Gait modification strategies for altering medial knee joint load: a systematic review.

PubMed

Simic, Milena; Hinman, Rana S; Wrigley, Tim V; Bennell, Kim L; Hunt, Michael A

2011-03-01

To evaluate the effect of gait modification strategies on the external knee adduction moment (KAM), a marker of medial knee joint load; determine potentially adverse effects; assess the methodologic quality; and identify areas of future research. Five electronic databases were searched. Studies evaluating the effects of gait modifications on the KAM in either healthy individuals or those with knee osteoarthritis (OA) were included. Methodologic quality was evaluated by 2 reviewers using the Downs and Black checklist. Twenty-four studies met the inclusion criteria, exploring 14 different gait modifications of varying sample sizes, age groups, and OA classifications. Contralateral cane use, increased step width, medial knee thrust, increased hip internal rotation, weight transfer to the medial foot, and increased lateral trunk lean demonstrated KAM reductions. Tai Chi gait, ipsilateral cane use, Nordic walking poles, and increased knee flexion exhibited increases in the KAM, demonstrating a potential detriment to their use. The effects of reduced stride length, as well as increases and reductions in either toe-out or gait speed, were inconsistent across the studies and gait cycle. This review demonstrates that some gait modifications have the ability to alter knee load. Future research is required to determine the magnitude of modification required to maximize beneficial effects, the best method of training, long-term patient adherence, and if these biomechanical changes can translate into clinically relevant changes in symptoms or disease progression risk. Copyright © 2011 by the American College of Rheumatology.

Modifications to the NIST reference measurement procedure (RMP) for the determination of serum glucose by isotope dilution gas chromatography/mass spectrometry.

PubMed

Prendergast, Jocelyn L; Sniegoski, Lorna T; Welch, Michael J; Phinney, Karen W

2010-07-01

The definitive method (DM), now known as the reference measurement procedure (RMP), for the analysis of glucose in serum was originally published in 1982 by the National Institute of Standards and Technology (NIST). Over the years the method has been subject to a number of modifications to adapt to newer technologies and simplify sample preparation. We discuss here an adaptation of the method associated with serum glucose measurements using a modified isotope dilution gas chromatography/mass spectrometry (ID-GC/MS) method. NIST has used this modified method to certify the concentrations of glucose in SRM 965b, Glucose in Frozen Human Serum, and SRM 1950, Metabolites in Human Plasma. Comparison of results from the revised method with certified values for existing Standard Reference Materials (SRMs) demonstrated that these modifications have not affected the quality of the measurements, giving both good precision and accuracy, while reducing the sample preparation time by a day and a half.

Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

DOE PAGES

Kintz, Erica; Heiss, Christian; Black, Ian; ...

2017-02-06

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains weremore » engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.« less

Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kintz, Erica; Heiss, Christian; Black, Ian

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains weremore » engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.« less

Single ether group in a glycol-based ultra-thin layer prevents surface fouling from undiluted serum.

PubMed

Sheikh, Sonia; Yang, David Yi; Blaszykowski, Christophe; Thompson, Michael

2012-01-30

Through systematic structural modification, it is shown that the internal, single oxygen atom of simple monoethylene glycol-based organic films is essential for radically altering the fouling behaviour of quartz against undiluted serum, as characterized by the electromagnetic piezoelectric acoustic sensor. The synergy is strongest with distal hydroxyls.

The oxidative mechanism of heparin interferes with radical production by glucose and reduces the degree of glycooxidative modifications on human serum albumin.

PubMed

Finotti, P; Pagetta, A; Ashton, T

2001-04-01

Among substances which may prove useful in preventing or reducing the progression of glycooxidative modifications of proteins, heparin plays a unique role. To elucidate the mechanism whereby heparin may favourably influence the protein structure during glycation, human serum albumin (HSA) was glycated with both 25 and 50 mM glucose in the absence and presence of 12 microg.mL(-1) low-molecular-mass heparin. Glycation caused: (a) modifications of fluorescence emission and excitation spectra consistent with the covalent attachment of glucose to protein; (b) a significant increase in the esterase activity of HSA on p-nitrophenyl acetate; (c) a reduced susceptibility to tryptic digestion and (d) enhanced formation of high-molecular mass aggregates of HSA. These alterations were accompanied by oxidative reactions, as the EPR spectra showed a clear-cut radical signal, dependent on glucose concentration, further confirmed by measurement of the carbonyl content of HSA, as an indirect proof of oxidative damage. In the presence of heparin all the above alterations, especially at 25 mM glucose, turned out to be antagonized. The effects of heparin were dependent on its specific binding to HSA, which triggered an oxidative mechanism strikingly different from that caused by glucose. In the presence of heparin, only the radical species catalyzed by heparin was detected across all samples of glycated HSA, irrespective of glucose concentration. In addition, at 25 mM glucose, enhancement of the oxidative capacity of heparin was also observed. The results demonstrate that the oxidative mechanism sustained by heparin mediates biological effects that may be beneficial in reducing the extent of glycooxidative damage on HSA.

Alterations of serum macro-minerals and trace elements are associated with major depressive disorder: a case-control study.

PubMed

Islam, Md Rabiul; Islam, Md Reazul; Shalahuddin Qusar, M M A; Islam, Mohammad Safiqul; Kabir, Md Humayun; Mustafizur Rahman, G K M; Islam, Md Saiful; Hasnat, Abul

2018-04-10

Major depressive disorder (MDD) is a mixed disorder with the highly irregular course, inconsistent response to treatment and has no well-known mechanism for the pathophysiology. Major causes of depression are genetic, neurobiological, and environmental. However, over the past few years, altered serum levels of macro-minerals (MM) and trace elements (TE) have been recognized as major causative factors to the pathogenesis of many mental disorders. The purpose of this study was to determine the serum levels of MM (calcium and magnesium) and TE (copper, iron, manganese, selenium, and zinc) in MDD patients and find out their associations with depression risk. This prospective case-control study recruited 247 patients and 248 healthy volunteers matched by age and sex. The serum levels of MM and TE were analyzed by atomic absorption spectroscopy (AAS). Statistical analysis was performed with independent sample t-tests and Pearson's correlation test. We found significantly decreased concentrations of calcium and magnesium, iron, manganese, selenium, and zinc in MDD patients compared with control subjects (p < 0.05). But the concentration of copper was significantly increased in the patients than control subjects (p < 0.05). Data obtained from different inter-element relations in MDD patients and control subjects strongly suggest that there is a disturbance in the element homeostasis. Our study suggests that altered serum concentrations of MM and TE are major contributing factors for the pathogenesis of MDD. Alterations of these elements in serum levels of MDD patients arise independently and they may provide a prognostic tool for the assessment of depression risk.

Neutral buoyancy and sleep-deprived serum factors alter expression of cytokines regulating osteogenesis

NASA Astrophysics Data System (ADS)

Gorczynski, Reginald M.; Gorczynski, Christopher P.; Gorczynski, Laura Y.; Hu, Jiang; Lu, Jin; Manuel, Justin; Lee, Lydia

2005-05-01

We examined expression of genes associated with cytokine production, and genes implicated in regulating bone metabolism, in bone stromal and osteoblast cells incubated under standard ground conditions and under conditions of neutral buoyancy, and in the presence/absence of serum from normal or sleep-deprived mice. We observed a clear interaction between these two conditions (exposure to neutral buoyancy and serum stimulation) in promoting enhanced osteoclastogenesis. Both conditions independently altered expression of a number of cytokines implicated in the regulation of bone metabolism. However, using stromal cells from IL-1 and TNF α cytokine r KO mice, we concluded that the increased bone loss under microgravity conditions was not primarily cytokine mediated.

MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

EPA Science Inventory

Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

PubMed

Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

2006-01-01

Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

PubMed Central

2013-01-01

Background Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may

Serum Factors from Pseudoxanthoma Elasticum Patients Alter Elastic Fiber Formation In Vitro

PubMed Central

Le Saux, Olivier; Bunda, Severa; VanWart, Christopher M.; Douet, Vanessa; Got, Laurence; Martin, Ludovic; Hinek, Aleksander

2017-01-01

Pseudoxanthoma elasticum (PXE) is a heritable disorder mainly characterized by calcified elastic fibers in cutaneous, ocular, and vascular tissues. PXE is caused by mutations in ABCC6, a gene encoding an ABC transporter predominantly expressed in liver and kidneys. The functional relationship between ABCC6 and elastic fiber calcification is unknown. We speculated that ABCC6 deficiency in PXE patients induces a persistent imbalance in circulating metabolite(s), which may impair the synthetic abilities of normal elastoblasts or specifically alter elastic fiber assembly. Therefore, we compared the deposition of elastic fiber proteins in cultures of fibroblasts derived from PXE and unaffected individuals. PXE fibroblasts cultured with normal human serum expressed and deposited increased amounts of proteins, but structurally normal elastic fibers. Interestingly, normal and PXE fibroblasts as well as normal smooth muscle cells deposited abnormal aggregates of elastic fibers when maintained in the presence of serum from PXE patients. The expression of tropoelastin and other elastic fiber-associated genes was not significantly modulated by the presence of PXE serum. These results indicated that certain metabolites present in PXE sera interfered with the normal assembly of elastic fibers in vitro and suggested that PXE is a primary metabolic disorder with secondary connective tissue manifestations. PMID:16543900

Altered serum levels of TNF-α, IL-6, and IL-18 in depressive disorder patients.

PubMed

Fan, Ni; Luo, Yayan; Ou, Yufen; He, Hongbo

2017-07-01

Depressive disorder is associated with abnormal changes in cytokines levels. This study aimed to assess serum concentrations of tumor necrosis factor (TNF) α, interleukin (IL) 6, and IL-18 in depressive patients. The correlations between these three cytokine concentrations and the patients' clinical characteristics were also assessed. Serum TNF-α, IL-6, and IL-18 concentrations were assessed using enzyme-linked immunosorbent assay from 64 depressive patients and 80 healthy control subjects. Depressive symptoms of patients were assessed using Hamilton Depression Scale-17. Depressive patients had increased serum TNF-α and IL-6 concentrations but decreased IL-18 concentrations than controls. TNF-α and IL-6 concentrations were significantly positively associated with Hamilton Depression Scale-17 scores in depressive patients. These findings provided additional evidence that altered TNF-α, IL-6, and IL-18 activities may contribute to the pathophysiology of depressive disorder. Copyright © 2017 John Wiley & Sons, Ltd.

Probing the binding interaction of a phenazinium dye with serum transport proteins: a combined fluorometric and circular dichroism study.

PubMed

Bose, Debosreeta; Sarkar, Deboleena; Chattopadhyay, Nitin

2010-01-01

In the present investigation, an attempt has been made to study the interaction of phenosafranin (PSF), a cationic phenazinium dye with the transport proteins, bovine serum albumin (BSA) and human serum albumin (HSA), employing steady-state and time-resolved fluorometric and circular dichroism (CD) techniques. The photophysical properties of the dye are altered on binding with the serum proteins. An explicit study with respect to the modification of the fluorescence and fluorescence anisotropy upon binding, effect of denaturant, fluorescence lifetime and CD measurements reveal that the dye binds to both BSA and HSA with almost the same affinity. Far-UV CD spectra indicate a decrease in the percentage of alpha-helicity only for BSA upon binding with the probe. Near-UV CD responses indicate an alteration in the tertiary structure of both the transport proteins because of binding.

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload.

PubMed

Meroño, Tomás; Brites, Fernando; Dauteuille, Carolane; Lhomme, Marie; Menafra, Martín; Arteaga, Alejandra; Castro, Marcelo; Saez, María Soledad; Ballerga, Esteban González; Sorroche, Patricia; Rey, Jorge; Lesnik, Philippe; Sordá, Juan Andrés; Chapman, M John; Kontush, Anatol; Daruich, Jorge

2015-05-01

Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, P< 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n=7) presented a reduced β-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, P< 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43±5; non-C282Y: 25±8; controls: 32±7%; P< 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23±5; non-C282Y: 39±10; controls: 26±4%; P< 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

Dietary supplemental Kluyveromyces marxianus alters the serum metabolite profile in broiler chickens.

PubMed

Wang, Weiwei; Li, Zhui; Gan, Liping; Fan, Hao; Guo, Yuming

2018-06-18

Metabolomics is used to evaluate the bioavailability of food components, as well as to validate the metabolic changes associated with food consumption. This study was conducted to investigate the effects of the dietary supplement Kluyveromyces marxianus on the serum metabolite profile in broiler chickens. A total of 240 1-d-old broilers were divided into 2 groups with 8 replicates. Birds were fed basal diets without or with K. marxianus supplementation (5 × 1010 CFU kg-1 of diet). Serum samples were collected on d 21 and were analyzed by high-performance liquid chromatography with quadrupole time-of flight/mass spectrometry. The results showed that supplemental K. marxianus altered the concentrations of a variety of metabolites in the serum. Thereinto, a total of 39 metabolites were identified at higher (P < 0.05) concentrations while 21 metabolites were identified at lower (P < 0.05) concentrations in the treatment group as compared with the control. These metabolites were primarily involved with the regulation of amino acids and carbohydrate metabolism. Further metabolic pathway analysis revealed that glutamine and glutamate metabolism was the most relevant and critical pathway identified from these two groups. The activated pathway may partially interpret the beneficial effects of K. marxianus. Overall, the present research could promote our understanding of the probiotic action of K. marxianus and provide new insight into the design and application of K. marxianus-containing functional foods.

Response of the antioxidant enzymes of the erythrocyte and alterations in the serum biomarkers in rats following oral administration of nanoparticles.

PubMed

Canli, Esin G; Atli, Gülüzar; Canli, Mustafa

2017-03-01

In this study, Al 2 O 3 , CuO and TiO 2 nanoparticles (NPs) were administered to mature female rats (Rattus norvegicus var. albinos) via oral gavage (0, 0.5, 5, 50mg/kg b.w./day) for 14days to investigate their effects on 14 serum biomarkers and 4 antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase) activities in the erythrocyte. Data showed that Al 2 O 3 did not cause any significant (P>0.05) change in the parameters, except few cases, while CuO and TiO 2 caused significant alterations in antioxidant system parameters of the erythrocytes. Activities of catalase and superoxide dismutase significantly decreased in CuO and TiO 2 administered rats. Oppositely, glutathione peroxidase activity increased in CuO and TiO 2 administered rats. There were no significant alterations in the activity of glutathione S-transferase in the erythrocytes. Levels of glucose, cholesterol, bilirubin, triglyceride, triiodothyronine (T3), estradiol, prolactin and immunoglobulin M (IgM) in the serum altered after some of NP administrations, whereas cortisol, protein, creatinine, blood urea nitrogen (BUN), thyroxine (T4) and immunoglobulin G (IgG) levels in the serum did not change significantly after any of NP administration. There were outstanding increases in the levels of bilirubin and prolactin and decreases in the levels of triglyceride and estradiol. The present study demonstrated that the antioxidant enzymes in the erythrocyte were generally affected from copper and titanium NPs, while aluminium and copper NPs caused more significant alterations in serum biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Canine and Equine Mesenchymal Stem Cells Grown in Serum Free Media Have Altered Immunophenotype.

PubMed

Clark, Kaitlin C; Kol, Amir; Shahbenderian, Salpi; Granick, Jennifer L; Walker, Naomi J; Borjesson, Dori L

2016-04-01

Mesenchymal stem cell (MSC) therapy is being increasingly used to treat dogs and horses with naturally-occurring diseases. However these animals also serve as critical large animal models for ongoing translation of cell therapy products to the human market. MSC manufacture for clinical use mandates improvement in cell culture systems to meet demands for higher MSC numbers and removal of xeno-proteins (i.e. fetal bovine serum, FBS). While serum-free media (SFM) is commercially available, its affects on MSC phenotype and immunomodulatory functions are not fully known. The objective of this study was to determine if specific MSC culture conditions, MSC expansion in HYPERFlasks® or MSC expansion in a commercially available SFM, would alter MSC proliferation, phenotype or immunomodulatory properties in vitro. MSCs cultured in HYPERFlasks® were similar in phenotype, proliferative capacity and immunomodulatory functions to MSCs grown in standard flasks however MSC yield was markedly increased. HYPERFlasks® therefore provide a viable option to generate greater cell numbers in a streamlined manner. Canine and equine MSCs expanded in SFM displayed similar proliferation, surface phenotype and inhibitory effect on lymphocyte proliferation in vitro. However, MSCs cultured in the absence of FBS secreted significantly less PGE2, and were significantly less able to inhibit IFNγ secretion by activated T-cells. Immunomodulatory functions altered by expansion in SFM were species dependent. Unlike equine MSCs, in canine adipose-derived MSCs, the inhibition of lymphocyte proliferation was not principally modulated by PGE2. The removal of FBS from both canine and equine MSC culture systems resulted in altered immunomodulatory properties in vitro and warrants further investigation prior to moving towards FBS-free culture conditions.

33 CFR 149.15 - What is the process for submitting alterations and modifications affecting the design and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What is the process for submitting alterations and modifications affecting the design and construction of a deepwater port? 149.15 Section 149.15 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS DEEPWATER PORTS: DESIGN,...

[Alteration of intestinal permeability: the missing link between gut microbiota modifications and inflammation in obesity?].

PubMed

Genser, Laurent; Poitou, Christine; Brot-Laroche, Édith; Rousset, Monique; Vaillant, Jean-Christophe; Clément, Karine; Thenet, Sophie; Leturque, Armelle

2016-05-01

The increasing incidence of obesity and associated metabolic complications is a worldwide public health issue. The role of the gut in the pathophysiology of obesity, with an important part for microbiota, is becoming obvious. In rodent models of diet-induced obesity, the modifications of gut microbiota are associated with an alteration of the intestinal permeability increasing the passage of food or bacterial antigens, which contribute to low-grade inflammation and insulin resistance. In human obesity, intestinal permeability modification, and its role in the crosstalk between gut microbiota changes and inflammation at systemic and tissular levels, are still poorly documented. Hence, further characterization of the triggering mechanisms of such inflammatory responses in obese subjects could enable the development of personalized intervention strategies that will help to reduce the risk of obesity-associated diseases. © 2016 médecine/sciences – Inserm.

c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

DOE PAGES

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; ...

2015-08-12

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

PubMed Central

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

2015-01-01

Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

[Epigenetic alterations in acute lymphoblastic leukemia].

PubMed

Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Albumin modification and fragmentation in renal disease.

PubMed

Donadio, Carlo; Tognotti, Danika; Donadio, Elena

2012-02-18

Albumin is the most important antioxidant substance in plasma and performs many physiological functions. Furthermore, albumin is the major carrier of endogenous molecules and exogenous ligands. This paper reviews the importance of post-translational modifications of albumin and fragments thereof in patients with renal disease. First, current views and controversies on renal handling of proteins, mainly albumin, will be discussed. Post-translational modifications, namely the fragmentation of albumin found with proteomic techniques in nephrotic patients, diabetics, and ESRD patients will be presented and discussed. It is reasonable to hypothesize that proteolytic fragmentation of serum albumin is due to a higher susceptibility to proteases, induced by oxidative stress. The clinical relevance of the fragmentation of albumin has not yet been established. These modifications could affect some physiological functions of albumin and have a patho-physiological role in uremic syndrome. Proteomic analysis of serum allows the identification of over-expressed proteins and can detect post-translational modifications of serum proteins, hitherto hidden, using standard laboratory techniques. Copyright © 2011 Elsevier B.V. All rights reserved.

Regulation of heat shock protein message in Jurkat cells cultured under serum-starved and gravity-altered conditions

NASA Technical Reports Server (NTRS)

Lewis, M. L.; Hughes-Fulford, M.

2000-01-01

Although our understanding of effects of space flight on human physiology has advanced significantly over the past four decades, the potential contribution of stress at the cellular and gene regulation level is not characterized. The objective of this ground-based study was to evaluate stress gene regulation in cells exposed to altered gravity and environmentally suboptimal conditions. We designed primers to detect message for both the constitutive and inducible forms of the heat shock protein, HSP-70. Applying the reverse transcriptase-polymerase chain reaction (RT-PCR), we probed for HSP-70 message in human acute T-cell leukemia cells, Jurkat, subjected to three types of environmental stressors: (1) altered gravity achieved by centrifugation (hypergravity) and randomization of the gravity vector in rotating bioreactors, (2) serum starvation by culture in medium containing 0.05% serum, and (3) temperature elevation (42 degrees C). Temperature elevation, as the positive control, significantly increased HSP-70 message, while centrifugation and culture in rotating bioreactors did not upregulate heat shock gene expression. We found a fourfold increase in heat shock message in serum-starved cells. Message for the housekeeping genes, actin and cyclophilin, were constant and comparable to unstressed controls for all treatments. We conclude that gravitational perturbations incurred by centrifugal forces, exceeding those characteristic of a Space Shuttle launch (3g), and culture in rotating bioreactors do not upregulate HSP-70 gene expression. In addition, we found RT-PCR useful for evaluating stress in cultured cells. Copyright 2000 Wiley-Liss, Inc.

Effects of topographical and mechanical property alterations induced by oxygen plasma modification on stem cell behavior.

PubMed

Yang, Yong; Kulangara, Karina; Lam, Ruby T S; Dharmawan, Rena; Leong, Kam W

2012-10-23

Polymeric substrates intended for cell culture and tissue engineering are often surface-modified to facilitate cell attachment of most anchorage-dependent cell types. The modification alters the surface chemistry and possibly topography. However, scant attention has been paid to other surface property alterations. In studying oxygen plasma treatment of polydimethylsiloxane (PDMS), we show that oxygen plasma treatment alters the surface chemistry and, consequently, the topography and elasticity of PDMS at the nanoscale level. The elasticity factor has the predominant effect, compared with the chemical and topographical factors, on cell adhesions of human mesenchymal stem cells (hMSCs). The enhanced focal adhesions favor cell spreading and osteogenesis of hMSCs. Given the prevalent use of PDMS in biomedical device construction and cell culture experiments, this study highlights the importance of understanding how oxygen plasma treatment would impact subsequent cell-substrate interactions. It helps explain inconsistency in the literature and guides preparation of PDMS-based biomedical devices in the future.

Analysis of normal and truncated holo- and apo-retinol-binding protein (RBP) in human serum: altered ratios in chronic renal failure.

PubMed

Jaconi, S; Saurat, J H; Siegenthaler, G

1996-05-01

Retinol, the precursor of the retinoic acid hormone, is transported in the serum by a specific carrier, the retinol-binding protein (RBP). Compared to serum of healthy controls, the serum of patients with chronic renal failure (CRF) contains markedly increased levels of the RBP form truncated at the C terminal, des(182Leu-183Leu), (RBP2), which suggests that RBP2 is cleared by the kidney in healthy people but accumulates in serum of CRF patients (Jaconi S, et al. J Lipid Res 1995:36:1247-53). To understand better the mechanism of retinol transport, we have developed a new analytical strategy to analyze the various forms of RBP that circulate in the blood: RBP with and without retinol (holo- and apo-RBP, respectively), RBP bound or not to transthyretin (TTR) and to determine in which of these forms RBP2 circulates. We confirm, but now by direct measurement, that holo-RBP and, to a larger extent, apo-RBP are increased in CRF serum compared to normal serum. We also show that almost all apo-RBP and about 50% of total holo-RBP, corresponding to RBP excess in CRF serum, circulate free and are not complexed to TTR, the remaining 50% being complexed to TTR. This observation suggests that the high levels of free holo-RBP, not bound to TTR, which correspond to the increase in total RBPs measured in CRF serum, may alter the tissue uptake of retinol and be responsible for the signs of hypervitaminosis A observed in these patients. Secondly, we found that the truncation resulting in RBP2 does not alter its binding properties for retinol nor those of holo-RBP2 for TTR. We observed that the high amounts of free holo-RBP2 and holo-RBP in sera of CRF patients were low in normal serum, suggesting that these forms are cleared by the kidney in normal conditions. The possible role of free holo-RBPs is discussed in the context of retinol recycling.

Altered Serum Levels of Matrix Metalloproteinase-2, -9 in Response to Electroconvulsive Therapy for Mood Disorders.

PubMed

Shibasaki, Chiyo; Takebayashi, Minoru; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Yamawaki, Shigeto

2016-09-01

Inflammatory processes could underlie mood disorders. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMP) are inflammation-related molecules. The current study sought an association between mood disorders and systemic levels of MMPs and TIMPs. Serum was obtained from patients with mood disorders (n=21) and patients with schizophrenia (n=13) scheduled to undergo electroconvulsive therapy. Serum was also obtained from healthy controls (n=40). Clinical symptoms were assessed by the Hamilton Rating Score for Depression and the Brief Psychiatric Rating Scale. Serum levels of MMPs and TIMPs were quantified by ELISA. The serum levels of MMP-2 in mood disorder patients, but not in schizophrenia patients, prior to the first electroconvulsive therapy session (baseline) was significantly lower than that of healthy controls. At baseline, levels of MMP-9 and TIMP-2, -1 were not different between patients with mood disorder and schizophrenia and healthy controls. After a course of electroconvulsive therapy, MMP-2 levels were significantly increased in mood disorder patients, but MMP-9 levels were significantly decreased in both mood disorder and schizophrenia patients. In mood disorder patients, there was a significant negative correlation between depressive symptoms and serum levels of MMP-2 and a positive correlation between depressive symptoms and MMP-9. In addition, alterations of serum levels of MMP-2 and MMP-9 were significantly correlated each other and were associated with certain depressive symptoms. A change in inflammatory homeostasis, as indicated by MMP-2 and MMP-9, could be related to mood disorders, and these markers appear to be sensitive to electroconvulsive therapy. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

PubMed Central

2012-01-01

Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection. PMID:23272999

Alteration of serum concentrations of manganese, iron, ferritin, and transferrin receptor following exposure to welding fumes among career welders.

PubMed

Lu, Ling; Zhang, Long-Lian; Li, G Jane; Guo, Wenrui; Liang, Wannian; Zheng, Wei

2005-03-01

This study was performed to determine airborne manganese levels during welding practice and to establish the relationship between long-term, low-level exposure to manganese and altered serum concentrations of manganese, iron, and proteins associated with iron metabolism in career welders. Ninety-seven welders (average age of 36 years) who have engaged in electric arc weld in a vehicle manufacturer were recruited as the exposed group. Welders worked 7-8h per day with employment duration of 1-33 years. Control subjects consisted of 91 employees (average age of 35 years) in the same factory but not in the welding profession. Ambient manganese levels in welders' breathing zone were the highest inside the vehicle (1.5 +/- 0.7 mg/m3), and the lowest in the center of the workshop (0.2 +/- 0.05 mg/m3). Since the filter size was 0.8 microm, it is possible that these values may be likely an underestimation of the true manganese levels. Serum levels of manganese and iron in welders were about three-fold (p < 0.01) and 1.2-fold (p < 0.01), respectively, higher than those of controls. Serum concentrations of ferritin and transferrin were increased among welders, while serum transferrin receptor levels were significantly decreased in comparison to controls. Linear regression analyses revealed a lack of association between serum levels of manganese and iron. However, serum concentrations of iron and ferritin were positively associated with years of welder experience (p < 0.05). Moreover, serum transferrin receptor levels were inversely associated with serum manganese concentrations (p < 0.05). These findings suggest that exposure to welding fume among welders disturbs serum homeostasis of manganese, iron, and the proteins associated with iron metabolism. Serum manganese may serve as a reasonable biomarker for assessment of recent exposure to airborne manganese.

Preclinical Alterations in the Serum of COL(IV)A3(-)/(-) Mice as Early Biomarkers of Alport Syndrome.

PubMed

Muckova, Petra; Wendler, Sindy; Rubel, Diana; Büchler, Rita; Alert, Mandy; Gross, Oliver; Rhode, Heidrun

2015-12-04

The efficiency of the inhibition of the angiotensin converting enzyme, the most widely used therapy for the Alport syndrome, depends on the onset of the therapy-the earlier the better. Hence, early progressive biomarkers are urgently required to allow for preclinical diagnosis, an early start of possible therapy as well as the monitoring of this therapy. In the present study, an improved comprehensive and precise proteomic approach has been applied to the serum of juvenile Alport-mice, nontreated and treated, and wild-type controls of various ages to search for biomarkers. With a total of 2542 stringently altered proteins, the serum composition clearly shows a dependency on age, that is, stage, and therapy. Initially, the serum constituents indicate an enhanced extracellular matrix remodeling, cell damage, and the production of particular acute phase proteins. A panel of 15 potential biomarker candidates has been identified. In later stages, renal filtration failure and systemic acute phase reaction determine the composition of the serum; an effect that is well-known for manifested human Alport syndrome. With a small number of mouse urine samples, for example, the proteomic results for gelsolin could be verified using ELISA. Once verified in man, these early biomarkers would allow for a sensitive and specific diagnosis of the Alport syndrome in children as well as facilitate the monitoring of a possible therapy.

Alterations in the Rat Serum Proteome Induced by Prepubertal Exposure to Bisphenol A and Genistein

PubMed Central

2015-01-01

Humans are exposed to an array of chemicals via the food, drink and air, including a significant number that can mimic endogenous hormones. One such chemical is Bisphenol A (BPA), a synthetic chemical that has been shown to cause developmental alterations and to predispose for mammary cancer in rodent models. In contrast, the phytochemical genistein has been reported to suppress chemically induced mammary cancer in rodents, and Asians ingesting a diet high in soy containing genistein have lower incidence of breast and prostate cancers. In this study, we sought to: (1) identify protein biomarkers of susceptibility from blood sera of rats exposed prepubertally to BPA or genistein using Isobaric Tandem Mass Tags quantitative mass spectrometry (TMT-MS) combined with MudPIT technology and, (2) explore the relevance of these proteins to carcinogenesis. Prepubertal exposures to BPA and genistein resulted in altered expression of 63 and 28 proteins in rat sera at postnatal day (PND) 21, and of 9 and 18 proteins in sera at PND35, respectively. This study demonstrates the value of using quantitative proteomic techniques to explore the effect of chemical exposure on the rat serum proteome and its potential for unraveling cellular targets altered by BPA and genistein involved in carcinogenesis. PMID:24552547

Early social deprivation impairs pair bonding and alters serum corticosterone and the NAcc dopamine system in mandarin voles.

PubMed

Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo

2013-12-01

Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

PubMed Central

Nayak, Prasunpriya; Chatterjee, Ajay K

2003-01-01

Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders. PMID:12657166

Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols

PubMed Central

Holy, Xavier; Bégot, Laurent; Renault, Sylvie; Butigieg, Xavier; André, Catherine; Bonneau, Dominique; Savourey, Gustave; Collombet, Jean-Marc

2015-01-01

Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid–base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na+) or potassium (K+), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners’ renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na+ and K+) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID:26265754

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

PubMed Central

Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

2013-01-01

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium.

PubMed

Ryan, Zachary C; Ketha, Hemamalini; McNulty, Melissa S; McGee-Lawrence, Meghan; Craig, Theodore A; Grande, Joseph P; Westendorf, Jennifer J; Singh, Ravinder J; Kumar, Rajiv

2013-04-09

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost(-/-)) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.

Metabolic system alterations in pancreatic cancer patient serum: potential for early detection

PubMed Central

2013-01-01

. Biomarker PC-594 (an ultra long-chain fatty acid), was further validated using an independently-collected US Caucasian population (blinded analysis, n=60, p=9.9E-14, AUC=0.97 ±0.02). PC-594 levels across 1000 reference subjects showed an inverse correlation with age, resulting in a drop in the AUC from 0.99 ±0.01 to 0.90 ±0.02 for subjects aged 30 to 80, respectively. A PC-594 test positivity rate of 5.0% in low-risk reference subjects resulted in a PC sensitivity of 87% and a significant improvement in net clinical benefit based on decision curve analysis. Conclusions The serum metabolome of PC patients is significantly altered. The utility of serum metabolite biomarkers, particularly PC-594, for identifying subjects with elevated risk of PC should be further investigated. PMID:24024929

Medical image integrity control and forensics based on watermarking--approximating local modifications and identifying global image alterations.

PubMed

Huang, H; Coatrieux, G; Shu, H Z; Luo, L M; Roux, Ch

2011-01-01

In this paper we present a medical image integrity verification system that not only allows detecting and approximating malevolent local image alterations (e.g. removal or addition of findings) but is also capable to identify the nature of global image processing applied to the image (e.g. lossy compression, filtering …). For that purpose, we propose an image signature derived from the geometric moments of pixel blocks. Such a signature is computed over regions of interest of the image and then watermarked in regions of non interest. Image integrity analysis is conducted by comparing embedded and recomputed signatures. If any, local modifications are approximated through the determination of the parameters of the nearest generalized 2D Gaussian. Image moments are taken as image features and serve as inputs to one classifier we learned to discriminate the type of global image processing. Experimental results with both local and global modifications illustrate the overall performances of our approach.

Diet Modification for Hyperlipidemia

PubMed Central

Mann, Heather D.; Piotrowski, Pamela

1992-01-01

Hyperlipidemia is a major risk factor associated with cardiovascular disease. Dietary modification is effective in achieving and maintaining improved serum lipid levels. Nutritional care provided by a dietitian includes individual dietary and lifestyle assessment, formulating an appropriate dietary regimen, education, and follow-up assessments. PMID:21221406

Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

PubMed Central

Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

2016-01-01

Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691

Ecological Effects of Weather Modification: A Problem Analysis.

ERIC Educational Resources Information Center

Cooper, Charles F.; Jolly, William C.

This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

Ubiquitin modifications

PubMed Central

Swatek, Kirby N; Komander, David

2016-01-01

Protein ubiquitination is a dynamic multifaceted post-translational modification involved in nearly all aspects of eukaryotic biology. Once attached to a substrate, the 76-amino acid protein ubiquitin is subjected to further modifications, creating a multitude of distinct signals with distinct cellular outcomes, referred to as the 'ubiquitin code'. Ubiquitin can be ubiquitinated on seven lysine (Lys) residues or on the N-terminus, leading to polyubiquitin chains that can encompass complex topologies. Alternatively or in addition, ubiquitin Lys residues can be modified by ubiquitin-like molecules (such as SUMO or NEDD8). Finally, ubiquitin can also be acetylated on Lys, or phosphorylated on Ser, Thr or Tyr residues, and each modification has the potential to dramatically alter the signaling outcome. While the number of distinctly modified ubiquitin species in cells is mind-boggling, much progress has been made to characterize the roles of distinct ubiquitin modifications, and many enzymes and receptors have been identified that create, recognize or remove these ubiquitin modifications. We here provide an overview of the various ubiquitin modifications present in cells, and highlight recent progress on ubiquitin chain biology. We then discuss the recent findings in the field of ubiquitin acetylation and phosphorylation, with a focus on Ser65-phosphorylation and its role in mitophagy and Parkin activation. PMID:27012465

Altered activity of lysophospholipase D, which produces bioactive lysophosphatidic acid and choline, in serum from women with pathological pregnancy.

PubMed

Tokumura, A; Kume, T; Taira, S; Yasuda, K; Kanzaki, H

2009-05-01

Altered lipid metabolism is associated with human abnormal pregnancy, such as pre-eclampsia and preterm labor, and potentially leads to fetus loss. A causative factor for the onset and progress of the systemic multifactorial syndromes associated with the pathological pregnancy is oxidized low-density lipoprotein, an active identity of which was postulated to be lysophosphatidic acid (LPA). We previously found that LPA is produced extracellularly by plasma lysophospholipase D (lysoPLD) activity of autotaxin, a tumor cell motility-stimulating protein. In this study, a convenient assay based on the choline released from endogenous substrate or exogenous lysophosphatidylcholine (LPC) was used for comparison of serum lysoPLD activity among patients with normal and abnormal pregnancy. The serum choline-producing activity was found to be mainly due to autotaxin, and dependent on its dilution rate. There was some association between low dilution dependency of serum lysoPLD activity toward an exogenous LPC and high lysoPLD activity toward endogenous substrates in cases of patients with preterm labor and pre-eclampsia. However, there was no difference in the serum level of LPC between women with normal pregnancy and those with pathological pregnancy. These results indicate that production of bioactive LPA by lysoPLD activity is elevated by an unknown mechanism that may be related to increased availability of endogenous substrates LPC, but not its concentration in human serum. If the level of LPA in blood circulation is elevated in the pathological pregnancies in vivo, it may play a role in induction and/or progression of systemic vascular dysfunction seen patients with preterm labor or pre-eclampsia.

Alteration of methotrexate binding to human serum albumin induced by oxidative stress. Spectroscopic comparative study

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, M.; Sułkowska, A.; Równicka-Zubik, J.

2016-01-01

Changes of oxidative modified albumin conformation by comparison of non-modified (HSA) and modified (oHSA) human serum albumin absorption spectra, Red Edge Excitation Shift (REES) effect and fluorescence synchronous spectra were investigated. Studies of absorption spectra indicated that changes in the value of absorbance associated with spectral changes in the region from 200 to 250 nm involve structural alterations related to variations in peptide backbone conformation. Analysis of the REES effect allowed for the observation of changes caused by oxidation in the region of the hydrophobic pocket containing the tryptophanyl residue. Synchronous fluorescence spectroscopy confirmed changes of the position of the tryptophanyl and tyrosil residues fluorescent band. Effect of oxidative stress on binding of methotrexate (MTX) was investigated by spectrofluorescence, UV-VIS and 1HNMR spectroscopy. MTX caused the fluorescence quenching of non-modified (HSA) and modified (oHSA) human serum albumin molecule. The values of binding constants, Hill's coefficients and a number of binding sites in the protein molecule in the high affinity binding site were calculated for the binary MTX-HSA and MTX-oHSA systems. For these systems, qualitative analysis in the low affinity binding sites was performed with the use of the 1HNMR technique.

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease.

PubMed

Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

2015-01-01

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease

PubMed Central

Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

2015-01-01

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy. PMID:25531678

Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays

PubMed Central

Venâncio, Daniel P.; Andersen, Monica L.; Vilamaior, Patricia S. L.; Santos, Fernanda C.; Zager, Adriano; Tufik, Sérgio; Taboga, Sebastião R.; De Mello, Marco T.

2012-01-01

We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR. PMID:22927719

Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum

PubMed Central

Hinkelbein, Jochen; Jansen, Stefanie; Iovino, Ivan; Kruse, Sylvia; Meyer, Moritz; Cirillo, Fabrizio; Drinhaus, Hendrik; Hohn, Andreas; Klein, Corinna; Robertis, Edoardo De; Beutner, Dirk

2017-01-01

Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades “regulation of haemostasis” (four proteins), “metabolism” (five proteins), and “leukocyte mediated immune response” (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis PMID:28858246

Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

PubMed

Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

2013-11-01

High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, p<0.01) while ursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

Effect of nutrition education and diet modification in iron depleted preschool children in nurseries in Tehran: a pilot study.

PubMed

Khoshnevisan, Farnaz; Kimiagar, Masood; Kalantaree, Nasser; Valaee, Nasser; Shaheedee, Nooshin

2004-07-01

In view of the high prevalence of iron deficiency in preschool children and its consequences, this study was carried out to examine the effect of nutrition education and dietary modification on 438 two- to six-year-old nursery school children in Tehran in 1999. Sixty-two children who were judged anemic, iron-depleted, or having low iron stores were randomly allocated to "control," "dietary modification" (consuming one additional citrus fruit after lunch), and "nutrition education" (teaching the mothers proper eating patterns based on the food pyramid) groups. Food habits were surveyed, including 24-hour dietary recall and food frequency, as well as timing of consumption of special items; this survey was carried out for each child before and after intervention. After three months, blood samples were taken from the subjects. The prevalence of anemia, iron depletion, and low iron stores was 11.4, 62.8, and 15.1% respectively, with no significant differences observed in hemoglobin and percent transferrin saturation (%TS) between the groups. Mean+/-SD serum ferritin concentrations in "control," "diet modification," and "nutrition education" groups were 8.9+/-3.1, 9.5+/-3.7, and 6.9+/-2.3 microg/dL. The same figures at the end of intervention were 6.9+/-3.5, 11.2+/-5, and 10.7+/-5.9 microg/dL, respectively. Analysis of variance showed ferritin concentrations to be significantly different, in that there was a reduction in the control and elevation in the nutrition education groups. There was no significant difference in %TS before and after the intervention. During three months of intervention, changes in frequency of fruit and fruit juice intake after the meals in nutrition education and diet modification groups were significantly correlated to serum ferritin alteration. Frequency of fruit juice intake (rich in vitamin C) after meals (at least five times a week) can significantly increase serum ferritin within three months. Therefore, educating mothers of iron

30 CFR 18.81 - Field modification of approved (permissible) equipment; application for approval of modification...

Code of Federal Regulations, 2010 CFR

2010-07-01

..., and Permits To Use Experimental Equipment § 18.81 Field modification of approved (permissible... alter the basic functional design that was originally approved for the equipment. (c) Upon receipt of...

30 CFR 18.81 - Field modification of approved (permissible) equipment; application for approval of modification...

Code of Federal Regulations, 2013 CFR

2013-07-01

..., and Permits To Use Experimental Equipment § 18.81 Field modification of approved (permissible... alter the basic functional design that was originally approved for the equipment. (c) Upon receipt of...

30 CFR 18.81 - Field modification of approved (permissible) equipment; application for approval of modification...

Code of Federal Regulations, 2011 CFR

2011-07-01

..., and Permits To Use Experimental Equipment § 18.81 Field modification of approved (permissible... alter the basic functional design that was originally approved for the equipment. (c) Upon receipt of...

30 CFR 18.81 - Field modification of approved (permissible) equipment; application for approval of modification...

Code of Federal Regulations, 2012 CFR

2012-07-01

..., and Permits To Use Experimental Equipment § 18.81 Field modification of approved (permissible... alter the basic functional design that was originally approved for the equipment. (c) Upon receipt of...

Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs.

PubMed

Metzler-Zebeli, Barbara U; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

2015-01-01

Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid

Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs

PubMed Central

Metzler-Zebeli, Barbara U.; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

2015-01-01

Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid

Mutant p53 proteins alter cancer cell secretome and tumour microenvironment: Involvement in cancer invasion and metastasis.

PubMed

Cordani, Marco; Pacchiana, Raffaella; Butera, Giovanna; D'Orazi, Gabriella; Scarpa, Aldo; Donadelli, Massimo

2016-07-01

An ever-increasing number of studies highlight the role of mutant p53 proteins in the alteration of cancer cell secretome and in the modification of tumour microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge of the molecular mechanisms underlying the interplay between mutant p53 proteins and the microenvironment is becoming fundamental for the identification of both efficient anticancer therapeutic strategies and novel serum biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight data from available literature, suggesting that mutant p53 proteins are able to (i) alter the secretion of enzymes involved in the modulation of extracellular matrix components; (ii) alter the secretion of inflammatory cytokines; (iii) increase the extracellular acidification; and (iv) regulate the crosstalk between cancer and stromal cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder

PubMed Central

Pecorelli, Alessandra; Belmonte, Giuseppe; Meloni, Ilaria; Cervellati, Franco; Gardi, Concetta; Sticozzi, Claudia; De Felice, Claudio; Signorini, Cinzia; Cortelazzo, Alessio; Leoncini, Silvia; Ciccoli, Lucia; Renieri, Alessandra; Forman, Henry Jay; Hayek, Joussef; Valacchi, Giuseppe

2017-01-01

CDKL5 mutation is associated with an atypical Rett syndrome (RTT) variant. Recently, cholesterol homeostasis perturbation and oxidative-mediated loss of the high-density lipoprotein receptor SRB1 in typical RTT have been suggested. Here, we demonstrate an altered lipid serum profile also in CDKL5 patients with decreased levels of SRB1 and impaired activation of the defensive system Nrf2. In addition, CDKL5 fibroblasts showed an increase in 4-hydroxy-2-nonenal– and nitrotyrosine–SRB1 adducts that lead to its ubi-quitination and probable degradation. This study highlights a possible common denominator between two different RTT variants (MECP2 and CDKL5) and a possible common future therapeutic target. PMID:26006105

Bias modification training can alter approach bias and chocolate consumption.

PubMed

Schumacher, Sophie E; Kemps, Eva; Tiggemann, Marika

2016-01-01

Recent evidence has demonstrated that bias modification training has potential to reduce cognitive biases for attractive targets and affect health behaviours. The present study investigated whether cognitive bias modification training could be applied to reduce approach bias for chocolate and affect subsequent chocolate consumption. A sample of 120 women (18-27 years) were randomly assigned to an approach-chocolate condition or avoid-chocolate condition, in which they were trained to approach or avoid pictorial chocolate stimuli, respectively. Training had the predicted effect on approach bias, such that participants trained to approach chocolate demonstrated an increased approach bias to chocolate stimuli whereas participants trained to avoid such stimuli showed a reduced bias. Further, participants trained to avoid chocolate ate significantly less of a chocolate muffin in a subsequent taste test than participants trained to approach chocolate. Theoretically, results provide support for the dual process model's conceptualisation of consumption as being driven by implicit processes such as approach bias. In practice, approach bias modification may be a useful component of interventions designed to curb the consumption of unhealthy foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical modification of L-asparaginase from Cladosporium sp. for improved activity and thermal stability.

PubMed

Mohan Kumar, N S; Kishore, Vijay; Manonmani, H K

2014-01-01

L-Asparaginase (ASNase), an antileukemia enzyme, is facing problems with antigenicity in the blood. Modification of L-asparaginase from Cladosporium sp. was tried to obtain improved stability and improved functionality. In our experiment, modification of the enzyme was tried with bovine serum albumin, ovalbumin by crosslinking using glutaraldehyde, N-bromosuccinimide, and mono-methoxy polyethylene glycol. Modified enzymes were studied for activity, temperature stability, rate constants (kd), and protection to proteolytic digestion. Modification with ovalbumin resulted in improved enzyme activity that was 10-fold higher compared to native enzyme, while modification with bovine serum albumin through glutaraldehyde cross-linking resulted in high stability of L-asparaginase that was 8.5- and 7.62-fold more compared to native enzyme at 28°C and 37°C by the end of 24 hr. These effects were dependent on the quantity of conjugate formed. Modification also markedly prolonged L-asparaginase half-life and serum stability. N-Bromosuccinimide-modified ASNase presented greater stability with prolonged in vitro half-life of 144 hr to proteolytic digestion relative to unmodified enzyme (93 h). The present work could be seen as producing a modified L-asparaginase with improved activity and stability and can be a potential source for developing therapeutic agents for cancer treatment.

Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

PubMed

You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

2013-01-01

Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder.

PubMed

Pecorelli, Alessandra; Belmonte, Giuseppe; Meloni, Ilaria; Cervellati, Franco; Gardi, Concetta; Sticozzi, Claudia; De Felice, Claudio; Signorini, Cinzia; Cortelazzo, Alessio; Leoncini, Silvia; Ciccoli, Lucia; Renieri, Alessandra; Jay Forman, Henry; Hayek, Joussef; Valacchi, Giuseppe

2015-09-01

CDKL5 mutation is associated with an atypical Rett syndrome (RTT) variant. Recently, cholesterol homeostasis perturbation and oxidative-mediated loss of the high-density lipoprotein receptor SRB1 in typical RTT have been suggested. Here, we demonstrate an altered lipid serum profile also in CDKL5 patients with decreased levels of SRB1 and impaired activation of the defensive system Nrf2. In addition, CDKL5 fibroblasts showed an increase in 4-hydroxy-2-nonenal- and nitrotyrosine-SRB1 adducts that lead to its ubiquitination and probable degradation. This study highlights a possible common denominator between two different RTT variants (MECP2 and CDKL5) and a possible common future therapeutic target. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

PubMed

Santolaya-Forgas, J; Meyer, W J; Burton, B K; Scommegna, A

1997-01-01

to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.

CLOSTAT alters the serum metabolome of Holstein Steer Calves

USDA-ARS?s Scientific Manuscript database

Probiotics are gaining increased interest in calf feeding operations as some producers seek novel, non-antibiotic technologies to improve health and performance. Therefore, the objective of this study was to evaluate changes in serum metabolomic compounds of Holstein steer calves supplemented with C...

Epigenetics: Beyond Chromatin Modifications and Complex Genetic Regulation1

PubMed Central

Eichten, Steven R.; Schmitz, Robert J.; Springer, Nathan M.

2014-01-01

Chromatin modifications and epigenetics may play important roles in many plant processes, including developmental regulation, responses to environmental stimuli, and local adaptation. Chromatin modifications describe biochemical changes to chromatin state, such as alterations in the specific type or placement of histones, modifications of DNA or histones, or changes in the specific proteins or RNAs that associate with a genomic region. The term epigenetic is often used to describe a variety of unexpected patterns of gene regulation or inheritance. Here, we specifically define epigenetics to include the key aspects of heritability (stable transmission of gene expression states through mitotic or meiotic cell divisions) and independence from DNA sequence changes. We argue against generically equating chromatin and epigenetics; although many examples of epigenetics involve chromatin changes, those chromatin changes are not always heritable or may be influenced by genetic changes. Careful use of the terms chromatin modifications and epigenetics can help separate the biochemical mechanisms of regulation from the inheritance patterns of altered chromatin states. Here, we also highlight examples in which chromatin modifications and epigenetics affect important plant processes. PMID:24872382

Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery

PubMed Central

Jamali, Fakhreddin; Kunz-Dober, Cornelia M

1999-01-01

Aims Rapid onset of analgesia is essential in the treatment of acute pain. There is evidence that conditions of stress cause delayed and decreased pain relief from oral analgesic products through impaired absorption. The aim was to determine the effect of surgery for removal of wisdom teeth on the plasma concentration-time profile of ibuprofen enantiomers. Methods Racemic ibuprofen, 200 mg in one group (n=7) and 600 mg in another group (n=7) was administered 1 week before (control) and again after (test) surgical removal of wisdom teeth. Serum concentrations of ibuprofen enantiomers were measured for 6 h. Results During the control phase, S- and R-ibuprofen concentrations were within the suggested therapeutic range. Surgery resulted in a 2 h delay in the mean time to peak concentration, significant decreases in serum ibuprofen concentration following both doses, and a fall to sub-optimal serum concentrations following the 200 mg dose. During the first 2 h after the 200 mg dose, dental extraction resulted in a significant reduction of the area under serum drug concentration (AUC (0, 2 h) mg l−1 h) from 5.6±2.9 to 1.6±1.8 (P<0.01) and from 5.5±3.0 to 2.1±2.0 (P<0.05) for S and R-ibuprofen, respectively. Similar observations were made following the 600 mg dose for AUC (0, 2 h) of S-ibuprofen (from 14.2±6.1 to 7.2±5.5 mg l−1 h, P<0.05) with no significant difference for R-ibuprofen (from 14.4±9.5 to 5.8±7.1). AUC (0, 6 h) was also significantly reduced by surgery. The pattern of stereoselectivity in serum ibuprofen concentration was reversed by surgery such that the S enantiomer was predominant in the control phase but not in the post-surgery phase, which is suggestive of reduced metabolic chiral inversion. Conclusions Surgery for wisdom tooth removal resulted in substantial decreases in the serum concentration of ibuprofen enantiomers and a prolongation in the time to peak concentration. Reduced absorption and altered metabolism are the likely cause of

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. I. Serum growth hormone-binding protein.

