The PDZ-LIM protein CLP36 is required for actin stress fiber formation and focal adhesion assembly in BeWo cells.
CLP36 belongs to the ALP subfamily of PDZ-LIM proteins and has a PDZ domain at its N-terminal and a LIM domain at its C-terminal. It has been shown that CLP36 is localized to stress fibers through interaction with alpha-actinin, but its function is still unclear. To investigate the role of CLP36 in stress fibers, we suppressed CLP36 expression in BeWo cells by RNAi and examined the phenotypic changes. CLP36-knockdown resulted in cell spreading and the loss of stress fibers and focal adhesions. These changes were reversed by addition of exogenous CLP36, but not by addition of mutant forms of CLP36 that lacked the PDZ or LIM domain. These findings indicate that CLP36 plays a critical role in stress fiber formation and the assembly of focal adhesions in BeWo cells. In addition, the PDZ and LIM domains are both essential for CLP36 to function.


Multifocal contact lenses: A bibliometric study.
To analyze the state of scientific publications in multifocal contact lenses field through a bibliometric study. The database used to carry out the study was SCOPUS and contained the descriptors "multifocal contact lens", "bifocal contact lenses", "progressive contact lenses" and "presbyopia contact lenses", limited to the fields of title, keywords and abstract. The indicators applied in this research were: doubling time and annual growth rate, Price's transience index, Lotka's law of scientific productivity, and Bradford's zones. A total of 346 articles were published between 1960 and 2019. The growth in the number of publications matches the exponential adjustment slightly better (R = 0.53). The duplication time was 13.2 years. The productivity level is focused on articles with an average number of authors of just 2.06 per article. The Bradford core was formed by two journals, Optometry and Vision Science and Eye and Contact Lens. Research on multifocal contact lenses has exponential growth, without evidence of having reached a saturation point. The main countries in scientific production in this field are the United States and Australia.


DNA methylation remodeling in vitro and in vivo.
In mammals, global DNA demethylation in vivo occurs in the pre-implantation embryo and in primordial germ cells (PGCs) where it is hypothesized to create a blank slate or 'tabula rasa' upon which new DNA methylation patterns are written. However, global DNA demethylation in vivo is far from complete with a small number of loci protected from demethylation. Failure to demethylate, or overt demethylation results in compromised differentiation. Recent work has shown that reversion of primed human pluripotent stem cells to the naïve state leads to unbridled DNA demethylation which has unknown consequences on the quality differentiated cells created in vitro. Taken together understanding DNA methylation remodeling is critical for understanding the epigenetic foundations of life, and the quality of stem cells for regenerative medicine.


Proximal Gastrectomy with Double Tract Reconstruction Is an Alternative Revision Surgery for Intractable Complications After Sleeve Gastrectomy.
Gastric leakage and stricture are challenging complications of sleeve gastrectomy (SG). Failure of endoscopic intervention necessitates revision surgery. We describe two cases in which proximal gastrectomy with double tract reconstruction (PG with DTR) was performed in patients with chronic gastric fistula and twisted gastric tube after SG. Following resection of the affected part of the proximal stomach, reconstruction was achieved with three anastomoses [esophagojejunostomy (EJ), gastrojejunostomy (GJ), and jejunojejunostomy]. DTR provides two exit routes, the remnant stomach and the distal jejunum. The GJ was created 15 cm below the EJ with a stoma 10 mm in diameter, which can pass a standard endoscope. Both cases were a success without any short-term complications. PG with DTR could be an alternative option for refractory complications of SG.


Medical imaging community outreach program: lesson to students and impact to the community.
The community outreach program is one of the main activities of the University of Rwanda, and both staff and students get involved in this tremendous initiative to serve the community free of charge. The main objectives of this community engagement activity were to raise awareness of medical imaging services and abdominal ultrasound screening. The project proposal was planned by the Medical Imaging Department, University of Rwanda College of Medicine and Health Sciences, Remera Campus. It took place at Kigali's main car park. Two ultrasound machines were used, and screening was done by students under supervision of registered sonographers. A cross-sectional design with random sampling was employed, and SPSS version 21 was used for data analysis. Statistical techniques were used to calculate inter-observer reliability by comparing patient complaints and sonographic diagnosis. Herein we report the first medical imaging community outreach, on which 86 patients received ultrasound abdominal scans free of charge. Of these, 33 (38.5%) were male and 53 (61.5%) were female. Their ages varied from 20 to 76 years, with a mean age of 48. The screened organs included the liver, gall bladder, pancreas, spleen, kidneys, urinary bladder, prostate, uterus and ovaries, and abnormalities were identified in different organs. The results showed a high degree of reliability between what was presented by the patients and measurements found after diagnosis by the sonographer. The average measure of the intraclass correlation coefficient was 0.973, with 95% confidence intervals ranging from 0.959 to 0.983 (F (85,85) = 37.537, p < 0.001). This experience was beneficial to the Medical Imaging Sciences Department staff and students, as well as to the Society of Medical Imaging and Radiation in Rwanda. The results showed that this outreach was also very positive for the community at large.


Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells.
Presence of cytoplasmic tau aggregates is a hallmark of brains in patients with tauopathies such as Alzheimer's disease. However, the mechanism underlying formation of these insoluble tau aggregates remains elusive. In this study, we investigated the impact of prolonged nitric oxide (NO) exposure on neuronal SH-SY5Y cells overexpressing human tau. Treatment with the NO donor DETA NONOate for up to 48h resulted in an increase in S-nitrosation of cellular proteins, inactivation of proteasome, and impairment of respiration. Western blot analysis of Triton X-soluble fractions of NO-treated cells revealed that persistent NO treatment increased heterogeneity in tau molecule size, as a result of dephosphorylation, and induced the formation of sodium dodecyl sulfate (SDS)-stable oligomeric tau aggregates, stabilized by disulfide bonds. Moreover, further NO treatment induced the formation of SDS-stable insoluble tau mega-aggregates that were composed of dephosphorylated full-length tau molecules and other proteins, and were stabilized through disulfide bonds. Evaluation of the role of these tau aggregates as potential seeds for tau fibrillization and elucidation of their formation mechanism in our model, could lead to better understanding of the pathogenesis of tauopathies.


Bioavailability and disposition of metoclopramide after single- and multiple-dose administration in diabetic patients with gastroparesis.
The disposition of metoclopramide after acute and chronic administration was determined in four diabetic patients with gastroparesis who had a creatinine clearance of 70.8 +/- 10.7 mL/min (mean +/- SD). Single, 10-mg oral and intravenous doses were administered on days 1 and 2, respectively, followed by 10 mg orally every six hours for three weeks. A second, 10-mg intravenous bolus dose was administered on the last morning of chronic therapy. Metoclopramide concentrations were determined by high performance liquid chromatography. The elimination half-life, steady-state volume of distribution, and total body clearance after the initial intravenous dose were 3.9 +/- 1.2 hr, 2.7 +/- 0.3 L/kg, and 0.57 +/- 0.14 L/hr/kg, respectively. The initial bioavailability was 67.7 +/- 12.6%. After three weeks of chronic therapy, no significant differences in total body clearance (0.72 +/- 0.42 L/hr/kg) or bioavailability (77.5 +/- 16.8%) were observed. Thus the pharmacokinetics and bioavailability of metoclopramide were not altered during chronic therapy in these diabetic patients.


Effect of preganglionic stimulation or chronic decentralization on neurotensin-like immunoreactivity in sympathetic ganglia of the cat.
In pentobarbital-anesthetized cats, supramaximal stimulation (40 Hz, 2 h) of the preganglionic input to the acutely decentralized right stellate (RSG) or superior cervical (RSCG) ganglion resulted in a decrease in neurotensin (NT)-like immunoreactivity (IR), by 83% in the SG and by 46% in the SCG, as determined by radioimmunoassay. Chronic (7 days) decentralization of the ganglia resulted in a similar depletion of NT-like IR (SG: 86%; SCG: 76%). Supramaximal stimulation (40 Hz, 2 h) of the intact postganglionic outflow of either ganglion had no effect on NT-like IR. These data suggest that NT in the SG and SCG is present in preganglionic axons and is released by activation of these axons.


A mechanical momentum in ultrastructural development of the heart.
The question of whether mechanical moments participate in ultrastructural development of the heart cannot be decided by examining heart tissue samples during embryonic life, for during maturation processes in vivo mechanical factors are always present. The significance of mechanical moments can only be investigated in a system which allows a distinction to be made between pulsations of heart myocytes under conditions of contraction against and under conditions of contraction without mechanical stress. This double possibility is provided by cell culture. An example in which mechanical influences are absent are the so-called "minihearts"; these are cell agglomerations which are detached from the culture substrate. Their cell contractions do not act against any mechanical resistance. In the electron microscope they show abundant filaments, Z-line material and membrane specializations. The highest degree of development, however, does not exceed that characterizing the cells with which the cultures were started. Even some dedifferentiation and degeneration are apparent in the minihearts. No intercalated discs can be found even after 12 weeks, provided that the culture had been started with really isolated cells. The representatives in culture of a myocyte's connection with the heart's mechanical action are the cords, along which attached points alternate with free strands. The pulsation of these strands is restrained during each contraction by their ends, which are fixed on the culture substrate. Thus, the myocytes contract against a resistance, and in this respect their pulsations resemble those of the heart, in which the myocytes' contraction acts against the pressure of the blood. The myocyte culture under these mechanical condition, after a culture time of 10 weeks, produces electron micrographs of mature cells with reduced cytoplasm, aligned mitochondria and fibrils and intercalated discs.


Commercial octopus species from different geographical origins: Levels of polycyclic aromatic hydrocarbons and potential health risks for consumers.
Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants that have been raising global concern due to their carcinogenic and mutagenic properties. A total of 18 PAHs (16 USEPA priority compounds, benzo(j)fluoranthene and dibenzo(a,l)pyrene) were assessed in the edible tissues of raw octopus (Octopus vulgaris, Octopus maya, and Eledone cirrhosa) from six geographical origins available to Portuguese consumers. Inter- and intra-species comparison was statistically performed. The concentrations of total PAHs (∑PAHs) ranged between 8.59 and 12.8 μg/kg w.w. Octopus vulgaris caught in northwest Atlantic Ocean presented ΣPAHs significantly higher than those captured in Pacific Ocean and Mediterranean Sea, as well as than the other characterized species from western central and northeast Atlantic Ocean. PAHs with 2-3 rings were the predominant compounds (86-92% of ∑PAHs) but diagnostic ratios indicated the existence of pyrogenic sources in addition to petrogenic sources. Known and possible/probable carcinogenic compounds represented 11-21% of ΣPAHs. World and Portuguese per capita ingestion of ∑PAHs due to cephalopods consumption varied between 1.62-2.55 × 10-4 and 7.09-11.2 × 10-4 μg/kg body weight per day, respectively. Potential risks estimated for low and high consumers according to USEPA methodology suggested that a regular consumption of raw octopus does not pose public health risks.


