Alteration Products Research Articles

TET2 Regulates 5-Hydroxymethylcytosine Signature and CD4+ T-Cell Balance in Allergic Rhinitis

PurposePrevious studies have shown the role of ten-eleven translocation 2 (TET2) in CD4+ T cells. However, its function in CD4+ T cells under allergic inflammation is unclear. We aimed to investigate the epigenomic distribution of DNA 5-hydroxymethylcytosine (5hmC) and the role of TET2 in CD4+ T cells of allergic rhinitis (AR).MethodsThe hMeDIP-seq was performed to identify sequences with 5hmC deposition in CD4+ T cells of AR patients. Tet2-deficient or wild type mice were stimulated with ovalbumin (OVA) to develop an AR mouse model. The histopathology in nasal mucosae, Th1/Th2/Treg/Th17 cell percentage, concentrations of Th-related cytokines, expression of Tet and differential hydroxymethylated genes (DhMG), and the global deposition of 5hmC in sorted CD4+ T cells were detected.ResultsEpigenome-wide 5hmC landscape and DhMG in the CD4+ T cells of AR patients were identified. Tet2 depletion did not led to spontaneous inflammation. However, under the stimulation of allergen, OVA, loss of Tet2 resulted in the exacerbation of allergic inflammation, which was characterized by severer allergic symptoms, more inflammatory cells infiltrating the nasal lamina propria, sharper imbalances between Th1/Th2 and Treg/Th17 cells, and excessive secretion of OVA-specific IgE and Th2-related cytokines. Moreover, altered mRNA production of several DhMG and sharp decrease in 5hmC deposition were also observed in Tet2-deficient OVA-exposed mice.ConclusionsTET2 may regulate DNA 5hmC, DhMG expressions, and CD4+ T cell balance in AR.

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

Zeolite Minerals from Wat Ocheng, Ta Ang, Ratanakiri Province, Cambodia – Occurrence, Composition, and Paragenesis

ABSTRACT Located in the southwest corner of the Ratanakiri Volcanic Province, the Wat Ocheng basalt is the first known zeolite locality in Cambodia. The basalt is a fine-grained, vesicular to amygdaloidal, subalkaline to transitional alkaline intraplate tholeiite comprised of 30% lath-like plagioclase (average: Ab51An45Or4), 35% interstitial augite (average: Wo44En35Fs21), 25–30% zeolites after plagioclase and volcanic glass, and minor skeletal ulvöspinel. It contains mineralized amygdales ranging in size from 0.5 × 0.5 cm to 5 × 9 cm. Nine zeolite species occur at Wat Ocheng, including analcime, chabazite-Ca, gonnardite, natrolite, phillipsite-Ca, and thomsonite-Ca, along with clays, aragonite, calcite, and pyrite. All the zeolite species are being described from Cambodia for the first time. The zeolite and secondary mineral assemblages observed at Wat Ocheng are similar to those reported from other alkaline basalt localities, including those in neighboring Vietnam, and are a product of alteration of the primary Ca-Na minerals and volcanic glass as a result of burial metamorphism and infiltration of heated meteoric waters. The mineral assemblage is not homogeneous across amygdales within the exposed lava flow, suggesting localized closed systems, likely the result of early precipitation of clay minerals and fine-grained zeolites. Decreased porosity and differences in fluid geochemistry would account for the diversity in the observed assemblages. Four stages of hydrothermal alteration and zeolitization have been defined based on mineral textures and chemistry. Zeolite formation began with fine-grained Ca- (chabazite-Ca and phillipsite-Ca) and Na- (analcime) dominant, high TSi (Si/Si+Al) species in Stage II following deposition of clay minerals in Stage I. Stage III is characterized by increasing Na+K contents and decreasing TSi. Crystallization of coarse-grained chabazite-Ca and phillipsite-Ca with increasing Na+K contents in the rims of the crystals followed the development of natrolite with a later-stage epitaxial overgrowth of thomsonite-Ca. The final stage of mineralization (Stage IV) included late-stage calcite, pyrite, and termination of growth of acicular sprays of thomsonite-Ca. Post-magmatic cooling and circulation of meteoric water and fluids derived from alluvial sediments overlying the basalts were involved in zeolitization. Thermal sources include an underlying basaltic andesite flow as well as regional deep-seated, extensional pull-apart structures, the result of a thinned lithosphere and injection of fertile mantle following the collision of the Eurasian and Indochina plates during the Himalayan Orogeny.

