Evolution of the Greater Caucasus Basement and Formation of the Main Caucasus Thrust, Georgia

Along the northern margin of the Arabia‐Eurasia collision zone in the western Greater Caucasus, the Main Caucasus Thrust (MCT) juxtaposes Paleozoic crystalline basement to the north against Mesozoic metasedimentary and volcaniclastic rocks to the south. The MCT is commonly assumed to be the trace of an active plate‐boundary scale structure that accommodates Arabia‐Eurasia convergence, but field data supporting this interpretation are equivocal. Here we investigate the deformation history of the rocks juxtaposed across the MCT in Georgia using field observations, microstructural analysis, U‐Pb and 40Ar/39Ar geochronology, and 40Ar/39Ar and (U‐Th)/He thermochronology. Zircon U‐Pb analyses show that Greater Caucasus crystalline rocks formed in the Early Paleozoic on the margin of Gondwana. Low‐pressure/temperature amphibolite‐facies metamorphism of these metasedimentary rocks and associated plutonism likely took place during Carboniferous accretion onto the Laurussian margin, as indicated by igneous and metamorphic zircon U‐Pb ages of ~330–310 Ma. 40Ar/39Ar ages of ~190–135 Ma from muscovite in a greenschist‐facies shear zone indicate that the MCT likely developed during Mesozoic inversion and/or rifting of the Caucasus Basin. A Mesozoic 40Ar/39Ar biotite age with release spectra indicating partial resetting and Cenozoic (<40 Ma) apatite and zircon (U‐Th)/He ages imply at least ~5–8 km of Greater Caucasus basement exhumation since ~10 Ma in response to Arabia‐Eurasia collision. Cenozoic reactivation of the MCT may have accommodated a fraction of this exhumation. However, Cenozoic zircon (U‐Th)/He ages in both the hanging wall and footwall of the MCT require partitioning a substantial component of this deformation onto structures to the south.Plain Language SummaryCollisions between continents cause deformation of the Earth’s crust and the uplift of large mountain ranges like the Himalayas. Large faults often form to accommodate this deformation and may help bring rocks once buried at great depths up to the surface of the Earth. The Greater Caucasus Mountains form the northernmost part of a zone of deformation due to the ongoing collision between the Arabian and Eurasian continents. The Main Caucasus Thrust (MCT) is a fault juxtaposing old igneous and metamorphic (crystalline) rocks against younger rocks that has often been assumed to be a major means of accommodating Arabia‐Eurasia collision. This study examines the history of rocks along the MCT with a combination of field work, study of microscopic deformation in rocks, and dating of rock formation and cooling. The crystalline rocks were added to the margins of present‐day Eurasia about 330–310 million years ago, and the MCT first formed about 190–135 million years ago. The MCT is likely at most one of many structures accommodating present‐day Arabia‐Eurasia collision.Key PointsAmphibolite‐facies metamorphism and plutonism in the Greater Caucasus basement took place ~330–310 MaThe Main Caucasus Thrust formed as a greenschist‐facies shear zone during Caucasus Basin inversion and/or rifting (~190–135 Ma)The Main Caucasus Thrust may have helped facilitate a portion of at least 5–8 km of basement exhumation during Arabia‐Eurasia collisionPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/1/tect21292-sup-0002-2019TC005828-ts01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/2/tect21292-sup-0006-2019TC005828-ts05.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/3/tect21292_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/4/tect21292-sup-0003-2019TC005828-ts02.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/5/tect21292-sup-0005-2019TC005828-ts04.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/6/tect21292.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154626/7/tect21292-sup-0004-2019TC005828-ts03.pd

Paleointensity Results From Pliocene Lavas of the Lesser Caucasus Obtained Using the Multispecimen Parallel Differential pTRM Method: A Comparison With Thellier- Thellier and IZZI Data

