Deglacial landform assemblage records fast ice-flow and retreat, Inner Hebrides, Scotland

High-resolution bathymetric data have been central to recent advances in the understanding of past dynamics of the former British–Irish Ice Sheet (BIIS). As approximately two-thirds of the former BIIS was probably marine-based during the Last Glacial Maximum (LGM) (c. 29–23 ka), geomorphic observations of the seabed are required increasingly to understand the extent, pattern and timing of past glaciation. Until recently, glacial reconstructions for the Inner Hebrides, offshore of western Scotland, have been based primarily on terrestrial observations. Previous workers have proposed generalized reconstructions in which the Inner Hebrides are located within a significant former ice-sheet flow pathway that drained the western Scottish sector of the BIIS, feeding the Barra Fan during the LGM and earlier glaciations (Fig. 1). Results from numerical ice-sheet modelling suggest that former ice-flow velocities within the region were on the order of hundreds to thousands of metres per year, but yield further insight by demonstrating how dynamic binge/purge cycles may have affected ice-sheet mass balance over time (Hubbard et al. 2009). Following the LGM, ice-sheet retreat through the area is estimated to have been in the order of 20 m per year (Clark et al. 2012). Here we present swath-bathymetric data from the Inner Hebrides that provide in situ constraints on ice-sheet flow and subsequent retreat dynamics from within this important sector of the BIIS

Cabergoline Withdrawal Before and After Menopause : Outcomes in Microprolactinomas

Natural course of prolactinomas after menopause is not fully elucidated. The aim of this study was to compare recurrence rate after cabergoline withdrawal in premenopausal vs. postmenopausal women with microprolactinoma. Sixty-two women with microprolactinoma treated with cabergoline for at least 1 year and followed for 2 years after drug withdrawal were retrospectively selected. Patients were divided into two groups: 48 patients stopped cabergoline before menopause ("PRE" group), while 14 after menopause ("POST" group). Recurrence was defined by prolactin levels above normal, confirmed on two occasions. Overall, 39/62 women relapsed. Patients who relapsed apparently had higher prolactin before withdrawal (median 216.2, range 21.2-464.3 mIU/L) compared with those in long-term remission (94.3, 29.7-402.8 mIU/L; p < 0.05), and the risk of recurrence seemed lower in POST women (4/14, 29%) than in PRE ones (35/48, 73%, p < 0.005, OR 0.149, 95% CI 0.040-0.558). However, none of the factors (prolactin before withdrawal, menopausal status, treatment duration, complete adenoma regression) showed a correlation with recurrence risk in multivariate analysis. The best strategy able to optimize CBG treatment and withdrawal's outcomes is still to be defined in microprolactinomas. Postmenopausal status cannot reliably predict long-term remission, and follow-up is needed also in women of this age

Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single cell resolution

Mitochondria are involved in a number of diverse cellular functions, including energy production, metabolic regulation, apoptosis, calcium homeostasis, cell proliferation, and motility, as well as free radical generation. Mitochondrial DNA (mtDNA) is present at hundreds to thousands of copies per cell in a tissue-specific manner. mtDNA copy number also varies during aging and disease progression and therefore might be considered as a biomarker that mirrors alterations within the human body. Here, we present a new quantitative, highly sensitive droplet digital PCR (ddPCR) method, droplet digital mitochondrial DNA measurement (ddMDM), to measure mtDNA copy number not only from cell populations but also from single cells. Our developed assay can generate data in as little as 3 h, is optimized for 96-well plates, and also allows the direct use of cell lysates without the need for DNA purification or nuclear reference genes. We show that ddMDM is able to detect differences between samples whose mtDNA copy number was close enough as to be indistinguishable by other commonly used mtDNA quantitation methods. By utilizing ddMDM, we show quantitative changes in mtDNA content per cell across a wide variety of physiological contexts including cancer progression, cell cycle progression, human T cell activation, and human aging

A two-part seabed geomorphology classification scheme : (v.2). Part 1 : morphology features glossary

This report updates the ‘Two-part Seabed Geomorphology classification scheme’ of Dove et al. (2016) and presents a new glossary (Part 1) of Seabed Morphology features. This Morphology glossary is intended to provide marine scientists with a robust and consistent way to characterise the seabed. Each glossary entry includes a feature definition and a representative schematic diagram to support clear and accurate classification. Feature terms and definitions are primarily drawn from the International Hydrographic Organization (IHO) guide for undersea feature names, which are herein modified and augmented with additional terms to ensure the final feature catalogue and glossary encompasses the diversity of morphologies observed at the seabed, while also minimising duplication and/or ambiguity. This updated classification system and new glossary are the result of a collaboration between marine geoscientists from marine mapping programmes/networks in Norway (MAREANO), Ireland (INFOMAR), UK (MAREMAP), and Australia (Geoscience Australia) (MIM-GA). A subsequent report will present the (Part 2) Geomorphology feature glossar

