bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Calbindin-D28k binding site on inositol monophosphatase may allow inhibition independent of the lithium site of action
Authors: Hoffman Amnon , Talgan Yftah , Fanous Joseph , Agam Galila , Eisenstein Miriam , Levi Itshak , Askira Yael , Almog Orna , Gilon Chaim 
Published: July 2019

AbstractAmong numerous reported biochemical effects the lithium-inhibitable enzyme inositol-monophosphatase (IMPase) remains a viable target for lithium&apos;s therapeutic mechanism of action. Calbindin-D28k (calbindin) interacts with IMPase enhancing its activity. In the present study in silico modeling of IMPase-calbindin binding using the program MolFit indicated that the 55-66 amino acid segment of IMPase anchors calbindin via Lys59 and Lys61 with a glutamate in between (Lys-Glu-Lys motif). The model further suggested that the Lys-Glu-Lys motif interacts with residues Asp24 and Asp26 of calbindin. Indeed, we found that differently from wildtype calbindin, IMPase was not activated by mutated calbindin in which Asp24 and Asp26 were replaced by alanine. Calbindin&apos;s effect was significantly reduced by a peptide with the sequence of amino acids 58-63 of IMPase (peptide 1) and by six amino-acid peptides including at least part of the Lys-Glu-Lys motif. The three amino-acid peptide Lys-Glu-Lys or five amino-acid peptides containing this motif were ineffective. Intracerebroventricular administration of peptide 1 resulted in a significant antidepressant-like reduced immobility in the Porsolt forced swim test (FST) compared with mice treated with a scrambled peptide or artificial cerebrospinal fluid. Based on the sequence of peptide 1, and to potentially increase the peptide&apos;s stability, cyclic and linear pre-cyclic analog peptides were synthesized. One cyclic and one linear pre-cyclic analog peptides exhibited an inhibitory effect on calbindin-activated brain IMPase activity in vitro. These findings may lead to the development of molecules capable of inhibiting IMPase activity at an alternative site than that of lithium.
Pachydermoperiostosis-Like Disease In Captive Red Ruffled Lemurs (Varecia Variegatus Rubra)
Authors: Rothschild Bruce , Neiffer Donald , Marks Steve 
Published: July 2019

AbstractPachydermatoperiostosis, a rare form of hypertrophic osteoarthropathy, is of unknown etiology and previously thought limited to humans. The only periosteal reaction previously reported in prosimians is related to renal disease. Notation of hypertrophic osteoarthritis in three prosimians led to recognition that this was the first non-human documentation of the disease. Three related red ruffed lemurs (Varecia variegatus rubra) had diaphyseal periosteal reaction classic for hypertrophic osteoarthropathy. Workup was negative for known underlying causes and for the secondary hyperparathyroidism which produces bone alterations in black Eulemur macao, black and white Varecia variegatatus varigatus and ringtail Lemur catta lemurs. Recognition of facial coarsening allows identification of the primary form of hypertrophic osteoarthropathy, categorized in humans as primary hypertrophic osteoarthropathy. This is the first recognition of the phenomenon in the order primates, exclusive of humans, and represents a new model for this rare disease.
Circulating Neutrophils from Trauma Patients Induce Apoptosis Through Dephosphorylation of Epithelial Cell Caspase-8
Authors: Kapus Andras , Marshall John , Jia Songhui , Parodo Jean , Battisti-Charbonney Emmanuel , Tsang Jennifer , Jia Sangyang , Rotstein Ori 
Published: July 2019

AbstractActivated neutrophils can cause oxidant-mediated bystander injury to host cells. This injury has previously been ascribed to the direct effects of oxidants on membrane phospholipids. We show here that oxidants released by neutrophils activated in vivo in survivors of multiple trauma or in vitro by exposure to bacterial lipopolysaccharide (LPS) can also promote the apoptotic death of epithelial cells, through the SHP-1-mediated dephosphorylation of epithelial cell caspase-8. Neutrophils from a cohort of patients who sustained serious injury induced the apoptotic death of cultured epithelial cells in a manner that was dependent on the activity of the NADPH oxidase and the generation of neutrophil-derived reactive oxygen intermediates. Caspase-8 is constitutively tyrosine phosphorylated in a panel of resting epithelial cells, but undergoes dephosphorylation in response to hydrogen peroxide (H2O2), activated neutrophils, or inhibition of Src kinases. Mutation of either of 2 key caspase-8 tyrosine residues, Y397 and Y465 to a non-phosphorylatable phenylalanine accelerates the apoptosis of epithelial cells transfected with caspase-8, while mutation of the same tyrosine residues to the phosphomimetic glutamic acid, or transfection with the Src kinases Lyn or c-Src inhibits H2O2-induced apoptosis. Exposure to either H2O2 or LPS-stimulated neutrophils, increases the phosphorylation and activity of the phosphatase SHP-1, increases the activity of caspases-8 and -3, and accelerates epithelial cell apoptosis. Together these data reveal a novel mechanism for neutrophil-mediated tissue injury through oxidant-dependent SHP-1-mediated dephosphorylation of caspase-8 resulting in enhanced epithelial cell apoptosis.
Arrhenius' theory of partial dissociation and hydration of electrolytes in solutions replaces existing activity concepts
Authors: Heyrovska Raji 
Published: July 2019

AbstractThe author shows that Arrhenius's theory of partial electrolytic dissociation was immaturely displaced about eight decades ago by the empirical concept of ionic activities and the assumption of complete dissociation of electrolytes at all concentrations. The latter brought the theory of electrolytes over the next decades into a complicated state without any physical significance. Therefore, the author started a systematic investigation of the available data and could completely restore the original theory of partial dissociation. Now solution properties can be easily understood and quantitatively explained in terms of absolute concentrations and volumes of ions and ion pairs and hydration.
Firing statistics and correlations in spiking neurons: a level-crossing approach
Authors: Badel Laurent 
Published: July 2019

AbstractWe present a time-dependent level-crossing theory for linear dynamical systems perturbed by colored Gaussian noise. We apply these results to approximate the firing statistics of conductance-based integrate-and-fire neurons receiving excitatory and inhibitory Poissonian inputs. Analytical expressions are obtained for three key quantities characterizing the neuronal response to time-varying inputs: the mean firing rate, the linear response to sinusoidally-modulated inputs, and the pairwise spike-correlation for neurons receiving correlated inputs. The theory yields tractable results that are shown to accurately match numerical simulations, and provides useful tools for the analysis of interconnected neuronal populations.
The Strauss-Kahn Syndrome
Authors: Skopec Robert 
Published: July 2019

AbstractAccumulating evidence shows that the central nervous system (CNS) regulates the activity of the immune system. Concerning the role of immune system in cancer, psychosocial influences on immune function provide a mechanism of association between psychosocial factors (like interpersonal aggression) and cancer prognosis. Social conflicts between males, involving high aggression stress and threat (psychosocial conflicts) produce both an allostatic state and allostatic load. The costs for aggressors (Hawks) and victims (losers) tested under semi laboratory conditions are quite different. Testosterone does not cause aggression, only exaggerates the pre-existing pattern and response to environmental triggers of aggression. The individual's personality type (authoritarian Hawk or Dove) has major impact on psychoneuroimmune mechanisms linking aggression stress through inflammation to cancer. Due to the latest connotations we propose this personality phenomenon label as "the Strauss-Kahn syndrome".
Involvement of proteasome b1i subunit, LMP2, on uterine leiomyosarcma tumorigenesis
Authors: Hayashi Takuma , Horiuchi Akiko , Konishi Ikuo 
Published: July 2019

AbstractAlthough the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone; however, the development of human uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine LMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with human uterine LMS, in order to establish a clinical treatment method. Homozygous deficient mice for a proteasome subunit　b1i/LMP2 spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. Defective LMP2 expression in human uterine LMS was demonstrated, but present in human LMA. Therefore, loss in LMP2 expression may be one of the risk factors for human uterine LMS. LMP2 may be a potential diagnostic-biomarker and targeted- molecule for a new therapeutic approach.
Preservation of C Hexagons in C Allotrope Transformations
Authors: Bucknum Michael , Castro Eduardo 
Published: July 2019

