We used molecular cloning and functional analyses to extend the family of Neu differentiation factors (NDFs) and to explore the biochemical activity of different NDF isoforms. Exhaustive cloning revealed the existence of six distinct fibroblastic pro-NDFs, whose basic transmembrane structure includes an immunoglobulin-like motif and an epidermal growth factor (EGF)-like domain. Structural variation is confined to three domains: the C-terminal portion of the EGF-like domain (isoforms a and 0), the adjacent juxtamembrane stretch (isoforms 1 to 4), and the variable-length cytoplasmic domain (isoforms a, b, and c). Only certain combinations of the variable domains exist, and they display partial tissue specificity in their expression:pro-NDF-a2 is the predominant form in mesenchymal cells, whereas pro-NDF-01 is the major neuronal isoform. Only the transmembrane isoforms were glycosylated and secreted as biologically active 44-kDa glycoproteins, implying that the transmembrane domain functions as an internal signal peptide. Extensive glycosylation precedes proteolytic cleavage of pro-NDF but has no effect on receptor binding. By contrast, the EGF-like domain fully retains receptor binding activity when expressed separately, but its I-type C terminus displays higher aflinity than a-type NDFs. Likewise, structural heterogeneity of the cytoplasmic tails may determine isoform-specific rate of pro-NDF processing. Taken together, these results suggest that different NDF isoforms are generated by alternative splicing and perfonn distinct tissue-specific functions.The neu proto-oncogene (also known as HER-2 or c-erbB-2) encodes a 185-kDa receptor tyrosine kinase. The transmembrane glycoprotein is present in many epithelial and neural tissues (6,13,18,22,27,28,33,34). Although adult tissues generally exhibit a lower level of pl85seu expression than corresponding fetal tissues, pl85neu expression levels are frequently elevated in certain human neoplasms. Overexpression of pl85neu occurs in approximately 20% of breast, stomach, pancreatic, bladder, and ovarian carcinomas (20) and is associated with poor prognosis for breast and ovarian cancers. Increased pl85neu expression also occurs in certain nonmalignant neoplasias, such as adenomatous polyps (5, 7), Barrett's esophagus (17), and polycystic kidneys (14).Many growth factors, cytokines, and neurotrophic factors activate receptor tyrosine kinases. The activated receptors become phosphorylated on tyrosine residues, thereby initiating intracellular signaling, leading to cellular responses (4,35). Phosphorylation of the pl85neu receptor on tyrosine residues can be stimulated by proteins purified from several sources (9,15,16,21,30). Purification of the rat and human p185neu stimulatory proteins led to the isolation of cDNAs encoding novel epidermal growth factor (EGF)-related proteins (15,30,36). The 44-kDa rat factor, named Neu differentiation factor (NDF), stimulates pl85neu tyrosine phosphorylation and induces the production of milk components (casein and lipids) in certain br...

Preparation of Nickel-substituted Goethite and Hematite Ni(II)-substituted goethite and hematite samples used for kinetic release experiments were prepared using modified previously reported methods (Schwertmann and Cornell, 2000). Ni(II)-goethite was synthesized by slowly adding 125 mL of a solution containing 0.98 M ferric nitrate and 0.02 M Ni(II) chloride to 225 mL of 5 M NaOH. The slurry was then diluted to 1 L and placed in an oven at 70 °C for 5 days. Ni(II)-hematite was prepared by slowly adding 600 mL of a solution containing 0.198 M ferric nitrate and 0.002 M Ni(II) chloride to 360 mL of 1 M NaOH. The pH of this slurry was then adjusted to 8.5 by dropwise addition of 1.0 or 0.1 M NaOH. The suspension was then placed in an oven set to 98 °C for 11 days. Once removed from the oven and cooled to room temperature, both materials were treated with 0.25 M HCl for 2 hr using a solid to solution ratio of 1:100. This acid treatment was employed to remove residual adsorbed cations and amorphous Ni-containing iron oxides. The materials were then washed with DI water by centrifugation until a pH of >5 was achieved. The solids were resuspened into 250 mL of DI water and stored as a suspension until further use. An aliquot was removed and oven dried at 70 °C to obtain powder that was used for sample characterization. Mineral surface area (Table DR1) was determined by collecting nitrogen B.E.T. adsorption isotherms at 77 K using a Quantachrome instruments Autosorb-1. X-ray diffraction (Rigaku Geigerflex D-MAX/A diffractometer using Cu-Kα radiation) confirmed that the Ni-substituted Fe oxides consisted of goethite or hematite and contained no other crystalline impurities. Ni content (Table DR1) was determined by inductively-coupled plasma optical emission spectrometry (ICP-OES, Perkin-Elmer Optima 7300DV) after digestion of the solid in a 20% HNO 3 :5% HCl (trace metal grade, Fisher Scientific) mixture. The digested sample liquid was diluted as necessary before analysis. Fe(II)-catalyzed Nickel Incorporation into Goethite and Hematite All experiments were conducted under anoxic conditions in an anaerobic chamber (Coy Laboratory Products, Inc.) containing a 3% H 2 /97% N 2 atmosphere with a Pd catalyst to eliminate residual O 2. Doubly deionized water (18.2 MΩ cm) was sparged with ultra-high purity N 2 gas prior to being brought into the anaerobic chamber. Trace oxygen levels in the chamber atmosphere were further lowered by a secondary oxygen trap; the chamber atmosphere was bubbled in sequence through a 15% pyrogallol/ 50% KOH solution and deionized water. The KOH solution also served to remove trace amounts of CO 2 from the chamber. The filtered gas stream was used to re-sparge and further deoxygenate the deionized water and any solution not prepared in the chamber. Dissolved oxygen content of the deionized water was estimated colorimetrically (CHEMetrics test kit K-7511) and all analyses were below the detection limit of 1 μg/L. Fe(II) stock solutions were prepared from deoxygenated deionized water and reagentgrade ...

