178 research outputs found

    Negative Cell Cycle Regulation and DNA Damage-inducible Phosphorylation of the BRCT Protein 53BP1

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    In a screen designed to discover suppressors of mitotic catastrophe, we identified the Xenopus ortholog of 53BP1 (X53BP1), a BRCT protein previously identified in humans through its ability to bind the p53 tumor suppressor. X53BP1 transcripts are highly expressed in ovaries, and the protein interacts with Xp53 throughout the cell cycle in embryonic extracts. However, no interaction between X53BP1 and Xp53 can be detected in somatic cells, suggesting that the association between the two proteins may be developmentally regulated. X53BP1 is modified via phosphorylation in a DNA damage-dependent manner that correlates with the dispersal of X53BP1 into multiple foci throughout the nucleus in somatic cells. Thus, X53BP1 can be classified as a novel participant in the DNA damage response pathway. We demonstrate that X53BP1 and its human ortholog can serve as good substrates in vitro as well as in vivo for the ATM kinase. Collectively, our results reveal that 53BP1 plays an important role in the checkpoint response to DNA damage, possibly in collaboration with ATM

    RELATIONSHIP BETWEEN VERTICAL STIFFNESS AND REACTIVE STRENGTH INDEX MODIFIED IN COLLEGE-AGED MALES DURING JUMPING

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    The present study analyzed ground reaction forces that occur during a counter-movement vertical jump (CMVJ) to examine how measures assessing stretch-shortening cycle (SSC) interact. The participants consisted of thirteen recreationally active males that volunteered for this study. Vertical ground reaction forces were measured using a force platform sampling at 1000 Hz and exported into an RStudio vertical jump program for further analysis. A simple linear regression was performed to investigate the relationship between vertical stiffness and modified reactive strength index (RSImod). Modified reactive strength index was a significant predictor of vertical stiffness (p = .010, Adj. R2= .421). These results suggest that further examination of the mathematical equation used for RSImod is needed to eliminate possible effects of confounding variables as relationship differences were observed with the vertical stiffness measure that has been used for adequate assessment of the lower extremity muscle-tendon units’ status during counter-movement vertical jumping and other movements utilizing the SSC

    The political power of twitter

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    In June 2016, the British voted by 52 per cent to leave the EU, a club the UK joined in 1973. This paper examines Twitter public and political party discourse surrounding the BREXIT withdrawal agreement. In particular, we focus on tweets from four different BREXIT exit strategies known as “Norway”, “Article 50”, the “Backstop” and “No Deal” and their effect on the pound and FTSE 100 index from the period of December 10th 2018 to February 24th 2019. Our approach focuses on using a Naive Bayes classification algorithm to assess political party and public Twitter sentiment. A Granger causality analysis is then introduced to investigate the hypothesis that BREXIT public sentiment, as measured by the twitter sentiment time series, is indicative of changes in the GBP/EUR Fx and FTSE 100 Index. Our results from the Twitter public sentiment indicate that the accuracy of the “Article 50” scenario had the single biggest effect on short run dynamics on the FTSE 100 index, additionally the “Norway” BREXIT strategy has a marginal effect on the FTSE 100 index whilst there was no significant causation to the GBP/EUR Fx. The BREXIT Political party sentiment for the “No Deal” was indicative of short term dynamics on the GBP/EUR Fx at a marginal rate. Our test concluded that there was no causality on the FTSE 100

    Relationship of Blood Lactate and Sweat Lactate on Exercise Intensity

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    Typical procedures for measuring blood lactate involve either finger stick blood samples or venous blood draws. The literature is equivocal regarding whether sweat lactate values change with exercise intensity. Recently, wearable technology devices have been developed to measure sweat lactate. Purpose: To examine the relationship between sweat lactate and blood lactate values during incremental exercise. Methods: This study consisted of 12 (8 male, 4 female) healthy recreationally active individuals (VO2peak 35.5 ± 7.6 ml/kg/min) between the ages of 18 and 25 (22 ± 2 yrs) who volunteered for the study. Participants performed an exercise test on a cycle ergometer to volitional fatigue to determine blood lactate, lactate threshold, VO2peak, and peak heart rate (HR). Blood lactate was collected via finger stick at each 3-min stage of exercise. Participants performed a subsequent exercise session at 40, 60, and 80% heart rate reserve (HRR). During the 20-min stages of this test, blood and sweat lactate were collected during each intensity level. Sweat lactate was collected in a sweat “pouch” at each state of exercise. Sweat lactate samples were analyzed via the lactate oxidase method on a Chemwell 2910 chemistry analyzer. Blood lactate samples were analyzed using a Lactate Plus analyzer. Whole body sweat rate was calculated from pre- and post-exercise body weight at each intensity, factoring in water consumed and urine voided. Results: Sweat rate increased with increasing intensity (40%: 9.66 ± 7.58; 60%: 18.10 ± 12.51; 80% 24.32 ± 15.44 ml/min). Sweat lactate significantly differed between 60 and 80% intensities (15.66 ± 5.73, 12.52 ± 4.44 mmol/L, respectively), P = 0.03. Blood lactate levels at 40, 60, and 80% intensities were 2.67 ± 1.15, 3.60 ± 1.90, and 4.83 ± 1.52, respectively (P \u3c 0.001). CONCLUSION: These findings agree with Buono, Lee, & Miller, 2010 who found sweat lactate decreases as sweat rate increases. It is likely that sweat lactate decreases with increasing exercise intensity due to dilution as sweat rate increases. From this data, it appears that sweat lactate does not demonstrate a relationship with blood lactate that warrants replacing blood lactate in exercise testing with sweat lactate. This may be due to the lactate in sweat originating from eccrine glands and thus is not reflective of muscle metabolism

    Improved Orbital Constraints and Hα\alpha Photometric Monitoring of the Directly Imaged Protoplanet Analog HD 142527 B

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    Companions embedded in the cavities of transitional circumstellar disks have been observed to exhibit excess luminosity at Hα\alpha, an indication that they are actively accreting. We report 5 years (2013-2018) of monitoring of the position and Hα\alpha excess luminosity of the embedded, accreting low-mass stellar companion HD 142527 B from the MagAO/VisAO instrument. We use pyklip, a python implementation of the Karhounen-Loeve Image Processing algorithm, to detect the companion. Using pyklip forward modeling, we constrain the relative astrometry to 12mas1-2 \mathrm{mas} precision and achieve sufficient photometric precision (±0.2mag,3%\pm0.2 \mathrm{mag}, 3\% error) to detect changes in the Hα\alpha contrast of the companion over time. In order to accurately determine the relative astrometry of the companion, we conduct an astrometric calibration of the MagAO/VisAO camera against 20 years of Keck/NIRC2 images of the Trapezium cluster. We demonstrate agreement of our VisAO astrometry with other published positions for HD 142527 B, and use orbitize! to generate a posterior distribution of orbits fit to the relative astrometry of HD 142527 B. Our data suggest that the companion is close to periastron passage, on an orbit significantly misinclined with respect to both the wide circumbinary disk and the recently observed inner disk encircling HD 142527 A. We translate observed H-alpha contrasts for HD 142527 B into mass accretion rate estimates on the order of 49×1010Myr14-9\times10^{-10} \mathrm{M_\odot}\mathrm{yr}^{-1}. Photometric variation in the H-alpha excess of the companion suggests that the accretion rate onto the companion is variable. This work represents a significant step towards observing accretion-driven variability onto protoplanets, such as PDS 70 b\&c.Comment: Accepted to the Astronomical Journal. 32 pages, 16 figures, 8 tables, 4 appendice

    The Giant Accreting Protoplanet Survey (GAPlanetS) -- Results from a Six Year Campaign to Image Accreting Protoplanets

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    Accreting protoplanets represent a window into planet formation processes. We report H{\alpha} differential imaging results from the deepest and most comprehensive accreting protoplanet survey to date, acquired with the Magellan Adaptive Optics (MagAO) system's VisAO camera. The fourteen transitional disks targeted are ideal candidates for protoplanet discovery due to their wide, heavily depleted central cavities, wealth of non-axisymmetric circumstellar disk features evocative of ongoing planet formation, and ongoing stellar accretion. To address the twin challenges of morphological complexity in the target systems and PSF instability, we develop novel approaches for frame selection and optimization of the Karhounen-Loeve Image Processing algorithm pyKLIP. We detect one new candidate protoplanet, CS Cha "c", at a separation of 75mas and a {\Delta}mag of 5.1 and robustly recover the HD142527 B and HD100453 B low mass stellar companions across multiple epochs. Though we cannot rule out a substantial scattered light contribution to its emission, we also recover LkCa 15 b. Its presence inside of the cleared disk cavity and consistency with a forward-modeled point source suggest that it remains a viable protoplanet candidate. The protoplanet PDS 70 c was marginally recovered under our conservative general methodology. However, through targeted optimization in H{\alpha} imagery, we tentatively recover PDS 70 c in three epochs and PDS 70 b in one epoch. Of the many other previously-reported companions and companion candidates around objects in the sample, we do not recover any additional robust candidates. However, lack of recovery at moderate H{\alpha} contrast does not rule out the presence of protoplanets at these locations, and we report limiting H{\alpha} contrasts in such cases.Comment: Accepted for publication in A

    Hospital Epidemics Tracker (HEpiTracker): Description and pilot study of a mobile app to track COVID-19 in hospital workers

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    Background: Hospital workers have been the most frequently and severely affected professional group during the COVID-19 pandemic, and have a big impact on transmission. In this context, innovative tools are required to measure the symptoms compatible with COVID-19, the spread of infection, and testing capabilities within hospitals in real time. Objective: We aimed to develop and test an effective and user-friendly tool to identify and track symptoms compatible with COVID-19 in hospital workers. Methods: We developed and pilot tested Hospital Epidemics Tracker (HEpiTracker), a newly designed app to track the spread of COVID-19 among hospital workers. Hospital staff in 9 hospital centers across 5 Spanish regions (Andalusia, Balearics, Catalonia, Galicia, and Madrid) were invited to download the app on their phones and to register their daily body temperature, COVID-19-compatible symptoms, and general health score, as well as any polymerase chain reaction and serological test results. Results: A total of 477 hospital staff participated in the study between April 8 and June 2, 2020. Of note, both health-related (n=329) and non-health-related (n=148) professionals participated in the study; over two-thirds of participants (68.8%) were health workers (43.4% physicians and 25.4% nurses), while the proportion of non-health-related workers by center ranged from 40% to 85%. Most participants were female (n=323, 67.5%), with a mean age of 45.4 years (SD 10.6). Regarding smoking habits, 13.0% and 34.2% of participants were current or former smokers, respectively. The daily reporting of symptoms was highly variable across participating hospitals; although we observed a decline in adherence after an initial participation peak in some hospitals, other sites were characterized by low participation rates throughout the study period. Conclusions: HEpiTracker is an already available tool to monitor COVID-19 and other infectious diseases in hospital workers. This tool has already been tested in real conditions. HEpiTracker is available in Spanish, Portuguese, and English. It has the potential to become a customized asset to be used in future COVID-19 pandemic waves and other environments

    In vitro Induction of Entamoeba histolytica Cyst-like Structures from Trophozoites

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    Inhibition of encystment can be conceived as a potentially useful mechanism to block the transmission of Entamoeba histolytica under natural conditions. Unfortunately, amoeba encystment has not been achieved in vitro and drugs inhibiting the formation of cysts are not available. Luminal conditions inducing encystment in vivo are also unknown, but cellular stress such as exposure to reactive oxygen species from immune cells or intestinal microbiota could be involved. A role for certain divalent cations as cofactors of enzymes involved in excystment has also been described. In this study, we show that trophozoite cultures, treated with hydrogen peroxide in the presence of trace amounts of several cations, transform into small-sized spherical and refringent structures that exhibit resistance to different detergents. Ultrastructural analysis under scanning and transmission electron microscopy revealed multinucleated structures (some with four nuclei) with smooth, thick membranes and multiple vacuoles. Staining with calcofluor white, as well as an ELISA binding assay using wheat germ agglutinin, demonstrated the presence of polymers of N-acetylglucosamine (chitin), which is the primary component of the natural cyst walls. Over-expression of glucosamine 6-phosphate isomerase, likely to be the rate-limiting enzyme in the chitin synthesis pathway, was also confirmed by RT-PCR. These results suggest that E. histolytica trophozoites activated encystment pathways when exposed to our treatment

    Characterization of S3Pvac Anti-Cysticercosis Vaccine Components: Implications for the Development of an Anti-Cestodiasis Vaccine

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    Background: Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis.Methodology/ Principal Findings: In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. on the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms.Conclusions/ Significance: These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates
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