Blockchain Enabled Credibility Applications: Extant Issues, Frameworks and Cases

The credibility of information is known as a major cause of a wide range of issues, such as: altered product information in food supply chains; fake transactions on E-commerce platforms; lengthy claim settlement time in agricultural insurance; and costly borrowings in agricultural financing. For a more specific example in food supply chains, end customers want to check the product information, but either doubt the authenticity of information, or simply do not have access to the information. The reason is that upstream suppliers and downstream retailers are often reluctant to share data, fearing privacy loss or business secret leakage. The consequence is that regulatory departments may face enormous challenges to identify accurate contamination sources, if there is scarce information or falsely recorded information at any stage of the food supply chain. In this paper, we focus on four common scenarios demanding information credibility in the agricultural supply chain: product traceability, E-commerce platforms, agricultural insurance, and agricultural financing. We review some high-profile smart credibility applications with emphasis on how blockchain related technologies can provide the information credibility by examining extant issues and relevant frameworks.

Interactions between hydrated cement pastes and aggressive ammonium: experimental batches characterization

Agricultural and food industries concrete facilities face chemically aggressive conditions that can damage their microstructure and reduce their lifespan. They are particularly exposed to ammonium-rich environments from natural microbial activity. The poorly crystalline mineralogy of hydrated cement pastes, the compositional variability of the phases and their reactivity make the geochemical behaviour of such materials difficult to investigate and predict over both large periods of time and wide variety of chemical compositions. This work aims (i) to assess the stability of the cement phases involved in ammonium-rich conditions as well as to identify the alteration products, and (ii) to understand the mechanisms and intensity of alteration. To do this, experiments were carried out both on OPC paste powder and on monolithic OPC pastes, degraded by an ammonium nitrate solution in semi-batch conditions. The powder was gradually added to the aggressive solution while the monoliths were immersed for 16 weeks in regularly renewed solution. The pH and the concentration of the chemical elements in solution were monitored over the experiments. The microstructural, chemical and mineralogical changes of the samples were analysed by scanning electron microscopy, electron probe micro-analysis and X-Ray diffraction and showed phenomena of dissolution, leaching and carbonation.

ПЕТРО- И ПАЛЕОМАГНЕТИЗМ МАФИТОВЫХ ДАЕК СЕРГЕЕВСКОГО ТЕРРЕЙНА (ЮЖНЫЙ СИХОТЭ-АЛИНЬ)

The paper presents the results of paleomagnetic and rock magnetic studies of rocks from the mafic dikes of the Sergeevka terrane that intruded the basement rocks. Currently, they are widespread in coastal outcrops of the eastern part of the Peter the Great Bay of the Sea of Japan between Anna and Priboinaya bays in the south of Primorsky Krai. Structural information allows us to conclude that dikes of both the eastern (Srednyaya Bay-Priboinaya Bay) and the western (Anna Bay-Cape De Livron) clusters intruded from the igneous centers of the same strike. Rocks of the dikes have undergone significant secondary alterations. Inverse magnetic fabric in the dikes is the result of high-temperature decomposition and granulation of primary titanomagnetites during postmagmatic deformations and metamorphism, traces of which are clearly visible in the microscopic and microprobe study of secondary alteration products. All this testifies to a significant secondary change in the rocks of the dikes after their intrusion. This is the secondary heating of the dikes above a temperature of 600 °C, that is, above the Curie point of magnetite (578 °C). The nature of the isolated high-temperature NRM component of the dikes is not primary, but secondary, that is, metachronous. The paleomagnetic data constrained the time of the metamorphic event leading to the remagnetization of mafic dikes of the Sergeevka terrane to ca. 250 Ma. The calculated paleolatitude of the Sergeevka terrane at the time of acquisition of the metachronous NRM component by mafic dikes (21.8 ± 4.2° N) is consistent with the paleolatitudes of the northeastern edge of the North China Craton at the Late Permian/Early Triassic boundary.

Mineralogy of the RBT 04262 Martian meteorite as determined by micro‐Raman and micro‐X‐ray fluorescence spectroscopies

AbstractMartian meteorites and terrestrial analogs represent the only samples available on Earth for studying mineralogy features of our neighbor planet Mars. This work characterizes the Roberts Massif (RBT) 04262 Martian meteorite by using mainly Raman spectroscopy. By means of this technique, it was confirmed that the meteorite matrix is composed by pyroxene and plagioclase (converted to maskelynite due to the shock pressure). Olivine‐coarse grains embedded in the matrix were also observed. These grains were coated by hydrated magnesium and calcium sulfates, which would belong to the Mars sulfate deposits or to the terrestrial weathering. Although the sulfates could be formed on Mars due to the oxidation of sulfides or elemental sulfur along the sulfur Mars cycle, their distribution along cracks and fractures confirm that are weathering products. However, other S‐bearing compounds that belong to Mars were found, such as elemental sulfur and a thermally transformed iron sulfide. Finally, the calcium phosphate merrillite and titanomagnetite were also detected. Taking this into account, the minerals found were classified into primary minerals that belong to Mars (pyroxene, olivine, elemental sulfur, and titanomagnetite), secondary ones that are alteration products of the primary minerals (maskelynite, iron sulfide, and merrillite), and terrestrial weathering products (sulfates gypsum and epsomite).

Characterisation of Uranophane and Boltwoodite by Raman, luminescence and laser-induced breakdown spectroscopy

Among the wide range of spent nuclear fuel alteration products, uranophane-type uranyl silicates have attracted particular attention due to their ability to incorporate additional ions into their crystal structures, including other radionuclides. Two such mineral phases, uranophane (s.s.) (Ca(UO2)2(SiO3OH)2·5(H2O)) and boltwoodite ((K,Na)(UO2)(SiO3OH)·1.5H2O), have been characterised by Raman, luminescence and laser-induced breakdown spectroscopy. Well-defined Raman features were observed in each case with the two minerals being differentiated by detection of the ν3(SiO4)2- and δ(SiOH) modes for uranophane but not boltwoodite. Some distinction between uranophane-α and -β was observed by Raman, but the phase sensitivity was more apparent in the luminescence emission peak positions. The luminescence signal emitted for boltwoodite was much weaker than with uranophane, suggesting that the associated K+ and Na+ cations in the former are more efficient at chemical quenching than Ca2+. This study also reports the first luminescence excitation data for uranophane and boltwoodite.

The Barzavand and Neysian Copper Deposits, NW Naein, Central Iran zone: Constraints on styles mineralization and geochemical signatures of hydrothermal alterations.

Field observations in the northwest of Naein (Central Iran zone) indicate various types of alteration products have extended into pyroclastic and volcanic units with Oligo- miocene age. It seems the Zefreh (with NW- SE trend) and Kachumesqal (with E-W trend) faults are effective factors in the formation of Neysian and Barzavand copper deposits respectively. Alteration in Barzavand copper deposit (with stratabound form) includes pyritization, propylitization, zeolitization, saussuritization, uralitization and silicification, while in Neysian (with oval form) include phyllic, advanced argillic, argillic and propylitic. Geochemical studies in Barzavand show the positive correlation between (La/Lu)N, (La/Yb)N and (La/Sm)N and CaO (r= 0.70 to 0.96) related to propylitization of host rock basalt and increase in pH of fluids responsible for mineralization that play important role in differentiation of lanthanides in study area. The Barzavand copper deposit has submarine volcanism, diagenesis, burial metamorphism and weathering stages during its evolution. Remarkable geochemical features in Neysian include high (La/Lu)N, Ba and Sr values than La, Ce and Y. It seems that extensive alteration occurred along with hypogene and supergene processes in Neysian. According to alteration properties, mineralogy and the whole-rock geochemistry, the Barzavand and Neysian copper deposits are most similar to Manto- type and porphyry copper deposits respectively.

