The Tres Arroyos granite–pegmatite system is located in the SW margin of the Nisa-Alburquerque Variscan batholith. Two granitic facies (monzogranite and marginal leucogranite) and three types of ...aplite–pegmatite dykes (barren, intermediate and highly evolved Li-rich), have been distinguished in the area, with a zoned distribution from the granite southwards. Trace elements in quartz from the five facies have been analysed by LA-ICP-MS in order to obtain information about the petrogenetic links among the different lithologies of this system, as well as to better understand the regional and individual fractionation processes that led to the distinct rocks. Aluminium, Ti, Li and Ge show continuous trends from the monzogranite, through the marginal granitic facies, the barren and intermediate aplite–pegmatites, up to the most evolved Li-rich dykes. Titanium and Ge contents, respectively, decrease and increase gradually with fractionation. In contrast, Al and Li show a more complex trend, with an initial descending trend to the marginal granitic facies, and then showing the highest Al and Li contents in the quartz from the most fractionated Li-rich aplite–pegmatites. This suggests the influence of different competing factors controlling the incorporation of these trace elements in quartz, such as the chemical composition of the melt, the P and T conditions and the rate of crystallization. Based on the good correlation between Al and Li, the substitution Si4+↔Al3++Li+ seems to be the dominant mechanism of Li incorporation into quartz. The negligible amount of other trace elements suggests that the remaining Al was mainly compensated with H+ ions, via the Si4+↔Al3+ + H+ substitution.
A continuous fractionation trend from the monzogranite up to the most fractionated aplite–pegmatites is inferred from geochemical modelling by applying the Rayleigh equation for fractional crystallization. Fractionation rates over 50% are needed to obtain the marginal granite and the barren aplite–pegmatites compositions, and over 99% for the most evolved dykes. No pattern in the chemical variation of the trace elements in quartz from different layers in the layered aplite–pegmatites has been found, suggesting the lack of internal fractionation processes, most probably due to the rapid crystallization of the pegmatitic melt, intruded into a colder country rock.
•Trace elements in quartz reflect magmatic fractionation.•Crystallization conditions influence the content in trace elements in quartz.•Granite–pegmatites from Tres Arroyos belong to the same highly fractionated system.•Chemical composition of the system evolved via fractional crystallization mechanisms.
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•Li-rich aplite-pegmatites are abundant in the Central Iberian Zone.•They are related to the extreme fractionation of Variscan granitic melts.•A model for the petrogenetic links among ...granites and pegmatites is proposed.•The most likely parental granitic series are determined.•The model may be extended to the rest of the European Variscan Belt.
The Central Iberian Zone (CIZ) is characterised by a large volume of Variscan granitic intrusions, which can be grouped into five types: (1) two-mica peraluminous leucogranites (S1); (2) P-rich highly peraluminous granites (S2); (3) P-poor moderately peraluminous granites (S3); (4) moderately to low peraluminous granites (S4); and (5) I-type low peraluminous granites (I). Though not as abundant as granites, aplite-pegmatite rocks are nonetheless widespread in this region, occurring either as fields of aplite-pegmatite dykes or as leucogranitic cupolas. They are commonly enriched in Li-(F-P) minerals such as spodumene, petalite, micas, and phosphates of the amblygonite-montebrasite and triphylite-lithiophilite series. Many of the Li-rich bodies show an aplitic texture, frequently with the development of layered units. Coarse crystals are also common, but are mostly smaller than 12 cm long. They usually do not show internal fractionation, zoning or a quartz-core, and often have high values in Li2O (>1.3 wt%), and high Na, F and P contents. Evidence in support of a petrogenetic link among peraluminous granites and aplite-pegmatite bodies is provided by field relationships and geochemical affinities. The Li-(F-P)-mineralisation is closely related to the S1 series in the northern CIZ realm, whereas in the southern portion of the CIZ the parental granites correspond to the S2 series. The granites of the S3 and S4 series, and the I-type granite suite are not related to the Li mineralisation. The S1 and S2 granites are interpreted to derive mainly from the partial melting of highly peraluminous, Ca-poor and P-rich Neoproterozoic metasediments during the Variscan orogeny. The melts are presumed to evolve favoured by a high content in fluxing components, such as P, F, B, Li, and H2O, which contributed to the lowering of viscosity, solidus temperature and polymerisation degree. This is in parallel to the increasing of the diffusion rates and mobility of the highly fractionated melts. The residual melts, enriched in incompatible elements such as Li and F, as well as B, Sn and other rare elements, tend to accumulate at the top of the granitic cupolas. Therefore, Li-rich dykes as observed in many aplite-pegmatite fields of the CIZ are arguably the result of the opening of the system, whereas Li-rich granitic cupolas form when the system remains closed. Lithium-rich rocks, comparable to those of the CIZ, are found in other parts of the European Variscan Belt also related to P-rich, Ca-poor, highly peraluminous S-type granites originated during the Variscan Orogeny. Accordingly, we postulate the existence of an extense Li-metallogenetic province including mainly the CIZ in Spain and Portugal, the Massif Central in France, the Bohemian Massif in the Czech Republic and Germany, the western Carpathians in the Slovak Republic, and the Cornwall region in the south west of England.
Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa ...subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear.
To study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 wild-type and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss.
We demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vitro, in vivo, ex vivo, in patient-derived organoid cultures and in a patient with metastatic PCa. Mechanistically, CHD1 regulates 53BP1 stability and CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair.
Our study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas.
This paper addresses the study of a pillow lava interbedded with Late Albian-Early Cenomanian sediments that crops out in Armintza (Bizkaia, Northern Spain). The lava flow is an alkaline basalt with ...abundant macrocrysts of clinopyroxene, kaersutite, Ca-rich plagioclase (50-86% An) and ilmenite, which display a variety of textures and complex zoning patterns indicative of open-system magmatic behaviour. Macrocryst cores are likely to be inherited antecrysts that underwent complex processes under deep pre-eruptive conditions (≈ 700-800 MPa). Microcrysts and macrocryst rims formed during magmatic ascent and emplacement at shallower levels (≈ 35 MPa). Hypothetical melts in equilibrium with clinopyroxenes and amphiboles have trace element compositions like metasomatic vein melts containing amphibole, and their patterns overlap with those of the Armintza pillow lava. This suggests a metasomatised lithospheric mantle with amphibole-rich veins as a potential source for the alkaline basaltic melt. It is even conceivable that the Armintza pillow lava and other alkaline volcanic manifestations of the Basque-Cantabrian Basin were part of the same magma plumbing system through which a series of time-limited eruptions of different batches of magma ascended from the lithospheric mantle to the upper crust during the Albian to the Santonian.
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Huntington’s disease (HD) is a hereditary neurodegenerative disease, with peripheral consequences that negatively contribute to quality of life. Circulating microRNAs (cmiRNAs) are ...being explored for their roles in intercellular communication and gene expression regulation, which allows gaining insight into the regulation of crosstalk between neuronal and peripheral tissues. Here, we explore the cmiRNA profile of plasma samples from fifteen symptomatic patients, with 40–45 CAG repeats in the HTT gene, and seven healthy matched controls. Isolated miRNAs from plasma samples were run against human miRNome panels, which have sequences for 752 human mature miRNAs. We found that 168 cmiRNAs are altered in symptomatic patients. Considering Bonferroni’s correction, miR-877-5p, miR-223-3p, miR-223-5p, miR-30d-5p, miR-128, miR-22-5p, miR-222-3p, miR-338-3p, miR-130b-3p, miR-425-5p, miR-628-3p, miR-361-5p, miR-942 are significantly increased in HD patients as compared with controls. Moreover, after patient’s organization according to approved HD scales, miR-122-5p is significantly decreased in HD patients with Unified Huntington’s Disease Rating Scale >24, whereas an increase in miR-100-5p levels and a decrease in miR-641 and miR-330-3p levels were recorded when patients were rearranged by Total Functional Capacity. These results suggest that cmiRNA profile could be further modified by disease progression, making cmiRNAs useful as monitoring biomarkers. Analysis of target genes indicated a general overexpression of cmiRNAs implicated in metabolism regulation. Profiling cmiRNA of HD subjects opens the possibility of personalized therapies for different groups of HD patients, based on disease modifiers: regulation of altered pathways might contribute to not only alleviate disease symptoms, but also influence HD progression.
The Jálama pluton (JP) is a Variscan peraluminous granitoid that intruded into low-grade metasediments from the Central Iberian Zone (CIZ). It comprises a sillimanite-bearing two-mica monzogranite in ...the inner zone, followed by a tourmaline-bearing two-mica monzogranite, and a marginal tourmaline-muscovite leucogranite in the northern half of the pluton. Microgranitoid enclaves and metasedimentary xenoliths occur locally in monzogranites. The change in rock type from the central monzogranite to the marginal leucogranite corresponds to decreasing TiO
2
, MgO, FeO, CaO, Sr, Ba, Zr, and ΣREE, and increasing SiO
2
, Na
2
O, P
2
O
5
, Rb, Li, Cs, Ta, Sn, and W. Fe/(Fe+Mg) ratios in biotite, muscovite and tourmaline increase with increasing Fe/(Fe+Mg) in bulk rock, suggesting an important control of the bulk-rock composition on mineral chemistry. The high peraluminosity, the low CaO and high P contents, as well as the similarity of ε(Nd)
300
values in both the granites and metasediments of the southern CIZ constitute strong evidences for a crustal origin of the granite suite, probably by melting of these metasedimentary rocks. Field and petrographic observations, together with mineralogical and geochemical data, suggest that assimilation and mingling/mixing acted in concert with fractional crystallization during the formation of the JP. These processes may also have been important in the evolution of other granitoids from this region.
The Berry-Havey pegmatite (Oxford pegmatite field, Androscoggin County, Maine, U.S.A.), enriched in Li, F, B, Be, and P, is intruded in hornblende-rich amphibolite, with minor biotite or diopside. ...The pegmatite has a complex internal structure, with four texturally and compositionally different zones that show an increasing degree of evolution inward: wall zone, intermediate zone, core margin, and core zone. The main minerals are quartz, feldspars, Al-micas, tourmaline, with minor Fe-micas, garnet, beryl, amblygonite-montebrasite, Fe-Mn phosphates, and apatite. Tourmaline is present in all zones of the pegmatite, showing different textures: black anhedral crystals in the wall and intermediate zones; black prisms of up to 40 cm in length in the intermediate zone; black tapered prisms, surrounded by a pseudo-graphic intergrowth of quartz or albite with black ± green/bluish tourmaline, and constituting a continuous layer under the core zone; multicolored and "watermelon" zoned crystals in the core zone; and gemmy deep green and color-zoned "watermelon" tourmaline prisms, up to 15 cm length, inside the pockets. A complete chemical evolution from Mg-rich schorl in the wall zone to elbaite with an important deprotonation in the pockets inside the core zone is observed. The most plausible exchange vectors for this chemical evolution are FeMg-1, YAlWOYR2+W(OH)-1 and AlXX(R2+Na)-1 (where R2+ = Fe2++Mg2++Mn2++Zn2+), for the tourmalines from the wall and intermediate zones. In the core margin, tourmaline composition evolves from schorl toward Li-rich species through the substitution (YAlYLiYR2+-2). Later, during the crystallization of the core zone, this exchange vector combined with the substitution (XYAl0.5XNa-1YLi-0.5). Finally, the gemmy tourmalines from the pockets show a deprotonation related to the exchange vector YAlWO2YLi-1W(OH)-2 and may be classified as darrellhenryite. These substitutions may reflect an increase in oxygen fugacity and a decrease in Li and F related to the crystallization of lepidolite and amblygonite-montebrasite in the core zone adjacent to or within the pockets. The crystallization of these minerals would reduce the availability of Li and F for the very latest tourmaline crystals, growing inside the pockets, where the deprotonation becomes important. Chemical and textural variation in tourmaline is consistent with a fractional crystallization process for the internal evolution of the Berry-Havey pegmatite. Crystallization of the tourmaline layer under the core zone may be related to the exsolution of the fluid phase implied in the formation of pockets.
A considerable body of evidence accumulated especially during the last decade, demonstrating that early nutrition and lifestyle have long-term effects on later health and disease ("developmental or ...metabolic programming").
Researchers involved in the European Union funded international EarlyNutrition research project consolidated the scientific evidence base and existing recommendations to formulate consensus recommendations on nutrition and lifestyle before and during pregnancy, during infancy and early childhood that take long-term health impact into account. Systematic reviews were performed on published dietary guidelines, standards and recommendations, with special attention to long-term health consequences. In addition, systematic reviews of published systematic reviews on nutritional interventions or exposures in pregnancy and in infants and young children aged up to 3 years that describe effects on subsequent overweight, obesity and body composition were performed. Experts developed consensus recommendations incorporating the wide-ranging expertise from additional 33 stakeholders.
Most current recommendations for pregnant women, particularly obese women, and for young children do not take long-term health consequences of early nutrition into account, although the available evidence for relevant consequences of lifestyle, diet and growth patterns in early life on later health and disease risk is strong.
We present updated recommendations for optimized nutrition before and during pregnancy, during lactation, infancy and toddlerhood, with special reference to later health outcomes. These recommendations are developed for affluent populations, such as women and children in Europe, and should contribute to the primary prevention of obesity and associated non-communicable diseases.
Abstract
A new type of Li mineralisation in hard rock has been found to occur in the Valdeflórez area (Cáceres, Spain), where there is 111.3 Mt of resources and a mean value of 0.61 wt% of Li
2
O. ...Lithium is mainly held by very fine-grained micas, important constituents of Ordovician psammopelitic rocks belonging to the Palaeozoic metasedimentary sequence of the Cáceres syncline. The mineralised zone has an elliptical surface shape with a dimension of ~ 700 × 500 m. Lithium-bearing rocks show a characteristic layered appearance, in which light grey quartz-micaceous laminae < 1 mm to some centimetres in thickness, with a variable ratio of quartz to mica, alternate with fine to very fine-grained, dark grey to black tourmalinite laminae parallel to the regional foliation. Subvertical quartz + (montebrasite)-veins that cut the regional foliation at an extremely high angle are also common in this area. Mineralisation and the associated veins are likely to be linked to the intrusion of the nearby Cabeza de Araya pluton. The infiltration of granite-derived Li-, F-, B- and P-rich aqueous fluids into the host rocks through fractures related to shearing processes is considered to be the cause of the formation of Li-rich micas and intense tourmalinisation at the expense of pre-existing phyllosilicates.
In this paper we report a combined zircon U–Pb–O isotopes and bulk-rock Sr–Nd–O isotopes study on granitic rocks from the Jálama pluton, Central Iberian Zone. Zircon U--Pb ages of representative ...granitic rock samples are bracketed in the range of 306–304 ± 3 Ma, but within the level 2σ errors of U--Pb ages. Therefore it is not possible to establish differences in intrusion ages between the main granitic units that make up the Jálama pluton. Microgranular enclaves appear to be slightly older (309 ± 2 Ma), but they do overlap with the age of the granitic rocks. Sr--Nd isotopic data for enclaves of tonalitic composition preclude a simple mantle or crustal origin, but high mean zircon δ18O values of 8.65 ± 0.9‰ and δ18O(WR) values of 9.96–10.56‰ reflect a largely crustally contaminated magma. The combination of field relations, petrography, bulk-rock geochemistry, Sr-Nd-O isotopic data, zircon δ18O values and U--Pb ages provide compelling evidence that the granites from the Jálama pluton: (i) were coevally formed involving assimilation and mingling/mixing concomitant to fractional crystallization; and (ii) represent typical S-type granites that evolved from a same crustal source, potentially metasedimentary rocks from the Schist Greywacke Complex by considering the Neoproterozoic ages of the inherited zircons.
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•The Jálama pluton is a Variscan peraluminous granitoid from the Central Iberian Zone.•It includes three units with minor microgranular and metasedimentary enclaves.•Zircon U--Pb ages of granitic rocks are in the range of 309–304 Ma.•The δ18O(Zr) values for the granites indicate a crustal source.•Bulk-rock (Sr-Nd-O) isotopic data are consistent with a crustal origin.
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