The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression

AbstractDuring the last decades a considerable amount of research has been focused on cancer. Recently, tumor cell metabolism has been considered as a possible target for cancer therapy. It is widely accepted that tumors display enhanced glycolytic activity and impaired oxidative phosphorylation (Warburg effect). Therefore, it seems reasonable that disruption of glycolysis might be a promising candidate for specific anti-cancer therapy. Nevertheless, the concept of aerobic glycolysis as the paradigm of tumor cell metabolism has been challenged, as some tumor cells exhibit high rates of oxidative phosphorylation. Mitochondrial physiology in cancer cells is linked to the Warburg effect. Besides, its central role in apoptosis makes this organelle a promising “dual hit target” to selectively eliminate tumor cells. From a metabolic point of view, the fermenting yeast Saccharomyces cerevisiae and tumor cells share several features. In this paper we will review these common metabolic properties as well as the possible origins of the Crabtree and Warburg effects. This article is part of a Special Issue entitled: Bioenergetics of Cancer

Millimagnitude Photometry for Transiting Extrasolar Planetary Candidates III: Accurate Radius and Period for OGLE-TR-111-b

We present accurate V-band photometry for a planetary transit of OGLE-TR-111 acquired with VIMOS at the ESO Very Large Telescope. The measurement of this transit allows to refine the planetary radius, obtaining R_p= 1.01 +/- 0.06 R_J. Given the mass of M_p = 0.53 M_J previously measured from radial velocities, we confirm that the density is rho_p= 0.6 +/- 0.2 g/cm^3. We also revise the ephemeris for OGLE-TR-111-b, obtaining an accurate orbital period P= 4.014484 +/- 0.000014 days, and predicting that the next observable transits would occur around December 2006, and after that only in mid-2008. Even though this period is different from previously published values, we cannot yet rule out a constant period.Comment: 16 pages (including figures), 5 figures, 1 table. Accepted for publication in the Astrophysical Journa

Millimagnitude Photometry for Transiting Extrasolar Planetary Candidates IV: The Puzzle of the Extremely Red OGLE-TR-82 Primary Solved

We present precise new V, I, and K-band photometry for the planetary transit candidate star OGLE-TR-82. Good seeing V-band images acquired with VIMOS instrument at ESO VLT allowed us to measure V=20.6+-0.03 mag star in spite of the presence of a brighter neighbour about 1" away. This faint magnitude answers the question why it has not been possible to measure radial velocities for this object. One transit of this star has been observed with GMOS-S instrument of GEMINI-South telescope in i and g-bands. The measurement of the transit allows us to verify that this is not a false positive, to confirm the transit amplitude measured by OGLE, and to improve the ephemeris. The transit is well defined in i-band light curve, with a depth of A_i=0.034 mag. It is however, less well defined, but deeper (A_g=0.1 mag) in the g-band, in which the star is significantly fainter. The near-infrared photometry obtained with SofI array at the ESO-NTT yields K=12.2+-0.1 and V-K=8.4+-0.1, so red that it is unlike any other transit candidate studied before. Due to the extreme nature of this object, we have not yet been able to measure velocities for this star, but based on the new data we consider two different possible configurations:(1) a nearby M7V star, or (2) a blend with a very reddened distant red giant. The nearby M7V dwarf hypothesis would give a radius for the companion of R_p=0.3+-0.1 R_J, i.e. the size of Neptune. Quantitative analysis of near-IR spectroscopy finally shows that OGLE-TR-82 is a distant, reddened metal poor early K giant. This result is confirmed by direct comparison with stellar templates that gives the best match for a K3III star. Therefore, we discard the planetary nature of the companion. Based on all the new data, we conclude that this system is a main-sequence binary blended with a background red giant.Comment: 26 pages, 9 figures, ApJ accepte

Relation between liver lipid content and plasma biochemical indicators in dairy cows