On the Surface and Beyond. Degradation Morphologies Affecting Plant Ash-Based Archaeological Glass from Kafir Kala (Samarkand, Uzbekistan)

The study focuses on an assemblage of glass finds from the citadel of Kafir Kala, Uzbekistan, located along one of the major Eurasian branches of the “Silk Roads” with a consistent occupation between the 8th and 12th century CE. Glass fragments for this study were selected based on marked surface alterations they showed, with stratified deposits of different thickness and colours. Starting from a preliminary observation under Optical Microscope, fragments were clustered into four main groups based on the surface appearance of the alterations; Scanning Electron Microscopy investigations of the stratigraphy of the alteration products were then carried out, to evaluate micro-textural, morphological and compositional features. Data from the analyses allowed identifying preferential patterns of development of the various degradation morphologies, linkable to compositional alterations of the glass due to burial environment and the alkali leaching action of the water. Iridescence, opaque weathering (at times associated with black stains), and blackening were identified as recurring degradation morphologies; as all but one sample were made of plant ash-based glass, results show no specific correlation between glass composition and the occurrence of one or the other degradation pattern, often found together. Framed in a broad scenario, the paper aims to set the basis for the development of a study approach dedicated to the degradation morphologies affecting archaeological glasses, a topic still lacking systematisation and in-depth dedicated literature.

Chlorite alteration in pegmatite from the Madan Pb-Zn deposits: mineral association, chemical composition and temperature of formation

Chlorites are common constituent of the secondary mineral assemblage formed as alteration products after aluminosilicate host rocks in the Pb-Zn deposits in Madan district. In concordant pegmatite body from the Petrovitsa deposit, they are formed after mica flakes. Such transformation often results in abundant rutile grains. The dominant chlorite compositions fall in the clinochlore-chamosite series. Minor and trace elements incorporation of Li, B, V, Co, Ni, Zn, Ga, Rb, Sr, Cs, and Ba is detected. Calculated To of formation ranges within 298–306 °C.

Pathogenic Aspects of Inherited Platelet Disorders

Inherited platelet disorders (IPDs) constitute a large heterogeneous group of rare bleeding disorders. These are classified into: (1) quantitative defects, (2) qualitative disorders, or (3) altered platelet production rate disorders or increased platelet turnover. Classically, IPD diagnostic is based on clinical phenotype characterization, comprehensive laboratory analyses (platelet function analysis), and, in former times, candidate gene sequencing. Today, molecular genetic analysis is performed using next-generation sequencing, mostly by targeting enrichment of a gene panel or by whole-exome sequencing. Still, the biochemical and molecular genetic characterization of patients with congenital thrombocytopathias/thrombocytopenia is essential, since postoperative or posttraumatic bleeding often occurs due to undiagnosed platelet defects. Depending upon the kind of surgery or trauma, this bleeding may be life-threatening, e.g., after tonsillectomy or in brain surgery. Undiagnosed platelet defects may lead to additional surgery, hysterectomy, pulmonary bleeding, and even resuscitation. In addition, these increased bleeding symptoms can lead to wound healing problems. Only specialized laboratories can perform the special platelet function analyses (aggregometry, flow cytometry, or immunofluorescent microscopy of the platelets); therefore, many IPDs are still undetected.

Seafloor Magnetism Under Hydrothermal Alteration: Insights From Magnetomineralogy and Magnetic Properties of the Southwest Indian Ridge Basalts

AbstractTitanomagnetites in mid‐ocean ridge basalt (MORB) experience variable post crystallization alterations associated with seafloor tectonic and environmental processes. Compared to low‐temperature oxidation, seafloor hydrothermal alteration is thought to be more destructive but its magnetic aftermaths are insufficiently documented. Here we present comprehensive rock magnetic and electron microscopic analyses of fresh and hydrothermally‐altered MORBs dredged from the Longqi and Yuhuang hydrothermal fields, Southwest Indian Ridge. We observe large variations in magnetic properties of fresh MORBs, originated from relative proportions of nano‐scale single‐domain to vortex state and micron‐scale vortex to multi‐domain state dendritic titanomagnetites. Progressive hydrothermal alteration produces secondary magnetite through recrystallization of exsolved and dissolved Fe from primary titanomagnetite. Exsolution is evident by a dual Verwey transition signature and coexisting Ti‐poor titanomagnetites and sphenes in partially chloritized basalts. A schematic model is proposed to explain the variations in magnetomineralogy and magnetic properties with progressive hydrothermal alteration. Intermediate hydrothermal alteration products retain a secondary chemical remanent magnetization (CRM) which is related to the long‐term magnetization variations in oceanic basalts. The established framework allows characterizing MORB hydrothermal alteration and ultimately contributes to resolving the complexity of seafloor magnetism.