PubMed

Martha, P M; Rogol, A D; Carlsson, L M; Gesundheit, N; Blizzard, R M

1993-08-01

consequence, alterations may develop in the relative amounts of free vs. bound GH present in serum during the midpubertal years compared to those present during either the prepubertal or postpubertal periods. The majority of the known age-related increase in serum GHBP levels probably occurs before the period of active pubertal development. These findings strengthen further the concept that the midpubertal changes in GH secretion serve a primary role in generating the growth spurt.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum vitamin D levels are not altered after controlled diesel ...

EPA Pesticide Factsheets

Past research has suggested that exposure to urban air pollution may be associated with vitamin D deficiency in human populations. Vitamin D is widely known for its importance in bone growth/remodeling, muscle metabolism, and its ability to promote calcium absorption in the gut; deficiency in vitamin D results in the development of rickets in children and osteomalacia in adults. In the current study, we assessed whether vitamin D levels are altered under controlled exposures to a commonly measured urban air pollutant, diesel. For this study, we exposed 12 healthy volunteers to clean air and diesel exhaust (300 μg/m3) for 2 hours while undergoing intermittent exercise. Venous blood was collected before, 0 hrs post-, and 18 hrs post-exposure, and 25-hydroxyvitamin D [25(OH)D] was measured in the serum. The average baseline value of 25(OH)D (mean ± standard error) was 22.9 ± 2.5 ng/mL. Four subject’s baseline values were vitamin D deficient (30 ng/mL). Additionally, there was no significant change in the baseline values between the clean air and diesel exposures (paired t-test, p = 0.54), suggesting minimal variability in 25(OH)D over the experiment's time course. Small inductions in 25(OH)D were found following clean air exposures (12.5 ± 4.9% and a 7.1 ± 5.0% for 0 hrs post- and 18 hrs post-exposure values compared to baseline, respectively). Minimal changes in 25(OH)D were observed following diesel exhaust exposures 0 hrs (3.5 ± 5.2%) and 18 hrs followin

Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease.

PubMed

Tin, Adrienne; Grams, Morgan E; Maruthur, Nisa M; Astor, Brad C; Couper, David; Mosley, Thomas H; Selvin, Elizabeth; Coresh, Josef; Kao, Wen Hong Linda

2015-04-01

Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. As the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45-65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min per 1.73 m(2) in years 1987-89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7 mmol/l or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35-1.87) for CKD and 2.39 (95% CI: 1.61-3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates.

Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease

PubMed Central

Tin, Adrienne; Grams, Morgan E.; Maruthur, Nisa M.; Astor, Brad C.; Couper, David; Mosley, Thomas H.; Selvin, Elizabeth; Coresh, Josef; Linda Kao, Wen Hong

2014-01-01

Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. Since the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45 to 65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min/1.73m2 in years 1987–89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1,965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7mmol/L or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35–1.87) for CKD and 2.39 (95% CI: 1.61–3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates. PMID:25272232

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

Covalent Surface Modifications of Carbon Nanotubes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavia Sanders, Adriana; O'Bryan, Greg

A report meant to document the chemistries investigated by the author for covalent surface modification of CNTs. Oxidation, cycloaddition, and radical reactions were explored to determine their success at covalently altering the CNT surface. Characterization through infrared spectroscopy, Raman spectroscopy, and thermo gravimetric analysis was performed in order to determine the success of the chemistries employed. This report is not exhaustive and was performed for CNT surface modification exploration as it pertains to the "Next Gen" project.

Physiological serum copper concentrations found in malignancies cause unfolding induced aggregation of human serum albumin in vitro.

PubMed

Rizvi, Asim; Furkan, Mohd; Naseem, Imrana

2017-12-15

Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed. Copyright © 2017. Published by Elsevier Inc.

Total serum homocysteine as an indicator of vitamin B12 and folate status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, R.C.; Hall, C.A.

1988-10-01

Presented is a modification of an assay for total serum homocysteine (Hcy) in which the Hcy plus radioactive adenosine is converted enzymatically to labeled S-adenosylhomocysteine (AdoHcy). The modifications included a commerical source for the AdoHcy hydrolase, adenosine labeled with either /sup 14/C or /sup 3/H, and separation of the AdoHcy by thin layer chromatography. The assay was sensitive to 25 pmol. Hcy levels in sera from 18 controls ranged from 6.9 to 12.1 mumol/L with a mean of 9.1 and a SD of 1.5 mumol/L. The total serum Hcy was increased in vitamin B12 and folate deficiency. The level wasmore » high in congenital defects of vitamin B12 metabolism, blocking the methylation of Hcy regardless of the serum vitamin B12 levels, but was normal in the absence of tissue deficiency even if the serum vitamin B12 levels were low. The procedure has been found practical in two years of use and requires only 0.1 mL of serum.« less

Epigenetic Modifications of Major Depressive Disorder

PubMed Central

Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

2016-01-01

Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders. PMID:27527165

Element speciation during nuclear glass alteration

NASA Astrophysics Data System (ADS)

Galoisy, L.; Calas, G.; Bergeron, B.; Jollivet, P.; Pelegrin, E.

2011-12-01

Assessing the long-term behavior of nuclear glasses implies the prediction of their long-term performance. An important controlling parameter is their evolution during interaction with water under conditions simulating geological repositories. After briefly recalling the major characteristics of the local and medium-range structure of borosilicate glasses of nuclear interest, we will present some structural features of this evolution. Specific structural tools used to determine the local structure of glass surfaces include synchrotron-radiation x-ray absorption spectroscopy with total electron yield detection. The evolution of the structure of glass surface has been determined at the Zr-, Fe-, Si- and Al-K edges and U-LIII edge. During alteration in near- or under-saturated conditions, some elements such as Fe change coordination, as other elements such as Zr only suffer structural modifications in under-saturated conditions. Uranium exhibits a modification of its speciation from an hexa-coordinated U(VI) in the borosilicate glass to an uranyl group in the gel. These structural modifications may explain the chemical dependence of the initial alteration rate and the transition to the residual regime. They also illustrate the molecular-scale origin of the processes at the origin of the glass-to-gel transformation. Eventually, they explain the provisional trapping of U by the alteration gel: the uranium retention factors in the gel depend on the alteration conditions, and thus on the nature of the resulting gel and on the trapping conditions.

Public perceptions of hurricane modification.

PubMed

Klima, Kelly; Bruine de Bruin, Wändi; Morgan, M Granger; Grossmann, Iris

2012-07-01

If hurricane modification were to become a feasible strategy for potentially reducing hurricane damages, it would likely generate public discourse about whether to support its implementation. To facilitate an informed and constructive discourse, policymakers need to understand how people perceive hurricane modification. Here, we examine Florida residents' perceptions of hurricane modification techniques that aim to alter path and wind speed. Following the mental models approach, we conducted a survey study about public perceptions of hurricane modification that was guided by formative interviews on the topic. We report a set of four primary findings. First, hurricane modification was perceived as a relatively ineffective strategy for damage reduction, compared to other strategies for damage reduction. Second, hurricane modification was expected to lead to changes in projected hurricane path, but not necessarily to the successful reduction of projected hurricane strength. Third, more anger was evoked when a hurricane was described as having changed from the initially forecasted path or strength after an attempted modification. Fourth, unlike what we expected, participants who more strongly agreed with statements that recognized the uncertainty inherent in forecasts reported more rather than less anger at scientists across hurricane modification scenarios. If the efficacy of intensity-reduction techniques can be increased, people may be willing to support hurricane modification. However, such an effort would need to be combined with open and honest communications to members of the general public. © 2011 Society for Risk Analysis.

Spectroscopic analysis of the impact of oxidative stress on the structure of human serum albumin (HSA) in terms of its binding properties

NASA Astrophysics Data System (ADS)

Maciążek-Jurczyk, M.; Sułkowska, A.

2015-02-01

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis (RA). Reactive oxygen species (ROS) are produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. ROS result in oxidation of serum albumin, which causes a number of structural changes in the spatial structure, may influence the binding and cause significant drug interactions, particularly in polytherapy. During the oxidation modification of amino acid residues, particularly cysteine and methionine may occur. The aim of the study was to investigate the influence of oxidative stress on human serum albumin (HSA) structure and evaluate of possible alterations in the binding of the drug to oxidized human serum albumin (oHSA). HSA was oxidized by a chloramine-T (CT). CT reacts rapidly with sulfhydryl groups and at pH 7.4 the reaction was monitored by spectroscopic techniques. Modification of free thiol group in the Cys residue in HSA was quantitatively determined by the use of Ellman's reagent. Changes of albumin conformation were examined by comparison of modified (oHSA) and nonmodified human serum albumin (HSA) absorption spectra, emission spectra, red-edge shift (REES) and synchronous spectroscopy. Studies of absorption spectra indicated that changes in the value of absorbance associated with spectral changes in the region of 200-250 nm involve structural alterations in peptide backbone conformation. Synchronous fluorescence spectroscopy technique confirmed changes of position of tryptophanyl and tyrosyl residues fluorescent band caused by CT. Moreover analysis of REES effect allowed to observe structural changes caused by CT in the region of the hydrophobic pocket containing the tryptophanyl residue. Effect of oxidative stress on binding of anti-rheumatic drugs, sulfasalazine (SSZ) and sulindac (SLD) in the high and low affinity binding sites was

Workshop on Parent-Body and Nebular Modification of Chondritic Materials

NASA Technical Reports Server (NTRS)

Zolensky, M. E. (Editor); Krot, A. N. (Editor); Scott, E. R. D. (Editor)

1997-01-01

Topics considered include: thermal Metamorphosed Antarctic CM and CI Carbonaceous Chondrites in Japanese Collections, and Transformation Processes of Phyllosilicates; use of Oxygen Isotopes to Constrain the Nebular and Asteroidal Modification of Chondritic Materials; effect of Revised Nebular Water Distribution on Enstatite Chondrite Formation; interstellar Hydroxyls in Meteoritic Chondrules: Implications for the Origin of Water in the Inner Solar System; theoretical Models and Experimental Studies of Gas-Grain Chemistry in the Solar Nebula; chemical Alteration of Chondrules on Parent Bodies; thermal Quenching of Silicate Grains in Protostellar Sources; an Experimental Study of Magnetite Formation in the Solar Nebula; the Kaidun Meteorite: Evidence for Pre- and Postaccretionary Aqueous Alteration; a Transmission Electron Microscope Study of the Matrix Mineralogy of the Leoville CV3 (Reduced-Group) Carbonaceous Chondrite: Nebular and Parent-Body Features; rubidium-Strontium Isotopic Systematic of Chondrules from the Antarctic CV Chondrites Yamato 86751 and Yamato 86009: Additional Evidence for Late Parent-Body Modification; oxygen-Fugacity Indicators in Carbonaceous Chondrites: Parent-Body Alteration or High-Temperature Nebular Oxidation; thermodynamic Modeling of Aqueous Alteration in CV Chondrites; asteroidal Modification of C and O Chondrites: Myths and Models; oxygen Fugacity in the Solar Nebular; and the History of Metal and Sulfides in Chondrites.

The ethics of molecular memory modification.

PubMed

Hui, Katrina; Fisher, Carl E

2015-07-01

Novel molecular interventions have recently shown the potential to erase, enhance and alter specific long-term memories. Unique features of this form of memory modification call for a close examination of its possible applications. While there have been discussions of the ethics of memory modification in the literature, molecular memory modification (MMM) can provide special insights. Previously raised ethical concerns regarding memory enhancement, such as safety issues, the 'duty to remember', selfhood and personal identity, require re-evaluation in light of MMM. As a technology that exploits the brain's updating processes, MMM helps correct the common misconception that memory is a static entity by demonstrating how memory is plastic and subject to revision even in the absence of external manipulation. Furthermore, while putatively safer than other speculative technologies because of its high specificity, MMM raises notable safety issues, including potential insidious effects on the agent's emotions and personal identity. Nonetheless, MMM possesses characteristics of a more permissible form of modification, not only because it is theoretically safer, but because its unique mechanism of action requires a heightened level of cooperation from the agent. Discussions of memory modification must consider the specific mechanisms of action, which can alter the weight and relevance of various ethical concerns. MMM also highlights the need for conceptual accuracy regarding the term 'enhancement'; this umbrella term will have to be differentiated as new technologies are applied to a widening array of purposes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Early paternal deprivation alters levels of hippocampal brain-derived neurotrophic factor and glucocorticoid receptor and serum corticosterone and adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles.

PubMed

Wu, Ruiyong; Song, Zhenzhen; Wang, Siyang; Shui, Li; Tai, Fadao; Qiao, Xufeng; He, Fengqin

2014-01-01

In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels. © 2014 S. Karger AG, Basel.

ACTION OF SERUM ON FIBROBLASTS IN VITRO

PubMed Central

Carrel, Alexis; Ebeling, Albert H.

1923-01-01

It may be concluded that, under the conditions of the experiments: 1. The duration of life of fibroblasts is not altered by the presence of 7 per cent serum in a medium composed of fibrin and Tyrode solution, but is slightly decreased when the concentration of the serum reaches 25 per cent. 2. Fibroblasts cultivated in serum or in Tyrode solution are only in a condition of survival; they do not build up new protoplasm from the serum proteins and their mass does not increase. 3. When embryonic tissue juice is added to the medium, the tissues increase in mass. But the rate of growth is the same in media containing 0 per cent and 10 per cent serum. In 25 per cent serum, however, the rate of growth slightly decreases. Even in the presence of embryonic tissue juice, serum does not increase the rate of growth of connective tissue. 4. The nitrogenous compounds contained in serum are not used as food material by fibroblasts growing in vitro. PMID:19868757

Paternal deprivation alters play-fighting, serum corticosterone and the expression of hypothalamic vasopressin and oxytocin in juvenile male mandarin voles.

PubMed

Wang, Jianli; Tai, Fadao; Yan, Xingfu; Yu, Peng

2012-11-01

Although early paternal deprivation significantly affects offspring behavioral and neuroendocrine development, the link between paternal deprivation and social play behavior remains unclear. Mandarin voles (Microtus mandarinus) are socially monogamous and display bi-paternal care. The present study examined the development of social play in juvenile male mandarin voles and the paternal influence on play-fighting, vasopressin- and oxytocin-immunoreactive neurons and serum corticosterone and testosterone levels. The results show that social play was more pronounced during postnatal days 28-35, differing from the ontogenetic pattern of other forms of social behavior. On postnatal day 35, the peak in play-fighting activity, paternal deprivation reduced boxing/wrestling levels and vasopressin-immunoreactive neurons in the anterior hypothalamus and oxytocin-immunoreactive neurons in the paraventricular nucleus, but increased vasopressin-immunoreactive neurons in the paraventricular nucleus and corticosterone levels. These results suggest that mandarin voles engage in social play according to an inverted U-shaped curve in ontogeny, and paternal deprivation influences the development of offspring play-fighting; hypothalamic vasopressin, oxytocin and serum corticosterone may play a modulatory role in the alteration of play-fighting elicited by paternal deprivation; decreased play-fighting may correlate with depressed vasopressin levels in the anterior hypothalamus.

Porphyrin mediated photo-modification of the structure and function of human serum albumin

NASA Astrophysics Data System (ADS)

Rozinek, Sarah C.

Photosensitization reactions involve irradiating (with visible light) molecules with a high efficiency for either electron transfer or entering an excited triplet state (photosensitizer). Such reactions are applied to photodynamic cancer therapy, many medical laser-treatments, and a potential array of disinfection and pest elimination techniques. To understand the biophysical mechanisms of how these applications are effective at the protein level, the group of Dr. Brancaleon (UTSA) has investigated the irradiation of several dye-protein combinations, and discovered effects on protein structure and function. To further that work, we have investigated irradiation of the protein, human serum albumin (HSA), photosensitized by either protoporphyrin IX (PPIX) or meso-tetrakis(4-sulfonatophenyl)porphyrin (TSPP). HSA is the most abundant plasma protein, making it a likely substrate in PDT, and it possesses a specific binding pocket for iron-PPIX (heme) and possibly other porphyrin derivatives. The results of our research are summarized as follows. First, a thorough characterization of the binding of each photosensitizer to albumin was completed, elucidating a probable binding location for TSPP. Next, fluorescence lifetime emission of the single tryptophan residue, alongside circular dichroism, found tertiary structural changes around tryptophan and an overall 20% decrease in protein secondary structure after irradiation with TSPP bound. Finally, to determine if protein function was lost after photosensitization, size exclusion chromatography found modified albumin still recognizable by its receptor-protein, and comparative ex vivo up-take studies revealed that modified albumin is not processed the same way as native albumin in live tapeworm larva (Mesocestoides corti). Thus we found that visible light can induce partial unfolding of a protein by using a photo-activated ligand. These small structural modifications were sufficient to affect the protein's biological function.

Phosphorylation-related modification at the dimer interface of 14-3-3ω dramatically alters monomer interaction dynamics.

PubMed

Denison, Fiona C; Gökirmak, Tufan; Ferl, Robert J

2014-01-01

14-3-3 proteins are generally believed to function as dimers in a broad range of eukaryotic signaling pathways. The consequences of altering dimer stability are not fully understood. Phosphorylation at Ser58 in the dimer interface of mammalian 14-3-3 isoforms has been reported to destabilise dimers. An equivalent residue, Ser62, is present across most Arabidopsis isoforms but the effects of phosphorylation have not been studied in plants. Here, we assessed the effects of phosphorylation at the dimer interface of Arabidopsis 14-3-3ω. Protein kinase A phosphorylated 14-3-3ω at Ser62 and also at a previously unreported residue, Ser67, resulting in a monomer-sized band on native-PAGE. Phosphorylation at Ser62 alone, or with additional Ser67 phosphorylation, was investigated using phosphomimetic versions of 14-3-3ω. In electrophoretic and chromatographic analyses, these mutants showed mobilities intermediate between dimers and monomers. Mobility was increased by detergents, by reducing protein concentration, or by increasing pH or temperature. Urea gradient gels showed complex structural transitions associated with alterations of dimer stability, including a previously unreported 14-3-3 aggregation phenomenon. Overall, our analyses showed that dimer interface modifications such as phosphorylation reduce dimer stability, dramatically affecting the monomer-dimer equilibrium and denaturation trajectory. These findings may have dramatic implications for 14-3-3 structure and function in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

[Serum glycosaminoglycans in Graves' disease patients].

PubMed

Winsz-Szczotka, Katarzyna B; Olczyk, Krystyna Z; Koźma, Ewa M; Komosińska-Vassev, Katarzyna B; Wisowski, Grzegorz R; Marcisz, Czesław

2006-01-01

The aim of the study was to determine the blood serum sulfated glycosaminoglycans (GAGs) and hyaluronic acid (HA) concentration of Graves' disease patients before treatment and after attainment of the euthyroid state. The study was carried out on the blood serum obtained from 17 patients with newly recognised Graves' disease and from the same patients after attainment of the euthyroid state. Graves' patients had not any clinical symptoms neither of ophthalmopathy nor pretibial myxedema. GAGs were isolated from the blood serum by the multistage extraction and purification using papaine hydrolysis, alkali elimination, as well as cetylpyridium chloride binding. Total amount of GAGs was quantified by the hexuronic acids assay. HA content in obtained GAGs sample was evaluated by the ELISA method. Increased serum concentration of sulfated GAGs in non-treated Graves' disease patients was found. Similarly, serum HA level in untreated patients was significantly elevated. The attainment of euthyroid state was accompanied by the decreased serum sulfated GAGs level and by normalization of serum HA concentration. In conclusion, the results obtained demonstrate that the alterations of GAGs metabolism connected with Graves' disease can lead to systemic changes of the extracellular matrix properties.

Experimental Study on the Efficacy of Site-Specific PEGylated Human Serum Albumins in Resuscitation From Hemorrhagic Shock.

PubMed

Song, Xinlei; Zhang, Shu; Cheng, Yanna; Zhao, Ting; Lian, Qianqian; Lu, Lu; Wang, Fengshan

2016-11-01

To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. Laboratory. Male Wistar rats. Prospective study. Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids. The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability. Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.

Role of epigenetic modifications in luminal breast cancer

PubMed Central

Abdel-Hafiz, Hany A; Horwitz, Kathryn B

2015-01-01

Luminal breast cancers represent approximately 75% of cases. Explanations into the causes of endocrine resistance are complex and are generally ascribed to genomic mechanisms. Recently, attention has been drawn to the role of epigenetic modifications in hormone resistance. We review these here. Epigenetic modifications are reversible, heritable and include changes in DNA methylation patterns, modification of histones and altered microRNA expression levels that target the receptors or their signaling pathways. Large-scale analyses indicate distinct epigenomic profiles that distinguish breast cancers from normal and benign tissues. Taking advantage of the reversibility of epigenetic modifications, drugs that target epigenetic modifiers, given in combination with chemotherapies or endocrine therapies, may represent promising approaches to restoration of therapy responsiveness in these cases. PMID:25689414

On the genetic modification of psychology, personality, and behavior.

PubMed

Neitzke, Alex B

2012-12-01

I argue that the use of heritable modifications for psychology, personality, and behavior should be limited to the reversal or prevention of relatively unambiguous instances of pathology or likely harm (e.g. sociopathy). Most of the likely modifications of psychological personality would not be of this nature, however, and parents therefore should not have the freedom to make such modifications to future children. I argue by examining the viewpoints of both the individual and society. For individuals, modifications would interfere with their capacity for self-determination in a way that undermines the very concept of self-determination. I argue that modification of psychology and personality is unlike present parenting in morally significant ways. For society, modification offers a medium for power to manipulate the makeup of persons and populations, possibly causing biological harm to the species and altering our conceptions of social responsibility.

The determination of ultrafiltrable calcium and magnesium in serum.

PubMed

Danielson, B G; Pallin, E; Sohtell, M

1982-01-01

Ultrafiltrate of human serum was investigated in order to evaluate the serum content of calcium and magnesium. The acid and base concentrations and pH of the serum was altered through titration with HCl- or NaOH-solutions. The Pco2 was varied in the titrated serum using different carbon dioxide tensions. This was performed when serum was filtered in a recycling system. It is shown that the analysis of calcium and magnesium have to be done under anaerobic conditions or at standardized pH and Pco2 situations, as the concentrations vary with both pH and Pco2. The concentration ratio between ultrafiltrate and serum for calcium and magnesium was found to be 0.56 and 0.74 respectively at pH=7.41 and Pco2=40 mmHg.

N-Glycomic Changes in Serum Proteins in Type 2 Diabetes Mellitus Correlate with Complications and with Metabolic Syndrome Parameters

PubMed Central

Bonfigli, Anna Rita; Boemi, Massimo; Olivieri, Fabiola; Ceriello, Antonio; Genovese, Stefano; Spazzafumo, Liana; Borelli, Vincenzo; Bacalini, Maria Giulia; Salvioli, Stefano; Garagnani, Paolo; Dewaele, Sylviane; Libert, Claude; Franceschi, Claudio

2015-01-01

Background Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome. Methods We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6±8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5±12.4 years). N-glycome was evaluated in serum glycoproteins. Results We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, α(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with α(1,6)- and α(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme “unhealthy” phenotype (T2DM+ with MS). Conclusions Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non

Effect of supplemental vitamin D and calcium on serum sclerostin levels.

PubMed

Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa; Palermo, Nancy J

2014-04-01

Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults. We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ≥65 years. Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay. In the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calcium-supplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels. Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined.

Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

PubMed

Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

2017-06-01

The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

PubMed

Peng, Xian-E; Wu, Yun-Li; Zhu, Yi-Bing; Huang, Rong-Dong; Lu, Qing-Qing; Lin, Xu

2015-01-01

Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

Aging is associated with altered inflammatory, arachidonic acid cascade and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex

PubMed Central

Keleshian, Vasken L.; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated. PMID:23336521

Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels

PubMed Central

Zhu, Yi-bing; Huang, Rong-dong; Lu, Qing-Qing; Lin, Xu

2015-01-01

Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = —0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

Expulsion of Nippostrongylus brasiliensis from rats protected with serum. I. The efficacy of sera from singly and multiply infected donors related to time of administration and volume of serum injected.

PubMed Central

Miller, H R

1980-01-01

Several of the parameters related to the efficacy of passive protection against Nippostrongylus brasiliensis were studied in female hybrid (PVG/c x DA)F1 and outbred Wistar rats. The time after infection at which immune serum was given did, to some extent, alter the degree of protection conferred. There was substantial protection 8 days after challenge in rats given hyperimmune serum (HIS) either as daily injections 4-7 days post-infection or as a single dose on day 4. Eight separate experiments in which HIS was injected 4 days after challenge with 1000 l3 resulted in expulsion of 96 +/- 2% of the worm burdens by day 8. In a further six experiments, following infection with 2000 l3 and using the same protocol, 85 +/- 3% of the worm burden was expelled by day 8. A lag of 2 days between serum transfer and commencement of worm expulsion was consistently observed and, within the space of a further 2-4 days, more than 95% of the parasites were expelled. Transplanted 'normal' and 'damaged' adult worms were also susceptible to the passive transfer of HIS. Sera recovered from rats immunized with two or three challenges (hyperimmune sera) were more protective than sera from rats given one challenge. Serum from rats challenged for the first time 6 days previously conferred significant protection against a 1000 l3 infection and sera recovered 8 and 10-12 days post-infection with 4000 l3 protected recipients with increasing effectiveness. Thoracic duct lymph collected on the tenth day of infection with 4000 l3 was also protective. The response to both primary infection and hyperimmune serum was dose-dependent. The consistently good protection achieved in the present study when compared with the variable success of previous experiments (reviewed by Ogilvie & Jones, 1971) may be a function of the strain and sex of the rats used, together with modifications of the immunization protocols. The relevance of these findings to mucosal defences against N. brasiliensis is discussed

Improvement in Serum Biochemical Alterations and Oxidative Stress of Liver and Pancreas following Use of Royal Jelly in Streptozotocin-Induced Diabetic Rats

PubMed Central

Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

2016-01-01

Objective This study aimed to evaluate the effects of royal jelly (RJ) on serum biochemical alterations and oxidative stress status in liver and pancreas of streptozotocin (STZ)- induced diabetic rats. Materials and Methods In this experimental study, thirty two male Wistar rats were divided into the following four groups (n=8/group): i. Control (C), ii. Diabetic (D), iii. Royal jelly (R), and iv. Royal jelly-treated diabetic (D/R) groups. Diabetes was induced by single intraperitoneal (IP) injection of STZ (60 mg/kg). The RJ [100 mg/kg body weight (BW)] was administered orally for 42 days. Blood samples were used to determine serum levels of insulin, high density lipoprotein cholesterol (HDL-c), total protein (TP), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and fasting blood glucose (FBG). Also, the antioxidant status was evaluated by determining the levels of malondialdehyde (MDA), catalase (CAT) and ferric reducing antioxidant power (FRAP) in liver and pancreas. Data were analyzed by one-way analysis of variance (ANOVA) with P<0.05 as the significant level. Results STZ-induced diabetic rats showed a significant elevation in the serum levels of AST, ALT, ALP and FBG, whereas there was a significant decrease in serum levels of insulin, albumin, HDL-c and TP (P<0.05). Treatment of the diabetic rats with RJ restored the changes of the above parameters to their normal levels (P<0.05). In addition, RJ significantly improved reduced levels of FRAP and CAT as well as high MDA level in liver and pancreas (P<0.05). Conclusion RJ improves oxidative damage induced by STZ in the liver and pancreas of rats; therefore, it can be considered as an effective and alternative treatment for diabetes. PMID:27602318

Improvement in Serum Biochemical Alterations and Oxidative Stress of Liver and Pancreas following Use of Royal Jelly in Streptozotocin-Induced Diabetic Rats.

PubMed

Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

2016-01-01

This study aimed to evaluate the effects of royal jelly (RJ) on serum biochemical alterations and oxidative stress status in liver and pancreas of streptozotocin (STZ)- induced diabetic rats. In this experimental study, thirty two male Wistar rats were divided into the following four groups (n=8/group): i. Control (C), ii. Diabetic (D), iii. Royal jelly (R), and iv. Royal jelly-treated diabetic (D/R) groups. Diabetes was induced by single intraperitoneal (IP) injection of STZ (60 mg/kg). The RJ [100 mg/kg body weight (BW)] was administered orally for 42 days. Blood samples were used to determine serum levels of insulin, high density lipoprotein cholesterol (HDL-c), total protein (TP), albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and fasting blood glucose (FBG). Also, the antioxidant status was evaluated by determining the levels of malondialdehyde (MDA), catalase (CAT) and ferric reducing antioxidant power (FRAP) in liver and pancreas. Data were analyzed by one-way analysis of variance (ANOVA) with P<0.05 as the significant level. STZ-induced diabetic rats showed a significant elevation in the serum levels of AST, ALT, ALP and FBG, whereas there was a significant decrease in serum levels of insulin, albumin, HDL-c and TP (P<0.05). Treatment of the diabetic rats with RJ restored the changes of the above parameters to their normal levels (P<0.05). In addition, RJ significantly improved reduced levels of FRAP and CAT as well as high MDA level in liver and pancreas (P<0.05). RJ improves oxidative damage induced by STZ in the liver and pancreas of rats; therefore, it can be considered as an effective and alternative treatment for diabetes.

Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

PubMed Central

Nguyen, Leonard T.; Chau, Johnny K.; Perry, Nicole A.; de Boer, Leonie; Zaat, Sebastian A. J.; Vogel, Hans J.

2010-01-01

Background Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the “antimicrobial centre” of bovine lactoferricin as well as an antimicrobial sequence obtained through the screening of a hexapeptide combinatorial library. Methodology/Principal Findings HPLC, mass spectrometry and antimicrobial assays were carried out to explore the consequences of the modifications on the serum stability and microbicidal activity of the peptides. The results show that C-terminal amidation increases the antimicrobial activity but that it makes little difference to its proteolytic degradation in human serum. On the other hand, N-terminal acetylation decreases the peptide activities but significantly increases their protease resistance. Peptide cyclization of the hexameric peptides was found to be highly effective for both serum stability and antimicrobial activity. However the two cyclization strategies employed have different effects, with disulfide cyclization resulting in more active peptides while backbone cyclization results in more proteolytically stable peptides. However, the benefit of backbone cyclization did not extend to longer 11-mer peptides derived from the same region of lactoferricin. Mass spectrometry data support the serum stability assay results and allowed us to determine preferred proteolysis sites in the peptides. Furthermore, isothermal titration calorimetry experiments showed that the peptides all had weak interactions with albumin, the most abundant protein in human serum. Conclusions/Significance Taken together, the results provide insight into the behavior of the peptides in human serum and will therefore aid in advancing antimicrobial peptide design towards systemic applications. PMID:20844765

Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

PubMed

Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

2014-11-01

Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maternal serum thrombospondin-1 is significantly altered in cases with established preeclampsia.

PubMed

Ulu, İpek; Çekmez, Yasemin; Yıldırım Köpük, Şule; Özer, Nida; Yoğurtçuoğlu, Eser Evrim; Anğın, Pınar; Kıran, Gürkan

2018-02-22

The aim of the study was to investigate whether maternal serum TSP-1 level was associated with PE. In our case control study, 84 pregnant women in the third trimester were included. Forty-one of them were healthy and 43 of them were with the diagnosis of PE. The diagnosis was based on the definitions of the National High Blood Pressure Education Program working Group on High Blood Pressure in Pregnancy. Preeclamptic patients were divided into two subgroups as mild and severe. Blood pressure (BP) of pregnant women were obtained in left-side lying position using a mercury sphygmomanometer after at least 10 minutes of rest. Ten milliliters of venous blood was taken from every pregnant women and dispensed into lithium heparin and serum was obtained. Samples were stored at -80 °C until analyzed. Serum TSP-1 level was measured using enzyme-linked immunosorbent assay (ELISA). All tests were two-tailed and p < .05 was considered to be statistically significant. TSP-1 level was significantly lower in PE group than in controls (p = .003). Platelet counts were similar in two groups (p = .26). TSP-1 levels were significantly lower in severe PE than in mild PE cases. According to the subgroup analysis, TSP-1 level was found significantly lower in severe preeclampsia group compared to control group (p = .015). In light of the association between endothelial dysfunction and preeclampsia, we claim that lower levels of TSP-1 which is released mostly from endothelial cells seem to reflect disease severity in PE. Our study reveals that maternal serum TSP-1 levels decrease in pregnant women presenting with PE and TSP-1 may be a new biomarker for the detection of PE and even severity of it. Further studies especially prospective ones with greater numbers of cases are needed.

Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions.

PubMed

Treuel, Lennart; Brandholt, Stefan; Maffre, Pauline; Wiegele, Sarah; Shang, Li; Nienhaus, G Ulrich

2014-01-28

Recent studies have firmly established that cellular uptake of nanoparticles is strongly affected by the presence and the physicochemical properties of a protein adsorption layer around these nanoparticles. Here, we have modified human serum albumin (HSA), a serum protein often used in model studies of protein adsorption onto nanoparticles, to alter its surface charge distribution and investigated the consequences for protein corona formation around small (radius ∼5 nm), dihydrolipoic acid-coated quantum dots (DHLA-QDs) by using fluorescence correlation spectroscopy. HSA modified by succinic anhydride (HSAsuc) to generate additional carboxyl groups on the protein surface showed a 3-fold decreased binding affinity toward the nanoparticles. A 1000-fold enhanced affinity was observed for HSA modified by ethylenediamine (HSAam) to increase the number of amino functions on the protein surface. Remarkably, HSAsuc formed a much thicker protein adsorption layer (8.1 nm) than native HSA (3.3 nm), indicating that it binds in a distinctly different orientation on the nanoparticle, whereas the HSAam corona (4.6 nm) is only slightly thicker. Notably, protein binding to DHLA-QDs was found to be entirely reversible, independent of the modification. We have also measured the extent and kinetics of internalization of these nanoparticles without and with adsorbed native and modified HSA by HeLa cells. Pronounced variations were observed, indicating that even small physicochemical changes of the protein corona may affect biological responses.

Serum lipid alterations in GBA-associated Parkinson's disease.

PubMed

Guedes, Leonor Correia; Chan, Robin Barry; Gomes, Marcos António; Conceição, Vasco A; Machado, Raquel Bouça; Soares, Tiago; Xu, Yimeng; Gaspar, Paulo; Carriço, Joao André; Alcalay, Roy N; Ferreira, Joaquim J; Outeiro, Tiago Fleming; Miltenberger-Miltenyi, Gabriel

2017-11-01

Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2. 64 patients (29 GBA positive vs. 35 non-GBA-carriers including 18 LRRK2 positive and 17 non-mutated) were analyzed for chitotriosidase activity and for the concentration of 40 lipid classes using HPLC-MS. 29/415 patients (6.9%) carried 8 different GBA mutations associated with Gaucher or Parkinson's, including one novel mutation. Chitotriosidase activity was similar across the genetic groups, while the levels of key lipids were altered in GBA mutation carriers: Monohexosylceramide, Ceramide and Sphingomyelin were elevated; while Phosphatidic acid (PA), Phosphatidylethanolamine (PE), Plasmalogen phosphatidylethanolamine (PEp) and Acyl Phosphatidylglycerol (AcylPG) were decreased. The results suggest an important role for these lipids in GBA mediated Parkinson's disease and assist in the identification of common pathways between Gaucher and Parkinson's. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Four Surgical Modifications to the Classic Elastase Perfusion Aneurysm Model Enable Haemodynamic Alterations and Extended Elastase Perfusion.

PubMed

Busch, Albert; Chernogubova, Ekaterina; Jin, Hong; Meurer, Felix; Eckstein, Hans-Henning; Kim, Mia; Maegdefessel, Lars

2018-04-24

Abdominal aortic aneurysm (AAA) is an individual and socioeconomic burden in today's ageing society. Treatment relies on surgical exclusion of the dilated aorta by open or endovascular repair. For research purposes, animal models are necessary and the elastase induced aneurysm model closely mimics end stage human aneurysm disease. To improve the translational value of this model, four modifications to the classic elastase perfusion procedure (PPE) in relation to human aneurysm morphology were conducted. In ten week old male C57BL/6J wild type mice the PPE procedure was modified in four ways using two different techniques. Flow alteration was simulated by partial ligation of the common iliac artery or the distal aorta. Additionally, careful exploration of the abdominal aortic branches allowed PPE induction at the suprarenal and iliac level. Molecular biology, ultrasound, and immunohistochemistry were used to evaluate these pilot results. Two aortic outflow obstructions simulating distal aortic or iliac stenosis significantly increase murine AAA diameter (p = .046), and affect local vascular wall remodelling. Suprarenal aortic dissection allows a juxtarenal aneurysm to be induced, similar to the angiotensin II induced aneurysm model. A separate investigation for canonical activation of transforming growth factor β in the two embryonically distinct juxtarenal and infrarenal segments showed no distinct difference. Creating an aortoiliac bifurcated aneurysm completes the mimicry of human aneurysm morphology. The alteration of the classic PPE aneurysm by outflow modulation and further elastase perfusion to the juxtarenal and aortoiliac segment modifies morphology and diameter, and thus increases the translational value in future research. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Fatty acyltranferases in serum in cystic fibrosis (CF) patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zielenski, J.; Newman, L.J.; Slomiany, B.L.

1987-05-01

Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15 l of serum was mixed with 0.85 nmol ( UC)palmitoyl CoA, 200 g of serine and threonine and incubated at 37C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation ofmore » ( UC)palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of ( UC)palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids.« less

Aflatoxin B1-induced epigenetic alterations: An overview.

PubMed

Dai, Yaqi; Huang, Kunlun; Zhang, Boyang; Zhu, Liye; Xu, Wentao

2017-11-01

Aflatoxin B1 (AFB1) is widely distributed in nature, especially in a variety of food commodities. It is confirmed to be the most toxic of all the aflatoxins. The toxicity of AFB1 has been well investigated, and it may result in severe health problems including carcinogenesis, mutagenesis, growth retardation, and immune suppression. Epigenetic modifications including DNA methylation, histone modifications and regulation of non-coding RNA play an important role in AFB1-induced disease and carcinogenesis. To better understand the evidence for AFB1-induced epigenetic alterations and the potential mechanisms of the toxicity of AFB1, we conducted a review of published studies of AFB1-induced epigenetic alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Site specific modification of the human plasma proteome by methylglyoxal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimzey, Michael J.; Kinsky, Owen R.; Yassine, Hussein N.

Increasing evidence identifies dicarbonyl stress from reactive glucose metabolites, such as methylglyoxal (MG), as a major pathogenic link between hyperglycemia and complications of diabetes. MG covalently modifies arginine residues, yet the site specificity of this modification has not been thoroughly investigated. Sites of MG adduction in the plasma proteome were identified using LC–MS/MS analysis in vitro following incubation of plasma proteins with MG. Treatment of plasma proteins with MG yielded 14 putative MG hotspots from five plasma proteins (albumin [nine hotspots], serotransferrin, haptoglobin [2 hotspots], hemopexin, and Ig lambda-2 chain C regions). The search results revealed two versions of MG-argininemore » modification, dihydroxyimidazolidine (R + 72) and hydroimidazolone (R + 54) adducts. One of the sites identified was R257 in human serum albumin, which is a critical residue located in drug binding site I. This site was validated as a target for MG modification by a fluorescent probe displacement assay, which revealed significant drug dissociation at 300 μM MG from a prodan–HSA complex (75 μM). Moreover, twelve human plasma samples (six male, six female, with two type 2 diabetic subjects from both genders) were analyzed using multiple reaction monitoring (MRM) tandem mass spectrometry and revealed the presence of the MG-modified albumin R257 peptide. These data provide insights into the nature of the site-specificity of MG modification of arginine, which may be useful for therapeutic treatments that aim to prevent MG-mediated adverse responses in patients. - Highlights: • Methylglyoxal (MG) selectively modifies arginine sites in human plasma proteome. • Dihydroxyimidazolidine and hydroimidazolone adducts on serum albumin identified • MG modification on albumin R257 associated with loss of drug site I binding capacity • MRM-tandem mass spectrometry enables sensitive detection of albumin MG-R257. • Site-specific MG modification may

Alterations in adipokines in feline hepatic lipidosis.

PubMed

Mazaki-Tovi, M; Abood, S K; Segev, G; Schenck, P A

2013-01-01

Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. Serum concentrations of adiponectin and leptin are altered in feline HL. Client-owned cats: 55 healthy and 45 with liver disease. Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 μg/mL), HL and concurrent disease (4.4 μg/mL), or other liver disease (6.1 μg/mL), as compared with healthy cats (1.5 μg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Environmental Alterations of Epigenetics Prior to the Birth

PubMed Central

Lo, Chiao-Ling; Zhou, Feng C.

2014-01-01

The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, non-coding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late onset neuropsychiatric diseases, or idiosyncratic mental disorders. PMID:25131541

Environmental alterations of epigenetics prior to the birth.

PubMed

Lo, Chiao-Ling; Zhou, Feng C

2014-01-01

The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, noncoding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late-onset neuropsychiatric diseases, or idiosyncratic mental disorders. © 2014 Elsevier Inc. All rights reserved.

Surface modification of protein enhances encapsulation in chitosan nanoparticles

NASA Astrophysics Data System (ADS)

Koyani, Rina D.; Andrade, Mariana; Quester, Katrin; Gaytán, Paul; Huerta-Saquero, Alejandro; Vazquez-Duhalt, Rafael

2018-04-01

Chitosan nanoparticles have a huge potential as nanocarriers for environmental and biomedical purposes. Protein encapsulation in nano-sized chitosan provides protection against inactivation, proteolysis, and other alterations due to environmental conditions, as well as the possibility to be targeted to specific tissues by ligand functionalization. In this work, we demonstrate that the chemical modification of the protein surface enhances the protein loading in chitosan nanocarriers. Encapsulation of green fluorescent protein and the cytochrome P450 was studied. The increase of electrostatic interactions between the free amino groups of chitosan and the increased number of free carboxylic groups in the protein surface enhance the protein loading, protein retention, and, thus, the enzymatic activity of chitosan nanoparticles. The chemical modification of protein surface with malonic acid moieties reduced drastically the protein isoelectric point increasing the protein interaction with the polycationic biomaterial and chitosan. The chemical modification of protein does not alter the morphology of chitosan nanoparticles that showed an average diameter of 18 nm, spheroidal in shape, and smooth surfaced. The strategy of chemical modification of protein surface, shown here, is a simple and efficient technique to enhance the protein loading in chitosan nanoparticles. This technique could be used for other nanoparticles based on polycationic or polyanionic materials. The increase of protein loading improves, doubtless, the performance of protein-loaded chitosan nanoparticles for biotechnological and biomedical applications.

Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene.

PubMed

Huang, Peiwu; Ren, Xiaohu; Huang, Zhijun; Yang, Xifei; Hong, Wenxu; Zhang, Yanfang; Zhang, Hang; Liu, Wei; Huang, Haiyan; Huang, Xinfeng; Wu, Desheng; Yang, Linqing; Tang, Haiyan; Zhou, Li; Li, Xuan; Liu, Jianjun

2014-08-17

Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease. Copyright © 2014. Published by Elsevier Ireland Ltd.

Hypochlorite modification of sphingomyelin generates chlorinated lipid species that induce apoptosis and proteome alterations in dopaminergic PC12 neurons in vitro

PubMed Central

Nusshold, Christoph; Kollroser, Manfred; Köfeler, Harald; Rechberger, Gerald; Reicher, Helga; Üllen, Andreas; Bernhart, Eva; Waltl, Sabine; Kratzer, Ingrid; Hermetter, Albin; Hackl, Hubert; Trajanoski, Zlatko; Hrzenjak, Andelko; Malle, Ernst; Sattler, Wolfgang

2014-01-01

Recent observations link myeloperoxidase (MPO) activation to neurodegeneration. In multiple sclerosis MPO is present in areas of active demyelination where the potent oxidant hypochlorous acid (HOCl), formed by MPO from H2O2 and chloride ions, could oxidatively damage myelin-associated lipids. The purpose of this study was (i) to characterize reaction products of sphingomyelin (SM) formed in response to modification by HOCl, (ii) to define the impact of exogenously added SM and HOCl-modified SM (HOCl-SM) on viability parameters of a neuronal cell line (PC12), and (iii) to study alterations in the PC12 cell proteome in response to SM and HOCl-SM. MALDI-TOF-MS analyses revealed that HOCl, added as reagent or generated enzymatically, transforms SM into chlorinated species. On the cellular level HOCl-SM but not SM induced the formation of reactive oxygen species. HOCl-SM induced severely impaired cell viability, dissipation of the mitochondrial membrane potential, and activation of caspase-3 and DNA damage. Proteome analyses identified differential expression of specific subsets of proteins in response to SM and HOCl-SM. Our results demonstrate that HOCl modification of SM results in the generation of chlorinated lipid species with potent neurotoxic properties. Given the emerging connections between the MPO–H2O2–chloride axis and neurodegeneration, this chlorinating pathway might be implicated in neuropathogenesis. PMID:20226853

Serum magnesium and calcium levels in infertile women during a cycle of reproductive assistance.

PubMed

Grossi, Elena; Castiglioni, Sara; Moscheni, Claudia; Antonazzo, Patrizio; Cetin, Irene; Savasi, Valeria Maria

2017-05-01

Magnesium (Mg) and calcium (Ca) are essential cations for women's preconception health. It is well known that, in blood, the concentration of ionized form of these two cations is temporally altered during menstrual cycle, suggesting a correlation between sex steroid hormones and serum calcium and magnesium levels. Evidence from literature suggests that in assisted reproductive technology increasing estrogens during ovarian hyperstimulation may also modulate serum magnesium and calcium levels. Therefore, we first examined total serum magnesium and calcium levels during follicular phase in a large population of infertile patients who underwent intrauterine insemination (IUI). The results were compared to a group of fertile women. Successively, we studied the total serum magnesium and calcium concentrations in infertile patients before and after ovarian hyperstimulation for in vitro fertilization (IVF). Results highlight that total serum concentration of magnesium and calcium does not seem altered in infertile women. During stimulation with gonadotropins, the values of the two cations do not change significantly in ovarian-stimulated women. However, we found a downward trend in the total magnesium and calcium levels in relation to the rising estrogens.

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

PubMed

Hicks, R R; Baldwin, S A; Scheff, S W

1997-01-01

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels.

PubMed

O'Connell, Charles W; Gerona, Roy R; Friesen, Matthew W; Ly, Binh T

2015-07-01

Ibogaine, a psychotropic indole alkaloid, is gaining popularity among medical subcultures for its purported anti addictive properties. Its use has been associated with altered mental status, ataxia, gastrointestinal distress, ventricular arrhythmias, and sudden and unexplained deaths.Its pharmacokinetics in toxic states is not well understood. Case report:A 33-year-old man overdosed on ibogaine in an attempt to quit his use of heroin. He developed altered state of consciousness, tremor, ataxia,nausea, vomiting, and transient QT interval prolongation, which all remitted as he cleared the substance. Ibogaine was confirmed in his urine and serum with a peak serum concentration of 377 ng/mL. Nonlinear elimination kinetics and a formula match to its active metabolite noriobgaine were observed as well. This case presents the unique description of serial serum concentrations as well as urine and product-confirmed ibogaine toxicity with transient toxin-related QT interval prolongation.

Introduction to the thematic minireview series on redox-active protein modifications and signaling.

PubMed

Banerjee, Ruma

2013-09-13

The dynamics of redox metabolism necessitate cellular strategies for sensing redox changes and for responding to them. A common mechanism for receiving and transmitting redox changes is via reversible modifications of protein cysteine residues. A plethora of cysteine modifications have been described, including sulfenylation, glutathionylation, and disulfide formation. These post-translational modifications have the potential to alter protein structure and/or function and to modulate cellular processes ranging from division to death and from circadian rhythms to secretion. The focus of this thematic minireview series is cysteine modifications in response to reactive oxygen and nitrogen species.

Detecting the impact of bank and channel modification on invertebrate communities in Mediterranean temporary streams (Sardinia, SW Italy).

PubMed

Buffagni, Andrea; Tenchini, Roberta; Cazzola, Marcello; Erba, Stefania; Balestrini, Raffaella; Belfiore, Carlo; Pagnotta, Romano

2016-09-15

We hypothesized that reach-scale, bank and channel modification would impact benthic communities in temporary rivers of Sardinia, when pollution and water abstraction are not relevant. A range of variables were considered, which include both artificial structures/alterations and natural features observed in a stream reach. Multivariate regression trees (MRT) were used to assess the effects of the explanatory variables on invertebrate assemblages and five groups, characterized by different habitat modification and/or features, were recognized. Four node variables determined the splits in the MRT analysis: channel reinforcement, tree-related bank and channel habitats, channel modification and bank modification. Continuity of trees in the river corridor diverged among MRT groups and significant differences among groups include presence of alders, extent of channel shading and substrate diversity. Also, the percentage of in-stream organic substrates, in particular CPOM/Xylal, showed highly significant differences among groups. For practical applications, thresholds for the extent of channel reinforcement (40%) and modification (10%) and for bank alteration (≈30%) were provided, that can be used to guide the implementation of restoration measures. In moderately altered river reaches, a significant extent of tree-related habitats (≈5%) can noticeably mitigate the effects of morphological alteration on aquatic invertebrates. The outcomes highlight the importance of riparian zone management as an opportune, achievable prospect in the restoration of Mediterranean temporary streams. The impact of bank and channel modification on ecological status (sensu WFD) was investigated and the tested benthic metrics, especially those based on abundance data, showed legible differences among MRT groups. Finally, bank and channel modification appears to be a potential threat for the conservation of a few Sardo-Corsican endemic species. The introduction of management criteria that

Thyroxine-induced changes in the glycosylation pattern and in brain and serum levels of rat alpha-fetoprotein.

PubMed

Naval, J; Calvo, M; Lampreave, F; Piñeiro, A

1986-01-01

We have studied the effect of thyroid disfunction during the postnatal period, on the serum and brain levels of rat alpha-fetoprotein (AFP) and albumin. Hypothyroidism was induced by treatment of pregnant rats and their newborn pups with 2-mercapto-1-methylimidazole(methimazole). Hyperthyroidism was provoked in newborns by daily injections of thyroxine (0.25 micrograms/g body wt) from the 3rd postnatal day weaning. Impaired growth, lower brain size, altered behaviour and morphological features observed were according to an altered thyroid status. Hypothyroid rats showed a significantly reduction in serum AFP concentration (78% of control values at 8 days of age) and a slight increase in that of albumin. level could be appreciated. Thyroxine supplementation (0.2 micrograms/rat/day) corrected most of these alterations. Hyperthyroidism induced a drastic fall in both serum and brain AFP levels (about 48% of the corresponding control values). Albumin concentration in serum was augmented significantly from the 12th postnatal day, but its brain levels did not change significantly. In hyperthyroid rats, a significant reduction (37% relative to controls) in the concanavalin A-non reactive microform of AFP, was observed. This alteration of the glycosylation pattern of AFP could be due to the inhibition by thyroxine of the activity of the hepatic enzyme GlcNAc-transferase III.

Epigenetic modifications in prostate cancer.

PubMed

Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

2014-01-01

Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout

PubMed Central

Tan, Philip K.; Farrar, Jennifer E.; Gaucher, Eric A.; Miner, Jeffrey N.