AbstractIn this Letter is described the analogous hexagon preserving C allotrope transformations of graphite to diamond, as a packing of C spheres on the one hand, and alternatively C nanotubes to the C allotrope hexagonite, as a packing of C cylinders on the other hand.
The carbon allotrope glitter as n-diamond and i-carbon nanocrystals
Authors: Bucknum Michael , Castro Eduardo 
Published: July 2019

AbstractDiffraction data taken from nanocrystalline n-diamond and i-carbon forms is fit to a so-called glitter model, in which the geometry of the C lattice has been optimized by density functional theory (DFT). A calculated theoretical diffraction pattern for glitter is shown to be a close fit to the experimental data for these novel C forms.
Accurate estimation of homologue-specific DNA concentration-ratios in cancer samples allows long-range haplotyping
Authors: Carter Scott , Meyerson Matthew , Getz Gad 
Published: July 2019

AbstractInterpretation of allelic copy measurements at polymorphic markers in cancer samples presents distinctive challenges and opportunities. Due to frequent gross chromosomal alterations occurring in cancer (aneuploidy), many genomic regions are present at homologous-allele imbalance. Within such regions, the unequal contribution of alleles at heterozygous markers allows for direct phasing of the haplotype derived from each individual parent. In addition, genome-wide estimates of homologue specific copy- ratios (HSCRs) are important for interpretation of the cancer genome in terms of fixed integral copy-numbers. We describe HAPSEG, a probabilistic method to interpret bi- allelic marker data in cancer samples. HAPSEG operates by partitioning the genome into segments of distinct copy number and modeling the four distinct genotypes in each segment. We describe general methods for fitting these models to data which are suit- able for both SNP microarrays and massively parallel sequencing data. In addition, we demonstrate a specially tailored error-model for interpretation of systematic variations arising in microarray platforms. The ability to directly determine haplotypes from cancer samples represents an opportunity to expand reference panels of phased chromosomes, which may have general interest in various population genetic applications. In addition, this property may be exploited to interrogate the relationship between germline risk and cancer phenotype with greater sensitivity than is possible using unphased genotype. Finally, we exploit the statistical dependency of phased genotypes to enable the fitting of more elaborate sample-level error-model parameters, allowing more accurate estimation of HSCRs in cancer samples.
Emergence of macroscopic simplicity from the Tumor Necrosis Factor-alpha signaling dynamics
Authors: Hayashi Kentaro , Piras Vincent , Tomita Masaru , Tsuchiya Masa , Selvarajoo Kumar 
Published: July 2019

AbstractThe Tumor Necrosis Factor-α (TNF-α), a cytokine produced during the innate immune response to invading pathogens, is involved in numerous fundamental cellular processes. Here, to understand the temporal activation profiles of the TNF-α regulated signaling network, we developed a dynamic computational model based on the perturbation-response approach and the law of information (signaling flux) conservation. Our simulations show that the temporal average population response of the TNF-α stimulated transcription factors NF-κB and AP-1, and 3 groups of 180 downstream gene expressions follow first-order equations. Using the model, in contrast to a well-known previous study, our model suggests that the continuous activation of the third group of genes is not mainly due to the poor rate of mRNA decay process, rather, the law of signaling flux conservation stipulates the presence of secondary signaling, such as feedback mechanism or autocrine signaling, is crucial. Although the living system is perceived as sophisticated and complex, notably, our work reveals the presence of simple governing principles in cell population dynamics.
Accelerated Macromolecular Solution Structure Recovery
Authors: Zwart Petrus , Liu Haiguang 
Published: July 2019

AbstractSmall Angle X-ray Scattering (SAXS) is a standard technique for the determination of low-resolution shapes of macromolecules and their complexes, adding important insights in understanding biological function. We present a novel and computationally efficient method for shape reconstruction from SAXS data. High-quality molecular shapes are calculated in less than two minutes, providing real-time feedback during SAXS experiments.
Invasive monitoring of the clinical effects of high intra-abdominal pressure for insertion of the first trocar.
Authors: Miyahira Susana , Miguel Gustavo , Azevedo Glicia , Marigliani Bianca , Borborema José , Hypolito Octavio , Azevedo Joao-Luiz , Gama Fernanda , Azevedo Otavio , Becker Junior Otavio , Bernardes Linda , Machado Afonso 
Published: July 2019

