Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7.
The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation. More recently, the metabolic involvement of further hypothalamic uncharacterized neuron populations has been suggested. In this review, we discuss the potential homeostatic implication of hypothalamic GABAergic neurons that produce Acyl-Coa-binding domain containing protein 7 (ACBD7), precursor of the nonadecaneuropeptide (NDN), which has recently been characterized as a potent anorexigenic neuropeptide capable of relaying the leptin anorectic/thermogenic effect via the melanocortin system.


Primary cortical neuronal cultures reduce cellular energy utilization during anoxic energy deprivation.
It has been widely hypothesized that neurons reduce cellular energy use in response to periods of energy deprivation. To test this hypothesis, we measured rates of energy use under normoxia and anoxia in immature (6 days in vitro) and mature (13 days in vitro) neuronal cultures. During anoxic incubation immature and mature cultures reduced cellular energy use by 80% and 45%, respectively. Reduced cellular energy use dramatically affected ATP depletion in neuronal cultures under anoxia. Intracellular ATP stores were expected to deplete within 3 min of anoxia. However, ATP was maintained at decreased but stabilized concentrations for at least 3 h. The capacity of neuronal cultures to reduce cellular energy use during anoxia correlated with their sensitivity towards simulated ischemia. Immature cultures, with the largest capacity to reduce cellular energy use, survived simulated ischemia 2.5 times longer than mature cultures. The addition of glutamate receptor antagonists to mature cultures further decreased cellular energy use during anoxia and significantly extended their survival time under simulated ischemia. This study verifies that primary cortical neuronal cultures reduce cellular energy use during energy deprivation. Additionally, we show that maturation of glutamate receptor activity increases non-depressible energy demand in neuronal cultures.


Anxiety and alcoholism.
The prevalence and the co-occurrence of anxiety disorders and alcoholism in individuals, families, and the general population have been documented in both epidemiologic and clinical investigations. In patients who fulfill the criteria for one of those conditions, clinicians should consider the possibility of the presence of the other disorder--currently, at a previous time, or at some point in the future. A lifetime history of alcohol abuse and anxiety disorders obtained from both the patient and the family members may assist in determining the appropriate treatment.


Applications of X-ray powder diffraction in materials chemistry.
X-ray powder diffraction is a standard technique in materials chemistry, yet it is often still used in the laboratory as a "one-hit" technique, e.g. for fingerprinting and following the progress of reactions. It is important, however, that the wealth of information available from powder data is not overlooked. While it is only possible here to scratch the surface of possibilities, a range of examples from our research is used to emphasize some of the more accessible techniques and to highlight successes as well as potential problems. The first example is the study of solid solution formation in the oxide systems Ba(3-3x)La(2x)V2O8 and Sr(4-x)Ba(x)Mn3O10 and in the silicate-hydroxyapatite bioceramic, Ca10(PO4)6-x(SiO4)x(OH)2-x. Database mining is also explored, using three phases within the pseudobinary phase diagram Li3SbO4-CuO as examples. All three phases presented different challenges: the structure of Li3SbO4 had been previously reported in higher symmetry than was actually the case, Li3Cu2SbO6 was found to be isostructural with Li2TiO3 but the cation ordering had to be rationalized, and Li3CuSbO5 was believed to be triclinic, presenting challenges in indexing the powder pattern. Quantitative phase analysis is briefly discussed, with the emphasis both on success (determination of amorphous phase content in a novel cadmium arsenate phase) and on possible failure (compositional analysis in bone mineral); the reasons for the problems in the latter are also explored. Finally, the use of an area detector system has been shown to be of value in the study of orientational effects (or lack of them) in non- and partially-ordered biomaterials, including p-HEMA, annulus fibrosis of lumbar discs, and keratin in the horn of cow's hooves.


Vasoactive intestinal peptide prevents PKCε-induced intestinal epithelial barrier disruption during EPEC infection.
We previously showed that vasoactive intestinal peptide (VIP) protects against bacterial pathogen-induced epithelial barrier disruption and colitis, although the mechanisms remain poorly defined. The aim of the current study was to identify cellular pathways of VIP-mediated protection with use of pharmacological inhibitors during enteropathogenic Escherichia coli (EPEC) infection of Caco-2 cell monolayers and during Citrobacter rodentium-induced colitis. EPEC-induced epithelial barrier disruption involved the PKC pathway but was independent of functional cAMP, Rho, and NF-κB pathways. VIP mediated its protective effects by inhibiting EPEC-induced PKC activity and increasing expression of the junctional protein claudin-4. Short-term treatment with TPA, which is known to activate PKC, was inhibited by VIP pretreatment, while PKC degradation via long-term treatment with TPA mimicked the protective actions of VIP. Immunostaining for specific PKC isotypes showed upregulated expression of PKCθ and PKCε during EPEC infection. Treatment with specific inhibitors revealed a critical role for PKCε in EPEC-induced barrier disruption. Furthermore, activation of PKCε and loss of barrier integrity correlated with claudin-4 degradation. In contrast, inhibition of PKCε by VIP pretreatment or the PKCε inhibitor maintained membrane-bound claudin-4 levels, along with barrier function. Finally, in vivo treatment with the PKCε inhibitor protected mice from C. rodentium-induced colitis. In conclusion, EPEC infection increases intracellular PKCε levels, leading to decreased claudin-4 levels and compromising epithelial barrier integrity. VIP inhibits PKCε activation, thereby attenuating EPEC-induced barrier disruption.


Small-angle X-ray scattering and rheological characterization of aqueous lignosulfonate solutions.
Lignosulfonate is a colloidal polyelectrolyte widely used as a dispersant in various industrial applications and produced during chemical pulping of wood chips. Here we present a systematic small-angle X-ray scattering (SAXS) and rheological study of fractionated lignosulfonate (mass weighted molar mass M w 18 000 g/mol) dissolved in water and 0.2 M NaCl. The concentration range varied from semidilute to concentrated regime. SAXS intensity of all solutions followed the Porod law at all concentrations, which is a clear indication of a compact shape of the lignosulfonate particle. In water, below 10 mass % lignosulfonate, the average interparticle distance obtained from SAXS patterns relates to concentration via a power law with exponent -0.28. Deviation of the power law exponent from ideal -0.33 and a linear decrease in volume fraction normalized Porod constant as a function of concentration are taken as indications of self-association of lignosulfonate. In saline solutions at high lignosulfonate mass fractions the average distance between lignosulfonate particles was longer and the average particle size was larger than those in aqueous solutions. The intrinsic viscosity in saline solution also was larger than that in aqueous solution. Lignosulfonate solutions showed Newtonian viscosity, except at very high concentrations. The variation of the relative zero-shear viscosity eta(0),r) with concentration was interpreted with the Krieger-Dougherty equation. An oblate spheroid shape with an axial ratio of 3.5 describes the average shape of the lignosulfonate particles in saline solutions based on SAXS intensities, the size distribution obtained using gel permeation chromatography, and rheological characterization. The largest dimension of the particles was about 8 nm. SAXS and rheology studies as a function of temperature reveal indications of temperature-dependent self-association.


Single-molecule rupture dynamics on multidimensional landscapes.
We explore emergent effects of multidimensionality of the free energy landscape on single-molecule kinetics under constant force. The proposed minimal model reveals the existence of a spectrum of unusual scenarios for the force-dependent lifetime, all of which are shown to occur on a free energy landscape with a single transition state. We present an analytical solution that governs single-molecule responses to a constant force and relates them to microscopic parameters of the system.


Starch Derived Porous Carbon Nanosheets for High-Performance Photovoltaic Capacitive Deionization.
Capacitive deionization (CDI) is an emerging technology that uniquely integrates energy storage and desalination. In this work, porous carbon nanosheets (PCNSs) with an ultrahigh specific surface area of 2853 m2/g were fabricated by the simple carbonization of starch followed by KOH activation for the electrode material of photovoltaic CDI. The CDI cell consisting of PCNSs electrodes exhibited a high salt adsorption capacity (SAC) of 15.6 mg/g at ∼1.1 V in 500 mg/L NaCl as well as high charge efficiency and low energy consumption. KOH activation played a key role in the excellent CDI performance as it not only created abundant pores on the surface of PCNSs but also made it fluffy and improved its graphitization degree, which are beneficial to the transport of ions and electrons. PCNSs are supposed to be a promising candidate for CDI electrode materials. The combination of solar cells and CDI may provide a new approach to reduce the energy cost of CDI and boost its commercial competitiveness.


Toward the rational design of lipid gene vectors: shape coupling between lipoplex and anionic cellular lipids controls the phase evolution of lipoplexes and the efficiency of DNA release.
A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon interaction with anionic cellular lipids, resulting in DNA release. At the early stages of interaction, we found a universal behavior of lipoplex/anionic lipid (AL) mixtures: the lipoplex structure is slightly perturbed, while the one-dimensional DNA lattice between cationic membranes is largely diluted by ALs. This finding is in excellent agreement with previous suggestions on the mechanism of DNA unbinding from lipoplexes by ALs. Upon further interaction, the propensity of a given lipoplex structure to be solubilized by anionic cellular lipids strongly depends on the shape coupling between lipoplex and ALs. Furthermore, we investigated the effect of the membrane charge density and a general correlation resulted: the higher the membrane charge density of anionic membranes, the higher their ability to solubilize the structure of lipoplexes and to promote DNA release. Lastly, the formation of nonlamellar phases in lipoplex/AL mixtures is regulated by the propensity of anionic cellular lipids to adopt nonlamellar phases. Remarkably, also phase transition rates and DNA release were found to be strongly affected by the shape coupling between lipoplex and ALs. It thus seems likely that the structural and phase evolution of lipoplexes may only be meaningful in the context of specific anionic cellular membranes. These results highlight the phase properties of the carrier lipid/cellular lipid mixtures as a decisive factor for optimal DNA release and suggest a potential strategy for the rational design of efficient cationic lipid carriers.


[Not Available].
By the end of World War I the Hungarian Psychoanalytic movement was strong and deeply integrated into the cultural and intellectual life of Budapest. The city was ready to be the center of the European psychoanalysis. The paper discusses how Budapest lost its growing eminence as a center, but because of the political-social changes in Hungary in the years 1918-1920. The paper will examine the two waves of Hungarian emigration between the world wars, the first in the early twenties to the Weimar Republic, and then in the thirties, to the United States and Australia. These movements of important Hungarian psychoanalysts, account both becoming weaker of the Budapest School and at the same time its influence in other countries. The author highlights the outstanding role of the American Psychoanalytic Association's setting up the Emergency Committee on Relief and Immigration in saving the lives of many European colleagues. America was open to European psychoanalysis at that time and in return immigrants facilitated the development of modern psychotherapy and psychoanalysis. The influence of Vienna, Budapest and Berlin can be traced in contemporary psychoanalytic culture in the United States. The documentation for this paper was researched in Washington, D.C., New York and London, supported by fellowships and grants from the Woodrow Wilson International Center and the Soros Foundation.


Catalytic Metallodrugs: Substrate-Selective Metal Catalysts as Therapeutics.
Metal complexes that catalyze inactivation and degradation of biomolecular targets can be developed into novel therapeutics (catalytic metallodrugs) against a variety of diseases. Despite recent advances in the field, a lack of substrate selectivity is a major hindrance to the development of catalytic metallodrugs for application in clinical practice. Improved targeting can minimize nonselective activity and the potential for side effects. Herein, we focus on recent developments toward novel metal catalysts that exhibit substrate selectivity against a variety of therapeutically relevant biomolecules. Design strategies for developing selective catalytic metallodrugs are also highlighted.


Does better education mitigate risky health behavior? A mendelian randomization study.
Education and risky health behaviors are strongly negatively correlated. Education may affect health behaviors by enabling healthier choices through higher disposable income, increasing information about the harmful effects of risky health behaviors, or altering time preferences. Alternatively, the observed negative correlation may stem from reverse causality or unobserved confounders. Based on the data from the Cardiovascular Risk in Young Finns Study linked to register-based information on educational attainment and family background, this paper identifies the causal effect of education on risky health behaviors. To examine causal effects, we used a genetic score as an instrument for years of education. We found that individuals with higher education allocated more attention to healthy habits. In terms of health behaviors, highly educated people were less likely to smoke. Some model specifications also indicated that the highly educated consumed more fruit and vegetables, but the results were imprecise in this regard. No causal effect was found between education and abusive drinking. In brief, inference based on genetic instruments showed that higher education leads to better choices in some but not all dimensions of health behaviors.


Differentiation of poliovirus type I isolates in the 1982 epidemic from Sabin-I strain by antigenic and temperature markers.
Poliovirus type 1 strains recovered from patients with poliomyelitis during the epidemic of 1982, were distinct antigenically from Sabin-1 strain by comparing homologous and heterologous neutralization rate constants of Sabin-1 specific antiserum. With the reproductive capacity at 40 degrees C, these isolates could be easily differentiated from vaccine strain. It was suggested that the epidemic of poliomyelitis in 1982 was not caused by vaccine strain. The 24 isolates reacted with LSc and/or Sabin-1 antisera to the same extent. It was speculated that they might be antigenically similar if not identical. Three isolates which were collected from the later part of epidemic formed small plaques at 40 degrees C. Rabbit antisera against poliovirus strains 3844, Sabin-1, Mahoney and Brunhilde were produced. Antigenic relatedness among the strains was tested by kinetic neutralization. The strain 3844 was distinct from Brunhilde, Mahoney and Sabin-1. Asymmetric cross-reactions between Mahoney and Sabin-1 strains were clearly demonstrated.


MS-FRAN: A Novel Multi-Source Domain Adaptation Method for EEG-Based Emotion Recognition.
Electroencephalogram (EEG)-based emotion recognition has gradually become a research hotspot. However, the large distribution differences of EEG signals across subjects make the current research stuck in a dilemma. To resolve this problem, in this article, we propose a novel and effective method, Multi-Source Feature Representation and Alignment Network (MS-FRAN). The effectiveness of proposed method mainly comes from three new modules: Wide Feature Extractor (WFE) for feature learning, Random Matching Operation (RMO) for model training, and Top- h ranked domain classifier selection (TOP) for emotion classification. MS-FRAN is not only effective in aligning the distributions of each pair of source and target domains, but also capable of reducing the distributional differences among the multiple source domains. Experimental results on the public benchmark datasets SEED and DEAP have demonstrated the advantage of our method over the related competitive approaches for cross-subject EEG-based emotion recognition.


Negative correlation of LIV-1 and E-cadherin expression in hepatocellular carcinoma cells.
LIV-1, a zinc transporter, is a mediator downstream of STAT3 both in zebrafish and mammalian cells, and is involved in epithelial-mesenchymal transition (EMT). Despite LIV-1 participates in cancer growth and metastasis, little is known about the association of LIV-1 with human liver cancer development. Therefore, the expression of LIV-1 mRNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) in 4 cultured cell lines (3 carcinoma and 1 normal liver cell lines), and the localization of LIV-1 protein was investigated by immunohistochemistry. Expression of LIV-1 protein was analyzed by Western blot both in 4 cultured cell lines and 120 liver tissues (100 carcinoma and 20 histologically normal tissues), and the relationship between its expression and clinicopathological finding was investigated in 100 hepatocellular carcinoma(HCC) tissues. Then stable siRNA expressing Hep-G2 cells were generated to assess the function of LIV-1 in liver cancer cells. We found that LIV-1 mRNA was more highly expressed in liver cancer cell lines compared to normal liver cell line. Western blot showed the expression of LIV-1 was higher in 61% liver carcinoma tissues than that in normal liver tissues. Down-regulated LIV-1 cells showed significant inhibition of proliferation in vitro and reduction of tumor growth in vivo. Furthermore, E-cadherin expression increased in LIV-1 siRNA expressing Hep-G2. These findings indicated that LIV-1 may induce the EMT in HCC cells.


[Clinical and psychopatological features of endogenous depressions in young women].
To study the features of psychopatological structure of endogenous depression in young women and to identify correlations between various clinical types of depression and their nosological affilation. The results of clinical/psychopathological examination of 107 female patients, aged 16 to 25 years, with endogenous depression with one of the following ICD-10 diagnosis: (F34.0; F31.3-F31.5; F21.3-F.21.4+F31.3-F31.5; F60.X+F31.3-F31.5) were analyzed. Several types of endogenous depression were identified: 1) hysterical depression with hysterical-conversions, and also the phenomena of delusional fantasies; 2) dysmorphic depression with predominance of over-valued ideas of physical disability, self-inferiority and eating disorder; 3) depersonalization depression with depersonalization-derealization symptoms; 4) psychopath-like depression with exaggerated behavior, opposition and impulsivity; 5) existential depression with a feeling of losing the life meaning and often pessimistic worldview; 6) psychasthenic depression with the low self-esteem and exaggerated introspection combined with obsessive-phobic disorder; 7) anxious-melancholic depression with anxiety, melancholy and ideas of self-accusation and self-inferiority; 8) depression with symptoms of adolescent asthenic insolvency with difficulties of understanding information, increasing intellectual exhaustion. We revealed differences in motives for committing non-suicidal self-harm behavior and suicidal behavior in typological variants of depressions. Hysteroform and psychopathic depressions prevail in personality disorders, while psychosthenic-like, anxious-melancholic and existential depressions are more frequent in affective disorders. Depersonalization depressions are more common in schizotypal disorder. When comparing the types of depressions in boys as reported in previous research with those in girls, the prevalence of hysteroform and anxious-melancholic variants in girls is revealed.


miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma.
Abnormal expression of HGF is found in various cancers and correlates with tumor proliferation, metastasis and angiogenesis. However, the regulatory mechanism of the HGF-VEGF axis remains unclear. The expression characteristic of HGF in human gastric cancer tissues was shown by an immunohistochemistry assay, and the expression levels of target protein were detected by Western blot. The relative levels of miR-26a/b and target mRNA were examined by qRT-PCR. We used bioinformatics tools to search for miRNAs that can potentially target HGF. A luciferase assay was used to confirm direct targeting. Furthermore, the functions of miR-26a/b and HGF were evaluated by cell proliferation and migration assays in vitro and by the mouse xenograft tumor model in vivo. We found that the HGF protein was clearly increased while miR-26a/b were dramatically down-regulated in gastric cancer. miR-26a/b directly bind to the 3'-UTR of HGF mRNA at specific targeting sites. We demonstrated that the repression of the HGF-VEGF pathway by miR-26a/b overexpression suppressed gastric cancer cell proliferation and migration. Furthermore, miR-26a/b also showed an anti-tumor effect in the xenograft mouse model by suppressing tumor growth and angiogenesis. miR-26a/b could suppress tumor tumorigenesis and angiogenesis by targeting the HGF-VEGF axis and could serve as a potential treatment modality for targeted therapy in the clinical treatment of gastric cancer.


Parenteral opioids for labor pain relief: a systematic review.
Parenteral opioids are commonly used for labor pain relief and have been the subject of research for many years. The objectives of this review were to determine the safety and effectiveness of parenteral opioids in this context. Of 85 trials systematically reviewed, 48 comprising more than 9800 were included, but the number of trials contributing data to individual outcome measures is very limited. Epidural provides better pain relief. However, if women opt for systemic analgesia, no strong preference for any of the opioids can be recommended. Pethidine is the most commonly used opioid worldwide, and although there are considerable doubts about its analgesic effectiveness and concerns about its potential maternal, fetal, and neonatal side effects, it has the virtue of familiarity and low cost. There is as yet no convincing research evidence to show that alternative opioids are better. In view of the large number of women who receive opioids in labor and the paucity of research evidence about the relative effectiveness and side effects of different opioids and opioids compared with other methods (apart from epidural), well-designed and suitably sized trials of pethidine versus the main alternatives that address substantive outcomes for mothers and babies are strongly recommended.


Inelastic Coulomb scatterings of doped armchair carbon nanotubes.
For doped armchair carbon nanotubes, the free electrons in the conduction bands would cause the intraband single-particle and collective excitations. Both kinds of excitations would be split into two modes because of two different Fermi-momentum states (kF'S). The excited carriers might be deexcited through such Coulomb excitations. Regarding the case where the transferred momentum L = 0, the two single-particle and the lower-frequency collective excitation modes could be the efficient deexcitation channels. In the lowest bands, the decay rates of the electron states exhibit weak Fermi energy (E(F)) dependence, but the decay rates of the hole states become greater with the increase of E(F) except for the right-side k(F). Concerning the states in the higher bands, the L not equal 0 excitations also take part in the deexcitation processes. Both the electron and hole states have the same decay rates except for the case where the carriers decay to the lowest states. The decay rates contrast sharply with those of undoped carbon nanotubes and two-dimensional intercalated graphenes. It is domenated by the Fermi energy, the geometric structure and the dimensionalities. The femtosecond time-resolved photoelectron, transmission and fluorescence spectroscopies could be used to verify the predicted results.


Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China.
The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient's adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.


Acid-catalyzed synthesis of methylene-bridged (S)-tyrosine-phenol dimers.
The efficient synthesis of 2,2'-arylmethylene dimers from 3-hydroxymethyl or 3-methoxymethyl-5-halo-(S)-tyrosines and para-substituted phenols under acid-catalyzed reaction conditions using either conventional or microwave-assisted protocols is described.


Missed isolated volar dislocation of the scaphoid.
A patient presented with volar dislocation of the scaphoid, the diagnosis of which had been missed for two weeks. He was treated with open reduction through a combined volar and dorsal approach with decompression of the median nerve, internal fixation, and a cast for eight weeks. One year postoperatively the functional result was good. A radiograph showed no sign of avascular necrosis.


A replication silencer element in a plus-strand RNA virus.
Replication represents a key step in the infectious cycles of RNA viruses. Here we describe a regulatory RNA element, termed replication silencer, that can down-regulate complementary RNA synthesis of a positive-strand RNA virus via an RNA-RNA interaction. This interaction occurs between the 5-nucleotide-long, internally positioned replication silencer and the extreme 3'-terminus of the viral RNA comprising part of the minimal minus-strand initiation promoter. Analysis of RNA synthesis in vitro, using model defective interfering (DI) RNA templates of tomato bushy stunt virus and a partially purified, RNA-dependent RNA polymerase preparation from tombusvirus-infected plants, revealed that this interaction inhibits minus-strand synthesis 7-fold. This functional interaction was supported further by: (i) RNA structure probing; (ii) phylogenetic analysis; (iii) inhibition of activity by short complementary DNAs; and (iv) compensatory mutational analysis. The silencer was found to be essential for accumulation of DI RNAs in protoplasts, indicating that it serves an important regulatory role(s) in vivo. Because similar silencer-promoter interactions are also predicted in other virus genera, this type of RNA-based regulatory mechanism may represent a widely utilized strategy for modulating replication.


Dihydromatricaria acid: acetylenic acid secreted by soldier beetle.
The aposematic cantharid beetle Chauliognathus lecontei produces a defensive secretion, from glands in its thorax and abdomen, containing 8-cis-dihydromatricaria acid. Similar acetylenic compounds are known only from certain fungi and flowering plants.


Genome-Wide Identification and Characterization of Long Non-Coding RNA in Wheat Roots in Response to Ca2+ Channel Blocker.
It remains unclear whether plant lncRNAs are responsive to Ca2+-channel blocking. When using the Ca2+-channel blocker, LaCl3, to treat germinated wheat seeds for 24 h, we found that both root length and mitosis were inhibited in the LaCl3-treated groups. The effect of the Ca2+-channel blocker was verified in three ways: a [Ca2+]cyt decrease detected using Fluo-3/AM staining, a decrease in the Ca content measured using inductively coupled plasma mass spectrometry, and an inhibition of Ca2+ influx detected using Non-invasive Micro-test Technology. Genome-wide high throughput RNA-seq and bioinformatical methods were used to identify lncRNAs, and found 177 differentially expressed lncRNAs that might be in responsive to Ca2+-channel blocking. Among these, 108 were up-regulated and 69 were down-regulated. The validity of identified lncRNAs data from RNA-seq was verified using qPCR. GO and KEGG analysis indicated that a number of lncRNAs might be involved in diverse biological processes upon Ca2+-channel blocking. Further GO analysis showed that 23 lncRNAs might play roles as transcription factor (TF); Moreover, eight lncRNAs might participate in cell cycle regulation, and their relative expressions were detected using qPCR. This study also provides diverse data on wheat lncRNAs that can deepen our understanding of the function and regulatory mechanism of Ca2+-channel blocking in plants.


Peripheral Hypoarousal but Not Preparation-Vigilance Impairment Endures in ADHD Remission.
Objective: This study investigates whether impairments associated with persistent ADHD-impaired attention allocation (P3 amplitude), peripheral hypoarousal (skin conductance level [SCL]), and adjustment in preparatory state (contingent negative variation [CNV])-reflect enduring deficits unrelated to ADHD outcome or are markers of ADHD remission. Method: Young people with childhood ADHD (73 persisters and 18 remitters) and 144 controls were compared on neurophysiological measures during two conditions (baseline and fast-incentive) of a four-choice reaction time task. Results: ADHD remitters differed from persisters, and were indistinguishable from controls, on baseline P3 amplitude and fast-incentive CNV amplitude (p ≤ .05). ADHD remitters differed from controls (p ≤ .01), and were indistinguishable from persisters (p > .05), on baseline SCL. Conclusion: Preparation-vigilance measures were markers of ADHD remission, confirming previous findings with other measures. Yet, SCL-measured peripheral hypoarousal emerges as an enduring deficit unrelated to ADHD improvement. Future studies should explore potential compensatory mechanisms that enable efficient preparation-vigilance processes in ADHD remitters.


Metastatic pulmonary calcinosis and leukocytoclastic vasculitis in a patient with multiple myeloma.
Both leukocytoclastic vasculitis and metastatic pulmonary calcification are conditions that rarely occur during the course of multiple myeloma. We present a multiple myeloma patient that had severe dyspnea due to metastatic pulmonary calcinosis, and ulceronecrotic skin lesions caused by leukocytoclastic vasculitis. After 3 courses of standarddose chemotherapy all skin and pulmonary lesions disappeared. Autologous peripheral stem cell transplantation was performed and during 1 year of follow-up the patient was in complete remission; after 1 year, laboratory test results indicated disease relapse. Although the patient was treated with bortezomib and dexamethasone, the disease progressed. Non-myeloablative allogeneic stem cell transplantation was performed, but despite of all treatment the patient died due to disease progression. None declared.


Differences in Molecular Characteristics of Segment 8 in Rice black-streaked dwarf virus and Southern rice black-streaked dwarf virus.
Rice black-streaked dwarf virus (RBSDV) and Southern rice black-streaked dwarf virus (SRBSDV) cause maize rough dwarf disease (MRDD) and rice black-streaked dwarf disease (RBSDD) in China. RBSDV segment 8 (S8) contains the only deletion mutation in the genomes of these viruses, which are both members of the genus Fijivirus. To illuminate the molecular differences between the RBSDV and SRBSDV genomes and better understand the evolution of these viruses, and to determine which virus is specifically associated with MRDD and RBSDD in each region, S8 was analyzed in 66 virus isolates collected from 10 geographic locations in China and 14 S8 sequences obtained from the National Center for Biotechnology Information GenBank. Phylogenetic analysis showed that the pathogen associated with MRDD and RBSDD in the Yellow and Huai River valleys was RBSDV, whereas the pathogen associated with these diseases in Sanya was SRBSDV. Codon usage bias in S8 differed significantly between RBSDV and SRBSDV, as indicated by effective number of codons used by a gene (Nc) and GC values, Nc plots, and variation explained by the first axis in correspondence analysis. The nucleotide identities among these 66 RBSDV and SRBSDV isolates ranged from 66.2 to 68.2%, and were considerably lower than the nucleotide identities within RBSDV (from 94.1 to 99.9%) or SRBSDV (from 93.9 to 100%) isolates. Most S8 polymorphisms were identified in the region from 1,000 to 1,200 bp in RBSDV and in the region from 500 to 700 bp in SRBSDV. The difference in the lengths of RBSDV (1,936 bp) and SRBSDV (1,928 bp) was due to an 8-bp deletion in the 3'-untranslated region of SRBSDV. Six recombination events were detected in S8 in RBSDV and two recombination events were detected in S8 in SRBSDV. Recombination breakpoints were found within the region containing the deletion mutation in nine isolates. However, no recombination events were detected between RBSDV and SRBSDV. Both of these viruses were under negative and purifying selection, although the ratio of nonsynonymous mutations to synonymous mutations (Ka/Ks) for RBSDV S8 (0.0530) was not significantly lower than that of SRBSDV S8 (0.0823, P = 0.1550). We found that SRBSDV was more highly genetically differentiated (product of effective population size and the migration rate among populations < 1; values for the among-populations component of genetic variation or normalized variation > 0.33; and P values of the sequence statistic, the rank statistic, and the nearest-neighbor statistic < 0.01) than RBSDV. However, gene flow between RBSDV and SRBSDV was not frequent.


Cone Beam Computed Tomographic imaging in orthodontics.
Over the last 15 years, cone beam computed tomographic (CBCT) imaging has emerged as an important supplemental radiographic technique for orthodontic diagnosis and treatment planning, especially in situations which require an understanding of the complex anatomic relationships and surrounding structures of the maxillofacial skeleton. CBCT imaging provides unique features and advantages to enhance orthodontic practice over conventional extraoral radiographic imaging. While it is the responsibility of each practitioner to make a decision, in tandem with the patient/family, consensus-derived, evidence-based clinical guidelines are available to assist the clinician in the decision-making process. Specific recommendations provide selection guidance based on variables such as phase of treatment, clinically-assessed treatment difficulty, the presence of dental and/or skeletal modifying conditions, and pathology. CBCT imaging in orthodontics should always be considered wisely as children have conservatively, on average, a three to five times greater radiation risk compared with adults for the same exposure. The purpose of this paper is to provide an understanding of the operation of CBCT equipment as it relates to image quality and dose, highlight the benefits of the technique in orthodontic practice, and provide guidance on appropriate clinical use with respect to radiation dose and relative risk, particularly for the paediatric patient.


Optimality of general lattice transformations with applications to the Bain strain in steel.
This article provides a rigorous proof of a conjecture by E. C. Bain in 1924 on the optimality of the so-called Bain strain based on a criterion of least atomic movement. A general framework that explores several such optimality criteria is introduced and employed to show the existence of optimal transformations between any two Bravais lattices. A precise algorithm and a graphical user interface to determine this optimal transformation is provided. Apart from the Bain conjecture concerning the transformation from face-centred cubic to body-centred cubic, applications include the face-centred cubic to body-centred tetragonal transition as well as the transformation between two triclinic phases of terephthalic acid.


Modulation of prelanding lower-limb muscle responses in athletes with multiple ankle sprains.
The objective of this study was to investigate modulation in prelanding muscle responses and its associated impact force on landing from unexpected and self-initiated drops in male basketball players with a history of bilateral multiple ankle sprains (BMAS). Prelanding EMG responses were recorded in four lower-limb muscles, together with the impact force on landing, while 20 healthy and 19 basketball players with BMAS performed unexpected, self-initiated drops from a height of 30 cm. Group differences were detected after self-initiated but not unexpected drops. Two main changes in prelanding EMG responses were observed in the injured basketball players during the self-initiated drops. First, tibialis anterior (TA) was activated significantly earlier in the injured group, whereas left tensor fascia latae appeared closer to the moment of landing (P < 0.025) than in the healthy players. Second, cocontraction indexes between left TA and peroneus longus, and left TA and medial gastrocnemius, were significantly greater in the injured than in the healthy players (P < 0.025). On landing, higher magnitude-of-impact forces were observed in the injured players on the right leg (by 23%, P = 0.012). In basketball players with BMAS, modulation of prelanding muscle response latencies occurred in injured (ankle) and uninjured (hip) joints during self-initiated but not unexpected drops. Greater cocontraction index between the left ankle muscle pairs in preparation for landing from self-initiated drops, and a significantly higher magnitude of impact force in the right leg on landing, were observed in the injured players.


Mesenchymal adipose stem cells maintain the capacity for differentiation and survival in culture beyond the long term.
Mesenchymal cells (MSCs) are considered to be cellular populations of common embryological origin. For clinical research applications, MSCs are expanded and increased with cells obtained from a primary culture. By extracting cells from tissue and encouraging them to reproduce, the stem cell population ends up dominating the culture due to a high proliferation rate and self-renewal. The first subcultures between the third and sixth are chosen in order to obtain the maximum number of cells with optimal differentiation capacity. However, few studies have reported long-term cultivation of MSCs. The objective of this study was to advance the knowledge on the characteristics of MSCs by assessing their capacity for self-renewal and phenotypic maintenance beyond 50 cell subcultures, which is defined as the normal limit for cellular survival. Rat subcutaneous adipose tissue was the source of mesenchymal adipose stem cells (MASCs) cultured over 175 subcultures. Early 1 to 5 and late 25 to 30 subcultures were used to induce cellular differentiation to become adipogenic, chondrogenic and osteogenic connective tissue cells. MASCs characteristics were studied using flow cytometry, transmission electron microscopy (TEM), and immunohistochemical and reverse transcription polymerase chain reaction (RT-qPCR) assays. The MASCs maintained cell differentiation capacity for more than 30 subcultures but lost potentiality starting at 60 up to 175 subcultures. MASCs showed the embryonic phenotypes OCT3/4 and Nanog indefinitely, and developed compensatory mechanisms, such as autophagy, to achieve cell survival over a long time period. Therefore, long-term subcultures showed that MASCs could maintain their potential for clinical research use.


[Diagnosis of Kayser Fleischer Ring: Can Early Diagnosis Improve the Outcome of Wilson's Disease?]
Wilson's disease is a rare genetic disease of copper metabolism that leads to increased accumulation of copper in the body. Deposits are found mainly in the liver, brain and eye. If left untreated, the disease can lead to movement disorders, personality changes, liver failure and even death. There are many possible differential diagnoses. Diagnosis can only be made through specific test procedures. The ophthalmologist therefore has a special role in the early detection of a Wilson's disease. In our clinic, a 19-year old female patient presented with a faint Kayser-Fleischer corneal ring with otherwise normal ophthalmological findings. The patient had progressive liver failure and received a liver transplant two months after first presentation in the eye clinic. An early ophthalmological co-evaluation with a thorough examination is of great importance for rapid diagnosis. The copper deposits are found in the Descemet membrane and begin in the Schwalbe's line. The so-called Kayser-Fleischer ring can be seen on the Descemet membrane up to 5 mm away from the limbus. Other possible ophthalmological manifestations are chalcosis of the entire Descemet, icterus of the sclera or a sunflower cataract. In the absence of copper deposits in the slit lamp examination, gonioscopy should always be performed if Wilson's disease is suspected. Early diagnosis can protect patients from unnecessary complications and operations. Wilson's disease has a good prognosis if treated.


Identification of rhodamine 123-positive stem cell subpopulations in canine hepatocellular carcinoma cells.
The majority of cases of chemotherapy for hepatocellular carcinoma (HCC) are not effective in human or veterinary medicine due to resistance against anticancer agents. In human medicine, hepatocellular carcinoma stem cells (HCSCs) were recently identified as cytokeratin 19 (CK19)-, cluster of differentiation (CD)-44-, and CD133-positive. However, there are few previous reports regarding canine HCSC (cHCSC). Additionally, to the best of our knowledge, the chemoresistance against anticancer agents of these cHCSCs has not been investigated. In the present study staining of cHCSCs was performed with rhodamine 123, a low-toxicity fluorescent dye for mitochondria, by flow cytometry. There were two subpopulations in the HCC cell line defined by their higher (RhoHi) and lower (RhoLo) fluorescence intensity of rhodamine 123. The RhoHi subpopulation demonstrated a higher Nanog gene expression, sphere-forming ability, and chemoresistance against gemcitabine. However, there was no significant difference between RhoHi and RhoLo regarding the proliferation rate and chemoresistance against mitoxantrone and doxorubicin. The present results indicate that the expression of rhodamine 123 identifies different stem cell subpopulations in a canine HCC cell line.


Tilting Whole Body Vibration improves quality of life in women with fibromyalgia: a randomized controlled trial.
The aim of this study was to analyze the effect of 12-week tilting Whole Body Vibration therapy (WBV) on Health Related Quality of Life (HRQoL) in fibromylagia (FM) within the context of a randomized control trial (ISRCTN16950947). Thirty-six (36) women with FM were randomly allocated to either an exercise or a control group. The women in the exercise group were assigned to a 12-week course of tilting WBV (12.5-Hz frequency; 3-mm amplitude). HRQoL was assessed using the Fibromyalgia Impact Questionnaire (FIQ) and a 15D questionnaire. A 12-week course of tilting WBV therapy was associated with improvements in FIQ scores (12%) but not in the 15D questionnaire. Tilting WBV was a feasible intervention that prevented the loss of HRQoL in previously physically untrained women with FM.


A focus on computer vision for non-contact monitoring of catalyst degradation and product formation kinetics.
Chemists know the value of looking at a reaction for clues about reaction progress and success, but what-it-looks-like has never been quantified. Reid and co-workers (C. Yan, M. Cowie, C. Howcutt, K. M. P. Wheelhouse, N. S. Hodnett, M. Kollie, M. Gildea, M. H. Goodfellow and M. Reid, Chem. Sci., 2023, 14, 5323-5331, https://doi.org/10.1039/d2sc05702f) have developed an approach that uses camera footage of reactions to obtain quantitative descriptors of changes in reaction mixtures to support kinetic analysis.


Apoptosis and engulfment by bronchial epithelial cells. Implications for allergic airway inflammation.
Insult or injury to the lung epithelial cells from pathogens, pollutants, and allergens can initiate the process of apoptotic cell death. Although "Creola bodies," which are clusters of uncleared, apoptotic, epithelial cells, have been seen in the sputum of patients with asthma, the clearance of these dying epithelial cells and the consequence of failed clearance in the airway have not been directly addressed. We have observed that bronchial epithelial cells efficiently engulf their apoptotic neighbors and produce antiinflammatory cytokines when engulfing apoptotic cells. Furthermore, when the phagocytic capacity of bronchial epithelial cells was impaired, mice developed severe, IL-33-dependent, allergic airway inflammation. This inflammation could be ameliorated by exogenous administration of the antiinflammatory cytokine IL-10. Our data suggest that the process of apoptotic cell engulfment is a mechanism by which bronchial epithelial cells regulate the inflammatory environment within the lung. Collectively, these studies suggest that impaired engulfment pathways in airway epithelial cells can contribute to allergic airway inflammation and that targeting these pathways may be of benefit in human airway inflammation.


The effects of triclabendazole on the lung fluke, Paragonimus uterobilateralis in the experimental host Sigmodon hispidus.
The new veterinary drug triclabendazole (Fasinex) was tested for its anthelmintic activity against adult Paragonimus uterobilateralis in experimentally infected cotton rats, Sigmodon hispidus. After a single dose of 50, 100 or 150 mg/kg b.w. triclabendazole or after two doses of 5 or 10 mg/kg b.w. given at an interval of 24 hours, 56-61% of the flukes were dead at three to five weeks after treatment. Two doses of 50 or 75 mg/kg b.w. triclabendazole killed all flukes. The flukes, which were still alive three to five weeks after treatment, were significantly smaller than the un-treated controls. Histological sections from these flukes showed severely damaged tissues. It is assumed that these flukes would have died later.


Online survey seeks to improve management of extravasation.
A NHS trust is aiming to improve the management of extravasation in the UK by filling a gap in national reporting with an online survey.


Of goals and habits: age-related and individual differences in goal-directed decision-making.
In this study we investigated age-related and individual differences in habitual (model-free) and goal-directed (model-based) decision-making. Specifically, we were interested in three questions. First, does age affect the balance between model-based and model-free decision mechanisms? Second, are these age-related changes due to age differences in working memory (WM) capacity? Third, can model-based behavior be affected by manipulating the distinctiveness of the reward value of choice options? To answer these questions we used a two-stage Markov decision task in in combination with computational modeling to dissociate model-based and model-free decision mechanisms. To affect model-based behavior in this task we manipulated the distinctiveness of reward probabilities of choice options. The results show age-related deficits in model-based decision-making, which are particularly pronounced if unexpected reward indicates the need for a shift in decision strategy. In this situation younger adults explore the task structure, whereas older adults show perseverative behavior. Consistent with previous findings, these results indicate that older adults have deficits in the representation and updating of expected reward value. We also observed substantial individual differences in model-based behavior. In younger adults high WM capacity is associated with greater model-based behavior and this effect is further elevated when reward probabilities are more distinct. However, in older adults we found no effect of WM capacity. Moreover, age differences in model-based behavior remained statistically significant, even after controlling for WM capacity. Thus, factors other than decline in WM, such as deficits in the in the integration of expected reward value into strategic decisions may contribute to the observed impairments in model-based behavior in older adults.


Blood Service in a Region of China's Qinghai-Tibetan Plateau.
Objectives: The purpose of this paper is to describe blood services in the Aba Tibetan and Qiang Regions, (hereinafter referred to as Aba Prefecture), a region of China's Qinghai-Tibetan Plateau, the third largest area of Tibet and the main inhabited area of the Qiang people. Design: We present a comprehensive investigation into blood donations, donors, screening and supply in the 13 counties of Aba Prefecture based on data from 2013 to 2018. Geography and population were also used to analyze the differences in blood services among different regions. Participants: The number of blood donors totaled 19,047. Results: Over the past 6 years, blood donations have increased by 29 and clinical blood usage by 45%. The blood donation rate was 3.4‱ and per capita blood use was 1.04 mL, both of which were significantly lower than the national average, and blood donation decreased with altitude. It should be noted that the donation rate of the Tibetan and Qiang peoples is much lower than that of the Han population. Moreover, the rejection rate of blood in laboratory testing was found to be higher than the national average, especially in counties located at higher altitudes. Conclusions: Blood donations and usage increased every year in Aba Prefecture, but blood shortage is still an important issue. In addition, the prevalence of transfusion-transmitted diseases is relatively high, which may be linked to lower-education and unfavorable geographical and medical conditions.


[Allergic vasculitis caused by vitamin B6].
A patient developed extensive bulloushaemorrhagic lesions on the lower legs after taking analgesic preparations. Allergologic tests yielded an Arthus-type reaction with vitamin B6. The histological and immunofluorescence examination of a lesional and test site biopsy showed the picture of a superficial and deep vasculitis with deposits of C3 at the basement membrane of dermal venules.


Decreasing the energy consumption of memory devices by enhancing the conjugation extent of the terminal electron-donating moieties within molecules.
Three small organic molecules that contained a phenothiazine backbone and triphenylamine (TPA), carbazole (CZ), or anthracene (AN) as a terminal electron donor were synthesized and fabricated in ITO/organic film/Al sandwiched memory devices. The influence of the extent of conjugation in the three molecules on the performance of their corresponding devices was investigated and the results showed that all of the fabricated devices exhibited nonvolatile ternary WORM character, whilst the switch threshold voltages decreased on moving from TPA to CZ and AN, which is promising for low-power-consumption data storage. These results revealed that tailoring the extent of conjugation in the terminal electron donor in the D-A molecules could effectively optimize the device performance, in particular the switch-threshold voltage, which could be instructive for the design of low-energy-consumption memory materials.


Bruxism: Is There an Indication for Muscle-Stretching Exercises?
Bruxism is a common phenomenon involving repetitive activation of the masticatory muscles. Muscle-stretching exercises are a recommended part of several international guidelines for musculoskeletal disorders and may be effective in management of the jaw muscle activity that gives rise to bruxism. However, most studies of muscle-stretching exercises have mainly focused on their influence on performance (eg, range of motion, coordination, and muscle strength) of the limb or trunk muscles of healthy individuals or individuals with sports-related injuries. Very few have investigated stretching of the human masticatory muscles and none muscle-stretching exercises in the management of (sleep) bruxism. This article reviews the literature on muscle-stretching exercises and their potential role in the management of sleep bruxism or its consequences in the musculoskeletal system.


Suppression of experimental allergic encephalomyelitis by transfer of lymph node cells from Lewis rats pretreated with complete Freund's adjuvant.
Experimental allergic encephalomyelitis (EAE) in Lewis rats was suppressed by pretreatment with complete Freund's adjuvant (CFA) 14-16 days before immunization with basic protein (BP) in CFA. Suppression of active EAE was also accomplished clinically and even histologically if lymph node cells from CFA-treated donors were passively transferred. Obviously this depends first on a certain amount of transferred lymph node cells (about 3 X 108) and secondly on the interval between CFA application and cell harvest (more than 14 days). No suppression was obtained by transfer of serum from CFA-treated donors. This indicates that there is a suppressor cell population which can be raised or stimulated by CFA and which is capable of suppressing the immune response EAE.


Intersubunit interactions in human cytidine deaminase.
In order to design new efficient cytidine based drugs, an intersubunit interactions study related to the active site has been performed on the wild-type cytidine deaminase (CDA) and on the mutant enzyme F137W/W113F. F137 is the homologous to the Bacillus subtilis CDA F125 involved in the subunit interactions. In presence of the dissociating agent SDS, wild-type human CDA dissociate into enzymatically inactive monomers without intermediate forms via a non-cooperative transition. Extensive dialysis or dilution of the inactivated monomers restores completely the activity. The presence of the strong human CDA competitive inhibitor 5-fluorozebularine disfavour dissociation of the tetramer into subunits in the wild-type CDA but not in mutant enzyme F137W/W113F.


Ventricular cross stimulation in a dual chamber pacing system: phenomenon analysis.
Seven cases of ventricular cross stimulation from a group of 23 patients implanted with DDD devices are presented. In two patients the phenomenon was observed at the moment of DDD programming at nominal values, and in five other patients it was reproduced by increasing the atrial output voltage up to ten volts. In all 23 patients cross stimulation disappeared permanently within 24 hours after implantation. From the onset of cross stimulation to its end, atrial and ventricular threshold voltages were unchanged, while the atrial and ventricular impedances significantly decreased. These results suggest that an important role in the phenomenon occurs by impedance variation at the interface between the pulse generator and body tissue.


Interstitial lung disease following FOLFOX + FOLFIRI and bevacizumab therapy associated with leucovorin: A case report.
Chemotherapy-induced interstitial lung disease in colorectal cancer patients is rare but represents a life-threatening adverse reaction. We report here a case of interstitial lung disease following chemotherapy for metastatic colorectal cancer and the interesting results of the drug-induced lymphocyte stimulation test and leukocyte migration test. After chemotherapy with oxaliplatin plus infusional 5-fluorouracil and leucovorin (FOLFOX) plus bevacizumab followed by irinotecan plus infusional 5-fluorouracil and leucovorin (FOLFIRI), the patient was hospitalized with fever and chills. Laboratory data showed neutropenia and eosinophilia. Computed tomography revealed ground-glass opacities in both lungs; therefore, we diagnosed chemotherapy-induced interstitial lung disease. Steroid therapy was effective. We suspected irinotecan to be the etiological drug for interstitial lung disease in this patient because interstitial lung disease developed after switching the regimen from FOLFOX to FOLFIRI. However, drug-induced lymphocyte stimulation test and leukocyte migration test results were positive for only leucovorin and negative for irinotecan and 5-fluorouracil. This is the first case to show positive results on the drug-induced lymphocyte stimulation test and leukocyte migration test for only leucovorin and negative results for antineoplastic drugs. Our findings suggest that all drugs included in chemotherapy regimens have the potential to induce interstitial lung disease, and if rechallenge chemotherapy is considered, the drug-induced lymphocyte stimulation test and leukocyte migration test are expected to be useful for determining the drug that needs to be excluded.


Voyager spacecraft images of Jupiter and Saturn.
The images of Jupiter and Saturn and their satellites taken by the Voyager spacecraft TV cameras are shown and described. The scientific findings of the Voyager mission instruments and experiments are summarized.


Does amphetamine preferentially increase the extracellular concentration of dopamine in the mesolimbic system of freely moving rats?
It was suggested recently that a fundamental property of drugs that are rewarding, and thus have a high potential for abuse, is that they preferentially increase the extracellular concentration of dopamine (DA) in mesolimbic structures. This hypothesis was tested here by use of microdialysis in freely moving rats to determine the effects of systemic d-amphetamine administration on the extracellular concentration of DA in the so-called "limbic" (nucleus accumbens) and "motor" (dorsolateral caudate nucleus) subdivisions of the striatal complex. Amphetamine (2.03, 4.07, or 8.14 mumols/kg) greatly increased the extracellular concentration of DA in both structures, but there was no evidence of a preferential effect in the nucleus accumbens. The two higher doses of amphetamine actually increased extracellular DA to a greater extent in the dorsolateral caudate, but there was no significant regional difference if the data were expressed as a percent of baseline. These data do not support the hypothesis that drugs of abuse preferentially increase the extracellular concentration of DA in mesolimbic structures, although other ways in which amphetamine may selectively influence mesolimbic DA activity are discussed.


[A comparison of the long-term efficacy of cochlear implantation at early and late age].
This study aims to investigate the effects of age factor on the long-term efficacy of cochlear implantation. The electronic records of patients, who underwent cochlear implantation with the initial diagnosis of bilateral severe to profound sensorineural hearing loss in our clinic between January 2001 and December 2008, were analyzed retrospectively. The patients were divided into two groups according to their age at the time of cochlear implantation, including group 1 with the patients less than four years of age and group 2 with the patients more than four years of age. Groups were evaluated and compared for the in terms of demographic characteristics, Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) at three years following surgery. A total of 37 patients underwent cochlear implantation. Of them, 18 patients (48.6%) were operated at less than four years of age, while 19 patients (51.4%) were operated at more than four years of age. No significant difference was found between the groups in terms of sex, educational level and profession of the parents, operated side and duration of implant use. According to CAP and SIR categories, group 1 patients had statistically significantly higher level of the CAP and SIR categories (p=0.009 and p<0.001 respectively). Our study results suggested that the age of cochlear implantation has significant effects on long-term hearing and speech abilities. Cochlear implantation carried out at earlier ages (<4) enhances more satisfactory results in terms of long-term efficacy.


Evaluation of Stability of Amylose Inclusion Complexes Depending on Guest Polymers and Their Application to Supramolecular Polymeric Materials.
This paper describes the evaluation of the stability of amylose-polymer inclusion complexes under solution state in dimethyl sulfoxide (DMSO) depending on guest polymers. The three complexes were prepared by the vine-twining polymerization method using polytetrahydrofuran (PTHF), poly(ε-caprolactone) (PCL), and poly(l-lactide) (PLLA) as guest polymers. The stability investigation was conducted at desired temperatures (25, 30, 40, 60 °C) in DMSO solutions of the complexes. Consequently, the amylose-PTHF inclusion complex was dissociated at 25 °C, while the other complexes were stable under the same conditions. When the temperatures were elevated, the amylose-PCL and amylose-PLLA complexes were dissociated at 40 and 60 °C, respectively. We also found that amylose inclusion supramolecular polymers which were prepared by the vine-twining polymerization using primer-guest conjugates formed films by the acetylation of amylose segments. The film from acetylated amylose-PLLA supramolecular polymer had higher storage modulus than that from acetylated amylose-PTHF supramolecular polymer, as a function of temperature.


Electromagnetic induction methods applied to an abandoned manure handling site to determine nutrient buildup.
Movement of nutrients from livestock manure handling sites has the potential to negatively impact the environment. This study was conducted using electromagnetic induction (EMI) measurements to develop apparent soil electrical conductivity (EC(a)) maps to identify regions of nutrient buildup beneath an abandoned compost site. A trailer-mounted EM-38 coupled with a global positioning satellite system was towed across an area used for composting of feedlot manure. The resulting EC(a) maps were compared with known locations of compost rows confirming the alignment of row locations with high EC(a) regions. The identified rows were cored and compared with the region between the rows. The identified rows with a compost history demonstrated significant (P < 0.05) increases in soluble salts (1.6 times greater), NO3 (6.0 times greater), and Cl (2.0 times greater) compared with the area between the rows at a 1.5-m depth. Image processing techniques were used to display yearly changes that were associated with nutrient movement and transformations in the soil beneath the site. Correlations between EMI measurements and soil core analyses for NO3-N, Cl, and EC provided ancillary support for the EMI methods. The use of EMI for mapping of sites having a history of livestock waste application was effective in delineating high nutrient buildup areas and for observing spatial EC(a) changes over time.


Measurement and Characterization of Hydrogen-Deuterium Exchange Chemistry Using Relaxation Dispersion NMR Spectroscopy.
One-dimensional heteronuclear relaxation dispersion NMR spectroscopy at 13C natural abundance successfully characterized the dynamics of the hydrogen-deuterium exchange reaction occurring at the Nε position in l-arginine by monitoring Cδ in varying amounts of D2O. A small equilibrium isotope effect was observed and quantified, corresponding to ΔG = -0.14 kcal mol-1. A bimolecular rate constant of kD = 5.1 × 109 s-1 M-1 was determined from the pH*-dependence of kex (where pH* is the direct electrode reading of pH in 10% D2O and kex is the nuclear spin exchange rate constant), consistent with diffusion-controlled kinetics. The measurement of ΔG serves to bridge the millisecond time scale lifetimes of the detectable positively charged arginine species with the nanosecond time scale lifetime of the nonobservable low-populated neutral arginine intermediate species, thus allowing for characterization of the equilibrium lifetimes of the various arginine species in solution as a function of fractional solvent deuterium content. Despite the system being in fast exchange on the chemical shift time scale, the magnitude of the secondary isotope shift due to the exchange reaction at Nε was accurately measured to be 0.12 ppm directly from curve-fitting D2O-dependent dispersion data collected at a single static field strength. These results indicate that relaxation dispersion NMR spectroscopy is a robust and general method for studying base-catalyzed hydrogen-deuterium exchange chemistry at equilibrium.


The HealtheSteps™ lifestyle prescription program to improve physical activity and modifiable risk factors for chronic disease: a pragmatic randomized controlled trial.
Our objective was to determine the influence of the HealtheSteps™ lifestyle prescription program on physical activity and modifiable risk factors for chronic disease in individuals at risk. One hundred eighteen participants were recruited from 5 sites in Southwestern Ontario, Canada and randomized to either the intervention (HealtheSteps™ program, n = 59) or a wait-list control group (n = 59). The study comprised three phases: an Active Phase (0 to 6 months) consisted of bi-monthly in-person lifestyle coaching with access to a suite of eHealth technology supports (Heathesteps app, telephone coaching and a private HealtheSteps™ social network) followed by a Minimally-Supported Phase I (6 to 12 months), in which in-person coaching was removed, but participants still had access to the full suite of eHealth technology supports. In the final stage, Minimally-Supported Phase II (12 to 18 months), access to the eHealth technology supports was restricted to the HealtheSteps™ app. Assessments were conducted at baseline, 6, 12 and 18 months. The study primary outcome was the 6-month change in average number of steps per day. Secondary outcomes included: self-reported physical activity and sedentary time; self-reported eating habits; weight and body composition measures; blood pressure and health-related quality of life. Data from all participants were analyzed using an intent-to-treat approach. We applied mixed effects models for repeated measurements and adjusted for age, sex, and site in the statistical analyses. Participants in HealtheSteps™ increased step counts (between-group [95% confidence interval]: 3132 [1969 to 4294], p < 0.001), decreased their sitting time (- 0.08 [- 0.16 to - 0.006], p = 0.03), and improved their overall healthful eating (- 1.5 [- 2.42 to - 0.58], p = 0.002) to a greater extent compared to control at 6 months. Furthermore, exploratory results showed that these individuals maintained these outcomes 12 months later, after a minimally-supported phase; and retained improvements in sedentary time and improved healthful eating after 18 months. No differences in self-reported physical activity, health-related quality of life, weight, waist circumference or blood pressure were observed between groups at 6 months. Our findings suggest that HealtheSteps™ is effective at increasing physical activity (i.e., step counts per day), decreasing weekday sitting time, and improving healthful eating in adults at increased risk for chronic disease after 6 months; however, we did not see change in other risk factors. Nonetheless, the maintenance of these behaviours with minimal support after 12 and even 18 months indicates the promise of HealtheSteps™ for long-term sustainability. The trial was registered on April 6, 2015 with ClinicalTrials.gov (identifier: NCT02413385 ).


Anoxic-ischemic encephalopathy: clinical and electrophysiological associations with outcome.
Prognostic determination of patients in coma after resuscitation from cardiac arrest is both common and difficult. We explored clinical and electrophysiological testing to determine their associations with favorable and poor outcomes. We studied 75 comatose patients resuscitated from cardiac arrest, excluding those who were brain dead or continuously sedated; none received hypothermia therapy. Clinical examinations were performed on day 1. The following proportions recovered awareness: 2 of 18 patients with absent pupillary reflexes; 18 of 57 with preserved pupillary reflexes (p = 0.08); 2 of 32 with absent corneal reflexes; 16 of 43 with preserved corneal reflexes (p = 0.001); 0 of 15 with absent oculovestibular reflexes; and 8 of 29 with preserved oculovestibular reflexes (p < 0.037). Purposeful movements were associated with a high probability of recovery, whereas other categories were unfavorable. Other categories of motor response were associated with an increased proportion of those who died without recovering awareness, but each category had some survivors. Somatosensory evoked potentials (SSEPs) were recorded from 47 patients. One of 21 patients with loss of the N20 component survived, compared with survival of 11 of 26 patients in whom it was present (p = 0.003). All 5 patients with preserved N70 responses recovered awareness in a subgroup of 33 patients. Sixteen of 22 subjects with mild electroencephalogram (EEG) abnormalities recovered consciousness, compared with the survival of 3 of 50 patients with malignant EEG patterns (p = 0.0000001). Combining SSEP with EEG findings produced even greater predictive value. It seems unlikely that any single test will prove to have 100% predictive value for outcome; further studies combining clinical, EEG, and SSEP testing are warranted.


Klebsiella pneumoniae as a cause of pneumonia and septicemia in a civet kitten (Civettictis civetta) in the Jos Zoo, Nigeria.
A fatal case of acute pneumonia and septicemia that occurred in a captive civet kitten (Civettictis civetta) in the Jos Zoo, Nigeria is reported. Diagnosis was based on clinical signs, necropsy findings, and the isolation of Klebsiella pneumoniae from the lung, intestine, liver and heart blood of the animal. This is the first report of clinical K. pneumoniae infection in a wild or captive animal in Nigeria.


Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation.
The human mitochondrial outer membrane is biophysically unique as it is the only membrane possessing transmembrane β-barrel proteins (mitochondrial outer membrane proteins, mOMPs) in the cell. The most vital of the three mOMPs is the core protein of the translocase of the outer mitochondrial membrane (TOM) complex. Identified first as MOM38 in Neurospora in 1990, the structure of Tom40, the core 19-stranded β-barrel translocation channel, was solved in 2017, after nearly three decades. Remarkably, the past four years have witnessed an exponential increase in structural and functional studies of yeast and human TOM complexes. In addition to being conserved across all eukaryotes, the TOM complex is the sole ATP-independent import machinery for nearly all of the ∼1000 to 1500 known mitochondrial proteins. Recent cryo-EM structures have provided detailed insight into both possible assembly mechanisms of the TOM core complex and organizational dynamics of the import machinery and now reveal novel regulatory interplay with other mOMPs. Functional characterization of the TOM complex using biochemical and structural approaches has also revealed mechanisms for substrate recognition and at least five defined import pathways for precursor proteins. In this review, we discuss the discovery, recently solved structures, molecular function, and regulation of the TOM complex and its constituents, along with the implications these advances have for alleviating human diseases.


Late complications of coarctation of the aorta.
The mechanism of the late complications after coarctation repair remains unclear, and this common congenital heart disease affects patients and perplexes physicians in terms of prevention and treatment. From 2004 to 2008, 13 patients (1 adolescent and 12 adults) with repaired or unrepaired coarctation of the aorta were operated on in this department due to valve disorder or aortic aneurysm. The late complications were mitral and tricuspid regurgitation with congestive heart failure in 1, aortic valve disorder in 4, ascending aortic aneurysm in 3, saccular arch aneurysm in 1, and pseudoaneurysm in ascending, at isthmus, and descending aorta (Ortner's syndrome) in 1 patient each, respectively. Recoarctation occurred in 3 (25%) patients, 23, 29, and 36 years after coarctation repair. One patient had persistent hypertension. Patients with repaired coarctation of the aorta may eventually develop late complications including valve disorders, aortic aneurysm or pseudoaneurysm, in adolescence or adulthood, especially in the patient population associated with bicuspid aortic valve or complex congenital heart defects. Patients with unrepaired coarctation of the aorta, who can live to adulthood easily, may have a lack of associated anomalies. A regular follow-up is recommended for the patients with coarctation of the aorta in order to have a full-scope observation and prompt treatment when necessary.


MEASURING PHENOTYPIC SELECTION ON AN ADAPTATION: LAMELLAE OF DAMSELFLIES EXPERIENCING DRAGONFLY PREDATION.
Previous studies suggest that the evolution of increased caudal lamellae size to increase swimming speed was an adaptation of Enallagma damselflies for coexisting with large, predatory dragonflies in fishless lakes. To test whether dragonfly predation still exerts selection pressures for increased lamellae size, I performed a field experiment in which I manipulated the abilities of dragonfly larvae to inflict mortality on Enallagma boreale larvae and compared differences in lamellae size and shape between treatments. In cages where dragonflies were free to forage on damselflies, surviving E. boreale larvae had lamellae that were larger in lateral surface area, and that were wider relative to their length, as compared with larvae recovered from treatments in which dragonflies were not permitted to forage on damselflies. Selection differentials of about 0.25 phenotypic standard deviation units were measured for both of these characters. These results indicate that dragonfly predation still exerts significant selection pressures on damselfly antipredator adaptations. The results of this study are discussed in the context of studies of adaptation.


[3H]-p-azidopuromycin photoaffinity labeling of Escherichia coli ribosomes: evidence for site-specific interaction at U-2504 and G-2502 in domain V of 23S ribosomal RNA.
Previously we (1) showed that [3H]-p-azidopuromycin was a functional puromycin analogue that, on photolysis in the presence of 70S ribosomes from Escherichia coli, photoincorporated site specifically into proteins L23, L18/22, and L15 [Nicholson, A.W., Hall, C.C., Strycharz, W.A., & Cooperman, B.S. (1982) Biochemistry 21, 3809-3817] and (2) used immunoelectron microscopy to localize the principal sites of p-azidopuromycin photoincorporation within the 50S subunit [Olson, H.M., Nicholson, A.W., Cooperman, B.S., & Glitz, D.G. (1985) J. Biol. Chem. 260, 10326-10331]. These studies are here continued by identification of the principal sites of [3H]-p-azidopuromycin photoincorporation into ribosomal RNA. The major portion of such photoincorporation, 72%, takes place into 23S rRNA. Analysis by hybridization of the photoaffinity-labeled rRNA to restriction enzyme fragments of plasmid pKK3535, which contains rrnB DNA, using a refinement of a recently developed methodology [Hall, C.C., Smith, J.E., & Cooperman, B.S. (1985) Biochemistry 24, 5702-5711], shows that the most prominent [3H]-p-azidopuromycin photoincorporation occurs within bases 2445-2668 in domain V [Noller, H.F. (1984) Annu. Rev. Biochem. 53, 119-162] of 23S rRNA. Photoincorporation into this region is site specific, as demonstrated by the decrease in photoincorporation of radioactivity when unlabeled puromycin is included in the photolysis solution. Significant site-specific photoincorporation also occurs within bases 489-681 in domain II of 23S RNA. Further localization, by the method of reverse transcriptase primer extension [Barta, A., Steiner, G., Brosius, J., Noller, H.F., & Kuechler, E. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 3607-3611], provides evidence that U-2504 and G-2502 are the principal sites of p-azidopuromycin interaction.(ABSTRACT TRUNCATED AT 250 WORDS)


Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study.
In 1979 we initiated a phase III study in the Southwest Oncology Group (SWOG) which was designed to determine the value of chest radiation in limited-stage small-cell lung cancer patients achieving complete response after induction chemotherapy, and to test the use of wide-field v more limited-volume radiation in patients with partial responses (PRs) and patients with stable disease (SD). The induction chemotherapy (VMV-VAC) consisted of vincristine, 2 mg intravenously (IV) every week for six doses; methotrexate, 60 mg/m2 IV days 1 and 43; VP-16, 50 mg/m2/d IV days 1 to 5 and 43 to 47; doxorubicin, 60 mg/m2 IV days 22 and 64; and cyclophosphamide, 1,000 mg/m2 IV days 22 and 64. Four hundred ninety-four patients were registered, of whom 473 were eligible. Of 466 response-evaluable patients, 153 (33%) achieved complete disease remission (CR) with chemotherapy. A total of 387 patients entered the consolidation phase of treatment after chemotherapy and response determination. CR patients were prospectively randomized to receive chest radiation, consisting of 4,800 rad administered in a split-course scheme, or to continue chemotherapy without interruption. The treatment volume was based on tumor extent before the induction chemotherapy. Maintenance chemotherapy consisted of cyclophosphamide and VP-16 administered for four cycles before a period of reinduction chemotherapy consisting of VMV-VAC as described above. Patients receiving chest radiation therapy were given the same maintenance and reinduction chemotherapy programs following completion of the chest radiation. One hundred ninety-one eligible patients achieving PR or SD status after induction chemotherapy were randomized to a preinduction treatment volume or to a postinduction reduced tumor volume, with treatment portals designed according to tumor extent before or after induction chemotherapy, respectively. After completion of the entire treatment plan, there were 218 (47%) CRs and 121 (26%) PRs. These figures represent the greatest response achieved at any point in the treatment program. The median survival for all eligible patients was 57 weeks (74 weeks for CRs). Overall survival for CR patients was not different for patients who did or did not receive chest radiation. However, patterns of tumor relapse were affected by the chest radiation, as 38 of 42 relapsing patients who did not receive radiation had intrathoracic recurrences in comparison to only 20 of 36 radiated patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Impaired object recognition following prolonged withdrawal from extended-access cocaine self-administration.
Cocaine addicts have a number of cognitive deficits that persist following prolonged abstinence. These include impairments in executive functions dependent on the prefrontal cortex, as well as deficits on learning and memory tasks sensitive to hippocampal function. Recent preclinical studies using non-human animals have demonstrated that cocaine treatment can produce persistent deficits in executive functions, but there is relatively little evidence that treatment with cocaine produces persistent deficits in performance on hippocampal-dependent tasks. We recently demonstrated that extended (but not limited) access to self-administered cocaine is especially effective in producing persistent deficits on a test of cognitive vigilance, and therefore, we used this procedure to examine the effects of limited or extended access to cocaine self-administration on recognition memory performance, which is sensitive to hippocampal function. We found that extended access to cocaine produced deficits in recognition memory in rats that persisted for at least 2 weeks after the cessation of drug use. We conclude that the deficits in learning and memory observed in cocaine addicts may be at least in part due to repeated drug use, rather than just due to a pre-existing condition, and that in studying the neural basis of such deficits procedures involving extended access to self-administered cocaine may be especially useful.


Glycoproteins in Claudin-Low Breast Cancer Cell Lines Have a Unique Expression Profile.
Claudin proteins are components of epithelial tight junctions; a subtype of breast cancer has been defined by the reduced expression of mRNA for claudins and other genes. Here, we characterize the expression of glycoproteins in breast cell lines for the claudin-low subtype using liquid chromatography/tandem mass spectrometry. Unsupervised clustering techniques reveal a group of claudin-low cell lines that is distinct from nonmalignant, basal, and luminal lines. The claudin-low cell lines express F11R, EPCAM, and other proteins at very low levels, whereas CD44 is expressed at a high level. Comparison of mRNA expression to glycoprotein expression shows modest correlation; the best agreement occurs when the mRNA expression level is lowest and little or no protein is detected. These findings from cell lines are compared to those for tumor samples by the Clinical Proteomic Tumor Analysis Consortium (CPTAC). The CPTAC samples contain a group low in CLDN3. The samples low in CLDN3 proteins share many differentially expressed glycoproteins with the claudin-low cell lines. In contrast to the situation for cell lines or patient samples classified as claudin-low by RNA expression, however, most of the tumor samples low in CLDN3 protein express the estrogen receptor or HER2. These tumor samples express CD44 protein at low rather than high levels. There is no correlation between CLDN3 gene expression and protein expression in these CPTAC samples; hence, the claudin-low subtype defined by gene expression is not the same group of tumors as that defined by low expression of CLDN3 protein.


Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ.
Temporomandibular disorders (TMDs) have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7) plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG) is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ). Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored. Estrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ), the G protein coupled estrogen receptor (GPR30), and Nav1.7 in TG were examined using immunohistofluorescence. Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1.7 expression and head withdrawal threshold in ovariectomized rats. ERα and ERβ, but not GPR30, were mostly co-localized with Nav1.7 in neurons in TG. In the nerve growth factor-induced and ERα-transfected PC12 cells, 17β-estradiol dose-dependently enhanced Nav1.7 promoter activity, whereas mutations of the estrogen response element at -1269/-1282 and -1214/-1227 in the promoter completely abolished its effect on the promoter activity. Estradiol could upregulate trigeminal ganglionic Nav1.7 expression to contribute to hyperalgesia of inflamed TMJ.


[Docking method for drug discovery].
The effective integration of detailed structural information with computational chemistry, medicinal chemistry, and informatics transforms the dream of virtual screening into reality. One of the most important technologies essential for virtual screening is an effective docking method to find molecules that efficaciously interact with their target molecules. Since an efficient docking method can be a powerful tool for virtual screening, many different approaches to solving docking problems have been proposed. Docking problems have not yet been solved and none of the currently available programs are perfect in predicting all possible scenarios. Despite the limits and imperfections of the methodology, currently available docking methods are very useful for drug discovery. The basic principles and limits of docking methods together with matters for attention in applying the methods are described in this paper.


Hypodense eosinophils: characterization of surface molecule expression.
Distinct eosinophil populations have been characterized on the basis of discontinuous Percoll density gradients. In peripheral blood, normal individuals show a low number of normodense and hypodense eosinophils, contrasting with the high amount of hypodense cells in patients who have allergies. To characterize these two eosinophil populations, we analyzed membrane expression of several antigens and cytokine receptors in normodense and hypodense eosinophils from patients who have allergies and controls. Hypodense eosinophils expressed higher levels of CD122, CD69, and CD4 in both patients with allergies and control individuals when compared to normodense eosinophils. The expression of CD125, CD124, CD25, CD132, and CD23 were similar in both cell types.


Complexity of visual icons studied via signal detection theory.
Two investigations on how humans perceive information from visually rendered complex objects, such as military icons (glyphs) were conducted. A signal detection theory framework was employed to evaluate the sensitivity and specificity of human subject performance. The 6 adults tested showed that as complexity increased, their accuracy in performance decreased. Study 1 showed that complex dimensions (features) could not be assigned arbitrarily. Study 2 developed a rank ordering for features of an iconic object.


Effects of aging on human skeletal muscle myosin heavy-chain mRNA content and protein isoform expression.
The purpose of this investigation was to determine the role played by pretranslational events in the decreased rate of myosin heavy-chain (MyHC) protein synthesis in old age. It was hypothesized that the decreased rate of MyHC protein synthesis reported in the elderly population is, at least in part, related to lower MyHC messenger RNA (mRNA) in old age. MyHC protein expression and mRNA levels for the three MyHC isoforms expressed in human muscle, that is, types I, IIa, and IIx/d, were measured in percutaneous vastus lateralis muscle biopsies from 16 young and 16 old healthy men. The MyHC isoform mRNA content was determined by quantitative, real-time reverse transcriptase polymerase chain reaction, and it was normalized to 18S ribosomal RNA; the relative MyHC protein isoform content was measured on silver-stained 7% sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. The old men demonstrated signs of sarcopenia, such as loss of muscle force, a trend toward a loss in lean body mass, and an increased percentage of body fat. Statistically significant correlations were observed between the isoform expression of different MyHCs at the protein and mRNA levels. However, the expression of the different MyHC isoforms at the mRNA and protein levels did not differ between the young and old men. Thus, the present results do not support the hypothesis that pretranslational events in MyHC protein synthesis are playing a significant role in the development of sarcopenia.


Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase.
How to improve the efficacy and reverse the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of lung adenocarcinoma with EGFR-activating mutation. Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis over-expressed in various types of cancer including lung cancer. Elevated PHGDH expression is correlated with a worse overall survival in clinical lung adenocarcinoma patients. Here we investigated the role of PHGDH in lung adenocarcinoma with the acquisition of resistance to erlotinib. Methods: The necessary genes required for the acquired erlotinib resistance in lung adenocarcinoma cells were screened out by RNA-Seq analysis. Then the protein and mRNA levels of PHGDH were confirmed by immunoblotting and qRT-PCR in the erlotinib resistant cells. The effects of PHGDH inhibition or overexpression on erlotinib resistance were examined using cell culture and tumor xenograft mouse models respectively. To explore mechanism, the ROS level and DNA damage marker, γH2AX, were tested by DCFH-DA staining and immunofluorescence after PHGDH inhibition. Results: We found that PHGDH level was significantly increased in the lung adenocarcinoma PC9ER4 and HCC827ER9 cells that acquired resistance to erlotinib. Perturbation of PHGDH by siPHGDH transfection or NCT-503, a small molecular PHGDH inhibitor, synergistically augmented the tumoricidal effect and restored sensitivity to erlotinib in cell lines and xenografts. Over-expression of PHGDH caused xenografts resistant to erlotinib. Furthermore, multiple DNA damage repair pathways related genes were changed by PHGDH depletion specifically in erlotinib resistant cells. ROS stress and DNA damage marker γH2AX were enhanced by siPHGDH and NCT-503, which was reversed by NAC. Conclusion: Our study indicated that PHGDH inhibition has potential therapeutic value in lung adenocarcinoma with the acquired resistance to EGFR-TKIs.


Glycosylated extracellular domains of membrane immunoglobulin M contribute to its association with mb-1/B29 gene products and the B cell receptor complex.
It has recently become clear that the B cell antigen receptor, membrane immunoglobulin (mIg) is part of a complex composed of a number of different polypeptides. In a manner analogous to the T cell receptor, mIg has been found to be associated with several tyrosine kinases, and other proteins, which although not kinases themselves become targets of kinase activity upon binding of mIg to antigen. Thus the B cell receptor complex appears to be a structure whose function during signal transduction is to facilitate the interaction of tyrosine kinases with their proper substrates, and to coordinate the phosphorylation of these proteins with the binding of antigen to mIg. In an effort to understand the nature of the interactions which mediate the organization of the B cell receptor complex, we have explored binding of components of the complex including Ig-alpha and Ig-beta to IgM. Previous results have indicated that binding was mediated by transmembrane domains. Our results indicate that extracellular domains of IgM may also contribute to its association with Ig alpha and beta and other members of the B cell receptor complex.


High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients.
Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.


Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders.
Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel therapeutic targets in the treatment of FGIDs and IBDs. GC-C receptor activation by its endogenous paracrine hormones uroguanylin and guanylin, and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions. These include fluid and electrolyte homeostasis, maintenance of the intestinal barrier, anti-inflammatory activity and regulation of epithelial regeneration. Studies of the GC-C paracrine signalling axis have revealed the therapeutic potential of these receptors in treating GI disorders, including chronic idiopathic constipation and irritable bowel syndrome-constipation. This review focuses on the evolving understanding of GC-C function in health and disease, and strategies for translating these principles into new treatments for FGIDs and IBDs.


Single enantiomer drugs: should they be developed?
Biological interactions are stereoselective; thus the interactions of drugs with corresponding biological targets must also be stereoselective. However, many drugs used today are racemic mixtures. For example, approximately 25% or 1 in 4 marketed drugs are mixtures of agents (racemates) rather than single chemical entities (enantiomers). One of these enantiomers can be inactive or even counterproductive to the therapeutic use of the drug: either by reducing the efficacy of the active enantiomer or by causing unnecessary tolerability problems or even toxicity through differential pharmacodynamics. The presence of a therapeutically inactive or counterproductive enantiomer can also complicate the pharmacokinetics of the active enantiomer and the interpretation of the therapeutic drug monitoring (e.g., plasma levels) if the assay is not capable of separately quantitating the two enantiomers. This article reviews the history of stereoisomers and the relevant pharmacological principles, then discusses recent changes in rules governing drug approval and the potential advantages to the patient and the manufacturer of developing single enantiomers.