Self-degradation of heat shock proteins

The 70-kDa heat shock protein of Drosophila decays in vivo at a much faster rate than other abundantly labeled proteins. Degradation also occurs in vitro, even during electrophoresis. It appears that this degradation is not mediated by a general protease and that the 70-kDa heat shock protein has a slow proteolytic action upon itself. Heat-induced proteins in CHO cells and a mouse cell line also degrade spontaneously in vitro, as do certain non-heat shock proteins from Drosophila tissues as well as the cell lines

Control of the colossal magnetoresistance by strain effect in Nd0.5_{0.5}Ca0.5_{0.5}MnO3_{3} thin films

Thin films of Nd$_{0.5}$Ca$_{0.5}$MnO$_{3}$ manganites with colossal magnetoresistance (CMR) properties have been synthesized by the Pulsed Laser Deposition technique on (100)-SrTiO$_{3}$. The lattice parameters of these manganites and correlatively their CMR properties can be controlled by the substrate temperature $T_{S}$. The maximum CMR effect at 75K, calculated as the ratio $\rho (H=0T)/\rho (H=7T)$ is 10$^4$ for a deposition temperature of $T_{S}=680$ degC. Structural studies show that the Nd$_{0.5}$Ca$_{0.5}$MnO$_{3}$ film is single phase, [010]-oriented and has a pseudocubic symmetry of the perovskite subcell with a=3.77$\AA$ at room temperature. We suggest that correlation between lattice parameters, CMR and substrate temperature $T_{S}$ result mainly from substrate-induced strains which can weaken the charge-ordered state at low temperature.Comment: 9 pages, 4 figures. To be published in Applied Physics Letter

Stress deformations and structural quenching in Sm0.5Ca0.5MnO3 thin films allow a huge decrease of the charge order melting magnetic field

Thin films of Sm0.5Ca0.5MnO3 manganites with charge ordering (CO) properties and colossal magnetoresistance were synthesized by pulsed laser deposition technique on (100)-SrTiO3 and (100)-LaAlO3 substrates. We first compare the structural modifications as function of the substrate and film thickness. Secondly, measuring transport properties in magnetic fields up to 24T, we establish the temperature-field phase diagram describing the stability of the CO state and compare it to bulk material. We show that some structural modification induced by the substrate occurs and that the CO melting magnetic field is greatly reduced. Moreover, with the temperature decrease, no modification of the lattice parameters is observed. We then propose an explanation based on the quenching of the unit cell of the film that adopts the in-plane lattice parameters of the substrate and thus, prevents the complete growth of the CO state at low temperature.Comment: to be published in Journal of Applied Physic

Risk factors for liposomal bupivacaine resistance after total hip or knee arthroplasties: A retrospective observational cohort in 237 patients

Purpose: Liposomal bupivacaine demonstrated promise decreasing postoperative pain in total hip and total knee arthroplasty (THA/TKA). Some randomized trials have shown non-superior results; however, confounding variables were not accounted for in such analyses. This study attempts to determine risk factors associated with failure of pain management in patients receiving liposomal bupivacaine. Methods: Postoperative pain scores were collected following primary or revision arthroplasties between January 2016 and December 2017. Retrospective analysis of institutional total joint quality and outcomes registry was screened and patients undergoing primary or revision arthroplasties who completed a multi-modal pain management including liposomal bupivacaine were included in the study. Patients with a history of infection/deviated from the institutional pain management protocol were excluded. Results: A total of 237 patients were included for analysis. Younger patients less than 64 years old had significantly higher pain scores between 0 and 12 h and \u3e 24 h. Active smokers had significantly higher pain scores between 0 and 6 h and \u3e 24 h. Patients with a history of opioid use/pain management had significantly higher pain scores at 6-12 h and 24-48 h. Regression analysis indicated risk factors for resistance to liposomal bupivacaine are younger patients less than 64 years old, those undergoing primary THA, and patients with a history of smoking/pain management/opioid use. Conclusion: We identify risk factors for resistance to liposomal bupivacaine, which include younger age less than 64 years old, history of smoking/pain management/opioid use. Future studies should use these risk factors as exclusion criteria when using liposomal bupivacaine or initiating any randomized trials regarding efficacy

Orbital Ordering Structures in (Nd,Pr)0.5Sr0.5MnO3 Manganite Thin Films on Perovskite (011) Substrates