ObjectiveWe sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with covid-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic).MethodsWe prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit.ResultsA total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34–62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury.ConclusionAcute myocardial injury is common in patients with covid-19 and is associated with adverse prognosis.

Triplet–triplet annihilation (TTA) is studied in a wide range of fluorescent host:guest emitter systems used in organic light‐emitting devices (OLEDs). Strong TTA is observed in host:guest systems in which the dopant has a limited charge‐trapping capability. On the other hand, systems in which the dopant can efficiently trap charges show insignificant TTA, an effect that is due, in part, to the efficient quenching of triplet excitons by the trapped charges. Fluorescent host:guest systems with the strongest TTA are found to give the highest OLED electroluminescence efficiency, a phenomenon attributed to the role of TTA in converting triplet excitons into additional singlet excitons, thus appreciably contributing to the light output of OLEDs. The results shed light on and give direct evidence for the phenomena behind the recently reported very high efficiencies attainable in fluorescent host:guest OLEDs with quantum efficiencies exceeding the classical 25% theoretical limit.

Delayed electroluminescence measurements are used to probe and differentiate between triplet-triplet-annihilation (TTA) and triplet-polaron-quenching (TPQ) processes and their correlation with efficiency roll-off in fac-tris(2-phenylpyridine) iridium-based phosphorescent organic light emitting devices. Investigations on devices employing 4,4′-bis(9-carbazolyl)-1,1′-biphenyl (CBP) and 4,4′,4″-tris(N-carbazolyl) triphenylamine, two widely used host materials, show that the efficiency roll-off is primarily due to TPQ processes. Guest-guest TTA, on the other hand, is found to play no major role, contrary to speculations, especially at low guest concentrations. Evidence of host-host TTA in certain cases, and its possible contribution to exciton quenching in the case of devices with CBP host, is also reported.

Proteinase-activated receptor 2 (PAR2) is a G proteincoupled receptor that is activated by trypsin-like proteinases. PAR2 is detected in breast tumor specimens; however, it is not clear how PAR2 level in breast cancer cell/tissues compares with normal cell/tissues. Here, we show the elevation of PAR2 protein level in 76 of 105 breast tumor specimens but only 5 of 24 normal breast tissues. PAR2 level is also higher in breast cancer cell lines than that in normal breast cells and non-cancerous breast cell lines. To determine the role of PAR2 in breast carcinogenesis, we examined the effect of PAR2 agonists on cell proliferation and migration. Our studies show that PAR2 agonists (PAR2-activating peptide and trypsin) are neither potent growth enhancers nor chemoattractants to breast cancer cells. Instead, PAR2 agonists induce significant chemokinesis. PAR2-mediated chemokinesis is G ai -dependent, and inhibiting Src kinase activity or silencing c-Src expression blocks PAR2-mediated chemokinesis. These results suggest that c-Src works downstream of G ai to mediate this PAR2 agonist-induced event. To characterize c-Src effector, we reveal that PAR2 agonists activate JNKs in a Src-dependent manner and that JNK activity is essential for PAR2-mediated chemokinesis. Moreover, PAR2 agonist stimulation leads to paxillin Ser 178 phosphorylation and paxillin(S178A) mutant inhibits PAR2-mediated chemokinesis. In conclusion, our studies show that PAR2 agonists facilitate breast cancer cell chemokinesis through the G ai -c-Src-JNKpaxillin signaling pathway.

A major environmental concern associated with coal fly ash is the mobilization of trace elements that may contaminate water. To better evaluate proper use of fly ash, determine appropriate disposal methods, and monitor postdisposal conditions, it is important to understand the speciation of trace elements in fly ash and their possible environmental impact. The speciation of selenium, arsenic, and zinc was determined in five representative Class C fly ash samples from combustion of subbituminous Powder River Basin coal using synchrotron-based X-ray absorption spectroscopy to provide an improved understanding of the mechanisms of trace element association with the fly ash. Selenium in all fly ash samples occurs predominantly as Se(IV), with the exception of one sample, in which there was a minor amount of Se(0). Se(0) is likely associated with the high content of unburned coal in the sample. Arsenic exists in the fly ash as a single phase most consistent with calcium pyroarsenate. In contrast, zinc occurs as two distinct species in the silicate glass matrix of the fly ash. This work demonstrates that residual carbon in fly ash may reduce potential Se mobility in the environment by retaining it as less soluble elemental Se instead of Se(IV). Further, this work suggests that As and Zn in Class C fly ash will display substantially different release and mobilization behaviors in aquatic environments. While As release will primarily depend upon the dissolution and hydrolysis of calcium pyroarsenate, Zn release will be controlled by the dissolution of alkaline aluminosilicate glass in the ash.

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