Compartment-specific protein interactions in beryllium lung disease.

The study provides insights into proteins that may be relevant in BeS and CBD. It provides a framework to investigate the global changes in lung compartment-specific inflammatory cells to better understand the potential interplay of proteins in CBD. https://bit.ly/3PLNTXC.

Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice.

BACKGROUND/OBJECTIVES: The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis. The purpose of this study was to determine the role of ECM sulfated GAGs in adipose tissue homeostasis. METHODS: Adipose tissue and metabolic homeostasis in mice deficient in xylosyltransferase 2 (Xylt2-/-) were examined by histologic analyses, gene expression analyses, whole body fat composition measurements, and glucose tolerance test. Adipose tissue inflammation and adipocyte precursors were characterized by flow cytometry and in vitro culture of mesenchymal stem cells. RESULTS: Xylt2-/- mice have low body weight due to overall reductions in abdominal fat deposition. Histologically, the adipocytes are reduced in size and number in both gonadal and mesenteric fat depots of Xylt2-/- mice. In addition, these mice are glucose intolerant, insulin resistant, and have increased serum triglycerides as compared to Xylt2 + / + control mice. Furthermore, the adipose tissue niche has increased inflammatory cells and enrichment of proinflammatory factors IL6 and IL1ß, and these mice also have a loss of adipose tissue vascular endothelial cells. Lastly, xylosyltransferease-2 (XylT2) deficient mesenchymal stem cells from gonadal adipose tissue and bone marrow exhibit impaired adipogenic differentiation in vitro. CONCLUSIONS: Decreased GAGs due to the loss of the key GAG assembly enzyme XylT2 causes reduced steady state adipose tissue stores leading to a unique lipodystrophic model. Accumulation of an adipocytic precursor pool of cells is discovered indicating an interruption in differentiation. Therefore, adipose tissue GAGs are important in the homeostasis of adipose tissue by mediating control of adipose precursor development, tissue inflammation, and vascular development.

Fostering Strategies to Expand the Consumption of Edible Insects: The Value of a Tripartite Coalition between Academia, Industry, and Government.

Although many insect-based foods are nutritious and often an inexpensive option for human and domesticated animal consumption, there remains a negligible market for such foods in many countries. Several environmental and economic considerations underscore the potential value of insect-based foods, and emerging science suggests that diets incorporating such foods might also convey some genuine health benefits. However, if expanded markets for insect-based foods in cultures naïve to entomophagy are to be pursued, it will be important to develop multifaceted and coordinated strategies to 1) delineate authentic health benefits, 2) explore means of optimizing insect husbandry and food processing, 3) examine cultural barriers to acceptance, 4) formulate workable approaches to marketing, and 5) address relevant food regulations. We sought to construct a multidisciplinary coalition whose goals are to investigate the above-mentioned 5 issues. Eighteen individuals from government, industry, and academia, with collective expertise in the fields of entomology, insect husbandry, human nutrition, sustainable agriculture, entomophagy, consumer product development and marketing, food-processing technologies, food regulatory affairs, and the anthropology of food selection, convened a 1-d summit and formed a tripartite organization to integrate their varied perspectives. Collaborative efforts are underway among members of this coalition to accomplish these multiple goals. Coordinating efforts between accomplished experts in relevant fields of academia, government, and industry will greatly expand our knowledge of and appreciation for the potential benefits of insect-based foodstuffs to individuals, to society, and to the sustainability of the global food supply, and thereby inform us as to how to proceed in a judicious and intelligent manner.

Is it time for a new practice environment? Part III: designing and constructing your new practice environment.

In school, architects are taught "Form follows function," but all too often this concept is forgotten or not followed in planning medical practice environments. Things such as the architecture (look) of the building, the budget, the view from the office, etc., drive planning decisions when none of those can help promote doctor-patient interaction. The planning of a medical practice environment should follow an operational approach that is focused on the concept that best utilizing the doctors' time to provide care to more people is the ultimate goal. All decisions, from where the building is located, to where the exam rooms are located within the building, to how communication is handled, should all be based on how they best facilitate patent and doctor interaction.

Is it time for a new practice environment? Part II: an operational approach to determining space needs.

In today's practice of medicine, seeing patients requires space. The amount and type of space a practice needs are based on the volume of patients to be seen, services provided, and the number of providers in the practice. To evaluate whether or not your current practice space effectively houses your practice or if a new building could better support your practice, the amount and type of space the practice needs must be determined. Once this space needs assessment is done, it can be used to evaluate the current practice environment, and if need be develop preliminary drawings to evaluate new space. Both operational flow and the economics of creating the new improved practice (whether it is a renovation of existing space or brand new space) should be compared.

Is it time for a new practice environment? An operational look at your practice.

In this era of reimbursement not keeping pace with overhead and healthcare reform an unknown, it is more important than ever to assess the use of the doctors' and mid-level providers' time in your practice. There could be a very large untapped revenue source in the misallocated time of these providers that could help your practice increase patient volume and therefore practice revenue. Accessing this untapped revenue source may require additional resources in space and staff. To determine the level of untapped revenue and the investment that will be required to access that revenue, an objective assessment of your current practice flow is required.

TNF-alpha drives matrix metalloproteinase-9 in squamous oral carcinogenesis.

OBJECTIVES/HYPOTHESIS: It is well known that invasion is a seminal event in the progression of oral and other head and neck carcinoma sites. We have previously demonstrated tumor necrosis factor (TNF)-alpha and its dependent cytokines are upregulated in saliva during oral carcinogenesis. TNF-dependent events stimulate nuclear factor (NF)-kappaB and many NF-kappaB-dependent genes are associated with cancer progression. MATERIALS AND METHODS: In the present study, we examined NF-kappaB stimulation of matrix metalloproteinase (MMP)-9 in a precancerous keratinocyte cell line that models leukoplakia (Rhek cells). We stimulated Rhek cells with both TNF-alpha and phorbol myristate acetate, known stimulants of NF-kappaB. We then assayed MMP-9 transcription and secretion by luciferase reporter genes, quantitative real-time polymerase chain reaction, and fluorometric enzyme-linked immunosorbent serologic assay. RESULTS: We discovered that the MMP-9 promoter was significantly stimulated by phorbol myristate acetate and TNF-alpha on luciferase reporter gene assays. Further, we uncovered that functional MMP-9 promoter activation was accompanied by significant increases in MMP-9 gene expression, as judged by quantitative real-time polymerase chain reaction. Functional activation of the MMP-9 protein was stimulated by TNF-alpha and PMA on a fluorescent enzyme-linked immunosorbent serologic assay. Finally, we searched our salivary proteomic database for increases in MMP-9 and discovered it was the third most significant protein in salivas of oral cavity cancer patients over normal controls. CONCLUSIONS: We conclude the milieu cytokine, TNF-alpha, has the capacity to provide stimulation of events related to early invasion of oral cavity cancer, as judged by its ability to stimulate MMP-9.

Promotion of iridium-catalyzed methanol carbonylation: mechanistic studies of the cativa process.

The iridium/iodide-catalyzed carbonylation of methanol to acetic acid is promoted by carbonyl complexes of W, Re, Ru, and Os and simple iodides of Zn, Cd, Hg, Ga, and In. Iodide salts (LiI and Bu(4)NI) are catalyst poisons. In situ IR spectroscopy shows that the catalyst resting state (at H(2)O levels > or = 5% w/w) is fac,cis-[Ir(CO)(2)I(3)Me](-), 2. The stoichiometric carbonylation of 2 into [Ir(CO)(2)I(3)(COMe)](-), 6, is accelerated by substoichiometric amounts of neutral promoter species (e.g., [Ru(CO)(3)I(2)](2), [Ru(CO)(2)I(2)](n), InI(3), GaI(3), and ZnI(2)). The rate increase is approximately proportional to promoter concentration for promoter:Ir ratios of 0-0.2. By contrast anionic Ru complexes (e.g., [Ru(CO)(3)I(3)](-), [Ru(CO)(2)I(4)](2)(-)) do not promote carbonylation of 2 and Bu(4)NI is an inhibitor. Mechanistic studies indicate that the promoters accelerate carbonylation of 2 by abstracting an iodide ligand from the Ir center, allowing coordination of CO to give [Ir(CO)(3)I(2)Me], 4, identified by high-pressure IR and NMR spectroscopy. Migratory CO insertion is ca. 700 times faster for 4 than for 2 (85 degrees C, PhCl), representing a lowering of Delta G(++) by 20 kJ mol(-1). Ab initio calculations support a more facile methyl migration in 4, the principal factor being decreased pi-back-donation to the carbonyl ligands compared to 2. The fac,cis isomer of [Ir(CO)(2)I(3)(COMe)](-), 6a (as its Ph(4)As(+) salt), was characterized by X-ray crystallography. A catalytic mechanism is proposed in which the promoter [M(CO)(m)I(n)] (M = Ru, In; m = 3, 0; n = 2, 3) binds I(-) to form [M(CO)(m)I(n+1)](-)H(3)O(+) and catalyzes the reaction HI(aq) + MeOAc --> MeI + HOAc. This moderates the concentration of HI(aq) and so facilitates catalytic turnover via neutral 4.