Structural study of orbital-ordered manganite thin films has been conducted using synchrotron radiation, and a ground state electronic phase diagram is made. The lattice parameters of four manganite thin films, Nd0.5Sr0.5MnO3 (NSMO) or Pr0.5Sr0.5MnO3 (PSMO) on (011) surfaces of SrTiO3 (STO) or [(LaAlO3){0.3}(SrAl0.5Ta0.5O3){0.7}] (LSAT), were measured as a function of temperature. The result shows, as expected based on previous knowledge of bulk materials, that the films' resistivity is closely related to their structures. Observed superlattice reflections indicate that NSMO thin films have an antiferro-orbital-ordered phase as their low-temperature phase while PSMO film on LSAT has a ferro-orbital-ordered phase, and that on STO has no orbital-ordered phase. A metallic ground state was observed only in films having a narrow region of A-site ion radius, while larger ions favor ferro-orbital-ordered structure and smaller ions stabilize antiferro-orbital-ordered structure. The key to the orbital-ordering transition in (011) film is found to be the in-plane displacement along [0-1 1] direction.Comment: 19pages, 11 figure

High magnetic field transport measurement of charge-ordered Pr0.5_{0.5}Ca0.5_{0.5}MnO3_3 strained thin films

We have investigated the magnetic-field-induced phase transition of charge-ordered (CO) Pr$_{0.5}$Ca$_{0.5}$MnO$_3$ thin films, deposited onto (100)-oriented LaAlO$_3$ and (100)-oriented SrTiO$_3$ substrates using the pulsed laser deposition technique, by measuring the transport properties with magnetic fields up to 22T. The transition to a metallic state is observed on both substrates by application of a critical magnetic field ($H_C>10T$ at 60K). The value of the field required to destroy the charge-ordered insulating state, lower than the bulk compound, depends on both the substrate and the thickness of the film. The difference of the critical magnetic field between the films and the bulk material is explained by the difference of in-plane parameters at low temperature (below the CO transition). Finally, these results confirm that the robustness of the CO state, depends mainly on the stress induced by the difference in the thermal dilatations between the film and the substrate.Comment: 10 pages, 6 figures. To be published in Phys. Rev.

Synthesis of new organoelement copolymers based on polydimethylsiloxanes and aminophosphonates

© 2018 Based on commercially available 3-Aminopropyl (diethoxy)methylsilane new alkoxysilane with functional aminophosphonate group - diethyl (2-((3-(diethoxy (methyl)silyl)propyl)amino)propan-2-yl)phosphonate were synthesized and characterized. Obtained functional alkoxysilane were transformed to tetrasiloxane in active medium in the presence of acetic acid and then copolymerized with octamethylcyclotetrasiloxane (D4). The chemical structure of the resulting polymer was studied and confirmed by a combination of physical methods, namely,1H,13C,31P and29Si NMR, GPC, and IR spectroscopy. The thermophysical and rheological properties of the polymer were also studied

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay: Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer

BACKGROUND: Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/or early recurrence. Herein we present a method for detecting microinsertions/deletions/indels (MIDIs) at ultra-high analytical selectivity. MIDIs comprise about 15% of mutations. METHODS AND FINDINGS: We describe MIDI-Activated Pyrophosphorolysis (MAP), a method of ultra-high analytical selectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplex slippage and mis-pyrophosphorolysis. MAP generally has an analytical selectivity of one mutant molecule per >1 billion wild type molecules and an analytical sensitivity of one mutant molecule per reaction. The analytical selectivity of MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allele specific amplification (PAP-A) for detecting MIDIs. The utility of this method is illustrated in two ways. 1) We demonstrate that two EGFR deletions commonly found in lung cancers are not present in tissue from four normal human lungs (10(7) copies of gDNA each) or in blood samples from 10 healthy individuals (10(7) copies of gDNA each). This is inconsistent, at least at an analytical sensitivity of 10(-7), with the hypotheses of (a) hypermutation or (b) strong selection of these growth factor-mutated cells during normal lung development leads to accumulation of pre-neoplastic cells with these EGFR mutations, which sometimes can lead to lung cancer in late adulthood. Moreover, MAP was used for large scale, high throughput "gene pool" analysis. No germline or early embryonic somatic mosaic mutation was detected (at a frequency of >0.3%) for the 15/18 bp EGFR deletion mutations in 6,400 individuals, suggesting that early embryonic EGFR somatic mutation is very rare, inconsistent with hypermutation or strong selection of these deletions in the embryo. 2) The second illustration of MAP utility is in personalized monitoring of therapy and early recurrence in cancer. Tumor-specific p53 mutations identified at diagnosis in the plasma of six patients with stage II and III breast cancer were undetectable after therapy in four women, consistent with clinical remission, and continued to be detected after treatment in two others, reflecting tumor progression. CONCLUSIONS: MAP has an analytical selectivity of one part per billion for detection of MIDIs and an analytical sensitivity of one molecule. MAP provides a general tool for monitoring ultra-rare mutations in tissues and blood. As an example, we show that the personalized cancer signature in six out of six patients with non-metastatic breast cancer can be detected and that levels over time are correlated with the clinical course of disease