2016-01-01

Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice. This difference in transport kinetics of URAT1 orthologs, along with inability of modern apes to oxidize uric acid due to loss of the uricase enzyme, prompted us to ask whether these events occurred concomitantly during primate evolution. Ancestral URAT1 sequences were computationally inferred and ancient transporters were resurrected and assayed, revealing that affinity for uric acid was increased during the evolution of primates. This molecular fine-tuning occurred between the origins of simians and their diversification into New- and Old-World monkey and ape lineages. Remarkably, it was driven in large-part by only a few amino acid replacements within the transporter. This alteration in primate URAT1 coincided with changes in uricase that greatly diminished the enzymatic activity and took place 27–77 Ma. These results suggest that the modifications to URAT1 transporters were potentially adaptive and that maintaining more constant, high levels of serum uric acid may have provided an advantage to our primate ancestors. PMID:27352852

Pressure sores and blood and serum dysmetabolism in spinal cord injury patients.

PubMed

Scivoletto, G; Fuoco, U; Morganti, B; Cosentino, E; Molinari, M

2004-08-01

Spinal cord injury (SCI) patients with pressure sores were studied before and after surgical intervention for ulcer healing and compared with matched SCI patients without sores and with patients with pressure sores and other diseases. To analyse the relationship between pressure sores and anaemia and serum protein alteration in SCI patients. To study the pathogenesis of these alterations and suggest appropriate therapy. Spinal cord unit in Rome, Italy. A total of 13 SCI patients with pressure sores, 13 comparable patients without pressure sores and four patients with other diseases and pressure sores. Haematochemical parameters. Patients with pressure sore showed significant decreased red cells, decreased haemoglobin and haematocrit, increased white cells and ferritin and decreased transferrin and transferrin saturation; total hypoproteinemia and hypoalbuminemia with increased Alfa-1 and gamma globulins increased erythrocyte sedimentation rate and C-reactive protein were also present. The alterations returned to normal after surgical intervention for pressure sore healing. Patients with pressure sores suffer from anaemia and serum protein alteration that fells within the range of metabolic alteration of chronic disorders and neoplastic diseases. The alterations depend on a decreased utilisation of iron stores in the reticuloendothelial system and on inhibition of the hepatic synthesis of albumin. With regard to treatment, iron treatment should be avoided because of the risk of haemochromatosis.

Effect of antacid and ascorbic acid on serum salicylate concentration.

PubMed

Hansten, P D; Hayton, W L

1980-01-01

To determine the effect of antacid or ascorbic acid administration on plateau serum salicylate concentrations, nine healthy subjects were given each of the following treatments by balanced block design: choline salicylate (equivalent to 3.76 or 5.62 Gm/day of aspirin); choline salicylate plus magnesium-aluminum hydroxide (120 ml/day); or choline salicylate plus ascorbic acid (3 Gm/day). In subjects developing a control serum salicylate level above 10 mg/dl, antacid administration produced a decrease in serum salicylate level (mean 19.8 mg/dl vs. 15.8 mg/dl) (P less than 0.01). Ascorbic acid administration was not associated with a significant change in serum salicylate. The reduction in serum salicylate following antacid appears to be due to antacid-induced alkalinization of the urine with resultant increase in renal salicylate clearance. Antacid administration should be considered a potential cause of altered serum salicylate concentration in patients receiving large doses of salicylate.

Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’

PubMed Central

Kapoor, Utkarsh

2017-01-01

The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications. PMID:28566301

Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc, and serum oxytocin in mandarin voles.

PubMed

Cao, Yan; Wu, Ruiyong; Tai, Fadao; Zhang, Xia; Yu, Peng; An, Xiaolei; Qiao, Xufeng; Hao, Ping

2014-01-01

Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation-dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation. Copyright © 2013 Elsevier Inc. All rights reserved.

Genome-wide analyses of four major histone modifications in Arabidopsis hybrids at the germinating seed stage.

PubMed

Zhu, Anyu; Greaves, Ian K; Dennis, Elizabeth S; Peacock, W James

2017-02-07

Hybrid vigour (heterosis) has been used for decades in cropping agriculture, especially in the production of maize and rice, because hybrid varieties exceed their parents in plant biomass and seed yield. The molecular basis of hybrid vigour is not fully understood. Previous studies have suggested that epigenetic systems could play a role in heterosis. In this project, we investigated genome-wide patterns of four histone modifications in Arabidopsis hybrids in germinating seeds. We found that although hybrids have similar histone modification patterns to the parents in most regions of the genome, they have altered patterns at specific loci. A small subset of genes show changes in histone modifications in the hybrids that correlate with changes in gene expression. Our results also show that genome-wide patterns of histone modifications in geminating seeds parallel those at later developmental stages of seedlings. Ler/C24 hybrids showed similar genome-wide patterns of histone modifications as the parents at an early germination stage. However, a small subset of genes, such as FLC, showed correlated changes in histone modification and in gene expression in the hybrids. The altered patterns of histone modifications for those genes in hybrids could be related to some heterotic traits in Arabidopsis, such as flowering time, and could play a role in hybrid vigour establishment.

A strategy to improve serum-tolerant transfection activity of polycation vectors by surface hydroxylation.

PubMed

Luo, Xiao-hua; Huang, Fu-wei; Qin, Si-yong; Wang, Hua-fen; Feng, Jun; Zhang, Xian-zheng; Zhuo, Ren-xi

2011-12-01

The aim of this contribution is to develop a universal method to promote the serum-tolerant capability of polycation-based gene delivery system. A "hydroxylation camouflage" strategy was put forward by coating the polycation vectors with hydroxyl-enriched "skin". Branched polyethyleneimine (PEI) was herein used as the polycation model and modified via the catalyst-free aminolysis reaction with 5-ethyl-5-(hydroxymethyl)-1,3-dioxan-2-oxo (EHDO). PEI-g-EHDO, PEI and alkylated PEI derivative termed as PEI-g-DPA were comparatively explored with respect to the transfection efficiency in the serum-free and serum-conditioned medium. The resultant data indicate that the serum-tolerant capability largely depended on the surface composition and substitution degree. In addition to the reduced surface charge, the introduced function caused by hydroxyl coating is believed to play a crucial role for the improved properties of PEI-g-EHDOs. The EHDO modification can effectively inhibit the adsorption of BSA proteins onto polyplexes surface. And the polyplexes stability was remarkably enhanced in the presence of DNase and heparin after EHDO modification. Note that the transfection activity of PEI-g-EHDO(34.5%) in the serum-conditioned medium was even higher than that without serum addition. In contrast, serum addition led to appreciable reduction in the transfection efficiency mediated by PEI and PEI-g-DPAs. Specifically, as far as the transfection activity in the presence of serum is concerned, PEI-g-EHDO could be up to 30-fold higher than unmodified PEI25k. PEI-g-EHDO(34.5%) displayed little to no hemolytic effect and high cell-biocompatibility with nearly no cytotoxicity detected in 293T cells and HeLa cells. Taking into account the high biocompatibility and serum-tolerant transfection activity, PEI-g-EHDO(34.5%) holds great potential for the use as efficient gene vector. More importantly, it is expected that such "hydroxylation camouflage" strategy may be universally applicable

Analysis of human serum phosphopeptidome by a focused database searching strategy.

PubMed

Zhu, Jun; Wang, Fangjun; Cheng, Kai; Song, Chunxia; Qin, Hongqiang; Hu, Lianghai; Figeys, Daniel; Ye, Mingliang; Zou, Hanfa

2013-01-14

As human serum is an important source for early diagnosis of many serious diseases, analysis of serum proteome and peptidome has been extensively performed. However, the serum phosphopeptidome was less explored probably because the effective method for database searching is lacking. Conventional database searching strategy always uses the whole proteome database, which is very time-consuming for phosphopeptidome search due to the huge searching space resulted from the high redundancy of the database and the setting of dynamic modifications during searching. In this work, a focused database searching strategy using an in-house collected human serum pro-peptidome target/decoy database (HuSPep) was established. It was found that the searching time was significantly decreased without compromising the identification sensitivity. By combining size-selective Ti (IV)-MCM-41 enrichment, RP-RP off-line separation, and complementary CID and ETD fragmentation with the new searching strategy, 143 unique endogenous phosphopeptides and 133 phosphorylation sites (109 novel sites) were identified from human serum with high reliability. Copyright © 2012 Elsevier B.V. All rights reserved.

Serum phosphorus and mortality in the Third National Health and Nutrition Examination Survey (NHANES III): effect modification by fasting.

PubMed

Chang, Alex R; Grams, Morgan E

2014-10-01

Serum phosphorus levels have been associated with mortality in some but not all studies. Because dietary intake prior to measurement can affect serum phosphorus levels, we hypothesized that the association between serum phosphorus level and mortality is strongest in those who have fasted longer. Prospective cohort study. Nationally representative sample of 12,984 participants 20 years or older in the Third National Health and Nutrition Examination Survey (1988-1994). Serum phosphorus level, fasting duration (dichotomized as ≥ 12 or < 12 hours). All-cause and cardiovascular mortality determined by death certificate data from the National Death Index. Serum phosphorus measured in a central laboratory and fasting duration recorded as time since food or drink other than water was consumed. Individuals fasting 12 or more hours had lower serum phosphorus levels than those fasting less than 12 hours (3.34 vs 3.55 mg/dL; P < 0.001) and higher correlation with repeat measurement (0.66 vs 0.53; P = 0.002). In multivariable-adjusted Cox regression models, the highest quartile of serum phosphorus was associated with increased mortality in participants fasting 12 or more hours (adjusted HR, 1.74; 95% CI, 1.38-2.20; reference, lowest quartile) but not in participants fasting less than 12 hours (adjusted HR, 1.08; 95% CI, 0.89-1.32; P for interaction = 0.002). Relationships were consistent using 8 hours as the fasting cutoff point or cardiovascular mortality as the outcome. Observational study, lack of fibroblast growth factor 23 or intact parathyroid hormone measurements. Fasting but not nonfasting serum phosphorus levels were associated with increased mortality. Risk prognostication based on serum phosphorus may be improved using fasting levels. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Alterations in Aspergillus brasiliensis (niger) ATCC 9642 membranes associated to metabolism modifications during application of low-intensity electric current.

PubMed

Velasco-Alvarez, Nancy; Gutiérrez-Rojas, Mariano; González, Ignacio

2017-12-01

The effects of electric current on membranes associated with metabolism modifications in Aspergillus brasiliensis (niger) ATCC 9642 were studied. A 450-mL electrochemical cell with titanium ruthenium-oxide coated electrodes and packed with 15g of perlite, as inert support, was inoculated with A. brasiliensis spores and incubated in a solid inert-substrate culture (12 d; 30°C). Then, 4.5days after starting the culture, a current of 0.42mAcm -2 was applied for 24h. The application of low-intensity electric current increased the molecular oxygen consumption rate in the mitochondrial respiratory chain, resulting in high concentrations of reactive oxygen species, promoting high lipoperoxidation levels, according to measured malondialdehyde, and consequent alterations in membrane permeability explained the high n-hexadecane (HXD) degradation rates observed here (4.7-fold higher than cultures without current). Finally, cell differentiation and spore production were strongly stimulated. The study contributes to the understanding of the effect of current on the cell membrane and its association with HXD metabolism. Copyright © 2017. Published by Elsevier B.V.

Practical methods for handling human periodontal ligament stem cells in serum-free and serum-containing culture conditions under hypoxia: implications for regenerative medicine.

PubMed

Murabayashi, Dai; Mochizuki, Mai; Tamaki, Yuichi; Nakahara, Taka

2017-07-01

Stem cell-based therapies depend on the reliable expansion of patient-derived mesenchymal stem cells (MSCs) in vitro. The supplementation of cell culture media with serum is associated with several risks; accordingly, serum-free media are commercially available for cell culture. Furthermore, hypoxia is known to accelerate the expansion of MSCs. The present study aimed to characterize the properties of periodontal ligament-derived MSCs (PDLSCs) cultivated in serum-free and serum-containing media, under hypoxic and normoxic conditions. Cell growth, gene and protein expression, cytodifferentiation potential, genomic stability, cytotoxic response, and in vivo hard tissue generation of PDLSCs were examined. Our findings indicated that cultivation in serum-free medium does not affect the MSC phenotype or chromosomal stability of PDLSCs. PDLSCs expanded in serum-free medium exhibited more active growth than in fetal bovine serum-containing medium. We found that hypoxia does not alter the cell growth of PDLSCs under serum-free conditions, but inhibits their osteogenic and adipogenic cytodifferentiation while enabling maintenance of their multidifferentiation potential regardless of the presence of serum. PDLSCs expanded in serum-free medium were found to retain common MSC characteristics, including the capacity for hard tissue formation in vivo. However, PDLSCs cultured in serum-free culture conditions were more susceptible to damage following exposure to extrinsic cytotoxic stimuli than those cultured in medium supplemented with serum, suggesting that serum-free culture conditions do not exert protective effects against cytotoxicity on PDLSC cultures. The present work provides a comparative evaluation of cell culture in serum-free and serum-containing media, under hypoxic and normoxic conditions, for applications in regenerative medicine.

Post-Translational Modification Biology of Glutamate Receptors and Drug Addiction

PubMed Central

Mao, Li-Min; Guo, Ming-Lei; Jin, Dao-Zhong; Fibuch, Eugene E.; Choe, Eun Sang; Wang, John Q.

2011-01-01

Post-translational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues in their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling, and protein–protein interactions), subcellular redistribution (trafficking, endocytosis, synaptic delivery, and clustering), and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamine). Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction. PMID:21441996

Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth.

PubMed

D'Silva, Arlene M; Hyett, Jon A; Coorssen, Jens R

2018-04-30

Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder. Identifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare preterm (<37 weeks) and preterm (≥37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a

Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

ERIC Educational Resources Information Center

Cohen, Jonathan C.; And Others

1986-01-01

Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

Micro-RNA Profiling in Human Serum Reveals Compartment-Specific Roles of miR-571 and miR-652 in Liver Cirrhosis

PubMed Central

Roderburg, Christoph; Mollnow, Tobias; Bongaerts, Brenda; Elfimova, Natalia; Vargas Cardenas, David; Berger, Katharina; Zimmermann, Henning; Koch, Alexander; Vucur, Mihael; Luedde, Mark; Hellerbrand, Claus; Odenthal, Margarete; Trautwein, Christian; Tacke, Frank; Luedde, Tom

2012-01-01

Background and Aims Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles in liver cirrhosis were identified in screening approaches on liver parenchyma, mostly in rodent models. Therefore, in the present study we performed a systematic screening approach in order to identify miRNAs with altered levels in the serum of patients with chronic liver disease and liver cirrhosis. Methods We performed a systematic, array-based miRNA expression analysis on serum samples from patients with liver cirrhosis. In functional experiments we evaluated the relationship between alterations of miRNA serum levels and their role in distinct cellular compartments involved in hepatic cirrhosis. Results The array analysis and the subsequent confirmation by qPCR in a larger patient cohort identified significant alterations in serum levels of miR-513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum levels closely correlated with disease stages, thus revealing potential as a novel biomarker for hepatic cirrhosis. Further analysis revealed that up-regulation of miR-571 in serum reflected a concordant regulation in cirrhotic liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic cytokine TGF-β. In contrast, alterations in serum levels of miR-652 were stage-independent, reflecting a concordant down-regulation of this miRNA in circulating monocytes of patients with liver cirrhosis, which was inducible by proinflammatory stimuli like bacterial lipopolysaccharide. Conclusion Alterations of miR571 and miR-652 serum levels in patients with chronic liver disease reflect their putative roles in the mediation of fibrogenic and inflammatory processes in distinct cellular

Serum caffeine and paraxanthine concentrations and menstrual cycle function: correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study.

PubMed

Schliep, Karen C; Schisterman, Enrique F; Wactawski-Wende, Jean; Perkins, Neil J; Radin, Rose G; Zarek, Shvetha M; Mitchell, Emily M; Sjaarda, Lindsey A; Mumford, Sunni L

2016-07-01

Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements. We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation. The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race. Caffeine intake, irrespective of the beverage source, may be associated with

Influence of cattle temperament on blood serum fatty acid content

USDA-ARS?s Scientific Manuscript database

Cattle temperament has been reported to influence blood metabolites. Specifically, temperament was related with increased circulation of serum NEFA, decreased blood urea nitrogen, and reduced insulin sensitivity. Metabolic alterations such as these may impact cattle immune function, performance trai...

Identification and characterization of ana o 3 modifications on arginine-111 residue in heated cashew nuts

USDA-ARS?s Scientific Manuscript database

Heating foods can alter the physical, chemical, and biological characteristics of the proteins we consume. Raw and roasted cashew nut extracts were evaluated for allergen modifications by mass-spectrometry. We did not identify modifications on Ana o 1 or Ana o 2, but we observed two independent mo...

Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder.

PubMed

Wan, Yunqiang; Liu, Yuanhui; Wang, Xiaobin; Wu, Jiali; Liu, Kezhi; Zhou, Jun; Liu, Li; Zhang, Chunxiang

2015-01-01

Major depression is a debilitating disease. To date, the development of biomarkers of major depressive disorder (MDD) remains a challenge. Recently, alterations in the expression of microRNAs (miRNAs) from post-mortem brain tissue and peripheral blood have been linked to MDD. The goals of this study were to detect the differential miRNAs in cerebrospinal fluid (CSF) and serum of MDD patients. First, the relative expression levels of 179 miRNAs (relative high levels in serum) were analyzed by miRNA PCR Panel in the CSF of MDD patients. Then, the differentially altered miRNAs from CSF were further assessed by qRT-PCR in the serum of the same patients. Finally, the serum differentially altered miRNAs were further validated by qRT-PCR in the serum of another MDD patients. The CSF-results indicated that 11 miRNAs in MDD patients were significantly higher than these in control subjects, and 5 miRNAs were significantly lower than these in control subjects. The serum-results from the same patients showed that 3 miRNAs (miR-221-3p, miR-34a-5p, and let-7d-3p) of the 11 miRNAs were significantly higher than these in control subjects, and 1 miRNA (miR-451a) of 5 miRNAs was significantly lower than these in control subjects. The up-regulation of miR-221-3p, miR-34a-5p, let-7d-3p and down-regulation of miR-451a was further validated in another 32 MDD patients. ROC analysis showed that the area under curve of let-7d-3p, miR-34a-5p, miR-221-3p and miR-451a was 0.94, 0.98, 0.97 and 0.94, with specificity of 90.48%, 95.24%, 90.48% and 90.48%, and sensitivity of 93.75%, 96.88%, 90.63% and 84.85%, respectively. In addition, target gene prediction found that the altered miRNAs are involved in affecting some important genes and pathway related to MDD. Our results suggested that differentially altered miRNAs in CSF might be involved in MDD, and serum miR-221-3p, miR-34a-5p, let-7d-3p, and miR-451a might be able to serve as biomarkers for MDD.

Pregnancy amelioration of arthritis in SKG mice corresponds with alterations in serum amyloid A3 levels.

PubMed

Shaw, Laura A; Stefanski, Adrianne L; Peterson, Lisa K; Rumer, Kristen K; Vondracek, Andrea; Phang, Tzu L; Sakaguchi, Shimon; Winn, Virginia D; Dragone, Leonard L

2012-06-30

OBJECTIVES: Pregnancy leads to rheumatoid arthritis remission in humans. The objective of this study was to determine if the SKG mouse could serve as a model for pregnancy-associated inflammatory arthritis amelioration. In addition, the maternal peripheral blood mononuclear cell (PBMC) transcriptome was assessed to define a biomarker associated with remission. METHODS: Cohorts of zymosan-treated pregnant SKG mice and controls were monitored for arthritis progression. Microarray analysis evaluated alterations in gene expression in maternal PBMCs at embryonic day 14.5 (E14.5) between arthritic and pregnancy-remitted mice. A selected target, serum amyloid A3 (SAA3), was further investigated using quantitative reverse transcriptase PCR (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). RESULTS: Pregnancy resulted in complete or partial remission in the majority of the zymosan-treated SKG mice. Twenty-seven transcripts were differentially expressed in the PBMCs between arthritic and pregnancy-remitted mice. Expression and plasma SAA3 levels decreased with pregnancy-induced arthritis amelioration and plasma SAA3 levels correlated with arthritis severity. CONCLUSIONS: These results establish the SKG mouse as a model system to study pregnancy-induced amelioration of arthritis. These studies also establish SAA3 as a biomarker of arthritis amelioration in SKG mice. This model can be used to elucidate the molecular and cellular mechanisms underlying the impact of pregnancy on the maternal immune system that results in arthritis amelioration.

Assessment of nutritional status and serum leptin in children with inflammatory bowel disease.

PubMed

Aurangzeb, Brekhna; Leach, Steven T; Lemberg, Daniel A; Day, Andrew S

2011-05-01

Children with inflammatory bowel disease (IBD) commonly have altered nutrition and growth. Measurement of serum leptin may enhance other modalities to assess the nutritional state of children with IBD. The aim of the present study was to define the nutritional status of children with newly diagnosed IBD by measuring anthropometry and serum leptin levels. Twenty-eight children newly diagnosed with IBD and 56 age- and sex-matched controls were enrolled prospectively. Anthropometry (weight, height, and body mass index [BMI] expressed as z scores) and serum leptin levels were measured. The children with IBD had lower mean BMI z scores and weight-for-age percentiles than controls (P = 0.05 and P = 0.01, respectively). The mean (standard deviation) serum leptin levels of the children with IBD were 2.4 (± 1.9) pg/mL, compared with 5.2 (± 4.6) pg/mL for controls (P = 0.01). The BMI percentile correlated positively with leptin levels in both groups. Following adjustment for BMI percentiles, serum leptin levels were lower in children with IBD than in controls (P = 0.02). Leptin levels did not correlate with serum markers of inflammation or disease activity scores. Detailed and focused nutritional assessment should be an integral part of the management of all children with IBD. Children at the time of diagnosis of IBD have significant undernutrition and have lower serum leptin levels than controls. The inflammatory state in IBD appears not to alter leptin metabolism. Further study of the effect of leptin in IBD is required.

Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism.

PubMed

Martos-Moreno, G Á; Kratzsch, J; Körner, A; Barrios, V; Hawkins, F; Kiess, W; Argente, J

2011-10-01

To investigate the impact of obesity, weight loss and oral glucose ingestion on serum visfatin and vaspin levels in prepubertal children. A total of 100 prepubertal obese Caucasian children (OB) and 42 controls (C) were studied. The OB group was studied at baseline and after moderate (n=46) and extensive (n=14) body mass index (BMI) reduction by conservative treatment, undergoing body composition studies (dual-energy X-ray absorptiometry) and oral glucose tolerance tests (OGTTs). Serum visfatin and vaspin levels were studied throughout the OGTT, as were their relationships with insulin, leptin, leptin soluble receptor (sOB-R), adiponectin (total and high molecular weight), resistin, interleukin-6 (IL-6) and tumor necrosis factor-α levels at every time point. OB had higher visfatin (P<0.001), but similar vaspin than C. BMI reduction decreased visfatin levels (P<0.001), with BMI, waist circumference and the surrogate markers of body fat (leptin and sOB-R) showing significant correlations (P<0.05) with this peptide, but not with vaspin. Visfatin and vaspin decreased during the OGTT (P<0.001). Weight reduction did not alter visfatin dynamics in the OGTT, but decreased the area under the curve (AUC) for vaspin (P<0.001), with a correlation between the AUCs for vaspin and insulin after weight loss (P<0.05). Visfatin levels were positively correlated with resistin and IL-6, after controlling for BMI and HOMA (homeostatic model assessment) index at every time point in the study. Serum visfatin, but not vaspin, levels are influenced by body fat content in obese children, whereas both adipokines are modulated by glucose intake in a BMI-dependent manner.

Heterogeneous polymer modification: Polyolefin maleation in supercritical carbon dioxide and amorphous fluoropolymer surface modification

NASA Astrophysics Data System (ADS)

Hayes, Heather J.

1999-11-01

Three distinct heterogeneous polymer modification reactions are explored in this work. The first is a bulk reaction commonly conducted on polyolefins---the free radical addition of maleic anhydride. This reaction was run using supercritical carbon dioxide (SC CO2) as the solvent. The second was the chemical surface modification of an amorphous fluorocopolymer of tetrafluoroethylene and a perfluorodioxole monomer (Teflon AF). Several reactions were explored to reduce the surface of the fluorocopolymer for the enhancement of wettability. The last modification was also on Teflon AF and involved the physical modification of the surface through the transport polymerization of xylylene in order to synthesize a novel bilayer membrane. The bulk maleation of poly-4-methyl-1-pentene (PMP) was the focus of the first project. SC CO2 was utilized as both solvent and swelling agent to promote this heterogeneous reaction and led to successful grafting of anhydride groups on both PMP and linear low density polyethylene. Varying the reaction conditions and reagent concentrations allowed optimization of the reaction. The grafted anhydride units were found to exist as single maleic and succinic grafts, and the PMP became crosslinked upon maleation. The surface of a fluoropolymer can be difficult to alter. An examination of three reactions was made to determine the reactivity of Teflon AF: sodium naphthalenide treatment (Na-Nap), aluminum metal modification through deposition and dissolution, and mercury/ammonia photosensitization. The fluorocopolymer with the lower perfluorodioxole percentage was found to be more reactive towards modification with the Na-Nap treatment. The other modification reactions appeared to be nearly equally reactive toward both fluorocopolymers. The functionality of the Na-Nap-treated surface was examined in detail with the use of several derivatization reactions. In the final project, an asymmetric gas separation membrane was synthesized using Teflon AF as

Serum caffeine and paraxanthine concentrations and menstrual cycle function: correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study12

PubMed Central

Schisterman, Enrique F; Wactawski-Wende, Jean; Perkins, Neil J; Radin, Rose G; Zarek, Shvetha M; Mitchell, Emily M; Sjaarda, Lindsey A; Mumford, Sunni L

2016-01-01

Background: Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements. Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Design: Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation. Results: The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race. Conclusion: Caffeine intake

28 CFR 36.302 - Modifications in policies, practices, or procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... mobility impairments to make all their purchases at that aisle. (e)(1) Reservations made by places of... the public accommodation can demonstrate that making the modifications would fundamentally alter the...'s control (e.g., voice control, signals, or other effective means). (5) Care or supervision. A...

28 CFR 36.302 - Modifications in policies, practices, or procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... mobility impairments to make all their purchases at that aisle. (e)(1) Reservations made by places of... the public accommodation can demonstrate that making the modifications would fundamentally alter the...'s control (e.g., voice control, signals, or other effective means). (5) Care or supervision. A...

28 CFR 36.302 - Modifications in policies, practices, or procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... mobility impairments to make all their purchases at that aisle. (e)(1) Reservations made by places of... the public accommodation can demonstrate that making the modifications would fundamentally alter the...'s control (e.g., voice control, signals, or other effective means). (5) Care or supervision. A...

Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout.

PubMed

Tan, Philip K; Farrar, Jennifer E; Gaucher, Eric A; Miner, Jeffrey N

2016-09-01

Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice. This difference in transport kinetics of URAT1 orthologs, along with inability of modern apes to oxidize uric acid due to loss of the uricase enzyme, prompted us to ask whether these events occurred concomitantly during primate evolution. Ancestral URAT1 sequences were computationally inferred and ancient transporters were resurrected and assayed, revealing that affinity for uric acid was increased during the evolution of primates. This molecular fine-tuning occurred between the origins of simians and their diversification into New- and Old-World monkey and ape lineages. Remarkably, it was driven in large-part by only a few amino acid replacements within the transporter. This alteration in primate URAT1 coincided with changes in uricase that greatly diminished the enzymatic activity and took place 27-77 Ma. These results suggest that the modifications to URAT1 transporters were potentially adaptive and that maintaining more constant, high levels of serum uric acid may have provided an advantage to our primate ancestors. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The epidemiology of serum sex hormones in postmenopausal women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cauley, J.A.; Kuller, L.H.; LeDonne, D.

1989-06-01

Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sexmore » hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.« less

tRNAmodpred: a computational method for predicting posttranscriptional modifications in tRNAs

PubMed Central

Machnicka, Magdalena A.; Dunin-Horkawicz, Stanislaw; de Crécy-Lagard, Valerie; Bujnicki, Janusz M.

2016-01-01

tRNA molecules contain numerous chemically altered nucleosides, which are formed by enzymatic modification of the primary transcripts during the complex tRNA maturation process. Some of the modifications are introduced by single reactions, while other require complex series of reactions carried out by several different enzymes. The location and distribution of various types of modifications vary greatly between different tRNA molecules, organisms and organelles. We have developed a computational method tRNAmodpred, for predicting modifications in tRNA sequences. Briefly, our method takes as an input one or more unmodified tRNA sequences and a set of protein sequences corresponding to a proteome of a cell. Subsequently it identifies homologs of known tRNA modification enzymes in the proteome, predicts tRNA modification activities and maps them onto known pathways of RNA modification from the MODOMICS database. Thereby, theoretically possible modification pathways are identified, and products of these modification reactions are proposed for query tRNAs. This method allows for predicting modification patterns for newly sequenced genomes as well as for checking tentative modification status of tRNAs from one species treated with enzymes from another source, e.g. to predict the possible modifications of eukaryotic tRNAs expressed in bacteria. tRNAmodpred is freely available as web server at http://genesilico.pl/trnamodpred/. PMID:27016142

Genomic and Epigenomic Alterations in Cancer.

PubMed

Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

2016-07-01

Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis.

PubMed

Iyer, Sapna; Park, Min-Jung; Moons, David; Kwan, Raymond; Liao, Jian; Liu, Li; Omary, M Bishr

2017-01-22

Acute pancreatitis has several underlying etiologies, and results in consequences ranging from mild to complex multi-organ failure. The wide range of pathology suggests a genetic predisposition for progression. We compared the susceptibility to acute pancreatitis in BALB/c and FVB/N mice, coupled with proteomic analysis, in order to identify potential protein associations with pancreatitis progression. Pancreatitis was induced in BALB/c and FVB/N mice by administration of cerulein or feeding a choline-deficient, ethionine-supplemented (CDE) diet. Histology and changes in serum amylase were examined. Proteome profiling in cerulein-treated mice was performed using 2-dimensional differential in gel electrophoresis (2D-DIGE) followed by mass spectrometry analysis and biochemical validation. Male and female FVB/N mice manifested more severe cerulein-induced pancreatitis as compared with BALB/c mice, but both strains were similarly susceptible to CDE-induced pancreatitis. Few of the 2D-DIGE alterations were validated by immunoblotting. Clusterin was markedly up-regulated after cerulein-induced pancreatitis in FVB/N but less-so in BALB/c mice. Pyrroline-5-carboxylate reductase (Pycr1), an enzyme involved in proline biosynthesis, had higher basal levels in FVB/N male and female mouse pancreata compared with BALB/c pancreata, and was relatively more resistant to degradation in FVB/N pancreata. However, serum and pancreas tissue proline levels were similar in the two strains. FVB/N is more susceptible than BALB/c mice to cerulein-induced but not CDE-induced pancreatitis. Most of the 2D-DIGE alterations in the two strains likely relate to posttranslational modifications rather than protein level differences. Clusterin levels increase dramatically in association with pancreatitis severity, while Pycr1 is higher in FVB/N versus BALB/c pancreata basally and after induction of pancreatitis. Changes in proline metabolism may represent a novel potential genetic modifier in the

Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers

PubMed Central

Okugawa, Yoshinaga; Grady, William M.; Goel, Ajay

2015-01-01

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colon epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer “epigenome” has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, is presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC. PMID:26216839

Serum level of scorpion toxins, electrolytes and electrocardiogram alterations in Mexican children envenomed by scorpion sting.

PubMed

Osnaya-Romero, N; Acosta-Saavedra, L C; Goytia-Acevedo, R; Lares-Asseff, I; Basurto-Celaya, G; Perez-Guille, G; Possani, L D; Calderón-Aranda, E S

2016-11-01

The scorpion Centruroides limpidus limpidus (C.l.l.) is endemic in México, producing hundreds of accidents in humans; children being one of the most susceptible targets. Few studies reported that severe envenoming by scorpion venom induces cardiac damage and electrolytes abnormalities in children, but the relationship of envenoming severity and toxic blood levels is unknown. The aim of this study was to determine the relationship among clinical status of envenoming, serum electrolyte, electrocardiographic abnormalities, and serum toxin levels in 44 children stung by scorpion over a period of 6 months in the State of Morelos, Mexico. The patients were said to be asymptomatic, when they presented just local symptoms, and were said to be symptomatic when showing local symptoms and at least one systemic symptom. The clinical status was evaluated at the admission at the emergency room of the Hospital, and 30 min after the administration of polyspecific F(ab')2 anti-scorpion therapy to symptomatic children. Forty-one percent of the children were asymptomatic and 59% symptomatic. Potassium and sodium imbalance and an elongation of the QT interval were detected; the rate of hypokalemia was higher in symptomatic than on asymptomatic children (50% and 6%, respectively). Hypokalemia persisted in 19% in symptomatic patients, whereas sodium reached normal levels 30 min after anti-venom therapy. The hypokalemia statistically correlated with elongation of the QT interval. The concentration of the toxic components of C.l.l in serum was significantly higher in symptomatic than asymptomatic children, and the serum levels of the toxic component significantly decreased to undetectable levels after the application of anti-venom therapy. Despite the small size of the sample, this study establishes that severity of envenoming was statistically related to potassium imbalance in serum, QT interval and the concentration of toxic components in serum, which decreased at undetectable levels

Changes to histone modifications following prenatal alcohol exposure: An emerging picture.

PubMed

Chater-Diehl, Eric J; Laufer, Benjamin I; Singh, Shiva M

2017-05-01

Epigenetic mechanisms are important for facilitating gene-environment interactions in many disease etiologies, including Fetal Alcohol Spectrum Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs in animal models has illuminated the complex role of these mechanisms in FASD. In contrast, histone modifications have not been as well researched, due in part to being less stable than DNA methylation and less well-characterized in disease. It is now apparent that even changes in transient marks can have profound effects if they alter developmental trajectories. In addition, many histone methylations are now known to be relatively stable and can propagate themselves. As technologies and knowledge have advanced, a small group has investigated the role of histone modifications in FASD. Here, we synthesize the data on the effects of prenatal alcohol exposure (PAE) on histone modifications. Several key points are evident. AS with most alcohol-induced outcomes, timing and dosage differences yield variable effects. Nevertheless, these studies consistently find enrichment of H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone acetyltransferases and methyltransferases. The consistency of these alterations may implicate them as key mechanisms underlying FASD. Histone modification changes do not often correlate with gene expression changes, though some important examples exist. Encouragingly, attempts to reproduce specific histone modification changes are very often successful. We comment on possible directions for future studies, focusing on further exploration of current trends, expansion of time-point and dosage regimes, and evaluation of biomarker potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Physical and chemical modification of starches: A review.

PubMed

Zia-Ud-Din; Xiong, Hanguo; Fei, Peng

2017-08-13

The development of green material in the last decade has been increased, which tends to reduce the impact of humans on the environment. Starch as an agro-sourced polymer has become very popular recently due to its characteristics, such as wide availability, low cost, and total compostability without toxic residues. Starch is the most abundant organic compound found in nature after cellulose. Starches are inherently unsuitable for most applications and, therefore, must be modified physically and/or chemically to enhance their positive attributes and/or to minimize their defects. Modification of starches is generally carried out by using physical methods that are simple and inexpensive due to the absence of chemical agents. However, chemical modification involves the exploitation of hydroxyl group present in the starches that brings about the desired results for the utilization of starches for specific applications. All these techniques have the tendency to produce starches with altered physicochemical properties and modified structural attributes for various food and nonfood applications. This paper reviews the recent knowledge and developments using physical modification methods, some chemical modification methods, and a combination of both to produce a novel molecule with substantial applications, in food industry along with future perspectives.

Increased serum phosphate concentrations in patients with advanced chronic kidney disease treated with diuretics.

PubMed

Caravaca, Francisco; García-Pino, Guadalupe; Martínez-Gallardo, Rocío; Ferreira-Morong, Flavio; Luna, Enrique; Alvarado, Raúl; Ruiz-Donoso, Enrique; Chávez, Edgar

2013-01-01

Serum phosphate concentrations usually show great variability in patients with advanced chronic kidney disease (ACKD) not on dialysis. Diuretics treatment can have an influence over the severity of mineral-bone metabolism alterations related to ACKD, but their effect on serum phosphate levels is less known. This study aims to determine whether diuretics are independently associated with serum phosphate levels, and to investigate the mechanisms by which diuretics may affect phosphate metabolism. 429 Caucasian patients with CKD not on dialysis were included in this cross-sectional study. In addition to conventional serum biochemical measures, the following parameters of renal phosphate excretion were assessed: 24-hours urinary phosphate excretion, tubular maximum phosphate reabsorption (TmP), and fractional excretion of phosphate (FEP). 58% of patients were on treatment with diuretics. Patients on diuretics showed significantly higher mean serum phosphate concentration (4.78 ± 1.23 vs. 4.24 ± 1.04 mg/dl; P<.0001), and higher TmP per GFR (2.77 ± 0.72 vs. 2.43 ± 0.78 mg/dl; P<.0001) than those not treated with diuretics. By multivariate linear and logistic regression, significant associations between diuretics and serum phosphate concentrations or hyperphosphataemia remained after adjustment for potential confounding variables. In patients with the highest phosphate load adjusted to kidney function, those treated with diuretics showed significantly lower FEP than those untreated with diuretics. Treatment with diuretics is associated with increased serum phosphate concentrations in patients with ACKD. Diuretics may indirectly interfere with the maximum renal compensatory capacity to excrete phosphate. Diuretics should be considered in the studies linking the relationship between serum phosphate concentrations and cardiovascular alterations in patients with CKD.

A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

PubMed Central

Petit, François M; Hébert, Marylise; Picone, Olivier; Brisset, Sophie; Maurin, Marie-Laure; Parisot, Frédéric; Capel, Liliane; Benattar, Clarisse; Sénat, Marie-Victoire; Tachdjian, Gérard; Labrune, Philippe

2009-01-01

Alpha feto-protein (AFP) is a major plasma protein produced by the yolk sac and the liver during the fetal period. During the second trimester of pregnancy, APF and βhCG serum concentrations are commonly used for screening Down syndrome. AFP deficiency is rare (estimated to be 1/105 000 newborns) and only one sequence alteration has previously been reported in the AFP gene. We report a new mutation in exon 5 of the AFP gene, leading to a total absence of AFP on 2nd-trimester maternal serum screening for Down syndrome, confirmed on the amniotic fluid. Despite this, fetal development and birth were normal. After PCR-amplification, the whole AFP gene was sequenced. The new mutation was a guanine to adenine transition in position 543 creating a premature stop codon in position 181. In order to search for eventual modifications of the amniotic fluid profile, proteins were separated by electrophoresis and compared with 10 normal amniotic fluids sampled at the same developmental age (18 weeks). In the amniotic fluid of our patient albumin rate was reduced whereas alpha1 and beta protein fractions were increased, suggesting that AFP deficiency may modify the distribution of protein fractions. This observation emphasizes the complex molecular mechanisms of compensation of serum protein deficiency. Studies on other families with AFP deficiency are necessary to confirm this observation. PMID:18854864

Serum concentrations of trace elements and their relationships with paraoxonase-1 in morbidly obese women.

PubMed

Luciano-Mateo, Fedra; Cabré, Noemí; Nadal, Martí; García-Heredia, Anabel; Baiges-Gaya, Gerard; Hernández-Aguilera, Anna; Camps, Jordi; Joven, Jorge; Domingo, José Luis

2018-07-01

The metabolic alterations associated with obesity include mineral dysregulation. Essential trace elements are nutrients with a relevant function in a large number of cellular processes and multiple roles in the correct functioning of metabolic enzymes. Paraoxonase-1 (PON1) is an antioxidant and anti-inflammatory enzyme that is compromised in obesity. In the present study, the potential alterations in trace elements in morbidly obese women were assessed in relation to serum PON1 activity and concentration, as well as to other obesity-related comorbidities such as diabetes mellitus and fatty liver. We recruited 41 morbidly obese women and 51 control individuals. The serum concentrations of 30 elements, PON1 paraoxonase and lactonase activities, and PON1 concentration were measured. We observed significant alterations in the levels of As, Ba, Cu, Ca, Fe, Mg, Na, Se, Sr, and Zn in obese women; some of them (As, Ca, Cr, Cu, Mg, and Se) being significantly correlated with serum PON1 values. The most relevant changes were observed in the concentrations of As, Sr and Mg, the last of which was also significantly associated with diabetes mellitus. The current results raise the possibility that increased ingestion and/or storage of a number of trace elements may be factors predisposing to obesity-related comorbidities and metabolic alterations. Copyright © 2018 Elsevier GmbH. All rights reserved.

Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation.

PubMed

Konduru, Nagarjun V; Murdaugh, Kimberly M; Swami, Archana; Jimenez, Renato J; Donaghey, Thomas C; Demokritou, Philip; Brain, Joseph D; Molina, Ramon M

2016-08-01

Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated (65)ZnO or silica-coated (65)ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for (65)Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated (65)ZnO were shorter (initial - <1 min; terminal - 2.5 min) than uncoated (65)ZnO (initial - 1.9 min; terminal - 38 min). Interestingly, the silica-coated (65)ZnO group had higher (65)Zn associated with red blood cells and higher initial uptake in the liver. The (65)Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology and nanomedical applications of NPs.

Identification of Maillard reaction induced chemical modifications on Ara h 1

USDA-ARS?s Scientific Manuscript database

The Maillard reaction is a non-enzymatic glycation reaction between proteins and reducing sugars that can modify nut allergens during thermal processing. These modifications can alter the structural and immunological properties of these allergens, and may result in increased IgE binding. Here, we ...

Protection against hyperoxia by serum from endotoxin treated rats: absence of superoxide dismutase induction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berg, J.T.; Smith, R.M.

Endotoxin greatly reduces lung injury and pleural effusions in adult rats exposed to normobaric hyperoxia (> 98% oxygen for 60 hours). This study reports that serum from endotoxin treated donor rats protects serum recipients against hyperoxic lung injury without altering lung superoxide dismutase (SOD) activity. Rats pretreated with endotoxin alone were protected and exhibited an increase in lung SOD activity as previously reported by others. Protection by serum was not due to the transfer of residual endotoxin or SOD. These results show, that protection from oxygen toxicity can occur in rats without an increase in lung SOD and suggest thatmore » a serum factor may be involved.« less

Pregnancy amelioration of arthritis in SKG mice corresponds with alterations in serum amyloid A3 levels

PubMed Central

Shaw, Laura A; Stefanski, Adrianne L; Peterson, Lisa K; Rumer, Kristen K; Vondracek, Andrea; Phang, Tzu L; Sakaguchi, Shimon; Winn, Virginia D; Dragone, Leonard L

2012-01-01

Objectives: Pregnancy leads to rheumatoid arthritis remission in humans. The objective of this study was to determine if the SKG mouse could serve as a model for pregnancy-associated inflammatory arthritis amelioration. In addition, the maternal peripheral blood mononuclear cell (PBMC) transcriptome was assessed to define a biomarker associated with remission. Methods: Cohorts of zymosan-treated pregnant SKG mice and controls were monitored for arthritis progression. Microarray analysis evaluated alterations in gene expression in maternal PBMCs at embryonic day 14.5 (E14.5) between arthritic and pregnancy-remitted mice. A selected target, serum amyloid A3 (SAA3), was further investigated using quantitative reverse transcriptase PCR (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). Results: Pregnancy resulted in complete or partial remission in the majority of the zymosan-treated SKG mice. Twenty-seven transcripts were differentially expressed in the PBMCs between arthritic and pregnancy-remitted mice. Expression and plasma SAA3 levels decreased with pregnancy-induced arthritis amelioration and plasma SAA3 levels correlated with arthritis severity. Conclusions: These results establish the SKG mouse as a model system to study pregnancy-induced amelioration of arthritis. These studies also establish SAA3 as a biomarker of arthritis amelioration in SKG mice. This model can be used to elucidate the molecular and cellular mechanisms underlying the impact of pregnancy on the maternal immune system that results in arthritis amelioration. PMID:23097751

Status of lifestyle modifications in hypertension.

PubMed

Chhabra, M K; Lal, A; Sharma, K K

2001-09-01

Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients.

Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis.

PubMed

Prause, J; Goswami, A; Katona, I; Roos, A; Schnizler, M; Bushuven, E; Dreier, A; Buchkremer, S; Johann, S; Beyer, C; Deschauer, M; Troost, D; Weis, J

2013-04-15

Intracellular accumulations of mutant, misfolded proteins are major pathological hallmarks of amyotrophic lateral sclerosis (ALS) and related disorders. Recently, mutations in Sigma receptor 1 (SigR1) have been found to cause a form of ALS and frontotemporal lobar degeneration (FTLD). Our goal was to pinpoint alterations and modifications of SigR1 in ALS and to determine how these changes contribute to the pathogenesis of ALS. In the present study, we found that levels of the SigR1 protein were reduced in lumbar ALS patient spinal cord. SigR1 was abnormally accumulated in enlarged C-terminals and endoplasmic reticulum (ER) structures of alpha motor neurons. These accumulations co-localized with the 20s proteasome subunit. SigR1 accumulations were also observed in SOD1 transgenic mice, cultured ALS-8 patient's fibroblasts with the P56S-VAPB mutation and in neuronal cell culture models. Along with the accumulation of SigR1 and several other proteins involved in protein quality control, severe disturbances in the unfolded protein response and impairment of protein degradation pathways were detected in the above-mentioned cell culture systems. Furthermore, shRNA knockdown of SigR1 lead to deranged calcium signaling and caused abnormalities in ER and Golgi structures in cultured NSC-34 cells. Finally, pharmacological activation of SigR1 induced the clearance of mutant protein aggregates in these cells. Our results support the notion that SigR1 is abnormally modified and contributes to the pathogenesis of ALS.

A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

PubMed Central

Zaborske, John M.; Bauer DuMont, Vanessa L.; Wallace, Edward W. J.; Pan, Tao; Aquadro, Charles F.; Drummond, D. Allan

2014-01-01

Natural selection favors efficient expression of encoded proteins, but the causes, mechanisms, and fitness consequences of evolved coding changes remain an area of aggressive inquiry. We report a large-scale reversal in the relative translational accuracy of codons across 12 fly species in the Drosophila/Sophophora genus. Because the reversal involves pairs of codons that are read by the same genomically encoded tRNAs, we hypothesize, and show by direct measurement, that a tRNA anticodon modification from guanosine to queuosine has coevolved with these genomic changes. Queuosine modification is present in most organisms but its function remains unclear. Modification levels vary across developmental stages in D. melanogaster, and, consistent with a causal effect, genes maximally expressed at each stage display selection for codons that are most accurate given stage-specific queuosine modification levels. In a kinetic model, the known increased affinity of queuosine-modified tRNA for ribosomes increases the accuracy of cognate codons while reducing the accuracy of near-cognate codons. Levels of queuosine modification in D. melanogaster reflect bioavailability of the precursor queuine, which eukaryotes scavenge from the tRNAs of bacteria and absorb in the gut. These results reveal a strikingly direct mechanism by which recoding of entire genomes results from changes in utilization of a nutrient. PMID:25489848

Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period.

PubMed

Miyazaki, Teruo; Nagasaka, Hironori; Komatsu, Haruki; Inui, Ayano; Morioka, Ichiro; Tsukahara, Hirokazu; Kaji, Shunsaku; Hirayama, Satoshi; Miida, Takashi; Kondou, Hiroki; Ihara, Kenji; Yagi, Mariko; Kizaki, Zenro; Bessho, Kazuhiko; Kodama, Takahiro; Iijima, Kazumoto; Yorifuji, Tohru; Matsuzaki, Yasushi; Honda, Akira

2018-04-14

Citrin (mitochondrial aspartate-glutamate transporter) deficiency causes the failures in both carbohydrate-energy metabolism and the urea cycle, and the alterations in the serum levels of several amino acids in the stages of newborn (NICCD) and adult (CTLN2). However, the clinical manifestations are resolved between the NICCD and CTLN2, but the reasons are still unclear. This study evaluated the serum amino acid profile in citrin-deficient children during the healthy stage. Using HPLC-MS/MS analysis, serum amino acids were evaluated among 20 citrin-deficient children aged 5-13 years exhibiting normal liver function and 35 age-matched healthy controls. The alterations in serum amino acids characterized in the NICCD and CTLN2 stages were not observed in the citrin-deficient children. Amino acids involved in the urea cycle, including arginine, ornithine, citrulline, and aspartate, were comparable in the citrin-deficient children to the respective control levels, but serum urea was twofold higher, suggestive of a functional urea cycle. The blood sugar level was normal, but glucogenic amino acids and glutamine were significantly decreased in the citrin-deficient children compared to those in the controls. In addition, significant increases of ketogenic amino acids, branched-chain amino acids (BCAAs), a valine intermediate 3-hydroxyisobutyrate, and β-alanine were also found in the citrin-deficient children. The profile of serum amino acids in the citrin-deficient children during the healthy stage showed different characteristics from the NICCD and CTLN2 stages, suggesting that the failures in both urea cycle function and energy metabolism might be compensated by amino acid metabolism. In the citrin-deficient children during the healthy stage, the characteristics of serum amino acids, including decrease of glucogenic amino acids, and increase of ketogenic amino acids, BCAAs, valine intermediate, and β-alanine, were found by comparison to the age-matched healthy control

Nontoxic Genetic Engineering of Mesenchymal Stem Cells Using Serum-Compatible Pullulan-Spermine/DNA Anioplexes

PubMed Central

Thakor, Devang K.; Obata, Hideaki; Nagane, Kentaro; Saito, Shigeru

2011-01-01

Genetic modification of stem cells could be applied to initiate/enhance their secretion of therapeutic molecules, alter their biological properties, or label them for in vivo tracking. We recently developed a negatively charged gene carrier (“anioplex”) based on pullulan-spermine, a conjugate prepared from a natural polysaccharide and polyamine. In rat mesenchymal stem cells (MSCs), anioplex-derived reporter gene activity was comparable to or exceeded that obtained using a commercial cationic lipid reagent. Transfection in the growth medium with 15% serum and antibiotics was approximately sevenfold more effective than in serum-free conditions. Cytotoxicity was essentially indiscernible after 24 h of anioplex transfection with 20 μg/mL DNA, in contrast to cationic lipid transfection that resulted in 40%–60% death of target MSCs. Anioplex-derived reporter gene activity persisted throughout the entire 3-week study, with post-transfection MSCs appearing to maintain osteogenic, adipogenic, and chondrogenic multipotency. In particular, chondrogenic pellet formation of differentiating human MSCs was significantly inhibited after lipofection but not after aniofection, which further indicates the biological inertness of pullulan-spermine/DNA anioplexes. Collectively, these data introduce a straightforward technology for genetic engineering of adult stem/progenitor cells under physiological niche-like conditions. Moreover, reporter gene activity was observed in rat spinal cords after minimally invasive intrathecal implantation, suggesting effective engraftment of donor MSCs. It is therefore plausible that anioplex-transfected MSCs or other stem/progenitor cells with autologous potential could be applied to disorders such as neurotrauma or neuropathic pain that involve the spinal cord and brain. PMID:20698746

Reduced serum concentrations of brain-derived neurotrophic factor (BDNF) in transsexual Brazilian men.

PubMed

Fontanari, Anna Martha Vaitses; Costa, Angelo Brandelli; Aguiar, Bianca; Tusset, Cíntia; Andreazza, Tahiana; Schneider, Maiko; da Rosa, Eduarda Dias; Soll, Bianca Machado Borba; Schwarz, Karine; da Silva, Dhiordan Cardoso; Borba, André Oliveira; Mueller, Andressa; Massuda, Raffael; Lobato, Maria Inês Rodrigues

2016-09-06

Serum BDNF levels are significantly decreased in transsexual Brazilian women when compared to cis-sexual men. Since transsexual men are also exposed to chronic social stress and have a high prevalence of associated psychopathologies, it is plausible to inquire if BDNF serum levels are altered in transsexual men as well. Therefore, our objective was to evaluate differences in BDNF serum level of transsexual men when compared to cis-sexual men and women. Our sample comprises 27 transsexual men, 31 cis-sexual women and 30 cis-sexual men recruited between 2011 and 2015. We observed that BDNF serum concentration is decreased in transsexual men comparing to cis-sexual men and women. Cross-sex hormone treatment, chronic social stress or long-term gender dysphoria (GD) could explain the variation found in BDNF serum levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

When gene medication is also genetic modification--regulating DNA treatment.

PubMed

Foss, Grethe S; Rogne, Sissel

2007-07-26

The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

Diagonal chromatography to study plant protein modifications.

PubMed

Walton, Alan; Tsiatsiani, Liana; Jacques, Silke; Stes, Elisabeth; Messens, Joris; Van Breusegem, Frank; Goormachtig, Sofie; Gevaert, Kris

2016-08-01

An interesting asset of diagonal chromatography, which we have introduced for contemporary proteome research, is its high versatility concerning proteomic applications. Indeed, the peptide modification or sorting step that is required between consecutive peptide separations can easily be altered and thereby allows for the enrichment of specific, though different types of peptides. Here, we focus on the application of diagonal chromatography for the study of modifications of plant proteins. In particular, we show how diagonal chromatography allows for studying proteins processed by proteases, protein ubiquitination, and the oxidation of protein-bound methionines. We discuss the actual sorting steps needed for each of these applications and the obtained results. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. Copyright © 2016 Elsevier B.V. All rights reserved.

An improved electrophoretic method for the determination of serum milk protein variants in Gyr-Holstein cows.

PubMed

Ramos, P R; Urtado, S L; Almeida, M R; Bortolozzi, J; Silva, E T

1992-01-01

Milk serum proteins such as alpha-lactalbumin (ALA) and beta-lactoglobulin (BLG) present biochemical polymorphism which is under the control of codominant autosomal alleles. In the present report, we propose modifications of traditional electrophoretic techniques such as increasing the running gel concentration from 5 to 10% and the addition of 5 M urea to the stacking gel, which permitted the detection of two variants (A and B) at the ALA and BLG loci. About 8 microliters of milk serum (6 mg/ml protein) and 10 microliters of total fresh milk were applied. Bovine serum albumin (BSA) and immunolactoglobulins (ILG) could also be discriminated. Total fresh milk was as useful as the purified serum milk proteins for the discrimination of ALA and BLG serum milk protein polymorphism by alkaline vertical slab polyacrylamide gel electrophoresis. However, BSA and ILG ran with caseins, which prevented their characterization in this system.

Thermal biology mediates responses of amphibians and reptiles to habitat modification.

PubMed

Nowakowski, A Justin; Watling, James I; Thompson, Michelle E; Brusch, George A; Catenazzi, Alessandro; Whitfield, Steven M; Kurz, David J; Suárez-Mayorga, Ángela; Aponte-Gutiérrez, Andrés; Donnelly, Maureen A; Todd, Brian D

2018-03-01

Human activities often replace native forests with warmer, modified habitats that represent novel thermal environments for biodiversity. Reducing biodiversity loss hinges upon identifying which species are most sensitive to the environmental conditions that result from habitat modification. Drawing on case studies and a meta-analysis, we examined whether observed and modelled thermal traits, including heat tolerances, variation in body temperatures, and evaporative water loss, explained variation in sensitivity of ectotherms to habitat modification. Low heat tolerances of lizards and amphibians and high evaporative water loss of amphibians were associated with increased sensitivity to habitat modification, often explaining more variation than non-thermal traits. Heat tolerances alone explained 24-66% (mean = 38%) of the variation in species responses, and these trends were largely consistent across geographic locations and spatial scales. As habitat modification alters local microclimates, the thermal biology of species will likely play a key role in the reassembly of terrestrial communities. © 2018 John Wiley & Sons Ltd/CNRS.

Surface modification: advantages, techniques, and applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Natesan, K.

2000-03-01

Adequate performance of materials at elevated temperatures is a potential problem in many systems within the chemical, petroleum, process, and power-generating industries. Degradation of materials occurs because of interaction between the structural material and the exposure environment. These interactions are generally undesired chemical reactions that can lead to accelerated wastage and alter the functional requirements and/or structural integrity of the materials. Therefore, material selection for high-temperature applications must be based not only on a material strength properties but also on resistance to the complex environments prevalent in the anticipated exposure environment. As plants become larger, the satisfactory performance and reliabilitymore » of components play a greater role in plant availability and economics. However, system designers are becoming increasingly concerned with finding the least expensive material that will satisfactorily perform the design function for the desired service life. This present paper addresses the benefits of surface modification and identified several criteria for selection and application of modified surfaces in the power sector. A brief review is presented on potential methods for modification of surfaces, with the emphasis on coatings. In the final section of the paper, several examples address the requirements of different energy systems and surface modification avenues that have been applied to resolve the issues.« less

Serum potassium level and dietary potassium intake as risk factors for stroke.

PubMed

Green, D M; Ropper, A H; Kronmal, R A; Psaty, B M; Burke, G L

2002-08-13

Numerous studies have found that low potassium intake and low serum potassium are associated with increased stroke mortality, but data regarding stroke incidence have been limited. Serum potassium levels, dietary potassium intake, and diuretic use in relation to risk for stroke in a prospectively studied cohort were investigated. The study comprised 5,600 men and women older than 65 years who were free of stroke at enrollment. Baseline data included serum potassium level, dietary potassium intake, and diuretic use. Participants were followed for 4 to 8 years, and the incidence and types of strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L, and low potassium intake as less than 2.4 g/d. Among diuretic users, there was an increased risk for stroke associated with lower serum potassium (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics, there was an increased risk for stroke associated with low dietary potassium intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum potassium and atrial fibrillation had a 10-fold greater risk for stroke compared with those with higher serum potassium and normal sinus rhythm. A lower serum potassium level in diuretic users, and low potassium intake in those not taking diuretics were associated with increased stroke incidence among older individuals. Lower serum potassium was associated with a particularly high risk for stroke in the small number of diuretic users with atrial fibrillation. Further study is required to determine if modification of these factors would prevent strokes.

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum

PubMed Central

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

PubMed

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Metabolomics Reveals Altered Lipid Metabolism in a Mouse Model of Endometriosis.

PubMed

Dutta, Mainak; Anitha, Mallappa; Smith, Philip B; Chiaro, Christopher R; Maan, Meenu; Chaudhury, Koel; Patterson, Andrew D

2016-08-05

Endometriosis is a common chronic estrogen-dependent gynecological disease affecting 10% of women in their reproductive age. It is characterized by proliferation of functional endometrial glands and stroma outside the uterine cavity. In the present study, we used mass spectrometry-based lipidomics to investigate the alterations in serum lipid profiles of mice induced with endometriosis. We identified several dysregulated lipids such as phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, and triglycerides and show that triglycerides may be due to a general inflammatory condition in the peritoneum. We also show that in addition to phosphatidylcholine alteration, there is also an effect in the ratio of phosphatidylcholine/phosphatidylethanolamine in serum of mice induced with the disease and that this change may be due to increased expression of the phosphatidylethanolamine N-methyltransferase gene. The study provides new insight into the etiology of endometriosis.

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

PubMed Central

Groebner, Jennifer L.; Tuma, Pamela L.

2015-01-01

The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease. PMID:26393662

The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.

PubMed

Groebner, Jennifer L; Tuma, Pamela L

2015-09-18

The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the "tubulin code" are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.

The effects of coffee consumption on serum lipids and lipoprotein in healthy individuals.

PubMed

Onuegbu, A J; Agbedana, E O

2001-01-01

The changes in total serum cholestrol, serum triglyceride, HDL-cholesterol and LDL-cholesterol after twenty eight (28) days of consumption of moderate quantity of a commercial coffee preparation (NESCAFE brand) were studied in 30 human subjects consisting of 20 male and 10 female healthy adults. Significant increases in the mean total serum cholesterol concentration (110.8-126.5 mg/100 mls) and LDL- cholesterol concentration (78.4-94.5 mg/100 ml) were observed in the subjects. No significant differences were obtained in the mean HDL cholesterol concentration and in the mean serum triglyceride levels. The differences observed in the mean total serum cholesterol, LDL cholesterol, HDL- cholesterol and triglyceride concentrations in the individual male and female groups studied were not statistically significant. The results from this study suggest that short-term consumption of coffee may increase the total serum cholesterol and LDL cholesterol levels. It is therefore possible that long-term consumption of coffee may lead to clinically significant alterations in serum lipid profile and could be important in the aetiology of atherosclerotic vascular diseases such as coronary heart disease.

The contribution of hepatic inactivation of testosterone to the lowering of serum testosterone levels by ketoconazole.

PubMed

Wilson, V S; LeBlanc, G A

2000-03-01

Hepatic biotransformation processes can be modulated by chemical exposure and these alterations can impact the biotransformation of endogenous substrates. Furthermore, chemically mediated alterations in the biotransformation of endogenous steroid hormones have been implicated as a mechanism by which steroid hormone homeostasis can be disrupted. The fungicide ketoconazole has been shown to lower serum testosterone levels and alter both gonadal synthesis and hepatic inactivation of testosterone. The present study examined whether the effects of ketoconazole on the hepatic biotransformation of testosterone contribute to its lowering of serum testosterone levels. Results also were used to validate further the use of the androgen-regulated hepatic testosterone 6alpha/15alpha-hydroxylase ratio as an indicator of androgen status. Male CD-1 mice were fed from 0 to 160 mg/kg ketoconazole in honey. Four h after the initial treatment, serum testosterone levels, gonadal testosterone secretion, and hepatic testosterone hydroxylase activity decreased, and the hepatic testosterone 6alpha/15alpha-hydroxylase ratio increased in a dose-dependent manner. Immunoblot analysis indicated that the transient decline in hepatic biotransformation was not due to reduced P450 protein levels. Rather, hepatic testosterone biotransformation activities were found to be differentially susceptible to direct inhibition by ketoconazole. Differential inhibition was also responsible for the increase seen in the 6alpha/15alpha-hydroxylase ratio. The changes in serum testosterone levels could be explained by decreased gonadal synthesis of testosterone and were not impacted by decreased hepatic biotransformation of testosterone. These results demonstrate that changes in the hepatic hydroxylation of testosterone by ketoconazole, and perhaps other chemicals, have little or no influence serum testosterone levels.

Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level.

PubMed

Zheng, Qin; Zhou, Feifei; Cui, Xinyuan; Liu, Mulin; Li, Yulin; Liu, Shuai; Tan, Jichun; Yan, Qiu

2018-01-01

Polycystic ovary syndrome (PCOS), characterized by female infertility and metabolic abnormalities, is one of the most common endocrine disorders. The etiology of PCOS remains unknown. The comprehensive analysis of protein alterations in PCOS patients is meaningful for identifying diagnostic biomarkers of PCOS. Here, we explored the clinical value of serum proteins as novel biomarkers to detect PCOS with low progesterone level. A total of 43 patients with PCOS and 30 healthy women were enrolled. Protein array was used to detect the variations of serum proteins between PCOS patients and healthy women. The level of five serum proteins was further confirmed by ELISA and western blot. The human ovarian granulosa cells (KGN) was cultured to examine the underlying mechanism of PCOS. CCK8 assay and western blot were carried out to evaluate the alterations in proliferative ability, TUNEL assay and DAPI staining to detect the apoptosis of KGN cells. Among the 507 proteins, we identified 76 differentially expressed serum proteins (≧1.5 fold), with 40 elevated and 36 decreased proteins. Moreover, 47 proteins were newly reported in PCOS. The alterations in the five significantly decreased proteins (EREG, inhibin βA, IDE, PDGF-D and KNG1) were further confirmed by ELISA and western blot. The level of these proteins were directly associated with the low progesterone, and the expression could be upregulated by progesterone. EREG and inhibin βA also promoted the proliferation and inhibited the apoptosis of ovarian granulosa cells. The study highlights that serum proteins are differentially expressed in PCOS patients and healthy women, and EREG and inhibin βA levels are upregulated by progesterone, which are correlated with ovarian functions. The study suggests that EREG and inhibin βA may be applied as novel potential biomarkers for PCOS with low progesterone level. © 2018 The Author(s). Published by S. Karger AG, Basel.

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

PubMed

Rich, Tyvin; Innominato, Pasquale F; Boerner, Julie; Mormont, M Christine; Iacobelli, Stefano; Baron, Benoit; Jasmin, Claude; Lévi, Francis

2005-03-01

Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine

Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

PubMed

Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

2014-08-25

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pseudouridine and N6-methyladenosine modifications weaken PUF protein/RNA interactions

PubMed Central

AlSadhan, Ishraq; Merriman, Dawn K.; Al-Hashimi, Hashim M.; Herschlag, Daniel

2017-01-01

RNA modifications are ubiquitous in biology, with over 100 distinct modifications. While the vast majority were identified and characterized on abundant noncoding RNA such as tRNA and rRNA, the advent of sensitive sequencing-based approaches has led to the discovery of extensive and regulated modification of eukaryotic messenger RNAs as well. The two most abundant mRNA modifications—pseudouridine (Ψ) and N6-methyladenosine (m6A)—affect diverse cellular processes including mRNA splicing, localization, translation, and decay and modulate RNA structure. Here, we test the hypothesis that RNA modifications directly affect interactions between RNA-binding proteins and target RNA. We show that Ψ and m6A weaken the binding of the human single-stranded RNA binding protein Pumilio 2 (hPUM2) to its consensus motif, with individual modifications having effects up to approximately threefold and multiple modifications giving larger effects. While there are likely to be some cases where RNA modifications essentially fully ablate protein binding, here we see modest responses that may be more common. Such modest effects could nevertheless profoundly alter the complex landscape of RNA:protein interactions, and the quantitative rather than qualitative nature of these effects underscores the need for quantitative, systems-level accounting of RNA:protein interactions to understand post-transcriptional regulation. PMID:28138061

Nature, frequency and determinants of prescription modifications in Dutch community pharmacies

PubMed Central

Buurma, Henk; de Smet, Peter A G M; van den Hoff, Olga P; Egberts, Antoine C G

2001-01-01

Aims To examine the nature, frequency and determinants of prescription modifications in Dutch community pharmacies. Methods A prospective case-control study comparing modified prescriptions with nonmodified prescriptions was carried out in 141 Dutch community pharmacies. 2014 modified prescriptions (cases), collected in the selected pharmacies on a predetermined day in a specific period (25th February until 12th March 1999) and 2581 nonmodified prescriptions (controls) randomly selected on the same day were studied. The nature and frequency of prescription modifications and patient, drug and prescriber related determinants for a modified prescription were assessed. Results The overall incidence of prescription modifications was 4.3%, with a mean of 14.3 modifications per pharmacy per day. For prescription only medicines (POM) the incidence was 4.9%. The majority of POM modifications concerned a clarification (71.8%). In 22.2% a prescription could potentially have had clinical consequences when not altered; in more than half of the latter it concerned a dose error (13.7% of all cases). POM prescriptions of patients of 40–65 years had a significantly lower chance of modification compared with those of younger people (OR = 0.74 [0.64–0.86]). With respect to medication-class, we found a higher chance of POM modifications in the respiratory domain (OR = 1.48 [1.23-1.79]) and a decreased chance for nervous system POMs (OR = 0.71 [0.61–0.83]). With regard to prescriber-related determinants modifications were found three times more often in non printed prescriptions than in printed ones (OR = 3.30 [2.90-3.75]). Compared with prescriptions by the patient's own GP, prescriptions of specialists (OR = 1.82 [1.57-2.11]), other GP's (OR = 1.49 [1.02-2.17]) and other prescribers such as dentists and midwives (OR = 1.95 [1.06-3.57]) gave a higher probability of prescription modifications. When a GP had no on-line access to the computer of the pharmacy the chance of a

Functional O-GlcNAc modifications: Implications in molecular regulation and pathophysiology

PubMed Central

Wells, Lance

2016-01-01

O-linked β-N-acetylglucosamine (O-GlcNAc) is a regulatory post-translational modification of intracellular proteins. The dynamic and inducible cycling of the modification is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in response to UDP-GlcNAc levels in the hexosamine biosynthetic pathway (HBP). Due to its reliance on glucose flux and substrate availability, a major focus in the field has been on how O-GlcNAc contributes to metabolic disease. For years this post-translational modification has been known to modify thousands of proteins implicated in various disorders, but direct functional connections have until recently remained elusive. New research is beginning to reveal the specific mechanisms through which O-GlcNAc influences cell dynamics and disease pathology including clear examples of O-GlcNAc modification at a specific site on a given protein altering its biological functions. The following review intends to focus primarily on studies in the last half decade linking O-GlcNAc modification of proteins with chromatin-directed gene regulation, developmental processes, and several metabolically related disorders including Alzheimer’s, heart disease and cancer. These studies illustrate the emerging importance of this post-translational modification in biological processes and multiple pathophysiologies. PMID:24524620

Altered cytokine production by specific human peripheral blood cell subsets immediately following space flight

NASA Technical Reports Server (NTRS)

Crucian, B. E.; Cubbage, M. L.; Sams, C. F.

2000-01-01

In this study, flow cytometry was used to positively identify the specific lymphocyte subsets exhibiting space flight-induced alterations in cytokine production. Whole blood samples were collected from 27 astronauts at three points (one preflight, two postflight) surrounding four space shuttle missions. Assays performed included serum/urine stress hormones, white blood cell (WBC) phenotyping, and intracellular cytokine production following mitogenic stimulation. Absolute levels of peripheral granulocytes were significantly elevated following space flight, but the levels of circulating lymphocytes and monocytes were unchanged. Lymphocyte subset analysis demonstrated a decreased percentage of T cells, whereas percentages of B cells and natural killer (NK) cells remained unchanged after flight. Nearly all the astronauts exhibited an increased CD4/CD8 T cell ratio. Assessment of naive (CD45RA+) vs. memory (CD45RO+) CD4+ T cell subsets was ambiguous, and subjects tended to group within specific missions. Although no significant trend was seen in absolute monocyte levels, a significant decrease in the percentage of the CD14+ CD16+ monocytes was seen following space flight in all subjects tested. T cell (CD3+) production of interleukin-2 (IL-2) was significantly decreased after space flight, as was IL-2 production by both CD4+ and CD8+ T cell subsets. Production of interferon-gamma (IFN-gamma) was not altered by space flight for the CD8+ cell subset, but there was a significant decrease in IFN-gamma production for the CD4+ T cell subset. Serum and urine stress hormone analysis indicated significant physiologic stresses in astronauts following space flight. Altered peripheral leukocyte subsets, altered serum and urine stress hormone levels, and altered T cell cytokine secretion profiles were all observed postflight. In addition, there appeared to be differential susceptibility to space flight regarding cytokine secretion by T cell subsets. These alterations may be the

Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction.

PubMed

Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Bråthen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

2009-10-08

When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.

Technical modification of the Balb/c 3T3 cell transformation assay: the use of serum-reduced medium to optimise the practicability of the protocol.

PubMed

Hayashi, Kumiko; Sasaki, Kiyoshi; Asada, Shin; Tsuchiya, Toshiyuki; Hayashi, Makoto; Yoshimura, Isao; Tanaka, Noriho; Umeda, Makoto

2008-12-01

The two-stage Balb/c 3T3 model of cell transformation can mimic the two-stage carcinogenicity bioassay, and has been recognised as a screening method for detecting potential tumour initiators and promoters. A technical modification to the original protocol (which involved the use of M10F medium, consisting of MEM plus 10% fetal bovine serum [FBS]) has been previously proposed, in order to increase its efficacy, namely: the introduction of enriched, serum-reduced medium (DF2F medium, comprising DMEM/F12 plus 2% FBS and other supplements). The aim of this study was to further modify the protocol, so as to attain higher practicability for the assay. The protocol was further optimised by: a) reducing the number of plates required, through the use of larger plates; b) reducing the cost of the assay by retaining the reduced serum concentration and by using 2microg/ml insulin, rather than the more-complex insulin-transferrin-ethanolamine-sodium selenite (ITES) supplement (i.e. DF2F2I medium); and c) extending the culture period from 24-25 days to 31-32 days, resulting in clearer foci (the number of medium changes did not increase, as less-frequent medium changes were performed during the extended culture period). Growth curve construction revealed that variations in the saturation densities of the parental Balb/c 3T3 cell line and its three transformed clones were highest when M10F medium was replaced with DF2F2I medium just before cells reached confluence. We applied this newly-optimised protocol to the assessment of: a) the tumour initiating activity of 3-methylcholanthrene (MCA), N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C, methylmethane sulphonate, CdCl(2) and phenacetin, combining a post-treatment of 100ng/ml 12-O-tetradecanoylphorbol-13-acetate at the promotion stage; and b) the tumour promoting activity of insulin, lithocholic acid, CdCl(2) and phenobarbital, with pre-treatment of 0.2microg/ml MCA at the initiation stage. In the present study, only

Serum potassium level is associated with metabolic syndrome: a population-based study.

PubMed

Sun, Kan; Su, Tingwei; Li, Mian; Xu, Baihui; Xu, Min; Lu, Jieli; Liu, Jianmin; Bi, Yufang; Ning, Guang

2014-06-01

Evidence has suggested that low serum potassium concentration or low dietary potassium intake can result in many metabolic disorders. Our objective was to evaluate the association between serum potassium level and risk of prevalent metabolic syndrome. We conducted a cross-sectional study in 10,341 participants aged 40 years or older. Metabolic syndrome was defined according to guidelines from the National Cholesterol Education Program with modification. The prevalence rate of metabolic syndrome was 51.7% in participants with hypokalemia and 37.7% in those with normokalemia. With the reduction of serum potassium quartiles, participants were tended to have higher level of triglycerides and uric acid, lower level of high-density lipoprotein cholesterol (HDL-C), larger waist circumference and more severe insulin resistance. Serum potassium level significantly decreased with the increasing number of metabolic syndrome components. Compared with subjects in the highest quartile of serum potassium level, multivariate adjusted odds ratios for prevalent metabolic syndrome in the lowest quartile was 1.48 (95% confidence interval, 1.16-1.87). Moreover, compared with subjects without central obesity, hypertriglyceridemia, low HDL-C and elevated fasting plasma glucose, those with each of these metabolic syndrome components have lower level of serum potassium after adjusted for age and sex. Low serum potassium level significantly associated with prevalence of metabolic syndrome in middle-aged and elderly Chinese. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects.

PubMed

De Riccardis, L; Buccolieri, A; Muci, M; Pitotti, E; De Robertis, F; Trianni, G; Manno, D; Maffia, M

2018-05-01

Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

PCBs Alter Dopamine Mediated Function in Aging Workers

DTIC Science & Technology

2008-01-01

in Aging Workers PRINCIPAL INVESTIGATOR: Richard F. Seegal, Ph.D. CONTRACTING ORGANIZATION: Health Research Incorporated... Health Perspectives, describes the associations between serum PCB concentrations and occupational exposure as well as fish consumption; the senior author...Alter Dopamine Mediated Function in Aging Workers 5a. CONTRACT NUMBER 5b. GRANT NUMBER DAMD17-02-1-0173 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

Serum electrolyte and protein changes after intravenous injection of sodium and meglumine diatrizoate (urograffin-370).

PubMed

Nzeh, D A; Erasmus, R T; Aiyedun, B A

1994-03-01

Serum electrolyte and protein changes in 35 Nigerian patients undergoing intravenous urography were evaluated after injection of 60 mls sodium and meglumine diatrizoate (Urograffin-370). Statistically, significant changes were noted in the values of serum calcium, proteins and albumin at 5 and 30 minutes after the injection (P < 0.005). The mean percentage decreases noted were calcium 13%, protein 17% and albumin 13%. At 30 minutes post-injection, the serum protein and albumin levels had incompletely recovered while calcium values continued to decrease. Non-statistically, significant changes were observed in the values of serum sodium, potassium and phosphate at 5 and 30 minutes respectively following contrast medium injection. Alterations in the levels of serum electrolytes especially calcium are most probably responsible for such adverse effects as convulsions and cardiac arrhythmias.

Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability

PubMed Central

Seal, Ruth; Temperley, Richard; Wilusz, Jeffrey; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M. A.

2005-01-01

PARN, a poly(A)-specific ribonuclease, binds the 5′ cap-structure of mRNA and initiates deadenylation-dependent decay. Eukaryotic initiation factor 4E (eIF4E) also binds to the cap structure, an interaction that is critical for initiating cap-dependent translation. The stability of various mRNA transcripts in human cell lines is reduced under conditions of serum starvation as determined by both functional and chemical half-lives. Serum starvation also leads to enhanced cap association by PARN. In contrast, the 5′ cap occupancy by eIF4E decreases under serum-deprivation, as does the translation of reporter transcripts. Further, we show that PARN is a phosphoprotein and that this modification can be modulated by serum status. Taken together, these data are consistent with a natural competition existing at the 5′ cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications. These phosphorylation-induced changes in the interplay of PARN and eIF4E may determine whether the mRNA is translated or decayed. PMID:15653638

Enhancing the Properties of Carbon and Gold Substrates by Surface Modification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harnisch, Jennifer Anne

2001-01-01

The properties of both carbon and gold substrates are easily affected by the judicious choice of a surface modification protocol. Several such processes for altering surface composition have been published in literature. The research presented in this thesis primarily focuses on the development of on-column methods to modify carbon stationary phases used in electrochemically modulated liquid chromatography (EMLC). To this end, both porous graphitic carbon (PGC) and glassy carbon (GC) particles have been modified on-column by the electroreduction of arenediazonium salts and the oxidation of arylacetate anions (the Kolbe reaction). Once modified, the carbon stationary phases show enhanced chromatographic performancemore » both in conventional liquid chromatographic columns and EMLC columns. Additionally, one may also exploit the creation of aryl films to by electroreduction of arenediazonium salts in the creation of nanostructured materials. The formation of mercaptobenzene film on the surface of a GC electrode provides a linking platform for the chemisorption of gold nanoparticles. After deposition of nanoparticles, the surface chemistry of the gold can be further altered by self-assembled monolayer (SAM) formation via the chemisorption of a second thiol species. Finally, the properties of gold films can be altered such that they display carbon-like behavior through the formation of benzenehexathiol (BHT) SAMs. BHT chemisorbs to the gold surface in a previously unprecedented planar fashion. Carbon and gold substrates can be chemically altered by several methodologies resulting in new surface properties. The development of modification protocols and their application in the analytical arena is considered herein.« less

Serum gastrin concentrations in dogs with liver disorders.

PubMed

Mazaki-Tovi, M; Segev, G; Yas-Natan, E; Lavy, E

2012-07-07

Dogs with liver disorders often display gastrointestinal signs that may be triggered by ulceration. The liver is important for inactivation of some forms of gastrin. Therefore, hypergastrinaemia has been implicated in the pathogenesis of gastrointestinal ulcerations related to liver dysfunction. The aim of this study was to determine serum gastrin concentrations in dogs with liver disease. Fasted blood samples were collected from 15 dogs with newly diagnosed liver disease and 18 healthy dogs. Gastrin concentrations were significantly lower in dogs with congenital portosystemic shunt compared with healthy dogs (P=0.003). No significant difference (P=0.6) in gastrin concentration was revealed between dogs with hepatocellular disease and healthy dogs. Serum gastrin concentrations were not significantly associated with the occurrence of vomiting, anorexia, diarrhoea, or melaena in dogs with liver disorders. These findings did not provide support for the role of hypergastrinaemia in the development of gastrointestinal signs associated with liver disease in dogs. Decreased serum concentrations of gastrin in a dog with liver disease may suggest the presence of portosystemic shunt. Further investigation is warranted to determine the importance of hyopogastrinaemia in congenital postosystemic shunts in dogs and to evaluate potential alterations in serum gastrin concentrations in specific hepatocellular diseases.

Serum beta-2 microglobulin level in sympathetic ophthalmitis.

PubMed

Sen, D K; Sarin, G S; Mathur, M D

1990-04-01

Serum beta-2 microglobulin (beta 2-m) levels were measured in 12 patients with sympathetic ophthalmitis, 34 with neglected traumatic uveitis following penetrating injury and 36 healthy subjects by ELISA technique. There was no significant alteration of its level in patients with traumatic uveitis. However, its levels were significantly increased in patients with sympathetic ophthalmitis. They were high even in the early stage of the disease. Serum beta 2-m levels paralleled the severity of disease. It decreased significantly at the remission stage. Four patients came back with relapse of the condition and the level of serum beta 2-m was again found to be elevated in them. It is proposed that estimation of beta 2-m can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. It is also suggested that a rise in serum beta 2-m in patients with traumatic uveitis following perforating injuries may point to the onset of sympathetic ophthalmitis. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease and predict relapse.

Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis.

PubMed

Yamada, Daisuke; Asano, Yoshihide; Takahashi, Takehiro; Masui, Yuri; Aozasa, Naohiko; Akamata, Kaname; Noda, Shinji; Tamaki, Zenshiro; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

2012-01-01

Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6 years compared with healthy controls, but not in those with disease duration of >6 years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.

Administration of vitamin D3 by injection or drinking water alters serum 25-hydroxycholecalciferol concentrations of nursery pigs

PubMed Central

Ma, Jingyun; Lim, Jina; Monegue, H. James; Stuart, Robert L.

2018-01-01

Objective Two experiments were conducted to evaluate vitamin D3 administration to nursery pigs by injection or in drinking water on serum 25-hydroxycholecalciferol (25-OHD3) concentrations. Methods At weaning, 51 pigs (27 and 24 pigs in experiments 1 and 2, respectively) were allotted to vitamin D3 treatments. Treatments in experiment 1 were: i) control (CON), no vitamin administration beyond that in the diet, ii) intramuscular (IM) injection of 40,000 IU of vitamin D3 at weaning, and iii) water administration, 5,493 IU of vitamin D3/L drinking water for 14 d postweaning. Treatments in experiment 2 were: i) control (CON), no vitamin administration, and ii) water administration, 92 IU of d-α-tocopherol and 5,493 IU of vitamin D3/L drinking water for 28 d postweaning. The lightest 2 pigs within each pen were IM injected with an additional 1,000 IU of d-α-tocopherol, 100,000 IU of retinyl palmitate, and 100,000 IU of vitamin D3. Results In both experiments, serum 25-OHD3 was changed after vitamin D3 administration (p<0.05). In experiment 1, injection and water groups had greater values than CON group through d 35 and 21 post-administration, respectively (p<0.05). In experiment 2, serum values peaked at d 3 post-administration in the injection groups regardless of water treatments (p<0.05) whereas CON and water-only groups had peaks at d 14 and 28 post-administration, respectively (p<0.05). Even though the injection groups had greater serum 25-OHD3 concentrations than the non-injection groups through d 7 post-administration regardless of water treatments (p<0.05), the water-only group had greater values than the injection-only group from d 21 post-administration onward (p<0.05). Conclusion Serum 25-OHD3 concentrations in pigs increased either by vitamin D3 injection or drinking water administration. Although a single vitamin D3 injection enhanced serum 25-OHD3 concentrations greater than water administration in the initial period post-administration, a continuous

Increased serum concentrations of adiponectin in canine hypothyroidism.

PubMed

Mazaki-Tovi, Michal; Abood, Sarah K; Kol, Amir; Farkas, Amnon; Schenck, Patricia A

2015-02-01

Serum concentrations of adiponectin were compared between sex-matched hypothyroid (n = 18) and euthyroid (n = 18) client-owned dogs with comparable ages and body condition scores (BCS). Concentrations of adiponectin (mean; 95% confidence interval) were significantly (P < 0.01) higher in hypothyroid (17.2 µg/mL; 12.1-20.5 µg/mL) than healthy (8.0 µg/mL; 5.6-11.4 µg/mL) dogs following adjustment for potential confounders (BCS, age and sex). Serum concentrations of adiponectin were significantly negatively associated with concentrations of total thyroxine (P <0.05) and positively correlated with concentrations of cholesterol (r = 0.6, P <0.01) in hypothyroid dogs. In conclusion, this study demonstrated increased serum concentrations of adiponectin in dogs with hypothyroidism. Suggestive of the presence of resistance to adiponectin that could have contributed to development of hyperlipidemia and insulin resistance in these dogs or alternatively, could be a consequence of these metabolic alterations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prednisone treatment alters the serum amylase and lipase activities in normal dogs without causing pancreatitis.

PubMed Central

Fittschen, C; Bellamy, J E

1984-01-01

In order to test the hypothesis that treatment with glucocorticoids causes pancreatitis in dogs, 18 mongrel dogs were divided into three groups of six individuals, each group receiving prednisone at different doses orally or intramuscularly for two weeks. Two groups consisting of six dogs each served as controls. Treatment for two weeks with oral prednisone at 1.2 mg/kg body weight or at 4 mg/kg body weight daily decreased the serum amylase activities, but increased the serum lipase activities. Postmortem examinations revealed microscopic evidence of mild pancreatitis in only one dog given prednisone, that clinically appeared normal. It was concluded that daily doses of 4 mg prednisone/kg body weight or less given orally or intramuscularly for two weeks do not cause pancreatitis in dogs. PMID:6202383

A comparison of serum and plasma cytokine values using a multiplexed assay in cats.

PubMed

Gruen, Margaret E; Messenger, Kristen M; Thomson, Andrea E; Griffith, Emily H; Paradise, Hayley; Vaden, Shelly; Lascelles, B D X

2016-12-01

Degenerative joint disease (DJD) is highly prevalent in cats, and pain contributes to morbidity. In humans, alterations of cytokine concentrations have been associated with joint deterioration and pain. Similar changes have not been investigated in cats. Cytokine concentrations can be measured using multiplex technology with small samples of serum or plasma, however, serum and plasma are not interchangeable for most bioassays. Correlations for cytokine concentrations between serum and plasma have not been evaluated in cats. To evaluate the levels of detection and agreement between serum and plasma samples in cats. Paired serum and plasma samples obtained from 38 cats. Blood was collected into anti-coagulant free and EDTA Vacutainer ® tubes, serum or plasma extracted, and samples frozen at -80°C until testing. Duplicate samples were tested using a 19-plex feline cytokine/chemokine magnetic bead panel. Agreement between serum and plasma for many analytes was high, however correlation coefficients ranged from -0.01 to 0.97. Results from >50% of samples were below the lower limit of quantification for both serum and plasma for nine analytes, and for an additional three analytes for plasma only. While serum and plasma agreement was generally good, detection was improved using serum samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Serological, biochemical and enzymatic alterations in rodents after experimental envenomation with Hadruroides lunatus scorpion venom.

PubMed

Costal-Oliveira, F; Guerra-Duarte, C; Castro, K L P; Tintaya, B; Bonilla, C; Silva, W; Yarlequé, A; Fujiwara, R; Melo, M M; Chávez-Olórtegui, C

2015-09-01

Toxic effects of Peruvian Hadruroides lunatus scorpion venom on different biochemical and enzymatic parameters in blood serum of Wistar rats and Swiss mice were determined after experimental envenomation. An increase in enzymatic activities of Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and levels of serum protein and albumin were observed while a decrease in creatinine level in serum was perceived after 30 min of envenomation. No alterations in urea levels and in kidney histology were detected in the envenomed rats. The global leukocytes count was diminished, with decrease in lymphocytes, eosinophils and neutrophils levels in the bloodstream, while no alterations were found in hematological parameters of red series in rats injected with H. lunatus venom. IL-2, IL-4, IL-6, INF-γ, TNF, IL-17A and IL-10 levels were evaluated 0.5, 3 and 6 h after experimental envenomation of mice with H. lunatus venom. From all the analyzed cytokines, only IL-6 showed an increase in serum levels. Taken together, these results point out that envenomation by H. lunatus can impair hematological and immunological parameters and therefore might be monitored in accidents involving this species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells

PubMed Central

Streng-Ouwehand, Ingeborg; Ho, Nataschja I; Litjens, Manja; Kalay, Hakan; Boks, Martine Annemarie; Cornelissen, Lenneke AM; Kaur Singh, Satwinder; Saeland, Eirikur; Garcia-Vallejo, Juan J; Ossendorp, Ferry A; Unger, Wendy WJ; van Kooyk, Yvette

2016-01-01

Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated by C-type lectin receptors that recognize glycan structures. We show that the modification of Ovalbumin (OVA) with the glycan-structure LewisX (LeX) re-directs OVA to the C-type lectin receptor MGL1. LeX-modification of OVA favored Th1 skewing of CD4+ T cells and enhanced cross-priming of CD8+ T cells. While cross-presentation of native OVA requires high antigen dose and TLR stimuli, LeX modification reduces the required amount 100-fold and obviates its dependence on TLR signaling. The OVA-LeX-induced enhancement of T cell cross-priming is MGL1-dependent as shown by reduced CD8+ effector T cell frequencies in MGL1-deficient mice. Moreover, MGL1-mediated cross-presentation of OVA-LeX neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intracellular storage of antigen in Rab11+LAMP1+ compartments. We conclude that controlled neo-glycosylation of antigens can crucially influence intracellular routing of antigens, the nature and strength of immune responses and should be considered for optimizing current vaccination strategies. DOI: http://dx.doi.org/10.7554/eLife.11765.001 PMID:26999763

Structure, chaperone-like activity and allergenicity profile of bovine caseins upon peroxynitrite modification: New evidences underlying mastitis pathomechanisms.

PubMed

Sadeghian, Tanaz; Tavaf, Zohreh; Oryan, Ahmad; Shokouhi, Raheleh; Pourpak, Zahra; Moosavi-Movahedi, Ali Akbar; Yousefi, Reza

2018-01-01

Mastitis, an inflammatory reaction frequently develops in response to intra-mammary bacterial infection‌‌, may induce the generation of peroxynitrite (PON)‌ which is a highly potent reactive oxygen and nitrogen species. Caseins as the intrinsically unfolded proteins seem feasible substrates to react with PON. Therefore, in the current study, structural and functional aspects of both β-casein (β-CN) and whole casein fraction (WCF) were evaluated after PON modification, using a variety of techniques. Modification of the bovine caseins with PON results in an important enhancement in the carbonyl, nitrotryptophan, nitrotyrosine and dityrosine content of these proteins‌. The results of fluorescence and far UV-CD assessments suggested significant structural alteration of caseins upon PON-modification. The chaperone-like activity of β-casein was significantly altered after PON modification. The results of scanning electron microscopy suggest that bovine caseins display unique morphological features after treatment with PON. Also, the PON-modified caseins preserved their allergenicity profile and displayed partial resistance against digestion by the pancreatic proteases. Ascorbic acid, an important antioxidant component of milk, was also capable to significantly prevent the PON-induced structural damages in bovine milk caseins. In conclusion, our results suggest that PON may have significant role in the structural and functional alteration of milk caseins. Also, the PON-induced structural damaging effects of caseins might be effectively prevented by a sufficient level of milk antioxidant components particularly by ascorbic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.

PubMed

Philbrook, Nicola A; Winn, Louise M

2015-11-15

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT)

PubMed Central

Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

2018-01-01

Abstract Background Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Methods Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Results Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. Conclusion The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. PMID:29025075

Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells

PubMed Central

Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

2014-01-01

Blood–brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0·05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

PubMed

Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

2014-11-01

Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. © 2014 John Wiley & Sons Ltd.

IL8 and IL16 levels indicate serum and plasma quality.

PubMed

Kofanova, Olga; Henry, Estelle; Quesada, Rocio Aguilar; Bulla, Alexandre; Linares, Hector Navarro; Lescuyer, Pierre; Shea, Kathi; Stone, Mars; Tybring, Gunnel; Bellora, Camille; Betsou, Fay

2018-02-09

Longer pre-centrifugation times alter the quality of serum and plasma samples. Markers for such delays in sample processing and hence for the sample quality, have been identified. Twenty cytokines in serum, EDTA plasma and citrate plasma samples were screened for changes in concentration induced by extended blood pre-centrifugation delays at room temperature. The two cytokines that showed the largest changes were further validated for their "diagnostic performance" in identifying serum or plasma samples with extended pre-centrifugation times. In this study, using R&D Systems ELISA kits, EDTA plasma samples and serum samples with a pre-centrifugation delay longer than 24 h had an IL16 concentration higher than 313 pg/mL, and an IL8 concentration higher than 125 pg/mL, respectively. EDTA plasma samples with a pre-centrifugation delay longer than 48 h had an IL16 concentration higher than 897 pg/mL, citrate plasma samples had an IL8 concentration higher than 21.5 pg/mL and serum samples had an IL8 concentration higher than 528 pg/mL. These robust and accurate tools, based on simple and commercially available ELISA assays can greatly facilitate qualification of serum and plasma legacy collections with undocumented pre-analytics.

Serum copper levels in users of multiload intra-uterine contraceptive devices.

PubMed

Arowojolu, A O; Otolorin, E O; Ladipo, O A

1989-12-01

The systemic absorption of copper incorporated into multiload intra-uterine contraceptive devices (IUDs), as indicated by serum copper levels in users of such devices, was assessed in a prospective longitudinal study. One hundred and ten healthy Nigerian women using either multiload copper 250 (MLCU 250) or multiload copper 375 (MLCU 375) IUDs participated in the study. Their serum copper levels were estimated serially during 12 months of continuous use of the devices. The mean (+/- s.e.m.) pre-insertion serum copper levels of our subjects using MLCU 250 (17.0 +/- 3 mumol/l) and MLCU 375 (16.7 +/- 0.5 mumol/l) were found to be lower than those reported in Americans (22.2 mumol/l) and in Germans (20.2 mumol/l), although similar to levels in Indians (17.0 mumol/l). There was no significant difference in the mean serum copper levels estimated before and after 1 month of continuous use of the device. Serial estimations of the serum copper levels in users showed that there was no alteration in these levels after a period of 12 months of continuous IUD use. We therefore conclude that the copper incorporated into multiload IUDs appears not to influence the concentration of serum copper of users.

Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling.

PubMed

Henze, Andrea; Aumer, Franziska; Grabner, Arthur; Raila, Jens; Schweigert, Florian J

2011-10-01

Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips® (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30 Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.

Effects of Iron Supplementation and Activity on Serum Iron Depletion and Hemoglobin Levels in Female Athletes

ERIC Educational Resources Information Center

Cooter, G. Rankin; Mowbray, Kathy W.

1978-01-01

Research revealed that a four-month basketball training program did not significantly alter serum iron, total iron binding capacity, hemoglobin, and percent saturation levels in female basketball athletes. (JD)

Biochar modification to enhance sorption of inorganics from water.

PubMed

Sizmur, Tom; Fresno, Teresa; Akgül, Gökçen; Frost, Harrison; Moreno-Jiménez, Eduardo

2017-12-01

Biochar can be used as a sorbent to remove inorganic pollutants from water but the efficiency of sorption can be improved by activation or modification. This review evaluates various methods to increase the sorption efficiency of biochar including activation with steam, acids and bases and the production of biochar-based composites with metal oxides, carbonaceous materials, clays, organic compounds, and biofilms. We describe the approaches, and explain how each modification alters the sorption capacity. Physical and chemical activation enhances the surface area or functionality of biochar, whereas modification to produce biochar-based composites uses the biochar as a scaffold to embed new materials to create surfaces with novel surface properties upon which inorganic pollutants can sorb. Many of these approaches enhance the retention of a wide range of inorganic pollutants in waters, but here we provide a comparative assessment for Cd 2+ , Cu 2+ , Hg 2+ , Pb 2+ , Zn 2+ , NH 4 + , NO 3 - , PO 4 3- , CrO 4 2- and AsO 4 3- . Copyright © 2017 Elsevier Ltd. All rights reserved.

Serum retinol, alpha-tocopherol, and beta-carotene levels are not altered by excess ingestion of diacylglycerol-containing plant sterol esters.

PubMed

Saito, Shinichiro; Tomonobu, Kazuichi; Kudo, Naoto; Shiiba, Daisuke; Hase, Tadashi; Tokimitsu, Ichiro

2006-01-01

Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, beta-carotene, and alpha-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. There were no subjective adverse effects or changes in serum retinol, alpha-tocopherol, and beta-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise. Copyright 2006 S. Karger AG, Basel.

Alterations in the lipid metabolism of rat aorta: effects of vitamin a deficiency.

PubMed

Gatica, Laura V; Vega, Verónica A; Zirulnik, Fanny; Oliveros, Liliana B; Gimenez, María S

2006-01-01

Antioxidants are known to reduce cardiovascular disease by reducing the concentration of free radicals in the vessel wall and by preventing the oxidative modification of low-density lipoproteins. The prooxidative effect of a vitamin-A-deficient diet on the aorta has previously been demonstrated by us. In this study, the lipid metabolism in the aorta of rats fed on a vitamin-A-deficient diet was evaluated. Vitamin A deficiency induced a hypolipidemic effect (lower serum triglyceride and cholesterol levels) and a decreased serum paraoxonase 1/arylesterase activity. The concentrations of triglycerides, total cholesterol, free and esterified cholesterol, and phospholipids were increased in the aorta of vitamin-A-deficient rats. The phospholipid compositions showed an increase in phosphatidylcholine (PC), phosphatidylinositol plus phosphatidylserine and phosphatidylethanolamine, a decrease in sphingomyelin, and no change in phosphatidylglycerol. In the aorta, the increase in triglycerides was associated with an increased fatty acid synthesis and mRNA expression of diacylglycerol acyltransferase 1. The increased PC content was attributed to an increased synthesis, as measured by [methyl-(14)C]choline incorporation into PC and high CTP:phosphocholine cytidylyltransferase-alpha mRNA expression. The cholesterol synthesis, evaluated by [1-(14)C]acetate incorporated into cholesterol and mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, did not change. The lipoprotein lipase and lectin-like oxidized low-density lipoprotein receptor 1 mRNA expression levels increased in the aorta of vitamin-A-deficient animals. The incorporation of vitamin A into the diet of vitamin-A-deficient rats reverted all the changes observed. These results indicate that a vitamin-A-deficient diet,in addition to having a prooxidative effect, alters the aorta lipid metabolism.

[New topics regarding equations for GFR estimation based on serum creatinine and cystatin C].

PubMed

Horio, Masaru

2014-02-01

Japanese GFR equations and CKD-EPI equations based on standardized serum creatinine and standardized cystatin C are recommended in recent Japanese CKD guides and KDIGO guidelines for CKD management, respectively. CKD-EPIcreat overestimates GFR in Japanese subjects, probably due to the difference in muscle mass between Japanese and Caucasians. Unlike CKD-EPIcreat, CKD-EPIcys performs well in Japanese subjects, indicating the advantages of using cystatin C as a GFR marker. KDIGO guidelines suggest measuring eGFRcys in adults with eGFRcreat of 45-59 ml/min/1.73 m2 who do not have markers of kidney damage if confirmation of CKD is required. Creatinine is excreted by glomerular filtration, but also secreted by the tubules. Alteration of the tubular secretion of creatinine may influence the performance of GFR equations based on serum creatinine. Multivariate analysis showed that GFR and serum albumin levels were independent parameters affecting the fractional excretion of creatinine (FE-Cr). Alteration of FE-Cr according to the serum albumin levels may be one of the reasons for the bias of GFR equations based on serum creatinine. Low GFR is a risk factor for all-cause and cardiovascular mortality in a general population. However, the relationship between eGFR and the hazard risk of events is different depending on whether cystatin C or creatinine is used to calculate eGFR. The association between eGFRcys and the hazard risk is much stronger compared with eGFRcreat. Cystatin C may be a useful alternative to creatinine for detecting a high risk of complications in a general population and subjects with CKD.

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

PubMed Central

Fan, Ni; Luo, Yayan; Xu, Ke; Zhang, Minling; Ke, Xiaoyin; Huang, Xini; Ding, Yi; Wang, Daping; Ning, Yuping; Deng, Xuefeng; He, Hongbo

2016-01-01

Objective Exposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed. Methods 155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS). Results Serum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p < 0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r = −0.210, p < 0.01) and negative subscore (r = −0.300, p < 0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18. Conclusions Serum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers. PMID:26589393

O-Linked β-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to decode pathogenesis of diabetic retinopathy.

PubMed

Gurel, Zafer; Sheibani, Nader

2018-01-31

The incidence of diabetes continues to rise among all ages and ethnic groups worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects the retinal neurovasculature causing serious vision problems, including blindness. Its pathogenesis and severity is directly linked to the chronic exposure to high glucose conditions. No treatments are currently available to stop the development and progression of DR. To develop new and effective therapeutic approaches, it is critical to better understand how hyperglycemia contributes to the pathogenesis of DR at the cellular and molecular levels. We propose alterations in O-GlcNAc modification of target proteins during diabetes contribute to the development and progression of DR. The O-GlcNAc modification is regulated through hexosamine biosynthetic pathway. We showed this pathway is differentially activated in various retinal vascular cells under high glucose conditions perhaps due to their selective metabolic activity. O-GlcNAc modification can alter protein stability, activity, interactions, and localization. By targeting the same amino acid residues (serine and threonine) as phosphorylation, O-GlcNAc modification can either compete or cooperate with phosphorylation. Here we will summarize the effects of hyperglycemia-induced O-GlcNAc modification on the retinal neurovasculature in a cell-specific manner, providing new insight into the role of O-GlcNAc modification in early loss of retinal pericytes and the pathogenesis of DR. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Identification of Protein Succination as a Novel Modification of Tubulin

PubMed Central

Piroli, Gerardo G.; Manuel, Allison M.; Walla, Michael D.; Jepson, Matthew J.; Brock, Jonathan W.C.; Rajesh, Mathur P.; Tanis, Ross M.; Cotham, William E.; Frizzell, Norma

2015-01-01

Protein succination is a stable post-translational modification that occurs when fumarate reacts with cysteine residues to generate S-(2-succino)cysteine (2SC). We demonstrate that both alpha (α) and beta (β) tubulin are increasingly modified by succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice. Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the pharmacological compound dimethylfumarate (DMF, 500 μM) inhibited polymerization up to 35% and 59%, respectively. Using mass spectrometry we identified Cys347α, Cys376α, Cys12β and Cys303β as sites of succination in porcine brain tubulin and the relative abundance of succination at these cysteines increased in association with fumarate concentration. The increase in succination after incubation with fumarate altered tubulin recognition by an anti-α-tubulin antibody. Succinated tubulin in adipocytes cultured in high glucose vs. normal glucose also had reduced reactivity with the anti-αtubulin antibody; suggesting that succination may interfere with tubulin:protein interactions. DMF reacted rapidly with 11 of the 20 cysteines in the αβ tubulin dimer, decreased the number of free sulfhydryls and inhibited the proliferation of 3T3-L1 fibroblasts. Our data suggests that inhibition of tubulin polymerization is an important, undocumented mechanism of action of DMF. Taken together, our results demonstrate that succination is a novel post-translational modification of tubulin and suggest that extensive modification by fumarate, either physiologically or pharmacologically, may alter microtubule dynamics. PMID:24909641

Serum levels of folate and cobalamin in women with recurrent spontaneous abortion.