Abstract
Background:
To analyze the effects of transitory, high intra-abdominal pressure on clinical, hemodynamic, blood gas and metabolic parameters.Methods: Sixty-seven laparoscopic patients were divided into groups P12 (n = 30, maximum intra-abdominal pressure of 12 mmHg) and P20 (n = 37, maximum intra-abdominal pressure of 20 mmHg). Through radial artery cannulation, mean arterial pressure (MAP) was assessed and blood gas analysis – pH, arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), bicarbonate (HCO3) and base excess (BE) – was performed. These parameters were evaluated in both groups at time point zero, before CO2 insufflation; at time point one (TP1), when intra-abdominal pressure of 12 mmHg was reached in both groups; at time point two (TP2), 5 minutes after reaching intra-abdominal pressure of 12 mmHg in group P12 and of 20 mmHg in group P20; and at time point three (TP3), 10 minutes after reaching intra-abdominal pressure of 12 mmHg in group P12 and 10 minutes after TP1 in group P20, when intra-abdominal pressure decreased from 20 mmHg to 12 mmHg. Values out of the normal range or the occurrence of atypical phenomena suggestive of organic disease indicated clinical changes.

Results:
Significant variations in MAP, pH, HCO3 and BE were observed in group P20; these changes, however, were within normal limits. Clinical changes were also within normal limits, and no pathological phenomena were observed.

Conclusions:
Brief, intra-abdominal hypertension for the insertion first trocar insertion causes variations in MAP, pH, HCO3 and BE without adverse effects, and it may protect from iatrogenic injury.
Relationship of arterial and exhaled CO2 during elevated artificial pneumoperitoneum pressure for introduction of the first trocar.
Authors: Hypolito Octavio , Azevedo Joao-Luiz , Miyahira Susana , Scarpelli Fabiana , Becker Junior Otavio , Machado Afonso , Azevedo Otavio , Azevedo Glicia , Marigliani Bianca , Borborema Jose , Bernardes Linda , Miguel Gustavo 
Published: July 2019

AbstractThe present study evaluated the correlation between arterial CO2 and exhaled CO2 during brief high-pressure pneumoperitoneum. Patients were randomly distributed into two groups: P12 group (n=30) received a maximum intraperitoneal pressure of 12mmHg, and P20 group (n=37) received a maximum intraperitoneal pressure of 20mmHg. Arterial CO2 was evaluated by radial arterial catheter and exhaled CO2 was measured by capnometry at the following time points: before insufflation, once intraperitoneal pressure reached 12mmHg , 5 minutes after intraperitoneal pressure reached 12mmHg for the P12 group or 20mmHg for the P20 group, and 10 minutes after intraperitoneal pressure reached 12mmHg for the P12 group or when intraperitoneal pressure had decreased from 20mmHg to 12mmHg, for the P20 group. During brief durations of very high intraperitoneal pressure (20mmHg), there was a strong correlation between arterial CO2 and exhaled CO2. Capnometry can be effectively used to monitor patients during transient increases in artificial pneumoperitoneum pressure.
Density alteration in non-physiological cells
Authors: Wang Ming , Li Hai-Cheng , Li Lin-Na , Li Ju-Xiang , Liu Yu , Zhu Yuan-Chang , Wu Bin-Bin , Wu Xiao-Hua , Lan Fei-Fei , Fei Jia , Wei Jian-Ge 
Published: July 2019

AbstractIn the present study an important phenomenon of cells was discovered: the change of intracellular density in cell&apos;s response to drug and environmental factors. For convenience, this phenomenon is named as &quot;density alteration in non-physiological cells&quot; ( DANCE). DANCE was determined by discontinuous sucrose gradient centrifugation (DSGC), in which cells were separated into several bands. The number and position of the bands in DSGC varied with the change of cell culture conditions, drugs, and physical process, indicating that cell&apos;s response to these factors was associated with alteration of intracellular density. Our results showed that the bands of cells were molecularly different from each other, such as the expression of some mRNAs. For most cells tested, intracellular density usually decreased when the cells were in bad conditions, in presence of drugs, or undergoing pathological changes. However, unlike other tissue cells, brain cells showed increased intracellular density in 24 hrs after the animal death. In addition, DANCE was found to be related to drug resistance, with higher drug-resistance in cells of lower intracellular density. Further study found that DANCE also occurred in microorganisms including bacteria and fungus, suggesting that DANCE might be a sensitive and general response of cells to drugs and environmental change. The mechanisms for DANCE are not clear. Based on our study the following causes were hypothesized: change of metabolism mode, change of cell membrane function, and pathological change. DANCE could be important in medical and biological sciences. Study of DANCE might be helpful to the understanding of drug resistance, development of new drugs, separation of new subtypes from a cell population, forensic analysis, and importantly, discovery of new physiological or pathological properties of cells.
Down-regulation of serotonergic genes expression in the raphe nuclei of midbrain under chronic social defeat stress in male mice
Authors: Boyarskikh Ul’yana , Bondar Natalya , Filipenko Maxim , Kudryavtseva Natalia 
Published: July 2019

Abstract
Background:
There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of the midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings.Methodology/Principal Findings:The serotonergic genes were the Tph2, Sert, Maoa and Htr1a. The Bdnf, Creb, Cphn, Gapdh, Hprt, B2M, 18S and Actb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. Under CSDS the Cphn, Gapdh, Hprt, B2M, 18S, Actb genes are also down-regulated. The expression of the serotonergic genes as well as the Cphn and Creb genes is not restored to the control level after the 2 weeks of relative rest. mRNA levels of other genes are not recovered to the control levels, although some up-regulation was observed in rested losers. Significant positive correlations were found between the total time of avoidance behavior demonstrated by the 21-day defeaters in agonistic interactions and Sert, Maoa, Bdnf, Gapdh and 18S mRNA levels.

Conclusions:
CSDS experience inducing the development of mixed anxious/depression-like state in male mice down-regulates the serotonergic genes expression associated with the synthesis, inactivation and reception of serotonin. The Bdnf and Creb genes as well as the cell and metabolic Cphn, Gapdh, Hprt, B2M, Actb and 18S genes in the midbrain raphe nuclei are also down-regulated under CSDS. Period of relative rest is not enough for most genes to recover expression to the control levels.
Combining Transfer of TTF-1 and Pax-8 Gene: a Potential Strategy to Promote Radioiodine Therapy of Thyroid Carcinoma
Authors: Mu Da , Huang Rui , Ma Xiaojuan , Li Suping , Kuang Anren 
Published: July 2019

AbstractCotransfer of TTF-1 and Pax-8 gene to tumor cells, resulting in the reexpression of iodide metabolism-associated proteins, such as sodium iodide symporter (NIS), thyroglobulin (Tg), thyroperoxidase (TPO), offers the possibility of radioiodine therapy to non-iodide-concentrating tumor because the expression of iodide metabolism-associated proteins in thyroid are mediated by the thyroid transcription factors TTF-1 and Pax-8. The human TTF-1 and Pax-8 gene were transducted into the human thyroid carcinoma (K1 and F133) cells by the recombinant adenovirus, AdTTF-1 and AdPax-8. Reexpression of NIS mRNA and protein, but not TPO and Tg mRNA and protein, was detected in AdTTF-1-infected F133 cells, following with increasing radioiodine uptake (6.1~7.4 times), scarcely iodide organification and rapid iodide efflux (t1/2≈8 min in vitro, t1/2≈4.7 h in vivo).In contrast, all of the reexpression of NIS, TPO and Tg mRNA and proteins in F133 cells were induced by the synergetic effect of TTF-1 and Pax-8. AdTTF-1 and AdPax-8 coinfected K1 and F133 cells could effectively accumulate radioiodine (6.6-7.5 times) and obviously retarded radioiodine retention (t1/2≈25-30 min in vitro, t1/2≈12 h in vivo) (p<0.05).Accordingly, the effect of radioiodine therapy of TTF-1 and Pax-8 cotransducted K1 and F133 cells (21-25% survival rate in vitro) was better than that of TTF-1-transducted cells(40% survival rate in vitro) (p<0.05). These results indicate that single TTF-1 gene transfer may have limited efficacy of radioiodine therapy because of rapid radioiodine efflux. The cotransduction of TTF-1 and Pax-8 gene, with resulting NIS-mediated radioiodine accumulation and TPO and Tg-mediated radioiodine organification and intracellular retention, may lead to effective radioiodine therapy of thyroid carcinoma.