bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Changes in Gene Expression Profiles in AML Patients During Induction Chemotherapy
Authors: Jakobsen Ingrid , Sundkvist Max , Björn Niclas , Gréen Henrik , Lotfi Kourosh 
Published: June 2021

Abstract
Background: Elucidation of the genetic mechanisms underlying treatment response to standard induction chemotherapy in AML patients is warranted, in order to aid in risk-adapted treatment decisions as novel treatments are emerging. In this pilot study, we explored the treatment-induced expression patterns in a small cohort of AML patients by analyzing differential gene expression (DGE) over the first two days of induction chemotherapy.Methods: Blood samples were collected from ten AML patients at baseline (before treatment initiation) and during the first two days of treatment (Day 1; approximately 24 h, and Day 2; approximately 48 h after treatment initiation, respectively) and RNA was extracted for subsequent RNA sequencing. DGE between time points were assessed by pairwise analysis using the R package edgeR version 3.18.1 in all patients as well as in relation to treatment response (complete remission, CR, vs non-complete remission, nCR). Ingenuity Pathway Analysis (Qiagen) software was used for pathway analysis and visualization.Results: After initial data quality control, two patients was excluded from further analysis, resulting in a final cohort of eight patients with data from all three timepoints. DGE analysis demonstrated activation of pathways with genes directly or indirectly associated with NF-κB signaling. Significant activation of the NF-κB pathway was seen in 50% of the patients two days after treatment start, while iNOS pathway effects could be identified already after one day. nCR patients displayed activation of pathways associated with cell cycle progression, oncogenesis and anti-apoptotic behavior, including the STAT3 pathway and Salvage pathways of pyrimidine ribonucleotides. Notably, a significant induction of cytidine deaminase, an enzyme responsible for the deamination of Ara-C, could be observed between baseline and Day 2 in the nCR patients but not in patients achieving CR.Conclusions: In conclusion, we show that time-course analysis of gene expression represents a feasible approach to identify relevant pathways affected by standard induction chemotherapy in AML patients. This poses as a potential method for elucidating new drug targets and biomarkers for categorizing disease aggressiveness and evaluating treatment response. However, more studies on larger cohorts are warranted to elucidate the transcriptional basis for drug response.
PER2 Mediates CREB-Dependent Light Induction of Per1
Authors: Brenna Andrea , Ripperger Jürgen A. , Saro Gabriella , Glauser Dominique , Yang Zhihong , Albrecht Urs 
Published: June 2021

Abstract
Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 133 (S133). This modification leads CREB to recruit the co-factor CRCT1 and the histone acetyltransferase CBP to stimulate the transcription of genes containing a CRE element in their promoters, such as Period 1 (Per1). However, the details of this pathway are poorly understood. Here we provide evidence that PER2 acts as a co-factor of CREB to facilitate the formation of a transactivation complex on the CRE element of the Per1 gene regulatory region in response to light. Using in vitro and in vivo approaches, we show that PER2 modulates the interaction between CREB and its co-regulator CRTC1 to support complex formation only after a light or forskolin stimulus. Furthermore, the absence of PER2 abolished the interaction between the histone acetyltransferase CBP and CREB. This process was accompanied by a reduction of histone H3 acetylation and decreased recruitment of RNA Pol II to the Per1 gene. Collectively, our data show that PER2 supports the stimulus-dependent induction of the Per1 gene via modulation of the CREB/CRTC1/CBP complex. Remarkably, our results indicate that the molecular mechanism that transduces the light signal to the clock is similar to the one in the filamentous fungus Neurospora crassa to induce frequency (Frq). This suggests an evolutionarily conserved mechanism of this process despite the divergent sequences of the individual components.
Revision of Immersaria and a New Lecanorine Genus in Lecideaceae (Lichenized Ascomycota, Lecanoromycetes)
Authors: Xie Congmiao , Wang Li Song , Zhao Zun Tian , Zhang Yan Yun , Wang Xin Yu , Zhang Lu Lu 
Published: June 2021

Abstract
The species Immersaria cupreoatra has repeatedly been reassigned between Bellemerea and Immersaria. This caused us to reconsider the relationships between Bellemerea and the lecanorine species of Immersaria, and to question the monophyly of Immersaria. Among 25 genera of the family Lecideaceae, most have lecideine apothecia, with the exception of Bellemerea and Koerberiella, which have lecanorine apothecia. According to previous classifications, Immersaria included species with both lecanorine and lecideine apothecia. A five-loci phylogenetic tree (nrITS, nrLSU, RPB1, RPB2 and mtSSU) for Lecideaceae showed that Immersaria was split into two clades: firstly all the lecideine apothecia species, and secondly all the lecanorine apothecia species. The latter were closely related to the remaining lecanorine apothecia genera: Bellemerea and Koerberiella. Therefore, the genus concept of Immersaria was revised accordingly, and a new lecanorine genus Lecaimmeria was proposed. Furthermore, five new species for Immersaria, and seven new species and three new combinations for the new genus Lecaimmeria were proposed. Keys to Immersaria, the new genus Lecaimmeria and allied genera were provided.
Mild Poikilocapnic Hypoxia Increases Very Low Frequency Haemoglobin Oxygenation Oscillations in Prefrontal Cortex
Authors: Gruszecka Agnieszka , Waskow Monika , Malkiewicz Marta A. , Neary J. Patrick , Singh Jyotpal , Teckchandani Taylor , Kratzig Gregory P. , Wszedybyl-Winklewska Magdalena , Frydrychowski Andrzej F. , Rumiński Jacek , Głowacka Natalia , Lass Piotr , Winklewski Pawel J. , Gruszecki Marcin 
Published: June 2021

Abstract
The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, ECG, HbO2 from right hemisphere and changes of SAS width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, BMI = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). We analysed the recorded signals using wavelet transform (WT). We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia that there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminishes in the whole frequency range which could be explained by brain oedema. Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease, including SARS-CoV-2.
In-Depth Study of the Microcrystalline Cellulose Amino-Functionalization Efficiency
Authors: Neves Roberta Motta , Ornaghi Heitor Luiz , Duchemin Benoit , Zattera Ademir José , Amico Sandro Campos 
Published: June 2021

Abstract
Microcrystalline cellulose (MCC) has unique properties and its use as reinforcement for polymer composites has been increasing. However, the intrinsic incompatibility with most polymers requires surface modification to improve chemical compatibility prior to its incorporation into a polymer. In this paper, an in-depth study of silanization of MCC using 3-aminopropyltriethoxysilane (APTES), at different concentration, was done. The grafting amount of APTES onto MCC was determined by different methods: from residual mass and from nitrogen content. Solid-state 13C and 29Si nuclear magnetic resonance (NMR), field emission scanning electron microscopy with energy dispersive X-ray (SEM-EDX), spectroscopy plasma optical emission spectrometry (ICP), and a deep study of structural properties by X-ray diffraction were carried out. A better correlation for grafting amount of APTES onto MCC was observed for nitrogen content method than residual mass according the Pearson’s correlation. 13C NMR revealed all the carbon structures from cellulose and from APTES molecules and 29Si NMR revealed D, T and Q Si structures. The silane treatment did not alter the shape of MCC and all treated samples showed Si characteristic peak at ~ 1.75 kEv. From ICP was observed higher Si content before MCC addition than after, evidencing, once again, APTES grafting. The exposure to APTES in acidic medium caused several effects on the MCC, splitting larger Iβ crystallites in half and along the more reactive hydrophilic sides. The diameter of the smaller IVI crystallites was largely reduced by the treatment, especially when the silane concentration was 1:5 (m/v), above which the diameter increases again.
Core-Shell Magnetic Fe3O4/CNC@MOF Composites with Peroxidase-Like Activity for Colorimetric Detection of Phenol
Authors: Hou Chen , Fu Linhui , Wang Yang , Chen Wenqiang , Chen Fang , Zhang Sufeng , Wang Jianzhi 
Published: June 2021

Abstract
Rapid and accurate detection of phenolic wastewater from industries has created global concern. Herein, core-shell magnetic cellulose nanocrystals supported MOF (Fe3O4/CNC@ZIF-8) with robust peroxidase-like activity was synthesized with tannic acid as modifier and bridge. The peroxidase-mimic catalytic activity of as-prepared Fe3O4/CNC@ZIF-8 was further investigated using o-phenylenediamine (OPD) as peroxidase substrates in the presence of H2O2. Moreover, the experimental conditions were optimized and the kinetic analysis results showed that Fe3O4/CNC@ZIF-8 had higher affinity towards both the substrate OPD and H2O2 than horseradish peroxidase (HRP). Finally, a phenol colorimetric assay with a linear range of 2-200 µM and a detection limit of 0.316 µM was constructed. The catalytic mechanism of Fe3O4/CNC@ZIF-8 with phenol was further investigated by fluorescence test and the generated •OH was proved to act a crucial role to produce quinoid radicals. Additionally, the synthesized magnetic material had excellent stability and recyclability and ease to separation. These results suggest that the Fe3O4/CNC@ZIF-8 may be one of the promising candidates as peroxidase mimic for colorimetric detection of phenol.
Significance of Linkage Disequilibrium and Epistasis on the Genetic Variances in Non-Inbred and Inbred Populations
Authors: Viana José Marcelo Soriano , Garcia Antonio Augusto Franco 
Published: June 2021

Abstract
Background The influence of linkage disequilibrium (LD), epistasis, and inbreeding on the genotypic variance continues to be an important area of investigation in genetics and evolution. Although the current knowledge about biological pathways and gene networks imply that epistasis is important in determining quantitative traits, the empirical evidence for a range of species and traits is that the genetic variance is most additive. This is confirmed by some recent theoretical studies. However, because these investigations have assumed linkage equilibrium, only additive effects, or simplified assumptions for the two- and high-order epistatic effects, the objective of this investigation was to provide additional information about the impact of LD and epistasis on the genetic variances in non-inbred and inbred populations, using a simulated data set.Results The epistatic variance in generation 0 corresponded to 1 to 10% of the genotypic variance, with 30% of epistatic genes, but it corresponded to 5 to 45% assuming 100% of epistatic genes. After 10 generations of random cross or selfing the ratio epistatic variance/genotypic variance increased in the range of 15 to 1,079%. The epistatic variances are maximized assuming dominant epistasis, duplicate genes with cumulative effects, and non-epistatic gene interaction. A minimization occurs with complementary, recessive, and dominant and recessive epistasis. In non-inbred populations, the genetic covariances have negligible magnitude compared with the genetic variances. In inbred populations, excepting for duplicate epistasis, the sum of the epistatic covariances was in general negative and with magnitude higher than the non-additive variances, especially under 100% of epistatic genes.Conclusions The LD level for genes, even under a relatively low gene density, has a significant effect on the genetic variances in non-inbred and inbred populations. Assuming digenic epistasis, the additive variance is in general the most important component of the genotypic variance in non-inbred and inbred populations. The ratio epistatic variance/genotypic variance is proportional to the percentage of interacting genes and increases with random cross and selfing. In general, the additive x additive variance is the most important component of the epistatic variance. The maximization of the epistatic variance depends on the allele frequency, LD level, and epistasis type.
Pyruvate Carboxylase Supports MCF10A-Ras Cell Survival in Extracellular Matrix Detached Conditions
Authors: Sheeley Madeline P , Keisel Violet A , Atallah Nadia M. , Donkin Shawn S. , Hursting Stephen D. , Wendt Michael K. , Teegarden Dorothy 
Published: June 2021

Abstract
Background: Throughout metastatic progression, cancer cells acquire anchorage independence, or the ability to survive detached from the extracellular matrix (ECM). While untransformed epithelial cells reduce energy metabolism when detached, cancer cells display metabolic flexibility to continue important metabolic processes. Glucose and glutamine are predominant nutrients utilized for energy as well as other purposes, and their metabolism is regulated by cancer cells.Methods: The purpose of the current studies was to determine the effects of detachment on glucose and glutamine metabolism in human breast epithelial MCF10A cells transfected with the Harvey-ras oncogene (MCF10A-ras), a model of early-stage cancer. Detachment was simulated with poly-HEMA coated plates, and intracellular metabolic flux was determined using stably labeled 13C5-glutamine and 13C6-glucose tracers.Results: Results show reduced glutamine flux in detached cells as determined by reduced accumulation of label in glutamate (21%), malate (30%), and aspartate (23%) from 13C5-glutamine. Detachment also reduced flux of 13C6-glucose to pyruvate and lactate pools by 51% and 29%, respectively. Similarly, detachment reduced total intracellular pool sizes of pyruvate (51%), lactate (49%), α-ketoglutarate (43%), fumarate (32%), malate (19%), alanine (35%), serine (35%), and glutamate (28%) compared to attached cells, but citrate and aspartate pool sizes were unchanged. Compared to attached cells, detachment increased pyruvate carboxylase (PC) mRNA abundance and protein expression by 131% and 190%, respectively. In detachment, PC activity, determined by 13C6-glucose derived M + 3 isotopomers, was shown to preferentially replenish malate and aspartate, but not citrate pools. In addition, doxycycline-inducible shRNA depletion of PC significantly decreased, while doxycycline-inducible PC overexpression significantly increased, detached cell viability. Further, a switch from glutamine to PC activity for anaplerosis was demonstrated, as supplementation with the cell permeable analog of the tricarboxylic acid cycle intermediate, α-ketoglutarate, a downstream metabolite of glutamine, decreased PC mRNA abundance in detached cells.Conclusion: Collectively, these results suggest that detached breast cancer cells increase PC activity in response to decreased glutamine-derived anaplerosis to promote cell survival.
Augmented Perpetual Manifolds and Perpetual Mechanical Systems-Part II: Theorem and a Corollary for Dissipative Mechanical Systems Behaving as Perpetual Machines
Authors: GEORGIADES FOTIOS 
Published: June 2021

Abstract
Perpetual points in mathematics defined recently, and their significance in nonlinear dynamics and their application in mechanical systems is currently ongoing research. The perpetual points significance relevant to mechanics so far is that they form the perpetual manifolds of rigid body motions of mechanical systems. The concept of perpetual manifolds extended to the definition of augmented perpetual manifolds that an externally excited multi-degree of freedom mechanical system is moving as a rigid body. As a continuation of this work, herein the internal force’s and their associated energies, for a motion of multi-degree of freedom dissipative flexible mechanical system with solutions in the exact augmented perpetual manifolds, leads to the proof of a theorem that based on a specific decomposition with respect to their state variables dependence, all the internal forcing vectors are equal to zero. Therefore there is no energy storage as potential energy, and the process is internally isentropic. This theorem provides the conditions that a mechanical system behaves as a perpetual machine of a 2nd and a 3rd kind. Then in a corollary, the behavior of a mechanical system as a perpetual machine of third kind further on is examined. The developed theory leads to a discussion for the conditions of the violation of the 2nd law of thermodynamics for mechanical systems that their motion is described in the exact augmented perpetual manifolds. Moreover, the necessity of a reversible process to violate the 2nd thermodynamics law, which is not valid, is shown. The findings of the theorem analytically and numerically are verified. The energies of a perpetual mechanical system in the exact augmented perpetual manifolds for two types of external forces have been determined. Then, in two examples of mechanical systems, all the analytical findings with numerical simulations, certified with excellent agreement. This work is essential in physics since the 2nd law of thermodynamics is not admitting internally isentropic processes in the dynamics of dissipative mechanical systems. In mechanical engineering, the mechanical systems operating in exact augmented perpetual manifolds, with zero internal forces, there is no degradation of any internal part of the machine due to zero internal stresses. Also, the operation of a machine in the exact augmented perpetual manifolds is of extremely high significance to avoid internal damage, and there is no energy loss.
Four-Dimensional Computed Tomography Evaluation of Shoulder Joint Motion in Collegiate Baseball Pitchers
Authors: Momma Daisuke , Orías Alejandro A Espinoza , Irie Tohru , Irie Tomoyo , Kondo Eiji , Iwasaki Norimasa , Inoue Nozomu 
Published: June 2021

Abstract
The purpose of this study is to evaluate the glenohumeral contact area, center of glenohumeral contact area, and center of humeral head during simulated pitching motion in collegiate baseball pitchers using four-dimensional computed tomography (4D CT). We obtained 4D CT data from the dominant and non-dominant shoulders of eight collegiate baseball pitchers during the cocking motion. CT image data of each joint were reconstructed using a 3D reconstruction software package. The glenohumeral contact area, center of glenohumeral contact area, center of humeral head, and oblateness of humeral head were calculated from 3D bone models using customized software. The center of glenohumeral contact area translated significantly from anterior to posterior during maximum external rotation to maximum internal rotation. The center of humeral head translated from posterior to anterior during maximum external rotation to maximum internal rotation. There was a high negative correlation between anterior translation of the center of glenohumeral contact area and center of humeral head, and a positive correlation between the translation and the oblateness. 4D CT analyses demonstrated that the center of humeral head translated in the opposite direction to that of the center of glenohumeral contact area during external rotation to internal rotation in abduction in the dominant and non-dominant shoulders. This diametric translation can be explained by the oblateness of the humeral head. 4D CT scanning and the software for bone surface modeling of the glenohumeral joint enabled quantitative assessment of glenohumeral micromotion and identified humeral head oblateness as the cause of diametric change.
Abnormal Lipid Droplets Accumulation Induced Cognitive Deficits in Obstructive Sleep Apnea Syndrome Mice via JNK/SREBP/ACC Pathway but Not Through PDP1/PDC Pathway
Authors: Li Dongze , Yu Yan , Xu Na , Li Wanting , Hou Yanyan , Wang Xi , Sun Yeying , Lu Wenxue , Qu Guiwu , Lv Changjun , Han Fang 
Published: June 2021

Abstract
IntroductionThe mechanisms of chronic intermittent hypoxia (CIH)-induced cognitive deficits remain unclear. Studies have shown that the neuronal metabolism disorders might contribute to the CIH induced-hippocampal impairment. MethodsWe assessed the CIH exposure influences of C57BL/6 mice on the activity of nerve, measured projects related to lipid metabolism, and treated with drugs SMND-309. ResultsOur study found that 12 weeks CIH treatment induced lipid droplets (LDs) accumulation in hippocampal neurocytes of mice, and caused severe neuro damage including neuron lesions, neuroblast (NB) apoptosis and abnormal glial activation. