Parasitic nematodes exert antimicrobial activity and benefit from microbiota-driven support for host immune regulation

Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes. Here we asked if the small intestinal parasite Heligmosomoides polygyrus produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. We found that H. polygyrus excretory/secretory products exhibited antimicrobial activity against gram(+/-) bacteria. Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme. Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3(+)RORγt(+) regulatory T cells and decreased parasite fecundity. Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes. Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice

S100B and homocysteine in the acute alcohol withdrawal syndrome

Elevations of serum homocysteine levels are a consistent finding in alcohol addiction. Serum S100B levels are altered in different neuropsychiatric disorders but not well investigated in alcohol withdrawal syndromes. Because of the close connection of S100B to ACTH and glutamate secretion that both are involved in neurodegeneration and symptoms of alcoholism the relationship of S100B and homocysteine to acute withdrawal variables has been examined. A total of 22 male and 9 female inpatients (mean age 46.9 ± 9.7 years) with an ICD-10 diagnosis of alcohol addiction without relevant affective comorbidity were examined on admission and after 24, 48, and 120 h during withdrawal. S100B and homocysteine levels in serum were collected, and severity of withdrawal symptoms (AWS-scale), applied withdrawal medication, initial serum ethanol levels and duration of addiction were recorded. Serum S100B and homocysteine levels declined significantly (P < .05) over time. Both levels declined with withdrawal syndrome severity. Females showed a trend to a more intense decline in serum S100B levels compared to males at day 5 (P = .06). Homocysteine levels displayed a negative relationship to applied amount of clomethiazole (P < .05) and correlated with age of onset of addiction. No withdrawal seizures were recorded during the trial. As it is known for homocysteine, S100B revealed to decline rapidly over withdrawal treatment in alcoholism. This effect is more pronounced in female patients. S100B could be of relevance in the neurobiology of alcohol withdrawal syndromes. It may be indirectly related to the level of stress level or glutamatergic activity during alcohol withdrawal

Quantification of FAM20A in human milk and identification of calcium metabolism proteins

BACKGROUND: FAM20A, a recently discovered protein, is thought to have a fundamental role in inhibiting ectopic calcification. Several studies have demonstrated that variants of FAM20A are causative for the rare autosomal recessive disorder, enamel-renal syndrome (ERS). ERS is characterized by defective mineralization of dental enamel and nephrocalcinosis suggesting that FAM20A is an extracellular matrix protein, dysfunction of which causes calcification of the secretory epithelial tissues. FAM20A is a low-abundant protein that is difficult to detect in biofluids such as blood, saliva, and urine. Thus, we speculated the abundance of FAM20A to be high in human milk, since the secretory epithelium of lactating mammary tissue is involved in the secretion of highly concentrated calcium. Therefore, the primary aim of this research is to describe the processes/methodology taken to quantify FAM20A in human milk and identify other proteins involved in calcium metabolism. METHOD: This study used mass spectrometry-driven quantitative proteomics: (1) to quantify FAM20A in human milk of three women and (2) to identify proteins associated with calcium regulation by bioinformatic analyses on whole and milk fat globule membrane fractions. RESULTS: Shotgun MS/MS driven proteomics identified FAM20A in whole milk, and subsequent analysis using targeted proteomics also successfully quantified FAM20A in all samples. Combination of sample preparation, fractionation, and LC-MS/MS proteomics analysis generated 136 proteins previously undiscovered in human milk; 21 of these appear to be associated with calcium metabolism. CONCLUSION: Using mass spectrometry-driven proteomics, we successfully quantified FAM20A from transitional to mature milk and obtained a list of proteins involved in calcium metabolism. Furthermore, we show the value of using a combination of both shotgun and targeted driven proteomics for the identification of this low abundant protein in human milk

Vibration and buckling of thin-walled composite I-beams with arbitrary lay-ups under axial loads and end moments

A finite element model with seven degrees of freedom per node is developed to study vibration and buckling of thin-walled composite I-beams with arbitrary lay-ups under constant axial loads and equal end moments. This model is based on the classical lamination theory, and accounts for all the structural coupling coming from material anisotropy. The governing differential equations are derived from the Hamilton’s principle. Numerical results are obtained for thin-walled composite I-beams to investigate the effects of axial force, bending moment and fiber orientation on the buckling moments, natural frequencies, and corresponding vibration mode shapes as well as axial-moment-frequency interaction curves

Liquid racism and the Danish Prophet Muhammad cartoons

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 The Author.This article examines reactions to the October 2005 publication of the Prophet Muhammad cartoons in the Danish newspaper Jyllands-Posten. It does so by using the concept of ‘liquid racism’. While the controversy arose because it is considered blasphemous by many Muslims to create images of the Prophet Muhammad, the article argues that the meaning of the cartoons is multidimensional, that their analysis is significantly more complex than most commentators acknowledge, and that this complexity can best be addressed via the concept of liquid racism. The article examines the liquidity of the cartoons in relation to four readings. These see the cartoons as: (1) a criticism of Islamic fundamentalism; (2) blasphemous images; (3) Islamophobic and racist; and (4) satire and a defence of freedom of speech. Finally, the relationship between postmodernity and the rise of fundamentalism is discussed because the cartoons, reactions to them, and Islamic fundamentalism, all contain an important postmodern dimension.ESR

Time--delay autosynchronization of the spatio-temporal dynamics in resonant tunneling diodes

The double barrier resonant tunneling diode exhibits complex spatio-temporal patterns including low-dimensional chaos when operated in an active external circuit. We demonstrate how autosynchronization by time--delayed feedback control can be used to select and stabilize specific current density patterns in a noninvasive way. We compare the efficiency of different control schemes involving feedback in either local spatial or global degrees of freedom. The numerically obtained Floquet exponents are explained by analytical results from linear stability analysis.Comment: 10 pages, 16 figure

Discrete Determinants and the Gel'fand-Yaglom formula

I present a partly pedagogic discussion of the Gel'fand-Yaglom formula for the functional determinant of a one-dimensional, second order difference operator, in the simplest settings. The formula is a textbook one in discrete Sturm-Liouville theory and orthogonal polynomials. A two by two matrix approach is developed and applied to Robin boundary conditions. Euler-Rayleigh sums of eigenvalues are computed. A delta potential is introduced as a simple, non-trivial example and extended, in an appendix, to the general case. The continuum limit is considered in a non--rigorous way and a rough comparison with zeta regularised values is made. Vacuum energies are also considered in the free case. Chebyshev polynomials act as free propagators and their properties are developed using the two-matrix formulation, which has some advantages and appears to be novel. A trace formula, rather than a determinant one, is derived for the Gel'fand-Yaglom function.Comment: 29 pages. Submitted version. Typos corrected and adjustments made. Comments and references adde

Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase

Activation of the thick ascending limb (TAL) Na+-K+-2Cl--cotransporter (NKCC2) by the antidiuretic hormone arginine-vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5ng/h, 3d) significantly lowered renal EET levels (-56 +/- 3% for 5,6-EET, -50 +/- 3.4% for 11,12-EET, and -60 +/- 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 +/- 37%) and protein levels (+120 +/- 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 {mu}M 14,15-EET for 30 min reduced phosphorylation of NKCC2 at the AVP-sensitive threonine residues T96 and T101 (-66 +/-5%; p<0.05) while 14,15-DHET had no effect. Concomitantly, isolated perfused cTAL pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symetric chloride concentrations. In sum, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis