487 research outputs found
Sexism in the Sports World
Sports have been a male dominated field years, and women have not been acknowledged for their achievements. The differences between men and women stems from their physiology, gender stereotypes and the perception of female athletes in the media. There has been bridges in the gaps of gender inequality after the passing of Title IX, but other stereotypes that have hindered women from furthering their careers in sports, whether it be athletically or socially. Until the socialization of women in the sports changes, there will not be progress made in society
Distinct Functional Roles of beta-Tubulin Isotypes inMicrotubule Arrays of Tetrahymena thermophila, aModel Single-Celled Organism
Background
The multi-tubulin hypothesis proposes that each tubulin isotype performs a unique role, or subset of roles, in the universe of microtubule function(s). To test this hypothesis, we are investigating the functions of the recently discovered, noncanonical β-like tubulins (BLTs) of the ciliate, Tetrahymena thermophila. Tetrahymena forms 17 distinct microtubular structures whose assembly had been thought to be based on single ι- and β-isotypes. However, completion of the macronuclear genome sequence of Tetrahymena demonstrated that this ciliate possessed a β-tubulin multigene family: two synonymous genes (BTU1 and BTU2) encode the canonical β-tubulin, BTU2, and six genes (BLT1-6) yield five divergent β-tubulin isotypes. In this report, we examine the structural features and functions of two of the BLTs (BLT1 and BLT4) and compare them to those of BTU2.
Methodology/Principal Findings
With respect to BTU2, BLT1 and BLT4 had multiple sequence substitutions in their GTP-binding sites, in their interaction surfaces, and in their microtubule-targeting motifs, which together suggest that they have specialized functions. To assess the roles of these tubulins in vivo, we transformed Tetrahymena with expression vectors that direct the synthesis of GFP-tagged versions of the isotypes. We show that GFP-BLT1 and GFP-BLT4 were not detectable in somatic cilia and basal bodies, whereas GFP-BTU2 strongly labeled these structures. During cell division, GFP-BLT1 and GFP-BLT4, but not GFP-BTU2, were incorporated into the microtubule arrays of the macronucleus and into the mitotic apparatus of the micronucleus. GFP-BLT1 also participated in formation of the microtubules of the meiotic apparatus of the micronucleus during conjugation. Partitioning of the isotypes between nuclear and ciliary microtubules was confirmed biochemically.
Conclusion/Significance
We conclude that Tetrahymena uses a family of distinct β-tubulin isotypes to construct subsets of functionally different microtubules, a result that provides strong support for the multi-tubulin hypothesis
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European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects.
Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mitochondrial membrane potential compared to cisplatin-treated-H cybrids. After cisplatin treatment, J cybrids showed increased gene expression of BAX, CASP3, and CYP51A, but lower levels of SFRP1 compared to untreated-J cybrids. The cisplatin-treated-H cybrids had elevated expression of CDKN1A/P21, which has a role in cisplatin toxicity, compared to untreated-H cybrids. The cisplatin-treated H had higher transcription levels of ABCC1, DHRS2/HEP27, and EFEMP1 compared to cisplatin-treated-J cybrids. Conclusions: Cybrid cell lines that contain identical nuclei but either H mtDNA mitochondria or J mtDNA mitochondria respond differently to cisplatin treatments suggesting involvement of the retrograde signaling (from mitochondria to nucleus) in the drug-induced cell death. Varying toxicities and transcription levels of the H vs. J cybrids after cisplatin treatment support the hypothesis that mtDNA variants play a role in the expression of genes affecting resistance and side effects of cisplatin
Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: A mechanistic insight
The polyphenol oleuropein aglycone modulates the PARP1-SIRT1 interplay: an in vitro and in vivo study
The Case for the Dual Halo of the Milky Way
Carollo et al. have recently resolved the stellar population of the Milky Way
halo into at least two distinct components, an inner halo and an outer halo.
