Dietary unsaturated fatty acids affect the mammary gland integrity and health in lactating dairy cows

Background Information about the effects of unsaturated fatty acids (UFA) supplementation on the health and integrity of the mammary gland in lactating dairy cows is lacking. Therefore, the aim of this study was to determine the effects of unprotected dietary UFA on the global expression pattern of genes in the mammary gland tissue of grazing dairy cows, and to translate this information into relevant biological knowledge. Methods Twenty-eight Holstein-Friesian dairy cows were randomly assigned to 4 different concentrated UFA-sources for 23 days after which all cows were switched to a non-UFA-supplemented concentrate for an additional 28 days. On the last day of both periods, mammary gland biopsies were taken to study genome-wide differences in gene expression on Bovine Genome Arrays. Results Supplementation with UFA reduced the concentration of short chain fatty acids (FA), C16 FA and saturated FA in the milk, whereas that of trans-FA increased. One major finding was that canonical pathways associated with remodelling and immune functions of the mammary gland were predominantly down-regulated during UFA supplementation and negatively correlated with the concentration of milk trans-FA. Conclusions Supplementing grazing dairy cows with unprotected dietary UFA can affect the remodelling and immune functions of the mammary gland with potential consequences for its integrity and health, as well as milk quality

Alteration of gene expression in mammary gland tissue of dairy cows in response to dietary unsaturated fatty acids

The aim of this study was to determine the effects of supplementing unprotected dietary unsaturated fatty acids (UFAs) from different plant oils on gene expression in the mammary gland of grazing dairy cows. A total of 28 Holstein–Friesian dairy cows in mid-lactation were blocked according to parity, days in milk, milk yield and fat percentage. The cows were then randomly assigned to four UFA sources based on rapeseed, soybean, linseed or a mixture of the three oils for 23 days, after which, all 28 cows were switched to a control diet for an additional 28 days. On the last day of both periods, mammary gland biopsies were taken to study genome-wide differences in gene expression on Affymetrix GeneChip® Bovine Genome Arrays (no. 900493) by ServiceXS (Leiden, The Netherlands). Supplementation with UFAs resulted in increased milk yield but decreased milk fat and protein percentages. Furthermore, the proportion of de novo fatty acids (FAs) in the milk was reduced, whereas that of long-chain FAs increased. Applying a statistical cut-off of false discovery rate of q-value

Analysis of the relationship between disease activity and damage in patients with systemic lupus erythematosus—a 5-yr prospective study

Objective. To determine whether initial damage, disease duration, age, initial health status, average disease activity over the 5 yr or an average medication score covering the follow-up period would predict an increase in damage in patients with systemic lupus erythematosus (SLE) within the next 5 yr. Methods. A 5-yr prospective longitudinal study of a cohort of 141 consecutive patients with SLE attending a specialist lupus out-patient clinic in London from their first assessment between July 1994 and February 1995. Disease activity was assessed using the BILAG system, initial health status by the Medical Outcome Survey Short Form 20 with an extra question about fatigue (SF-20+) and damage by the SLICC/ACR Damage Index (SDI). Damage was reassessed 5 yr later. Statistical analysis was carried out using multiple logistic regression analysis (logXact). Results. One hundred and thirty-three female and eight male SLE patients (97 Caucasians, 16 Afro-Caribbeans, 22 Asians and 6 others) were included, their age at inclusion was 41.1 ± 12.5 yr and their disease duration 10.2 ± 6.3 yr. The mean measures at inclusion were: total BILAG 5.2 (range 0-17), total SDI 1.2 (0-7) and medication score 1.2 (0-3). Six patients were lost to follow-up because they had moved. Of the remaining 135 patients total damage had increased in 40 patients and 10 patients had died. At the end of the study, at 4.63 ± 0.19 yr, the total SDI had increased to 1.6 ± 1.7. Multiple logistic regression analysis revealed that death and increase in damage were strongly predicted by a high total disease activity over the entire study period (P<0.001) as we had hypothesized. When the total BILAG score was replaced by the average number of A-flares the prediction of accrual of damage during the study period was again highly significant (P = 0.004). Conclusions. In this first prospective study of its type a highly significant impact of total disease activity, as measured over 5 yr using the BILAG system, on the development of total damage was revealed. Moreover, these results provide further proof of the validity of the SDI and support the BILAG concept of the A-flare

General Relativistic versus Newtonian: a universality in radiation hydrodynamics

We compare Newtonian and general relativistic descriptions of the stationary accretion of self-gravitating fluids onto compact bodies. Spherical symmetry and thin gas approximation are assumed. Luminosity depends, amongst other factors, on the temperature and the contribution of gas to the total mass, in both -- general relativistic ($L_{GR}$) and Newtonian ($L_N$) -- models. We discover a remarkable universal behaviour for transonic flows: the ratio of respective luminosities $L_{GR}/L_N$ is independent of the fractional mass of the gas and depends on asymptotic temperature. It is close to 1 in the regime of low asymptotic temperatures and can grow by one order of magnitude for high temperatures. These conclusions are valid for a wide range of polytropic equations of state.Comment: 8 pages, 4 figure

Three Questions on Lorentz Violation

We review the basics of the two most widely used approaches to Lorentz violation - the Stardard Model Extension and Noncommutative Field Theory - and discuss in some detail the example of the modified spectrum of the synchrotron radiation. Motivated by touching upon such a fundamental issue as Lorentz symmetry, we ask three questions: What is behind the search for Lorentz violation? Is String Theory a physical theory? Is there an alternative to Supersymmetry?Comment: 16 pages; invited luecture at DICE2006 - Piombino, Italy - September 200