PubMed

Sütterlin, M; Bussen, S; Ruppert, D; Steck, T

1997-10-01

We evaluated the folate and cobalamin status in 29 non-pregnant women with a history of recurrent spontaneous abortion (three or more consecutive) of unknown aetiology in comparison to 29 healthy nulligravidae of similar reproductive age (controls). Serum concentrations of folate and cobalamin showed no significant differences between the two groups. No correlation between age and vitamin concentrations was found. In the study group there was a significant negative correlation of the number of previous abortions and the concentration of serum folate. Patients with at least four previous miscarriages had significantly lower serum values of folic acid than women with three abortions, but not than controls. The underlying cause of this finding remains unclear. In conclusion, the serum concentrations of folic acid and vitamin B12 are not significantly altered in women with unexplained recurrent spontaneous abortions, and an association between a deficiency of these vitamins and an increased risk of pregnancy loss appears to be questionable in the majority of gestations.

49 CFR 37.43 - Alteration of transportation facilities by public entities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...

49 CFR 37.43 - Alteration of transportation facilities by public entities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...

49 CFR 37.43 - Alteration of transportation facilities by public entities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...

49 CFR 37.43 - Alteration of transportation facilities by public entities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...

Serum-free culture of rat proximal tubule cells with enhanced function on chitosan.

PubMed

Chang, Shao-Hsuan; Chiang, I-Ni; Chen, Yi-Hsin; Young, Tai-Horng

2013-11-01

The proximal tubule performs a variety of important renal functions and is the major site for nutrient reabsorption. The purpose of this study is to culture rat renal proximal tubule cells (PTCs) on chitosan without serum to maintain a transcellular pathway to transport water and ions effectively without loss of highly differentiated cell function. The effect of chitosan, which is structurally similar to glycosaminoglycans, in the absence of serum on the primary cultured PTCs was compared that of collagen with or without serum. Two days after seeding, more tubule fragments and higher PTC viability were observed on chitosan than on collagen with or without serum. Proliferation marker Ki-67 immunostaining and phosphorylated extracellular-regulated kinase (ERK) expression results displayed similar proliferation capability of PTCs established on chitosan without serum and collagen with 2% fetal bovine serum after 4 days of incubation. When grown to confluence, PTCs formed a monolayer with well-organized tight junctions and formation of domes on chitosan without serum. Moreover, evaluation of the transepithelial electrical resistance showed that both chitosan and serum were involved in the modification of water and ion transport in confluent cells. By showing the direct suppression of PTC growth and dome formation treated with heparinase, we demonstrated that the interaction between cell surface heparin sulfate proteoglycan and chitosan played an important role in PTC proliferation and differentiation. A successful primary culture of PTCs has now been produced on chitosan in serum-free culture condition, which offers potential applications for chitosan in renal tissue engineering. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cannabinoid HU210 Protects Isolated Rat Stomach against Impairment Caused by Serum of Rats with Experimental Acute Pancreatitis

PubMed Central

Cao, Ming-hua; Li, Yong-yu; Xu, Jing; Feng, Ya-jing; Lin, Xu-hong; Li, Kun; Han, Tong; Chen, Chang-Jie

2012-01-01

Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis. PMID:23285225

Binding affinity of aluminium to human serum transferrin and effects of carbohydrate chain modification as studied by HPLC/high-resolution ICP-MS--speciation of aluminium in human serum.

PubMed

Nagaoka, Megumi Hamano; Maitani, Tamio

2005-09-01

Aluminium (Al) in the blood is bound to transferrin (Tf), a glycoprotein of about 80kDa that is characterized by its need for a synergistic anion. In this focused review, the binding affinity of Al to Tf is surveyed in the context of our recent studies using on-line high-performance liquid chromatography/high-resolution inductively coupled plasma mass spectrometry (HPLC/HR-ICP-MS). Al in human serum without any in vitro Al-spikes was present in a form bound to the N-lobe site of Tf. The influences of sialic acid in the carbohydrate chain of human serum Tf (hTf) were studied using asialo-hTf, obtained by treatment with sialidase. The binding affinity of Fe was similar between asialo-hTf and native-hTf, while that of Al for asialo-hTf was larger than that for native-hTf, especially in the presence of oxalate, a synergistic anion. The above findings are discussed in relation to diseases in which the serum concentrations of carbohydrate-deficient Tf and oxalate are augmented.

Serum concentrations of brain-derived neurotrophic factor in patients with gender identity disorder.

PubMed

Fontanari, Anna-Martha V; Andreazza, Tahiana; Costa, Ângelo B; Salvador, Jaqueline; Koff, Walter J; Aguiar, Bianca; Ferrari, Pamela; Massuda, Raffael; Pedrini, Mariana; Silveira, Esalba; Belmonte-de-Abreu, Paulo S; Gama, Clarissa S; Kauer-Sant'Anna, Marcia; Kapczinski, Flavio; Lobato, Maria Ines R

2013-10-01

Gender Identity Disorder (GID) is characterized by a strong and persistent cross-gender identification that affects different aspects of behavior. Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and neuroplasticity. Altered BDNF-signaling is thought to contribute to the pathogenesis of psychiatric disordersand is related to traumatic life events. To examine serum BDNF levels, we compared one group of DSM-IV GID patients (n = 45) and one healthy control group (n = 66). Serum BDNF levels were significantly decreased in GID patients (p = 0.013). This data support the hypothesis that the reduction found in serum BDNF levels in GID patients may be related to the psychological abuse that transsexuals are exposed during their life. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Relationship between Dietary Fatty Acids and Inflammatory Genes on the Obese Phenotype and Serum Lipids

PubMed Central

Joffe, Yael T.; Collins, Malcolm; Goedecke, Julia H.

2013-01-01

Obesity, a chronic low-grade inflammatory condition is associated with the development of many comorbidities including dyslipidemia. This review examines interactions between single nucleotide polymorphisms (SNP) in the inflammatory genes tumor necrosis alpha (TNFA) and interleukin-6 (IL-6) and dietary fatty acids, and their relationship with obesity and serum lipid levels. In summary, dietary fatty acids, in particular saturated fatty acids and the omega-3 and omega-6 polyunsaturated fatty acids, impact the expression of the cytokine genes TNFA and IL-6, and alter TNFα and IL-6 production. In addition, sequence variants in these genes have also been shown to alter their gene expression and plasma levels, and are associated with obesity, measures of adiposity and serum lipid concentrations. When interactions between dietary fatty acids and TNFA and IL-6 SNPs on obesity and serum lipid were analyzed, both the quantity and quality of dietary fatty acids modulated the relationship between TNFA and IL-6 SNPs on obesity and serum lipid profiles, thereby impacting the association between phenotype and genotype. Researching these diet–gene interactions more extensively, and understanding the role of ethnicity as a confounder in these relationships, may contribute to a better understanding of the inter-individual variability in the obese phenotype. PMID:23698162

The relationship between dietary fatty acids and inflammatory genes on the obese phenotype and serum lipids.

PubMed

Joffe, Yael T; Collins, Malcolm; Goedecke, Julia H

2013-05-21

Obesity, a chronic low-grade inflammatory condition is associated with the development of many comorbidities including dyslipidemia. This review examines interactions between single nucleotide polymorphisms (SNP) in the inflammatory genes tumor necrosis alpha (TNFA) and interleukin-6 (IL-6) and dietary fatty acids, and their relationship with obesity and serum lipid levels. In summary, dietary fatty acids, in particular saturated fatty acids and the omega-3 and omega-6 polyunsaturated fatty acids, impact the expression of the cytokine genes TNFA and IL-6, and alter TNFα and IL-6 production. In addition, sequence variants in these genes have also been shown to alter their gene expression and plasma levels, and are associated with obesity, measures of adiposity and serum lipid concentrations. When interactions between dietary fatty acids and TNFA and IL-6 SNPs on obesity and serum lipid were analyzed, both the quantity and quality of dietary fatty acids modulated the relationship between TNFA and IL-6 SNPs on obesity and serum lipid profiles, thereby impacting the association between phenotype and genotype. Researching these diet-gene interactions more extensively, and understanding the role of ethnicity as a confounder in these relationships, may contribute to a better understanding of the inter-individual variability in the obese phenotype.

Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction

PubMed Central

Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Bråthen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

2009-01-01

Background When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. Results We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). Conclusion We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs. PMID:19814792

Retinal O-linked N-acetylglucosamine protein modifications: implications for postnatal retinal vascularization and the pathogenesis of diabetic retinopathy

PubMed Central

Sieg, Kelsey M.; Shallow, Keegan D.; Sorenson, Christine M.; Sheibani, Nader

2013-01-01

Purpose Hyperglycemia activates several metabolic pathways, including the hexosamine biosynthetic pathway. Uridine diphosphate N-acetylglucosamine (GlcNAc) is the product of the hexosamine biosynthetic pathway and the substrate for O-linked GlcNAc (O-GlcNAc) modification. This modification affects a wide range of proteins by altering their activity, cellular localization, and/or protein interactions. However, the role O-GlcNAcylation may play in normal postnatal retinal vascular development and in the ocular complications of diabetes, including diabetic retinopathy, requires further investigation. Methods The total levels of O-GlcNAc-modified proteins were evaluated by western blot analysis of lysates prepared from retinas obtained at different days during postnatal retinal vascularization and oxygen-induced ischemic retinopathy. Similar experiments were performed with retinal lysate prepared from diabetic Ins2Akita/+ mice with different durations of diabetes and retinal vascular cells cultured under various glucose conditions. The localization of O-GlcNAc-modified proteins in the retinal vasculature was confirmed by immunofluorescence staining. The impact of altered O-GlcNAcylation on the migration of retinal vascular cells was determined using scratch wound and transwell migration assays. Results We detected an increase in protein O-GlcNAcylation during mouse postnatal retinal vascularization and aging, in part through the regulation of the enzymes that control this modification. The study of the diabetic Ins2Akita/+ mouse retina showed an increase in the O-GlcNAc modification of retinal proteins. We also observed an increase in retinal O-GlcNAcylated protein levels during the neovascularization phase of oxygen-induced ischemic retinopathy. Our fluorescence microscopy data confirmed that the alterations in retinal O-GlcNAcylation are similarly represented in the retinal vasculature and in retinal pericytes and endothelial cells. Particularly, the migration of

The Dose–Response Association between Nitrogen Dioxide Exposure and Serum Interleukin-6 Concentrations

PubMed Central

Perret, Jennifer L.; Bowatte, Gayan; Lodge, Caroline J.; Knibbs, Luke D.; Gurrin, Lyle C.; Kandane-Rathnayake, Rangi; Johns, David P.; Lowe, Adrian J.; Burgess, John A.; Thompson, Bruce R.; Thomas, Paul S.; Wood-Baker, Richard; Morrison, Stephen; Giles, Graham G.; Marks, Guy; Markos, James; Tang, Mimi L. K.; Abramson, Michael J.; Walters, E. Haydn; Matheson, Melanie C.; Dharmage, Shyamali C.

2017-01-01

Systemic inflammation is an integral part of chronic obstructive pulmonary disease (COPD), and air pollution is associated with cardiorespiratory mortality, yet the interrelationships are not fully defined. We examined associations between nitrogen dioxide (NO2) exposure (as a marker of traffic-related air pollution) and pro-inflammatory cytokines, and investigated effect modification and mediation by post-bronchodilator airflow obstruction (post-BD-AO) and cardiovascular risk. Data from middle-aged participants in the Tasmanian Longitudinal Health Study (TAHS, n = 1389) were analyzed by multivariable logistic regression, using serum interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) as the outcome. Mean annual NO2 exposure was estimated at residential addresses using a validated satellite-based land-use regression model. Post-BD-AO was defined by post-BD forced expiratory ratio (FEV1/FVC) < lower limit of normal, and cardiovascular risk by a history of either cerebrovascular or ischaemic heart disease. We found a positive association with increasing serum IL-6 concentration (geometric mean 1.20 (95% CI: 1.1 to 1.3, p = 0.001) per quartile increase in NO2). This was predominantly a direct relationship, with little evidence for either effect modification or mediation via post-BD-AO, or for the small subgroup who reported cardiovascular events. However, there was some evidence consistent with serum IL-6 being on the causal pathway between NO2 and cardiovascular risk. These findings raise the possibility that the interplay between air pollution and systemic inflammation may differ between post-BD airflow obstruction and cardiovascular diseases. PMID:28481326

On the identification of biomarkers for non-small cell lung cancer in serum and pleural effusion.

PubMed

Rodríguez-Piñeiro, A M; Blanco-Prieto, S; Sánchez-Otero, N; Rodríguez-Berrocal, F J; de la Cadena, M Páez

2010-06-16

The current imperative need for new biomarkers of non-small cell lung cancer (NSCLC) prompted us to compare the proteome of serum and pleural effusion samples from cancer patients with those with benign lung diseases as pneumonia or tuberculosis. Samples were prefractionated through affinity chromatography prior to 2D-DIGE to detect proteins with altered expression in cancer patients. Overall, we identified more potential biomarkers in pleural effusion, which is closer to the affected organ, than in serum. Nevertheless, in both cases principal component analysis demonstrated that the pattern of significantly altered proteins discriminates between disease groups. The biomarker candidates comprise proteins increased in malignant pleural effusions as gelsolin and the metalloproteinase inhibitor 2, and others with lower levels as S100-A8 and S100-A9. The most interesting protein was the pigment epithelium-derived factor (PEDF), which is related to angiogenesis inhibition, and was significantly overexpressed both in serum and pleural effusion from NSCLC patients. More than 12 PEDF isoforms were specifically immunodetected in both fluids in 2-D blots, most of them overexpressed in NSCLC. Thus, further validation would be ideally directed to quantify individual PEDF isoforms, as it may be only one or some of them the ones altered in the cancer process. Copyright 2010 Elsevier B.V. All rights reserved.

High serum serotonin in sudden infant death syndrome.

PubMed

Haynes, Robin L; Frelinger, Andrew L; Giles, Emma K; Goldstein, Richard D; Tran, Hoa; Kozakewich, Harry P; Haas, Elisabeth A; Gerrits, Anja J; Mena, Othon J; Trachtenberg, Felicia L; Paterson, David S; Berry, Gerard T; Adeli, Khosrow; Kinney, Hannah C; Michelson, Alan D

2017-07-18

Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, likely comprises heterogeneous disorders with the common phenotype of sudden death without explanation upon postmortem investigation. Previously, we reported that ∼40% of SIDS deaths are associated with abnormalities in serotonin (5-hydroxytryptamine, 5-HT) in regions of the brainstem critical in homeostatic regulation. Here we tested the hypothesis that SIDS is associated with an alteration in serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly elevated (95%) in SIDS infants ( n = 61) compared with autopsied controls ( n = 15) [SIDS, 177.2 ± 15.1 (mean ± SE) ng/mL versus controls, 91.1 ± 30.6 ng/mL] ( P = 0.014), as determined by ELISA. This increase was validated using high-performance liquid chromatography. Thirty-one percent (19/61) of SIDS cases had 5-HT levels greater than 2 SDs above the mean of the controls, thus defining a subset of SIDS cases with elevated 5-HT. There was no association between genotypes of the serotonin transporter promoter region polymorphism and serum 5-HT level. This study demonstrates that SIDS is associated with peripheral abnormalities in the 5-HT pathway. High serum 5-HT may serve as a potential forensic biomarker in autopsied infants with SIDS with serotonergic defects.

Strong Cation Exchange Chromatography in Analysis of Posttranslational Modifications: Innovations and Perspectives

PubMed Central

Edelmann, Mariola J.

2011-01-01

Strong cation exchange (SCX) chromatography has been utilized as an excellent separation technique that can be combined with reversed-phase (RP) chromatography, which is frequently used in peptide mass spectrometry. Although SCX is valuable as the second component of such two-dimensional separation methods, its application goes far beyond efficient fractionation of complex peptide mixtures. Here I describe how SCX facilitates mapping of the protein posttranslational modifications (PTMs), specifically phosphorylation and N-terminal acetylation. The SCX chromatography has been mainly used for enrichment of these two PTMs, but it might also be beneficial for high-throughput analysis of other modifications that alter the net charge of a peptide. PMID:22174558

Ocean acidification alters fish populations indirectly through habitat modification

NASA Astrophysics Data System (ADS)

Nagelkerken, Ivan; Russell, Bayden D.; Gillanders, Bronwyn M.; Connell, Sean D.

2016-01-01

Ocean ecosystems are predicted to lose biodiversity and productivity from increasing ocean acidification. Although laboratory experiments reveal negative effects of acidification on the behaviour and performance of species, more comprehensive predictions have been hampered by a lack of in situ studies that incorporate the complexity of interactions between species and their environment. We studied CO2 vents from both Northern and Southern hemispheres, using such natural laboratories to investigate the effect of ocean acidification on plant-animal associations embedded within all their natural complexity. Although we substantiate simple direct effects of reduced predator-avoidance behaviour by fishes, as observed in laboratory experiments, we here show that this negative effect is naturally dampened when fish reside in shelter-rich habitats. Importantly, elevated CO2 drove strong increases in the abundance of some fish species through major habitat shifts, associated increases in resources such as habitat and prey availability, and reduced predator abundances. The indirect effects of acidification via resource and predator alterations may have far-reaching consequences for population abundances, and its study provides a framework for a more comprehensive understanding of increasing CO2 emissions as a driver of ecological change.

Serum sickness

MedlinePlus

Drug allergy - serum sickness; Allergic reaction - serum sickness; Allergy - serum sickness ... Unlike other drug allergies , which occur very soon after receiving the medicine, serum sickness develops 7 to 21 days after the first exposure ...

Modeling the impact of hydromorphological alterations by dams and channelization on fish habitat.

NASA Astrophysics Data System (ADS)

Parasiewicz, Piotr; Suska, Katarzyna

2017-04-01

As a consequence of introduction of Water Framework Directive it has been discovered that hydromorphological pressures are one of the main causes of impact on aquatic fauna. However, the impact may vary depending on river type and fish community. To test this hypothesis, we modelled alterations of fish habitat on 6 river sections across Poland using MesoHABSIM approach. The original models of habitat for Target Fish Community were based on repeated field surveys in reference river sections, classified into four fish-ecological classes. Introducing to the models three hydromorphological modification types (damming, channelization and dredging) changed persistent habitat availability for the fish community. The change was measured with Habitat Stress Days Alteration index. Overall the modifications caused increase of habitat stress days, but impact varied depending on season, hydromorphologic river type and expected fish community.

Genetic modifications of pigs for medicine and agriculture

PubMed Central

Whyte, Jeffrey J.; Prather, Randall S.

2011-01-01

SUMMARY Genetically modified swine hold great promise in the fields of agriculture and medicine. Currently, these swine are being used to optimize production of quality meat, to improve our understanding of the biology of disease resistance, and to reduced waste. In the field of biomedicine, swine are anatomically and physiologically analogous to humans. Alterations of key swine genes in disease pathways provide model animals to improve our understanding of the causes and potential treatments of many human genetic disorders. The completed sequencing of the swine genome will significantly enhance the specificity of genetic modifications, and allow for more accurate representations of human disease based on syntenic genes between the two species. Improvements in both methods of gene alteration and efficiency of model animal production are key to enabling routine use of these swine models in medicine and agriculture. PMID:21671302

Iron Dextran treatment does not induce serum protein carbonyls in the newborn pig

USDA-ARS?s Scientific Manuscript database

Oxidation of serum proteins can lead to carbonyl formation which alters their function and is often associated with stress-related diseases. Since it is recommended that all pigs reared in modern production facilities be given supplemental iron at birth to prevent anemia, and metals can catalyze th...

Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).

PubMed

Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

2018-03-01

Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Evaluation of Aspergillus PCR protocols for testing serum specimens.

PubMed

White, P Lewis; Mengoli, Carlo; Bretagne, Stéphane; Cuenca-Estrella, Manuel; Finnstrom, Niklas; Klingspor, Lena; Melchers, Willem J G; McCulloch, Elaine; Barnes, Rosemary A; Donnelly, J Peter; Loeffler, Juergen

2011-11-01

A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance.

Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins

PubMed Central

Stephens, Andrew D.; Liu, Patrick Z.; Banigan, Edward J.; Almassalha, Luay M.; Backman, Vadim; Adam, Stephen A.; Goldman, Robert D.; Marko, John F.

2018-01-01

Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed “blebs” are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. A number of prior studies suggest that lamins dictate nuclear morphology, but the contributions of altered chromatin compaction remain unclear. We show that chromatin histone modification state dictates nuclear rigidity, and modulating it is sufficient to both induce and suppress nuclear blebs. Treatment of mammalian cells with histone deacetylase inhibitors to increase euchromatin or histone methyltransferase inhibitors to decrease heterochromatin results in a softer nucleus and nuclear blebbing, without perturbing lamins. Conversely, treatment with histone demethylase inhibitors increases heterochromatin and chromatin nuclear rigidity, which results in reduced nuclear blebbing in lamin B1 null nuclei. Notably, increased heterochromatin also rescues nuclear morphology in a model cell line for the accelerated aging disease Hutchinson–Gilford progeria syndrome caused by mutant lamin A, as well as cells from patients with the disease. Thus, chromatin histone modification state is a major determinant of nuclear blebbing and morphology via its contribution to nuclear rigidity. PMID:29142071

MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.

PubMed

Huang, Xiao; Qin, Xianhui; Yang, Wenbin; Liu, Lishun; Jiang, Chongfei; Zhang, Xianglin; Jiang, Shanqun; Bao, Huihui; Su, Hai; Li, Ping; He, Mingli; Song, Yun; Zhao, Min; Yin, Delu; Wang, Yu; Zhang, Yan; Li, Jianping; Yang, Renqang; Wu, Yanqing; Hong, Kui; Wu, Qinhua; Chen, Yundai; Sun, Ningling; Li, Xiaoying; Tang, Genfu; Wang, Binyan; Cai, Yefeng; Hou, Fan Fan; Huo, Yong; Wang, Hong; Wang, Xiaobin; Cheng, Xiaoshu

2018-03-01

This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase ( MTHFR ) C677T genotypes and serum folate levels. This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5±8.5 versus 14.4±8.1 μmol/L; P =0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach ≈15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2018 American Heart Association, Inc.

Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

PubMed Central

Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

2016-01-01

Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis. PMID:26776680

Serum neuron specific enolase - a novel indicator for neuropsychiatric systemic lupus erythematosus?

PubMed

Hawro, T; Bogucki, A; Krupińska-Kun, M; Maurer, M; Woźniacka, A

2015-12-01

Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE. © The Author(s) 2015.

Treatment of obesity hypoventilation syndrome and serum leptin.

PubMed

Yee, Brendon J; Cheung, Jane; Phipps, Paul; Banerjee, Dev; Piper, Amanda J; Grunstein, Ronald R

2006-01-01

Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels. The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations. We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study. The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred. Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

[Modifications of vital signs during hygiene care in intensive care patients: an explorative study].

PubMed

Lucchini, Alberto; Giacovelli, Matteo; Elli, Stefano; Gariboldi, Roberto; Pelucchi, Giulia; Bondi, Herman; Brambilla, Daniela

2009-01-01

Hygiene care in critical patients may alter vital signs. Aim of this paper is to measure vital signs and their modifications in critical patients during hygiene care and measure differences with pre and post hygiene values. Vital signs of 6 patients two hours before, during and 90 minutes after hygienic care were measured. During and 2 hours after the end of hygiene a modification of vital signs was observed compared to basic values (mean values during/90 min after, compared to baseline): heart rate +11.20%/ +1.48; systolic blood pressure +22.68%/+1.56; arterial capillary saturimetry -4.31/+0.27, Respiratory frequency +8.10/+2.66, tidal volume +4,04/-7,51, CO2 min/vol +5,34/- 22.33, bladder temperature -0.85/-0.60. Hygiene care in critical care patients may significantly alter vital signs. Therefore a strict haemodinamic and respiratory monitoring is warranted as well as protocols for the management of sedation and of vasoactive support.

Serum sialic acid levels in patients with sympathetic ophthalmitis.

PubMed

Lamba, P A; Pandey, P K; Sarin, G S; Mathur, M D

1993-12-01

Serum sialic acid levels were measured in 16 patients with sympathetic ophthalmitis, 36 with neglected traumatic uveitis following penetrating injury and 40 healthy subjects. There was no significant alteration of its level in patients with traumatic uveitis. However, its level was significantly elevated in patients with sympathetic ophthalmitis. It was high even in the early stage of the disease. It decreased significantly at the remission stage. It is proposed that measurement of sialic acid level in serum can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease.

Base modification strategies to modulate immune stimulation by an siRNA.

PubMed

Valenzuela, Rachel Anne P; Suter, Scott R; Ball-Jones, Alexi A; Ibarra-Soza, José M; Zheng, Yuxuan; Beal, Peter A

2015-01-19

Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi-based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2'-OMe or 2'-F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence-dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll-like receptor 8 (TLR8) bound to small-molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson-Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson-Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson-Crick face is generally more effective at blocking TNFα production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5'-end were more effective at blocking cytokine production than those placed at the 3'-end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies

PubMed Central

Kontaxi, Christiana; Piccardo, Pedro; Gill, Andrew C.

2017-01-01

Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an “unfolded” conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation. We are only beginning to define the site-specific impact of each type of lysine modification on tau biology as well as the possible interplay between them, but, like phosphorylation, these modifications are likely to play critical roles in tau's normal and pathobiology. This review summarizes the latest findings focusing on lysine post-translational modifications that occur at both endogenous tau protein and pathological tau forms in AD and other tauopathies. In addition, it highlights the significance of a site-dependent approach of studying tau post-translational modifications under normal and pathological conditions. PMID:28848737

Modifications in small nuclear RNAs and their roles in spliceosome assembly and function.

PubMed

Bohnsack, Markus T; Sloan, Katherine E

2018-06-01

Modifications in cellular RNAs have emerged as key regulators of all aspects of gene expression, including pre-mRNA splicing. During spliceosome assembly and function, the small nuclear RNAs (snRNAs) form numerous dynamic RNA-RNA and RNA-protein interactions, which are required for spliceosome assembly, correct positioning of the spliceosome on substrate pre-mRNAs and catalysis. The human snRNAs contain several base methylations as well as a myriad of pseudouridines and 2'-O-methylated nucleotides, which are largely introduced by small Cajal body-specific-RNPs. Modified nucleotides typically cluster in functionally important regions of the snRNAs, suggesting that their presence could optimise the interactions of snRNAs with each other or with pre-mRNAs, or may affect the binding of spliceosomal proteins. snRNA modifications appear to play important roles in snRNP biogenesis and spliceosome assembly, and have also been proposed to influence the efficiency and fidelity of pre-mRNAs splicing. Interestingly, alterations in the modification status of snRNAs have recently been observed in different cellular conditions, implying that some snRNA modifications are dynamic and raising the possibility that these modifications may fine-tune the spliceosome for particular functions. Here, we review the current knowledge on the snRNA modification machinery and discuss the timing, functions and dynamics of modifications in snRNAs.

Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia.

PubMed

Florez, Helena; Mandelikova, Stanislava; Filella, Xavier; Monegal, Ana; Guañabens, Núria; Peris, Pilar

2017-12-30

Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Serum Concentrations of Trace Elements in Patients with Tuberculosis and Its Association with Treatment Outcome

PubMed Central

Choi, Rihwa; Kim, Hyoung-Tae; Lim, Yaeji; Kim, Min-Ji; Kwon, O Jung; Jeon, Kyeongman; Park, Hye Yun; Jeong, Byeong-Ho; Koh, Won-Jung; Lee, Soo-Youn

2015-01-01

Deficiencies in essential trace elements are associated with impaired immunity in tuberculosis infection. However, the trace element concentrations in the serum of Korean patients with tuberculosis have not yet been investigated. This study aimed to compare the serum trace element concentrations of Korean adult patients with tuberculosis with noninfected controls and to assess the impact of serum trace element concentration on clinical outcome after antituberculosis treatment. The serum concentrations of four trace elements in 141 consecutively recruited patients with tuberculosis and 79 controls were analyzed by inductively coupled plasma-mass spectrometry. Demographic characteristics were also analyzed. Serum cobalt and copper concentrations were significantly higher in patients with tuberculosis compared with controls, while zinc and selenium concentrations were significantly lower (p < 0.01). Moreover, serum selenium and zinc concentrations were positively correlated (ρ = 0.41, p < 0.05). A high serum copper concentration was associated with a worse clinical outcome, as assessed after one month of antituberculosis therapy. Specifically, culture-positive patients had higher serum copper concentrations than culture-negative patients (p < 0.05). Patients with tuberculosis had altered serum trace element concentrations. Further research is needed to elucidate the roles of individual trace elements and to determine their clinical impact on patients with tuberculosis. PMID:26197334

The relationship between oxidized serum albumin and blood pressure in hypoalbuminemic peritoneal dialysis patients.

PubMed

Hasan, Kamal; Hassan, Fadi; Michelis, Regina

2017-01-01

Oxidative stress produces molecular modifications of serum albumin that disturb its biological functions and interfere with its detection by the bromocresol green assay (BCG). Oxidative stress, inflammation, and hypoalbuminemia are common peritoneal dialysis (PD). This study aimed to evaluate the relationship between serum albumin, oxidized serum albumin (OSA), oncotic pressure, and blood pressure in hypoalbuminemic PD patients. Twenty-four PD patients with serum albumin levels <3.5 g/dl enrolled in the study. Data were compared between participants with the mean arterial pressure (MAP) <105 mmHg (n = 12) and MAP ≥ 105 mmHg (n = 12). Serum albumin levels were ≤3.0 g/dl and similar in both groups (p = 0.298). The calculated OSA and oncotic pressure were significantly higher in patients with MAP ≥ 105 mmHg than in those with MAP < 105 mmHg. MAP was positively and marginally correlated with serum albumin levels (measured by BCG) (r = 0.34, p = 0.05), and positively and significantly correlated with the calculated OSA and oncotic pressure (r = 0.44, p = 0.015, r = 0.58, p = 0.002; respectively). The oncotic pressure was positively correlated with the calculated OSA (r = 0.47, p = 0.011). OSA, undetectable by the commonly used BCG, may contribute to higher blood pressure in hypoalbuminemic PD patients.

Thermal aggregation of glycated bovine serum albumin.

PubMed

Rondeau, Philippe; Navarra, Giovanna; Cacciabaudo, Francesco; Leone, Maurizio; Bourdon, Emmanuel; Militello, Valeria

2010-04-01

Aggregation and glycation processes in proteins have a particular interest in medicine fields and in food technology. Serum albumins are model proteins which are able to self-assembly in aggregates and also sensitive to a non-enzymatic glycation in cases of diabetes. In this work, we firstly reported a study on the glycation and oxidation effects on the structure of bovine serum albumin (BSA). The experimental approach is based on the study of conformational changes of BSA at secondary and tertiary structures by FTIR absorption and fluorescence spectroscopy, respectively. Secondly, we analysed the thermal aggregation process on BSA glycated with different glucose concentrations. Additional information on the aggregation kinetics are obtained by light scattering measurements. The results show that glycation process affects the native structure of BSA. Then, the partial unfolding of the tertiary structure which accompanies the aggregation process is similar both in native and glycated BSA. In particular, the formation of aggregates is progressively inhibited with growing concentration of glucose incubated with BSA. These results bring new insights on how aggregation process is affected by modification of BSA induced by glycation. Copyright 2009 Elsevier B.V. All rights reserved.

Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

PubMed Central

2014-01-01

Background The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Methods Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Results Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Conclusion Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment

Impact of Dental Implant Surface Modifications on Osseointegration

PubMed Central

Smeets, Ralf; Stadlinger, Bernd; Schwarz, Frank; Beck-Broichsitter, Benedicta; Jung, Ole; Precht, Clarissa; Kloss, Frank; Gröbe, Alexander; Heiland, Max

2016-01-01

Objective. The aim of this paper is to review different surface modifications of dental implants and their effect on osseointegration. Common marketed as well as experimental surface modifications are discussed. Discussion. The major challenge for contemporary dental implantologists is to provide oral rehabilitation to patients with healthy bone conditions asking for rapid loading protocols or to patients with quantitatively or qualitatively compromised bone. These charging conditions require advances in implant surface design. The elucidation of bone healing physiology has driven investigators to engineer implant surfaces that closely mimic natural bone characteristics. This paper provides a comprehensive overview of surface modifications that beneficially alter the topography, hydrophilicity, and outer coating of dental implants in order to enhance osseointegration in healthy as well as in compromised bone. In the first part, this paper discusses dental implants that have been successfully used for a number of years focusing on sandblasting, acid-etching, and hydrophilic surface textures. Hereafter, new techniques like Discrete Crystalline Deposition, laser ablation, and surface coatings with proteins, drugs, or growth factors are presented. Conclusion. Major advancements have been made in developing novel surfaces of dental implants. These innovations set the stage for rehabilitating patients with high success and predictable survival rates even in challenging conditions. PMID:27478833

Cage Change Influences Serum Corticosterone and Anxiety-Like Behaviors in the Mouse

PubMed Central

Rasmussen, Skye; Miller, Melinda M.; Filipski, Sarah B.; Tolwani, Ravi J.

2011-01-01

Environmental variables and husbandry practices can influence physiology and alter behavior in mice. Our study evaluated the effects of cage change on serum corticosterone levels and anxiety-like behaviors in C57BL/6 male mice. We examined the effects of 3 different methods of performing cage transfer and of transferring mice to a clean or a dirty familiar cage microenvironment. The 3 different handling methods were forceps transfer, gentle transfer with gloved hands, and a passive transfer technique that did not involve active handling. Active handling methods and transfer to both clean and dirty cage microenvironments significantly increased serum corticosterone 15 min after cage change; however, at 60 min after cage change, levels were comparable to those of unmanipulated mice. Although the effects were transient, cage change altered anxiety-like behaviors in the open field when behavioral testing was performed on the same day. These results demonstrate that the timing of cage change can influence behavioral results, an effect that is an important consideration for rodent behavioral studies. PMID:21838975

Quadratic genetic modifications: a streamlined route to cosmological simulations with controlled merger history

NASA Astrophysics Data System (ADS)

Rey, Martin P.; Pontzen, Andrew

2018-02-01

Recent work has studied the interplay between a galaxy's history and its observable properties using `genetically modified' cosmological zoom simulations. The approach systematically generates alternative histories for a halo, while keeping its cosmological environment fixed. Applications to date altered linear properties of the initial conditions, such as the mean overdensity of specified regions; we extend the formulation to include quadratic features, such as local variance, that determines the overall importance of smooth accretion relative to mergers in a galaxy's history. We introduce an efficient algorithm for this new class of modification and demonstrate its ability to control the variance of a region in a one-dimensional toy model. Outcomes of this work are twofold: (i) a clarification of the formulation of genetic modifications and (ii) a proof of concept for quadratic modifications leading the way to a forthcoming implementation in cosmological simulations.

Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Stajszczyk, M; Wojakowski, W; Goss, M; Machalski, M; Telega, A; Brulinski, K; Magiera-Molendowska, H

2000-09-01

Cancer patients often present altered serum lipid profile including changes of HDL cholesterol level. The aim of our work was to evaluate serum level of HDL cholesterol in patients with squamous cell and small cell lung cancer and its dependence on histological type and clinical stage of lung cancer. Fasting serum level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung cancer and compared to a control group of healthy men. All lung cancer patients, as well as subgroups of squamous cell and small cell lung cancer had statistically significantly lower HDL cholesterol concentration than controls. There were no statistically significant differences of HDL cholesterol level between the histological types or between clinical stages of each histological type of lung cancer.

Ca-Fe and Alkali-Halide Alteration of an Allende Type B CAI: Aqueous Alteration in Nebular or Asteroidal Settings

NASA Technical Reports Server (NTRS)

Ross, D. K.; Simon, J. I.; Simon, S. B.; Grossman, L.

2012-01-01

Ca-Fe and alkali-halide alteration of CAIs is often attributed to aqueous alteration by fluids circulating on asteroidal parent bodies after the various chondritic components have been assembled, although debate continues about the roles of asteroidal vs. nebular modification processes [1-7]. Here we report de-tailed observations of alteration products in a large Type B2 CAI, TS4 from Allende, one of the oxidized subgroup of CV3s, and propose a speculative model for aqueous alteration of CAIs in a nebular setting. Ca-Fe alteration in this CAI consists predominantly of end-member hedenbergite, end-member andradite, and compositionally variable, magnesian high-Ca pyroxene. These phases are strongly concentrated in an unusual "nodule" enclosed within the interior of the CAI (Fig. 1). The Ca, Fe-rich nodule superficially resembles a clast that pre-dated and was engulfed by the CAI, but closer inspection shows that relic spinel grains are enclosed in the nodule, and corroded CAI primary phases interfinger with the Fe-rich phases at the nodule s margins. This CAI also contains abundant sodalite and nepheline (alkali-halide) alteration that occurs around the rims of the CAI, but also penetrates more deeply into the CAI. The two types of alteration (Ca-Fe and alkali-halide) are adjacent, and very fine-grained Fe-rich phases are associated with sodalite-rich regions. Both types of alteration appear to be replacive; if that is true, it would require substantial introduction of Fe, and transport of elements (Ti, Al and Mg) out of the nodule, and introduction of Na and Cl into alkali-halide rich zones. Parts of the CAI have been extensively metasomatized.

Chromite alteration processes within Vourinos ophiolite

NASA Astrophysics Data System (ADS)

Grieco, Giovanni; Merlini, Anna

2012-09-01

The renewed interest in chromite ore deposits is directly related to the increase in Cr price ruled by international market trends. Chromite, an accessory mineral in peridotites, is considered to be a petrogenetic indicator because its composition reflects the degree of partial melting that the mantle experienced while producing the chromium spinel-bearing rock (Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993). However, the understanding of chromite alteration and metamorphic modification is still controversial (e.g. Evans and Frost in Geochim Cosmochim Acta 39:959-972, 1975; Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993; Oze et al. in Am J Sci 304:67-101, 2004). Metamorphic alteration leads to major changes in chromite chemistry and to the growth of secondary phases such as ferritchromite and chlorite. In this study, we investigate the Vourinos complex chromitites (from the mines of Rizo, Aetoraches, Xerolivado and Potamia) with respect to textural and chemical analyses in order to highlight the most important trend of alteration related to chromite transformation. The present study has been partially funded by the Aliakmon project in collaboration between the Public Power Corporation of Greece and Institute of Geology and Mineral Exploration of Kozani.

RNA major groove modifications improve siRNA stability and biological activity

PubMed Central

Terrazas, Montserrat; Kool, Eric T.

2009-01-01

RNA 5-methyl and 5-propynyl pyrimidine analogs were substituted into short interfering RNAs (siRNAs) to probe major groove steric effects in the active RNA-induced silencing complex (RISC). Synthetic RNA guide strands containing varied combinations of propynyl and methyl substitution revealed that all C-5 substitutions increased the thermal stability of siRNA duplexes containing them. Cellular gene suppression experiments using luciferase targets in HeLa cells showed that the bulky 5-propynyl modification was detrimental to RNA interference activity, despite its stabilization of the helix. Detrimental effects of this substitution were greatest at the 5′-half of the guide strand, suggesting close steric approach of proteins in the RISC complex with that end of the siRNA/mRNA duplex. However, substitutions with the smaller 5-methyl group resulted in gene silencing activities comparable to or better than that of wild-type siRNA. The major groove modifications also increased the serum stability of siRNAs. PMID:19042976

Post-translational modifications of transthyretin affect the triiodonine-binding potential

PubMed Central

Henze, Andrea; Homann, Thomas; Serteser, Mustafa; Can, Ozge; Sezgin, Ozlem; Coskun, Abdurrahman; Unsal, Ibrahim; Schweigert, Florian J; Ozpinar, Aysel

2015-01-01

Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10), which is frequently affected by oxidative post-translational modifications. As Cys10 is part of the thyroid hormone-binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype- and site-specific manner with S-glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function-specific patterns of TTR with a substantial decrease in S-sulphonated, S-cysteinylglycinated and S-glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability. PMID:25311081

Dietary polyunsaturated fatty acids and adaptation to chronic hypoxia alter acyl composition of serum and heart lipids.

PubMed

Balková, Patricie; Jezková, Jana; Hlavácková, Markéta; Neckár, Jan; Stanková, Barbora; Kolár, Frantisek; Novák, Frantisek; Nováková, Olga

2009-11-01

The effects of dietary supplementation with fat of different fatty acid profile and chronic intermittent hypoxia (CIH) on the fatty acid composition of serum and heart lipids were analysed. Adult male Wistar rats were fed a standard non-fat diet enriched with 10 % of lard, fish oil (n-3 PUFA) or maize oil (n-6 PUFA) for 10 weeks. After 4 weeks on the diets, each group was divided in two subgroups, either exposed to CIH in a barochamber (7000 m, twenty-five exposures) or kept at normoxia. In normoxic rats, the fish oil diet increased the level of conjugated dienes. The n-6:n-3 PUFA ratio in serum TAG, phospholipids (PL), cholesteryl esters (CE) and heart TAG, PL and diacylglycerols (DAG) followed the ratio in the fed diet (in the sequence maize oil>lard>fish oil). In heart TAG, PL and DAG, 20 : 4n-6 and 18 : 2n-6 were replaced by 22 : 6n-3 in the fish oil group. The main fatty acid in CE was 20 : 4n-6 in the lard and maize oil groups whereas in the fish oil group, half of 20 : 4n-6 was replaced by 20 : 5n-3. CIH further increased 20 : 5n-3 in CE in the fish oil group. CIH decreased the n-6:n-3 PUFA ratio in serum CE, heart TAG, PL and DAG in all dietary groups and stimulated the activity of catalase in the maize and fish oil groups. In conclusion, PUFA diets and CIH, both interventions considered to be cardioprotective, distinctly modified the fatty acid profile in serum and heart lipids with specific effects on conjugated diene production and catalase activity.

[Association between serum zinc level and hypercholesterolemia and insulin resistance in Brazilian children].

PubMed

Albuquerque, Fernanda Martins de; Filgueiras, Mariana De Santis; Rocha, Naruna Pereira; Castro, Ana Paula Pereira; Milagres, Luana Cupertino; Pessoa, Milene Cristine; Fransceschini, Sylvia do Carmo Castro; Novaes, Juliana Farias de

2018-02-05

The objective of the study was to assess the association between serum zinc level and cardiometabolic factors in prepubertal Brazilian children. This was a cross-sectional study in a representative sample of schoolchildren 8 to 9 years of age in public and private urban schools in Viçosa, Minas Gerais State, Brazil. Body composition was assessed with dual-energy x-ray absorptiometry. The study measured serum glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides, apolipoproteins A (Apo A) and B, uric acid, leptin, homocysteine, ultrasenstive C-reactive protein, and serum zinc. Arterial pressure was measured with automatic inflation equipment. Zinc deficiency was observed in 1.3% of the children. Girls showed the worst cardiometabolic profile, with higher prevalence of increased android fat, triglycerides, insulin resistance, leptin, zinc, and Apo A. In the first tertile of serum zinc concentration, prevalence of insulin resistance was 96% higher (PR = 1.96; 95%CI: 1.04-3.66) and hypercholesterolemia was 23% lower (PR = 0.77; 95%CI: 0.61-0.96) than in the reference category (grouped 2nd and 3rd tertiles of serum zinc concentration). Despite the low prevalence of zinc deficiency, insulin resistance was more prevalent in children in the lowest third of serum zinc concentration. It is important to prevent cardiometabolic alterations in childhood, especially insulin resistance, with an emphasis on serum zinc level.

Modification of the classical Lancefield assay of group A streptococcal killing to reduce inter-donor variation.

PubMed

Reglinski, Mark; Lynskey, Nicola N; Sriskandan, Shiranee

2016-05-01

The lack of a surrogate-of-immunity assay presents a major barrier to Streptococcus pyogenes research. Modification of the Lancefield assay to include an antibody digestion step reduced inter-donor variation and permitted detection of the anti-streptococcal activity of intravenous immunoglobulin and convalescent serum, thus facilitating retrospective evaluation of immunity using stored samples. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Serum lipoprotein changes in dogs with renal disease.

PubMed

Behling-Kelly, E

2014-01-01

People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated. Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high-density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration. Prospective study of client-owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students. Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein-to-creatinine ratio were measured by standard methods. Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD. Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study. Copyright © 2014 by the American College of Veterinary Internal Medicine.

BSA modification to reduce CTAB induced nonspecificity and cytotoxicity of aptamer-conjugated gold nanorods

NASA Astrophysics Data System (ADS)

Yasun, Emir; Li, Chunmei; Barut, Inci; Janvier, Denisse; Qiu, Liping; Cui, Cheng; Tan, Weihong

2015-05-01

Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells.Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications

Serum-based diagnostic prediction of oral submucous fibrosis using FTIR spectrometry

NASA Astrophysics Data System (ADS)

Rai, Vertika; Mukherjee, Rashmi; Routray, Aurobinda; Ghosh, Ananta Kumar; Roy, Seema; Ghosh, Barnali Paul; Mandal, Puspendu Bikash; Bose, Surajit; Chakraborty, Chandan

2018-01-01

Oral submucous fibrosis (OSF) is found to have the highest malignant potentiality among all other pre-cancerous lesions. However, its detection prior to tissue biopsy can be challenging in clinics. Moreover, biopsy examination is invasive and painful. Hence, there is an urgent need of new technology that facilitates accurate diagnostic prediction of OSF prior to biopsy. Here, we used FTIR spectroscopy coupled with chemometric techniques to distinguish the serum metabolic signatures of OSF patients (n = 30) and healthy controls (n = 30). Serum biochemical analyses have been performed to further support the FTIR findings. Absorbance intensities of 45 infrared wavenumbers differed significantly between OSF and normal serum FTIR spectra representing alterations in carbohydrates, proteins, lipids and nucleic acids. Nineteen prominent significant wavenumbers (P ≤ 0.001) at 1020, 1025, 1035, 1039, 1045, 1078, 1055, 1100, 1117, 1122, 1151, 1169, 1243, 1313, 1398, 1453, 1544, 1650 and 1725 cm- 1 provided excellent segregation of OSF spectra from normal using multivariate statistical techniques. These findings provided essential information on the metabolic features of blood serum of OSF patients and established that FTIR spectroscopy coupled with chemometric analysis can be potentially useful in the rapid and accurate preoperative screening/diagnosis of OSF.

Antidepressant-Like Effects of Acupuncture-Insights From DNA Methylation and Histone Modifications of Brain-Derived Neurotrophic Factor.

PubMed

Jiang, Huili; Zhang, Xuhui; Lu, Jun; Meng, Hong; Sun, Yang; Yang, Xinjing; Zhao, Bingcong; Bao, Tuya

2018-01-01

Sensitive and stable biomarkers that facilitate depression detection and monitor the antidepressant efficiency are currently unavailable. Thus, the objective is to investigate the potential of DNA methylation and histone modifications of brain-derived neurotrophic factor (BDNF) in monitoring severity and antidepressive effects of acupuncture. The depression rat model was imitated by social isolation and chronic unpredicted mild stress (CUMS). The expression of serum BDNF was detected by enzyme-linked immunosorbent assay (ELISA), the hippocampal BDNF, acetylation levels in histone H3 lysine 9 (acH3K9), and HDAC2 by Western blot, the hippocampal mRNA of BDNF by RT-polymerase chain reaction (PCR). The DNA methylation patterns of the promoter I of BDNF was detected by MS-PCR. We investigated that the expression of BDNF in serum and hippocampus were significantly downregulated compared with controls. The same trend was found in mRNA of BDNF. Notably, acupuncture reversed the downregulation of BDNF in serum and hippocampus and mRNA of BDNF compared with model group. Acupuncture reversed the CUMS-induced downregulation of hippocampal acH3K9. On the contrary, the CUMS-induced upregulation of hippocampal HDAC2 in model group was significantly reversed by acupuncture. Collectively, the antidepressant effect of acupuncture might be mediated by regulating the DNA methylation and histone modifications of BDNF, which may represent novel biomaker for detection of depression and monitoring severity and antidepressive effects.

Cell Wall Modifications in Arabidopsis Plants with Altered α-l-Arabinofuranosidase Activity[C][W

PubMed Central

Chávez Montes, Ricardo A.; Ranocha, Philippe; Martinez, Yves; Minic, Zoran; Jouanin, Lise; Marquis, Mélanie; Saulnier, Luc; Fulton, Lynette M.; Cobbett, Christopher S.; Bitton, Frédérique; Renou, Jean-Pierre; Jauneau, Alain; Goffner, Deborah

2008-01-01

Although cell wall remodeling is an essential feature of plant growth and development, the underlying molecular mechanisms are poorly understood. This work describes the characterization of Arabidopsis (Arabidopsis thaliana) plants with altered expression of ARAF1, a bifunctional α-l-arabinofuranosidase/β-d-xylosidase (At3g10740) belonging to family 51 glycosyl-hydrolases. ARAF1 was localized in several cell types in the vascular system of roots and stems, including xylem vessels and parenchyma cells surrounding the vessels, the cambium, and the phloem. araf1 T-DNA insertional mutants showed no visible phenotype, whereas transgenic plants that overexpressed ARAF1 exhibited a delay in inflorescence emergence and altered stem architecture. Although global monosaccharide analysis indicated only slight differences in cell wall composition in both mutant and overexpressing lines, immunolocalization experiments using anti-arabinan (LM6) and anti-xylan (LM10) antibodies indicated cell type-specific alterations in cell wall structure. In araf1 mutants, an increase in LM6 signal intensity was observed in the phloem, cambium, and xylem parenchyma in stems and roots, largely coinciding with ARAF1 expression sites. The ectopic overexpression of ARAF1 resulted in an increase in LM10 labeling in the secondary walls of interfascicular fibers and xylem vessels. The combined ARAF1 gene expression and immunolocalization studies suggest that arabinan-containing pectins are potential in vivo substrates of ARAF1 in Arabidopsis. PMID:18344421

Bulk- and surface-modified combinable PDMS capillary sensor array as an easy-to-use sensing device with enhanced sensitivity to elevated concentrations of multiple serum sample components.

PubMed

Fujii, Yuji; Henares, Terence G; Kawamura, Kunio; Endo, Tatsuro; Hisamoto, Hideaki

2012-04-21

To enhance sensitivity and facilitate easy sample introduction into a combinable poly(dimethylsiloxane) (PDMS) capillary (CPC) sensor array, PDMS was modified in bulk and on its surface to prepare "black" PDMS coated with a silver layer and self-assembled monolayer (SAM). India ink, a traditional Japanese black ink, was added to the PDMS pre-polymer for bulk modification. The surface was modified by a silver mirror reaction followed by SAM formation using cysteine. These modifications enhanced the fluorescence signals by reflecting them from the surface and reducing background interference. A decrease in the water contact angle led to enhanced sensitivity and easy sample introduction. Furthermore, a CPC sensor array for multiplex detection of serum sample components was prepared that could quantify the analytes glucose, potassium, and alkaline phosphatase (ALP). When serum samples were introduced by capillary action, the CPC sensor array showed fluorescence responses for each analyte and successfully identified the components with elevated concentrations in the serum samples.

Serum trace elements in obese women with or without diabetes

PubMed Central

Yerlikaya, F. Hümeyra; Toker, Aysun; Arıbaş, Alpay

2013-01-01

Background & objectives: Relationship of trace elements with obesity and diabetes is complex, alterations in their metabolism can be induced by the diseases and their complications. To study the role of the trace elements in diabetes and obesity, serum trace elements levels (Cr, Se, Fe, Zn, Cu and Mn) were measured in obese women with or without diabetes as well as healthy women. Further, correlation between serum trace elements levels and glucose, insulin, homeostasis model assessment (HOMA-IR), glycated haemoglobin (HbA1c), body mass index (BMI), waist circumferences, waist -to -hip ratio and high-sensitivity C-reactive protein(hsCRP) were also determined in these women. Methods: This study was performed with morbidly obese (BMI >40 kg/m2) women with diabetes (n=41), without diabetes (n=45) and 50 healthly non obese women. Anthropometric measurements were taken and levels of serum Zn, Cr, Fe Cu and Mn were determined. Biochemical parameters included serum glucose, insulin, lipids, haemoglobin, hsCRP and HbA1C. Results: The levels of Zn (P<0.001), Mn (P<0.05), Fe (P<0.05) were significantly lower and the level of Cu (P<0.001) and Cu / Zn ratio (P<0.05) were significantly higher in the diabetic obese women than those of the healthy women. Also, the levels of Zn and Fe were significantly lower and the levels of Cu were significantly higher in the non diabetic obese women than those of the healthy group. Serum Zn levels negatively and serum Cu levels positively correlated with anthropometric values in diabetic and non diabetic obese women. Further, serum Zn, Mn and Cr levels negatively correlated and serum Se levels positively correlated glycaemia control parameters in diabetic obese women. In addition, serum Zn levels negatively correlated with hsCRP in diabetic and nondiabetic obese females. Interpretation & conclusions: Our findings showed significant association between Zn and Fe deficiencies and obesity. Also, obese women with diabetes may be at a greater risk

Modifications to particles as they move through landscapes: connecting soils and sediments

NASA Astrophysics Data System (ADS)

Owens, Philip N.

2016-04-01

In many areas of the world, soils are eroded leading to the movement of particles towards the global ocean. Along this journey, there are modifications to these particles and we tend to refer to this altered material as sediment in recognition that such material may no longer be fully reflective of its source. These modifications are brought about by physical, chemical and biological processes, and by the inclusion of additional sources of material, such as channel banks. The degree of modification is partly a function of the inherent properties of the original soil material but also reflects landscape type, and the temporal and spatial scales of investigation. This presentation will consider the changes in particles between soil profiles and sediment transported in river systems, drawing on examples from studies in Canada and beyond. It is hoped that by understanding the transformation of such material we can predict better its movement and impacts.

UC/MALDI-MS analysis of HDL; evidence for density-dependent post-translational modifications

NASA Astrophysics Data System (ADS)

Johnson, Jeffery D.; Henriquez, Ronald R.; Tichy, Shane E.; Russell, David H.; McNeal, Catherine J.; Macfarlane, Ronald D.

2007-12-01

The purpose of this study is to determine whether the nature of the post-translational modifications of the major apolipoproteins of HDL is different for density-distinct subclasses. These subclasses were separated by ultracentrifugation using a novel density-forming solute to yield a high-resolution separation. The serum of two subjects, a control with a normolipidemic profile and a subject with diagnosed cardiovascular disease, was studied. Aliquots of three HDL subclasses were analyzed by MALDI and considerable differences were seen when comparing density-distinct subclasses and also when comparing the two subjects. A detailed analysis of the post-translational modification pattern of apoA-1 shows evidence of considerable protease activity, particularly in the more dense fractions. We conclude that part of the heterogeneity of the population of HDL particles is due to density-dependent protease activity.

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

PubMed

Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2 , known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

PubMed Central

Rompala, Gregory R.; Mounier, Anais; Wolfe, Cody M.; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E.

2018-01-01

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

PubMed

Chauhan, Abhishek; Yadav, Suraj Singh; Dwivedi, Pradeep; Lal, Nand; Usman, Kauser; Khattri, Sanjay

2016-09-01

Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD. © 2016 Wiley Periodicals, Inc.

Lower serum oestrogen concentrations associated with faster intestinal transit.

PubMed Central

Lewis, S. J.; Heaton, K. W.; Oakey, R. E.; McGarrigle, H. H.

1997-01-01

Increased fibre intake has been shown to reduce serum oestrogen concentrations. We hypothesized that fibre exerts this effect by decreasing the time available for reabsorption of oestrogens in the colon. We tested this in volunteers by measuring changes in serum oestrogen levels in response to manipulation of intestinal transit times with senna and loperamide, then comparing the results with changes caused by wheat bran. Forty healthy premenopausal volunteers were placed at random into one of three groups. The first group took senna for two menstrual cycles then, after a washout period, took wheat bran, again for two menstrual cycles. The second group did the reverse. The third group took loperamide for two menstrual cycles. At the beginning and end of each intervention a 4-day dietary record was kept and whole-gut transit time was measured; stools were taken for measurement of pH and beta-glucuronidase activity and blood for measurement of oestrone and oestradiol and their non-protein-bound fractions and of oestrone sulphate. Senna and loperamide caused the intended alterations in intestinal transit, whereas on wheat bran supplements there was a trend towards faster transit. Serum oestrone sulphate fell with wheat bran (mean intake 19.8 g day(-1)) and with senna; total- and non-protein-bound oestrone fell with senna. No significant changes in serum oestrogens were seen with loperamide. No significant changes were seen in faecal beta-glucuronidase activity. Stool pH changed only with senna, in which case it fell. In conclusion, speeding up intestinal transit can lower serum oestrogen concentrations. PMID:9252210

Evaluation of Aspergillus PCR Protocols for Testing Serum Specimens▿†

PubMed Central

White, P. Lewis; Mengoli, Carlo; Bretagne, Stéphane; Cuenca-Estrella, Manuel; Finnstrom, Niklas; Klingspor, Lena; Melchers, Willem J. G.; McCulloch, Elaine; Barnes, Rosemary A.; Donnelly, J. Peter; Loeffler, Juergen

2011-01-01

A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance. PMID:21940479

Comparative epigenetic influence of autologous versus fetal bovine serum on mesenchymal stem cells through in vitro osteogenic and adipogenic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fani, Nesa; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran

Mesenchymal stem cells (MSCs) derived from bone marrow (BM) represents a useful source of adult stem cells for cell therapy and tissue engineering. MSCs are present at a low frequency in the BM; therefore expansion is necessary before performing clinical studies. Fetal bovine serum (FBS) as a nutritional supplement for in vitro culture of MSCs is a suitable additive for human cell culture, but not regarding subsequent use of these cells for clinical treatment of human patients due to the risk of viral and prion transmission as well as xenogeneic immune responses after transplantation. Recently, autologous serum (AS) has beenmore » as a supplement to replace FBS in culture medium. We compared the effect of FBS versus AS on the histone modification pattern of MSCs through in vitro osteogenesis and adipogenesis. Differentiation of stem cells under various serum conditions to a committed state involves global changes in epigenetic patterns that are critically determined by chromatin modifications. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR showed significant changes in the acetylation and methylation patterns in lysine 9 (Lys9) of histone H3 on the regulatory regions of stemness (Nanog, Sox2, Rex1), osteogenic (Runx2, Oc, Sp7) and adipogenic (Ppar-γ, Lpl, adiponectin) marker genes in undifferentiated MSCs, FBS and AS. All epigenetic changes occurred in a serum dependent manner which resulted in higher expression level of stemness genes in undifferentiated MSCs compared to differentiated MSCs and increased expression levels of osteogenic genes in AS compared to FBS. Adipogenic genes showed greater expression in FBS compared to AS. These findings have demonstrated the epigenetic influence of serum culture conditions on differentiation potential of MSCs, which suggest that AS is possibly more efficient serum for osteogenic differentiation of MSCs in cell therapy purposes. - Highlights: • Bone marrow derived MSC could proliferate in AS as well as

Muscle force modification strategies are not consistent for gait retraining to reduce the knee adduction moment in individuals with knee osteoarthritis.

PubMed

Shull, Peter B; Huang, Yangjian; Schlotman, Taylor; Reinbolt, Jeffrey A

2015-09-18

While gait retraining paradigms that alter knee loads typically focus on modifying kinematics, the underlying muscle force modifications responsible for these kinematic changes remain largely unknown. As humans are generally thought to select uniform gait muscle patterns such as strategies based on fatigue cost functions or energy minimization, we hypothesized that a kinematic gait change known to reduce the knee adduction moment (i.e. toe-in gait) would be accompanied by a uniform muscle force modification strategy for individuals with symptomatic knee osteoarthritis. Ten subjects with self-reported knee pain and radiographic evidence of medial compartment knee osteoarthritis performed normal gait and toe-in gait modification walking trials. Two hundred muscle-actuated dynamic simulations (10 steps for normal gait and 10 steps from toe-in gait for each subject) were performed to determine muscle forces for each gait. Results showed that subjects internally rotated their feet during toe-in gait, which decreased the foot progression angle by 7° (p<0.01) and reduced the first peak knee adduction moment by 20% (p<0.01). While significant muscle force modifications were evidenced within individuals, there were no consistent muscle force modifications across all subjects. It may be that self-selected muscle pattern changes are not uniform for gait modification particularly for individuals with knee pain. Future studies focused on altering knee loads should not assume consistent muscle force modifications for a given kinematic gait change across subjects and should consider muscle forces in addition to kinematics in gait retraining paradigms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of serum cobalamin concentrations in dogs of 164 dog breeds (2006-2010).

PubMed

Grützner, Niels; Cranford, Shannon M; Norby, Bo; Suchodolski, Jan S; Steiner, Jörg M

2012-11-01

Altered serum cobalamin concentrations have been observed in dogs with gastrointestinal disorders such as exocrine pancreatic insufficiency (EPI) or gastrointestinal inflammation. The aims of the current study were 1) to identify breeds with a higher proportion of dogs with a decreased serum cobalamin concentration, 2) to determine whether dogs with such decreased concentrations tend to have serum canine trypsin-like immunoreactivity (cTLI) concentrations diagnostic for EPI, and 3) to compare the number of submissions for serum cobalamin analysis by breed to the American Kennel Club (AKC) breed ranking list of 2009. In this retrospective study, results of 28,675 cobalamin tests were reviewed. Akitas, Chinese Shar-Peis, German Shepherd Dogs, Greyhounds, and Labrador Retrievers had increased proportions of serum cobalamin concentrations below the lower limit of the reference interval (<251 ng/l; all P < 0.0001). Akitas, Chinese Shar-Peis, German Shepherd Dogs, and Border Collies had increased proportions of serum cobalamin concentrations below the detection limit of the assay (<150 ng/l; all P < 0.0001). Akitas, Border Collies, and German Shepherd Dogs with serum cobalamin concentrations <150 ng/l were more likely to have a serum cTLI concentration considered diagnostic for EPI (≤2.5 µg/l; all P ≤ 0.001). The breed with the highest proportion of samples submitted for serum cobalamin analysis in comparison with the AKC ranking list was the Greyhound (odds ratio: 84.6; P < 0.0001). In Akitas and Border Collies, further investigations are warranted to clarify if a potentially breed-specific gastrointestinal disorder is responsible for the increased frequency of decreased serum cobalamin and cTLI concentrations.

Serum potassium, mortality, and kidney outcomes in the Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Chen, Yan; Chang, Alex R.; McAdams DeMarco, Mara A.; Inker, Lesley A.; Matsushita, Kunihiro; Ballew, Shoshana H.; Coresh, Josef; Grams, Morgan E.

2017-01-01

Objectives To investigate the association between serum potassium, mortality, and kidney outcomes in the general population and whether potassium-altering medications modify these associations. Patients and Methods We studied 15,539 adults in the Atherosclerosis Risk in Communities (ARIC) study. Cox proportional hazard regression was used to investigate the association of serum potassium at baseline (1987–1989), evaluated categorically (hypokalemia, <3.5 mmol/L; normokalemia, ≥3.5 and < 5.5 mmol/L; hyperkalemia, ≥5.5 mmol/L) and continuously using linear spline terms (knots at 3.5 and 5.5 mmol/L), with mortality, sudden cardiac death (SCD), incident chronic kidney disease (CKD), and end-stage renal disease (ESRD). The end date of follow up for all outcomes was December 31, 2012. We also evaluated whether classes of potassium-altering medications modified the association between serum potassium and adverse outcomes. Results Overall, 2.7% of the participants had hypokalemia and 2.1% had hyperkalemia. In a fully adjusted model, hyperkalemia was significantly associated with mortality (HR: 1.24; 95% CI: 1.04–1.49) but not SCD, CKD, or ESRD. Hypokalemia as a categorical variable was not associated with any outcome; however, associations of hypokalemia with all-cause mortality and kidney outcomes were observed among those who were not taking potassium-wasting diuretics (all P for interaction <.001). Conclusions Higher values of serum potassium were associated with higher risk of mortality in the general population. Lower levels of potassium were associated with adverse kidney outcomes and mortality among participants not taking potassium-wasting diuretics. PMID:27499535

RNomics and Modomics in the halophilic archaea Haloferax volcanii: identification of RNA modification genes

PubMed Central

Grosjean, Henri; Gaspin, Christine; Marck, Christian; Decatur, Wayne A; de Crécy-Lagard, Valérie

2008-01-01

Background Naturally occurring RNAs contain numerous enzymatically altered nucleosides. Differences in RNA populations (RNomics) and pattern of RNA modifications (Modomics) depends on the organism analyzed and are two of the criteria that distinguish the three kingdoms of life. If the genomic sequences of the RNA molecules can be derived from whole genome sequence information, the modification profile cannot and requires or direct sequencing of the RNAs or predictive methods base on the presence or absence of the modifications genes. Results By employing a comparative genomics approach, we predicted almost all of the genes coding for the t+rRNA modification enzymes in the mesophilic moderate halophile Haloferax volcanii. These encode both guide RNAs and enzymes. Some are orthologous to previously identified genes in Archaea, Bacteria or in Saccharomyces cerevisiae, but several are original predictions. Conclusion The number of modifications in t+rRNAs in the halophilic archaeon is surprisingly low when compared with other Archaea or Bacteria, particularly the hyperthermophilic organisms. This may result from the specific lifestyle of halophiles that require high intracellular salt concentration for survival. This salt content could allow RNA to maintain its functional structural integrity with fewer modifications. We predict that the few modifications present must be particularly important for decoding, accuracy of translation or are modifications that cannot be functionally replaced by the electrostatic interactions provided by the surrounding salt-ions. This analysis also guides future experimental validation work aiming to complete the understanding of the function of RNA modifications in Archaeal translation. PMID:18844986

Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels.

PubMed

Wójcik, Jacek; Dudek, Dominika; Schlegel-Zawadzka, Małgorzata; Grabowska, Mariola; Marcinek, Antoni; Florek, Ewa; Piekoszewski, Wojciech; Nowak, Rafał J; Opoka, Włodzimierz; Nowak, Gabriel

2006-01-01

In the present study, we investigated the relationship between depressive symptoms and serum zinc and magnesium level in antepartum and postpartum women. All women received standard vitamin, zinc and magnesium supplementation. Sixty-six pregnant women in the Czerwiakowski Hospital in Kraków were assessed for prepartum depressive symptoms using the Beck Depression Inventory (BDI). Sixty-two and fifty-eight women were also assessed for postpartum depressive symptoms (using Edinburgh Postnatal Depression Rating Scale, EPDRS) at 3 and 30 days after delivery, respectively. Serum zinc and magnesium levels were also determined at these time points, however, the number of examined subjects were diminished. A significantly higher EPDRS score (by 45%), indicating severity of depressive symptoms, was found on the 3rd day after childbirth compared with the 30th postpartum day. Moreover, the early post-delivery period (3rd day) was characterized by a 24% lower serum zinc concentration than that found on the 30th day after childbirth. BDI scores assessed a month before childbirth revealed mild depressive symptoms, which was accompanied by a serum zinc concentration similar to that found on the 3rd day after delivery. No significant alterations were found in the magnesium levels between these time points. The present results demonstrated a relationship between severity of depressive symptoms and decreased serum zinc (but not magnesium) concentration in a very specific type of affective disorder, the postpartum depression.

Serum decoy receptor 3 level: a predictive marker for nodal metastasis and survival among oral cavity cancer patients.

PubMed

Tu, Hsi-Feng; Liu, Chung-Ji; Liu, Shyun-Yeu; Chen, Yu-Ping; Yu, En-Hao; Lin, Shu-Chun; Chang, Kuo-Wei

2011-03-01

Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression. Copyright © 2010 Wiley Periodicals, Inc.

Modification of orthogonal tRNAs: unexpected consequences for sense codon reassignment.

PubMed

Biddle, Wil; Schmitt, Margaret A; Fisk, John D

2016-12-01

Breaking the degeneracy of the genetic code via sense codon reassignment has emerged as a way to incorporate multiple copies of multiple non-canonical amino acids into a protein of interest. Here, we report the modification of a normally orthogonal tRNA by a host enzyme and show that this adventitious modification has a direct impact on the activity of the orthogonal tRNA in translation. We observed nearly equal decoding of both histidine codons, CAU and CAC, by an engineered orthogonal M. jannaschii tRNA with an AUG anticodon: tRNA Opt We suspected a modification of the tRNA Opt AUG anticodon was responsible for the anomalous lack of codon discrimination and demonstrate that adenosine 34 of tRNA Opt AUG is converted to inosine. We identified tRNA Opt AUG anticodon loop variants that increase reassignment of the histidine CAU codon, decrease incorporation in response to the histidine CAC codon, and improve cell health and growth profiles. Recognizing tRNA modification as both a potential pitfall and avenue of directed alteration will be important as the field of genetic code engineering continues to infiltrate the genetic codes of diverse organisms. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Brief communication: Artificial cranial modification in Kow Swamp and Cohuna.

PubMed

Durband, Arthur C

2014-09-01

The crania from Kow Swamp and Cohuna have been important for a number of debates in Australian paleoanthropology. These crania typically have long, flat foreheads that many workers have cited as evidence of genetic continuity with archaic Indonesian populations, particularly the Ngandong sample. Other scientists have alleged that at least some of the crania from Kow Swamp and the Cohuna skull have been altered through artificial modification, and that the flat foreheads possessed by these individuals are not phylogenetically informative. In this study, several Kow Swamp crania and Cohuna are compared to known modified and unmodified comparative samples. Canonical variates analyses and Mahalanobis distances are generated, and random expectation statistics are used to calculate statistical significance for these tests. The results of this study agree with prior work indicating that a portion of this sample shows evidence for artificial modification of the cranial vault. Many Kow Swamp crania and Cohuna display shape similarities with a population of known modified individuals from New Britain. Kow Swamp 1, 5, and Cohuna show the strongest evidence for modification, but other individuals from this sample also show evidence of culturally manipulated changes in cranial shape. This project provides added support for the argument that at least some Pleistocene Australian groups were practicing artificial cranial modification, and suggests that caution should be used when including these individuals in phylogenetic studies. Copyright © 2014 Wiley Periodicals, Inc.

Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors.

PubMed

Olson, Michael F

2018-05-04

The 20 members of the Rho GTPase family are key regulators of a wide-variety of biological activities. In response to activation, they signal via downstream effector proteins to induce dynamic alterations in the organization of the actomyosin cytoskeleton. In this review, post-translational modifications, mechanisms of dysregulation identified in human pathological conditions, and the ways that Rho GTPases might be targeted for chemotherapy will be discussed.

Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes

NASA Astrophysics Data System (ADS)

Ku, Ming-Chun; Fang, Chieh-Ming; Cheng, Juei-Tang; Liang, Huei-Chen; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Chiao-Chen; Tai, Jung-Hsiang; Chen, Shu-Hui

2016-06-01

Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.

Serum Potassium, Mortality, and Kidney Outcomes in the Atherosclerosis Risk in Communities Study.

PubMed

Chen, Yan; Chang, Alex R; McAdams DeMarco, Mara A; Inker, Lesley A; Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef; Grams, Morgan E

2016-10-01

To investigate the association between serum potassium, mortality, and kidney outcomes in the general population and whether potassium-altering medications modify these associations. We studied 15,539 adults in the Atherosclerosis Risk in Communities Study. Cox proportional hazard regression was used to investigate the association of serum potassium at baseline (1987-1989), evaluated categorically (hypokalemia, <3.5 mmol/L; normokalemia, ≥3.5 and <5.5 mmol/L; hyperkalemia, ≥5.5 mmol/L) and continuously using linear spline terms (knots at 3.5 and 5.5 mmol/L), with mortality, sudden cardiac death, incident chronic kidney disease, and end-stage renal disease. The end date of follow-up for all outcomes was December 31, 2012. We also evaluated whether classes of potassium-altering medications modified the association between serum potassium and adverse outcomes. Overall, 413 (2.7%) of the participants had hypokalemia and 321 (2.1%) had hyperkalemia. In a fully adjusted model, hyperkalemia was significantly associated with mortality (hazard ratio, 1.24; 95% CI, 1.04-1.49) but not sudden cardiac death, chronic kidney disease, or end-stage renal disease. Hypokalemia as a categorical variable was not associated with any outcome; however, associations of hypokalemia with all-cause mortality and kidney outcomes were observed among those who were not taking potassium-wasting diuretics (all P for interaction, <.001). Higher values of serum potassium were associated with a higher risk of mortality in the general population. Lower levels of potassium were associated with adverse kidney outcomes and mortality among participants not taking potassium-wasting diuretics. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Ambient and at-the-ear occupational noise exposure and serum lipid levels.

PubMed

Arlien-Søborg, Mai C; Schmedes, Astrid S; Stokholm, Z A; Grynderup, M B; Bonde, J P; Jensen, C S; Hansen, Å M; Frederiksen, T W; Kristiansen, J; Christensen, K L; Vestergaard, J M; Lund, S P; Kolstad, H A

2016-10-01

Occupational and residential noise exposure has been related to increased risk of cardiovascular disease. Alteration of serum lipid levels has been proposed as a possible causal pathway. The objective of this study was to investigate the relation between ambient and at-the-ear occupational noise exposure and serum levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides when accounting for well-established predictors of lipid levels. This cross-sectional study included 424 industrial workers and 84 financial workers to obtain contrast in noise exposure levels. They provided a serum sample and wore portable dosimeters that every 5-s recorded ambient noise exposure levels during a 24-h period. We extracted measurements obtained during work and calculated the full-shift mean ambient noise level. For 331 workers who kept a diary on the use of a hearing protection device (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the mean full-shift noise exposure level at the ear. Mean ambient noise level was 79.9 dB (A) [range 55.0-98.9] and the mean estimated level at the ear 77.8 dB (A) [range 55.0-94.2]. Ambient and at-the-ear noise levels were strongly associated with increasing levels of triglycerides, cholesterol-HDL ratio, and decreasing levels of HDL-cholesterol, but only in unadjusted analyses that did not account for HPD use and other risk factors. No associations between ambient or at-the-ear occupational noise exposure and serum lipid levels were observed. This indicates that a causal pathway between occupational and residential noise exposure and cardiovascular disease does not include alteration of lipid levels.

Alterations in oxidative responses and post-translational modification caused by p,p´-DDE in Mus spretus testes reveal Cys oxidation status in proteins related to cell-redox homeostasis and male fertility.

PubMed

Alhama, José; Fuentes-Almagro, Carlos A; Abril, Nieves; Michán, Carmen

2018-09-15

The major derivate of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p´-DDE), is a persistent pollutant previously associated with oxidative stress. Additionally, p,p´-DDE has been linked to several metabolic alterations related to sexual function in rodents. In this study, we analysed the effects of a non-lethal p,p´-DDE dose to Mus spretus mice in testes, focusing on oxidative damage to biomolecules, defence mechanisms against oxidative stress and post-translational protein modifications. No increase in lipid or DNA oxidation was observed, although antioxidative enzymatic defences and redox status of glutathione were altered in several ways. Global protein carbonylation and phosphorylation were significantly reduced in testes from p,p´-DDE-exposed mice; however, the total redox state of Cys thiols did not exhibit a defined pattern. We analysed the reversible redox state of specific Cys residues in detail with differential isotopic labelling and a shotgun labelling-based MS/MS proteomic approach for identification and quantification of altered peptides. Our results show that Cys residues are significantly affected by p,p´-DDE in several proteins related to oxidative stress and/or male fertility, particularly those participating in fertilization, sperm capacitation and blood coagulation. These molecular changes could explain the sexual abnormalities previously described in p,p´-DDE exposed organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

PubMed Central

Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

2014-01-01

Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is

Anxiety-linked attentional bias and its modification: Illustrating the importance of distinguishing processes and procedures in experimental psychopathology research.

PubMed

MacLeod, Colin; Grafton, Ben

2016-11-01

In this review of research concerning anxiety-linked attentional bias, we seek to illustrate a general principle that we contend applies across the breadth of experimental psychopathology. Specifically, we highlight how maintenance of a clear distinction between process and procedure serves to enhance the advancement of knowledge and understanding, while failure to maintain this distinction can foster confusion and misconception. We show how such clear differentiation has permitted the continuous refinement of assessment procedures, in ways that have led to growing confidence in the existence of the putative attentional bias process of interest, and also increasing understanding of its nature. In contrast, we show how a failure to consistently differentiate between process and procedure has contributed to confusion concerning whether or not attentional bias modification reliably alters anxiety vulnerability and dysfunction. As we demonstrate, such confusion can be avoided by distinguishing the process of attentional bias modification from the procedures that have been employed with the intention of evoking this target process. Such an approach reveals that procedures adopted with the intention of eliciting the attentional bias modification process do not always do so, but that successful evocation of the attentional bias modification process quite reliably alters anxiety symptomatology. We consider some of the specific implications for future research concerning attentional bias modification, while also pointing to the broader implications for experimental psychopathology research in general. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hippocampal dendritic spines modifications induced by perinatal asphyxia.

PubMed

Saraceno, G E; Castilla, R; Barreto, G E; Gonzalez, J; Kölliker-Frers, R A; Capani, F

2012-01-01

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although western blot analysis also showed a slight decrease in β-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA.

Increased levels of N(ε)- Carboxy methyl lysine (N(ε)-CML) are associated with topographic alterations in retinal pigment epithelium: A preliminary study.

PubMed

Mishra, Nibha; Saxena, Sandeep; Ruia, Surabhi; Prasad, Senthamizh; Singh, Vinita; Khanna, Vinay; Staffa, Robert; Gaspar, Ludovit; Kruzliak, Peter

2016-07-01

To evaluate the association of serum levels of N(ε)- Carboxy methyl lysine (N(ε)-CML), an advanced glycation end product with topographic alterations in retinal pigment epithelium (RPE) in diabetic retinopathy on spectral domain optical coherence tomography (SD-OCT). Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non-proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy (n=20) and healthy controls (n=20) between the ages of 40 and 65years were included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE alterations in more than two quadrants. Serum level of N(ε)-CML and glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical analysis was done. Significant increase in N(ε)-CML was observed with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact test revealed significant increase in grades of RPE alterations with increased severity of diabetic retinopathy (p<0.001). Univariate ordinal regression analysis was done to calculate the risk of progression in grades of RPE alteration with individual changes in variables like duration of diabetes (odds ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nε-CML (odds ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting progression in grades of RPE alteration revealed Nε-CML to be an independent predictor of increase in grades of RPE alteration (adjusted odds ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant. Increase in serum levels of N(ε)- Carboxy methyl lysine is significantly associated with topographic alterations in RPE. Grades of RPE alteration increase significantly with increased severity of diabetic retinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum proteomic profiling of major depressive disorder

PubMed Central

Bot, M; Chan, M K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B W J H

2015-01-01

Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P<0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology. PMID:26171980

Sanguinarine interacts with chromatin, modulates epigenetic modifications, and transcription in the context of chromatin.

PubMed

Selvi B, Ruthrotha; Pradhan, Suman Kalyan; Shandilya, Jayasha; Das, Chandrima; Sailaja, Badi Sri; Shankar G, Naga; Gadad, Shrikanth S; Reddy, Ashok; Dasgupta, Dipak; Kundu, Tapas K

2009-02-27

DNA-binding anticancer agents cause alteration in chromatin structure and dynamics. We report the dynamic interaction of the DNA intercalator and potential anticancer plant alkaloid, sanguinarine (SGR), with chromatin. Association of SGR with different levels of chromatin structure was enthalpy driven with micromolar dissociation constant. Apart from DNA, it binds with comparable affinity with core histones and induces chromatin aggregation. The dual binding property of SGR leads to inhibition of core histone modifications. Although it potently inhibits H3K9 methylation by G9a in vitro, H3K4 and H3R17 methylation are more profoundly inhibited in cells. SGR inhibits histone acetylation both in vitro and in vivo. It does not affect the in vitro transcription from DNA template but significantly represses acetylation-dependent chromatin transcription. SGR-mediated repression of epigenetic marks and the alteration of chromatin geography (nucleography) also result in the modulation of global gene expression. These data, conclusively, show an anticancer DNA binding intercalator as a modulator of chromatin modifications and transcription in the chromatin context.

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification*

PubMed Central

Ringel, Michael T.; Dräger, Gerald; Brüser, Thomas

2016-01-01

Pyoverdines are high affinity siderophores produced by a broad range of pseudomonads to enhance growth under iron deficiency. They are especially relevant for pathogenic and mutualistic strains that inhabit iron-limited environments. Pyoverdines are generated from non-ribosomally synthesized highly modified peptides. They all contain an aromatic chromophore that is formed in the periplasm by intramolecular cyclization steps. Although the cytoplasmic peptide synthesis and side-chain modifications are well characterized, the periplasmic maturation steps are far from understood. Out of five periplasmic enzymes, PvdM, PvdN, PvdO, PvdP, and PvdQ, functions have been attributed only to PvdP and PvdQ. The other three enzymes are also regarded as essential for siderophore biosynthesis. The structure of PvdN has been solved recently, but no function could be assigned. Here we present the first in-frame deletion of the PvdN-encoding gene. Unexpectedly, PvdN turned out to be required for a specific modification of pyoverdine, whereas the overall amount of fluorescent pyoverdines was not altered by the mutation. The mutant strain grew normally under iron-limiting conditions. Mass spectrometry identified the PvdN-dependent modification as a transformation of the N-terminal glutamic acid to a succinamide. We postulate a pathway for this transformation catalyzed by the enzyme PvdN, which is most likely functional in the case of all pyoverdines. PMID:27703013

Human TTR conformation altered by rhenium tris-carbonyl derivatives.

PubMed

Ciccone, Lidia; Policar, Clotilde; Stura, Enrico A; Shepard, William

2016-09-01

Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu(82), may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69Å, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. Copyright © 2016 Elsevier Inc. All rights reserved.

Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats.

PubMed

Xie, Wei; Wu, Qian; Kania-Korwel, Izabela; Tharappel, Job C; Telu, Sanjay; Coleman, Mitchell C; Glauert, Howard P; Kannan, Kurunthachalam; Mariappan, S V S; Spitz, Douglas R; Weydert, Jamie; Lehmler, Hans-Joachim

2009-10-01

Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague-Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate > perfluorooctanesulfonamide ~ N-ethyl perfluorooctanesulfonamidoacetate > perfluorooctanesulfonamidoethanol approximately N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased relative liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Ciprofibrate treatment increased liver weight and peroxisomal acyl Co-A oxidase activity in the liver and altered antioxidant enzyme activities in the uterus and liver. According to NMR metabolomic studies, ciprofibrate treated animals had altered serum lipid profiles compared to N-EtFOSE-treated and control animals, whereas putative markers of peroxisome proliferation in serum were not affected. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity.

Protein arginine methylation: a prominent modification and its demethylation.

PubMed

Wesche, Juste; Kühn, Sarah; Kessler, Benedikt M; Salton, Maayan; Wolf, Alexander

2017-09-01

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.

Altered minor-groove hydrogen bonds in DNA block transcription elongation by T7 RNA polymerase.

PubMed

Tanasova, Marina; Goeldi, Silvan; Meyer, Fabian; Hanawalt, Philip C; Spivak, Graciela; Sturla, Shana J

2015-05-26

DNA transcription depends upon the highly efficient and selective function of RNA polymerases (RNAPs). Modifications in the template DNA can impact the progression of RNA synthesis, and a number of DNA adducts, as well as abasic sites, arrest or stall transcription. Nonetheless, data are needed to understand why certain modifications to the structure of DNA bases stall RNA polymerases while others are efficiently bypassed. In this study, we evaluate the impact that alterations in dNTP/rNTP base-pair geometry have on transcription. T7 RNA polymerase was used to study transcription over modified purines and pyrimidines with altered H-bonding capacities. The results suggest that introducing wobble base-pairs into the DNA:RNA heteroduplex interferes with transcriptional elongation and stalls RNA polymerase. However, transcriptional stalling is not observed if mismatched base-pairs do not H-bond. Together, these studies show that RNAP is able to discriminate mismatches resulting in wobble base-pairs, and suggest that, in cases of modifications with minor steric impact, DNA:RNA heteroduplex geometry could serve as a controlling factor for initiating transcription-coupled DNA repair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Workshop on Parent-Body and Nebular Modification of Chondritic Materials

NASA Technical Reports Server (NTRS)

Krot, A. N. (Editor); Zolensky, M. E. (Editor); Scott, E. R. D. (Editor)

1997-01-01

The purpose of the workshop was to advance our understanding of solar nebula and asteroidal processes from studies of modification features in chondrites and interplanetary dust particles. As reflected in the program contained in this volume, the workshop included five regular sessions, a summary session, and a poster session. Twenty-three posters and 42 invited and contributed talks were presented. Part 1 of this report contains the abstracts of these presentations. The focus of the workshop included: (1) mineralogical, petrologic, chemical, and isotopic observations of the alteration mineralogy in interplanetary dust particles, ordinary and carbonaceous chondrites, and their components (Ca-Al-rich inclusions, chondrules, and matrix) to constrain the conditions and place of alteration; (2) sources of water in chondrites; (3) the relationship between aqueous alteration and thermal metamorphism; (4) short-lived radionuclides, AI-26, Mn-53, and I-129, as isotopic constraints on timing of alteration; (5) experimental and theoretical modeling of alteration reactions; and (6) the oxidation state of the solar nebula. There were approximately 140 participants at the workshop, probably due in part to the timeliness of the workshop goals and the workshop location. In the end few new agreements were achieved between warring factions, but new research efforts were forged and areas of fruitful future exploration were highlighted. Judged by these results, the workshop was successful.

Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome.

PubMed

Hernández-Ortega, Karina; Garcia-Esparcia, Paula; Gil, Laura; Lucas, José J; Ferrer, Isidre

2016-09-01

Ribosomes and protein synthesis have been reported to be altered in the cerebral cortex at advanced stages of Alzheimer's disease (AD). Modifications in the hippocampus with disease progression have not been assessed. Sixty-seven cases including middle-aged (MA) and AD stages I-VI were analyzed. Nucleolar chaperones nucleolin, nucleophosmin and nucleoplasmin 3, and upstream binding transcription factor RNA polymerase I gene (UBTF) mRNAs are abnormally regulated and their protein levels reduced in AD. Histone modifications dimethylated histone H3K9 (H3K9me2) and acetylated histone H3K12 (H3K12ac) are decreased in CA1. Nuclear tau declines in CA1 and dentate gyrus (DG), and practically disappears in neurons with neurofibrillary tangles. Subunit 28 ribosomal RNA (28S rRNA) expression is altered in CA1 and DG in AD. Several genes encoding ribosomal proteins are abnormally regulated and protein levels of translation initiation factors eIF2α, eIF3η and eIF5, and elongation factor eEF2, are altered in the CA1 region in AD. These findings show alterations in the protein synthesis machinery in AD involving the nucleolus, nucleus and ribosomes in the hippocampus in AD some of them starting at first stages (I-II) preceding neuron loss. These changes may lie behind reduced numbers of dendritic branches and reduced synapses of CA1 and DG neurons which cause hippocampal atrophy. © 2015 International Society of Neuropathology.

Characterization and application of a surface modification designed for QCM-D studies of biotinylated biomolecules.

PubMed

Nilebäck, Erik; Feuz, Laurent; Uddenberg, Hans; Valiokas, Ramūnas; Svedhem, Sofia

2011-10-15

The rapid development of surface sensitive biosensor technologies, especially towards nanoscale devices, requires increasing control of surface chemistry to provide reliable and reproducible results, but also to take full advantage of the sensing opportunities. Here, we present a surface modification strategy to allow biotinylated biomolecules to be immobilized to gold coated sensor crystals for quartz crystal microbalance with dissipation monitoring (QCM-D) sensing. The unique feature of QCM-D is its sensitivity to nanomechanical (viscoelastic) properties at the sensing interface. The surface modification was based on mixed monolayers of oligo(ethylene glycol) (OEG) disulfides, with terminal -OH or biotin groups, on gold. Mixtures containing 1% of the biotin disulfide were concluded to be the most appropriate based on the performance when streptavidin was immobilized to biotinylated sensors and the subsequent biotinylated bovine serum albumin (BSA) interaction was studied. The OEG background kept the unspecific protein binding to a minimum, even when subjected to serum solutions with a high protein concentration. Based on characterization by contact angle goniometry, ellipsometry, and infrared spectroscopy, the monolayers were shown to be well-ordered, with the OEG chains predominantly adopting a helical conformation but also partly an amorphous structure. Storage stability was concluded to depend mainly on light exposure while almost all streptavidin binding activity was retained when storing the sensors cold and dark for 8 weeks. The surface modification was also tested for repeated antibody-antigen interactions between BSA and anti-BSA (immobilized to biotinylated protein A) in QCM-D measurements lasting for >10h with intermediate basic regeneration. This proved an excellent stability of the coating and good reproducibility was obtained for 5 interaction cycles. With this kind of generic surface modification QCM-D can be used in a variety of biosensing

Do neighbourhoods matter? Neighbourhood disorder and long-term trends in serum cortisol levels.

PubMed

Dulin-Keita, Akilah; Casazza, Krista; Fernandez, Jose R; Goran, Michael I; Gower, Barbara

2012-01-01

Characteristics associated with low socioeconomic status neighbourhoods may put children at risk for unique chronic stressors that affect cortisol levels. This research sought to explore whether neighbourhood stressor exposure affected serum cortisol levels among children. A total of 148 African and European-American children with an average age of 8.28 years participated in a longitudinal study evaluating ethnic differences in body composition and disease risk. Five waves of data were included in analyses. Mixed modelling was used to explore neighbourhood stressors, which was a composite index of five items for zip code level poverty and physical disorder, and serum cortisol outcomes for the full sample, by race/ethnicity and gender. Adjustments were made for individual level correlates age, pubertal status, gender and total fat mass. Neighborhood disorder was predictive of lower serum cortisol levels among African-American children (p<0.05), such that higher neighbourhood stressor exposure resulted in lower serum cortisol over time compared with individuals in socially ordered neighbourhoods. Neighbourhood disorder was marginally significant and predictive of higher serum cortisol among European-American children (p<0.10). Transition to a higher pubertal status, nested in age was also predictive of lower serum cortisol levels (p<0.01) among European-American children. Children who are exposed to negative socioenvironmental climates over time are more likely to have altered serum cortisol levels. This may be an adaptive mechanism to cope with stress; however, disrupted cortisol levels may have negative effects on general physical and mental health.

Serum creatinine and alkaline phosphatase levels are associated with severe chronic periodontitis.

PubMed

Caúla, A L; Lira-Junior, R; Tinoco, E M B; Fischer, R G

2015-12-01

Periodontitis may alter systemic homeostasis and influence creatinine and alkaline phosphatase levels. Therefore, the aim of this study was to evaluate the relationship between severe chronic periodontitis and serum creatinine and alkaline phosphatase levels. One hundred patients were evaluated, 66 with severe chronic periodontitis (test group) and 34 periodontally healthy controls (control group). Medical, demographic and periodontal parameters were registered. Blood sample was collected after an overnight fast and serum creatinine and alkaline phosphatase levels were determined. There were significant differences between test and control groups in ethnicity, gender and educational level (p < 0.05). Patients with periodontitis showed a lower mean creatinine level (p < 0.05) and higher mean alkaline phosphatase level (p < 0.001) than the control group. There were significant correlations between periodontal parameters and serum creatinine and alkaline phosphatase levels. Severe chronic periodontitis was associated to lower creatinine and higher alkaline phosphatase levels. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of serum on cytotoxicity of nano- and micro-sized ZnO particles

NASA Astrophysics Data System (ADS)

Hsiao, I.-Lun; Huang, Yuh-Jeen

2013-09-01

Although an increasing number of in vitro studies are being published regarding the cytotoxicity of nanomaterials, the components of the media for toxicity assays have often varied according to the needs of the scientists. Our aim for this study was to evaluate the influence of serum—in this case, fetal bovine serum—in a cell culture medium on the toxicity of nano-sized (50-70 nm) and micro-sized (<1 μm) ZnO on human lung epithelial cells (A549). The nano- and micro-sized ZnO both exhibited their highest toxicity when exposed to serum-free media, in contrast to exposure in media containing 5 or 10 % serum. This mainly comes not only from the fact that ZnO particles in the serum-free media have a higher dosage-per-cell ratio, which results from large aggregates of particles, rapid sedimentation, absence of protein protection, and lower cell growth rate, but also that extracellular Zn2+ release contributes to cytotoxicity. Although more extracellular Zn2+ release was observed in serum-containing media, it did not contribute to nano-ZnO cytotoxicity. Furthermore, non-dissolved particles underwent size-dependent particle agglomeration, resulting in size-dependent toxicity in both serum-containing and serum-free media. A low correlation between cytotoxicity and inflammation endpoints in the serum-free medium suggested that some signaling pathways were changed or induced. Since cell growth, transcription behavior for protein production, and physicochemical properties of ZnO particles all were altered in serum-free media, we recommend the use of a serum-containing medium when evaluating the cytotoxicity of NPs.

A Routine 'Top-Down' Approach to Analysis of the Human Serum Proteome.

PubMed

D'Silva, Arlene M; Hyett, Jon A; Coorssen, Jens R

2017-06-06

Serum provides a rich source of potential biomarker proteoforms. One of the major obstacles in analysing serum proteomes is detecting lower abundance proteins owing to the presence of hyper-abundant species (e.g., serum albumin and immunoglobulins). Although depletion methods have been used to address this, these can lead to the concomitant removal of non-targeted protein species, and thus raise issues of specificity, reproducibility, and the capacity for meaningful quantitative analyses. Altering the native stoichiometry of the proteome components may thus yield a more complex series of issues than dealing directly with the inherent complexity of the sample. Hence, here we targeted method refinements so as to ensure optimum resolution of serum proteomes via a top down two-dimensional gel electrophoresis (2DE) approach that enables the routine assessment of proteoforms and is fully compatible with subsequent mass spectrometric analyses. Testing included various fractionation and non-fractionation approaches. The data show that resolving 500 µg protein on 17 cm 3-10 non-linear immobilised pH gradient strips in the first dimension followed by second dimension resolution on 7-20% gradient gels with a combination of lithium dodecyl sulfate (LDS) and sodium dodecyl sulfate (SDS) detergents markedly improves the resolution and detection of proteoforms in serum. In addition, well established third dimension electrophoretic separations in combination with deep imaging further contributed to the best available resolution, detection, and thus quantitative top-down analysis of serum proteomes.

Association of canine obesity with reduced serum levels of C-reactive protein.

PubMed

Veiga, Angela P M; Price, Christopher A; de Oliveira, Simone T; Dos Santos, Andréa P; Campos, Rómulo; Barbosa, Patricia R; González, Félix H D

2008-03-01

The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P < or = 0.05). Serum CRP concentrations were lower in obese dogs than in controls (P < or = 0.001). C-reactive protein was negatively correlated with insulin/glucose ratio (R = -0.42) and cholesterol (R = -0.39; P < or = 0.05). Furthermore, levels of cholesterol, triglycerides, and fructosamine were increased in the obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.

Recognition and modification of seX chromosomes.

PubMed

Nusinow, Dmitri A; Panning, Barbara

2005-04-01

Flies, worms and mammals employ dosage compensation complexes that alter chromatin or chromosome structure to equalize X-linked gene expression between the sexes. Recent work has improved our understanding of how dosage compensation complexes achieve X chromosome-wide association and has provided significant insight into the epigenetic modifications directed by these complexes to modulate gene expression. In flies, the prevailing view that dosage compensation complexes assemble on the X chromosome at approximately 35 chromatin-entry sites and then spread in cis to cover the chromosome has been re-evaluated in light of the evidence that these chromatin-entry sites are not required for localization of the complex. By contrast, identification of discrete recruitment elements indicates that nucleation at and spread from a limited number of sites directs dosage compensation complex localization on the worm X-chromosome. Studies in flies and mammals have extended our understanding of how ribonucleoprotein complexes are used to modify X chromatin, for either activation or repression of transcription. Finally, evidence from mammals suggests that the chromatin modifications that mediate dosage compensation are very dynamic, because they are established, reversed and re-established early in development.

ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

PubMed Central

Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

2010-01-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. PMID:20566332

Low serum uric acid levels in chronic insomnia patients: A case-control study.

PubMed

Zhao, Kai; Luan, Xiaoqian; Liu, Zhihua; Zhu, Zhuoying; Chen, Huijun; Shen, Huiping; Cai, Yan; Qiu, Huihua; Wang, Qiongzhang; Gu, Yingying; Zhu, Lin; He, Jincai

2017-09-14

Recent studies have demonstrated the presence of oxidative stress in insomnia patients. Uric acid (UA) is regarded as one of the most important antioxidants that may attenuate oxidative stress. The aim of our study was to investigate whether there is an alteration of serum UA levels in chronic insomnia patients. The association between sleep quality and serum UA in chronic insomnia patients was also investigated. We recruited 300 chronic insomnia patients and 300 age- and gender-matched normal controls. The uricase-PAP method was used to measure the concentration of UA both in patient and normal control subjects. The Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality of chronic insomniac participants. As a result, significantly lower serum UA levels were observed in patients with chronic insomnia when compared with normal control subjects (279.56±65.80 vs. 299.10±61.17μmol/L, t=-3.991, p<0.001). Low serum UA levels were correlated with high PSQI scores in multiple linear regression models (β=-0.322, p<0.001). Our results suggested that low serum UA levels were associated with the presence and severity of chronic insomnia. Copyright © 2017 Elsevier B.V. All rights reserved.

Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies?

PubMed

Batcheller, April; Cardozo, Eden; Maguire, Marcy; DeCherney, Alan H; Segars, James H

2011-12-01

To review recent data regarding subtle, but widespread, epigenetic alterations in phenotypically normal offspring conceived by assisted reproductive technologies (ART) compared with offspring conceived in vivo. A PubMed computer search was performed to identify relevant articles. Research institution. Not applicable. None. Not applicable. Studies in animals indicate that in vitro culture may be associated with widespread alterations in imprinted genes compared with in vivo-conceived offspring. Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation, including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceived by ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ART also were noted in additional studies, which suggested that the diagnosis of infertility may explain the differences between in vivo-conceived and ART offspring. These data suggest that ART is associated with widespread epigenetic modifications in phenotypically normal children, and that these modifications may increase the risk of adverse cardiometabolic outcomes. Further research is needed to elucidate the possible relationship between ART, genome-wide alterations in imprinted genes, and their potential relevance to subtle cardiometabolic consequences reported in ART offspring. Published by Elsevier Inc.

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

PubMed Central

Brundige, Dottie R.; Maga, Elizabeth A.; Klasing, Kirk C.

2009-01-01

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health. PMID:19847666

Consumption of pasteurized human lysozyme transgenic goats' milk alters serum metabolite profile in young pigs.

PubMed

Brundige, Dottie R; Maga, Elizabeth A; Klasing, Kirk C; Murray, James D

2010-08-01

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats' milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats' milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health.

Quantification of carbamylated albumin in serum based on capillary electrophoresis.

PubMed

Delanghe, Sigurd; Moerman, Alena; Pletinck, Anneleen; Schepers, Eva; Glorieux, Griet; Van Biesen, Wim; Delanghe, Joris R; Speeckaert, Marijn M

2017-09-01

Protein carbamylation, a nonenzymatic posttranslational modification promoted during uremia, is linked to a poor prognosis. In the present study, carbamylation of serum albumin was assayed using the symmetry factor on a capillary electrophoresis instrument (Helena V8). The symmetry factor has been defined as the distance from the center line of the peak to the back slope, divided by the distance from the center line of the peak to the front slope, with all measurements made at 10% of the maximum peak height. Serum albumin, creatinine, and urea concentrations were assayed using routine methods, whereas uremic toxins were determined using HPLC. In vitro carbamylation induced a marked albumin peak asymmetry. Reference values for the albumin symmetry factor were 0.69-0.92. In kidney patients, albumin peak asymmetry corresponded to the chronic kidney disease stage (p < 0.0001). The symmetry factor correlated well with serum urea (r = -0.5595, p < 0.0001) and creatinine (r = -0.5986, p < 0.0001) concentrations. Several protein-bound uremic toxins showed a significant negative correlation with the symmetry factor. Morphology of the albumin fraction was not affected by presence of glycated albumin and protein-bound antibiotics. In conclusion, the presented method provides a simple, practical way for monitoring protein carbamylation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploration of alloy surface and slurry modification to improve oxidation life of fused silicide coated niobium alloys

NASA Technical Reports Server (NTRS)

Levine, S. R.; Grisaffe, S. J.

1972-01-01

Edge and surface modifications of niobium alloys were investigated prior to coating with Si-20Cr-20Fe and slurry composition modification for performance in a 1370 C ambient pressure slow cycle test. The best coating obtained was Si-20Cr-20Mn with an average life of 63 cycles, compared to 40 for Si-20Cr-20Fe on FS-85 (100 percent improvement in weight parity life). Edge beading extended the lives of Si-20Cr-20Fe-coated Cb-752 and FS-85 to 57 and 41 cycles respectively (50 and 20 percent improvements in weight parity life respectively). W, Al2O3 and ZrO2(CaO) surface modifications altered coating crack frequency and microstructure and increased life somewhat.

Serum levels of the immune activation marker neopterin change with age and gender and are modified by race, BMI, and percentage of body fat.

PubMed

Spencer, Monique E; Jain, Alka; Matteini, Amy; Beamer, Brock A; Wang, Nae-Yuh; Leng, Sean X; Punjabi, Naresh M; Walston, Jeremy D; Fedarko, Neal S

2010-08-01

Neopterin, a GTP metabolite expressed by macrophages, is a marker of immune activation. We hypothesize that levels of this serum marker alter with donor age, reflecting increased chronic immune activation in normal aging. In addition to age, we assessed gender, race, body mass index (BMI), and percentage of body fat (%fat) as potential covariates. Serum was obtained from 426 healthy participants whose age ranged from 18 to 87 years. Anthropometric measures included %fat and BMI. Neopterin concentrations were measured by competitive ELISA. The paired associations between neopterin and age, BMI, or %fat were analyzed by Spearman's correlation or by linear regression of log-transformed neopterin, whereas overall associations were modeled by multiple regression of log-transformed neopterin as a function of age, gender, race, BMI, %fat, and interaction terms. Across all participants, neopterin exhibited a positive association with age, BMI, and %fat. Multiple regression modeling of neopterin in women and men as a function of age, BMI, and race revealed that each covariate contributed significantly to neopterin values and that optimal modeling required an interaction term between race and BMI. The covariate %fat was highly correlated with BMI and could be substituted for BMI to yield similar regression coefficients. The association of age and gender with neopterin levels and their modification by race, BMI, or %fat reflect the biology underlying chronic immune activation and perhaps gender differences in disease incidence, morbidity, and mortality.

