Testosterone and the Male Skeleton: A Dual Mode of Action

Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor

Astronomical component estimation (ACE v.1) by time-variant sinusoidal modeling

Accurately deciphering periodic variations in paleoclimate proxy signals is essential for cyclostratigraphy. Classical spectral analysis often relies on methods based on (fast) Fourier transformation. This technique has no unique solution separating variations in amplitude and frequency. This characteristic can make it difficult to correctly interpret a proxy's power spectrum or to accurately evaluate simultaneous changes in amplitude and frequency in evolutionary analyses. This drawback is circumvented by using a polynomial approach to estimate instantaneous amplitude and frequency in orbital components. This approach was proven useful to characterize audio signals (music and speech), which are non-stationary in nature. Paleoclimate proxy signals and audio signals share similar dynamics; the only difference is the frequency relationship between the different components. A harmonic-frequency relationship exists in audio signals, whereas this relation is non-harmonic in paleoclimate signals. However, this difference is irrelevant for the problem of separating simultaneous changes in amplitude and frequency. Using an approach with overlapping analysis frames, the model (Astronomical Component Estimation, version 1: ACE v.1) captures time variations of an orbital component by modulating a stationary sinusoid centered at its mean frequency, with a single polynomial. Hence, the parameters that determine the model are the mean frequency of the orbital component and the polynomial coefficients. The first parameter depends on geologic interpretations, whereas the latter are estimated by means of linear least-squares. As output, the model provides the orbital component waveform, either in the depth or time domain. Uncertainty analyses of the model estimates are performed using Monte Carlo simulations. Furthermore, it allows for a unique decomposition of the signal into its instantaneous amplitude and frequency. Frequency modulation patterns reconstruct changes in accumulation rate, whereas amplitude modulation identifies eccentricity-modulated precession. The functioning of the time-variant sinusoidal model is illustrated and validated using a synthetic insolation signal. The new modeling approach is tested on two case studies: (1) a Pliocene-Pleistocene benthic delta O-18 record from Ocean Drilling Program (ODP) Site 846 and (2) a Danian magnetic susceptibility record from the Contessa Highway section, Gubbio, Italy

Reconstructing seasonality through stable-isotope and trace-element analyses of the Proserpine stalagmite, Han-sur-Lesse cave, Belgium : indications for climate-driven changes during the last 400 years

Fast-growing speleothems allow for the reconstruction of palaeoclimate down to a seasonal scale. Additionally, annual lamination in some of these speleothems yields highly accurate age models for these palaeoclimate records, making these speleothems valuable archives for terrestrial climate. In this study, an annually laminated stalagmite from the Han-sur-Lesse cave (Belgium) is used to study the expression of the seasonal cycle in northwestern Europe during the Little Ice Age. More specifically, two historical 12-year-long growth periods (ca. 1593-1605 CE and 1635-1646 CE) and one modern growth period (1960-2010 CE) are analysed on a sub-annual scale for their stable-isotope ratios (delta C-13 and delta O-18) and trace-element (Mg, Sr, Ba, Zn, Y, Pb, U) contents. Seasonal variability in these proxies is confirmed with frequency analysis. Zn, Y and Pb show distinct annual peaks in all three investigated periods related to annual flushing of the soil during winter. A strong seasonal in-phase relationship between Mg, Sr and Ba in the modern growth period reflects a substantial influence of enhanced prior calcite precipitation (PCP). In particular, PCP occurs during summers when recharge of the epikarst is low. This is also evidenced by earlier observations of increased delta C-13 values during summer. In the 17th century intervals, there is a distinct antiphase relationship between Mg, Sr and Ba, suggesting that processes other than PCP, i.e. varying degrees of incongruent dissolution of dolomite, eventually related to changes in soil activity and/or land-use change are more dominant. The processes controlling seasonal variations in Mg, Sr and Ba in the speleothem appear to change between the 17th century and 1960-2010 CE. The Zn, Y, Pb, and U concentration profiles; stable-isotope ratios; and morphology of the speleothem laminae all point towards increased seasonal amplitude in cave hydrology. Higher seasonal peaks in soil-derived elements (e.g. Zn and Y) and lower concentrations of host-rock-derived elements (e.g. Mg, Sr, Ba) point towards lower residence times in the epikarst and higher flushing rates during the 17th century. These observations reflect an increase in water excess above the cave and recharge of the epikarst, due to a combination of lower summer temperatures and increased winter precipitation during the 17th century. This study indicates that the transfer function controlling Mg, Sr and Ba seasonal variability varies over time. Which process is dominant - either PCP, soil activity or dolomite dissolution - is clearly climate driven and can itself be used as a palaeoenvironment proxy