De novo protein folding on computers. Benefits and challenges.
There has been recent success in prediction of the three-dimensional folded native structures of proteins, most famously by the AlphaFold Algorithm running on Google's/Alphabet's DeepMind computer. However, this largely involves machine learning of protein structures and is not a de novo protein structure prediction method for predicting three-dimensional structures from amino acid residue sequences. A de novo approach would be based almost entirely on general principles of energy and entropy that govern protein folding energetics, and importantly do so without the use of the amino acid sequences and structural features of other proteins. Most consider that problem as still unsolved even though it has occupied leading scientists for decades. Many consider that it remains one of the major outstanding issues in modern science. There is crucial continuing help from experimental findings on protein unfolding and refolding in the laboratory, but only to a limited extent because many researchers consider that the speed by which real proteins folds themselves, often from milliseconds to minutes, is itself still not fully understood. This is unfortunate, because a practical solution to the problem would probably have a major effect on personalized medicine, the pharmaceutical industry, biotechnology, and nanotechnology, including for example "smaller" tasks such as better modeling of flexible "unfolded" regions of the SARS-COV-2 spike glycoprotein when interacting with its cell receptor, antibodies, and therapeutic agents. Some important ideas from earlier studies are given before moving on to lessons from periodic and aperiodic crystals, and a possible role for quantum phenomena. The conclusion is that better computation of entropy should be the priority, though that is presented guardedly.


The psbA-gene from a red alga resembles those from cyanobacteria and cyanelles.
Plastid DNA (ptDNA) from the unicellular red alga Cyanidium caldarium was isolated. A 5.8 kb Eco RI, fragment containing the entire psbA-gene was cloned and the nucleotide sequence of the psbA-gene determined. At the carboxyl terminus the encoded protein (D1) contains the seven amino acid-insertion which was found to be typical of the cyanobacteria and the cyanelles of Cyanophora paradoxa. However, the overall sequence homology does not support a direct relationship between the plastids of Cyanidium, cyanelles and the cyanobacteria. As in other photosynthetic organisms the psbA-gene is transcribed as a monocistronic mRNA. The ribosomal RNA operon was located 4 kb upstream of the psbA-gene.


Structural equation modelling of work related musculoskeletal disorders among dumper operators.
The aim of this study is to investigate the impact of personal factors, habitual factors, and work-related factors on work-related musculoskeletal disorders (WRMSDs) among dumper operators. In total, 248 dumper operators working in an iron ore mine were considered for this study. A questionnaire was developed and administered to collect dumper operators' personal, habitual, and work-related data. The reliability of the questionnaire was cross-checked by Cronbach alpha and the test-retest method. The values of Cronbach alpha for all latent variables were above 0.7, and the correlation coefficient of the questionnaire items at Time 1 and Time 2 was above 0.82. After verifying the validity (i.e., convergent and divergent) of the questionnaire data, the relationship between the factors under consideration was examined by structural equation modeling (SEM). The SEM demonstrated a moderate fit, with [Formula: see text] value of 1.386, comparative fit index (CFI) of 0.86, goodness-of-fit index (GFI) of 0.72, adjusted goodness-of-fit index (AGFI) of 0.69, Tucker-Lewis Index (TLI) of 0.83, normed fit index (NFI) of 0.71 and root mean square error of approximation (RMSEA) of 0.051. The SEM analysis revealed a positive relationship between WRMSDs and personal factors (with path coefficient = 0.313 and p < 0.05) as well as work-related factors (with path coefficient = 0.296 and p < 0.05). However, the relationship between WRMSDs and habitual factors was not statistically significant (with path coefficient = 0.142 and p > 0.05). Overall, this study provides valuable insights into the factors that influence the prevalence of WRMSDs among dumper operators. The findings highlight the significance of personal and work-related factors by which one can make a positive decision to prevent and reduce the incidence of WRMSDs among dumper operators.


A critical look at the embodied cognition hypothesis and a new proposal for grounding conceptual content.
Many studies have demonstrated that the sensory and motor systems are activated during conceptual processing. Such results have been interpreted as indicating that concepts, and important aspects of cognition more broadly, are embodied. That conclusion does not follow from the empirical evidence. The reason why is that the empirical evidence can equally be accommodated by a 'disembodied' view of conceptual representation that makes explicit assumptions about spreading activation between the conceptual and sensory and motor systems. At the same time, the strong form of the embodied cognition hypothesis is at variance with currently available neuropsychological evidence. We suggest a middle ground between the embodied and disembodied cognition hypotheses--grounding by interaction. This hypothesis combines the view that concepts are, at some level, 'abstract' and 'symbolic', with the idea that sensory and motor information may 'instantiate' online conceptual processing.


Depth of invasion for appendiceal metastasis of ovarian cancers: does it have any clinical significance?
Depth of appendiceal metastasis in patients with epithelial ovarian carcinoma (EOC) has not been previously analyzed for a possible relationship with clinico-pathological variables. Sixty-nine patients with EOC treated at Hacettepe University were retrospectively analyzed. All of the patients had appendiceal metastasis. Pathological slides were re-reviewed by the same pathologist. Appendiceal metastases were defined as serosal (if tumoral spread involved only serosa of the appendix) or sero-mucosal (if tumoral spread also involved either muscular or mucosal surfaces of the appendix). Univariate and multivariate analysis did not reveal a significant difference with respect to the prognostic variables between the groups. Thirty-nine patients had serosal appendiceal metastasis (56.5%), while the remaining 30 patients (43.5%) had appendiceal metastasis extending toward the muscular layer (seromucosal metastasis: 16 within muscularis mucosa, 14 within the mucosa of the appendix). The mean age at the time of diagnosis was 54.58 years (range, 26-88 years), with no significant difference between the groups (P = 0.9). Comparison of the survival rates between the two groups did not reveal a significant difference. Three-year survival rates were 23.3% in the serosal metastasis and 27.9% in the seromucosal metastasis group (P = 0.9). This figure was 25% for patients with only muscular metastasis and 41.6% for patients with appendiceal metastasis extending to the mucosal layer (P = 0.2). This is the first report to analyze the metastatic pattern of EOC on the appendix with respect to depth of invasion which could not reveal a significant difference.


Molecular mechanism of H+ conduction in the single-file water chain of the gramicidin channel.
The conduction of protons in the hydrogen-bonded chain of water molecules (or "proton wire") embedded in the lumen of gramicidin A is studied with molecular dynamics free energy simulations. The process may be described as a "hop-and-turn" or Grotthuss mechanism involving the chemical exchange (hop) of hydrogen nuclei between hydrogen-bonded water molecules arranged in single file in the lumen of the pore, and the subsequent reorganization (turn) of the hydrogen-bonded network. Accordingly, the conduction cycle is modeled by two complementary steps corresponding respectively to the translocation 1) of an ionic defect (H+) and 2) of a bonding defect along the hydrogen-bonded chain of water molecules in the pore interior. The molecular mechanism and the potential of mean force are analyzed for each of these two translocation steps. It is found that the mobility of protons in gramicidin A is essentially determined by the fine structure and the dynamic fluctuations of the hydrogen-bonded network. The translocation of H+ is mediated by spontaneous (thermal) fluctuations in the relative positions of oxygen atoms in the wire. In this diffusive mechanism, a shallow free-energy well slightly favors the presence of the excess proton near the middle of the channel. In the absence of H+, the water chain adopts either one of two polarized configurations, each of which corresponds to an oriented donor-acceptor hydrogen-bond pattern along the channel axis. Interconversion between these two conformations is an activated process that occurs through the sequential and directional reorientation of water molecules of the wire. The effect of hydrogen-bonding interactions between channel and water on proton translocation is analyzed from a comparison to the results obtained previously in a study of model nonpolar channels, in which such interactions were missing. Hydrogen-bond donation from water to the backbone carbonyl oxygen atoms lining the pore interior has a dual effect: it provides a coordination of water molecules well suited both to proton hydration and to high proton mobility, and it facilitates the slower reorientation or turn step of the Grotthuss mechanism by stabilizing intermediate configurations of the hydrogen-bonded network in which water molecules are in the process of flipping between their two preferred, polarized states. This mechanism offers a detailed molecular model for the rapid transport of protons in channels, in energy-transducing membrane proteins, and in enzymes.


Effect of aromatic acids on the influx of aromatic amino acids in rat brain slices.
The influx of [3H]phenylalanine, [3H]tyrosine and [3H]tryptophan into brain cells was studied using brain slices from adult rats. Each aromatic amino acid inhibited the influx of the others into the brain cells. Tryptophan inhibited non-competitively the influx of phenylalanine, and phenylalanine similarly that of tyrosine and tryptophan. On the other hand, tyrosine inhibited competitively the influx of phenylalanine, and similarly tryptophan that of tyrosine, and tyrosine that of tryptophan. Among the aromatic organic acids tested, only phenylpyruvate and homogentisate had any inhibitory effect on the influx of the aromatic amino acids. These effects were generally competitive, non-competitive inhibition being obtained only in the inhibition of phenylalanine influx by homogentisate. The existence of only one common transport system for aromatic amino acids appear to be unlikely.


Perirhinal cortex area 35 controls the functional link between the perirhinal and entorhinal-hippocampal circuitry: D-type potassium channel-mediated gating of neural propagation from the perirhinal cortex to the entorhinal-hippocampal circuitry.
In several experimental conditions, neuronal excitation at the perirhinal cortex (PC) does not propagate to the entorhinal cortex (EC) due to a "wall" of inhibition, which may help to create functional coupling and un-coupling of the PC and EC in the medial temporal lobe. However, little is known regarding the coupling control process. Herein, we propose that the deep layer of area 35 in the PC plays a pivotal role in opening the gate for coupling, thus allowing the activity in the PC to propagate to the EC. Using voltage-sensitive dye imaging for the brain slices of rodents, we show that a slowly inactivating potassium conductance in this area is essential to induce excitation overtaking the inhibitory control. This coupling between the distinct neural circuits persists for at least 1 h. We elucidate further implications of this network-level plastic behavior and its mechanism.


Tooth eruption and migration theories: can they account for the presence of a 13,000-year-old mesiodens in the vault of the palate?
A case of a mesiodens in the vault of the palate of a skull estimated to be approximately 13,000 years old is presented. The currently cited theories of tooth eruption were considered, and it was concluded that only the newly formulated BVT (blood vessel thrust) theory of tooth eruption can account for the migration of this mesiodens into that position.


Regional anesthesia in neonates and infants.
Optimal pain management can significantly impact the surgical outcome and length of stay in the neonatal intensive care unit (NICU). Regional anesthesia is an effective alternative that can be used in both term and preterm neonates. A variety of neuraxial and peripheral nerve blocks have been used for specific surgical and NICU procedures. Ultrasound guidance has increased the feasibility of using these techniques in neonates. Education and training staff in the use of continuous epidural infusions are important prerequisites for successful implementation of regional anesthesia in NICU management protocols.


Evaluation of Recombinant Multi-Epitope Outer Membrane Protein-Based Klebsiella pneumoniae Subunit Vaccine in Mouse Model.
Safety and protective efficacy of recombinant multi-epitope subunit vaccine (r-AK36) was evaluated in a mouse model. Recombinant AK36 protein comprised of immunodominant antigens from outer membrane proteins (Omp's) of Klebsiella pneumoniae namely OmpA and OmpK36. r-AK36 was highly immunogenic and the hyperimmune sera reacted strongly with native OmpA and OmpK36 proteins from different K. pneumoniae strains. Hyperimmune sera showed cross-reactivity with Omp's of other Gram-negative organisms. Humoral responses showed a Th2-type polarized immune response with IgG1 being the predominant antibody isotype. Anti-r-AK36 antibodies showed antimicrobial effect during in vitro testing with MIC values in the range of 25-50 μg/ml on different K. pneumoniae strains. The recombinant antigen elicited three fold higher proliferation of splenocytes from immunized mice compared to those with sham-immunized mice. Anti-r-AK36 antibodies also exhibited in vitro biofilm inhibition property. Subunit vaccine r-AK36 immunization promoted induction of protective cytokines IL-2 and IFN-γ in immunized mice. When r-AK36-immunized mice were challenged with 3 × LD100 dose, ∼80% of mice survived beyond the observation period. Passive antibody administration to naive mice protected them (67%) against the lethal challenge. Since the targeted OMPs are conserved among all K. pneumoniae serovars and due to the strong nature of immune responses, r-AK36 subunit vaccine could be a cost effective candidate against klebsiellosis.


Low dose thrombolysis: a nonoperative approach to renal artery occlusion.
Selective infusion of low dose streptokinase into the occluded renal arteries of 3 patients produced clot lysis. Clot lysis was achieved with a dose of 5,000 units per hour (1/100 systemic dose) when delivered via catheter to the clot site for 24 to 36 hours. No untoward consequences related to bleeding were encountered. In selected patients this technique permits re-establishment of renal arterial patency without surgery.


Bioconversion of ginsenosides Rb(1), Rb(2), Rc and Rd by novel β-glucosidase hydrolyzing outer 3-O glycoside from Sphingomonas sp. 2F2: cloning, expression, and enzyme characterization.
A new β-glucosidase gene (bglSp) was cloned from the ginsenoside converting Sphingomonas sp. strain 2F2 isolated from the ginseng cultivating filed. The bglSp consisted of 1344 bp (447 amino acid residues) with a predicted molecular mass of 49,399 Da. A BLAST search using the bglSp sequence revealed significant homology to that of glycoside hydrolase superfamily 1. This enzyme was overexpressed in Escherichia coli BL21 (DE3) using a pET21-MBP (TEV) vector system. Overexpressed recombinant enzymes which could convert the ginsenosides Rb(1), Rb(2), Rc and Rd to the more pharmacological active rare ginsenosides gypenoside XVII, ginsenoside C-O, ginsenoside C-Mc(1) and ginsenoside F(2), respectively, were purified by two steps with Amylose-affinity and DEAE-Cellulose chromatography and characterized. The kinetic parameters for β-glucosidase showed the apparent K(m) and V(max) values of 2.9±0.3 mM and 515.4±38.3 μmol min(-1)mg of protein(-1) against p-nitrophenyl-β-d-glucopyranoside. The enzyme could hydrolyze the outer C3 glucose moieties of ginsenosides Rb(1), Rb(2), Rc and Rd into the rare ginsenosides Gyp XVII, C-O, C-Mc(1) and F(2) quickly at optimal conditions of pH 5.0 and 37°C. A little ginsenoside F(2) production from ginsenosides Gyp XVII, C-O, and C-Mc(1) was observed for the lengthy enzyme reaction caused by the side ability of the enzyme.


Antibacterial performance of fully biobased chitosan-grafted-polybenzoxazine films: Elaboration and properties of released material.
A fully biobased benzoxazine monomer, V-fa (using vanillin and furfurylamine) was grafted onto chitosan (CS) at different weight ratios (CXVY) using "grafting to" benign Schiff base chemistry. Incorporation of V-fa onto CS increased the tensile strength and improved chemical resistance of the CS-graft-V-fa films. Reversible labile linkages, expansion of CS galleries and leaching out of phenolic species from biobased polymer films led to an improved antibacterial activity against Staphylococcus aureus, which is ∼125 times higher than the bare CS film, V-fa and oligomeric V-fa. The leached out species from films were analyzed extensively by NMR, FTIR, GPC, ABTS and HRMS analysis. Oxidative-stress seems to be responsible for antibacterial activity. Current work illustrates an attractive synthetic approach and the improved antibacterial performance of biobased CS-graft-poly(V-fa) films which may hold as a potential alternative for wound-healing and implant applications in future.


[Correlation of the antioxidant and coagulating blood systems under physiologic conditions].
Examinations carried out on intact animals and healthy people have revealed a paired and multiple correlation with exists between thromboplastic properties of erythrocytes, the level of malondialdehyde accumulation in their membranes and the superoxide dismutase activity.


The effects of stem girdling on biogeochemical cycles within a mixed deciduous forest in eastern Tennessee : II. Soil nitrogen mineralization and nitrification rates.
Nitrogen mineralization and net nitrification rates were 3-7 times greater in soil incubations from a girdled Liriodendron tulipifera (L.) stand than in a control stand. Neither litter nor root extracts had an inhibitory effect on nitrogen mineralization or nitrification rate. A lack of nitrification inhibitors also was demonstrated by the fact that ammonium added to the control stand was completely converted to nitrate upon incubation. Additions of sucrose increased CO2 evolution and decreased nitrogen mineralization and nitrification rates in the girdled plot soil, suggesting that nitrification could be effectively controlled by competition for NH 4+ supplies by heterotrophic soil organisms. CO2 evolution rates during incubation showed that heterotrophic as well as nitrifier activities were greater in the girdled plot soil than in the ungirdled plot soil, but the ratio of C to N mineralized was lower in the girdled plot soil. These results collectively indicate that nitrification is regulated by the availability of NH 4+ in these stands, and that the latter is strongly regulated by heterotrophic demand for N.


Analytical model for residual stresses in polymeric containers during cryogenic storage of hematopoietic stem cells.
Hematopoietic stem cell (HSC) therapy can significantly lower instances of infection in chemotherapy patients by accelerating the recovery of white blood cells in the body. However, therapy requires that HSCs be stored at cryogenic temperatures to retain the cells' ability to proliferate. Currently, cells are stored in polymeric blood bags that are subject to fracture at the extremely low storage temperatures, which leads to cell contamination, thereby reducing their effectiveness. Therefore, we have developed an analytical model to predict the accumulation of stresses that ultimately lead to crack initiation and bag fracture during cryogenic storage. Our model gives explicit relationships between stress state in the container and thermoelastic properties of the container material, container geometry, and environmental factors that include temperature of the system and pressure induced by excess gas evolving from the stored medium. Predictions based on the model are consistent with experimental observations of bag failures that occurred during cryogenic storage applications. Finally, the model can provide guidance in material selection and bag design to fabricate bags that will be less susceptible to fracture.


Plasma-cortisol levels in experimental heatstroke in dogs.
The effect of external heat-load, exercise and dehydration on dynamic changes in plasma cortisol during the development of heatstroke was investigated. Thirty-three unanesthetized dogs were tested under two sets of climatic conditions: comfort conditions and hot-dry climatic conditions, half of them while exercising. Half of the dogs in each group were rehydrated. None of the dogs that were investigated at room temperature suffered heatstroke. Of the dogs exposed to high ambient temperature, all of the exercising, as well as five out of six non-hydrated dogs and one rehydrated non-exercising dog suffered heatstroke. Significant dehydration (6%-7% of body weight), occurred only under high ambient temperature. Plasma cortisol levels of all dogs that suffered heatstroke rose conspicuously for at least 5 h and returned to normal levels 24 h later. Cortisol levels of dogs who did not experience heatstroke remained within the normal range. Cortisol levels correlated with the severity of the stress leading to heatstroke. High and rising levels of cortisol, several hours after body temperature returns to normal, may support the diagnosis of heatstroke.


Functional characterization and cloning of amino acid transporter B(0,+) (ATB(0,+)) in primary cultured rat pneumocytes.
Cationic amino acid transport in primary cultured rat pneumocytes exhibiting characteristics of alveolar epithelial type I-like cells are described. Asymmetry and activator ion dependency of (3)H-L-arginine uptake were characterized from the apical or basolateral fluid of pneumocytes grown on permeable support. Substrate specificity of transport was evaluated as a function of (3)H-L-arginine uptake inhibition in the presence of other amino acids. Transepithelial transport studies estimated (3)H-L-arginine flux in the apical-to-basolateral and basolateral-to-apical directions. Full length cDNA of rat amino acid transporter B(0,+) (rATB(0,+)) was cloned and its relative expression level studied. Results indicate that uptake of (3)H-L-arginine from apical fluid is dependent on Na(+) and Cl(-). Zwitterionic and cationic amino acids (excluding L-proline and anionic amino acids) inhibited uptake of (3)H-L-arginine from apical, but not basolateral incubation fluid. Apical-to-basolateral transepithelial flux of (3)H-L-arginine was 20x higher than basolateral-to-apical transport. Kinetic studies of (3)H-L-arginine uptake from apical fluid revealed maximal velocity (V(max)) and Michaelis-Menten constants (K(t)) of 33.32 +/- 2.12 pmol/mg protein/15 min and 0.50 +/- 0.11 mM, respectively, in a cooperative process having a coupling ratio of 1.18 +/- 0.16 with Na(+) and 1.11 +/- 0.13 with Cl(-). Expression of rATB(0,+) mRNA was identified by RT-PCR and Northern analysis. Corresponding cloned 3.2 kb rATB(0,+) cDNA sequence exhibits pronounced homology in deduced amino acid sequence to mouse (95% identity and 97% similarity) and human (89% identity and 95% similarity) ATB(0,+) homologues. We conclude that rat pneumocytes express ATB(0,+), which may partly contribute towards recovering cationic and neutral amino acids from alveolar luminal fluid.


Organic carbon and elemental carbon in Asia: a review from 1996 to 2006.
The principal sources of organic carbon (OC) and elemental carbon (EC) are anthropogenic or biogenic, whereas secondary sources are atmospheric oxidation processes of specific precursor gases. These compounds are considered atmospheric contaminants and adversely affect human health. Numerous studies have monitored atmospheric particulates and gaseous phases of OC and EC in Asia over the last decade. This work compares and analyzes different sample collection, pretreatment and analytical approaches. The principal carbonaceous sources are traffic exhaust and industrial emissions. The OC and EC concentrations are highest in high traffic areas, followed by urban sites, and lowest in suburban sites. Many characteristics of these sites, such a dense population, are important to research. The major OC to EC ratios in Asia cities were 1.0-3.0. This work elucidates the characteristics, sources, distributions, and characteristics of atmospheric carbonaceous species in Asia.


Self-selection of protein during pregnancy and lactation in rats.
Protein self-selection was investigated in female rats throughout pregnancy and lactation. In the first experiment, impregnated rats were presented with either a choice between low and high protein (casein) diets, or standard lab chow and their protein intake was compared to that of non-impregnated controls. Impregnated females showed an increase in both absolute and relative protein intake at the end of pregnancy and during the second week of lactation when compared to both their own baseline intake and that of non-impregnated rats. In the second experiment, lactating rats and non-lactating controls were presented with a choice between low and high protein (casein) diets, a high protein (soybean meal) and a high carbohydrate diet, or lab chow. Lactating rats consumed more protein than non-lactating rats regardless of diet condition, but percentage protein intake was found to differ across diet choice conditions. Differences in diet fraction choice are discussed in terms of protein: carbohydrate ratios, and how different sources of protein might be utilized differently within the body.


Divalent cations reduce depolarization of primary afferent terminations by GABA.
Divalent metal cations, including zinc, cadmium, cobalt, nickel, strontium, manganese, magnesium and calcium, reduced the depolarization by microelectrophoretic gamma-aminobutyric acid (GABA) and piperidine-4-sulphonic acid of the central terminations of muscle group Ia primary afferent fibres in the cat spinal cord without affecting the inhibition by GABA of the firing of spinal interneurones. There thus appears to be a difference in either the interaction of GABA with recognition sites, or in the mechanism by which such interaction activates chloride ionophores, at GABA-mediated bicuculline-sensitive synapses on the central terminals of peripheral primary afferent neurones and those on neurones located within the central nervous system.


Patterns of morbidity and rehospitalisation following spinal cord injury.
Longitudinal, descriptive design. The aim of this study was to investigate the frequency, cause and duration of rehospitalisations in individuals with spinal cord injury (SCI) living in the community. Australian spinal cord injury unit in collaboration with State Health Department. A data set was created by linking records from the NSW Department of Health Inpatient Statistics Collection between 1989-1990 and 1999-2000 with data from the Royal North Shore Hospital (RNSH) Spinal Cord Injuries Database using probabilistic record linkage techniques. Records excluded were nontraumatic injuries, age <16 years, spinal column injury without neurological deficit, full recovery (ASIA Grade E) and index admission not at RNSH. Descriptive statistics and time to readmission using survival analysis, stratified by ASIA impairment grade, were calculated. Over the 10-year period, 253 persons (58.6%) required one or more spinal-related readmissions, accounting for 977 rehospitalisations and 15,127 bed-days (average length of stay (ALOS) 15.5 days; median 5 days). The most frequent causes for rehospitalisation were genitourinary (24.1% of readmissions), gastrointestinal (11.0%), further rehabilitation (11.0%), skin-related (8.9%), musculoskeletal (8.6%) and psychiatric disorders (6.8%). Pressure sores accounted for only 6.6% of all readmissions, however, contributed a disproportionate number of bed-days (27.9%), with an ALOS of 65.9 (median 49) days and over 50% of readmissions (33 out of 64) occurred in only nine individuals aged under 30 years. Age, level and completeness of neurological impairment, all influenced differential rates of readmission depending on the type of complication. Overall rehospitalisation rates were high in the first 4 years after initial treatment episode, averaging 0.64 readmissions (12.6 bed-days) per person at risk in the first year and fluctuating between 0.52 and 0.61 readmissions (5.1-8.3 bed-days) per person at risk per year between the second to fourth years, before trending downwards to reach 0.35 readmissions (2.0 bed-days) as 10th year approaches. Time to readmission was influenced by degree of impairment, with significantly fewer people readmitted for ASIA D (43.2%) versus ASIA A, B and C (55.2-67.0%) impairments (P<0.0001). The mean duration to first readmission was 46 months overall, however, differed significantly between persons with ASIA A-C impairments (26-36 months) and ASIA D impairment (60 months). Identifying rates, causes and patterns of morbidity is important for future resource allocation and targeting preventative measures. For instance, the late complication of pressure sores in a small subgroup of young males, consuming disproportionately large resources, warrants further research to better understand the complex psychosocial and environmental factors involved and to develop effective countermeasures.


Contrasting molecular patterns of MHC class II alleles associated with the anti-Sm and anti-RNP precipitin autoantibodies in systemic lupus erythematosus.
To find evidence of a potential genetic predisposition to the anti-Sm or anti-RNP precipitin autoantibody responses. HLA-DR and DQ alleles determined by restriction fragment length polymorphism and/or oligotyping in 49 subjects with either anti-Sm alone or anti-RNP alone were compared with those in 139 race-matched normal control subjects and 59 race-matched lupus patients without anti-Sm and anti-RNP autoantibodies. Black patients with anti-Sm precipitin had increased frequencies of HLA-DR2 and the DQw6-associated DQA1*0102 (P = 0.007, odds ratio [OR] = 6.7) and DQB1*0602 (P = 0.001, OR = 9.1) chain alleles compared with normal black control subjects. Black patients with anti-RNP precipitin showed significant increases in the DQw5-associated DQA1*0101 (P = 0.03, OR = 5.5) and DQB1*0501 (P = 0.002, OR = 23.3) chain alleles compared with lupus patients without anti-Sm or RNP. While patients with anti-RNP precipitin showed an increased frequency of the DQw8-associated allele DQB1*0302 (P = 0.02, OR = 3.7) compared with normal controls, as well as an increased frequency of the DQw5-associated alleles DQA1*0101 and DQB1*0501 (P = 0.05, OR = 4.2) compared with lupus patients without anti-Sm or RNP. There were no specific HLA-DR2 or DR4 subtype associations found with either anti-Sm or RNP precipitin autoantibodies. There are distinct patterns of major histocompatibility complex class II allele associations with the anti-Sm versus the anti-RNP precipitin autoantibody responses, and HLA-DQ associations may be more primary than HLA-DR associations.


PI3Kγ Activates Integrin α4 and Promotes Immune Suppressive Myeloid Cell Polarization during Tumor Progression.
Immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) accumulate in tumors where they inhibit T cell-mediated antitumor immune responses and promote tumor progression. Myeloid cell PI3Kγ plays a role in regulating tumor immune suppression by promoting integrin α4-dependent MDSC recruitment to tumors and by stimulating the immunosuppressive polarization of MDSCs and TAMs. Here, we show that integrin α4 promotes immunosuppressive polarization of MDSCs and TAMs downstream of PI3Kγ, thereby inhibiting antitumor immunity. Genetic or pharmacological suppression of either PI3Kγ or integrin α4 blocked MDSC recruitment to tumors and also inhibited immune suppressive myeloid cell polarization, thereby reducing expression of IL10 and increasing expression of IL12 and IFNγ within tumors. Inhibition of PI3Kγ or integrin α4 within tumors stimulated dendritic cell and CD8+ T-cell recruitment and maturation, as well as tumor cell cytotoxicity in vivo, thereby inhibiting tumor growth. As blockade of PI3Kγ or integrin α4 prevents accumulation of MDSC and reduces myeloid cell expression of immunosuppressive factors that stimulate tumor immune escape, these results highlight PI3Kγ and integrin α4 as targets for the design of cancer therapeutics. Cancer Immunol Res; 5(11); 957-68. ©2017 AACR.


Quantification of the new triketone herbicides, sulcotrione and mesotrione, and other important herbicides and metabolites, at the ng/l level in surface waters using liquid chromatography-tandem mass spectrometry.
The LC/ESI/MSMS method allows the trace quantification (ng/l) of the new triketone herbicides, i.e. sulcotrione and mesotrione, and important herbicides and metabolites, in natural waters. Solid phase extraction (SPE) for sample enrichment is performed with OASIS (recoveries 94-112% for parent herbicides). Neutral and acidic compounds were analyzed separately with ESI in positive and negative mode, respectively. Quantification limits varied between 0.5 and 10 ng/l. The acidic herbicides detection was improved by a neutralizing post-column addition solution. The influence of ion suppression on quantification is discussed in detail. It is shown that we could overcome this problem and achieve reliable quantification using isotope labeled internal standards (ILIS) for every single analyte. The methods performance is illustrated with samples from a lake depth profile.


Incidence and survival trends in patients with primary tonsillar lymphoma: a large population-based study.
This study aims to reveal changes in the incidence and prognosis of patients with tonsillar lymphoma on a population level. The incidence, clinicopathological, and prognostic data of tonsillar lymphoma patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The Join-point software and R packages were utilized to analyze the annual percentage changes (APCs) and survival outcomes. The incidence of primary tonsillar lymphoma increased from 0.1204 per 100,000 person-years (95% CI, 0.0680-0.1962) in 1983 to 0.2158 (95% CI, 0.1675-0.2740) in 2015 with an APC of 1.20. When classified by decades, both cancer-specific survival (CSS) and overall survival (OS) improved with time. The 2006-2015 decade showed the highest rate of CSS and OS. Nevertheless, for disease-specific survival (DSS), the difference was not significant between 1996-2005 and 2006-2015 decades. The main cause of mortality among this cohort was heart diseases. Three nomograms were constructed to predict OS, CSS, and DSS for patients with primary tonsillar lymphoma, respectively. Histological subtype made the most contribution to poor prognosis in OS-predicting and CSS-predicting nomograms. While, for DSS, age at diagnosis made the most contribution to poor outcomes. The incidence of primary tonsillar lymphoma has increased in the past decades. The OS and CSS rates of tonsillar lymphoma improved continuously, while there was no significant improvement in DSS in the past decades. These changes indicated an improved management of tonsillar lymphoma with newer therapeutic agents and the need of multi-disciplinary treatments to offset the future burden of noncancer diseases.


Ocular Münchhausen syndrome induced by incest.
This report describes a young female patient whose long-lasting ocular problems were ultimately found to be due to self-induced damage of the corneas with chemicals, and later, self-inflicted perforation of the eye with a safety pin. More than one year after these ocular symptoms were presented, it was discovered that the eye diseases were in fact attempts by the patient to escape from the psychic anxieties which were the result of an incestuous relationship between the patient and her father.


