Urinary sodium-to-potassium ratio and intake of sodium and potassium among men and women from multiethnic general populations: the INTERSALT Study

The Na/K ratio may be more strongly related to blood pressure and cardiovascular disease than sodium or potassium. The casual urine Na/K ratio can provide prompt on-site feedback, and with repeated measurements, may provide useful individual estimates of the 24-h ratio. The World Health Organization has published guidelines for sodium and potassium intake, but no generally accepted guideline prevails for the Na/K ratio. We used standardized data on 24 h and casual urinary electrolyte excretion obtained from the INTERSALT Study for 10,065 individuals aged 20-59 years from 32 countries (52 populations). Associations between the casual urinary Na/K ratio and the 24-h sodium and potassium excretion of individuals were assessed by correlation and stratification analyses. The mean 24-h sodium and potassium excretions were 156.0 mmol/24 h and 55.2 mmol/24 h, respectively; the mean 24-h urinary Na/K molar ratio was 3.24. Pearson's correlation coefficients (r) for the casual urinary Na/K ratio with 24-h sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for the 24-h ratio. The urinary Na/K ratio predicted a 24-h urine Na excretion of <85 mmol/day (the WHO recommended guidelines) with a sensitivity of 99.7% and 94.0%, specificity of 39.5% and 48.0%, and positive predictive value of 96.3% and 61.1% at the cutoff point of 1 in 24 h and casual urine Na/K ratios, respectively. A urinary Na/K molar ratio <1 may be a useful indicator for adherence to the WHO recommended levels of sodium and, to a lesser extent, the potassium intake across different populations; however, cutoff points for Na/K ratio may be tuned for localization

Infinite-dimensional pp-adic groups, semigroups of double cosets, and inner functions on Bruhat--Tits builldings

We construct $p$-adic analogs of operator colligations and their characteristic functions. Consider a $p$-adic group $G=GL(\alpha+k\infty, Q_p)$, its subgroup $L=O(k\infty,Z_p)$, and the subgroup $K=O(\infty,Z_p)$ embedded to $L$ diagonally. We show that double cosets $\Gamma= K\setminus G/K$ admit a structure of a semigroup, $\Gamma$ acts naturally in $K$-fixed vectors of unitary representations of $G$. For each double coset we assign a 'characteristic function', which sends a certain Bruhat--Tits building to another building (buildings are finite-dimensional); image of the distinguished boundary is contained in the distinguished boundary. The latter building admits a structure of (Nazarov) semigroup, the product in $\Gamma$ corresponds to a point-wise product of characteristic functions.Comment: new version of the paper, 47pp, 3 figure

Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C

Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation–tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509

Root polytopes and abelian ideals

We study the root polytope $\mathcal P_\Phi$ of a finite irreducible crystallographic root system $\Phi$ using its relation with the abelian ideals of a Borel subalgebra of a simple Lie algebra with root system $\Phi$. We determine the hyperplane arrangement corresponding to the faces of codimension 2 of $\mathcal P_\Phi$ and analyze its relation with the facets of $\mathcal P_\Phi$. For $\Phi$ of type $A_n$ or $C_n$, we show that the orbits of some special subsets of abelian ideals under the action of the Weyl group parametrize a triangulation of $\mathcal P_\Phi$. We show that this triangulation restricts to a triangulation of the positive root polytope $\mathcal P_\Phi^+$.Comment: 41 pages, revised version, accepted for publication in Journal of Algebraic Combinatoric

Evolutionary Changes in the Complexity of the Tectum of Nontetrapods: A Cladistic Approach

Background: The tectum is a structure localized in the roof of the midbrain in vertebrates, and is taken to be highly conserved in evolution. The present article assessed three hypotheses concerning the evolution of lamination and citoarchitecture of the tectum of nontetrapod animals: 1) There is a significant degree of phylogenetic inertia in both traits studied (number of cellular layers and number of cell classes in tectum); 2) Both traits are positively correlated accross evolution after correction for phylogeny; and 3) Different developmental pathways should generate different patterns of lamination and cytoarchitecture. Methodology/Principal Findings: The hypotheses were tested using analytical-computational tools for phylogenetic hypothesis testing. Both traits presented a considerably large phylogenetic signal and were positively associated. However, no difference was found between two clades classified as per the general developmental pathways of their brains. Conclusions/Significance: The evidence amassed points to more variation in the tectum than would be expected by phylogeny in three species from the taxa analysed; this variation is not better explained by differences in the main course of development, as would be predicted by the developmental clade hypothesis. Those findings shed new light on th

Epstein-Barr Virus BGLF4 Kinase Retards Cellular S-Phase Progression and Induces Chromosomal Abnormality

Epstein-Barr virus (EBV) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus. The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1. However, the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression. Here, we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells. Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae. Using time-lapse microscopy, we found the fate of individual HeLa cells was determined by the expression level of BGLF4. In addition to slight cell growth retardation, BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells. In Saos-2 cells, BGLF4 induced the hyperphosphorylation of co-transfected RB, while E2F1 was not released from RB-E2F1 complexes. The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner. Detection with phosphoamino acid specific antibodies revealed that, in addition to Ser780, phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4. Taken together, our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression

Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis

Zn2+-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn2+-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential cofactor of the ATM kinase. Here we show that absence of ASCIZ leads to p53-independent late-embryonic lethality in mice. Asciz-deficient primary fibroblasts exhibit increased sensitivity to DNA base damaging agents MMS and H2O2, but Asciz deletion or knock-down does not affect ATM levels and activation in mouse, chicken, or human cells. Unexpectedly, Asciz-deficient embryos also exhibit severe respiratory tract defects with complete pulmonary agenesis and severe tracheal atresia. Nkx2.1-expressing respiratory precursors are still specified in the absence of ASCIZ, but fail to segregate properly within the ventral foregut, and as a consequence lung buds never form and separation of the trachea from the oesophagus stalls early. Comparison of phenotypes suggests that ASCIZ functions between Wnt2-2b/ß-catenin and FGF10/FGF-receptor 2b signaling pathways in the mesodermal/endodermal crosstalk regulating early respiratory development. We also find that ASCIZ can activate expression of reporter genes via its SQ/TQ-cluster domain in vitro, suggesting that it may exert its developmental functions as a transcription factor. Altogether, the data indicate that, in addition to its role in the DNA base damage response, ASCIZ has separate developmental functions as an essential regulator of respiratory organogenesis

The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization

Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes

Efeitos de reguladores de crescimento na frutificação do tomateiro cultivar «Miguel Pereira»

To study the influence on fruiting, (2-chloroethyl) trimethylammonium chloride (CCC) at concentration of 2,000 ppm, succinic acid-2,2-dimethylhydrazide (SADH) (3,000 ppm), gibberellic acid (GA) (200 ppm), and (2-chloroethyl) phosphonic acid (CEPA) (200 ppm) were applied. Treatments with CCC, CEPA, GA and SADH did not affect the total weight of tomato fruits. The growth regulators did not promote changes in fruit number. Applications of CCC and CEPA did not affect the fruit weight average; however, spraying with SADH and GA reduced the fruit weight average.Estudaram-se cm condições de campo (Piracicaba, SP), os efeitos da aplicação de reguladores de crescimentos no peso, número e peso médio dos frutos de tomateiro cultivar "Miguel Pereira". Quando as plantas apresentavam quatro folhas definitivas efetuou-se a pulverização com cloreto de (2-cloroetil) trimetilamônio 2.000 ppm, ácido succínico -2,2- dimetilhidrazida 3.000 ppm, ácido giberélico 200 ppm e ácido (2-cloroetil) fosfônica 200 ppm. Verificou-se que o CCC, CEPA, GA e SADH, não afetaram o peso total dos frutos de tomateiro. Os reguladores de crescimento não promoveram variação no número de frutos produzidos. Observou-se que tratamentos com CCC e CEPA não afetaram o peso médio do fruto; sendo que aplicação de SADH e GA reduziu o peso médio do fruto