This result has been criticized by Schoenrich et al., who claim that the
retrograde signature associated with the outer halo is due to the adoption of
faulty distances. We refute this claim, and demonstrate that the Schoenrich et
al. photometric distances are themselves flawed because they adopted an
incorrect main-sequence absolute magnitude relationship from the work of
Ivezi\'c et al. When compared to the recommended relation from Ivezi\'c et al.,
which is tied to a Milky Way globular cluster distance scale and accounts for
age and metallicity effects, the relation adopted by Schoenrich et al. yields
up to 18% shorter distances for stars near the main-sequence turnoff (TO). Use
of the correct relationship yields agreement between the distances assigned by
Carollo et al. and Ivezi\'{c} et al. for low-metallicity dwarfs to within
6-10%. Schoenrich et al. also point out that intermediate-gravity stars (3.5 <=
log g <= 4.0) with colors redder than the TO region are likely misclassified,
with which we concur. We implement a new procedure to reassign luminosity
classifications for the TO stars that require it. New derivations of the
rotational behavior demonstrate that the retrograde signature and high velocity
dispersion of the outer-halo population remains. We summarize additional lines
of evidence for a dual halo, including a test of the retrograde signature based
on proper motions alone, and conclude that the preponderance of evidence
strongly rejects the single-halo interpretation.Comment: 46 pages, 2 tables, 15 figures, Accepted for publication in the
Astrophysical Journa
Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group
Background To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. Methods We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population. Results Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm(3) were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability. Conclusion Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population
Discrepancy between prevalence and perceived effectiveness of treatment methods in myofascial pain syndrome: Results of a cross-sectional, nationwide survey
Background: Myofascial pain is a common dysfunction with a lifetime prevalence affecting up to 85% of the general population. Current guidelines for the management of myofascial pain are not available. In this study we investigated how physicians on the basis of prescription behaviour evaluate the effectiveness of treatment options in their management of myofascial pain. Methods: We conducted a cross-sectional, nationwide survey with a standardized questionnaire among 332 physicians (79.8% male, 25.6% female, 47.5 +/- 9.6 years) experienced in treating patients with myofascial pain. Recruitment of physicians took place at three German meetings of pain therapists, rheumatologists and orthopaedists, respectively. Physicians estimated the prevalence of myofascial pain amongst patients in their practices, stated what treatments they used routinely and then rated the perceived treatment effectiveness on a six-point scale (with 1 being excellent). Data are expressed as mean +/- standard deviation. Results: The estimated overall prevalence of active myofascial trigger points is 46.1 +/- 27.4%. Frequently prescribed treatments are analgesics, mainly metamizol/paracetamol (91.6%), non-steroidal anti-inflammatory drugs/coxibs (87.0%) or weak opioids (81.8%), and physical therapies, mainly manual therapy (81.1%), TENS (72.9%) or acupuncture (60.2%). Overall effectiveness ratings for analgesics (2.9 +/- 0.7) and physical therapies were moderate (2.5 +/- 0.8). Effectiveness ratings of the various treatment options between specialities were widely variant. 54.3% of all physicians characterized the available treatment options as insufficient. Conclusions: Myofascial pain was estimated a prevalent condition. Despite a variety of commonly prescribed treatments, the moderate effectiveness ratings and the frequent characterizations of the available treatments as insufficient suggest an urgent need for clinical research to establish evidence-based guidelines for the treatment of myofascial pain syndrome
Structure and Kinematics of the Stellar Halos and Thick Disks of the Milky Way Based on Calibration Stars from SDSS DR7
The structure and kinematics of the recognized stellar components of the
Milky Way are explored, based on well-determined atmospheric parameters and
kinematic quantities for 32360 calibration stars from the Sloan Digital Sky
Survey (SDSS) and its first extension, (SDSS-II), which included the sub-survey
SEGUE: Sloan Extension for Galactic Understanding and Exploration. Full space
motions for a sub-sample of 16920 stars, exploring a local volume within 4 kpc
of the Sun, are used to derive velocity ellipsoids for the inner- and
outer-halo components of the Galaxy, as well as for the canonical thick-disk
and proposed metal-weak thick-disk populations. We first examine the question
of whether the data require the presence of at least a two-component halo in
order to account for the rotational behavior of likely halo stars in the local
volume, and whether more than two components are needed. We also address the
question of whether the proposed metal-weak thick disk is kinematically and
chemically distinct from the canonical thick disk. In addition, we consider the
fractions of each component required to understand the nature of the observed
kinematic behavior of the stellar populations of the Galaxy as a function of
distance from the plane. Scale lengths and scale heights for the thick-disk and
metal-weak thick-disk components are determined. Spatial density profiles for
the inner- and outer-halo populations are inferred from a Jeans Theorem
analysis. The full set of calibration stars (including those outside the local
volume) is used to test for the expected changes in the observed stellar
metallicity distribution function with distance above the Galactic plane
in-situ, due to the changing contributions from the underlying stellar
populations. [abridged]Comment: Accepted for publication in the Ap
The impact of the COVID-19 pandemic on the Mediterranean region over 18 months : bridging the health outcomes and sustainable development goals
Background: The COVID-19 pandemic spread across the globe, including across the Mediterranean basin. This region presents diversity in economy, culture, and societal affairs. We attempted to evaluate the impact of COVID-19 on the population and on the Sustainable Development Goals (SDGs), our aim being to aid in the development of COVID-19 national plans. Methods: Epidemiological data was obtained from âOur World in Dataâ databases (January 2020 â July 2021). Case, mortality, and vaccination incidence comparisons were made across neighbouring countries. The SDG index, universal health coverage (UHC) and health workforce targets were collected for each country. Correlations between SDG targets and COVID-19 outcomes were analysed. Results: Similarities in morbidity and mortality outcomes were present across neighbouring countries, with a bidirectional relationship between cumulative fully vaccinated population and infectivity fatality rates. Positive relationships were present between SDG indexes, UHC and health workforces and COVID-19 cases, deaths, and vaccinations. Conclusion: At prima face, high-income countries seem to have sustained worse morbidity and mortality outcomes, despite having had better UHC and a greater health workforce in the pre-COVID-19 era however, one must also consider that factors such as health-seeking behaviour and underdiagnosis may have influenced this. Cross-border infectivity was, however, evident. Pan-Mediterranean action must therefore be taken to ensure COVID-19 transmissibility and mortality are reduced across borders, while ensuring an equitable health outcome across populations.peer-reviewe
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