The Zemaiciu Naumiestis granitoids: new evidences for Mesoproterozoic magmatism in western Lithuania

We report new occurrences of ca. 1460 Ma magmatism in western Lithuania, where large volumes of granitoid melts were intruded into host supracrustal and charnockitoid rocks, and formed the Zemaiciu Naumiestis pluton. Numerous granitoids of that age have previously been described from southern Sweden and from the Danish island of Bornholm, but none have been reported from the eastern side of the Baltic Sea, where the crystalline basement is covered by Phanerozoic sediments. Petrological studies demonstrate that the Zemaiciu Naumiestis intrusion consists of quartz monzodiorites, monzogranites and syenogranites. The dominant ferromagnesian mineral is biotite. Rare clinopyroxene grains occur in the quartz monzodiorites. The rocks are fine to coarse-grained, often porphyritic. Chemically, the studied granitoids are dominantly alkali-calcic and shoshonitic, metaluminous to peraluminous, and ferroan to magnesian. The geochemical data indicate that the pluton consists of two rock suites, one representing monzodiorites and monzogranites, and other mostly syenogranites. The suites originated from slightly different sources. The rocks within the Zemaiciu Naumiestis pluton are variably deformed and locally cataclased. Some are, however, rather massive. Two samples of monzogranite yielded ID-TIMS U-Pb zircon ages of 1462 +/- 8 (MSWD = 1.09) and 1459 +/- 3 Ma (MSWD = 0.28)

Pneumonia and Related Conditions in Critically Ill Patients—Insights from Basic and Experimental Studies

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia’s development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia. The theoretical study was carried out using the Columbia Open Health Data (COHD) resource, which provides access to clinical concept prevalence and co-occurrence from electronic health records. The experimental study included TREC/KREC assays in young adults (18–40 years) with community-acquired (CAP) (n = 164) or nosocomial (NP) (n = 99) pneumonia and healthy controls (n = 170). Co-occurring rates between pneumonia, sepsis, acute respiratory distress syndrome (ARDS) and some other related conditions common in intensive care units were the top among 4170, 3382 and 963 comorbidities in pneumonia, sepsis and ARDS, respectively. CAP patients had higher TREC levels, while NP patients had lower TREC/KREC levels compared to controls. Low TREC and KREC levels were predictive for the development of NP, ARDS, sepsis and lethal outcome (AUCTREC in the range 0.71–0.82, AUCKREC in the range 0.67–0.74). TREC/KREC analysis can be considered as a potential prognostic test in patients with pneumonia

Design, Synthesis and In Vitro Investigation of Cabozantinib-Based PROTACs to Target c-Met Kinase

(1) Background: This investigation aimed at developing a series of c-Met-targeting cabozantinib-based PROTACs. (2) Methods: Purification of intermediate and target compounds was performed using column chromatography, in vitro antiproliferation activity was measured using a standard MTT assay and a c-Met degradation assay was performed via the immunoblotting technique. (3) Results: Several compounds exhibited antiproliferative activity towards different cell lines of breast cancer (T47D, MDA-MB-231, SKBR3, HCC1954 and MCF7) at the same level as parent cabozantinib and 7-demethyl cabozantinib. Two target conjugates, bearing a VHL-ligand as an E3-ligase binding moiety and glycol-based linkers, exhibited the effective inhibition of c-Met phosphorylation and an ability to decrease the level of c-Met in HCC1954 cells at micromolar concentrations. (4) Conclusions: Two compounds exhibit c-Met inhibition activity in the nanomolar range and can be considered as PROTAC molecules due to their ability to decrease the total level of c-Met in HCC1954 cells. The structures of the offered compounds can be used as starting points for further evaluation of cabozantinib-based PROTACs

1.86 Ga key paleomagnetic pole from the Murmansk craton intrusions - Eastern Murman Sill Province, NE Fennoscandia: Multidisciplinary approach and paleotectonic applications

We present the first 1.86 Ga paleomagnetic key pole of Fennoscandia obtained for the dolerite sills of the Murmansk craton – Eastern Murman Sill Province, that outcrop in the northern part of the Kola Peninsula along the Barents Sea coast for a distance of 200 km (Slat = 68.5°; Slong = 37.9°; N = 16 sites; Plat = 54.7°; Plong = 234.7°; dp/dm = 4.3°/6.3°, Qv = 5). The age of the sills and their characteristic remanent magnetization (ChRM) was determined by four independent geochronometers: U-Pb – 1860 ± 4 and 1863 ± 7 Ma (ID-TIMS, baddeleyite), Sm-Nd – 1889 ± 57 Ma, Rb-Sr – 1850 Ma, Ar/Ar – 1865 ± 8 and 1857 ± 20 Ma (biotite). The primary nature of the ChRM is confirmed by the results of petrographic, geochemical, paleo- and rock magnetic studies, as well as by thermochronological data. The similarity of the petrographic and geochemical characteristics of sills from different localities indicates that these dolerite sills were formed during a single magmatic event and their cooling down to 580 °C occurred at depths of about 10 ± 2 km and lasted ∼2800 years or even faster. Paleogeographic reconstruction of Fennoscandia on the basis of the obtained paleomagnetic pole is in general agreement with the previously suggested configuration of core of the Nuna/Columbia supercontinent (Evans and Mitchell, 2011; Meert and Santosh, 2017). A new reliable Thellier-Coe paleointensity determination for this time reveals a rather low mean VDM = 1.8 (±0.1) × 1022 Am2 that supports the Proterozoic dipole low hypothesis (Biggin et al., 2009)