High-altitude illness: Management approach.
In high altitudes, usually above 2500 m, travelers are faced with decreased partial pressure of oxygen along with decreased barometric pressure. High-altitude illness, a syndrome of acute mountain sickness, high-altitude cerebral edema and high-altitude pulmonary edema, occurs due to the hypobaric hypoxia when there is inadequate acclimatization. This review provides detailed information about pathophysiology, clinical features, prevention and treatment strategies for high-altitude illness according to the current literature.


Prosopagnosia: a clinical, psychological, and anatomical study of three patients.
Three patients with prosopagnosia are described of whom two had right occipital lesions. An analysis of visual and perceptual functions demonstrated a defect in perceptual classification which appeared to be stimulus-specific. A special mechanism for facial recognition is postulated, and the importance of the right sided posterior lesion is stressed.


Complications associated with bone cementing for the treatment of giant cell tumors of bone.
Aretrospective review was conducted of giant cell tumors treated between 1984 and 1998 using the technique of aggressive curettage through a large bone window followed by acrylic cement reconstruction. Fifteen patients with a mean follow-up time of 46 months (range, 24-188 months) were identified. One patient had a local recurrence 24 months postoperatively. All the patients showed a radiolucent zone at the bone-cement interface up to 2.5 mm in width during the first 6 months after operation. However, the radiolucent zones were nonprogressive and did not affect the stability of the bone cement. Osteoarthritis of the knee joint occurred 14 years postoperatively in one patient with an intraarticular fracture at presentation. A stress fracture occurred in one patient who had the largest tumor in the distal femur. Acrylic cement reconstruction is a safe and effective procedure that provides local adjuvant therapy. Giant cell tumors with an associated intraarticular fracture remain a challenging problem to treat.


Hypomyelination in the cerebrum of the congenitally hypothyroid mouse (hyt).
2',3'-Cyclic nucleotide 3'-phosphohydrolase activity in the cerebrum of the inherited primary hypothyroid mouse (hyt/hyt) is reduced in comparison with the normal heterozygate (hyt/+). No differences were observed with regard to DNA and RNA content and the RNA/DNA ratio. The results of this study indicate that hypomyelination in the hypothyroid mouse is restricted to the cerebrum, and is not related to arrested glial proliferation.


Stereo-selective binding of monoclonal antibodies to the poly-γ-D-glutamic acid capsular antigen of Bacillus anthracis.
Bacillus anthracis is surrounded by an anti-phagocytic capsule that is entirely composed of γ-linked D-glutamic acid (γDPGA). γDPGA is required for virulence and is produced in large quantities following spore germination. We have previously described the isolation of several γDPGA-reactive mAbs. The reagents are effective in both immunoprotection and diagnostic applications. The current work was done to further investigate the specificity of γDPGA-reactive mAbs. The specificity of each mAb was characterized using surface plasmon resonance. Our results indicate that each mAb is stereoselective for binding to D-glutamic acid oligomers, but to varying degrees. In particular, mAb F26G3 is highly selective for γDPGA; alterations in stereochemistry disrupted recognition. These differences in mAb reactivity suggest that binding of γDPGA by mAb F26G3 is more specific than non-directional ionic interactions between a negatively charged antigen and a positively charged antibody.


[Computer-aided surgery of the paranasal sinuses and the anterior skull base].
Endoscopic or microscopic surgery for chronic rhinosinusitis with or without nasal polyps is a routine intervention in daily practice. It is often a delicate and difficult minimally invasive intervention in a narrow space, with a tunnel view of 4 mm in the case of endoscopy and frequent bleeding in chronically inflamed tissue. Therefore, orientation in such a "labyrinth" is often difficult. In the case of polyp recurrence or tumors, the normal anatomical landmarks are often missing, which renders orientation even more difficult. In such cases, computer-aided navigation together with images such as those from computed tomography or magnetic resonance imaging can support the surgeon to make the operation more accurate and, in some cases, faster. Computer-aided surgery also has great potential for education.


Neuropeptide Y stimulates retinal neural cell proliferation--involvement of nitric oxide.
Neuropeptide Y (NPY) is a 36 amino acid peptide widely present in the CNS, including the retina. Previous studies have demonstrated that NPY promotes cell proliferation of rat post-natal hippocampal and olfactory epithelium precursor cells. The aim of this work was to investigate the role of NPY on cell proliferation of rat retinal neural cells. For this purpose, primary retinal cell cultures expressing NPY, and NPY Y(1), Y(2), Y(4) and Y(5) receptors [Alvaro et al., (2007) Neurochem. Int., 50, 757] were used. NPY (10-1000 nM) stimulated cell proliferation through the activation of NPY Y(1), Y(2) and Y(5) receptors. NPY also increased the number of proliferating neuronal progenitor cells (BrdU(+)/nestin(+) cells). The intracellular mechanisms coupled to NPY receptors activation that mediate the increase in cell proliferation were also investigated. The stimulatory effect of NPY on cell proliferation was reduced by L-nitroarginine-methyl-esther (L-NAME; 500 microM), a nitric oxide synthase inhibitor, 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ; 20 microM), a soluble guanylyl cyclase inhibitor or U0126 (1 microM), an inhibitor of the extracellular signal-regulated kinase 1/2 (ERK 1/2). In conclusion, NPY stimulates retinal neural cell proliferation, and this effect is mediated through nitric oxide-cyclic GMP and ERK 1/2 pathways.


Regulation of nutrient utilization in filamentous fungi.
Organisms must accurately sense and respond to nutrients to survive. In filamentous fungi, accurate nutrient sensing is important in the establishment of fungal colonies and in continued, rapid growth for the exploitation of environmental resources. To ensure efficient nutrient utilization, fungi have evolved a combination of activating and repressing genetic networks to tightly regulate metabolic pathways and distinguish between preferred nutrients, which require minimal energy and resources to utilize, and nonpreferred nutrients, which have more energy-intensive catabolic requirements. Genes necessary for the utilization of nonpreferred carbon sources are activated by transcription factors that respond to the presence of the specific nutrient and repressed by transcription factors that respond to the presence of preferred carbohydrates. Utilization of nonpreferred nitrogen sources generally requires two transcription factors. Pathway-specific transcription factors respond to the presence of a specific nonpreferred nitrogen source, while another transcription factor activates genes in the absence of preferred nitrogen sources. In this review, we discuss the roles of transcription factors and upstream regulatory genes that respond to preferred and nonpreferred carbon and nitrogen sources and their roles in regulating carbon and nitrogen catabolism. KEY POINTS: • Interplay of activating and repressing transcriptional networks regulates catabolism. • Nutrient-specific activating transcriptional pathways provide metabolic specificity. • Repressing regulatory systems differentiate nutrients in mixed nutrient environments.


Altered oligosaccharides as the initiating autoantigen in rheumatoid arthritis.
The linkage of rheumatoid arthritis (RA) to infection though vague has remained a persistent notion for the past fifty years. The hypotheses that streptococcus was responsible; then M. Pneumoniae; the implication of a viral pathogenesis and, more especially, the Epstein-Barr virus, have all not withstood the test of Koch's postulates. Today, autoimmunity holds the field in the pathogenesis of RA. We know in fair detail what happens after failure of self-recognition develops. Why does synovial tissue become antigenic? Altered receptors of cell surface may be the loci of change, namely, glycoproteins and glycolipids. A hypothesis is constructed based on alteration by viral DNA of these cell surface markers that are then recognized as alien. Evidence is drawn from insulin dependent juvenile diabetes, glomerulonephritis, and Landsteiner blood groups. The initial lesion may be initiated by an infectious agent leading to a chain of events, the first link constituting change of the specific glycoprotein or glycolipid of a cell to one of antigenic challenge, thus stimulating an autoimmune reaction. The ultimate destructive-proliferative sequences of RA are then set in motion.


Cutoff Value of Qualitative HBsAg for Confirmatory HBsAg Using the Chemiluminescence Microparticle Immunoassay Method.
Confirmatory hepatitis B surface antigen (HBsAg) is an assay used to distinguish weakly reactive from false-positive HBsAg results. To determine the signal to cutoff (S/CO) value of chemiluminescence microparticle immunoassay (CMIA) HBsAg assay that should trigger follow-up confirmatory HBsAg testing. All specimens with an initial S/CO value of 0.90-100.00 were subjected to repeat HBsAg testing after high-speed centrifugation. The specimens with an initial S/CO value in that range remained in the same range and were then followed up with confirmatory HBsAg testing. In total, 132 specimens had an S/CO value between 0.90 and 100.00 after high-speed centrifugation, followed by confirmatory HBsAg retesting. The S/CO value of HBsAg specimens for which the results required verification with confirmatory HBsAg was 0.98 (100% sensitivity, 3.3% specificity) through 9.32 (47.1% sensitivity, 100% specificity). The HBsAg S/CO values (as determined by the chemiluminescent microparticle immunoassay [CMIA] method) that should trigger confirmatory HBsAg testing are 0.98-9.32.


Can Designer Indels Be Tailored by Gene Editing?: Can Indels Be Customized?
Genome editing with engineered nucleases (GEENs) introduce site-specific DNA double-strand breaks (DSBs) and repairs DSBs via nonhomologous end-joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical- or alternative-NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w.


Coronary Angiography After Transcatheter Aortic Valve Replacement (TAVR) to Evaluate the Risk of Coronary Access Impairment After TAVR-in-TAVR.
Background Transcatheter aortic valve replacement (TAVR)-in-TAVR is a possible treatment for transcatheter heart valve (THV) degeneration. However, the displaced leaflets of the first THV will create a risk plane (RP) under which the passage of a coronary catheter will be impossible. The aim of our study was to evaluate the potential risk of impaired coronary access (CA) after TAVR-in-TAVR. Methods and Results We prospectively performed coronary angiography after TAVR with different THVs in 137 consecutive patients, looking where the catheter crossed the valve frame. If coronary cannulation was achieved from below the RP, the distance between valve frame and aortic wall was measured by aortic angiography. CA after TAVR-in-TAVR was defined as feasible if the catheter passed above the RP, as theoretically feasible if passed under the RP with valve-to-aorta distance >2 mm, and as unfeasible if passed under the RP with valve-to-aorta distance ≤2 mm. Seventy-two patients (53%) received a Sapien 3 THV, 26 (19%) received an Evolut Pro/R THV, and 39 (28%) received an Acurate Neo THV. CA after TAVR-in-TAVR was considered feasible in 40.9% (68.1%, 19.2%, and 5.1%, respectively; P<0.001), theoretically feasible in 27.7% (8.3%, 42.3%, and 53.8%, respectively; P<0.001), and unfeasible in 31.4% (23.6%, 38.5%, and 41.1%, respectively; P=0.116). Independent predictors of impaired CA after TAVR-in-TAVR were female sex (odds ratio [OR], 3.99; 95% CI, 1.07-14.86; P=0.040), sinotubular junction diameter (OR, 0.62; 95% CI, 0.48-0.80; P<0.001), and implantation of a supra-annular THV (OR, 6.61; 95% CI, 1.98-22.03; P=0.002). Conclusions CA after TAVR-in-TAVR might be unfeasible in >30% of patients currently treated with TAVR. Patients with a small sinotubular junction and those who received a supra-annular THV are at highest risk of potential CA impairment with TAVR-in-TAVR.


Impact of methionine on net ketoacid production in humans.
An exogenous acid load (NH4Cl) inhibits net ketoacid production in the first week of starvation and the fourth to eighth weeks of ketogenic dieting. To determine whether an acid load produced by amino acid metabolism can similarly modify ketosis, five overweight volunteers ingested methionine (H2SO4), NH4Cl, and NaCl (control), in varying order, each day for seven days during weeks 5 to 8 of hypocaloric ketogenic dieting. During days 5 to 7 of each phase, blood pH, bicarbonate, and pCO2 were stable but lower in the NH4Cl phase (7.32 +/- 0.02, 18.1 +/- 1.2 mmol/L, 35.8 +/- 1.4 mmHg) and the methionine phase (7.33 +/- 0.01, 17.1 +/- 0.9 mmol/L, 34.0 +/- 2.0 mmHg) than in the NaCl phase (7.38 +/- 0.01, 22.3 +/- 0.2 mmol/L, 37.6 +/- 1.6 mmHg), P less than .05. Over this period, blood acetoacetate concentration was lower during the methionine and NH4Cl phases than during NaCl, P less than .05. In addition blood beta-hydroxybutyrate and total ketone-body concentrations were lower in the methionine than NaCl phases, P less than .05. Urinary acetoacetate and beta-hydroxybutyrate excretion fell with both acid loads, P less than .05. Compared with control values, urinary total ketone excretion was suppressed by 67 +/- 10% in the NH4Cl and 89 +/- 3% in the methionine periods. When NaCl was ingested after either of the acid loads, urinary ketone excretion increased by 300% to 700%. Thus, methionine ingestion, which results in an acid challenge equivalent to that of a large protein load, has an impact on net ketoacid production similar to that of NH4Cl.(ABSTRACT TRUNCATED AT 250 WORDS)


No effect of cAMP on protein synthesis in reticulocyte lysates.
The results of a series of experiments are interpreted to indicate that protein synthesis in reticulocyte lysates is not affected by the reticulocyte cAMP-dependent protein kinase. The catalytic subunit of this enzyme was isolated to apparent homogeneity. Also, the protein inhibitor of this protein kinase was isolated from muscle. Neither physiological concentrations of cAMP nor any of these protein components had a detectable effect on protein synthesis in reticulocyte lysates in the presence or absence of exogenous heme. Phosphorylation of the smallest subunit of eukaryotic initiation factor 2 or the 90,000 to 100,000-dalton peptide associated with eukaryotic initiation factor 2 kinase activity were not affected by the activity of the cAMP-dependent protein kinase under conditions in which exogenous heme has a pronounced effect on these reactions.


Synthesis and characterization of a new fluorescent phospholipid.
A novel fluorescent phospholipid, whose structure was tentatively assigned as 1-(2'-thio-1'-hydroxyethyl)-2-(ethylphosphatidyl)isoindole), was synthesized by reacting O-phthalaldehyde and beta-mercaptoethanol with phosphatidylethanolamine. The fluorescent lipid product was purified by silicic acid chromatography. The purity was demonstrated by thin-layer chromatography. This fluorescent phospholipid could not form stable lipid vesicles. However, a mixture of phosphatidylcholine and this fluorescent phospholipid did form stable vesicles after sonication, as demonstrated by Sepharose 4B column chromatography and electron microscopy. The absorption and fluorescence properties of this lipid, both as aqueous micelles or incorporated into vesicles, have been determined. The potential usage of this new fluorescent phospholipid in membrane studies is discussed.


Alkaline p-nitrophenylphosphate phosphatase activity from Halobacterium halobium. Selective activation by manganese and effect of other divalent cations.
1. Alkaline p-nitrophenylphosphate phosphatase (pNPPase) activity of Halobacterium halobium is selectively stabilized and stimulated by Mn2+ ions. 2. Mn2+ binding to native pNPPase is characterized by a dissociation constant of 0.35 mM at pH 8.5, 37 degrees C, with a Hill coefficient of 0.988. 3. Mn2+ behaves as a mixed type nonessential activator, increasing the Vmax value (beta = 6.09, pH 8.5) and decreasing the Km value for pNPP (alpha = 0.56, pH 8.5). The Ki value for inorganic phosphate (a competitive inhibitor) was also decreased in the presence of Mn2+. 4. Activation of native pNPPase by preincubation with Mn2+ is a slow temperature-dependent process, which can be described by an exponential relationship vs time. However, a weak but immediate activation was also detected. 5. Zn2+, Cu2+ and Ni2+ were found to inhibit both native and Mn(2+)-stimulated pNPPase, whereas Co2+ and Cd2+ inhibited the Mn(2+)-stimulated pNPPase but had no effect on the native enzyme form.


Assessing Novel Therapies Based on Late-Stage Efficacy: A Dangerous Concept?
Traditionally, the efficacy of novel cancer therapies has been confirmed in patients failing regular treatment before being tested in early disease. Improved understanding of the mechanisms guiding therapeutic efficacy may challenge this dogma, suggesting novel therapies to move into early evaluation based on biological rationales without late-stage efficacy evaluation.


Three-dimensional stiffness of the carpal arch.
The carpal arch of the wrist is formed by irregularly shaped carpal bones interconnected by numerous ligaments, resulting in complex structural mechanics. The purpose of this study was to determine the three-dimensional stiffness characteristics of the carpal arch using displacement perturbations. It was hypothesized that the carpal arch would exhibit an anisotropic stiffness behavior with principal directions that are oblique to the conventional anatomical axes. Eight (n=8) cadavers were used in this study. For each specimen, the hamate was fixed to a custom stationary apparatus. An instrumented robot arm applied three-dimensional displacement perturbations to the ridge of trapezium and corresponding reaction forces were collected. The displacement-force data were used to determine a three-dimensional stiffness matrix using least squares fitting. Eigendecomposition of the stiffness matrix was used to identify the magnitudes and directions of the principal stiffness components. The carpal arch structure exhibited anisotropic stiffness behaviors with a maximum principal stiffness of 16.4±4.6N/mm that was significantly larger than the other principal components of 3.1±0.9 and 2.6±0.5N/mm (p<0.001). The principal direction of the maximum stiffness was pronated within the cross section of the carpal tunnel which is accounted for by the stiff transverse ligaments that tightly bind distal carpal arch. The minimal principal stiffness is attributed to the less constraining articulation between the trapezium and scaphoid. This study provides advanced characterization of the wrist׳s three-dimensional structural stiffness for improved insight into wrist biomechanics, stability, and function.


Fish reovirus GCReV-109 VP33 protein elicits protective immunity in rare minnows.
Grass carp reovirus strain 109 (GCReV-109) was previously isolated from a grass carp (Ctenopharyngodon idellus) with hemorrhagic disease, and its complete genome has been sequenced. However, the infectivity of GCReV-109 has not been studied, and the viral protein VP33, encoded on genome segment S11, had no detectable sequence homology to other known reovirus proteins. In this study, we characterized GCReV-109 infections in vivo and in vitro, as well as the VP33 protein. Infectivity analysis showed that GCReV-109 caused severe hemorrhagic disease and 100% mortality at dilutions up to 10(-4) in rare minnows (Gobiocypris rarus) by 8 days postinfection, but no visible cytopathic effect was observed in GCReV-109-infected subcultured grass carp muscle (GCM) cells. To confirm that GCReV-109 could be propagated in GCM cells, three virus genome segments were detected by RT-PCR, and large numbers of virus particles were observed by transmission electron microscopy in samples from the infected GCM cells. The suspension of GCReV-109-infected GCM cells was pathogenic to rare minnows. VP33 protein was expressed and purified for generation of an anti-VP33 antiserum. In western blot analysis of purified GCReV-109 particles, the antiserum specifically recognized a protein band (approximately 33 kDa). This revealed that VP33 is a major structural protein of GCReV-109 that might have immunogenic properties. The protective efficacy of the anti-VP33 antiserum against GCReV-109 infection was tested. The death of infected fish was delayed and the mortality fell to 10% when fish were treated with the anti-VP33 antiserum, suggesting that it might be useful for the prevention and control of fish reoviral disease.


LIM domain proteins.
Sala and Oakes introduce LIM domain proteins and discuss their roles in transcription, cytokinesis, adhesion, motility and mechanosignaling.


Distinct roles of the medial prefrontal cortex in advantageous and disadvantageous inequity aversion.
Human beings have a strong preference for the fair distribution of resources in situations of both advantageous and disadvantageous inequity. Neuroimaging studies have shown that the process of advantageous and disadvantageous inequity aversion involves distinct brain regions. However, little is known about the causal roles of the dorsal medial prefrontal cortex (dmPFC) in these two types of inequity aversion. To clarify the roles of the dmPFC in both types of inequity aversion, 70 subjects were recruited and randomly assigned to two anodal transcranial direct current stimulation (tDCS) groups: tDCS over the dmPFC and tDCS over the primary visual cortex. Participants then completed a dictator game, which was used to measure the aversion to inequity. This study found that tDCS over the dmPFC decreased the aversion to disadvantageous inequity, but not that to advantageous inequity, and the treatment effect was modulated by equity cost. These results show that the dmPFC plays different roles in these two types of inequity aversion.


High-level overproduction of Thermus enzymes in Streptomyces lividans.
Biotechnology needs to explore the capacity of different organisms to overproduce proteins of interest at low cost. In this paper, we show that Streptomyces lividans is a suitable host for the expression of Thermus thermophilus genes and report the overproduction of the corresponding proteins. This capacity was corroborated after cloning the genes corresponding to an alkaline phosphatase (a periplasmic enzyme in T. thermophilus) and that corresponding to a beta-glycosidase (an intracellular enzyme) in Escherichia coli and in S. lividans. Comparison of the production in both hosts revealed that the expression of active protein achieved in S. lividans was much higher than in E. coli, especially in the case of the periplasmic enzyme. In fact, the native signal peptide of the T. thermophilus phosphatase was functional in S. lividans, being processed at the same peptide bond in both organisms, allowing the overproduction and secretion of this protein to the S. lividans culture supernatant. As in E. coli, the thermostability of the expressed proteins allowed a huge purification factor upon thermal denaturation and precipitation of the host proteins. We conclude that S. lividans is a very efficient and industry-friendly host for the expression of thermophilic proteins from Thermus spp.


Biodiversity of aerobic methylobacteria associated with the phyllosphere of the southern Moscow Oblast.
During the summer period (15–25°C), 34 strains of methylotrophic bacteria associated with different species of herbs, shrub, and trees in Pushchino (Moscow oblast, Russia) were isolated on the medium with methanol. Predominance of pink-colored Methylobacterium strains in the phyllosphere of many plants was confirmed by microscopy, enumeration of the colonies from grass leaves, and sequencing of the 16S rRNA genes. Colorless and yellow-pigmented methylotrophs belonged to the genera Methylophilus, Methylobacillus, Hansschlegelia, Methylopila, Xanthobacter, and Paracoccus. All isolates were able to synthesize plant hormones auxins from L-tryptophan (5−50 μg/mL) and are probably plant symbionts.


CDP-choline liposomes provide significant reduction in infarction over free CDP-choline in stroke.
Cytidine-5'-diphosphocholine (CDP-choline, Citicoline, Somazina) is in clinical use (intravenous administration) for stroke treatment in Europe and Japan, while USA phase III stroke clinical trials (oral administration) were disappointing. Others showed that CDP-choline liposomes significantly increased brain uptake over the free drug in cerebral ischemia models. Liposomes were formulated as DPPC, DPPS, cholesterol, GM(1) ganglioside; 7/4/7/1.57 molar ratio or 35.8/20.4/35.8/8.0 mol%. GM(1) ganglioside confers long-circulating properties to the liposomes by suppressing phagocytosis. CDP-choline liposomes deliver the agent intact to the brain, circumventing the rate-limiting, cytidine triphosphate:phosphocholine cytidylyltransferase in phosphatidylcholine synthesis. Our data show that CDP-choline liposomes significantly ( P < 0.01) decreased cerebral infarction (by 62%) compared to the equivalent dose of free CDP-choline (by 26%) after 1 h focal cerebral ischemia and 24 h reperfusion in spontaneously hypertensive rats. Beneficial effects of CDP-choline liposomes in stroke may derive from a synergistic effect between the phospholipid components of the liposomes and the encapsulated CDP-choline.


A review of the evidence for P2 being an independent component process: age, sleep and modality.
This article reviews the event-related potential (ERP) literature in relation to the P2 waveform of the human auditory evoked potential. Within the auditory evoked potential, a positive deflection at approximately 150-250 ms is a ubiquitous feature. Unlike other cognitive components such as N1 or the P300, remarkably little has been done to investigate the underlying neurological correlates or significance of this waveform. Indeed until recently, many researchers considered it to be an intrinsic part of the 'vertex potential' complex, involving it and the earlier N1. This review seeks to describe the evidence supportive of P2 being the result of independent processes and highlights several features, such as its persistence from wakefulness into sleep, the general consensus that unlike most other EEG phenomena it increases with age, and the fact that it can be generated using respiratory stimuli.


Identification of macrophage induced genes of Corynebacterium pseudotuberculosis by differential fluorescence induction.
Corynebacterium pseudotuberculosis is the etiological agent of the sheep disease caseous lymphadenitis. We have developed a promoter reporter system for this organism based on expression of the green fluorescent protein (gfp) gene from Aequorea victoria. A promoterless vector, pSM20, containing the gfp gene was constructed, and promoters were inserted upstream of the gfp gene. Upon transformation into C. pseudotuberculosis, fluorescence could be visualised by fluorescence microscopy, and relative promoter strength measured by flow cytometry. The usefulness of this system for measuring changes in gene expression was demonstrated by measuring fluorescence levels of heat shocked C. pseudotuberculosis carrying a dnaK promoter construct. Replication of C. pseudotuberculosis within J774 macrophages could be monitored by fluorescence microscopy. The establishment of the system allowed the use of differential fluorescence to identify genes that showed up-regulation following macrophage infection. Genes coding for a non-ribosomal peptide synthetase and the beta chain of a propionyl CoA carboxylase were identified as possessing promoters that demonstrated enhanced activity following macrophage infection by C. pseudotuberculosis.


beta-Endorphin enhances phagocytosis of latex particles in mouse peritoneal macrophages.
The effects of beta-endorphin (beta End) on phagocytosis in peritoneal macrophages were examined by using flow cytometry (FCM). Beta End enhanced phagocytosis in a dose-dependent manner. Leucine-enkephalin (Leu-Enk), methionine-enkephalin (Met-Enk), alpha-endorphin (alpha End), gamma-endorphin (gamma End), alpha End (18-31) and beta End (28-31) had no such activity. Beta End (1-27) and beta End (6-31) enhanced phagocytosis less effectively than beta End did. Naloxone did not inhibit the enhancement of phagocytosis induced by beta End. Unstimulated control phagocytosis was partially suppressed in Ca2(+)-free EGTA-containing solution and even in this solution beta End enhanced phagocytosis. However, the enhancement was suppressed in the solution containing BAPTA-AM. The present study showed that beta End enhanced extracellular Ca2+ ([Ca2+]o)-dependent and -independent phagocytosis and that the enhancement is largely dependent on intracellular Ca2+ ([Ca2+]i). These results support the contention that beta End is one of the mediators that modulates the immune system.


Bleomycin interactions with DNA. Studies on the role of the C-terminal cationic group of bleomycin A2 in association with and degradation of DNA.
The role of the cationic dimethylsulfonium group of bleomycin A2 in the binding of the drug to poly(dA-dT) has been investigated by proton NMR studies on the S-demethylated derivative. In contrast to the parent drug, the demethyl congener shows no intercalation of the aromatic bithiazole group which is adjacent to the former cationic group. However, chemical studies show that the demethyl derivative retains the capability to degrade DNA in the presence of iron(II), albeit at a reduced rate and to a lesser extent than the intact bleomycin A2. Thus, the cationic group is necessary for the intercalation of the bithiazole portion of the drug molecule; however, intercalation is not essential for the degradation of DNA.


Bacterioferritin from Mycobacterium smegmatis contains zinc in its di-nuclear site.
Bacterioferritins, also known as cytochrome b (1), are oligomeric iron-storage proteins consisting of 24 identical amino acid chains, which form spherical particles consisting of 24 subunits and exhibiting 432 point-group symmetry. They contain one haem b molecule at the interface between two subunits and a di-nuclear metal binding center. The X-ray structure of bacterioferritin from Mycobacterium smegmatis (Ms-Bfr) was determined to a resolution of 2.7 A in the monoclinic space group C2. The asymmetric unit of the crystals contains 12 protein molecules: five dimers and two half-dimers located along the crystallographic twofold axis. Unexpectedly, the di-nuclear metal binding center contains zinc ions instead of the typically observed iron ions in other bacterioferritins.


Replacement of sodium with choline in slow-cooling media improves human ovarian tissue cryopreservation.
Ovarian tissue cryopreservation is a promising technique for fertility preservation in young female cancer patients and efforts have been made to improve its effectiveness. During cooling and thawing, sodium ions significantly contribute to the 'solute effect' that plays a major role in disrupting cell membranes. Choline ions, which do not cross the cell membrane, should not contribute to the intracellular solute load. The present study assessed the effects of sodium substitution with choline in slow-cooling freezing media on human ovarian cortical strip cryopreservation. A total of 629 follicles (fresh control n=266; cryopreserved n=363), collected from ovarian biopsies of 11 women (22-40years) during laparoscopic surgery, were studied by light microscopy, immunohistochemistry and transmission electron microscopy to evaluate their morphology, apoptosis and ultrastructure. The results demonstrate that choline substitution leads to: (i) an improved preservation of oocytes and follicular cells; (ii) the recovery of a higher percentage of grade-1 follicles negative for p53, p21 and Apaf-1 apoptotic markers; (iii) a reduced mitochondrial damage as observed at an ultrastructural level; and (iv) a better preservation of ovarian tissue stroma. In conclusion, the use of choline-based media may represent a valuable tool to improve human ovarian tissue cryopreservation. Ovarian tissue cryopreservation is a promising fertility preservation approach for cancer patients before undergoing treatments that irreversibly reduce the ovarian reserve. Autotransplantation of ovarian cortical strips has resulted in viable offspring in animal models and human. Worldwide, 20 live births have been reported thus far following autotransplantation of frozen-thawed ovarian tissue. However, currently the success rate of this technology is far from being satisfactory. This could be due to inappropriate cryopreservation procedures that might impair the physiology of ovarian follicles. Sodium ions contained in freezing media significantly contribute to the 'solute effect' that plays a major role in disrupting cell membranes. Choline ions, which do not cross the cell membrane, would not be expected to contribute to the intracellular solute load. In the present study we assessed the effects of sodium substitution with choline in slow-cooling freezing media on human ovarian cortical strip cryopreservation. A total of 629 follicles, collected from ovarian biopsies of 11 women (aged 22-40years) during laparoscopic surgery, have been studied by light microscopy, immunohistochemistry and transmission electron microscopy to evaluate their morphology, apoptosis and ultrastructure. Results demonstrated that choline substitution allowed: (i) a better preservation of oocytes and follicular cells; (ii) the recovery of an higher percentage of healthy follicles negative for apoptotic markers; (iii) a lower mitochondria ultrastructural damage; and (iv) a better preservation of ovarian tissue stroma. In conclusion, the use of choline-based media could represent a valuable tool to cryopreserve human ovarian tissue for fertility preservation.


Hydrogen diffusion and its electrical properties variation as a function of the IGZO stacking structure.
The oxygen vacancies and hydrogen in oxide semiconductors are regarded as the primary sources of charge carriers and various studies have investigated the effect of hydrogen on the properties of oxide semiconductors. However, the carrier generation mechanism between hydrogen and oxygen vacancies in an a-IGZO semiconductor has not yet been clearly examined. In this study we investigated the effect of hydrogen and the variation mechanisms of electrical properties of a thin film supplied with hydrogen from the passivation layer. SiOx and SiNx, which are used as passivation or gate insulator layers in the semiconductor process, respectively, were placed on the top or bottom of an a-IGZO semiconductor to determine the amount of hydrogen penetrating the a-IGZO active layer. The hydrogen diffusion depth was sufficiently deep to affect the entire thin semiconductor layer. A large amount of hydrogen in SiNx directly affects the electrical resistivity of a-IGZO semiconductor, whereas in SiOx, it induces a different behavior from that in SiNx, such as inducing an oxygen reaction and O-H bond behavior change at the interface of an a-IGZO semiconductor. Moreover, the change in electrical resistivity owing to the contribution of free electrons could be varied based on the bonding method of hydrogen and oxygen.


Urinary excretion of immunoreactive sporidesmin metabolites in sheep in relation to factors influencing susceptibility to sporidesmin intoxication.
To study the urinary disposition of orally administered sporidesmins A and D in sheep and identify factors influencing their kinetics, particularly the influence of breeding for resistance and susceptibility to sporidesmin, the mycotoxin responsible for the hepatogenous photosensitisation, facial eczema. A competitive ELISA was used to monitor urinary output of immunoreactive metabolites after the intraruminal administration, to female Romney sheep, of either sporidesmin A or sporidesmin D, the nontoxic analogue. Preliminary characterisation of metabolites was carried out using HPLC with fractions monitored by ELISA. Maximum urinary excretion rates of immunoreactive metabolites occurred 2-8 h after dosing with sporidesmin D and 15-30 h after dosing with sporidesmin A. Sporidesmin D caused no liver injury, as detected by changes in serum enzyme activity, while the liver injury caused by sporidesmin A was greatest for the sheep with the highest cumulative output of metabolite. When sporidesmin D was administered in two separate doses to sheep bred for either resistance or susceptibility to facial eczema, the variability of metabolic output between sheep within groups was much less after the second dose. The mean urinary metabolite excretion was greater for the susceptible than the resistant sheep but the difference was not significant. Potentiation (caused by pre-administration of small doses of sporidesmin A) resulted in a more severe reaction to the dosed sporidesmin A. Urinary output of metabolite was less in the potentiated than in the unpotentiated sheep. When resistant and susceptible sheep were dosed with sporidesmin A after potentiation there was no difference between them in their cumulative totals or excretion rates of immunoreactive metabolites. However, the volume of urine produced by the susceptible sheep was lower and less variable than the resistant sheep and consequently the concentration of their urinary metabolites was higher. Preliminary ELISA examination of HPLC-fractionated urine from a sheep dosed with sporidesmin A indicated the presence of several metabolites of sporidesmin. Sporidesmin A and metabolites are rapidly excreted in urine but not as rapidly as sporidesmin D and its metabolites. Only minor differences between sheep bred for resistance and susceptibility were seen. Potentiation caused a more severe reaction to sporidesmin A and less urinary excretion of the sporidesmin and its metabolites. This work is part of a programme with the aim of identifying FE-resistant animals without the need for sporidesmin dosing.


Adaptor device for shortening guide catheters to access distal lesions in coronary angioplasty.
One of the challenges in interventional cardiology is accessing distal stenoses in both native coronary arteries and bypass grafts. This article reports the fabrication and use of an adaptor device that can be connected to the proximal segment of a shortened guide catheter for easier and safer access to these distal lesions.


An experimental and thermodynamic equilibrium investigation of the Pb, Zn, Cr, Cu, Mn and Ni partitioning during sewage sludge incineration.
The effects of different chlorides and operational conditions on the distribution and speciation of six heavy metals (Pb, Zn, Cr, Cu, Mn and Ni) during sludge incineration were investigated using a simulated laboratory tubular-furnace reactor. A thermodynamic equilibrium investigation using the FactSage software was performed to compare the experimental results. The results indicate that the volatility of the target metals was enhanced as the chlorine concentration increased. Inorganic-Cl influenced the volatilization of heavy metals in the order of Pb>Zn>Cr>Cu>Mn>Ni. However, the effects of organic-Cl on the volatility of Mn, Pb and Cu were greater than the effects on Zn, Cr and Ni. With increasing combustion temperature, the presence of organic-Cl (PVC) and inorganic-Cl (NaCl) improved the transfer of Pb and Zn from bottom ash to fly ash or fuse gas. However, the presence of chloride had no obvious influence on Mn, Cu and Ni. Increased retention time could increase the volatilization rate of heavy metals; however, this effect was insignificant. During the incineration process, Pb readily formed PbSiO4 and remained in the bottom ash. Different Pb compounds, primarily the volatile PbCl2, were found in the gas phase after the addition of NaCl; the dominant Pb compounds in the gas phase after the addition of PVC were PbCl2, Pb(ClO4)2 and PbCl2O4.


A new era of discovery in facial plastic surgery.
To review recent advances in our understanding of molecular biology and wound healing relevant to facial plastic surgery. Recent basic science literature relevant to molecular biology and wound healing and its clinical implications. During the 21st century, we will experience a new biological and informational age that will have profound implications for facial plastic surgery. This modern era will be driven by discoveries in molecular biology and wound healing that will result in new diagnosis and treatment modalities.


Hydrochemical behaviour of dissolved uranium in selected groundwaters of the Kłodzko Valley (SW Poland) and its application possibilities as an environmental tracer.
Waters from the Kłodzko Valley containing pharmacodynamics therapeutic agents are used for drinking and for balneotherapeutical purposes. These medicinal, highly mineralized waters are mostly of deep circulation. Moreover, outflowing water contain admixture of shallow circulation water of contemporary infiltration which negatively effects medicinal water quality. Due to the complicated pathways of groundwater circulation, the authors used uranium as an environmental indicator to gain deeper insight into the factors affecting the quality of exploited medicinal water and groundwater origin. The authors collected samples from 26 groundwater intakes from 3 Spas and from one mineral water bottling plant for analysis of 234,238U and 234U/238U activity ratios using α-spectrometry technique. Uranium was applied as a dilution tracer of medicinal mineral groundwater by shallow circulation low-mineralized water. The results of 234U/238U activity ratios in particular water intakes collected in different years were equal in the range of uncertainties although the uranium concentrations varied. The stability 234U/238U activity ratio parameter is a consequence of dilution of medicinal water by shallow circulation water of present infiltration with a very small amount or without uranium. Apart from simple water dilution, waters of deep circulation mixed with low mineralized shallow circulation water may also contain an admixture of third deeper circulation component with different both U content and 234U/238U ratio. In that case 234U/238U ratio may be applied as a hydrogeochemical tracer.


Rosemary (Rosmarinus officinalis L.) hydrosol based on serotonergic synapse for insomnia.
Rosemary (Rosmarinus officinalis L.) has been widely used as a traditional remedy for insomnia, depression and anxiety in China and Western countries. Modern pharmacological studies have shown that rosemary has important applications in neurological disorders. However, the mechanism of action of rosemary hydrosol in the treatment of insomnia is not known. Insomnia is closely linked to anxiety and depression, and its pathogenesis is related to biology, psychology, and sociology. Rosemary is a natural plant that has been used to treat insomnia and depression and has good biological activity, but its material basis and mechanism for the treatment of insomnia are not clear. Here, we report on the role of aqueous extracts of rosemary in the treatment of insomnia. The study was based on network pharmacology, using a combination of RNA-sequencing, "quantity-effect" weighting coefficients, and pharmacodynamic experiments. DL-4-chlorophenylalanine (PCPA) was intraperitoneally injected into SD rats to replicate the insomnia model with a blank, model, diazepam, and rosemary hydrosol low-, medium-, and high-dose groups were set up for the experiment. The key pathways in the treatment of insomnia with rosemary hydrosol were analyzed by molecular docking, open field assay, ELISA, western-Blot, Rt-PCR, and immunohistochemical assay. Rosemary hydrosol was analyzed by GC-MS to identify 19 components. 1579 differential genes were obtained by RNA-Seq analysis, 533 targets for rosemary hydrosol and 2705 targets for insomnia, and 29 key targets were obtained by intersection. The KEGG results were ranked by "quantity-effect" weighting coefficients, resulting in serotonergic synapse was the key pathway for the treatment of insomnia with rosemary hydrosol. Molecular docking results showed that 1,7,7-trimethylbicyclo[2.2.1] heptan-2-one, 3-methyl-4-isopropylphenol, caryophyllene, and citronellol of rosemary hydrosol acted synergistically to achieve a therapeutic effect on insomnia. Caryophyllene acts on the HTR1A target by upregulating 5-HT1AR, leading to increased 5-HT release, and upregulation of ADCY5, cAMP, PKA and GABAA at serotonergic synapses; citronellol upregulated ADCY5 and 1,7,7-trimethylbicyclo[2.2.1] heptan-2-one, and 3-methyl-4-isopropylphenol up-regulated GABAA to improve insomnia symptoms. In open-field experiments, ELISA kits (5-HT, GABA, and DA), Western-blotting, Rt-PCR and immunohistochemical assay experiments, insomnia rats in the low-, medium- and high-dose groups of rosemary hydrosol showed different degrees of improvement compared with the model group. It was shown that rosemary hydrosol may exert its therapeutic effects on insomnia through serotonergic synapses by combining RNA-Seq, "quantity-effect" weighting coefficients network pharmacology and pharmacodynamic experiments. We have provided a preliminary theoretical study for the development of rosemary hydrosol additive into a beverage for the treatment of insomnia, but it needs to be studied in depth. This study was conducted in rats and the results have limitations and may not apply to humans.


[Rapid Propagation in vitro of Dioscorea opposita 'Guangfeng'and Its Stomatal Observation,FCM Analysis of Chromosome Ploidy and ISSR Detection of DNA Mutation].
To study the rapid propagation in vitro of Dioscorea opposita'Guangfeng', and to observe the stomas of the transplanting plantlets and potted seedlings, to test chromosome ploidy by FCM, and to detect DNA mutation by ISSR,in order to provide the technical basis for the large-scale production of Dioscorea opposita 'Guangfeng' plantlets. The technique system of Dioscorea opposita 'Guangfeng'rapid propagation in vitro was established and optimized by plant tissue culture method. The parameters of transplanting plantlets and potted seedlings were studied as follows, the stomatal parameters were observed by transparent adhesive tape method, chromosome ploidy were analyzed by FCM, and DNA mutation were detected by ISSR molecular marker. The technique system of Dioscorea opposite 'Guangfeng' rapid propagation in vitro was as follows, slightly woody stem segment with a bud were selected and inoculated onto MS + KT 1 mg / L + NAA 0. 2 mg / L solid culture medium and cultured in the photoperiod of 14 h / d( the temperature was( 25 ± 2) ℃ and light intensity was 1 500 ~ 2 000 Lx) after disinfected for 1 min in 70% alcohol prior to sterilized for 12 min with 0. 1% Hg Cl2,the materials were washed with sterile water for 3 times, respectively. The new bud was cut off when it grew to 2 ~ 3cm and inoculated into MS + KT 2 mg / L + NAA 0. 5 mg / L liquid culture medium and continued to culture in above culture conditions. The whole plant was formed after cultured for about 90 d. The sealing membrane was opened in transplanting, and the plantlets was still placed in above culture conditions and cultured for 2 ~ 3 d, and then the whole plant was taken out, and the culture medium washed off and then transferred into the vessel with shallow liquid MS basic culture medium and domesticated indoor. The acclimated plantlets were taken out and transplanted in the outdoor pots with the sandy soil when the new shoots grew out, and watered one time with tap water in the morning and evening per day, the survival rate reached 100%. The results of stomatal observation, FCM analysis and ISSR detection of transplanting plantlets and potted seedlings showed that the stomatal parameters, chromosome ploidy and DNA mutation of plantlets and potted seedlings had no variation. The results reveal that the establishment and optimization of the technique system of Dioscorea opposita 'Guangfeng' rapid propagation in vitro is feasible, and the regenerated plants do not have genetic variation which can ensure the stability of the genetic.