Micro- and Nanotexture and Genesis of Ball Clays in the Lower Cretaceous (SE Iberian Range, NE Spain)

Ball clay deposits in the SE of the Iberian Range (NE Iberian Peninsula) consist of Albian clays and siltstones with greyish and blackish colors, interbedded with subbituminous coals. The ball clays are nowadays mined for the manufacture of white color ceramics. The mineralogy of these deposits consists mainly of kaolinite, illitic phases, and quartz. The euhedral to sub-euhedral morphology of the kaolinites suggests their in-situ origin. The anhedral morphology of the illites and the presence of frayed illites suggest a detrital origin. At the micro-scale, authigenic kaolinite booklets are observed filling pores and forming mica/kaolinite intergrowths, in which the kaolinite grows between the cleavage sheets of pre-existing detrital mica. At nanometer scale, illite/smectite (IS) phases are detected forming interlayers with mica and kaolinite, and evidence of the replacement of mica by kaolinite is observed. The matrix consists of defective illite and kaolinite, and random mixed layers of kaolinite-I/S (Kln-IS), illite-I/S (Ilt-IS), and I/S-smectite (IS-S). The textures of illite and the presence of different types of mixed layers suggest that the expandable phases and kaolinite are products of mica alteration. The effectivity of the alteration was probably a consequence of the low pH that occurred in the environment due to the presence of abundant organic- and acidic- rich fluids.

Geology and Geochemistry of Selected Gold Deposits in the Ailaoshan Metallogenic Belt, China: Origin of Ore-Forming Fluids

The formation of the Ailaoshan metallogenic belt was the result of: the Neoproterozoic super mantle plume, the Indosinian and South China blocks in the Late Triassic after the Paleo-Tethys Ocean closure, and Oligocene-Eocene continental-scale shearing related to the India-Eurasia collision. It is one of the most important Cenozoic gold ore province in the world. In this paper, the geological characteristics, isotopic geochemistry, and geochemical data of ore-forming fluids of four large-scale gold deposits in the Ailaoshan metallogenic belt (Mojiang Jinchang, Zhenyuan Laowangzhai, Yuanyang Daping, and Jinping Chang’an) are comprehensively compared. The features of host-rock alteration, metallogenetic periods and stages, geochronology, fluid inclusion, and C-H-O-S-Pb isotopes of gold deposits are summarized and analyzed. The gold mineralization in the Ailaoshan metallogenic belt occurred mostly in 50–30 Ma, belonging to the Himalayan period. The gold mineralization is closely related to silicification, argillation, carbonation, and pyritization due to the strong mineralization of hydrothermal fluid, the development of alteration products, and the inconspicuous spatial zonation of alteration types. The ore-forming fluid is mainly composed of mantle fluid (magmatic water) and metamorphic fluid (metamorphic water). The ore-forming materials of the Jinchang, Chang’an, and Laowangzhai gold deposits mainly originate the host-rock strata of the mining area, and the carbon is more likely to from marine carbonate. The carbon in the Daping gold deposit from the original magma formed by the partial melting of the mantle. Pb isotopes have characteristics of crustal origin, accompanied by mixing of mantle-derived materials and multisource sulfur mixing, and are strongly homogenized.

Abstract 12511: Differential Regulation of Circulating Damage-Associated Molecular Patterns in Patients With Coronary Artery Ectasia

Introduction: Coronary artery ectasia (CAE) defined as localized or diffuse non-obstructive coronary lesions is a rare but well-recognized pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE commonly coexists with coronary artery disease (CAD). Although inflammation appears to be involved, the pathophysiology behind CAE remains unclear. Danger-associated molecular patterns (DAMPs) are altered metabolism products of necrotic or stressed cells, which are deemed as alarm signals by the innate immune system. Inflammatory agents are DAMP generators and DAMPs create a pro-inflammatory state. Hypothesis: We aimed to investigate the different patterns of serum DAMPs in patients with CAE, obstructive CAD and normal coronary arteries and the prognostic role of these in the pathogenesis of CAE. Methods: In this prospective cross-sectional study, 28 patients with CAE and nonobstructive CAD were enrolled in the study, 19 patients with obstructive CAD but without CAE, and 18 control subjects with normal coronary arteries that have been matched with the CAE patients for age and sex were also enrolled in our study population. Venous blood samples of the participants were collected for serum DAMP evaluation. Results: Patients with CAE and non-obstructive CAD had increased (30-35%) serum levels of the DAMPs, the receptor for advanced glycation end products (RAGE) ligand S100B and the toll-like receptor 4 ligand heat shock protein (HSP)70 compared to control subjects and patients with CAD. Additionally, CAE and non-obstructive CAD patients had decreased (30-40%) serum levels of potential DAMPs, the antioxidant DJ-1 and soluble (s)RAGE, a decoy molecule that bind excess RAGE ligands, compared to control subjects and CAD patients. Positive correlations were observed between S100B and HSP70 (p=00564), and DJ-1 and sRAGE (p=0.00461). All evaluated serum DAMPs were not different in CAD patients compared to control subjects. Conclusion: The differential regulation of the DAMPs S100B, HSP70, DJ-1 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.

