An optimization of hematopoietic stem and progenitor cell isolation for scientific and clinical purposes by the application of a new parameter determining the hematopoietic graft efficacy.

The transplantation of hematopoietic stem and progenitor cells (HSPC) is an established lifesaving therapy. Bone marrow (BM), harvested from heparinized cadaveric organ donors, peripheral blood (PB) and cord blood (CB), are important sources of hematopoietic stem cells. HSPCs, which are used for transplantation purposes, are routinely evaluated in terms of number of mononuclear cells (MNCs), CD34+ MNCs count and viability. The efficacy of grafting is determined additionally in clonogenic tests in vitro. These tests deliver important information about the number of HSPCs and their proliferative potential. Unfortunately, they do not give a possibility to evaluate the functional HSPC chemotactic reactivity in the SDF-1 gradient, which is probably the key phenomenon for HSPC homing after transplantation procedure. Thus, the aim of our study was to optimize HSPC isolation according to their chemotactic reactivity in SDF-1 gradient. Using multiparameter cell sorter (FACS Aria, BD) we examined the HSPCs attracted by SDF-1 on a single cell level. The population of cells which participated in the chemotactic process was highly enriched in CXCR4+lin-AC133+CD45+ cells (referred as hematopoietic stem cells) and to our surprise in CXCR4+lin-AC133+CD45- cells (referred as pluripotent stem cells) in quantitative amounts. Since reactivity of HSPCs may depend on various factors involved in the protocol of their isolation and short-term storage, we tested the most commonly used anticoagulants (ACD, CPDA-1, EDTA and Heparin) and culture media (DME, IMDM, RPMI). HSPCs, harvested from CB, PB and BM, were subsequently investigated for clonogenic growth of CFU-GM in methylcellulose cultures and for the level of apoptosis by employing annexin V staining. Evaluating clonogenic potential, ability of chemotactic reactivity in SDF-1 gradient and intensification of apoptosis of HSPC as the most safe anticoagulant and medium were selected. This study has proved that chemotactic reactivity of HSPCs is a new but very important parameter which should be included in the procedure of their isolation

Copper-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes: Synthesis of cyclopropylboronates

This document is the accepted manuscript version of a Published Work that appeared in final form in Journal of American Chemical Society 136.45, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see DOI: 10.1021/ja510419zA novel Cu-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes to afford nonracemic cyclopropylboronates is described. Trapping the cyclopropylcopper intermediate with electrophilic amines allows for the synthesis of cyclopropylaminoboronic esters and demonstrates the potential of the approach for the synthesis of functionalized cyclopropanesWe thank the European Research Council (ERC-337776) and MINECO (CTQ2012-35957) for financial support. M. T. and A. P. thank MICINN for RyC and JdC contract

Rapid helium isotopic variability in Mauna Kea shield lavas from the Hawaiian Scientific Drilling Project

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 5 (2004): Q04G14, doi:10.1029/2002GC000439.This paper presents new magmatic helium isotopic compositions in a suite of lavas from phase II of the Hawaiian Scientific Drilling Project (HSDP2) core, which sampled Mauna Kea volcano to a maximum depth of 3098 m below sea level. Most of the measurements were performed by in vacuo crushing of olivine phenocrysts, but include submarine pillow glasses from the 2200 to 2500 meter depth interval, and orthopyroxene phenocrysts from an intrusive at 1880 m. The magmatic 3He/4He ratios range from 6 to 24.7 times atmospheric (Ra), which significantly extends the range of values for Mauna Kea volcano. The 3He/4He ratios are lowest (i.e., close to MORB values of ∼8 Ra) near the top of the Mauna Kea section and rise slowly, to 10–12 Ra, at 1000 m below sea level, consistent with results from the HSDP1 core. At depths greater than 1000 m in the core, primarily in the submarine lavas, there are brief periods when the 3He/4He ratios are higher than 14.5 Ra, always returning to a baseline value. Twelve such excursions were identified in the core; all but one are in the submarine section, and most (7) are in the deepest section, at depths of 1950 to 3070 m. The baseline 3He/4He value rises from 10–12 Ra near 1000 m depth to 12–14 Ra at 3000 m. The helium spikes are found only in lavas that are older than 380 Ka in age, based on an age model derived from Ar-Ar data (W. D. Sharp et al., manuscript in preparation, 2003). Excluding the excursions defined by single lava flows (3) and intrusive units (3), the average spike duration is approximately 15 (±9) Ka (n = 6). The high 3He/4He spikes are interpreted as pulses of magma from the center of the actively upwelling Hawaiian hot spot. The short duration of the high 3He/4He excursions suggests that Mauna Kea was never directly over high the 3He/4He component of the plume (during the HSDP2 eruptive period), presumed to be the plume center. Assuming that the Mauna Kea helium spikes result from melting of heterogeneities within the plume, their short duration implies that the length scales of heterogeneities in the solid upwelling mantle are between 60 m and 12 km (for upwelling rates of 2 to 40 cm/yr). The high 3He/4He are associated with high 208Pb/204Pb, and relatively low 143Nd/144Nd, Zr/Nb, and SiO2. The correlations with major elements, trace elements and isotopes demonstrate that helium is coupled to the other geochemical variations, and that the Mauna Kea isotopic variability is caused by heterogeneities within the upwelling plume.This work was supported by EAR/NSF through the Continental Dynamics and Instrumentation and Facilities programs

A Mediterranean-like dietary pattern with vitamin D3 (10 µg/d) supplements reduced the rate of bone loss in older Europeans with osteoporosis at baseline: results of a 1-y randomized controlled trial

Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking.  Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans.  Design: An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country.  Results: A total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ −2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD.  Conclusions: A 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012

Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status : the NU-AGE 1-year dietary intervention across five European countries

Objective Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty. Design We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet). Results Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks. Conclusion Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.Peer reviewe

The chemically zoned 1949 eruption on La Palma (Canary Islands): Petrologic evolution and magma supply dynamics of a rift zone eruption

The 1949 rift zone eruption along the Cumbre Vieja ridge on La Palma involved three eruptive centers, 3 km spaced apart, and was chemically and mineralogically zoned. Duraznero crater erupted tephrite for 14 days and shut down upon the opening of Llano del Banco, a fissure that issued first tephrite and, after 3 days, basanite. Hoyo Negro crater opened 4 days later and erupted basanite, tephrite, and phonotephrite, while Llano del Banco continued to issue basanite. The eruption ended with Duraznero erupting basanite with abundant crustal and mantle xenoliths. The tephrites and basanites from Duraznero and Llano del Banco show narrow compositional ranges and define a bimodal suite. Each batch ascended and evolved separately without significant intermixing, as did the Hoyo Negro basanite, which formed at lower degrees of melting. The magmas fractionated clinopyroxene +olivine±kaersutite±Ti-magnetite at 600–800 MPa and possibly 800–1100 MPa. Abundant reversely zoned phenocrysts reflect mixing with evolved melts at mantle depths. Probably as early as 1936, Hoyo Negro basanite entered the deep rift system at 200–350 MPa. Some shallower pockets of this basanite evolved to phonotephrite through differentiation and assimilation of wall rock. A few months prior to eruption, a mixing event in the mantle may have triggered the final ascent of the magmas. Most of the erupted tephrite and basanite ascended from mantle depths within hours to days without prolonged storage in crustal reservoirs. The Cumbre Vieja rift zone differs from the rift zones of Kilauea volcano (Hawaii) in lacking a summit caldera or a summit reservoir feeding the rift system and in being smaller and less active with most of the rift magma solidifying between eruptions

Strategies for two‐dimensional and three‐dimensional field computation in the design of permanent magnet motors

This study discusses strategies for the design of permanent magnet motors (PMMs) exploiting two-dimensional (2D) and 3D field models. Five most common methodologies are compared and errors arising from 2D classical models considered. Examples comparing 2D and 3D results are presented and discussed for two selected types of motors. An approach has been put forward which allows the accuracy of classical 2D models to be improved by introducing correction coefficients arising from preliminary 3D simulations. A possibility of employing quasi-3D models has also been explored for the design and analysis of PMMs with the stator and rotor lamination packets of different lengths. Comparative analysis of results has been provided arising from the 2D and 3D models for a classical and a double rotor PMM