Did atmospheric thermal tides cause a daylength locking in the Precambrian? A review on recent results

After the initial suggestion by Zahnle and Walker (1987) that the torque accelerating the spin rate of the Earth and produced by the heating of the atmosphere by the Sun could counteract the braking lunir-solar gravitational torque in the Precambrian, several authors have recently revisited this hypothesis. In these studies, it is argued that the geological evidences of the past spin state of the Earth play in favor of this atmospheric tidal locking of the length of the day (LOD). In the present review of the recent literature, we show that the drawn conclusions depend crucially on the consideration of the stromatolite geological LOD estimates obtained by Pannella at 1.88 and 2.0 Ga, which are subject to large uncertainties. When only the most robust cyclostatigraphic estimates of the LOD are retained, the LOD locking hypothesis is not supported. Moreover, the consideration of the published General Circulation Model numerical simulations and of new analytical models for the thermal atmospheric tides suggest that the atmospheric tidal resonance, which is the crucial ingredient for the LOD locking in the Precambrian, was never of sufficiently large amplitude to allow for this tidal LOD lock.Comment: 16 pages, 9 figure

Calcium and Vitamin D Supplementation in Men

Calcium and vitamin D supplements reverse secondary hyperparathyroidism and are widely prescribed to prevent osteoporotic fractures, with proven antifracture efficacy when targeted to individuals with documented insufficiencies. Men who should particularly be considered for calcium and vitamin D supplements include elderly or institutionalized individuals, patients with documented osteoporosis on antiresorptive or anabolic medication, and individuals receiving glucocorticoids. Benefits are most apparent when a daily dose of 1000–1200 mg calcium is complemented with 800 IU vitamin D. Compliance is the key to optimizing clinical efficacy. While (conventionally dosed) vitamin D has not been associated with safety concerns, recent meta-analytic data have provided evidence to suggest that calcium supplements (without coadministered vitamin D) may potentially be associated with cardiovascular risks

Is the bacterial leaf nodule symbiosis obligate for Psychotria umbellata? The development of a Burkholderia-free host plant

The bacterial leaf nodule symbiosis is an interaction where bacteria are housed in specialised structures in the leaves of their plant host. In the Rubiaceae plant family, host plants interact with Burkholderia bacteria. This interaction might play a role in the host plant defence system. It is unique due to its high specificity; the vertical transmission of the endophyte to the next generation of the host plant; and its supposedly obligatory character. Although previous attempts have been made to investigate this obligatory character by developing Burkholderia-free plants, none have succeeded and nodulating plants were still produced. In order to investigate the obligatory character of this endosymbiosis, our aims were to develop Burkholderia-free Psychotria umbellata plants and to investigate the effect of the absence of the endophytes on the host in a controlled environment

Detection of Burkholderia in the seeds of Psychotria punctata (Rubiaceae) – Microscopic evidence for vertical transmission in the leaf nodule symbiosis