Background: The incidence of metabolic disorders in dairy cows has increased as a result of intensive production practices and genetic selection for milk yield. Among such disorders, liver lipidosis is very frequently observed and has significant negative effects on cow health and milk yield. Severe energy supply deficit causes high fat mobilization, resulting in rapid body condition loss and liver lipid infiltration, which cannot always be detected by known blood biochemical indicators. The main objective of the study was to determine possible associations of blood biochemical parameters with liver lipid infiltration severity in high-yield multiparous Holstein cows along prepartum and postpartum periods. Materials, Methods & Results: Fifty-four high-yield Holstein cows from a herd managed in a free-stall system in the northwest region of the state of Rio Grande do Sul, Brazil were evaluated. Cows were divided in two groups according to their physiological status. Group 1 included 19 prepartum cows, with an average milk yield of 44.7 L/d in the previous lactation, and 2.8 average parity, and Group 2 included 35 postpartum cows, with an average milk yield of 46.8 L/d in the previous lactation, and 2.5 average parity. The farm produced 10,000 kg milk per year, containing 3.5% of fat, 3.2% of protein and 4.7% of lactose. Total cholesterol (CH), plasma triglycerides (TGp), beta-hydroxybutyrate (BHB), albumin (ALB), non-esterified free fatty acids (NEFA) levels, and aspartate aminotransferase (AST) and creatine kinase (CK) ac-tivities were analyzed in the plasma and liver triglycerides (TGl) levels were determined in liver tissue samples. The SPSS statistical software was used for the statistical analyses. The obtained data were analyzed for normality by the Shapiro-Wilk test and for homoscedasticity by Bartlett test. Data were submitted to analysis of variance, and means were compared by the t-test (PROC TTEST). Pearson correlation test (PROC CORR) was used to compare the results between prepartum and postpartum cows, and between those with and without lipidosis. An overall incidence of 20% severe hepatic lipidosis was determined both in prepartum and postpartum cows. Positive significant correlations were obtained between days in milk (DIM) and AST (r= 0.43; P < 0.01), CH and TGp (r= 0.44; P < 0.01), TGl and AST (r=0.32; P < 0.05), NEFA and AST (r= 0.45; P < 0.01) and CK and AST (r= 0.447; P < 0.01). Negative significant correlations were detected between TGp and DIM (r= -0.45; P < 0.01), and between TGl and TGp (r= -0.30; P < 0.05). Discussion: Prepartum cows showed moderate fat infiltration in the liver, while 25.7% of postpartum cows presented severe lipidosis. AST values increased as lactation progressed, suggesting a greater tendency of liver damage, in early postpartum. The obtained CK values were within the reference range, except for the cows with hepatic lipidosis, indicat¬ing that the measured AST activity was originated from the liver and not from the muscle tissues. TGp, NEFA and AST values indicate the degree of fat mobilization and, possibly, liver infiltration, while TGl indicates fat infiltration in the liver. Although negative energy balance (NEB) may trigger lipolysis and some degree of hepatic lipidosis, plasma BHB values did not significantly increase. The obtained results show that the evaluated plasma parameters may be useful to establish guidelines for the identification of changes in the metabolic profile of dairy cows during different production stages, as well as measures for the prevention and control of metabolic disorders

Hemogram-derived ratios as prognostic markers of ICU admission in COVID-19.

Background The vast impact of COVID-19 call for the identification of clinical parameter that can help predict a torpid evolution. Among these, endothelial injury has been proposed as one of the main pathophysiological mechanisms underlying the disease, promoting a hyperinflammatory and prothrombotic state leading to worse clinical outcomes. Leukocytes and platelets play a key role in inflammation and thrombogenesis, hence the objective of the current study was to study whether neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) as well as the new parameter neutrophil-to-platelet ratio (NPR), could help identify patients who at risk of admission at Intensive Care Units. Methods A retrospective observational study was performed at HM Hospitales including electronic health records from 2245 patients admitted due to COVID-19 from March 1 to June 10, 2020. Patients were divided into two groups, admitted at ICU or not. Results Patients who were admitted at the ICU had significantly higher values in all hemogram-derived ratios at the moment of hospital admission compared to those who did not need ICU admission. Specifically, we found significant differences in NLR (6.9 [4–11.7] vs 4.1 [2.6–7.6], p <  0.0001), PLR (2 [1.4–3.3] vs 1.9 [1.3–2.9], p = 0.023), NPR (3 [2.1–4.2] vs 2.3 [1.6–3.2], p <  0.0001) and SII (13 [6.5–25.7] vs 9 [4.9–17.5], p <  0.0001) compared to those who did not require ICU admission. After multivariable logistic regression models, NPR was the hemogram-derived ratio with the highest predictive value of ICU admission, (OR 1.11 (95% CI: 0.98–1.22, p = 0.055). Conclusions Simple, hemogram-derived ratios obtained from early hemogram at hospital admission, especially the novelty NPR, have shown to be useful predictors of risk of ICU admission in patients hospitalized due to COVID-19.post-print997 K

Millimagnitude Photometry for Transiting Extrasolar Planetary Candidates: II. Transits of OGLE-TR-113-b in the Optical and Near-IR

We present precise V and Ks-band transit photometry for the planetary host star OGLE-TR-113. Using the Ks-band photometry, we confirm the dwarf nature of OGLE-TR-113, and obtain new estimates for its effective temperature, distance and reddening. We employ the V-band photometry to obtain planetary and orbit parameters from the transit fit, a= (0.0232 \pm 0.0038) AU, orbital period P= (1.4324752 \pm 0.0000015) days, i= 86.7 - 90, R_p= (1.09 \pm 0.09) R_J. These values are in excellent agreement with previous works. Assuming a mass M_p= (1.32 \pm 0.19) M_J for the planet we obtain its mean density \rho= (1.26 \pm 0.50) g cm^{-3}, also in agreement with previous works. The transit observed in the Ks-band has a larger scatter and we find its amplitude to be consistent with that in the V-band. In this way, we find an independent confirmation of the planetary nature of OGLE-TR-113b.Comment: 26 pages, 10 figures, 1 table. Accepted for publication in the Astrophysical Journa

Commissioning and performance of the CMS silicon strip tracker with cosmic ray muons

46 páginas, 17 figuras, 8 tablas.-- Open Access.-- CMS Collaboration: et al.During autumn 2008, the Silicon Strip Tracker was operated with the full CMS experiment in a comprehensive test, in the presence of the 3.8 T magnetic field produced by the CMS superconducting solenoid. Cosmic ray muons were detected in the muon chambers and used to trigger the readout of all CMS sub-detectors. About 15 million events with a muon in the tracker were collected. The efficiency of hit and track reconstruction were measured to be higher than 99% and consistent with expectations from Monte Carlo simulation. This article details the commissioning and performance of the Silicon Strip Tracker with cosmic ray muons.Individuals have received support from the Marie-Curie IEF program (European Union); the Leventis Foundation; the A. P. Sloan Foundation; and the Alexander von Humboldt Foundation.Peer reviewe

Fine synchronization of the CMS muon drift-tube local trigger using cosmic rays

33 páginas, 12 figuras.-- Open Access.-- CMS Collaboration: et al.The CMS experiment uses self-triggering arrays of drift tubes in the barrel muon trigger to perform the identification of the correct bunch crossing. The identification is unique only if the trigger chain is correctly synchronized. In this paper, the synchronization performed during an extended cosmic ray run is described and the results are reported. The random arrival time of cosmic ray muons allowed several synchronization aspects to be studied and a simple method for the fine synchronization of the Drift Tube Local Trigger at LHC to be developed.Individuals have received support from the Marie-Curie IEF program (European Union); the Leventis Foundation; the A. P. Sloan Foundation; and the Alexander von Humboldt Foundation.Peer reviewe

Performance of the CMS Level-1 trigger during commissioning with cosmic ray muons and LHC beams

52 páginas, 25 figuras.-- Open Access.-- CMS Collaboration: et al.The CMS Level-1 trigger was used to select cosmic ray muons and LHC beam events during data-taking runs in 2008, and to estimate the level of detector noise. This paper describes the trigger components used, the algorithms that were executed, and the trigger synchronisation. Using data from extended cosmic ray runs, the muon, electron/photon, and jet triggers have been validated, and their performance evaluated. Efficiencies were found to be high, resolutions were found to be good, and rates as expected.Acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie IEF program (European Union); the Leventis Foundation; the A. P. Sloan Foundation; and the Alexander von Humboldt Foundation.Peer reviewe

Alignment of the CMS muon system with cosmic-ray and beam-halo muons

43 páginas, 11 figuras, 6 tablas.-- Open Access.-- CMS Collaboration: et al.The CMS muon system has been aligned using cosmic-ray muons collected in 2008 and beam-halo muons from the 2008 LHC circulating beam tests. After alignment, the resolution of the most sensitive coordinate is 80 microns for the relative positions of superlayers in the same barrel chamber and 270 microns for the relative positions of endcap chambers in the same ring structure. The resolution on the position of the central barrel chambers relative to the tracker is comprised between two extreme estimates, 200 and 700 microns, provided by two complementary studies. With minor modifications, the alignment procedures can be applied using muons from LHC collisions, leading to additional significant improvements.Individuals have received support from the Marie-Curie IEF program (European Union); the Leventis Foundation; the A. P. Sloan Foundation; and the Alexander von Humboldt Foundation.Peer reviewe