Calcium-fortified beverage supplementation on body composition in postmenopausal women

BACKGROUND: We investigated the effects of a calcium-fortified beverage supplemented over 12 months on body composition in postmenopausal women (n = 37, age = 48–75 y). METHODS: Body composition (total-body percent fat, %Fat(TB); abdominal percent fat, %Fat(AB)) was measured with dual energy x-ray absorptiometry. After baseline assessments, subjects were randomly assigned to a free-living control group (CTL) or the supplement group (1,125 mg Ca(++)/d, CAL). Dietary intake was assessed with 3-day diet records taken at baseline and 12 months (POST). Physical activity was measured using the Yale Physical Activity Survey. RESULTS: At 12 months, the dietary calcium to protein ratio in the CAL group (32.3 ± 15.6 mg/g) was greater than the CTL group (15.2 ± 7.5 mg/g). There were no differences from baseline to POST between groups for changes in body weight (CAL = 0.1 ± 3.0 kg; CTL = 0.0 ± 2.9 kg), %Fat(TB )(CAL = 0.0 ± 2.4%; CTL = 0.5 ± 5.4%), %Fat(AB )(CAL = -0.4 ± 8.7%; CTL = 0.6 ± 8.7%), or fat mass (CAL = 1.3 ± 2.6 kg; CTL = 1.3 ± 2.7 kg). CONCLUSION: These results indicate that increasing the calcium to protein ratio over two-fold by consuming a calcium-fortified beverage for 12 months did not decrease body weight, body fat, or abdominal fat composition in postmenopausal women

On the Gibbs states of the noncritical Potts model on Z^2

We prove that all Gibbs states of the q-state nearest neighbor Potts model on Z^2 below the critical temperature are convex combinations of the q pure phases; in particular, they are all translation invariant. To achieve this goal, we consider such models in large finite boxes with arbitrary boundary condition, and prove that the center of the box lies deeply inside a pure phase with high probability. Our estimate of the finite-volume error term is of essentially optimal order, which stems from the Brownian scaling of fluctuating interfaces. The results hold at any supercritical value of the inverse temperature.Comment: Minor typos corrected after proofreading. Final version, to appear in Probab. Theory Relat. Field

Selection of suitable reference genes for quantitative real-time polymerase chain reaction in human meningiomas and arachnoidea

<p>Abstract</p> <p>Findings</p> <p>At first 32 housekeeping genes were analyzed in six randomly chosen meningiomas, brain and dura mater using geNorm, NormFinder, Bestkeeper-1 software and the comparative ΔCt method. Reference genes were ranked according to an integration tool for analyzing reference genes expression based on those four algorithms. Eight highest ranked reference genes (CASC3, EIF2B1, IPO8, MRPL19, PGK1, POP4, PPIA, and RPL37A) plus GAPDH and ACTB were then analyzed in 35 meningiomas, arachnoidea, dura mater and normal brain. NormFinder and Bestkeeper-1 identified RPL37A as the most stable expressed gene in meningiomas and their normal control tissue. NormFinder also determined the best combination of genes: RPL37A and EIF2B1. Commonly used reference genes GAPDH and ACTB were considered least stable genes. The critical influence of reference genes on qPCR data analysis is shown for VEGFA transcription patterns.</p> <p>Background</p> <p>In meningiomas quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is most frequently used for accurate determination of gene expression using various reference genes. Although meningiomas are a heterogeneous group of tissue, no data have been reported to validate reference genes for meningiomas and their control tissues.</p> <p>Conclusions</p> <p>RPL37A is the optimal single reference gene for normalization of gene expression in meningiomas and their control tissues, although the use of the combination of RPL37A and EIF2B1 would provide more stable results.</p

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours

Background:The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups.Methods:We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients.Results:The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples.Conclusions:The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs

Murein and pseudomurein cell wall binding domains of bacteria and archaea—a comparative view

The cell wall, a major barrier protecting cells from their environment, is an essential compartment of both bacteria and archaea. It protects the organism from internal turgor pressure and gives a defined shape to the cell. The cell wall serves also as an anchoring surface for various proteins and acts as an adhesion platform for bacteriophages. The walls of bacteria and archaea are mostly composed of murein and pseudomurein, respectively. Cell wall binding domains play a crucial role in the non-covalent attachment of proteins to cell walls. Here, we give an overview of the similarities and differences in the biochemical and functional properties of the two major murein and pseudomurein cell wall binding domains, i.e., the Lysin Motif (LysM) domain (Pfam PF01476) and the pseudomurein binding (PMB) domain (Pfam PF09373) of bacteria and archaea, respectively

Single cell derived mRNA signals across human kidney tumors.

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer

High susceptibility to lipopolysaccharide-induced lethal shock in encephalomyocarditis virus-infected mice

Secondary bacterial infection in humans is one of the pathological conditions requiring clinical attention. In this study, we examined the effect of lipopolysaccharide (LPS) on encephalomyocarditis virus (EMCV) infected mice. All mice inoculated with EMCV at 5 days before LPS challenge died within 24 h. LPS-induced TNF-α mRNA expression was significantly increased in the brain and heart at 5 days after EMCV infection. CD11b+/TLR4+ cell population in the heart was remarkably elevated at 5 days after EMCV infection, and sorted CD11b+ cells at 5 days after EMCV infection produced a large amount of TNF-α on LPS stimulation in vivo and in vitro. In conclusion, we found that the infiltration of CD11b+ cells into infected organs is involved in the subsequent LPS-induced lethal shock in viral encephalomyocarditis. This new experimental model can help define the mechanism by which secondary bacterial infection causes a lethal shock in viral encephalomyocarditis

Opposing Effects of Sirtuins on Neuronal Survival: SIRT1-Mediated Neuroprotection Is Independent of Its Deacetylase Activity

Background: Growing evidence suggests that sirtuins, a family of seven distinct NAD-dependent enzymes, are involved in the regulation of neuronal survival. Indeed, SIRT1 has been reported to protect against neuronal death, while SIRT2 promotes neurodegeneration. The effect of SIRTs 3–7 on the regulation of neuronal survival, if any, has yet to be reported. Methodology and Principal Findings: We examined the effect of expressing each of the seven SIRT proteins in healthy cerebellar granule neurons (CGNs) or in neurons induced to die by low potassium (LK) treatment. We report that SIRT1 protects neurons from LK-induced apoptosis, while SIRT2, SIRT3 and SIRT6 induce apoptosis in otherwise healthy neurons. SIRT5 is generally localized to both the nucleus and cytoplasm of CGNs and exerts a protective effect. In a subset of neurons, however, SIRT5 localizes to the mitochondria and in this case it promotes neuronal death. Interestingly, the protective effect of SIRT1 in neurons is not reduced by treatments with nicotinamide or sirtinol, two pharmacological inhibitors of SIRT1. Neuroprotection was also observed with two separate mutant forms of SIRT1, H363Y and H355A, both of which lack deacetylase activity. Furthermore, LK-induced neuronal death was not prevented by resveratrol, a pharmacological activator of SIRT1, at concentrations at which it activates SIRT1. We extended our analysis to HT-22 neuroblastoma cells which can be induced to die by homocysteic acid treatment. While the effects of most of the SIRT proteins were similar to that observed in CGNs, SIRT6 was modestly protective against homocysteic acid toxicity in HT-22 cells. SIRT5 was generally localized in th

Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer

Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m−2 PPX or 75 mg m−2 docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease. Median survival (6.9 months in both arms, hazard ratio=1.09, P=0.257), 1-year survival (PPX=25%, docetaxel=29%, P=0.134), and time to progression (PPX=2 months, docetaxel=2.6 months, P=0.075) were similar between treatment arms. Paclitaxel poliglumex was associated with significantly less grade 3 or 4 neutropenia (P<0.001) and febrile neutropenia (P=0.006). Grade 3 or 4 neuropathy (P<0.001) was more common in the PPX arm. Patients receiving PPX had less alopecia and did not receive routine premedications. More patients discontinued due to adverse events in the PPX arm compared to the docetaxel arm (34 vs 16%, P<0.001). Paclitaxel poliglumex and docetaxel produced similar survival results but had different toxicity profiles. Compared with docetaxel, PPX had less febrile neutropenia and less alopecia, shorter infusion times, and elimination of routine use of medications to prevent hypersensitivity reactions. Paclitaxel poliglumex at a dose of 210 mg m−2 resulted in increased neurotoxicity compared with docetaxel