<div><p>Background and aims</p><p>The bacterial leaf nodule symbiosis is a close interaction between endophytes and their plant hosts, mainly within the coffee family. The interaction between Rubiaceae species and <i>Burkholderia</i> bacteria is unique due to its obligate nature, high specificity, and predominantly vertical transmission of the endophytes to the next generation of host plants. This vertical transmission is intriguing since it is the basis for the uniqueness of the symbiosis. However, unequivocal evidence of the location of the endophytes in the seeds is lacking. The aim of this paper is therefore to demonstrate the presence of the host specific endophyte in the seeds of <i>Psychotria punctata</i> and confirm its precise location. In addition, the suggested location of the endophyte in other parts of the host plant is investigated.</p><p>Methods</p><p>To identify and locate the endophyte in <i>Psychotria punctata</i>, a two-level approach was adopted using both a molecular screening method and fluorescent <i>in situ</i> hybridisation microscopy.</p><p>Key results</p><p>The endophytes, molecularly identified as <i>Candidatus</i> Burkholderia kirkii, were detected in the leaves, vegetative and flower buds, anthers, gynoecium, embryos, and young twigs. In addition, they were <i>in situ</i> localised in leaves, flowers and shoot apical meristems, and, for the first time, in between the cotyledons of the embryos.</p><p>Conclusions</p><p>Both independent techniques detected the host specific endophyte in close proximity to the shoot apical meristem of the embryo, which confirms for the first time the exact location of the endophytes in the seeds. This study provides reliable proof that the endophytes are maintained throughout the growth and development of the host plant and are transmitted vertically to the offspring.</p></div

Litholog generation with the StratigrapheR package and signal decomposition for cyclostratigraphic purposes

To establish an astronomical time scale, it is useful to perform a visual inspection of the lithological evolution, together with proxies record. It allows to have a clear understanding of the expression of Milankovitch cyclicity. However, performing such an inspection can be challenging due to the large amount of data and high spatial resolution required to perform a sound cyclostratigraphic analysis. To address this problem we present the StratigrapheR package in the free software environment R (https://CRAN.R-project.org/package=StratigrapheR). This package is designed to generate lithologs and to deal with stratigraphical information. StratigrapheR takes advantage of the repetitive nature of sections used for cyclostratigraphic purposes to automate as much as possible the litholog generation while still allowing the visualisation of discrepancies (e.g. lateral variations of thickness and irregular stratification boundaries) and of any particular features (e.g. fossil content, sedimentary structures, stratigraphical intervals, etc.). The package furthermore allows to import vector graphics as SVG files, to export the lithologs in PDF and SVG form, to manipulate stratigraphic interval data and to visualise oriented palaeomagnetic data. The lithologs made in StratigrapheR can be plotted at high resolution directly along the results of time series filtering and/or decomposition methods. This is particularly useful for high-frequency components inspection. Empirical Mode Decomposition (EMD) in particular can be used for visual inspection. It allows to compute different components -also called modes- by iteratively subtracting from the signal the mean envelope curves, defined by local minima and maxima. In the isolated modes, each contiguous local extrema are separated by a zero-crossing. This property furthermore allows the determination of instantaneous frequency and amplitude, using for instance the Hilbert transform. EMD typically decomposes standard cyclostratigraphic time series in maximum 15 modes, which allows all the instantaneous ratios of the modes frequencies - taken two by two- to be calculated in a realistic computational time. These instantaneous ratios of frequencies can then be used to find the signature of Milankovitch cycles by identifying relatively higher ratios distributions at values characteristic of the orbital cycles. Specific ratios intervals can then be isolated and linked back to the parts of the signal that are at their source

The Cyclostratigraphy Intercomparison Project (CIP): consistency, merits and pitfalls

Cyclostratigraphy is an important tool for understanding astronomical climate forcing and reading geological time in sedimentary sequences, provided that an imprint of insolation variations caused by Earth’s orbital eccentricity, obliquity and/or precession is preserved (Milankovitch forcing). Numerous stratigraphic and paleoclimate studies have applied cyclostratigraphy, but the robustness of the methodology and its dependence on the investigator have not been systematically evaluated. We developed the Cyclostratigraphy Intercomparison Project (CIP) to assess the robustness of cyclostratigraphic methods using an experimental design of three artificial cyclostratigraphic case studies with known input parameters. Each case study is designed to address specific challenges that are relevant to cyclostratigraphy. Case 1 represents an offshore research vessel environment, as only a drill-core photo and the approximate position of a late Miocene stage boundary are available for analysis. In Case 2, the Pleistocene proxy record displays clear nonlinear cyclical patterns and the interpretation is complicated by the presence of a hiatus. Case 3 represents a Late Devonian proxy record with a low signal-to-noise ratio with no specific theoretical astronomical solution available for this age. Each case was analyzed by a test group of 17-20 participants, with varying experience levels, methodological preferences and dedicated analysis time. During the CIP 2018 meeting in Brussels, Belgium, the ensuing analyses and discussion demonstrated that most participants did not arrive at a perfect solution, which may be partly explained by the limited amount of time spent on the exercises (∼4.5 hours per case). However, in all three cases, the median solution of all submitted analyses accurately approached the correct result and several participants obtained the exact correct answers. Interestingly, systematically better performances were obtained for cases that represented the data type and stratigraphic age that were closest to the individual participants’ experience. This experiment demonstrates that cyclostratigraphy is a powerful tool for deciphering time in sedimentary successions and, importantly, that it is a trainable skill. Finally, we emphasize the importance of an integrated stratigraphic approach and provide flexible guidelines on what good practices in cyclostratigraphy should include. Our case studies provide valuable insight into current common practices in cyclostratigraphy, their potential merits and pitfalls. Our work does not provide a quantitative measure of reliability and uncertainty of cyclostratigraphy, but rather constitutes a starting point for further discussions on how to move the maturing field of cyclostratigraphy forward

The Cyclostratigraphy Intercomparison Project (CIP): consistency, merits and pitfalls

Cyclostratigraphy is an important tool for understanding astronomical climate forcing and reading geological time in sedimentary sequences, provided that an imprint of insolation variations caused by Earth’s orbital eccentricity, obliquity and/or precession is preserved (Milankovitch forcing). Numerous stratigraphic and paleoclimate studies have applied cyclostratigraphy, but the robustness of the methodology and its dependence on the investigator have not been systematically evaluated. We developed the Cyclostratigraphy Intercomparison Project (CIP) to assess the robustness of cyclostratigraphic methods using an experimental design of three artificial cyclostratigraphic case studies with known input parameters. Each case study is designed to address specific challenges that are relevant to cyclostratigraphy. Case 1 represents an offshore research vessel environment, as only a drill-core photo and the approximate position of a late Miocene stage boundary are available for analysis. In Case 2, the Pleistocene proxy record displays clear nonlinear cyclical patterns and the interpretation is complicated by the presence of a hiatus. Case 3 represents a Late Devonian proxy record with a low signal-to-noise ratio with no specific theoretical astronomical solution available for this age. Each case was analyzed by a test group of 17-20 participants, with varying experience levels, methodological preferences and dedicated analysis time. During the CIP 2018 meeting in Brussels, Belgium, the ensuing analyses and discussion demonstrated that most participants did not arrive at a perfect solution, which may be partly explained by the limited amount of time spent on the exercises (∼4.5 hours per case). However, in all three cases, the median solution of all submitted analyses accurately approached the correct result and several participants obtained the exact correct answers. Interestingly, systematically better performances were obtained for cases that represented the data type and stratigraphic age that were closest to the individual participants’ experience. This experiment demonstrates that cyclostratigraphy is a powerful tool for deciphering time in sedimentary successions and, importantly, that it is a trainable skill. Finally, we emphasize the importance of an integrated stratigraphic approach and provide flexible guidelines on what good practices in cyclostratigraphy should include. Our case studies provide valuable insight into current common practices in cyclostratigraphy, their potential merits and pitfalls. Our work does not provide a quantitative measure of reliability and uncertainty of cyclostratigraphy, but rather constitutes a starting point for further discussions on how to move the maturing field of cyclostratigraphy forward