Translaminar Pressure Difference and Ocular Perfusion Pressure in Glaucomatous Eyes with Different Optic Disc Sizes

Purpose: Intracranial pressure (ICP) and ocular perfusion pressure (OPP) are both involved with the pathogenesis of glaucoma. The orbital ICP determines a retrolaminar counter pressure that is antagonistic to the intraocular pressure (IOP). The purpose of this study is to evaluate whether the translaminar pressure difference (TLPD) and the OPP varies in glaucoma patients with different optic disc sizes. Methods: In this university hospital-based, observational, cross-sectional clinical study, all patients underwent an ophthalmic evaluation. Blood pressure, height, weight, and the results of retinal nerve fiber layer examination with optical coherence tomography examination were recorded. TLPD and OPP were calculated for each patient using proxy algorithms to attain indirect surrogate parameter values. Patients’ eyes were stratified into three quantiles according to optic disc sizes and the differences compared. Data from both eyes were used after using the appropriate correction for inter-eye dependency. Results: The sample consisted of 140 eyes of 73 patients with primary open-angle glaucoma and suspects. Patients with large disc size presented with higher TLPD as compared to those with average and small-sized discs (2.4 ± 4.5, 2.8 ± 3.8, and 3.7 ± 4.7 mmHg for first, second, and third tertile, respectively (P < 0.000). OPP did not vary according to the optic disc size. Conclusion: Glaucoma patients with larger optic discs have higher TLPD. The pathological significance of this finding warrants further investigation

A swollen phase observed between the liquid-crystalline phase and the interdigitated phase induced by pressure and/or adding ethanol in DPPC aqueous solution

A swollen phase, in which the mean repeat distance of lipid bilayers is larger than the other phases, is found between the liquid-crystalline phase and the interdigitated gel phase in DPPC aqueous solution. Temperature, pressure and ethanol concentration dependences of the structure were investigated by small-angle neutron scattering, and a bending rigidity of lipid bilayers was by neutron spin echo. The nature of the swollen phase is similar to the anomalous swelling reported previously. However, the temperature dependence of the mean repeat distance and the bending rigidity of lipid bilayers are different. This phase could be a precursor to the interdigitated gel phase induced by pressure and/or adding ethanol.Comment: 7 pages, 6 figure

Structure of symmetric and asymmetric "ripple" phases in lipid bilayers

We reproduce the symmetric and asymmetric ``rippled'' $P_{\beta'}$ states of lipid membranes by Monte Carlo simulations of a coarse-grained molecular model for lipid-solvent mixtures. The structure and properties compare favorably with experiments. The asymmetric ripple state is characterized by a periodic array of fully interdigitated ``defect'' lines. The symmetric ripple state maintains a bilayer structure, but is otherwise structurally similar. The formation of both ripple states is driven by the propensity of lipid molecules with large head groups to exhibit splay.Comment: 4 pages, 4 figure

Sterols sense swelling in lipid bilayers

In the mimetic membrane system of phosphatidylcholine bilayers, thickening (pre-critical behavior, anomalous swelling) of the bilayers is observed, in the vicinity of the main transition, which is non-linear with temperature. The sterols cholesterol and androsten are used as sensors in a time-resolved simultaneous small- and wide angle x-ray diffraction study to investigate the cause of the thickening. We observe precritical behavior in the pure lipid system, as well as with sterol concentrations less than 15%. To describe the precritical behavior we introduce a theory of precritical phenomena.The good temperature resolution of the data shows that a theory of the influence of fluctuations needs modification. The main cause of the critical behavior appears to be a changing hydration of the bilayer.Comment: 11 pages, 7 ps figures included, to appear in Phys.Rev.