Surface modification of polymers for biocompatibility via exposure to extreme ultraviolet radiation.

PubMed

Inam Ul Ahad; Bartnik, Andrzej; Fiedorowicz, Henryk; Kostecki, Jerzy; Korczyc, Barbara; Ciach, Tomasz; Brabazon, Dermot

2014-09-01

Polymeric biomaterials are being widely used for the treatment of various traumata, diseases and defects in human beings due to ease in their synthesis. As biomaterials have direct interaction with the extracellular environment in the biological world, biocompatibility is a topic of great significance. The introduction or enhancement of biocompatibility in certain polymers is still a challenge to overcome. Polymer biocompatibility can be controlled by surface modification. Various physical and chemical methods (e.g., chemical and plasma treatment, ion implantation, and ultraviolet irradiation etc.) are in use or being developed for the modification of polymer surfaces. However an important limitation in their employment is the alteration of bulk material. Different surface and bulk properties of biomaterials are often desirable for biomedical applications. Because extreme ultraviolet (EUV) radiation penetration is quite limited even in low density mediums, it could be possible to use it for surface modification without influencing the bulk material. This article reviews the degree of biocompatibility of different polymeric biomaterials being currently employed in various biomedical applications, the surface properties required to be modified for biocompatibility control, plasma and laser ablation based surface modification techniques, and research studies indicating possible use of EUV for enhancing biocompatibility. © 2013 Wiley Periodicals, Inc.

[Changes in the secondary and tertiary structure of serum albumin in interactions with ligands of various structures].

PubMed

Trinus, F P; Braver-Chernobul'skaia, B S; Luĭk, A I; Boldeskul, A E; Velichko, A N

1984-01-01

High affinity interactions between blood serum albumin and five substances of various chemical structure, exhibiting distinct physiological activity, were accompanied by alterations in the protein tertiary structure, while the albumin secondary structure was involved in conformational transformation after less effective affinity binding.

Elevated serum galectin-9 levels in patients with atopic dermatitis.

PubMed

Nakajima, Rina; Miyagaki, Tomomitsu; Oka, Tomonori; Nakao, Momoko; Kawaguchi, Makiko; Suga, Hiraku; Morimura, Sohshi; Kai, Hiromichi; Asano, Yoshihide; Tada, Yayoi; Kadono, Takafumi; Sato, Shinichi; Sugaya, Makoto

2015-07-01

Galectin-9 is a member of the galectin family that has a wide spectrum of biological functions. Among them, galectin-9 has been known mainly as a potent chemoattractant for eosinophils. In addition, galectin-9 alters the T-cell balance by negatively regulating T-helper (Th)1 and Th17 cells, resulting in Th2 polarization. Atopic dermatitis (AD) is a skin allergic disease characterized by peripheral eosinophilia, mast cell activation and predominance of Th2 cells. To investigate possible roles of galectin-9 in AD, we measured serum galectin-9 levels in AD patients and investigated galectin-9 expression in lesional skin by immunohistochemistry. Serum galectin-9 levels in patients with AD were significantly higher than those in healthy controls and correlated with the Eczema Area and Severity Index. Serum galectin-9 levels were decreased after treatment, accompanied by improvement of skin lesions. Immunohistochemical study revealed that galectin-9 was expressed on epidermal keratinocytes and mast cells in lesional skin of AD. Our results suggest that elevated galectin-9 expression is associated with progression of AD and that galectin-9 could be a therapeutic target in AD. © 2015 Japanese Dermatological Association.

High-grade iron ore at Windarling, Yilgarn Craton: a product of syn-orogenic deformation, hypogene hydrothermal alteration and supergene modification in an Archean BIF-basalt lithostratigraphy

NASA Astrophysics Data System (ADS)

Angerer, Thomas; Hagemann, Steffen G.; Danyushevsky, Leonid

2013-08-01

, carbonate and quartz to form veins and breccia but did not generate significant volumes of iron ore. Ore stage 4 involved Mesozoic(?) to recent supergene oxidation and hydration in a weathering environment reaching down to depths of ˜100 to maximum 200 m below surface. Supergene ore formation involved goethite replacement of dolomite and quartz as well as martitisation. Important `ground preparation' for supergene modification and upgrade were mainly the formation of steep D1 to D4 structures, steep BIF/basalt margins and particularly the syn-D1 to syn-D2 carbonate alteration of BIF that is most susceptible to supergene dissolution. The Windarling deposits are structurally controlled, supergene-modified hydrothermal iron ore systems that share comparable physical, chemical and ore-forming characteristics to other iron ore deposits in the Yilgarn Craton (e.g. Koolyanobbing, Beebyn in the Weld Range, Mt. Gibson). However, the remarkable variety in pre-, syn- and post-deformational ore textures (relative to D1 and D2) has not been described elsewhere in the Yilgarn and are similar to the ore deposits in high-strain zones, such as of Brazil (Quadrilátero Ferrífero or Iron Quadrangle) and Nigeria. The overall similarity of alteration stages, i.e. the sequence of hydrothermal carbonate introduction and hypogene leaching, with other greenstone belt-hosted iron ore deposits supports the interpretation that syn-orogenic BIF alteration and upgrade was crucial in the formation of hypogene-supergene iron ore deposits in the Yilgarn Craton and possibly in other Archean/Paleoproterozoic greenstone belt settings worldwide.

Serum factors and clinical characteristics associated with serum E-Screen activity

PubMed Central

Wang, Jue; Trentham-Dietz, Amy; Hemming, Jocelyn D. C.; Hedman, Curtis J.; Sprague, Brian L.

2013-01-01

Background The E-Screen bioassay can measure the mitogenicity of human serum and thus may be useful as a biomarker in epidemiologic studies of breast cancer. While the assay’s MCF-7 cells are known to proliferate in response to estrogen, the specific determinants of variation in E-Screen activity in human serum samples are poorly understood. We sought to identify serum molecules and patient characteristics associated with serum E-Screen activity among postmenopausal women. Methods Postmenopausal women (N=219) aged 55–70 with no history of postmenopausal hormone use or breast cancer completed a questionnaire and provided a blood sample. Serum was analyzed for E-Screen activity and a variety of molecules including sex hormones, growth factors, and environmental chemicals. Stepwise selection procedures were used to identify correlates of E-Screen activity. Results Serum samples from all women had detectable E-Screen activity, with a median estradiol equivalents value of 0.027 ng/mL and interquartile range of 0.018–0.036 ng/mL. In the final multivariable-adjusted model, serum E-Screen activity was positively associated with serum estradiol, estrone, IGFBP-3, and testosterone levels (p<0.05), as well as body mass index (p=0.03). Serum E-Screen activity was lower among women with higher SHBG (p<0.0001) and progesterone levels (p=0.03). Conclusion Serum E-Screen activity varies according to levels of endogenous estrogens and other serum molecules. Obesity appears to confer additional serum mitogenicity beyond its impact on the measured hormones and growth factors. Impact By capturing mitogenicity due to a variety of patient and serum factors, the E-Screen may provide advantages for use as a biomarker in breast cancer studies. PMID:23588007

Subacute Exposure to N-Ethyl Perfluorooctanesulfonamidoethanol Results in the Formation of Perfluorooctanesulfonate and Alters Superoxide Dismutase Activity in Female Rats

PubMed Central

Xie, Wei; Wu, Qian; Kania-Korwel, Izabela; Tharappel, Job C.; Telu, Sanjay; Coleman, Mitchell C.; Glauert, Howard P.; Kannan, Kurunthachalam; Santhana Mariappan, S. V.; Spitz, Douglas R.; Weydert, Jamie; Lehmler, Hans-Joachim

2009-01-01

Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague-Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate ≫ perfluorooctanesulfonamide ∼ N-ethyl perfluorooctanesulfonamidoacetate ≫ perfluorooctanesulfonamidoethanol ∼ N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased relative liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Ciprofibrate treatment increased liver weight and peroxisomal acyl Co-A oxidase activity in the liver and altered antioxidant enzyme activities in the uterus and liver. According to NMR metabolomic studies, ciprofibrate treated animals had altered serum lipid profiles compared to N-EtFOSE-treated and control animals, whereas putative markers of peroxisome proliferation in serum were not affected. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity. PMID:19544052

The correlational research among serum CXCL13 levels, circulating plasmablasts and memory B cells in patients with systemic lupus erythematosus: A STROBE-compliant article.

PubMed

Fang, Chenglong; Luo, Tingting; Lin, Ling

2017-12-01

We investigated whether serum CXC ligand 13 protein (CXCL13) levels correlate with the circulating plasmablasts and memory B-cells alteration in systemic lupus erythematosus (SLE) patients. The diagnostic use of CXCL13 concentrations in active lupus was also analyzed.A total of 36 SLE patients and 18 healthy controls were included. Serum CXCL13 levels were examined by enzyme-linked immunosorbent assay. The frequency and absolute count of circulating plasmablasts and memory B cells were analyzed by flow cytometry. Receiver operating characteristic curves (ROC curves) were generated to analyze the utility of serum CXCL13 level and plasmablasts frequency as tools for the recognition of active SLE.Elevation of serum CXCL13 levels, higher plasmablasts frequency, and reduction of memory B-cells count were observed in SLE patients, compared with healthy controls. Interestingly, correlational analyses showed not only significantly positive association between CXCL13 levels and SLE Disease Activity Index (SLEDAI) or plasmablasts frequency, but an inverse correlation between CXCL13 concentration and memory B-cell count. ROC curves showed that serum CXCL13 level and plasmablasts frequency were practical in identifying active disease from overall SLE patients, with considerable accuracy.Serum CXCL13 levels correlate with the alteration of plasmablasts and memory B cells in SLE. CXCL13 may be used as a practical tool in judgment of active SLE.

Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS-PAGE and LC-MS.

PubMed

Gossmann, R; Fahrländer, E; Hummel, M; Mulac, D; Brockmeyer, J; Langer, K

2015-06-01

The behavior of nanosized drug carrier systems under cell culture conditions and therefore also the destiny in the body are highly influenced by the protein corona, which is formed upon entering a biological environment. Some of the adsorbed proteins, named opsonins, lead to a shortened plasma circulation half-life of the nanoparticles. Others are attributed to promote the transport of nanoparticles into other compartments of the body, just to mention two examples. Hence, detailed knowledge concerning the composition of the protein corona is of great importance. The aim of this work was to investigate the influence of the nanoparticle starting material and the surface modification on the composition of the adsorbed serum proteins in a cell culture environment. Therefore, positively charged nanoparticles based on the biodegradable polymer poly(dl-lactide-co-glycolide) (PLGA) stabilized with didodecyldimethylammonium bromide (DMAB) and negatively charged nanoparticles based on human serum albumin (HSA) were prepared and modified with hydrophilic polymers. By incubating the nanoparticles with fetal bovine serum (FBS) the adsorption of serum proteins on the colloidal system was investigated. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) a semi-quantitative analysis of the protein corona was performed and after enzymatic in-solution-digestion the adsorbed proteins were identified using high resolution LC-MS. Our study accentuates the influence of the core material, surface charge, and surface modification on the amount and nature of the adsorbed proteins. The combination of SDS-PAGE and LC-MS turns out to be a simple and reliable method to investigate the protein corona of nanoparticles. Copyright © 2015 Elsevier B.V. All rights reserved.

Modulation of farnesoid X receptor results in post-translational modification of poly (ADP-ribose) polymerase 1 in the liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Yan; Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS; Li, Guodong

2013-01-15

The farnesoid X receptor (FXR) is a bile acid-activated transcription factor belonging to the nuclear receptor superfamily. FXR deficiency in mice results in cholestasis, metabolic disorders, and tumorigenesis in liver and intestine. FXR is known to contribute to pathogenesis by regulating gene transcription; however, changes in the post-transcriptional modification of proteins associated with FXR modulation have not been determined. In the current study, proteomic analysis of the livers of wild-type (WT) and FXR knockout (FXR-KO) mice treated with a FXR synthetic ligand or vehicle was performed. The results identified five proteins as novel FXR targets. Since FXR deficiency in micemore » leads to liver tumorigenesis, poly (ADP-ribose) polymerase family, member 1 (Parp1) that is important for DNA repair, was validated in the current study by quantitative real-time PCR, and 1- and 2-dimensional gel electrophoresis/western blot. The results showed that Parp1 mRNA levels were not altered by FXR genetic status or by agonist treatment. However, total Parp1 protein levels were increased in FXR-KO mice as early as 3 month old. Interestingly, total Parp1 protein levels were increased in WT mice in an age-dependent manner (from 3 to 18 months), but not in FXR-KO mice. Finally, activation of FXR in WT mice resulted in reduction of phosporylated Parp1 protein in the liver without affecting total Parp1 protein levels. In conclusion, this study reveals that FXR genetic status and agonist treatment affects basal levels and phosphorylation state of Parp1, respectively. These alterations, in turn, may be associated with the hepatobiliary alterations observed in FXR-KO mice and participate in FXR agonist-induced protection in the liver. -- Highlights: ► Proteomic analysis identified novel FXR targets. ► FXR modification altered post-translational modification of the Parp1 protein. ► Altered Parp1 function may contribute to mechanisms of FXR regulation of liver functions.« less

Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers

PubMed Central

D’Sa, Carrol; Dileone, Ralph J.; Anderson, George M.; Sinha, Rajita

2013-01-01

Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse. PMID:22364688

Towards Enhanced Performance Thin-film Composite Membranes via Surface Plasma Modification

PubMed Central

Reis, Rackel; Dumée, Ludovic F.; Tardy, Blaise L.; Dagastine, Raymond; Orbell, John D.; Schutz, Jürg A.; Duke, Mikel C.

2016-01-01

Advancing the design of thin-film composite membrane surfaces is one of the most promising pathways to deal with treating varying water qualities and increase their long-term stability and permeability. Although plasma technologies have been explored for surface modification of bulk micro and ultrafiltration membrane materials, the modification of thin film composite membranes is yet to be systematically investigated. Here, the performance of commercial thin-film composite desalination membranes has been significantly enhanced by rapid and facile, low pressure, argon plasma activation. Pressure driven water desalination tests showed that at low power density, flux was improved by 22% without compromising salt rejection. Various plasma durations and excitation powers have been systematically evaluated to assess the impact of plasma glow reactions on the physico-chemical properties of these materials associated with permeability. With increasing power density, plasma treatment enhanced the hydrophilicity of the surfaces, where water contact angles decreasing by 70% were strongly correlated with increased negative charge and smooth uniform surface morphology. These results highlight a versatile chemical modification technique for post-treatment of commercial membrane products that provides uniform morphology and chemically altered surface properties. PMID:27363670

Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Qiang; Zhu, Binhai; Wu, Si

Various proteoforms may be generated from a single gene due to primary structure alterations (PSAs) such as genetic variations, alternative splicing, and post-translational modifications (PTMs). Top-down mass spectrometry is capable of analyzing intact proteins and identifying patterns of multiple PSAs, making it the method of choice for studying complex proteoforms. In top-down proteomics, proteoform identification is often performed by searching tandem mass spectra against a protein sequence database that contains only one reference protein sequence for each gene or transcript variant in a proteome. Because of the incompleteness of the protein database, an identified proteoform may contain unknown PSAs comparedmore » with the reference sequence. Proteoform characterization is to identify and localize PSAs in a proteoform. Although many software tools have been proposed for proteoform identification by top-down mass spectrometry, the characterization of proteoforms in identified proteoform-spectrum matches still relies mainly on manual annotation. We propose to use the Modification Identification Score (MIScore), which is based on Bayesian models, to automatically identify and localize PTMs in proteoforms. Experiments showed that the MIScore is accurate in identifying and localizing one or two modifications.« less

DNA modifications in models of alcohol use disorders.

PubMed

Tulisiak, Christopher T; Harris, R Adron; Ponomarev, Igor

2017-05-01

Chronic alcohol use and abuse result in widespread changes to gene expression, some of which contribute to the development of alcohol-use disorders (AUD). Gene expression is controlled, in part, by a group of regulatory systems often referred to as epigenetic factors, which includes, among other mechanisms, chemical marks made on the histone proteins around which genomic DNA is wound to form chromatin, and on nucleotides of the DNA itself. In particular, alcohol has been shown to perturb the epigenetic machinery, leading to changes in gene expression and cellular functions characteristic of AUD and, ultimately, to altered behavior. DNA modifications in particular are seeing increasing research in the context of alcohol use and abuse. To date, studies of DNA modifications in AUD have primarily looked at global methylation profiles in human brain and blood, gene-specific methylation profiles in animal models, methylation changes associated with prenatal ethanol exposure, and the potential therapeutic abilities of DNA methyltransferase inhibitors. Future studies may be aimed at identifying changes to more recently discovered DNA modifications, utilizing new methods to discriminate methylation profiles between cell types, thus clarifying how alcohol influences the methylomes of cell-type populations and how this may affect downstream processes. These studies and more in-depth probing of DNA methylation will be key to determining whether DNA-level epigenetic regulation plays a causative role in AUD and can thus be targeted for treatment of the disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

DNA modifications in models of alcohol use disorders

PubMed Central

Tulisiak, Christopher T.; Harris, R. Adron; Ponomarev, Igor

2016-01-01

Chronic alcohol use and abuse result in widespread changes to gene expression, some of which contribute to the development of alcohol use disorders (AUD). Gene expression is, in part, controlled by a group of regulatory systems often referred to as epigenetic factors, which includes, among other mechanisms, chemical marks made on the histone proteins around which genomic DNA is wound to form chromatin, and on nucleotides of the DNA itself. In particular, alcohol has been shown to perturb the epigenetic machinery, leading to changes in gene expression and cellular functions characteristic of AUD and, ultimately, to altered behavior. DNA modifications in particular are seeing increasing research in the context of alcohol use and abuse. To date, studies of DNA modifications in AUD have primarily looked at global methylation profiles in human brain and blood, gene-specific methylation profiles in animal models, methylation changes associated with prenatal ethanol exposure, and the potential therapeutic abilities of DNA methyltransferase inhibitors. Future studies may be aimed at identifying changes to more recently discovered DNA modifications, utilizing new methods to discriminate methylation profiles between cell types and clarifying how alcohol influences the methylomes of cell type populations and how this may affect downstream processes. These studies and more in-depth probing of DNA methylation will be key to determining whether DNA-level epigenetic regulation plays a causative role in AUD and can thus be targeted for treatment of the disorder. PMID:27865607

Serum metabolites are associated with all-cause mortality in chronic kidney disease.

PubMed

Hu, Jiun-Ruey; Coresh, Josef; Inker, Lesley A; Levey, Andrew S; Zheng, Zihe; Rebholz, Casey M; Tin, Adrienne; Appel, Lawrence J; Chen, Jingsha; Sarnak, Mark J; Grams, Morgan E

2018-06-02

Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects.

PubMed

Orr, J M; Abbott, F S; Farrell, K; Ferguson, S; Sheppard, I; Godolphin, W

1982-05-01

In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.

Effects of channel modifications on the hydrology of Chicod Creek basin, North Carolina, 1975-87

USGS Publications Warehouse

Mason, R.R.; Simmons, C.E.; Watkins, S.A.

1990-01-01

Drainage modifications in this Coastal Plain basin from 1978 to 1981 consisted of channel excavation and clearing of blockages. A study was begun in 1975 to define hydrologic conditions of the basin before, during, and after modifications and to determine what changes were attributed to modifications. Surface-water conditions were altered during and following modifications. Minimum flow at Juniper Branch was increased from less than 0.1 cu ft/sec to 0.4 cu ft/second;streamflow variability was reduced from an index of 0.87 to 0.49. In-channel velocity at Chicod Creek was increased from a mean of 0.4 ft/sec to 1.5 ft/sec. Substantial groundwater level declines were observed in wells 180 and 250 ft from Juniper Branch during the modifications phase;these were 0.4 and 0.2 ft, respectively. However, most surface-water and groundwater conditions returned nearly to premodification levels by 1987. Water-quality characteristics monitored during the investigation included physical, chemical, and bacteriological characteristics. Physical characteristics monitored were suspended sediment, temperature, dissolved oxygen, and pH. Of these physical characteristics, only sediment concentrations increased substantially during channel modifications. Chemical characteristics studied were major dissolved constituents, nutrients, trace metals, and pesticides. Substantial changes ranged from a decline in total iron concentrations of 77% to an increase in total nitrite concentrations of 130%. Changes in many chemical characteristics persisted following channel modifications. Bacterial counts did not change substantially.

Human umbilical cord blood serum promotes growth, proliferation, as well as differentiation of human bone marrow-derived progenitor cells.

PubMed

Phadnis, Smruti M; Joglekar, Mugdha V; Venkateshan, Vijayalakshmi; Ghaskadbi, Surendra M; Hardikar, Anandwardhan A; Bhonde, Ramesh R

2006-01-01

Fetal calf serum (FCS) is conventionally used for animal cell cultures due to its inherent growth-promoting activities. However animal welfare issues and stringent requirements for human transplantation studies demand a suitable alternative for FCS. With this view, we studied the effect of FCS, human AB serum (ABS), and human umbilical cord blood serum (UCBS) on murine islets of Langerhans and human bone marrow-derived mesenchymal-like cells (hBMCs). We found that there was no difference in morphology and functionality of mouse islets cultured in any of these three different serum supplements as indicated by insulin immunostaining. A comparative analysis of hBMCs maintained in each of these three different serum supplements demonstrated that UCBS supplemented media better supported proliferation of hBMCs. Moreover, a modification of adipogenic differentiation protocol using UCBS indicates that it can be used as a supplement to support differentiation of hBMCs into adipocytes. Our results demonstrate that UCBS not only is suitable for maintenance of murine pancreatic islets, but also supports attachment, propagation, and differentiation of hBMCs in vitro. We conclude that UCBS can serve as a better serum supplement for growth, maintenance, and differentiation of hBMCs, making it a more suitable supplement in cell systems that have therapeutic potential in human transplantation programs.

Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial

PubMed Central

Eckard, Carly; Cole, Renee; Lockwood, Joshua; Torres, Dawn M.; Williams, Christopher D.; Shaw, Janet C.

2013-01-01

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is now recognized as part of the metabolic syndrome, and is specifically related to obesity and insulin resistance. Lifestyle modification is advocated for the treatment of NAFLD, but few studies have evaluated its impact on liver histology. The purpose of this study was to investigate which, if any, specific diet and exercise recommendations are associated with histopathologic changes. Methods: A total of 56 participants were randomly assigned to 1 of 4 lifestyle modification subgroups for 6 months: standard care, low-fat diet and moderate exercise, moderate-fat/low-processed-carbohydrate diet and moderate exercise, or moderate exercise only. All subjects had biopsy-proven NAFLD, to include nonalcoholic steatohepatitis (NASH), and received a repeat 6-month biopsy to detect histopathologic changes. Other measures included blood assay of liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), fasting glucose, serum insulin, lipid panel, body weight, dietary intake, fat mass, and fitness level. Results: Among the 41 participants who completed the study (88% with NASH), a significant change was found in pre- to post-NAFLD activity score in the group as a whole (p < 0.001) with no difference detected between subgroups (p = 0.31). Our results confirm that lifestyle modification is effective in improving NAFLD and NASH. Conclusions: Regardless of intervention group, lifestyle modification improved liver histology, as verified by repeat biopsy, after a 6-month intervention. This study reinforces the importance of lifestyle modification as the primary treatment strategy for patients with NAFLD. PMID:23814606

Small molecule alteration of RNA sequence in cells and animals.

PubMed

Guan, Lirui; Luo, Yiling; Ja, William W; Disney, Matthew D

2017-10-18

RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat causative of myotonic muscular dystrophy type 1 (DM1), r(CUG) exp . The small molecule, 2H-4-Ru, binds to r(CUG) exp and converts guanosine residues to 8-oxo-7,8-dihydroguanosine upon photochemical irradiation. We demonstrate targeted modification upon irradiation in cell culture and in Drosophila larvae provided a diet containing 2H-4-Ru. Our results highlight a general chemical biology approach for altering RNA sequence in vivo by using small molecules and photochemistry. Furthermore, these studies show that addition of 8-oxo-G lesions into RNA 3' untranslated regions does not affect its steady state levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

PubMed

Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

2010-11-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

Developmental and genetic analysis of a short leaf mutant, a key resource for plant architecture modification in sorghum

USDA-ARS?s Scientific Manuscript database

Modification in plant architecture have been demonstrated as one of the major contributing factors that ushered in the Green Revolution resulting in achieving dramatic increases in grain yield for wheat and rice. For sorghum (Sorghum bicolor L. Moench.), possible alteration in plant architecture is ...

Effects of 12 Weeks Resistance Training on Serum Irisin in Older Male Adults.

PubMed

Zhao, Jiexiu; Su, Zhongjun; Qu, Chaoyi; Dong, Yanan

2017-01-01

Background: To assess the effects of resistance training on circulating irisin concentration in older male adults, and to investigate the association between resistance training induced alteration of irisin and body fat. Methods: Seventeen older adults (mean age is 62.1 years old) were randomized into old control group (male, n = 7), and old training group (male, n = 10). The control group has no any exercise intervention. The resistance training group underwent leg muscle strength and core strength training program two times/wk, 55 min/class for 12 weeks. Before and after the intervention, we evaluated serum irisin level and body composition. Results: Serum irisin level was significantly increased in the resistance training group after the 12 weeks intervention period ( P < 0.01), but not in the control group. In the resistance training group, the reduction in whole-body fat percent was negatively correlated with the increase in serum irisin level ( r = -0.705, P < 0.05). Conclusion: After the 12 weeks intervention, circulating irisin levels were significantly elevated in the older adults. In summary, serum irisin may be involved in the regulation of body fat in older male adults.

GC-MS Metabolomics Identifies Metabolite Alterations That Precede Subclinical Mastitis in the Blood of Transition Dairy Cows.

PubMed

Dervishi, Elda; Zhang, Guanshi; Dunn, Suzanna M; Mandal, Rupasri; Wishart, David S; Ametaj, Burim N

2017-02-03

The objectives of this study were to determine alterations in the serum metabolites related to amino acid (AA), carbohydrate, and lipid metabolism in transition dairy cows before diagnosis of subclinical mastitis (SCM), during, and after diagnosis of disease. A subclinical mastitis case was determined as a cow having somatic cell count (SCC) > 200 000/mL of milk for two or more consecutive reports. Blood samples were collected from 100 Holstein dairy cows at five time points at -8 and -4 weeks before parturition, at the week of SCM diagnosis, and +4 and +8 weeks after parturition. Twenty healthy control cows (CON) and six cows that were diagnosed with SCM were selected for serum analysis with GC-MS. At -8 weeks a total of 13 metabolites were significantly altered in SCM cows. In addition, at the week of SCM diagnosis 17 metabolites were altered in these cows. Four weeks after parturition 10 metabolites were altered in SCM cows and at +8 weeks 11 metabolites were found to be different between the two groups. Valine (Val), serine (Ser), tyrosine (Tyr), and phenylalanine (Phe) had very good predictive abilities for SCM and could be used at -8 weeks and -4 weeks before calving. Combination of Val, isoleucine (Ile), Ser, and proline (Pro) can be used as diagnostic biomarkers of SCM during early stages of lactation at +4 to +8 weeks after parturition. In conclusion, SCM is preceded and followed by alteration in AA metabolism.

Modification of opiate agonist binding by pertussis toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abood, M.E.; Lee, N.M.; Loh, H.H.

1986-03-05

Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin.more » This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.« less

Hippocampal Dendritic Spines Modifications Induced by Perinatal Asphyxia

PubMed Central

Saraceno, G. E.; Castilla, R.; Barreto, G. E.; Gonzalez, J.; Kölliker-Frers, R. A.; Capani, F.

2012-01-01

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although Western Blot analysis also showed a slight decrease in β-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA. PMID:22645692

Al cation induces aggregation of serum proteins.

PubMed

Chanphai, P; Kreplak, L; Tajmir-Riahi, H A

2017-07-15

Al cation is known to induce protein fibrillation and causes several neurodegenerative disorders. We report the spectroscopic, thermodynamic analysis and AFM imaging for the Al cation binding process with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. Hydrophobicity played a major role in Al-protein interactions with more hydrophobic b-LG forming stronger Al-protein complexes. Thermodynamic parameters ΔS, ΔH and ΔG showed Al-protein bindings occur via hydrophobic and H-bonding contacts for b-LG, while van der Waals and H-bonding interactions prevail in HSA and BSA adducts. AFM clearly indicated that aluminum cations are able to force BSA and b-LG into larger or more robust aggregates than HSA, with HSA 4±0.2 (SE, n=801) proteins per aggregate, for BSA 17±2 (SE, n=148), and for b-LG 12±3 (SE, n=151). Thioflavin T test showed no major protein fibrillation in the presence of Al cation. Al complexation induced major alterations of protein conformations with the order of perturbations b-LG>BSA>HSA. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased serum nonesterified fatty acid and low ionised calcium concentrations are associated with post partum colic in mares.

PubMed

Holcombe, S J; Embertson, R M; Kurtz, K A; Roessner, H A; Wismer, S E; Geor, R J; Kaneene, J B

2016-01-01

Increased serum nonesterified fatty acids (NEFA) and decreased serum electrolytes are linked to abdomasal displacements in post partum dairy cattle. Post partum colic in mares may be associated with metabolic changes specific to pregnancy and the periparturient period. To determine if fluctuations in serum NEFA, ionised calcium (iCa) and magnesium (iMg) occurred in periparturient mares and if these alterations were associated with post partum colic. Longitudinal observational study. Mares from 3 farms in central Kentucky were enrolled. Blood samples were collected 14 days prior to the estimated foaling date, within 4 days post parturition, and 14 and 28 days after foaling for batch analysis of serum NEFA, iCa and iMg. Health information was provided by farm managers and veterinarians. Data were analysed using Kruskal-Wallis χ(2) statistic for nonparametric data and a matched case/control approach. Repeated measures logistic regression models were developed. Serum NEFAs were higher at 14-1 day before foaling (mean ± s.d., mmol/l), 0.28 ± 0.12, P = 0.04 and from foaling to 4 days after foaling, 0.29 ± 0.20 (P = 0.05) in mares that developed colic compared with those that did not colic, 0.19 ± 0.05 and 0.21 ± 0.14, respectively. Ionised calcium was lower at 15-28 days post foaling in mares that showed colic, 1.50 ± 0.17 compared to mares that did not colic, 1.60 ± 0.12, P = 0.02. Risk of colic in post partum mares increased 38% for each 0.1 mmol/l increase in serum NEFA (odds ratio = 1.38, 95% confidence interval 1.06-1.81, P = 0.02). Mares with post partum colic had significantly higher serum NEFA and lower iCa prior to the colic episode compared with mares that did not develop colic. Monitoring these metabolic alterations may lead to predictive and preventive colic strategies for post partum mares. © 2015 EVJ Ltd.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C

PubMed Central

Weaver, Virginia M.; Kim, Nam-Soo; Lee, Byung-Kook; Parsons, Patrick J.; Spector, June; Fadrowski, Jeffrey; Jaar, Bernard G.; Steuerwald, Amy J.; Todd, Andrew C.; Simon, David; Schwartz, Brian S.

2011-01-01

Cadmium is a well known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) μg/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73 m2, respectively. The eGFR measures were moderately correlated (rs = 0.5; p less than 0.001). After adjustment, ln(urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln(urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient = 4.1 ml/min/1.73 m2; 95% confidence interval =1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential. PMID:21871619

Cytoplasmic dynein undergoes intracellular redistribution concomitant with phosphorylation of the heavy chain in response to serum starvation and okadaic acid.

PubMed

Lin, S X; Ferro, K L; Collins, C A

1994-11-01

Cytoplasmic dynein is a microtubule-binding protein which is considered to serve as a motor for retrograde organelle movement. In cultured fibroblasts, cytoplasmic dynein localizes primarily to lysosomes, membranous organelles whose movement and distribution in the cytoplasm have been shown to be dependent on the integrity of the microtubule cytoskeleton. We have recently identified conditions which lead to an apparent dissociation of dynein from lysosomes in vivo, indicating that alterations in membrane binding may be involved in the regulation of retrograde organelle movement (Lin, S. X. H., and C. A. Collins. 1993. J. Cell Sci. 105:579-588). Both brief serum withdrawal and low extracellular calcium levels induced this alteration, and the effect was reversed upon addition of serum or additional calcium. Here we demonstrate that the phosphorylation state of the dynein molecule is correlated with changes in its intracellular distribution in normal rat kidney fibroblasts. Dynein heavy chain phosphorylation level increased during serum starvation, and decreased back to control levels upon subsequent addition of serum. We found that okadaic acid, a phosphoprotein phosphatase inhibitor, mimicked the effects of serum starvation on both phosphorylation and the intracellular redistribution of dynein from a membrane-associated pool to one that was more soluble, with similar dose dependence for both phenomena. Cell fractionation by differential detergent extraction revealed that a higher proportion of dynein was present in a soluble pool after serum starvation than was found in comparable fractions from control cells. Our data indicate that cytoplasmic dynein is phosphorylated in vivo, and changes in phosphorylation state may be involved in a regulatory mechanism affecting the distribution of this protein among intracellular compartments.

THE ALTERATION OF INTRACELLULAR ENZYMES

PubMed Central

Kaplan, J. Gordin

1954-01-01

activated by concentrations of altering agent which cause no decrease in viability at all. Hence alteration, unlike death, may not be all-or-none per cell. 6. The fact that the biological criterion being examined was the activation of a water-soluble enzyme rules out the possibility that the reason for the logarithmic increase in altering activity with chain length was increase in concentration of the altering agent in some intracellular fat phase. It is concluded that these surface-active agents cause enzyme alteration by becoming adsorbed at some intracellular interface and thus causing, directly or indirectly, the modification of catalase properties. 7. It is considered that these data support, but do not provide critical proof for, the interfacial hypothesis, which states that catalase is present at the intracellular interface in question, but is desorbed into solution as a consequence of the alteration process. PMID:13211996

Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers.

PubMed

Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P V L N; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

2016-01-01

Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient's serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet's serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10-6 in Fischer's exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis.

Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers

PubMed Central

Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P. V. L. N.; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

2016-01-01

Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient’s serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet’s serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10−6 in Fischer’s exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis. PMID:26958841

Influence of storage conditions on aluminum concentrations in serum, dialysis fluid, urine, and tap water.

PubMed

Wilhelm, M; Ohnesorge, F K

1990-01-01

The influence of storage temperature, vessel type, and treatment on alterations of aluminum (Al) concentrations in serum, urine, and dialysis fluid samples was studied at three different concentrations for each sample over an 18-month period. Furthermore, the influence of acidification on Al levels in tap water, urine, and dialysis fluid samples was studied over a four-month period. Al was measured by atomic absorption spectrometry. Sample storage in glass vessels was unsuitable, whereas only minor alterations of Al levels were observed with storage in polypropylene tubes, polystyrene tubes, and Monovettes. By using appropriate plastic containers, acid washing of the vessels showed no improvement. Frozen storage was superior compared with 4 degrees C, whereas storage at -80 degrees C offered no advantage compared with storage at -20 degrees C. Acidification of tap water samples was necessary to stabilize Al levels during storage. No striking effect of acidification on Al levels in urine and dialysis fluid samples was found. It is concluded that longterm storage of serum, urine, tap water, and dialysis fluid samples is possible if appropriate conditions are used.

Aging induced ER stress alters sleep and sleep homeostasis

PubMed Central

Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

2014-01-01

Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

Effect of long-distance transportation on serum metabolic profiles of steer calves.

PubMed

Takemoto, Satoshi; Tomonaga, Shozo; Funaba, Masayuki; Matsui, Tohru

2017-12-01

Long-distance transportation is sometimes inevitable in the beef industry because of the geographic separation of major breeding and fattening areas. Long-distance transportation negatively impacts production and health of cattle, which may, at least partly, result from the disturbance of metabolism during and after transportation. However, alteration of metabolism remains elusive in transported cattle. We investigated the effects of transportation on the metabolomic profiles of Holstein steer calves. Non-targeted analysis of serum concentrations of low molecular weight metabolites was performed by gas chromatography mass spectrometry. Transportation affected 38 metabolites in the serum. A pathway analysis suggested that 26, 10, and 10 pathways were affected immediately after transportation, and 3 and 7 days after transportation, respectively. Some pathways were disturbed only immediately after transportation, likely because of feed and water withdrawal during transit. Nicotinate and nicotinamide metabolism, and citric acid cycle were affected for 3 days after transportation, whereas propionate metabolism, phenylalanine and tyrosine metabolism were affected throughout the experiment. Four pathways were not affected immediately after transportation, but were altered thereafter. These results suggested that many metabolic pathways had marked perturbations during transportation. Metabolites such as citric acid, propionate, tyrosine and niacin can be candidate supplements for mitigating transportation-induced adverse effects. © 2017 Japanese Society of Animal Science.

The Investigation of Serum Vaspin Level in Atherosclerotic Coronary Artery Disease

PubMed Central

Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

2012-01-01

Background It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Methods Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 oC by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Results Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Conclusion Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Keywords Coronary artery disease; Vaspin; Adipokine PMID:22505983

The investigation of serum vaspin level in atherosclerotic coronary artery disease.

PubMed

Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

2012-04-01

It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 (o)C by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Coronary artery disease; Vaspin; Adipokine.

Evaluation of serum uric acid levels in normal pregnant Nigerian women.

PubMed

Nwagha, U I; Ejezie, F E; Iyare, E E

2009-03-01

Hypertensive disorders in pregnancy are common in our environment. The aetiology is unknown and the prognostic indicators of the severity of maternal and fetal complications are variable. The level of uric acid, which is one of the prognostic indicators, is altered in normal pregnancy and as pregnancy advances. Base line values are thus extremely important to enable reasonable prognostic assessment in hypertensive pregnancies. To determine levels of serum uric acid during normal pregnancy in University of Nigeria Teaching Hospital (UNTH) Enugu. settings and methods: Sixty- five pregnant and 65 non-pregnant women with age range 20-38 years were recruited. The pregnant women were in their second and third trimesters, attending antenatal clinic at the University of Nigeria Teaching Hospital Enugu. Serum levels of uric acid were determined for the entire subjects. The serum uric acid levels were significantly lower in the pregnant women than in controls (P < 0.001). 0.15 +/- 0.03 mmol/L in the second trimester, 0.14 +/- 0.02 mmol/L in the third trimester and 0.29 +/- 0.04 mmoL for control. The low levels in pregnancy and as pregnancy progresses should be taken into consideration when monitoring hypertensive disorders in pregnancy using serum uric acid. Thus levels that are within normal for non pregnant population may indeed be an indication for intervention in pregnancies complicated by preeclampsia.

Dyslipidemia-associated alterations in B cell subpopulation frequency and phenotype during experimental atherosclerosis.

PubMed

Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A; Ramírez-Pineda, José R; Yassin, Lina M

2016-04-01

Lymphocytes, the cellular effectors of adaptive immunity, are involved in the chronic inflammatory process known as atherosclerosis. Proatherogenic and atheroprotective properties have been ascribed to B cells. However, information regarding the role of B cells during atherosclerosis is scarce. Both the frequency and the phenotype of B cell subpopulations were studied by flow cytometry in wild type and apolipoprotein-E-deficient (apoE(-/-)) mice fed a high-fat (HFD) or control diet. Whereas the proportion of follicular cells was decreased, transitional 1-like cells were increased in mice with advanced atherosclerotic lesions (apoE(-/-) HFD). B cells in atherosclerotic mice were more activated, indicated by their higher surface expression of CD80, CD86, CD40 and CD95 and increased serum IgG1 levels. In the aorta, a decreased frequency of B cells was observed in mice with advanced atherosclerosis. Low expression of CD19 was observed on B cells from the spleen, aorta and lymph nodes of apoE(-/-) HFD mice. This alteration correlated with serum levels of IgG1 and cholesterol. A reduction in CD19 expression was induced in splenic cells from young apoE(-/-) mice cultured with lipemic serum. These results show that mice with advanced atherosclerosis display a variety of alterations in the frequency and phenotype of B lymphocytes, most of which are associated with dyslipidemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Discrimination of rectal cancer through human serum using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Yang, Tianyue; Li, Siqi; Zhang, Su; Jin, Lili

2015-05-01

In this paper, surface-enhanced Raman spectroscopy (SERS) was used to detect the changes in blood serum components that accompany rectal cancer. The differences in serum SERS data between rectal cancer patients and healthy controls were examined. Postoperative rectal cancer patients also participated in the comparison to monitor the effects of cancer treatments. The results show that there are significant variations at certain wavenumbers which indicates alteration of corresponding biological substances. Principal component analysis (PCA) and parameters of intensity ratios were used on the original SERS spectra for the extraction of featured variables. These featured variables then underwent linear discriminant analysis (LDA) and classification and regression tree (CART) for the discrimination analysis. Accuracies of 93.5 and 92.4 % were obtained for PCA-LDA and parameter-CART, respectively.

Impact of diabetic serum on endothelial cells: An in-vitro-analysis of endothelial dysfunction in diabetes mellitus type 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muenzel, Daniela; Lehle, Karla; Haubner, Frank

2007-10-19

Diabetic endothelial dysfunction was characterized by altered levels of adhesion molecules and cytokines. Aim of our study was to evaluate the effects of diabetic serum on cell-growth and proinflammatory markers in human saphenous vein endothelial cells (HSVEC) from diabetic and non-diabetic patients. Diabetic serum showed (1) complementary proliferative activity for non-diabetic and diabetic HSVEC, (2) unchanged surface expression of adhesion molecules, and (3) elevated levels of sICAM-1 in HSVEC of all donors. The concentration of sVCAM-1 was increased only in diabetic cells. The proinflammatory state of diabetic HSVEC characterized by increased levels of cytokines was compensated. We concluded that evenmore » under normoglycemic conditions the serum itself contains critical factors leading to abnormal regulation of inflammation in diabetics. We introduced an in vitro model of diabetes representing the endothelial situation at the beginning of diabetes (non-diabetic cells/diabetic serum) as well as the diabetic chronic state (diabetic cells/diabetic serum)« less

Concentration-dependent reversible self-oligomerization of serum albumins through intermolecular β-sheet formation.

PubMed

Bhattacharya, Arpan; Prajapati, Roopali; Chatterjee, Surajit; Mukherjee, Tushar Kanti

2014-12-16

Proteins inside a cell remain in highly crowded environments, and this often affects their structure and activity. However, most of the earlier studies involving serum albumins were performed under dilute conditions, which lack biological relevance. The effect of protein-protein interactions on the structure and properties of serum albumins at physiological conditions have not yet been explored. Here, we report for the first time the effect of protein-protein and protein-crowder interactions on the structure and stability of two homologous serum albumins, namely, human serum albumin (HSA) and bovine serum albumin (BSA), at physiological conditions by using spectroscopic techniques and scanning electron microscopy (SEM). Concentration-dependent self-oligomerization and subsequent structural alteration of serum albumins have been explored by means of fluorescence and circular dichroism spectroscopy at pH 7.4. The excitation wavelength (λex) dependence of the intrinsic fluorescence and the corresponding excitation spectra at each emission wavelength indicate the presence of various ground state oligomers of serum albumins in the concentration range 10-150 μM. Circular dichroism and thioflavin T binding assay revealed formation of intermolecular β-sheet rich interfaces at high protein concentration. Excellent correlations have been observed between β-sheet content of both the albumins and fluorescence enhancement of ThT with protein concentrations. SEM images at a concentration of 150 μM revealed large dispersed self-oligomeric states with sizes vary from 330 to 924 nm and 260 to 520 nm for BSA and HSA, respectively. The self-oligomerization of serum albumins is found to be a reversible process; upon dilution, these oligomers dissociate into a native monomeric state. It has also been observed that synthetic macromolecular crowder polyethylene glycol (PEG 200) stabilizes the self-associated state of both the albumins which is contrary to expectations that the

Investigation of serum Ki-67 as a biomarker in tumor-bearing dogs.

PubMed

Neumann, Stephan; Schuettler, Julia; Frenz, Meike; Kaup, Franz-Josef; Gessler, Frank

2017-02-01

Because of the limited number of tumor markers in veterinary medicine, there is need for identifying new markers. Ki-67 has been investigated as a tissue marker of malignant alterations. We hypothesized that Ki-67 would also be measurable in serum and should therefore be elevated in cases of malignancy. The purpose of this prospective study was to measure Ki-67 in clinically healthy dogs, dogs with nonmalignant diseases, and dogs with malignant tumors. Samples from 8 healthy dogs, 13 dogs with nonmalignant diseases, and 20 dogs with malignant tumors were collected. Ki-67 was measured using the commercially available canine-specific ELISA. Results demonstrated undetectable Ki-67 serum concentrations in healthy dogs. Dogs with nonmalignant diseases displayed low Ki-67 serum concentrations. In contrast, dogs with malignancies showed significantly increased serum Ki-67 concentrations compared with the healthy (p<0.001) or nonmalignant diseased dogs (p<0.001). The degree of malignancy had a positive influence on serum Ki-67 levels. In contrast, no influence of tumor size on Ki-67 serum concentration was observed (p>0.05). Comparing healthy dogs and tumor bearing dogs a sensitivity of 0.75 and a specificity of 1.0 can be calculated using a Ki-67 cut-off value of 5.5pg/mL. When dogs with a low degree of malignancy were compared with dogs of moderate-to-severe degree malignant tumors a sensitivity of 1.0 and a specificity of 1.0 can be observed at a Ki-67 cut-off value of 19.25pg/mL. In conclusion, our results demonstrate an association of malignancies with elevated Ki-67 serum concentrations in dogs. Published by Elsevier Ltd.

Seasonal and sex-related variations in serum steroid hormone levels in wild and farmed brown trout Salmo trutta L. in the north-west of Spain.

PubMed

Fregeneda-Grandes, Juan M; Hernández-Navarro, Salvador; Fernandez-Coppel, Ignacio A; Correa-Guimaraes, Adriana; Ruíz-Potosme, Norlan; Navas-Gracia, Luis M; Aller-Gancedo, J Miguel; Martín-Gil, Francisco J; Martín-Gil, Jesús

2013-12-01

Serum steroid profiles were investigated in order to evaluate the potential use of circulating sex steroid levels as a tool for sex identification in brown trout. Changes in the serum concentrations of testosterone (T), progesterone (P), 17-β-estradiol (E2), and cortisol (F) in wild and farmed mature female and male brown trout, Salmo trutta L., were measured in each season (January, May, July, and October) in six rivers and four hatcheries located in the north-west of Spain. Serum cortisol levels in farmed brown trout were significantly higher and showed a seasonal pattern opposite to that found in wild trout. Because levels of the hormones under study can be affected by disruptive factors such as exposure to phytoestrogens (which alters the hypothalamic-pituitary-gonadal axis) and infection with Saprolegnia parasitica (which alters the hypothalamic-pituitary-adrenal axis), both factors are taken into account.

Mass spectrometric characterization of human serum albumin dimer: A new potential biomarker in chronic liver diseases.

PubMed

Naldi, Marina; Baldassarre, Maurizio; Nati, Marina; Laggetta, Maristella; Giannone, Ferdinando Antonino; Domenicali, Marco; Bernardi, Mauro; Caraceni, Paolo; Bertucci, Carlo

2015-08-10

Human serum albumin (HSA) undergoes several structural alterations affecting its properties in pro-oxidant and pro-inflammatory environments, as it occurs during liver cirrhosis. These modifications include the formation of albumin dimers. Although HSA dimers were reported to be an oxidative stress biomarker, to date nothing is known about their role in liver cirrhosis and related complications. Additionally, no high sensitive analytical method was available for HSA dimers assessment in clinical settings. Thus the HSA dimeric form in human plasma was characterized by mass spectrometry using liquid chromatography tandem mass spectrometry (LC-ESI-Q-TOF) and matrix assisted laser desorption time of flight (MALDI-TOF) techniques. N-terminal and C-terminal truncated HSA, as well as the native HSA, undergo dimerization by binding another HSA molecule. This study demonstrated the presence of both homo- and hetero-dimeric forms of HSA. The dimerization site was proved to be at Cys-34, forming a disulphide bridge between two albumin molecules, as determined by LC-MS analysis after tryptic digestion. Interestingly, when plasma samples from cirrhotic subjects were analysed, the dimer/monomer ratio resulted significantly increased when compared to that of healthy subjects. These isoforms could represent promising biomarkers for liver disease. Additionally, this analytical approach leads to the relative quantification of the residual native HSA, with fully preserved structural integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection of thermogenesis in rodents in response to anti-obesity drugs and genetic modification

PubMed Central

Arch, Jonathan R. S.; Trayhurn, Paul

2013-01-01

Many compounds and genetic manipulations are claimed to confer resistance to obesity in rodents by raising energy expenditure. Examples taken from recent and older literature, demonstrate that such claims are often based on measurements of energy expenditure after body composition has changed, and depend on comparisons of energy expenditure divided by body weight. This is misleading because white adipose tissue has less influence than lean tissue on energy expenditure. Application of this approach to human data would suggest that human obesity is usually due to a low metabolic rate, which is not an accepted view. Increased energy expenditure per animal is a surer way of demonstrating thermogenesis, but even then it is important to know whether this is due to altered body composition (repartitioning), or increased locomotor activity rather than thermogenesis per se. Regression analysis offers other approaches. The thermogenic response to some compounds has a rapid onset and so cannot be due to altered body composition. These compounds usually mimic or activate the sympathetic nervous system. Thermogenesis occurs in, but may not be confined to, brown adipose tissue. It should not be assumed that weight loss in response to these treatments is due to thermogenesis unless there is a sustained increase in 24-h energy expenditure. Thyroid hormones and fibroblast growth factor 21 also raise energy expenditure before they affect body composition. Some treatments and genetic modifications alter the diurnal rhythm of energy expenditure. It is important to establish whether this is due to altered locomotor activity or efficiency of locomotion. There are no good examples of compounds that do not affect short-term energy expenditure but have a delayed effect. How and under what conditions a genetic modification or compound increases energy expenditure influences the decision on whether to seek drugs for the target or take a candidate drug into clinical studies. PMID:23580228

Serum-free keloid fibroblast cell culture: an in vitro model for the study of aberrant wound healing.

PubMed

Koch, R J; Goode, R L; Simpson, G T

1997-04-01

The purpose of this study was to develop an in vitro serum-free keloid fibroblast model. Keloid formation remains a problem for every surgeon. Prior evaluations of fibroblast characteristics in vitro, especially those of growth factor measurement, have been confounded by the presence of serum-containing tissue culture media. The serum itself contains growth factors, yet has been a "necessary evil" to sustain cell growth. The design of this study is laboratory-based and uses keloid fibroblasts obtained from five patients undergoing facial (ear lobule) keloid removal in a university-affiliated clinic. Keloid fibroblasts were established in primary cell culture and then propagated in a serum-free environment. The main outcome measures included sustained keloid fibroblast growth and viability, which was comparable to serum-based models. The keloid fibroblast cell cultures exhibited logarithmic growth, sustained a high cellular viability, maintained a monolayer, and displayed contact inhibition. Demonstrating model consistency, there was no statistically significant difference between the mean cell counts of the five keloid fibroblast cell lines at each experimental time point. The in vitro growth of keloid fibroblasts in a serum-free model has not been done previous to this study. The results of this study indicate that the proliferative characteristics described are comparable to those of serum-based models. The described model will facilitate the evaluation of potential wound healing modulators, and cellular effects and collagen modifications of laser resurfacing techniques, and may serve as a harvest source for contaminant-free fibroblast autoimplants. Perhaps its greatest utility will be in the evaluation of endogenous and exogenous growth factors.

Specific histone modification responds to arsenic-induced oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Lu

To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P < 0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showedmore » that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: β = 0.16; P = 0.042, H3K18ac: β = − 0.24; P = 0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO{sub 2} treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage. - Highlights: • H3K18ac, H3K9me2 and H3K36me3 were associated with arsenic exposed levels. • H3K18ac and H3K36me3 were correlated with oxidative damage induced by arsenic. • H3K18ac and H3K36me3 might involve in transcriptional regulation of OSR genes. • Dysregulation of H3K18ac and H3K36me3 might be biomarkers of arsenic toxicity.« less

Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome

PubMed Central

Lee, Hong Sub; Lee, Kwang Jae

2017-01-01

Background/Aims The role of dietary factors in the pathogenesis of irritable bowel syndrome (IBS) is still unclear. The aim of this study was to compare IgG4 levels to common food antigens between patients with IBS and healthy controls. Methods Thirty-two patients diagnosed as IBS according to the Rome III criteria (12 diarrhea subgroup; 20 non-diarrhea subgroup) and 32 sex and age-matched healthy controls participated in the study. Serum IgG4 titers to 90 common foods were measured in each subject. The number of subjects with positivity defined as the cut-off value ≥ 0.7 U/mL was compared. Results Patients with IBS had significantly higher IgG4 titers to wheat, leek and taro compared to those of controls. Serum IgG4 titers to ginger, cocoa, walnut, white radish, onion, and lettuce in IBS patients tended to be higher than controls. IgG4 titers to wheat, gluten and gliadin in the diarrhea subgroup, and lettuce, leek and taro in the non-diarrhea subgroup tended to be higher compared with controls. The number of subjects with positivity to apple, orange, lettuce, and leek was significantly higher in IBS patients than controls. The number of subjects with positivity to apple, orange, gluten, and gliadin in the diarrhea subgroup, and egg white, pineapple, soybean, lettuce, and leek in the non-diarrhea subgroup was significantly higher compared with controls. Conclusions Serum IgG4 antibody levels to some common foods are abnormally elevated in IBS patients. The type of foods with abnormally elevated serum IgG4 titers in the diarrhea subgroup may be different from that in the non-diarrhea subgroup. PMID:28992678

Ibuprofen does not affect serum electrolyte concentrations after an ultradistance run

PubMed Central

Dumke, Charles L; Nieman, David C; Oley, Kevin; Lind, Robert H

2007-01-01

Objective To determine the effects of ibuprofen on serum electrolyte concentrations after a 160 km running race. Methods Twenty nine subjects (mean (SD) age 47.9 (7.4) years) ingested 600 mg ibuprofen the day before, and 1200 mg ibuprofen during, a 160 km competitive trail running race (approximately every 4 h in 200 mg doses). Twenty five control subjects (mean (SD) age 46.8 (10.3) years) avoided ingestion of ibuprofen before or during the race. Blood was drawn on the day before the race and immediately after the race. Serum biochemical profiles were analysed by a clinical laboratory. Significant effects of treatment and time were determined with a general linear model with repeated measures. Results Subjects in the two groups did not differ by age, training volume, race experience, body mass index, body fat, or finishing time (25.8 (3.3) vs 25.6 (3.9) h). Body weight did not change significantly over the race (measured before, mid‐race (90 km), and after). Ibuprofen ingestion did not significantly affect any of the serum markers including creatine kinase (p = 0.16). A significant decrease in serum sodium (p = 0.006), potassium (p = 0.001), chloride (p<0.001), calcium (p<0.001), albumin (p<0.001) and globulin (p<0.001) was observed after the race. Increases were seen in creatine kinase (p<0.001), creatinine (p<0.001), blood urea nitrogen (p<0.001), uric acid (p<0.001) and glucose (p<0.001) as the result of the race. Conclusions These data suggest that the non‐specific cyclo‐oxygenase inhibitor, ibuprofen, does not alter serum electrolyte concentrations during ultradistance running. However, the stress of ultradistance running appears to be related to significant changes in certain serum markers. PMID:17331976

Implications of recent research on microstructure modifications, through heat-related processing and trait alteration to bio-functions, molecular thermal stability and mobility, metabolic characteristics and nutrition in cool-climate cereal grains and other types of seeds with advanced molecular techniques.

PubMed

Ying, Yuguang; Zhang, Huihua; Yu, Peiqiang

2018-02-16

The cutting-edge synchrotron radiation based and globar-sourced vibrational infrared microspectroscopy have recently been developed. These novel techniques are able to reveal structure features at cellular and molecular levels with the tested tissues being intact. However, to date, the advanced techniques are unfamiliar or unknown to food and feed scientists and have not been used to study the molecular structure changes in cool-climate cereal grain seeds and other types of bio-oil and bioenergy seeds. This article aims to provide some recent research in cool-climate cereal grains and other types of seeds on molecular structures and metabolic characteristics of carbohydrate and protein, and implication of microstructure modification through heat-related processing and trait alteration to bio-functions, molecular thermal stability and mobility, and nutrition with advanced molecular techniques- synchrotron radiation based and globar-sourced vibrational infrared microspectroscopy in the areas of (1) Inherent microstructure of cereal grain seeds; (2) The nutritional values of cereal grains; (3) Impact and modification of heat-related processing to cereal grain; (4) Conventional nutrition evaluation methodology; (5) Synchrotron radiation-based and globar-sourced vibrational (micro)-spectroscopy for molecular structure study and molecular thermal stability and mobility, and (6) Recent molecular spectroscopic technique applications in research on raw, traits altered and processed cool-climate cereal grains and other types of seeds. The information described in this article gives better insights of research progress and update in cool-climate cereal grains and other seeds with advanced molecular techniques.

ALTERED SERUM SEX STEROIDS AND VITELLOGENIN INDUCTION IN WALLEYE (STIZOSTEDION VITREUM) COLLECTED NEAR A METROPOLITAN SEWAGE TREATMENT PLANT

EPA Science Inventory

Feral, male walleye collected from the Mississippi River below the St. Paul metropolitan sewage treatment plant (STP) contained measurable levels of the estrogen-inducible, female egg protein, vitellogenin. These same fish showed significantly decreased serum androgen and signifi...

Effect of the conditions of isolation on the physicochemical properties of human serum albumin in the norm and with pathology

NASA Astrophysics Data System (ADS)

Ivanov, A. I.; Zhbankov, R. G.; Korolenko, E. A.; Korolik, E. V.; Meleshchenko, L. A.; Sarnatskaya, V. V.; Nikolaev, V. G.; Nikolaichik, V. V.; Yushko, L. A.

1997-01-01

Differential scanning calorimetry and IR spectrosocopy were used to investigate the effect of the procedure of isolation of human serum albumin on its physicochemical characteristics. It is shown that fractionation of blood plasma with ethylene glycol followed by ion exchange chromatography can be used to obtain albumin of normal donors that is similar to the albumin in the nonfractionated plasma according to melting thermograms. Endotherms of human serum albumin samples that were obtained by affinity chromatography and preparative electrophoresis are bimodal, unlike the monophasic for albumin obtained by polyethylene glycol precipitation. These changes result from a higher content of nonetherified fatty acids in the albumin samples obtained by affinity chromatography and from modification of the secondary protein structure in the samples obtained by electrophoresis. Analysis of melting thermograms of serum albumin from patients with uremia, chronic hepatitis, and peritonitis shows that fractionation of blood with polyethylene glycol preserves the thermodynamic characteristics of the various pathological serum albumins to the greatest extent. The present results demonstrate the advantage of polyethylene glycol fractionation for isolation of native preparations of normal and “pathological” human serum albumin.

Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

PubMed Central

Cubero-Millán, Isabel; Molina-Carballo, Antonio; Machado-Casas, Irene; Fernández-López, Luisa; Martínez-Serrano, Sylvia; Tortosa-Pinto, Pilar; Ruiz-López, Aida; Luna-del-Castillo, Juan-de-Dios; Uberos, José; Muñoz-Hoyos, Antonio

2014-01-01

The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria) were divided into subgroups using the “Children’s Depression Inventory” (CDI). Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD) of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit. PMID:25257531

Exploiting Epigenetic Alterations in Prostate Cancer.

PubMed

Baumgart, Simon J; Haendler, Bernard

2017-05-09

Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

Lipolytic signaling in response to acute exercise is altered in female mice following ovariectomy

PubMed Central

Wohlers, Lindsay M.; Jackson, Kathryn C.; Spangenburg, Espen E.

2011-01-01

Impaired ovarian function alters lipid metabolism, ultimately resulting in increased visceral fat mass. Currently, we have a poor understanding of alterations in signaling events regulating lipolysis after ovarian function declines. The purpose of this study was to determine if cellular mechanisms regulating lipolysis are altered in mice after ovariectomy (OVX) and if OVX mice exhibit impaired lipolytic signaling when stimulated by acute exercise. SHAM and OVX mice were divided into two groups: control (SHAM cont; OVX cont) or acute treadmill exercise (SHAM ex; OVX ex). The omental/mesenteric (O/M) fat mass of all OVX mice was significantly greater than the SHAM mice. Serum glycerol and blood glucose levels were significantly elevated in OVX cont compared to SHAM cont. Treadmill exercise increased serum glycerol levels only in SHAM mice, with no exercise-induced change detected in OVX mice. NEFA levels were significantly elevated by acute exercise in the SHAM and OVX groups. In O/M fat from both OVX groups there were significant increases in cytosolic ATGL and PLIN2 in the fat cake fraction with concurrent reductions in PLIN1 in the fat cake compared to SHAM. Further, exercise induced significant increases in HSL Ser660 phosphorylation in SHAM mice, but not OVX mice. This suggests that reduced ovarian function has significant effects on critical lipolytic cell signaling mechanisms in O/M adipose tissue. PMID:21815195

Early Endothelial Bioactivity of Serum after Diesel Exhaust ...

EPA Pesticide Factsheets

Adverse cardiovascular effects of air pollution are often associated with a spike in systemic proinflammatory biomarkers, but causative linkage between circulating factors and deleterious outcomes following exposure remains elusive. Endothelial dysfunction is a consequence of systemic inflammation and precedes multiple cardiovascular pathologies. The purpose of this study was to examine the plausibility of serum-bound factors as initiators of an air pollution-induced pathologic sequelae beginning with endothelial injury, and later, cardiac dysfunction. We hypothesized that serum taken from diesel exhaust (DE)-exposed rats that develop cardiac dysfunction would alter aortic endothelial cell function in vitro. To assess cardiac function in vivo, left ventricular pressure (LVP) assessments were conducted in rats one day after a single 4 hour whole body exposure to 150 or 500 μg/m3 DE or filtered air. Rat aortic endothelial cells (RAEC) were then exposed to diluted serum (10%) collected 1 hour after exposure from a separate cohort of similarly exposed rats for measures of VCAM-1, cell viability, nitric oxide synthase (NOS) levels, and mRNA expression of key mediators of inflammation. Exposure of rats to 150 or 500 μg/m3 DE increased heart rate (HR) after exposure relative to rats exposed to filtered air, suggesting a shift towards increased sympathetic tone. LVP and HR in DE-exposed rats (500 μg/m3 DE) failed to recover to normal levels after challenge with the

Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice.

PubMed

Tajima, Soichiro; Ikeda, Yasumasa; Enomoto, Hideaki; Imao, Mizuki; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Miyamoto, Licht; Ishizawa, Keisuke; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-08-01

Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.

A Robust Analytical Approach for the Identification of Specific Protein Carbonylation Sites: Metal-Catalyzed Oxidations of Human Serum Albumin

PubMed Central

Ugur, Zafer; Gronert, Scott

2017-01-01

The formation of protein carbonyls in the metal-catalyzed oxidation of human serum albumin (HSA) is characterized using a new analytical approach that involves tagging the modification site with multiple hydrazide reagents. Protein carbonyl formation at lysine and arginine residues was catalyzed with copper and iron ions, and the resulting oxidation patterns in HSA are contrasted. A total of 18 modification sites were identified with iron ion catalysis and 14 with copper ion catalysis. However, with the more stringent requirement of identification with at least two tagging reagents, the number of validated modification sites drops to 10 for iron and 9 for copper. Of the 14 total validated sites, there were only five in common for the two metal ions. The results illustrate the value of using multiple tagging agents and highlight the selective and specific nature of metal-catalyzed protein oxidations. PMID:28303033

Serum uric Acid level and diverse impacts on regional arterial stiffness and wave reflection.

PubMed

Bian, Suyan; Guo, Hongyang; Ye, Ping; Luo, Leiming; Wu, Hongmei; Xiao, Wenkai

2012-01-01

Both increased arterial stiffness and hyperuricaemia are associated with elevated cardiovascular risks. Little is known about the relations of serum uric acid (UA) level to regional arterial stiffness and wave reflection. The aim of the study was to investigate the gender-specific association of serum UA and indices of arterial function in a community-based investigation in China. Cross-sectional data from 2374 adults (mean age 58.24 years) who underwent routine laboratory tests, regional pulse wave velocity (PWV) and pulse wave analysis measurements were analyzed in a gender-specific manner. None of the participants had atherosclerotic cardiovascular disease, chronic renal failure, systemic inflammatory disease, gout, or were under treatment which would affect serum UA level. Men had higher serum UA level than women. Subjects with hyperuricaemia had significantly higher carotid-ankle PWV in both genders (P< 0.05), and the carotid-femoral PWV (PWVc-f) was higher in women (P< 0.001) while the augmentation index was marginally lower in men (P = 0.049). Multiple regression analysis showed that serum UA was an independent determinant only for PWVc-f in women (β = 0.104, P = 0.027) when adjusted for atherogenic confounders. No other independent relationship was found between UA level and other surrogates of arterial stiffness. Serum UA levels are associated with alterations in systemic arterial stiffness that differ in men and women. Women might be more susceptible to large vascular damage associated with hyperuricaemia.

Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

PubMed

Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

2016-02-05

Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

PubMed

Caetano, Luiz Carlos; Bonfleur, Maria Lúcia; Ribeiro, Rosane Aparecida; Nardelli, Tarlliza Romanna; Lubaczeuski, Camila; do Nascimento da Silva, Juliana; Carneiro, Everardo Magalhães; Balbo, Sandra Lucinei

2017-03-01

Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1β or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

PubMed

Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

2016-08-01

The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of covalent modification by 4-hydroxy-2-nonenal on the noncovalent oligomerization of ubiquitin.

PubMed

Grasso, Giuseppe; Axelsen, Paul H

2017-01-01

When lipid membranes containing ω-6 polyunsaturated fatty acyl chains are subjected to oxidative stress, one of the reaction products is 4-hydroxy-2-nonenal (HNE)-a chemically reactive short chain alkenal that can covalently modify proteins. The ubiquitin proteasome system is involved in the clearing of proteins modified by oxidation products such as HNE, but the chemical structure, stability and function of ubiquitin may be impaired by HNE modification. To evaluate this possibility, the susceptibility of ubiquitin to modification by HNE has been characterized over a range of concentrations where ubiquitin forms non-covalent oligomers. Results indicate that HNE modifies ubiquitin at only two of the many possible sites, and that HNE modification at these two sites alters the ubiquitin oligomerization equilibrium. These results suggest that any role ubiquitin may have in clearing proteins damaged by oxidative stress may itself be impaired by oxidative lipid degradation products. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Diketo modification of curcumin affects its interaction with human serum albumin

NASA Astrophysics Data System (ADS)

Shaikh, Shaukat Ali M.; Singh, Beena G.; Barik, Atanu; Ramani, Modukuri V.; Balaji, Neduri V.; Subbaraju, Gottumukkala V.; Naik, Devidas B.; Indira Priyadarsini, K.

2018-06-01

Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU. The respective binding constants of CP, CI and CU with HSA were estimated to be 9.3 × 105, 8.4 × 105 and 2.5 × 105 M-1, which decreased with increasing salt concentration in the medium. The extent of decrease in the binding constant was the highest in CP followed by CI and CU. This revealed that along with hydrophobic interaction other binding modes like electrostatic interactions operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with these compounds suggested that both static and dynamic quenching mechanisms operate, where the contribution of static quenching is higher for CP and CI than that for CU. From fluorescence resonance energy transfer studies, the binding site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind in closer proximity with Trp214 as compared to CI and CP and the same was responsible for efficient energy transfer and the same was also established by fluorescence anisotropy measurements. Furthermore docking simulation complemented the experimental observation, where both electrostatic as well as hydrophobic interactions were indicated between HSA and CP, CI and CU. This study is useful in designing more stable CU derivatives having suitable binding properties with proteins like HSA.

Diketo modification of curcumin affects its interaction with human serum albumin.

PubMed

Shaikh, Shaukat Ali M; Singh, Beena G; Barik, Atanu; Ramani, Modukuri V; Balaji, Neduri V; Subbaraju, Gottumukkala V; Naik, Devidas B; Indira Priyadarsini, K

2018-06-15

Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU. The respective binding constants of CP, CI and CU with HSA were estimated to be 9.3×10 5 , 8.4×10 5 and 2.5×10 5 M -1 , which decreased with increasing salt concentration in the medium. The extent of decrease in the binding constant was the highest in CP followed by CI and CU. This revealed that along with hydrophobic interaction other binding modes like electrostatic interactions operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with these compounds suggested that both static and dynamic quenching mechanisms operate, where the contribution of static quenching is higher for CP and CI than that for CU. From fluorescence resonance energy transfer studies, the binding site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind in closer proximity with Trp214 as compared to CI and CP and the same was responsible for efficient energy transfer and the same was also established by fluorescence anisotropy measurements. Furthermore docking simulation complemented the experimental observation, where both electrostatic as well as hydrophobic interactions were indicated between HSA and CP, CI and CU. This study is useful in designing more stable CU derivatives having suitable binding properties with proteins like HSA. Copyright © 2018 Elsevier B.V. All rights reserved.

Bioactive Surface Modification of Hydroxyapatite

PubMed Central

Okazaki, Yohei; Hiasa, Kyou; Yasuda, Keisuke; Nogami, Keisuke; Mizumachi, Wataru; Hirata, Isao

2013-01-01

The purpose of this study was to establish an acid-etching procedure for altering the Ca/P ratio of the nanostructured surface of hydroxyapatite (HAP) by using surface chemical and morphological analyses (XPS, XRD, SEM, surface roughness, and wettability) and to evaluate the in vitro response of osteoblast-like cells (MC3T3-E1 cells) to the modified surfaces. This study utilized HAP and HAP treated with 10%, 20%, 30%, 40%, 50%, or 60% phosphoric acid solution for 10 minutes at 25°C, followed by rinsing 3 times with ultrapure water. The 30% phosphoric acid etching process that provided a Ca/P ratio of 1.50, without destruction of the grain boundary of HAP, was selected as a surface-modification procedure. Additionally, HAP treated by the 30% phosphoric acid etching process was stored under dry conditions at 25°C for 12 hours, and the Ca/P ratio approximated to 1.00 accidentally. The initial adhesion, proliferation, and differentiation (alkaline phosphatase (ALP) activity and relative mRNA level for ALP) of MC3T3-E1 cells on the modified surfaces were significantly promoted (P < 0.05 and 0.01). These findings show that the 30% phosphoric acid etching process for the nanostructured HAP surface can alter the Ca/P ratio effectively and may accelerate the initial adhesion, proliferation, and differentiation of MC3T3-E1 cells. PMID:23862150

[The alterations of proteins glycosylation in rheumatic diseases].

PubMed

Chludzińska, Anna; Chrostek, Lech; Cylwik, Bogdan

2012-08-01

The alterations in glycosylation of serum glycoproteins were reported in several pathological conditions including rheumatic diseases. The many studies demonstrated the occurrence of some differentially glycosylated plasma immunoglobulins, especially IgG in rheumatoid arthritis. The most characteristic features are the decrease in galactose content, the presence of N-acetylglucosamine and the increase in fucose content. The structure of oligosaccharides attached to the antibody Fc region affect the pharmacokinetics and antibody effector functions of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The changes in immunoglobulin glycosylation was suggested to be important in the etiology of rheumatoid athritis and correlated with the disease severity. In addition to impaired glycosylation of imunoglubulins, in rheumatic diseases exist the disturbances in glycosylation of both acute-phase and non acute-phase response, such as alpha-1 acid glycoprotein, haptoglobin and alpha-2 macroglobulin. The alterations in glycosylation of these glycoproteins were also correlated with the disease activity.

Study of adaptation to altered gravity through systems analysis of motor control.

PubMed

Fox, R A; Daunton, N G; Corcoran, M L

1998-01-01

Maintenance of posture and production of functional, coordinated movement demand integration of sensory feedback with spinal and supra-spinal circuitry to produce adaptive motor control in altered gravity (G). To investigate neuroplastic processes leading to optimal performance in altered G we have studied motor control in adult rats using a battery of motor function tests following chronic exposure to various treatments (hyper-G, hindlimb suspension, chemical distruction of hair cells, space flight). These treatments differentially affect muscle fibers, vestibular receptors, and behavioral compensations and, in consequence, differentially disrupt air righting, swimming, posture and gait. The time-course of recovery from these disruptions varies depending on the function tested and the duration and type of treatment. These studies, with others (e.g., D'Amelio et al. in this volume), indicate that adaptation to altered gravity involves alterations in multiple sensory-motor systems that change at different rates. We propose that the use of parallel studies under different altered G conditions will most efficiently lead to an understanding of the modifications in central (neural) and peripheral (sensory and neuromuscular) systems that underlie sensory-motor adaptation in active, intact individuals.

Study of adaptation to altered gravity through systems analysis of motor control

NASA Astrophysics Data System (ADS)

Fox, R. A.; Daunton, N. G.; Corcoran, M. L.

Maintenance of posture and production of functional, coordinated movement demand integration of sensory feedback with spinal and supra-spinal circuitry to produce adaptive motor control in altered gravity (G). To investigate neuroplastic processes leading to optimal performance in altered G we have studied motor control in adult rats using a battery of motor function tests following chronic exposure to various treatments (hyper-G, hindlimb suspension, chemical distruction of hair cells, space flight). These treatments differentially affect muscle fibers, vestibular receptors, and behavioral compensations and, in consequence, differentially disrupt air righting, swimming, posture and gait. The time-course of recovery from these disruptions varies depending on the function tested and the duration and type of treatment. These studies, with others (e.g., D'Amelio et al. in this volume), indicate that adaptation to altered gravity involves alterations in multiple sensory-motor systems that change at different rates. We propose that the use of parallel studies under different altered G conditions will most efficiently lead to an understanding of the modifications in central (neural) and peripheral (sensory and neuromuscular) systems that underlie sensory-motor adaptation in active, intact individuals.

Body mass index for predicting hyperglycemia and serum lipid changes in Brazilian adolescents.

PubMed

Vieira, Ana Carolina R; Alvarez, Marlene M; Kanaan, Salim; Sichieri, Rosely; Veiga, Gloria V

2009-02-01

To determine the best cut-offs of body mass index for identifying alterations of blood lipids and glucose in adolescents. A probabilistic sample including 577 adolescent students aged 12-19 years in 2003 (210 males and 367 females) from state public schools in the city of Niterói, Southeastern Brazil, was studied. The Receiver Operating Characteristic curve was used to identify the best age-adjusted BMI cut-off for predicting high levels of serum total cholesterol (> or =150 mg/dL), LDL-C (> or =100 mg/dL), serum triglycerides (> or =100 mg/dL), plasma glucose (> 100 mg/dL) and low levels of HDL-C (< 45 mg/dL). Four references were used to calculate sensitivity and specificity of BMI cut-offs: one Brazilian, one international and two American. The most prevalent metabolic alterations (>50%) were: high total cholesterol and low HDL-C. BMI predicted high levels of triglycerides in males, high LDL-C in females, and high total cholesterol and the occurrence of three or more metabolic alterations in both males and females (areas under the curve range: 0.59 to 0.67), with low sensitivity (57%-66%) and low specificity (58%-66%). The best BMI cut-offs for this sample (20.3 kg/m(2) to 21.0 kg/m(2)) were lower than those proposed in the references studied. Although BMI values lower than the International cut-offs were better predictor of some metabolic abnormalities in Brazilian adolescents, overall BMI is not a good predictor of these abnormalities in this population.

Ocean acidification alters fish–jellyfish symbiosis

PubMed Central

Nagelkerken, Ivan; Pitt, Kylie A.; Rutte, Melchior D.; Geertsma, Robbert C.

2016-01-01

Symbiotic relationships are common in nature, and are important for individual fitness and sustaining species populations. Global change is rapidly altering environmental conditions, but, with the exception of coral–microalgae interactions, we know little of how this will affect symbiotic relationships. We here test how the effects of ocean acidification, from rising anthropogenic CO2 emissions, may alter symbiotic interactions between juvenile fish and their jellyfish hosts. Fishes treated with elevated seawater CO2 concentrations, as forecast for the end of the century on a business-as-usual greenhouse gas emission scenario, were negatively affected in their behaviour. The total time that fish (yellowtail scad) spent close to their jellyfish host in a choice arena where they could see and smell their host was approximately three times shorter under future compared with ambient CO2 conditions. Likewise, the mean number of attempts to associate with jellyfish was almost three times lower in CO2-treated compared with control fish, while only 63% (high CO2) versus 86% (control) of all individuals tested initiated an association at all. By contrast, none of three fish species tested were attracted solely to jellyfish olfactory cues under present-day CO2 conditions, suggesting that the altered fish–jellyfish association is not driven by negative effects of ocean acidification on olfaction. Because shelter is not widely available in the open water column and larvae of many (and often commercially important) pelagic species associate with jellyfish for protection against predators, modification of the fish–jellyfish symbiosis might lead to higher mortality and alter species population dynamics, and potentially have flow-on effects for their fisheries. PMID:27358374

Ocean acidification alters fish-jellyfish symbiosis.

PubMed

Nagelkerken, Ivan; Pitt, Kylie A; Rutte, Melchior D; Geertsma, Robbert C

2016-06-29

Symbiotic relationships are common in nature, and are important for individual fitness and sustaining species populations. Global change is rapidly altering environmental conditions, but, with the exception of coral-microalgae interactions, we know little of how this will affect symbiotic relationships. We here test how the effects of ocean acidification, from rising anthropogenic CO2 emissions, may alter symbiotic interactions between juvenile fish and their jellyfish hosts. Fishes treated with elevated seawater CO2 concentrations, as forecast for the end of the century on a business-as-usual greenhouse gas emission scenario, were negatively affected in their behaviour. The total time that fish (yellowtail scad) spent close to their jellyfish host in a choice arena where they could see and smell their host was approximately three times shorter under future compared with ambient CO2 conditions. Likewise, the mean number of attempts to associate with jellyfish was almost three times lower in CO2-treated compared with control fish, while only 63% (high CO2) versus 86% (control) of all individuals tested initiated an association at all. By contrast, none of three fish species tested were attracted solely to jellyfish olfactory cues under present-day CO2 conditions, suggesting that the altered fish-jellyfish association is not driven by negative effects of ocean acidification on olfaction. Because shelter is not widely available in the open water column and larvae of many (and often commercially important) pelagic species associate with jellyfish for protection against predators, modification of the fish-jellyfish symbiosis might lead to higher mortality and alter species population dynamics, and potentially have flow-on effects for their fisheries. © 2016 The Author(s).

A view on elemental distribution alterations of coronary artery walls in atherogenesis

NASA Astrophysics Data System (ADS)

Pallon, J.; Homman, P.; Pinheiro, T.; Halpern, M. J.; Malmqvist, K.

1995-09-01

In this study, the Nuclear Microprobe technique was employed to investigate the elemental concentration alterations of minor and trace elements at the different cellular layers and structures of freeze-dried cryosections of human coronary arteries. Nuclear microprobe analyses enable to determine 7 elements, i.e., P, S, Cl, K, Ca, Fe and Zn in the artery walls. Furthermore, it was possible to identify early modifications of the artery due to the atherosclerosis progression that cannot be detected with specific staining or conventional histological methods. These modifications are shown to be related to abnormal Fe and Zn depositions in the surroundings of the elastic laminae. Later on, the calcifications of these regions occur, contributing to the elastic laminae damage and leading to the atheroma growing and maturation.

Serum cystatin C levels in preterm newborns in our setting: Correlation with serum creatinine and preterm pathologies.

PubMed

Bardallo Cruzado, Leonor; Pérez González, Elena; Martínez Martos, Zoraima; Bermudo Guitarte, Carmen; Granero Asencio, Mercedes; Luna Lagares, Salud; Marín Patón, Mariano; Polo Padilla, Juan

2015-01-01

Cystatin C (CysC) is a renal function marker that is not as influenced as creatinine (Cr) by endogenous or exogenous agents, so it is therefore proposed as a marker in preterm infants. To determine serum CysC values in preterm infants during the first week of life, compared to Cr. To analyze alterations caused by prematurity diseases. The design involved a longitudinal, observational study of prospective cohorts. Groups were based on gestational age (GA): Group A (24-27 weeks), Group B (28-33 weeks), Group C (34-36 weeks). Blood samples were collected at birth, within 48-72hours and after 7 days of life. SPSS v.20 software was used. The statistical methods applied included chi-squared test and ANOVA. A total of 109 preterm infants were included in the study. CysC levels were: 1.54mg/L (±0.28) at birth; 1.38mg/L (±0.36) within 48-72hours of life; 1.50mg/L (±0.31) after 7 days (p<0.05). Cr levels were: 0.64mg/dL (±0.17) at birth; 0.64mg/dL (±0.28) within 48-72hours; 0.56mg/dL (±0.19) after 7 days (P<.05). CysC values were lower in hypotensive patients and those with a respiratory disease (P<.05), and no alterations associated with other diseases were observed. There were no differences in Cr levels associated with any disease. Creatinine levels were higher in patients ≤1.500g (P<.05). Serum CysC decreased within 48-72hours of life, and this decline showed significance (P<.05). The levels increased after 7 days in all 3 GA groups, and there was no difference in CysC levels among the groups. More studies in preterm infants with hypotension and respiratory disease are required. CysC is a better glomerular filtration (GF) marker in ≤1.500g preterm infants. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

An impedimetric immunosensor for highly sensitive detection of IL-8 in human serum and saliva samples: A new surface modification method by 6-phosphonohexanoic acid for biosensing applications.

PubMed

Aydın, Elif Burcu; Sezgintürk, Mustafa Kemal

2018-08-01

In this study, we fabricated a sensitive and label-free impedimetric immunosensor based on 6-phosphonohexanoic acid (PHA) modified ITO electrode for detection of interleukin-8 (IL-8) in human serum and saliva. PHA was first employed to cancer biomarker sensing platform. Anti-IL-8 antibody was used as a biorecognition element and the detection principle of this immunosensor was based on monitoring specific interaction between anti-IL-8 antibody and IL-8 antigen. The morphological characterization of each electrode modification step was analyzed by scanning electron microscopy (SEM), SEM-energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM) while electrochemical characterization was performed by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and single frequency impedance (SFI) techniques. Moreover, the antibody immobilization on the electrode surface was proved Fourier-transform infrared spectroscopy (FTIR) and Raman Spectroscopy. This proposed impedimetric immunosensor exhibited good performances with a wide linear in the range from 0.02 pg/mL to 3 pg/mL as well as a relative low detection limit of 6 fg/mL. The impedimetric immunosensor had a good specificity, stability and reproducibility. This study proved that PHA was a suitable interface material to fabricate an electrochemical biosensor. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Selenylation Modification on Immune-Enhancing Activity of Garlic Polysaccharide

PubMed Central

Qin, Tao; Hu, Yuanliang; Wang, Deyun; Fan, Qiang; Zhang, Cunshuai; Chen, Xingying; Chen, Xiaolan; Liu, Cui; Gao, Zhenzhen; Li, Xiuping

2014-01-01

The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(34) to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h. PMID:24497946

Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

PubMed

Qiu, Shulei; Chen, Jin; Qin, Tao; Hu, Yuanliang; Wang, Deyun; Fan, Qiang; Zhang, Cunshuai; Chen, Xingying; Chen, Xiaolan; Liu, Cui; Gao, Zhenzhen; Li, Xiuping

2014-01-01

The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(3(4)) to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h.

Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases.

PubMed

Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying

2016-07-01

Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alterations of Innate Immunity Reactants in Transition Dairy Cows before Clinical Signs of Lameness

PubMed Central

Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Deng, Qilan; Goldansaz, Seyed A.; Dunn, Suzanna M.; Ametaj, Burim N.

2015-01-01

Simple Summary Lameness is prevalent in dairy cows and early diagnosis and timely treatment of the disease can lower animal suffering, improve recovery rate, increase longevity, and minimize cow loss. However, there are no indications of disease until it appears clinically, and presently the only approach to deal with the sick cow is intensive treatment or culling. The results suggest that lameness affected serum concentrations of the several parameters related to innate immunity and carbohydrate metabolism that might be used to monitor health status of transition dairy cows in the near future. Abstract The objectives of this study were to evaluate metabolic and innate immunity alterations in the blood of transition dairy cows before, during, and after diagnosis of lameness during periparturient period. Blood samples were collected from the coccygeal vain once per week before morning feeding from 100 multiparous Holstein dairy cows during −8, −4, disease diagnosis, and +4 weeks (wks) relative to parturition. Six healthy cows (CON) and six cows that showed clinical signs of lameness were selected for intensive serum analyses. Concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), haptoglobin (Hp), serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), lactate, non-esterified fatty acids (NEFA), and β-hydroxybutyrate (BHBA) were measured in serum by ELISA or colorimetric methods. Health status, DMI, rectal temperature, milk yield, and milk composition also were monitored for each cow during the whole experimental period. Results showed that cows affected by lameness had greater concentrations of lactate, IL-6, and SAA in the serum vs. CON cows. Concentrations of TNF tended to be greater in cows with lameness compared with CON. In addition, there was a health status (Hs) by time (week) interaction for IL-1, TNF, and Hp in lameness cows vs. CON ones. Enhanced serum concentrations of lactate, IL-6, and SAA at −8 and �

Improving CRISPR–Cas specificity with chemical modifications in single-guide RNAs

PubMed Central

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Dellinger, Douglas J

2018-01-01

Abstract CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2′-O-methyl-3′-phosphonoacetate, or ‘MP’) incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. PMID:29216382

Etiologies of altered mental status in patients with presumed ethanol intoxication.

PubMed

Martel, Marc L; Klein, Lauren R; Lichtenheld, Andrew J; Kerandi, Allan M; Driver, Brian E; Cole, Jon B

2018-06-01

Altered mental status is a commonly evaluated problem in the ED. Ethanol intoxication is common, and prehospital history may bias emergency physicians to suspect this as the cause of altered mental status. Quantitative ethanol measurement can rapidly confirm the diagnosis, or if negative, prompt further evaluation. Our objective was to identify the etiologies of altered mental status in ED patients initially presumed to be intoxicated with ethanol but found to have negative quantitative ethanol levels. This was a 5-year (2012-2016) electronic medical record review of ED patients presenting with altered mental status. Patients were included if they presented with presumed ethanol intoxication and had an initial ethanol concentration of zero. Etiologies of altered mental status were categorized into medical, traumatic, psychiatric, and drug-related causes. 29,322 patients presented during the study period with presumed alcohol intoxication, 1875 patients had negative ethanol levels. The etiology of altered mental status was due to illicit substances in 1337 patients (71%), psychiatric causes in 354 patients (19%), medical causes in 166 patients (9%) and trauma in 18 patients (1%). A total of 179 patients (10%) were admitted to the hospital; 19 patients (1%) to the ICU. The presumptive diagnosis of ethanol intoxication in patients presenting to the ED with altered mental status was inaccurate in 5% of patients. The etiology of altered mental status was serious and required hospitalization in 10% of the cohort. Rapid assessment of quantitative ethanol levels should be performed, breathalyzers may be preferred over serum testing. Copyright © 2018 Elsevier Inc. All rights reserved.

Global regulation of post-translational modifications on core histones.

PubMed

Galasinski, Scott C; Louie, Donna F; Gloor, Kristen K; Resing, Katheryn A; Ahn, Natalie G

2002-01-25

Full-length masses of histones were analyzed by mass spectrometry to characterize post-translational modifications of bulk histones and their changes induced by cell stimulation. By matching masses of unique peptides with full-length masses, H4 and the variants H2A.1, H2B.1, and H3.1 were identified as the main histone forms in K562 cells. Mass changes caused by covalent modifications were measured in a dose- and time-dependent manner following inhibition of phosphatases by okadaic acid. Histones H2A, H3, and H4 underwent changes in mass consistent with altered acetylation and phosphorylation, whereas H2B mass was largely unchanged. Unexpectedly, histone H4 became almost completely deacetylated in a dose-dependent manner that occurred independently of phosphorylation. Okadaic acid also partially blocked H4 hyperacetylation induced by trichostatin-A, suggesting that the mechanism of deacetylation involves inhibition of H4 acetyltransferase activity, following perturbation of cellular phosphatases. In addition, mass changes in H3 in response to okadaic acid were consistent with phosphorylation of methylated, acetylated, and phosphorylated forms. Finally, kinetic differences were observed with respect to the rate of phosphorylation of H2A versus H4, suggesting differential regulation of phosphorylation at sites on these proteins, which are highly related by sequence. These results provide novel evidence that global covalent modifications of chromatin-bound histones are regulated through phosphorylation-dependent mechanisms.

Fluoride Alters Serum Elemental (Calcium, Magnesium, Copper, and Zinc) Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going Children of Nalgonda District, India.

PubMed

Khandare, Arjun L; Validandi, Vakdevi; Boiroju, Naveen

2018-02-17

The present study aimed to determine the serum trace elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase (CA) activity and effect of intervention with safe drinking water for 5 years in the school children of fluorosis endemic area. For this purpose, three categories of villages were selected based on drinking water fluoride (F): Category I (control, F = 1.68 mg/L), category II (affected F = 3.77 mg/L), and category III (intervention village) where initial drinking water F was 4.51 mg/L, and since the last 5 years, they were drinking water containing < 1.0 mg/L F. The results revealed that urinary F was significantly (P < 0.05) higher in category II compared to categories I and III. A significant (P < 0.05) increase in serum Cu and Mg was observed in category II compared to category I. Serum Zn and Ca was significantly (P < 0.05) decreased in categories II and III compared to category I. The erythrocyte CA activity was decreased in the category II compared to category I. However, in the category III, erythrocyte CA activity was comparable to the control group. In conclusion, F exposure altered elemental homeostasis which has restored to some extent on intervention by safe drinking water for 5 years in school-going children.

Differences in urine cadmium associations with kidney outcomes based on serum creatinine and cystatin C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weaver, Virginia M., E-mail: vweaver@jhsph.edu; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD

Cadmium is a well-known nephrotoxicant; chronic exposure increases risk for chronic kidney disease. Recently, however, associations between urine cadmium and higher creatinine-based estimated glomerular filtration rate (eGFR) have been reported. Analyses utilizing alternate biomarkers of kidney function allow evaluation of potential mechanisms for these observations. We compared associations of urine cadmium with kidney function measures based on serum cystatin C to those with serum creatinine in 712 lead workers. Mean (standard deviation) molybdenum-corrected urine cadmium, Modification of Diet in Renal Disease (MDRD) eGFR and multi-variable cystatin C eGFR were 1.02 (0.65) {mu}g/g creatinine, and 97.4 (19.2) and 112.0 (17.7) mL/min/1.73more » m{sup 2}, respectively. The eGFR measures were moderately correlated (r{sub s}=0.5; p<0.001). After adjustment, ln (urine cadmium) was not associated with serum cystatin-C-based measures. However, higher ln (urine cadmium) was associated with higher creatinine-based eGFRs including the MDRD and an equation incorporating serum cystatin C and creatinine (beta-coefficient=4.1 mL/min/1.73 m{sup 2}; 95% confidence interval=1.6, 6.6). Urine creatinine was associated with serum creatinine-based but not cystatin-C-based eGFRs. These results support a biomarker-specific, rather than a kidney function, effect underlying the associations observed between higher urine cadmium and creatinine-based kidney function measures. Given the routine use of serum and urine creatinine in kidney and biomarker research, additional research to elucidate the mechanism(s) for these associations is essential.« less

Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia.

PubMed

Wu, Weiguang; Fan, Xiaobin; Yu, Yuecheng; Wang, Yingchun

2015-10-01

Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia. This retrospective case-control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated. The ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34±14.27pg/mL vs 251.49±16.15pg/mL, P=0.041, 1.07±0.09 vs 0.82±0.08, P=0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35±15.38pg/mL vs 223.53±18.61pg/mL, P=0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r=-0.549, P=0.003; r=-0.491, P=0.004) and was positively correlated with obestatin concentrations in preeclampsia (r=0.388, P=0.013). The findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Restricted access molecularly imprinted polymers obtained by bovine serum albumin and/or hydrophilic monomers' external layers: a comparison related to physical and chemical properties.

PubMed

Santos, Mariane Gonçalves; Moraes, Gabriel de Oliveira Isac; Nakamura, Maurício Gustavo; dos Santos-Neto, Álvaro José; Figueiredo, Eduardo Costa

2015-11-21

Molecularly imprinting polymers (MIPs) can be modified with external layers in order to obtain restricted access molecularly imprinted polymers (RAMIPs) able to exclude macromolecules and retain low weight compounds. These modifications have been frequently achieved using hydrophilic monomers, chemically bound on the MIP surface. Recently, our group proposed a new biocompatible RAMIP based on the formation of a bovine serum albumin coating on the surface of MIP particles. This material has been used to extract drugs directly from untreated human plasma samples, but its physicochemical evaluation has not been carried out yet, mainly in comparison with RAMIPs obtained by hydrophilic monomers. Thus, we proposed in this paper a comparative study involving the surface composition, microscopic aspect, selectivity, binding kinetics, adsorption and macromolecule elimination ability of these different materials. We concluded that the synthesis procedure influences the size and shape of particles and that hydrophilic co-monomer addition as well as coating with BSA do not alter the chemical recognition ability of the material. The difference between imprinted and non-imprinted polymers' adsorption was evident (suggesting that imprinted polymers have a better capacity to bind the template than the non-imprinted ones). The Langmuir model presents the best fit to describe the materials' adsorption profile. The polymer covered with hydrophilic monomers presented the best adsorption for the template in an aqueous medium, probably due to a hydrophilic layer on its surface. We also concluded that an association of the hydrophilic monomers with the bovine serum albumin coating is important to obtain materials with higher capacity of macromolecule exclusion.

Spectrum determination and modification of the AFRL Co-60 cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turinetti, J.R.; Kemp, W.T.; Chavez, J.R.

The AFRL Co-60 cell at Phillips Research Site, Kirtland Air Force Base, is a 1500 ft{sup 2} concrete room with a 5200 Ci, as of 18 December 1996, J.L. Shepherd Co-60 source. The source provides high dose rate ionizing radiation up to 12000 rad(Si)/min. The Co-60 cell is used to characterize total-dose gamma effects of microelectronic and photonic devices, circuits, and subsystems. The spectrum of a Co-60 facility includes more than the two photopeaks of gamma ray emission. If there is a large low energy contribution from scattering, dose enhancement might be a problem. It is important to know themore » spectrum of a Co-60 facility and understand how experimental modifications can change that spectrum. The AFRL Co-60 cell spectrum is found to be a clean spectrum with small low energy contributions and dominant Co-60 photopeaks. Experimental modifications to reduce dose enhancement such as the use of a Pb/Al box and even better a Pb/Sn/Cu/Al box are found to decrease the low energy contributions. Experimental modifications to reduce dose rate such as using lead attenuators in front of the experiment and/or raising the source partially are found to significantly alter the spectrum, sometimes creating large low energy contributions.« less

Modification of human serum albumin by the nerve agent VX: microbore liquid chromatography/electrospray ionization high-resolution time-of-flight tandem mass spectrometry method for detection of phosphonylated tyrosine and novel cysteine containing disulfide adducts.

PubMed

Kranawetvogl, Andreas; Worek, Franz; Thiermann, Horst; John, Harald

2016-10-15

Organophosphorus nerve agents still constitute a considerable threat to the health of military personnel and the civilian population. Long-term biomarkers are crucial for reliable verification of exposure to banned substances. Therefore, current research focuses on identification of endogenous protein targets showing covalent modifications by organophosphorus nerve agents (adducts). Purified human serum albumin and human plasma were incubated with the nerve agent VX followed by enzymatic proteolysis with pronase. Resulting peptide cleavage products were separated by microbore liquid chromatography (μLC) online coupled to positive electrospray ionization (ESI) with subsequent high-resolution time-of-flight tandem mass spectrometry (HR MS/MS) allowing identification of known and novel adducts. In addition to known phosphonylation of various tyrosine residues, albumin was found to be modified at diverse cysteine residues by covalent attachment of the leaving group of VX. These novel disulfide adducts were cleaved from at least two regions of the intact protein as dipeptides containing cysteine and proline either as CP or PC. A rapid and sensitive method was developed for simultaneous detection of the diverse covalent modifications of human albumin by VX. Identification of the novel leaving group adducts with human albumin expands the basic knowledge on molecular toxicology of the nerve agent VX. Furthermore, the presented μLC/ESI HR MS/MS method might be of relevance for verification of VX poisoning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Low Testosterone Alters the Activity of Mouse Prostate Stem Cells.

PubMed

Zhou, Ye; Copeland, Ben; Otto-Duessel, Maya; He, Miaoling; Markel, Susan; Synold, Tim W; Jones, Jeremy O

2017-04-01

Low serum testosterone (low T) has been repeatedly linked to worse outcomes in men with newly diagnosed prostate cancer (PC). How low T contributes to these outcomes is unknown. Here we demonstrate that exposure to low T causes significant changes in the mouse prostate and prostate stem cells. Mice were castrated and implanted with capsules to achieve castrate, normal, or sub-physiological levels of T. After 6 weeks of treatment, LC-MS/MS was used to quantify the levels of T and dihydrotestosterone (DHT) in serum and prostate tissue. FACS was used to quantify the percentages of purported prostate stem and transit amplifying (TA) cells in mouse prostates. Prostate tissues were also stained for the presence of CD68+ cells and RNA was extracted from prostate tissue or specific cell populations to measure changes in transcript levels with low T treatment. Despite having significantly different levels of T and DHT in the serum, T and DHT concentrations in prostate tissue from different T treatment groups were similar. Low T treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining prostate androgen levels. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all T treatment groups, demonstrating that the mouse prostate can maintain functional levels of androgens despite low serum T levels. Low T increased the frequency of prostate stem and TA cells in adult prostate tissue and caused major transcriptional changes in those cells. Gene ontology analysis suggested that low T caused inflammatory responses and immunofluorescent staining indicated that low T treatment led to the increased presence of CD68+ macrophages in prostate tissue. Low T alters the AR signaling axis which likely leads to maintenance of functional levels of prostate androgens. Low T also induces quantitative and qualitative changes in prostate stem cells which appear to lead to inflammatory

Metabolomic Quality Assessment of EDTA Plasma and Serum Samples.

PubMed

Malm, Linus; Tybring, Gunnel; Moritz, Thomas; Landin, Britta; Galli, Joakim

2016-10-01

Handling and processing of blood can significantly alter the molecular composition and consistency of biobank samples and can have a major impact on the identification of biomarkers. It is thus crucial to identify tools to determine the quality of samples to be used in biomarker discovery studies. In this study, a non-targeted gas chromatography/time-of-flight mass spectrometry (GC-TOFMS) metabolomic strategy was used with the aim of identifying quality markers for serum and plasma biobank collections lacking proper documentation of preanalytical handling. The effect of postcentrifugation delay was examined in serum stored in tubes with gel separation plugs and ethylenediaminetetraacetic acid (EDTA) plasma in tubes with or without gel separation plugs. The change in metabolic pattern was negligible in all sample types processed within 3 hours after centrifugation regardless of whether the samples were kept at 4°C or 22°C. After 8 and 24 hours postcentrifugation delay before aliquoting, there was a pronounced increase in the number of affected metabolites, as well as in the magnitude of the observed changes. No protective effect on the metabolites was observed in gel-separated EDTA plasma samples. In a separate series of experiments, lactate and glucose levels were determined in plasma to estimate the effect of precentrifugation delay. This separate experiment indicates that the lactate to glucose ratio may serve as a marker to identify samples with delayed time to centrifugation. Although our data from the untargeted GC-TOFMS analysis did not identify any specific markers, we conclude that plasma and serum metabolic profiles remain quite stable when plasma and serum are centrifuged and separated from the blood cells within 3 hours.

Macroinvertebrate community change associated with the severity of streamflow alteration

USGS Publications Warehouse

Carlisle, Daren M.; Eng, Kenny; Nelson, S.M.

2014-01-01

Natural streamflows play a critical role in stream ecosystems, yet quantitative relations between streamflow alteration and stream health have been elusive. One reason for this difficulty is that neither streamflow alteration nor ecological responses are measured relative to their natural expectations. We assessed macroinvertebrate community condition in 25 mountain streams representing a large gradient of streamflow alteration, which we quantified as the departure of observed flows from natural expectations. Observed flows were obtained from US Geological Survey streamgaging stations and discharge records from dams and diversion structures. During low-flow conditions in September, samples of macroinvertebrate communities were collected at each site, in addition to measures of physical habitat, water chemistry and organic matter. In general, streamflows were artificially high during summer and artificially low throughout the rest of the year. Biological condition, as measured by richness of sensitive taxa (Ephemeroptera, Plecoptera and Trichoptera) and taxonomic completeness (O/E), was strongly and negatively related to the severity of depleted flows in winter. Analyses of macroinvertebrate traits suggest that taxa losses may have been caused by thermal modification associated with streamflow alteration. Our study yielded quantitative relations between the severity of streamflow alteration and the degree of biological impairment and suggests that water management that reduces streamflows during winter months is likely to have negative effects on downstream benthic communities in Utah mountain streams. 

Not of African Descent: Dental Modification among Indigenous Caribbean People from Canímar Abajo, Cuba

PubMed Central

Roksandic, Mirjana; Alarie, Kaitlynn; Rodríguez Suárez, Roberto; Huebner, Erwin; Roksandic, Ivan

2016-01-01

Dental modifications in the Caribbean are considered to be an African practice introduced to the Caribbean archipelago by the influx of enslaved Africans during colonial times. Skeletal remains which exhibited dental modifications are by default considered to be Africans, African descendants, or post-contact indigenous people influenced by an African practice. Individual E-105 from the site of Canímar Abajo (Cuba), with a direct 14C AMS date of 990–800 cal BC, provides the first unequivocal evidence of dental modifications in the Antilles prior to contact with Europeans in AD 1492. Central incisors showing evidence of significant crown reduction (loss of crown volume regardless of its etiology) were examined macroscopically and with a scanning electron microscope (SEM) to determine if the observed alterations were due to deliberate modification or other (unintentional) factors considered: postmortem breakage, violent accidental breakage, non-dietary use of teeth, and wear caused by habitual or repeated actions. The pattern of crown reduction is consistent with deliberate dental modification of the type commonly encountered among African and African descendent communities in post-contact Caribbean archaeological assemblages. Six additional individuals show similar pattern of crown reduction of maxillary incisors with no analogous wear in corresponding mandibular dentition. PMID:27071012