 data together with selected physical properties of sea water for these cruises are provided here, as well as a description of the hardware used and an explanation of the data reduction techniques employed.Funding was provided by the National Oceanic and Atmospheric Administration under Grant No. NA85AA-D-AC117

Post-stroke Intranasal (+)-Naloxone Delivery Reduces Microglial Activation and Improves Behavioral Recovery from Ischemic Injury

Peer reviewe

Hydrographic observations from the US/PRC Cooperative Program in the Western Equatorial Pacific Ocean, cruises 1-4

In support of the Tropical Oceans and Global Atmosphere (TOGA) program, investigators from Woods Hole Oceanographic Institution (WHOI), NOAA Pacific Marine Envionmental Laboratory and the State Oceanic Administration (SOA) from both Qingdao (First Institute) and Guangzhou (South China Sea Branch) conducted hydrographic observations aboard the Chinese Research vessels Xiang Yang Hong 5 and Xiang Yang Hong 14 in the western equatorial Pacific. The objective of this component of the TOGA program was to document the water mass property distributions of the western equatorial Pacific Ocean and describe the oceanic velocity field. The four cruises summarized here were conducted during the period November 1985 to June 1988 and are the first half of an eight cruise repeated survey of the region scheduled to be completed in spring 1990. Conductivity-Temperatue-Depth-Oxygen (CTD/02) stations were collected to a minimum cast depth of 2,500 m or the bottom when shallower. The cruises reoccupied the same stations to provide temporal information. Summarized listings of CTD/O2 data together with selected physical properties of sea water for these cruises are provided here, as well as a description of the hardware used and an explanation of the data reduction tehniques employed.Funding was provided by the National Oceanic and Atmospheric Administration

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF

26085 Key efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis in the phase 3 ADVANCE trial

Background: In ADVANCE, apremilast 30 mg BID (APR) demonstrated efficacy in mild-to-moderate psoriasis vs placebo (PBO). We report subgroup analyses by baseline psoriasis-involved BSA (≤5%, \u3e5%). Methods: Biologic-naive adults with mild-to-moderate psoriasis (sPGA 2-3, BSA 2%-15%, PASI 2-15) inadequately controlled with or intolerant to ≥1 topical were randomized to APR or PBO for 16 weeks. At Week 16, endpoints were compared between treatment groups and by baseline BSA. Results: At baseline, 284 patients had BSA ≤5% (APR: 143; PBO: 141); 311 had BSA \u3e5% (APR: 154; PBO: 157). Overall, a greater proportion of APR patients achieved the primary endpoint, sPGA response (score 0/1 [clear/almost clear] with ≥2-point reduction at Week 16) vs PBO (21.6% vs 4.1%, P 5%: 54.6% vs 14.9%, P 5%: 45.4% vs 17.6%, P 5%: 50.6% vs 19.2%, P 5%: 11.0 vs 10.0 DLQI 5-point improvement (baseline DLQI \u3e5): - BSA≤5%: 56.6% vs 31.2%, P =.0002 - BSA\u3e5%: 64.4% vs 36.4%, P ˂.0001. Conclusions: Greater proportions of patients achieved efficacy outcomes and greater improvements in QOL with APR vs PBO. Comparable improvements were observed between mild and moderate subgroups