Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.

Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma.

The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS-CHOP fusion gene. We previously developed a mouse model of liposarcoma by expressing FUS-CHOP in murine mesenchymal stem cells. In order to understand how FUS-CHOP can initiate liposarcoma, we have now generated transgenic mice expressing altered forms of the FUS-CHOP protein. Transgenic mice expressing high levels of CHOP, which lacks the FUS domain, do not develop any tumor despite its tumorigenicity in vitro and widespread activity of the EF1alpha promoter. These animals consistently show the accumulation of a glycoprotein material within the terminally differentiated adipocytes, a characteristic figure of liposarcomas associated with FUS-CHOP. On the contrary, transgenic mice expressing the altered form of FUS-CHOP created by the in frame fusion of the FUS domain to the carboxy end of CHOP (CHOP-FUS) developed liposarcomas. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1alpha promoter. The characteristics of the liposarcomas arising in the CHOP-FUS mice were very similar to those previously observed in our FUS-CHOP transgenic mice indicating that the FUS domain is required not only for transformation but also influences the phenotype of the tumor cells. These results provide evidence that the FUS domain of FUS-CHOP plays a specific and critical role in the pathogenesis of liposarcoma.

The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice.

The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1alpha (EF1alpha) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-specific genes and a concordant block in the differentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARgamma, whereas it is not expressed in embryonic fibroblasts from these animals following induction to differentiation toward the adipocyte lineage, indicating that the in vitro system does not really reflect the in vivo situation and the developmental defect is downstream of PPARgamma expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1alpha promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the first in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

Gonadal influences on spinal cord and brain monoamines in male rats.

Concentrations of norepinephrine (NE), dopamine (DA), 3,4-dihydroxy phenylacetic acid (DOPAC), serotonin (HT) and 5-hydroxyindoleacetic acid (HIAA) were measured by high-performance liquid chromatography-electrical detection (HPLC-ED) in homogenates of lumbosacral spinal cord, mediobasal hypothalamus and cerebral cortex of male rats. The effects of castration and testosterone propionate (TP) (20 micrograms/day X 2 days) were compared. Castrated animals had the highest levels of DA and DOPAC in the cerebral cortex and NE, HT and HIAA in the spinal cord, as well as decreased hypothalamic DOPAC. Testosterone treatment returned spinal cord monoamine concentrations to intact control levels. These findings point to the spinopetal monoaminergic pathways as sensitive targets for androgen action.

Regional changes of brain Na+,K+-transporting adenosine triphosphatase related to ovarian function.

Synaptosomal Na+,K+-transporting ATPase activity of the mediobasal hypothalamus (MBH), the medial preoptic-suprachiasmatic (POSC) region and cerebral cortex was measured in rats at different stages of the estrous cycle and after ovariectomy and estradiol replacement. Enzyme activity of the MBH and POSC showed cyclic changes. In both regions it increased shortly before the proestrus surge of LH. However, the two areas responded to castration and estrogen treatment in an opposite fashion. No changes were detected in enzyme activity in the cerebral cortex. These findings are consistent with previous reports on cyclic changes in electrical activity and suggest that Na+,K+-ATPase activity could be a useful indicator of neural activity for the study of neuroendocrine interactions.

Androgens stimulate preoptic area Na+,K+-ATPase activity in male rats.

This paper describes the effects of castration and testosterone replacement on the Na+,K+-ATPase activity levels of the cerebral cortex (CC), preoptic-suprachiasmatic region (POSC) and mediobasal hypothalamus (MBH) in male rats. Na+,K+-ATPase activity was estimated as the ouabain-sensitive fraction of ADP and AMP generation rate, measured by high-pressure liquid chromatography (HPLC) with UV detection, from a standard incubation mixture containing 3 mM ATP. Orchidectomy, performed 4 weeks before sacrifice, decreased ATPase activity of MBH. Testosterone propionate treatment (50 micrograms/day X 2 days) to castrated animals resulted in a 4-fold increase in enzyme activity in the POSC, an effect that might be related to the behavioral effects of androgens. None of the treatments seemed to influence the enzyme activity of the cerebral cortex.

4-nitrophenyl phosphatase activity of the red blood cell membrane in essential hypertension.

In this paper we report the levels of the 4-nitrophenyl phosphate hydrolysing activity of the red blood cell membrane in 46 hypertensive patients as compared to 41 normal controls and eight secondary hypertensives. This activity has at least two components; one of them is dependent on the presence of magnesium and potassium ions, and more sensitive to sodium, ATP, heat and -SH blockers than the cation-independent activity. This component appears increased in membranes from essential hypertension patients, correlating to the clinical seriousness of the condition, while remaining at control level in the secondary hypertension patients. The cation-independent component of this activity does not differ significantly in any of the groups studied.

Rubidium and sodium transport across erythrocyte membrane: alterations due to a circulating factor.

Essential hypertension patients can be divided into two groups on the basis of the presence or absence of a plasma factor able to inhibit rubidium uptake and sodium extrusion by the red blood cells. Nearly fifty percent of the patients studied present this factor. Preliminary results show that it is dialyzable, has a molecular weight around 500 daltons and cannot be extracted by chloroform.

Changes in forebrain Na,K-ATPase activity and serum hormone levels during sexual behavior in male rats.

We have previously shown that Na,K-ATPase activity (the enzymatic machinery for the sodium pump) in brain areas such as the medial basal hypothalamus (MBH) and the preoptic-suprachiasmatic region (POSC) can be changed by experimental manipulations of gonadal function. We now report enzyme levels in brain regions as related to hormonal changes occurring during sexual behavior. Male rats were exposed to receptive females and decapitated immediately after displaying one of the following behavioral events: the start of copulatory activity, first ejaculation, and the beginning of a second copulatory series. A group of noncopulating animals were used as control. The variables measured included serum levels of LH, PRL and testosterone and Na,K-ATPase activity in MBH, POSC and parietal cerebral cortex (CC). A steady increase in enzyme activity in the POSC, but not the MBH or CC, was found in copulating animals. Serum LH levels changed in a similar fashion. A sharp increase in serum PRL levels, seemingly related to ejaculation, was also observed. These data are consistent with our previous findings on monoaminergic neurotransmission in brain regions related to male sexual behavior.

Neurochemical correlates of male sexual behavior.

This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non-mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies.

[A substitute treatment for dialysis?]. / Tratamiento sustitutivo de la diálisis?

One of the major problems regarding the administration of amino acids by intravenous feeding is the use of racemic mixtures that are forbidden by the pharmacological regulations; other current problems is the high cost of obtaining pure amino acids. Because of this, our group has been working in the obtention of L-amino acids (assimilables by living organisms) and ketoacids (used by the body as precursors of racemic amino acid mixtures) in a less expensive and simpler way, with the aim of using these products for different pathologies.

Rifampin: inhibition of ribonucleic acid synthesis after potentiation by amphotericin B in Saccharomyces cerevisiae.

The inhibition of Saccharomyces cerevisiae growth by amphotericin B and rifampin was studied. Rifampin alone had no effect on growth or macromolecular syntheses. Lethal amounts of amphotericin B produced a late inhibition of ribonucleic acid (RNA) synthesis simultaneous with the arrest of growth and protein synthesis. In contrast, low doses of amphotericin B along with rifampin caused an early arrest of RNA synthesis, followed by a later arrest of growth and protein synthesis. Used with rifampin, amphotericin B thus appears to increase cell permeability for rifampin, which in turn inhibits RNA synthesis; such results are consistent with some reports of inhibition of yeast RNA polymerase function by rifampin. Experiments with petite mutants ruled out any special effect of the antibiotics on mitochondrial RNA synthesis, so that nuclear RNA synthesis is affected. Acrylamide gel analyses of RNA pulse-labeled after addition of the two antibiotics in synergy showed that synthesis of all major classes of RNA was progressively and uniformly inhibited.

Human semen aspartate aminotransferase and alanine aminotransferase activity in male fertility studies.

The enzymatic activities of aminotransferases AST and ALT have been measured in the semen of a group of 98 subjects undergoing fertility studies, correlated with spermatic density and motility. An AST/ALT ratio was obtained for all patients. The results indicate that there exists a correlation between both enzymes' activities and spermatic density and motility. In two cases of excretory azoospermia, an elevated AST/ALT relation was obtained, while in two cases f secretory azoospermia a low AST/ALT ratio was seen. Aminotransferase values can thus be considered a useful piece of data in the evaluation of seminal quality, and the AST/ALT ratio used more specifically in te discrimination of the various types of azoospermia.

Metabolism of red blood cells in chronic renal failure. I. Glycolytic enzyme levels.

This paper starts a series on red blood cell (RBC) metabolism in patients with chronic renal failure (CRF). The glycolytic enzyme levels and in vitro half-lives of these patients' RBCs were determined. A number of enzymes (hexokinase, glucose-6-phosphate isomerase, fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase) showed higher activities than in normal control RBCs. Other enzyme activities were normal. These results were discussed and several possible mechanisms considered. We favour the point of view of a shortened life span of the RBCs in CRF, making the most unstable enzymes of the glycolytic sequence appear increase as compared with normal controls.

Hormone levels in serum and seminal plasma of men with different types of azoospermia.

Hormone concentrations in the serum and seminal plasma of 15 normozoospermic, 17 excretory azoospermic and 14 secretory azoospermic men were measured. The results indicate that: (a) serum FSH and LH levels are markedly elevated in secretory azoospermia, as compared with excretory azoospermia and normozoospermia; (b) serum 17 alpha-hydroxyprogesterone levels are somewhat raised in secretory azoospermia as compared with excretory azoospermia and normozoospermia; (c) serum testosterone levels are lower in both types of azoospermia with respect to normozoospermia; (d) in secretory azoospermia the oestradiol serum levels are relatively high and dihydrotestosterone serum levels relatively low, whereas the serum levels of these hormones in excretory azoospermia are similar to those in normozoospermic men; (e) in the seminal plasma of azoospermic patients the levels of prolactin, progesterone, testosterone, dihydrotestosterone and oestradiol were depressed, but only dihydrotestosterone levels could be of value in differentiating types of azoospermia because they are lower in secretory azoospermia. We suggest that the measurement of FSH, LH, 17 alpha-hydroxyprogesterone, dihydrotestosterone and oestradiol in serum and dihydrotestosterone in seminal plasma may be used in the differential diagnosis between secretory and excretory azoospermia when invasive tests are unavailable.