Regulation of cytokine gene expression by orosomucoid in neonatal swine adipose tissue

BACKGROUND: Porcine adipose tissue expresses orosomucoid (ORM1) mRNA, a protein with anti-inflammatory and immunomodulatory properties. Previous research has demonstrated that porcine ORM1 can reduce insulin stimulated glucose metabolism in porcine adipose tissue in vitro. The present study was designed to examine the preweaning ontogeny of ORM1 mRNA abundance in porcine subcutaneous adipose and to determine if ORM1 can regulate mRNA abundance of inflammatory cytokines that contribute to insulin resistance in primary cultures derived from neonatal porcine subcutaneous adipose tissue. Cultures were differentiated in vitro and subsequently the adipocyte containing cultures were incubated for 24 h with 0–5000 ng porcine ORM1/mL medium. Cultures were then harvested, total RNA extracted for use in reverse transcription and the mRNA abundance of cytokine mRNA quantified by real-time PCR. RESULTS: ORM1 mRNA abundance within neonatal adipose tissue does not change from d 1 to d 21 of age and is a very small fraction relative to liver mRNA abundance. The ORM1 mRNA level in porcine adipocytes and stromal-vascular cells are similar (P > 0.05). Treatment with ORM1 did not affect TNFα (tumor necrosis factor α) mRNA level (P > 0.05), while interleukin 6 (IL6) mRNA abundance was reduced 32 % at 1,000 ng ORM1/mL (P < 0.01). However, TNFα protein content in the cell culture media was reduced by ORM1 treatment (5,000 ng/mL, P < 0.05), whereas ORM1 had no detectable effect on the media content of IL6 (P > 0.05). The reduction of macrophage migration inhibitory factor (MIF) mRNA abundance by ORM1 was dose dependent (P < 0.01). Monocyte chemotactic protein (MCP) mRNA level was reduced 27 % by 1,000 ng ORM1/mL (P < 0.05). CONCLUSIONS: The data suggest that ORM1 has limited effects TNFα, IL6, MIF or MCP expression at the concentrations tested. Secondly, these cytokines do not appear to contribute to the reported insulin resistance induced by ORM1 in porcine adipose tissue in vitro as an increase in the abundance of these inflammatory cytokines would be predicted during an insulin resistant state

Spatially resolved H2 emission from the disk around T Tau N

We report the detection of quiescent H2 emission in a spatially resolved ring-like structure within 100 AU of T Tau N. We present evidence to show that the emission most likely arises from shocks in the atmosphere of a nearly face-on disk around T Tau N. Using high spatial resolution 3D spectroscopic K-band data, we trace the spatial distribution of several H2 NIR rovibrational lines in the vicinity of T Tau N. We detect weak H2 emission from the v=1-0 S(0), S(1), Q(1) lines and the v=2-1 S(1) line in a ring-like structure around T Tau N between 0.1'' (~15 AU) and 0.7'' (~100AU) from the star. The v=1-0 S(0) and v=2-1 S(1) lines are detected only in the outer parts of the ring structure. Closer to the star, the strong continuum limits our sensitivity to these lines. The total flux of the v=1-0 S(1) line is 1.8 *10^{-14} ergs s^{-1}cm^{-2}, similar to previous measurements of H2 in circumstellar disks. The velocity of the H2 emitting gas around T Tau N is consistent with the rest velocity of the star, and the H2 does not seem to be part of a collimated outflow. Both shocks impinging on the surface of a disk and irradiation of a disk by UV-photons and X-rays from the central star are plausible candidates for the H2 excitation mechanism. However, irradiation should not create a large degree of excitation at radii larger than 20 AU. Most likely the H2 emission arises in the atmosphere of a flared disk with radius 85-100 AU and mass 0.005-0.5Msun, where the gas is excited by shocks created when a wide-angle wind impinges on the disk. The H2 emission could also originate from shock excitation in the cavity walls of an envelope, but this requires an unusually high velocity of the wide-angle wind from T Tau N.Comment: Accepted by A&

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Diversity and Mega-Targets of Selection from the Characterization of a Barley Collection

Germplasm exchange is essential for assuring genetic gain in a breeding program. Two aspects of breeding programs are relevant to making them compatible for germplasm exchange: the amount of genetic diversity within programs and the identifi cation of breeding programs with similar breeding objectives and environments of selection (i.e., mega-targets of selection). The objective of this study was to develop a data-driven method to group breeding programs likely to be compatible for germplasm exchange and to use phenotypic characterization data of barley (Hordeum vulgare L.) from breeding programs to illustrate this method. In two locations in Uruguay we evaluated 20 traits in 353 genotypes of barley from 23 private and public breeding programs distributed worldwide. We found signifi cant amounts of genetic diversity for all traits, but differences in diversity among programs for only seven traits. We identifi ed programs with high (Western Australia Department of Agriculture; University of Saskatchewan; and Svalöf Weibull Ab, Sweden) and low diversity (winter program of Osijek Agricultural Institute, Croatia; spring program of Osijek Agricultural Institute, Croatia; Saatzucht Josef Breun, Germany; Busch Agricultural Resources; USDA-ARS, Aberdeen, ID; and University of Minnesota). We developed a methodology that groups programs with similar performance and response to the environments. We used the methodology to group the 23 breeding programs of barley into sets that might benefi t most from germplasm exchange. The identifi cation of compatible programs for germplasm exchange could be relevant for improving genetic gains in breeding programs

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed

Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy

Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is implicated in cell proliferation, differentiation, and apoptosis. Despite present advances, only the tip of the iceberg has so far been uncovered regarding the role of ECM compounds in influencing biotensegrity in pathological processes. Groups of cells, together with the surrounding ground substance, are subject to different and specific forces that certainly influence biological processes. In this paper, we review the current knowledge on the role of ECM elements in determining biotensegrity in malignant processes and describe their implication in therapeutic response, resistance to chemo- and radiotherapy, and subsequent tumor progression. Original data based on the study of neuroblastic tumors will be provided

The Human Ecology and Geography of Burning in an Unstable Savanna Environment

According to new ecological theories, many savannas are inherently in disequilibrium and can flip from tree-dominated to grass-dominated landscapes depending upon the disturbance regime. In particular, a shift in a fire regime to a more frequent and intensive one can radically alter the tree-to-grass ratio in a given savanna. Drawing upon the ecological buffering model we argue that savanna persistence requires a relatively stable fire regime. We hypothesize that anthropogenic burning practices perform this function by producing a regular annual spatiotemporal pattern of fire that is linked to vegetation type. We test this hypothesis using a study of two areas, one in Mali and the other Burkina Faso. We use two sources of satellite data to produce an 11-year time series of the spatiotemporal pattern of fires and an example of the annual burned area pattern these fires produce. We combine the analysis of satellite imagery with interviews of rural inhabitants who set fires to understand the logic underlying the patterns of fire. Analysis of a time series of imagery reveals a strikingly regular annual spatiotemporal pattern of burning for both study areas, which cannot be explained by the regional climatic pattern alone. We conclude that the regularity of the annual fire regime in West Africa is a human-ecological phenomenon closely linked to vegetation type and controlled by people\u27s burning practices. We argue that the anthropogenic burning regime serves to buffer the savanna and maintain its ecological stability

Identification of protein carbonyls in serum of the fetal and neonatal pig

Oxidation of serum proteins leads to non-reversible carbonyl formation which alters their function and is associated with stress-related disease processes. The primary objective of this study was to quantify and identify oxidized serum proteins in fetal and newborn piglets. Protein carbonyls were converted to hydrazones with dinitrophenyl hydrazine and quantified spectrophotometrically. For identification, serum protein carbonyls were derivatized with biotin hydrazide, separated by 2D PAGE and stained with FITCavidin. Biotin-labeled proteins were excised from gels and identified by mass spectrometry. At birth, carbonyls were determined to be ∼600 pmole/mg serum protein. Fetuses at 50 and 100 days of gestation had similar levels of protein carbonyls as newborns. Carbonyl levels were also similar for control and runt (birth) piglets between 1 and 21 days of age; however, distribution of many proteins varied by age and was also influenced by birth weight. Major oxidized proteins identified in fetal (f) and newborn (n) pigs included; albumin (f, n), transferrin (f, n), fetuin-A (f, n) alpha fetoprotein (f, n), plasminogen (f, n), fetuin-B (f), alpha-1-antitrypsin (f, n) alpha-1-acid glycoprotein (f) and immunoglobulins (n). While abundance and distribution of oxidized proteins changed over time, these changes appear to primarily reflect relative amounts of those proteins in serum

Bone marrow stromal cells attenuate sepsis via prostaglandin E2— dependent reprogramming of host macrophages to increase their interleukin-10 production

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/ or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.Sepsis, a serious medical condition that affects 18 million people per year worldwide, is characterized by a generalized inflammatory state caused by infection. Widespread activation of inflammation and coagulation pathways progresses to multiple organ dysfunction, collapse of the circulatory system (septic shock) and death. Because as many people die of sepsis annually as from acute myocardial infarction1, a new treatment regimen is desperately needed. In the last few years, it has been discovered that BMSCs are potent modulators of immune responses2-5. We wondered whether such cells could bring the immune response back into balance, thus attenuating the underlying pathophysiology that eventually leads to severe sepsis, septic shock and death6,7. As a model of sepsis, we chose cecal ligation and puncture (CLP), a procedure that has been used for more than two decades8. This mouse model closely resembles the human disease: it has a focal origin (cecum), is caused by multiple intestinal organisms, and results in septicemia with release of bacterial toxins into the circulation. With no treatment, the majority of the mice die 24-48 h postoperatively. Originally published Nature Medicine, Vol. 15, No. 1, Jan 200