Abstract
Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss ‘omics’ approaches to investigate polar biodiversity, including the current ...state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.
We compared 7‐month changes in bone structural properties in pre‐ and early‐pubertal girls randomized to exercise intervention (10‐minute, 3 times per week, jumping program) or control groups. Girls ...were classified as prepubertal (PRE; Tanner breast stage 1; n = 43 for intervention I and n = 25 for control C) or early‐pubertal (EARLY; Tanner stages 2 and 3; n = 43 for I and n = 63 for C). Mean ± SD age was 10.0 ± 0.6 and 10.5 ± 0.6 for the PRE and EARLY groups, respectively. Proximal femur scans were analyzed using a hip structural analysis (HSA) program to assess bone mineral density (BMD), subperiosteal width, and cross‐sectional area and to estimate cortical thickness, endosteal diameter, and section modulus at the femoral neck (FN), intertrochanter (IT), and femoral shaft (FS) regions. There were no differences between intervention and control groups for baseline height, weight, calcium intake, or physical activity or for change over 7 months (p > 0.05). We used analysis of covariance (ANCOVA) to examine group differences in changes of bone structure, adjusting for baseline weight, height change, Tanner breast stage, and physical activity. There were no differences in change for bone structure in the PRE girls. The more mature girls (EARLY) in the intervention group showed significantly greater gains in FN (+2.6%, p = 0.03) and IT (+1.7%, p = 0.02) BMD. Underpinning these changes were increased bone cross‐sectional area and reduced endosteal expansion. Changes in subperiosteal dimensions did not differ. Structural changes improved section modulus (bending strength) at the FN (+4.0%, p = 0.04), but not at the IT region. There were no differences at the primarily cortical FS. These data provide insight into geometric changes that underpin exercise‐associated gain in bone strength in early‐pubertal girls.
Context. The evolution of intermediate and low-mass stars on the asymptotic giant branch is dominated by their strong dust-driven winds. More massive stars evolve into red supergiants with a similar ...envelope structure and strong wind. These stellar winds are a prime source for the chemical enrichment of the interstellar medium. Aims. We aim to (1) set up simple and general analytical expressions to estimate mass-loss rates of evolved stars, and (2) from those calculate estimates for the mass-loss rates of the asymptotic giant branch, red supergiant, and yellow hypergiant stars in our galactic sample. Methods. The rotationally excited lines of carbon monoxide (CO) are a classic and very robust diagnostic in the study of circumstellar envelopes. When sampling different layers of the circumstellar envelope, observations of these molecular lines lead to detailed profiles of kinetic temperature, expansion velocity, and density. A state-of-the-art, nonlocal thermal equilibrium, and co-moving frame radiative transfer code that predicts CO line intensities in the circumstellar envelopes of late-type stars is used in deriving relations between stellar and molecular-line parameters, on the one hand, and mass-loss rate, on the other. These expressions are applied to our extensive CO data set to estimate the mass-loss rates of 47 sample stars. Results. We present analytical expressions for estimating the mass-loss rates of evolved stellar objects for 8 rotational transitions of the CO molecule and thencompare our results to those of previous studies. Our expressions account for line saturation and resolving of the envelope, thereby allowing accurate determination of very high mass-loss rates. We argue that, for estimates based on a single rotational line, the CO(2–1) transition provides the most reliable mass-loss rate. The mass-loss rates calculated for the asympotic giant branch stars range from 4 × 10-8 M⊙ yr-1 up to 8 × 10-5 M⊙ yr-1. For red supergiants they reach values between 2 × 10-7 M⊙ yr-1 and 3 × 10-4 M⊙ yr-1. The estimates for the set of CO transitions allow time variability to be identified in the mass-loss rate. Possible mass-loss-rate variability is traced for 7 of the sample stars. We find a clear relation between the pulsation periods of the asympotic giant branch stars and their derived mass-loss rates, with a levelling off at ~3 × 10-5 M⊙ yr-1 for periods exceeding 850 days. Conclusions.
Background
Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first‐choice treatment for male hypogonadism, with several side ...effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off‐label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males.
Methods
In this single‐centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response.
Results
In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found.
Conclusion
Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.
This retrospective study shows the good short and long‐term outcomes of clomiphene citrate on testosterone in hypogonadal males with good safety aspects.
Optical atomic clocks promise timekeeping at the highest precision and accuracy, owing to their high operating frequencies. Rigorous evaluations of these clocks require direct comparisons between ...them. We have realized a high-performance remote comparison of optical clocks over kilometer-scale urban distances, a key step for development, dissemination, and application of these optical standards. Through this remote comparison and a proper design of lattice-confined neutral atoms for clock operation, we evaluate the uncertainty of a strontium (Sr) optical lattice clock at the 1 x 10(-16) fractional level, surpassing the current best evaluations of cesium (Cs) primary standards. We also report on the observation of density-dependent effects in the spin-polarized fermionic sample and discuss the current limiting effect of blackbody radiation-induced frequency shifts.
Polypyrimidine tract-binding protein (PTB) is an RNA-binding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in ...a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matched-normal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and in vitro invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.
Rheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes ...such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs.
Genome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.
We have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.
Through genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.
Abstract We present JWST MIRI MRS observations of the edge-on protoplanetary disk around the young subsolar-mass star Tau 042021, acquired as part of the Cycle 1 GO program “Mapping Inclined Disk ...Astrochemical Signatures.” These data resolve the mid-IR spatial distributions of H 2 , revealing X-shaped emission extending to ∼200 au above the disk midplane with a semiopening angle of 35° ± 5°. We do not velocity-resolve the gas in the spectral images, but the measured semiopening angle of the H 2 is consistent with a magnetohydrodynamic wind origin. A collimated, bipolar jet is seen in forbidden emission lines from Ne ii , Ne iii , Ni ii , Fe ii , Ar ii , and S iii . Extended H 2 O and CO emission lines are also detected, reaching diameters of ∼90 and 190 au, respectively. Hot molecular emission is not expected at such radii, and we interpret its extended spatial distribution as scattering of inner disk molecular emission by dust grains in the outer disk surface. H i recombination lines, characteristic of inner disk accretion shocks, are similarly extended and are likely also scattered light from the innermost star–disk interface. Finally, we detect extended polycyclic aromatic hydrocarbon (PAH) emission at 11.3 μ m cospatial with the scattered-light continuum, making this the first low-mass T Tauri star around which extended PAHs have been confirmed, to our knowledge. MIRI MRS line images of edge-on disks provide an unprecedented window into the outflow, accretion, and scattering processes within protoplanetary disks, allowing us to constrain the disk lifetimes and accretion and mass-loss mechanisms.
Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were upregulated in epithelial ovarian cancer (EOC) and knockdown of PTB expression ...inhibited ovarian tumor cell growth and transformation properties. In this report, we show that knockdown of SRp20 expression in ovarian cancer cells also causes substantial inhibition of tumor cell growth and colony formation in soft agar and the extent of such inhibition appeared to correlate with the extent of suppression of SRp20. Massive knockdown of SRp20 expression triggered remarkable apoptosis in these cells. These results suggest that overexpression of SRp20 is required for ovarian tumor cell growth and survival. Immunohistochemical staining for PTB and SRp20 of two specialized tissue microarrays, one containing benign ovarian tumors, borderline/low malignant potential (LMP) ovarian tumors as well as invasive EOC and the other containing invasive EOC ranging from stage I to stage IV disease, reveals that PTB and SRp20 are both expressed differentially between benign tumors and invasive EOC, and between borderline/LMP tumors and invasive EOC. There were more all-negative or mixed staining cases (at least two evaluable section cores per case) in benign tumors than in invasive EOC, whereas there were more all-positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the majority of cases were stained all positive for both PTB and SRp20, and there were no significant differences in average staining or frequency of positive cancer cells between any of the tumor stages. Therefore, the expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive EOC.
Context. The evolution of intermediate and low-mass stars on the asymptotic giant branch is dominated by their strong dust-driven winds. More massive stars evolve into red supergiants with a similar ...envelope structure and strong wind. These stellar winds are a prime source for the chemical enrichment of the interstellar medium. Aims: We aim to (1) set up simple and general analytical expressions to estimate mass-loss rates of evolved stars, and (2) from those calculate estimates for the mass-loss rates of the asymptotic giant branch, red supergiant, and yellow hypergiant stars in our galactic sample. Methods: The rotationally excited lines of carbon monoxide (CO) are a classic and very robust diagnostic in the study of circumstellar envelopes. When sampling different layers of the circumstellar envelope, observations of these molecular lines lead to detailed profiles of kinetic temperature, expansion velocity, and density. A state-of-the-art, nonlocal thermal equilibrium, and co-moving frame radiative transfer code that predicts CO line intensities in the circumstellar envelopes of late-type stars is used in deriving relations between stellar and molecular-line parameters, on the one hand, and mass-loss rate, on the other. These expressions are applied to our extensive CO data set to estimate the mass-loss rates of 47 sample stars. Results: We present analytical expressions for estimating the mass-loss rates of evolved stellar objects for 8 rotational transitions of the CO molecule and thencompare our results to those of previous studies. Our expressions account for line saturation and resolving of the envelope, thereby allowing accurate determination of very high mass-loss rates. We argue that, for estimates based on a single rotational line, the CO(2-1) transition provides the most reliable mass-loss rate. The mass-loss rates calculated for the asympotic giant branch stars range from 4 \times 10^-8 M_ȯ yr^-1 up to 8 \times 10^-5 M_ȯ yr^-1. For red supergiants they reach values between 2 \times 10^-7 M_ȯ yr^-1 and 3 \times 10^-4 M_ȯ yr^-1. The estimates for the set of CO transitions allow time variability to be identified in the mass-loss rate. Possible mass-loss-rate variability is traced for 7 of the sample stars. We find a clear relation between the pulsation periods of the asympotic giant branch stars and their derived mass-loss rates, with a levelling off at ~3 \times 10^-5 M_ȯ yr^-1 for periods exceeding 850 days. Conclusions: Appendices are only available in electronic form at http://www.aanda.org
PDF