Grb2 monomer-dimer equilibrium determines normal versus oncogenic function

The adaptor protein growth factor receptor-bound protein 2 (Grb2) is ubiquitously expressed in eukaryotic cells and involved in a multitude of intracellular protein interactions. Grb2 plays a pivotal role in tyrosine kinase-mediated signal transduction including linking receptor tyrosine kinases to the Ras/mitogen-activated protein (MAP) kinase pathway, which is implicated in oncogenic outcome. Grb2 exists in a constitutive equilibrium between monomeric and dimeric states. Here we show that only monomeric Grb2 is capable of binding to SOS and upregulating MAP kinase signalling and that the dimeric state is inhibitory to this process. Phosphorylation of tyrosine 160 (Y160) on Grb2, or binding of a tyrosylphosphate-containing ligand to the SH2 domain of Grb2, results in dimer dissociation. Phosphorylation of Y160 on Grb2 is readily detectable in the malignant forms of human prostate, colon and breast cancers. The self-association/dissociation of Grb2 represents a switch that regulates MAP kinase activity and hence controls cancer progression

Identification and Characterization of NF-Y Transcription Factor Families in the Monocot Model Plant Brachypodium distachyon

BACKGROUND: Nuclear Factor Y (NF-Y) is a heterotrimeric transcription factor composed of NF-YA, NF-YB and NF-YC proteins. Using the dicot plant model system Arabidopsis thaliana (Arabidopsis), NF-Y were previously shown to control a variety of agronomically important traits, including drought tolerance, flowering time, and seed development. The aim of the current research was to identify and characterize NF-Y families in the emerging monocot model plant Brachypodium distachyon (Brachypodium) with the long term goal of assisting in the translation of known dicot NF-Y functions to the grasses. METHODOLOGY/PRINCIPAL FINDINGS: We identified, annotated, and further characterized 7 NF-YA, 17 NF-YB, and 12 NF-YC proteins in Brachypodium (BdNF-Y). By examining phylogenetic relationships, orthology predictions, and tissue-specific expression patterns for all 36 BdNF-Y, we proposed numerous examples of likely functional conservation between dicots and monocots. To test one of these orthology predictions, we demonstrated that a BdNF-YB with predicted orthology to Arabidopsis floral-promoting NF-Y proteins can rescue a late flowering Arabidopsis mutant. CONCLUSIONS/SIGNIFICANCE: The Brachypodium genome encodes a similar complement of NF-Y to other sequenced angiosperms. Information regarding NF-Y phylogenetic relationships, predicted orthologies, and expression patterns can facilitate their study in the grasses. The current data serves as an entry point for translating many NF-Y functions from dicots to the genetically tractable monocot model system Brachypodium. In turn, studies of NF-Y function in Brachypodium promise to be more readily translatable to the agriculturally important grasses

NF-Y Dependent Epigenetic Modifications Discriminate between Proliferating and Postmitotic Tissue

The regulation of gene transcription requires posttranslational modifications of histones that, in concert with chromatin remodeling factors, shape the structure of chromatin. It is currently under intense investigation how this structure is modulated, in particular in the context of proliferation and differentiation. Compelling evidence suggests that the transcription factor NF-Y acts as a master regulator of cell cycle progression, activating the transcription of many cell cycle regulatory genes. However, the underlying molecular mechanisms are not yet completely understood. Here we show that NF-Y exerts its effect on transcription through the modulation of the histone “code”. NF-Y colocalizes with nascent RNA, while RNA polymerase II is I phosphorylated on serine 2 of the YSPTSPS repeats within its carboxyterminal domain and histones are carrying modifications that represent activation signals of gene expression (H3K9ac and PAN-H4ac). Comparing postmitotic muscle tissue from normal mice and proliferating muscles from mdx mice, we demonstrate by chromatin immunoprecipitation (ChIP) that NF-Y DNA binding activity correlates with the accumulation of acetylated histones H3 and H4 on promoters of key cell cycle regulatory genes, and with their active transcription. Accordingly, p300 is recruited onto the chromatin of NF-Y target genes in a NF-Y-dependent manner, as demonstrated by Re-ChIP. Conversely, the loss of NF-Y binding correlates with a decrease of acetylated histones, the recruitment of HDAC1, and a repressed heterochromatic state with enrichment of histones carrying modifications known to mediate silencing of gene expression (H3K9me3, H3K27me2 and H4K20me3). As a consequence, NF-Y target genes are downregulated in this context. In conclusion, our data indicate a role of NF-Y in modulating the structure and transcriptional competence of chromatin in vivo and support a model in which NF-Y-dependent histone “code” changes contribute to the proper discrimination between proliferating and postmitotic cells in vivo and in vitro