We report paleointensity results obtained with the multispecimen method (MSP) over the Pliocene sequence of Apnia (Georgia) which records a polarity reversal. Paleointensity determinations with the multispecimen technique were performed on 12 flows with the original (MSP-DB) and the domain-state corrected (MSP-DSC) protocol. Eight MSP-DSC determinations passed the proposed quality criteria. To obtain highly reliable data through the agreement between intensity values from different methods, MSP results were combined with paleointensities from a previous study with Thellier-type methods and especially strict selection criteria (RCRIT) on same flows (Sánchez-Moreno et al., 2020). Application of this multimethod procedure resulted in three new paleointensities including both MSP and Thellier-type results and an additional one obtained with two different Thellier-type methods, yielding one paleointensity of 36.9 µT in the normal-polarity, and three paleointensities between 19.2 and 24.1 µT in the reverse-polarity section. Additionally, Thellier-type data have been reinterpreted in this study with more flexible criteria (TTP) and the results combined with the MSP data. As a result, four flows yield paleointensities including MSP and Thellier-type determinations and seven include paleointensities obtained with two different Thellier-type methods. Results range from 37.2 and 44.3 μT in the normal-polarity and from 12.5 to 24.6 μT in the reverse-polarity section. Comparison of results from the four flows yielding multimethod determinations applying RCRIT criteria with those from the same flows under TTP criteria yields no significant difference in paleointensity values and their experimental uncertainty. Thus, application of a multimethod approach supports the possibility of using TTP criteria.Project PID2019-105796/10.13039/501100011033 (Agencia Estatal de Investigación, Spain), project BU066U16 (Junta de Castilla y León, Spain) and pre-doctoral grant BES-2013-064060 (MINECO, Spain). MCR acknowledges funding from the Fulbright Commission and the Spanish Ministry of Science, Innovation and Universities for a research stay at Hawaii University at Manoa. AG is grateful to the financial support given by DGAPA-PAPIIT IN101717. At Montpellier laboratory, the FUReMAG rapid furnace construction was supported by the French National Agency for Research (ANR-12-BS06-0015)

Constitutive Overexpression of Muscarinic Receptors Leads to Vagal Hyperreactivity

BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE) activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS). Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE) gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2) and M(3) receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively) and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2) receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2) receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2) receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits). This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2) receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits) and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that cardiac muscarinic receptor overexpression plays a critical role in the development of vagal hyperreactivity, whereas AchE hyperactivity appears as a compensatory consequence of it. Since similar vagal disorders were observed recently by us in SIDS, muscarinic receptor overexpression could become a marker of risk of vasovagal syncopes and SIDS

miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth

Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3'UTR and significantly reduced Sp1-driven nuclear factor-kappa B activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

<p>Abstract</p> <p>Background</p> <p>Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).</p> <p>Methods</p> <p>We isolated a breast cancer cell population (CD44⁺CD24^-cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44⁺CD24^-phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.</p> <p>Results</p> <p>Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.</p> <p>Conclusions</p> <p>Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.</p

An Integrated Paleomagnetic, Multimethod- Paleointensity, and Radiometric Study on Cretaceous and Paleogene Lavas From the Lesser Caucasus: Geomagnetic and Tectonic Implications

Sixteen rhyolitic and dacitic Cretaceous and Paleocene-Eocene lavas from the Lesser Caucasus have been subjected to paleomagnetic and multimethod paleointensity experiments to analyze the variations of the Earth's magnetic field. Paleointensity experiments were performed with two methods. Thellier-type experiments with the IZZI method on 65 specimens (nine flows) yielded 15 successful determinations and experiments with the multispecimen method on 14 samples (seven flows) yielded two successful determinations. The joint analysis of the results obtained with both methods produced a mean FuK = (19.9 ± 3.7) µT for upper Cretaceous and FPg = (20.7 ± 3.3) µT for Paleogene sites. Low virtual axial dipole moments for the Cretaceous (3.4 × 1022 Am2) and Paleogene (3.5 × 1022 Am2) samples support the idea of a lower average dipole moment during periods of stable polarity of the Earth magnetic field. Mean flow paleomagnetic directions did not match expected upper Cretaceous to Paleogene directions calculated from the European Apparent Polar Wander Path. While inclination results roughly agreed with expected values, a group of sites showed nearly North-South paleodeclinations (D = 1.1° ± 14.2°), and another group displayed eastward deviated paleodeclinations (D = 72.9° ± 26.6°). These results suggest the occurrence of nearly vertical-axis rotations, probably as a result of continental collision since Oligocene. In addition to paleomagnetic and palaeointensity analyses, new K-Ar absolute age determinations have been performed on three of the studied sites, yielding Late Cretaceous ages (78.7 ± 1.7, 79.7 ± 1.6, and 83.4 ± 1.8 Ma (2σ)).Project PID2019-105796GB-100/AEI/10.13039/501100011033 (Agencia Estatal de Investigación, Spain). M. Calvo-Rathert acknowledges funding from the Fulbright Commission and the Spanish Ministry of Science, Innovation, and Universities for a research stay at Hawaii University at Manoa. A. Goguitchaichvili acknowledges financial support from UNAM-PAPIIT no. IN101920. N. García-Redondo acknowledges financial support from Junta de Castilla y León and the European Research Development Fund (ERDF). EHB acknowledges financial support for laboratory maintenance and measurements to SOEST-HIGP and National Science Foundation grants. These is SOEST 11143 and HIGP 2420 contribution

Geodynamics, seismicity, and seismic hazards of the Caucasus

Being a part of ongoing continental collision between the Arabian and Eurasian plates, the Caucasus region is a remarkable site of moderate to strong seismicity, where devastating earthquakes caused significant losses of lives and livelihood. In this article, we survey geology and geodynamics of the Caucasus and its surroundings; magmatism and heat flow; active tectonics and tectonic stresses caused by the collision and shortening; gravity and density models; and overview recent geodetic studies related to regional movements. The tectonic development of the Caucasus region in the Mesozoic-Cenozoic times as well as the underlying dynamics controlling its development are complicated processes. It is clear that the collision is responsible for a topographic uplift / inversion and for the formation of the fold-and-thrust belts of the Greater and Lesser Caucasus. Tectonic deformations in the region is influenced by the wedge-shaped rigid Arabian block indenting into the relatively mobile region and producing near N-S compressional stress and seismicity in the Caucasus. Regional seismicity is analysed with an attention to sub-crustal seismicity under the northern foothills of the Greater Caucasus, which origin is unclear – whether the seismicity associated with a descending oceanic crust or thinned continental crust. Recent seismic tomography studies are in favour of the detachment of a lithospheric root beneath the Lesser and Greater Caucasus. The knowledge of geodynamics, seismicity, and stress regime in the Caucasus region assists in an assessment of seismic hazard and risk. We look finally at existing gaps in the current knowledge and identify the problems, which may improve our understanding of the regional evolution, active tectonics, geodynamics, shallow and deeper seismicity, and surface manifestations of the lithosphere dynamics. Among the gaps are those related to uncertainties in regional geodynamic and tectonic evolution (e.g., continental collision and associated shortening and exhumation, lithosphere structure, deformation and strain-stress partitioning) and to the lack of comprehensive datasets (e.g., regional seismic catalogues, seismic, gravity and geodetic surveys)

Is Evolution of Blind Mole Rats Determined by Climate Oscillations?

The concept of climate variability facilitating adaptive radiation supported by the ‘‘Court Jester’’ hypothesis is disputed by the ‘‘Red Queen’’ one, but the prevalence of one or the other might be scale-dependent. We report on a detailed, comprehensive phylo-geographic study on the ,4 kb mtDNA sequence in underground blind mole rats of the family Spalacidae (or subfamily Spalacinae) from the East Mediterranean steppes. Our study aimed at testing the presence of periodicities in branching patterns on a constructed phylogenetic tree and at searching for congruence between branching events, tectonic history and paleoclimates. In contrast to the strong support for the majority of the branching events on the tree, the absence of support in a few instances indicates that network-like evolution could exist in spalacids. In our tree, robust support was given, in concordance with paleontological data, for the separation of spalacids from muroid rodents during the first half of the Miocene when open, grass-dominated habitats were established. Marine barriers formed between Anatolia and the Balkans could have facilitated the separation of the lineage ‘‘Spalax’’ from the lineage ‘‘Nannospalax’’ and of the clade ‘‘leucodon’’ from the clade ‘‘xanthodon’’. The separation of the clade ‘‘ehrenbergi’’ occurred during the late stages of the tectonically induced uplift of the Anatolian high plateaus and mountains, whereas the separation of the clade ‘‘vasvarii’’ took place when the rapidly uplifting Taurus mountain range prevented the Mediterranean rainfalls from reaching the Central Anatolian Plateau. The separation of Spalax antiquus and S. graecus occurred when the southeastern Carpathians were uplifted. Despite the role played by tectonic events, branching events that show periodicity corresponding to 400-kyr and 100-kyr eccentricity bands illuminate the important role of orbital fluctuations on adaptive radiation in spalacids. At the given scale, our results supports the ‘‘Court Jester’’ hypothesis over the ‘‘Red Queen’’ one