Cyclic RGD peptidomimetics containing bifunctional diketopiperazine scaffolds as new potent integrin ligands

The synthesis of eight bifunctional diketopiperazine (DKP) scaffolds is described; these were formally derived from 2,3-diaminopropionic acid and aspartic acid (DKP-1-DKP-7) or glutamic acid (DKP-8) and feature an amine and a carboxylic acid functional group. The scaffolds differ in the configuration at the two stereocenters and the substitution at the diketopiperazinic nitrogen atoms. The bifunctional diketopiperazines were introduced into eight cyclic peptidomimetics containing the Arg-Gly-Asp (RGD) sequence. The resulting RGD peptidomimetics were screened for their ability to inhibit biotinylated vitronectin binding to the purified integrins \u3b1 v\u3b2 3 and \u3b1 v\u3b2 5, which are involved in tumor angiogenesis. Nanomolar IC 50 values were obtained for the RGD peptidomimetics derived from trans DKP scaffolds (DKP-2-DKP-8). Conformational studies of the cyclic RGD peptidomimetics by 1H NMR spectroscopy experiments (VT-NMR and NOESY spectroscopy) in aqueous solution and Monte Carlo/Stochastic Dynamics (MC/SD) simulations revealed that the highest affinity ligands display well-defined preferred conformations featuring intramolecular hydrogen-bonded turn motifs and an extended arrangement of the RGD sequence [C\u3b2(Arg)-C\u3b2(Asp) average distance 658.8 \uc5]. Docking studies were performed, starting from the representative conformations obtained from the MC/SD simulations and taking as a reference model the crystal structure of the extracellular segment of integrin \u3b1 v\u3b2 3 complexed with the cyclic pentapeptide, Cilengitide. The highest affinity ligands produced top-ranked poses conserving all the important interactions of the X-ray complex. Copyright \ua9 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Variable response in alpine tree-ring stable isotopes following volcanic eruptions in the tropics and iceland

The importance of the stable isotopes in tree rings for the study of the climate variations caused by volcanic eruptions is still unclear. We studied δ18O, δD, δ13C stable isotopes of larch and cembran pine cellulose around four major eruptions with annual resolution, along with a superposed epoch analysis of 34 eruptions with 5-year resolution. Initial analysis of the tropical Tambora (1815 CE) and Samalas (1257 CE) eruptions showed a post-eruption decrease in δ18O values attributed to post-volcanic cooling and increased summer precipitation in Southern Europe, as documented by observations and climate simulations. The post-volcanic cooling was captured by the δD of speleothem fluid inclusion. The δ18O decrease was also observed in the analysis of 34 major tropical eruptions over the last 2000 years. In contrast, the eruptions of c. 750, 756, and 764 CE attributed to Icelandic volcanoes left no significant responses in the cellulose isotopes. Further analysis of all major Icelandic eruptions in the last 2000 years showed no consistent isotopic fingerprints, with the exception of lower post-volcanic δ13C values in larch. In summary, the δ18O values of cellulose can provide relevant information on climatic and hydroclimatic variations following major tropical volcanic eruptions, even when using the 5-year resolution wood samples of the Alpine Tree-Ring Isotope Record database

NMR Study of Spin Dynamics in V\u3csub\u3e7\u3c/sub\u3eZn and V\u3csub\u3e7\u3c/sub\u3eNi Molecular Rings

We present a 1H NMR investigation of spin dynamics in to finite integer spin molecular nanomagnetic rings, namely V7Zn and V7Ni. This study could be put in correlation with the problem of Haldane gap in infinite integer spin chains. While V7Zn is an approximation of a homometallic broken chain due to the presence of s = 0 Zn2+ ion uncoupled from nearest neighbor V2+ s = 1 ions, the V7Ni compound constitutes an example of a closed periodical s = 1 heterometallic chain. From preliminary susceptibility measurements on single crystals and data analysis, the exchange coupling constant J/kB results in the order of few kelvin. At room temperature, the frequency behavior of the 1H NMR spin–lattice relaxation rate 1/T1 allowed to conclude that the spin–spin correlation function is similar to the one observed in semi-integer spin molecules, but with a smaller cutoff frequency. Thus, the high-T data can be interpreted in terms of, e.g., a Heisenberg model including spin diffusion. On the other hand, the behavior of 1/T1 vs temperature at different constant fields reveals a clear peak at temperature of the order of J/kB, qualitatively in agreement with the well-known Bloembergen–Purcell–Pound model and with previous results on semi-integer molecular spin systems. Consequently, one can suggest that for a small number N of interacting s = 1 ions (N = 8), the Haldane conjecture does not play a key role on spin dynamics, and the investigated rings still keep the quantum nature imposed mainly by the low number of magnetic centers, with no clear topological effect due to integer spins

Sarcopenia and Menopause: The Role of Estradiol

During aging and menopausal transition in women, a progressive muscle degeneration (i.e. decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women