Sox10 contributes to the balance of fate choice in dorsal root ganglion progenitors

The development of functional peripheral ganglia requires a balance of specification of both neuronal and glial components. In the developing dorsal root ganglia (DRGs), these compo- nents form from partially-restricted bipotent neuroglial precursors derived from the neural crest. Work in mouse and chick has identified several factors, including Delta/Notch signal- ing, required for specification of a balance of these components. We have previously shown in zebrafish that the Sry-related HMG domain transcription factor, Sox10, plays an unex- pected, but crucial, role in sensory neuron fate specification in vivo. In the same study we described a novel Sox10 mutant allele, sox10baz1, in which sensory neuron numbers are elevated above those of wild-types. Here we investigate the origin of this neurogenic pheno- type. We demonstrate that the supernumerary neurons are sensory neurons, and that enteric and sympathetic neurons are almost absent just as in classical sox10 null alleles; peripheral glial development is also severely abrogated in a manner similar to other sox10 mutant alleles. Examination of proliferation and apoptosis in the developing DRG reveals very low levels of both processes in wild-type and sox10baz1, excluding changes in the bal- ance of these as an explanation for the overproduction of sensory neurons. Using chemical inhibition of Delta-Notch-Notch signaling we demonstrate that in embryonic zebrafish, as in mouse and chick, lateral inhibition during the phase of trunk DRG development is required to achieve a balance between glial and neuronal numbers. Importantly, however, we show that this mechanism is insufficient to explain quantitative aspects of the baz1 phenotype. The Sox10(baz1) protein shows a single amino acid substitution in the DNA binding HMG domain; structural analysis indicates that this change is likely to result in reduced flexibility in the HMG domain, consistent with sequence-specific modification of Sox10 binding to DNA. Unlike other Sox10 mutant proteins, Sox10(baz1) retains an ability to drive neurogenin1 transcription. We show that overexpression of neurogenin1 is sufficient to produce supernu- merary DRG sensory neurons in a wild-type background, and can rescue the sensory neu- ron phenotype of sox10 morphants in a manner closely resembling the baz1 phenotype. We conclude that an imbalance of neuronal and glial fate specification results from the Sox10 (baz1) protein\u2019s unique ability to drive sensory neuron specification whilst failing to drive glial development. The sox10baz1 phenotype reveals for the first time that a Notch-dependent lat- eral inhibition mechanism is not sufficient to fully explain the balance of neurons and glia in the developing DRGs, and that a second Sox10-dependent mechanism is necessary. Sox10 is thus a key transcription factor in achieving the balance of sensory neuronal and glial fates

New insight into cataract formation -- enhanced stability through mutual attraction

Small-angle neutron scattering experiments and molecular dynamics simulations combined with an application of concepts from soft matter physics to complex protein mixtures provide new insight into the stability of eye lens protein mixtures. Exploring this colloid-protein analogy we demonstrate that weak attractions between unlike proteins help to maintain lens transparency in an extremely sensitive and non-monotonic manner. These results not only represent an important step towards a better understanding of protein condensation diseases such as cataract formation, but provide general guidelines for tuning the stability of colloid mixtures, a topic relevant for soft matter physics and industrial applications.Comment: 4 pages, 4 figures. Accepted for publication on Phys. Rev. Let

Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes

Objectives. We have recently shown that CRP induces chemokine secretion and adhesion molecule up-regulation in human primary monocytes cultured in adherence. Given the increasing evidence on direct immunomodulatory properties of statins, we investigated their possible anti-inflammatory role on CRP-treated human monocytes. Methods. Monocytes were isolated by Ficoll-Percoll gradients and cultured in adherence to polystyrene. Chemokine secretion and adhesion molecule expression were detected by ELISA and flow cytometry. Migration assays were performed in modified Boyden chambers. Intracellular kinase activation was assessed by western blot. Results. Treatment with simvastatin or atorvastatin decreased CRP-induced release of CCL2, CCL3 and CCL4. In addition, both statins reduced CRP-induced intercellular adhesion molecule (ICAM-1) up-regulation, but had no effects on CD11b and CD18. Treatments with 1 μM simvastatin or atorvastatin significantly inhibited monocyte migration in response to CRP. CD32 and CD64 (CRP receptors) expression on monocytes was not affected by statins. Statin-induced inhibition of CRP-mediated chemokine secretion, ICAM-1 up-regulation and migration occurred through the inhibition of extracellular signal-regulated kinase (ERK) 1/2. Treatment with l-mevalonate or farnesylpyrophosphate, but not geranylgeranyl-pyrophosphate reversed the statin-induced effect on CRP-mediated functions and ERK 1/2 phosphorylation, confirming that statins blocked CRP-induced ERK 1/2 phosphorylation through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Conclusions. Statins inhibited CRP-induced chemokine secretion, ICAM-1 up-regulation and migration in human adherent monocytes, through the inhibition of HMG-CoA reductase-ERK 1/2 pathway. This pathway could represent a very promising target to reduce CRP-induced activities in monocyte-mediated diseases, such as atherosclerosis or R

NMR implementation of Quantum Delayed-Choice Experiment

We report the first experimental demonstration of quantum delayed-choice experiment via nuclear magnetic resonance techniques. An ensemble of molecules each with two spin-1/2 nuclei are used as target and the ancilla qubits to perform the quantum circuit corresponding the delayed-choice setup. As expected in theory, our experiments clearly demonstrate the continuous morphing of the target qubit between particle-like and wave-like behaviors. The experimental visibility of the interference patterns shows good agreement with the theory.Comment: Revised text, more figures adde