Characterization of Mine Waste from a Former Pb–Zn Mining Site: Reactivity of Minerals During Sequential Extractions

An integrated mineralogical and chemical characterization approach was applied to different types of mine waste collected from the ancient Pb–Zn mining area of Plombières. The combination of different methods to determine (pseudo-)total element concentrations, sequential extractions, and quantitative mineralogical analysis provided detailed information on the reactivity of minerals in the waste, as well as the associated metal(loid) release under different experimental conditions. Lithium borate (LiBO2) fusion was not suited to determine total metal(loid) concentrations in the investigated mine waste samples, due to the incomplete dissolution of the samples, and the volatilization of As and Cd during the fusion. Because some elements were below detection limit of X-ray fluorescence spectrometry (e.g., Cd), aqua regia digestion was useful to complement the chemical sample characterization, bearing in mind that only pseudo-total concentrations could be determined. Galena (PbS) and its alteration products, cerussite and anglesite (PbSO4), were the main lead minerals associated with the mining waste. Because of the high cerussite (PbCO3) content of the investigated samples (2–5 wt%), Pb not only shows the highest potential for recovery from the mining waste, but it also poses the highest environmental and human health risk. Zinc minerals showed a lower reactivity towards the BCR sequential extraction (sphalerite, ZnS) or were less abundant (willemite, Zn2SiO4). Quantitative XRD analysis allowed for better evaluation of the incomplete dissolution of some minerals, improving the interpretation of the sequential extraction results.

Regulation of Notch Signaling By O-Glycans during Lymphopoiesis and Myelopoiesis

IntroductionNotch signaling is essential for the optimal generation of T, B and myeloid cells. Epidermal growth factor-like (EGF) repeats in the extracellular domain of Notch receptors are modified by O-fucose and O-GlcNAc glycans transferred by protein O-fucosyltransferase 1 (POFUT1) and EGF O-GlcNAc-transferase (EOGT), respectively. EOGT promotes Notch ligand binding and Notch signaling in the developing retina in mice, and its loss is the basis of Adam's Oliver Syndrome 4 (AOS4) in humans. The loss of POFUT1 in humans leads to the Dowling Degos Disease 2 (DDD2). Thus, O-fucose and O-GlcNAc glycans may have different functions in Notch signaling, reflected in different requirements for T, B or myeloid cell development.Methods:Eogt control, Eogt null, Pofut1 floxed and Vav1-iCre transgenic mice were used to generate single and compound mutant mice with inactive Eogt, Pofut1 or both Eogt and Pofut1. Antibody markers of hematopoietic stem progenitor cell (HSPC), lymphoid and myeloid subsets were used to identify different T, B and myeloid cell subsets by flow cytometry using the Cytek TM Aurora Flow Cytometer. FCS files were analyzed using FlowJo software (BD). CD45.1+ (B6.SJL-Ptprc a Pepc b/BoyJ #002014) congenic mice were used for bone marrow transfer. Expression of NOTCH1 and binding of soluble Notch ligands to DN T cells was analyzed by flow cytometry. Expression of different Notch target genes was determined using qRT-PCR anlaysis.Results:Eogt null mice exhibited altered production of certain T cell subsets in thymus and B cell subsets in spleen, most similar to alterations observed in mice lacking LFNG, MFNG and RFNG. This phenotype was cell-autonomous as Eogt null bone marrow cells transferred defective T and B cell development to irradiated recipient mice. More severe defects in hematopoiesis were observed in mice conditionally lacking Pofut1 in hematopoietic stem cells (HSC) via Vav1-iCre. However , deletion of both O-fucose and O-GlcNAc glycans together in Eogt:Pofut1 double knockout HSC, led to the most severe decrease in common lymphoid and myeloid progenitors in bone marrow. In thymus, the dramatic reduction in T cell subsets observed in Pofut1 cKO mice was reduced further (in DN2 subsets) in Eogt:Pofut1 dKO mice. In spleen, there was a significantly greater decrease in follicular B and other B cell populations, and a greater increase in CD11b/c+ and Gr1+ myeloid cells in Eogt:Pofut1 dKO mice. Splenomegaly occurred in both Pofut1 cKO and Eogt:Pofut1 dKO mice, with a greater increase in extramedullary hematopoiesis in the dKO spleen. Binding of soluble DLL4-Fc was >90% reduced in Pofut1 cKO DN T cells, and not further reduced in dKO cells, while NOTCH1 expression at the cell surface was only slightly reduced. The relative expression of Notch target genes including Hes1, CD25, cMyc, and Deltex1 was similarly reduced in Pofut1 cKO and Eogt:Pofut1 dKO DN T cell progenitors.Conclsuion:The combined data suggest that O-fucose and O-GlcNAc glycans act in an additive fashion to optimize Notch signaling in lymphoid and myeloid differentiation.Keywords: Notch Signaling, O-Glycans, Protein O-fucosyltransferase 1 (POFUT1), O-GlcNAc transferase (EOGT), Lymphopoiesis, Myelopoiesis. DisclosuresStanley: Aviceda Therapeutics, Inc.: Consultancy, Current holder of stock options in a privately-held company.

Diabase from Drača open pit mine in central Serbia - quality assessment for building stone purposes

Vast masses of basic rocks are present as tectonic blocks and slices along the Eastern deep fault of the Vardar zone of Serbia. They are predominantly comprised of gabbro, with smaller part made up of diabase, and occurrences of granite, aplite and pegmatite dykes. Basic rock masses are trending along the line Kragujevac (Ždraljica)-Velika Pčelica-Bogalinac ~8 km west of Rekovac. A significantly smaller diabase massif is present along the same tectonic line, further toward SE, at Prevešt village by Kalenicka River, approximately 13 km south of Rekovac. Drača open pit mine is situated in this diabase massif. Geologic explorative works have confirmed the reserves of 1 846 695 t of stone mass for building purposes. For over a decade, Draca mine has been producing various types of building stone, mainly graded stone aggregate with favourable physico-mechanical properties for road-construction works. Chemical analyses and petrographic study have shown typical composition and fabric for this type of rock. Main constituents are plagioclase and pyroxene, with opaque minerals as accessory and varying secondary minerals – chlorite, calcite, in some places epidote and limonite. Pyrite enrichment is visible in some areas of the massif. Chlorite, calcite, epidote and pyrite are the products of propylitic alteration. Although products of alteration are present throughout the rock mass with variable intensity, as is typical for the basic rocks of the former ocean floor sequences, petrologic properties are favourable for building stone purposes. Physico-mechanical properties of diabase have favourable values and varying scattering degrees. Dry state uniaxial compressive strength average values from seven analyses vary in the range 130-169 MPa. Resistance to abrasion average values vary in the range 9.04-17.07 cm3/50cm2. Apparent density varies within the span 2759-2926 g/cm3 and real density 2804-2951 g/cm3. Water absorption values 0.08-1.04 %. Resistance to weathering through testing of stability using Sodium-sulphate values vary from 0.00 to 0.15 % and through frost resistance from 0.00 to 0.04 %. Porosity values are almost constant at 0.8 %. In more altered parts of the rock mass, porosity reaches 1.6 %. Graded crushed aggregate has favourable values of Los Angeles coefficient 14.2 and 14.3 % for gradation B. Taking into consideration all performed tests and analyses, it is concluded that diabase from Drača mine can be used as a building stone for production of aggregate for use in concrete and for road-construction (asphalt paving mixtures for moderate, light and very light traffic load as a top wearing layer; for lower and upper bearing layers; for classic and modern road foundations); for production of crushed and hewn stone for building; crushed stone for railroad ballast. Also, it can be and is used as a raw material for production of stone wool for thermal insulation purposes.

Energy Starvation in Daphnia magna from Exposure to a Lithium Cobalt Oxide Nanomaterial.

Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universal─but nonspecific─nanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (γ-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly.