Connective tissue activation

Connective tissue activating peptide-III (CTAP-III) isolated from human platelets is a potent mitogen for human connective tissue cells in culture in addition to stimulating glycosaminoglycan synthesis, glucose consumption, and lactate formation. The amino acid composition of apparently homogeneous CTAP-III was determined, confirming the presence of two disulfide links and providing a calculated molecular weight of 11,633 daltons. Comparison of the mitogenic activity of serum and plasma-serum suggests that CTAP-III is a major mitogenic component of human serum. Seventeen strains of human connective tissue cells (synovial, cartilage, dermal and thyroid) incorporated [ 3 H]-thymidine at up to 30 times control at levels under the influence of microgram quantities of CTAP-III and caused detectable increases in thymidine incorporation at levels as low as 10–29 ng/ml. Prostaglandin E 1 (0.01 Μg/ml) and dibutyryl cyclic AMP (25 Μg/ml) potentiated the glycosaminoglycan stimulating effect of CTAP-III, but not its mitogenic effect. Cycloheximide and actinomycin D blocked the biologic actions of CTAP-III. Cortisol and penicillamine had little effect on the mitogenic activity of CTAP-III, whereas antirheumatic agents such as acetylsalicylic acid and phenylbutazone opposed the mitogenic activity when added to cultures at clinically relevant concentrations. A weak antiheparin factor secreted by platelets, low affinity platelet factor 4 (LA-PF 4 ), was shown to be similar to CTAP-III in biologic actions, electrophoretic mobility, amino acid composition, and antigenic determinants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37739/1/1780220308_ftp.pd

The Base Excision Repair System of Salmonella enterica serovar Typhimurium Counteracts DNA Damage by Host Nitric Oxide

Intracellular pathogens must withstand nitric oxide (NO·) generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS) and possesses multiple systems to detoxify NO·. Consequently, the level of NO· stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER) system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP) sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO· sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO· fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO·–dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO·. These observations demonstrate that host-derived NO· damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Geology of the central Pine Nut and northern Buckskin Ranges, Nevada

Online access for this thesis was created in part with support from the Institute of Museum and Library Services (IMLS) administered by the Nevada State Library, Archives and Public Records through the Library Services and Technology Act (LSTA). To obtain high a quality image or document please contact the DeLaMare Library at https://unr.libanswers.com/ or call: 775-784-6945.The central Pine Nut and northern Buckskin area in Nevada contains early Mesozoic and late Paleozoic metamorphic rocks, Jurassic to mid-Tertiary intrusions, and stratified Cenozoic rocks

Lithium-Rich Claystone in the McDermitt Caldera, Nevada, USA: Geologic, Mineralogical, and Geochemical Characteristics and Possible Origin

Lithium deposits in tuffaceous sediments of the McDermitt caldera constitute possibly the world’s largest Li clay resource, yet their characteristics and origin are not established. The 40 × 25 km McDermitt caldera collapsed during the eruption of ~1000 km3 of a 16.4 Ma, zoned peralkaline to metaluminous tuff; minor caldera magmatism ceased by 16.1 Ma. About 200 m of sediments mostly composed of glass from regional pyroclastic eruptions accumulated in the caldera until about 15.7 Ma. Closed hydrologic system diagenesis (CHSD) altered the tuffaceous sediments to a consistent vertical mineral zonation of clay, analcime, K-feldspar, and albite. Entire sedimentary sections in the southern and western parts of the caldera basin have ≥1500 ppm Li. Lithium-rich intervals are dominantly claystone. The most thoroughly studied deposit is a laterally continuous, ~3000 ppm Li zone in the lower sedimentary section that also has high K, Rb, Mo, As, and Sb (and partly Mg and F). Lithium occurs as an illitic clay (tainiolite?). The overlying, upper sedimentary section averages <2000 ppm Li which resides in smectite (hectorite). A transitional zone has variably mixed smectite–illite clay and averages ~2000 ppm Li. An 40Ar/39Ar age of ~14.9 Ma on authigenic K-feldspar in the illite zone is ~1.2 Ma younger than the 16.1 Ma end of magmatism in the caldera, which mitigates against a simple hydrothermal origin. Closed hydrologic system diagenesis was essential to Li mineralization, but Li budget calculations suggest a source of Li in addition to the tuffaceous sediments is required. This additional source could be Li originally in highly enriched magma that entered the diagenetic system through either (1) Li in magma exsolved into a hydrous volatile phase during eruption. The Li-rich volatile phase coated glass shards or was trapped in pumice and was quickly leached by surface or groundwater upon deposition in the caldera. (2) Residual magma immediately following ash-flow eruption and caldera collapse generated Li-rich hydrothermal fluids that mixed with meteoric water in the closed caldera basin, generating a hybrid diagenetic fluid. The hydrothermal fluid and hybrid diagenetic fluids would have existed only during initial basin sedimentation between about 16.4 and 16.1 Ma

United States Department of Energy Grand Junction Office Report PGJ/F-135(82)

From Introduction: "The Vya 2º quadrangle (Fig. 1), in northwestern Nevada and small portions of California and Oregon, was evaluated to identify geologic environments and to delineate areas that have characteristics favorable for uranium deposits. Reconnaissance sampling in the Vya Quadrangle began in 1978, but final evaluation of the uranium favorability of the quadrangle was began in 1978, but final evaluation of the uranium favorability of the quadrangle was begun in June 1980.

United States Department of Energy Grand Junction Office Report PGJ/F-061(82)

From Introduction: "The Klamath Falls Quadrangle, in south-central Oregon between lat 42º and 43º N. and long 120º and 122º W. (Fig. 1), was evaluated to identify geologic environments and delineate areas with characteristics favorable for the occurrence of uranium deposits.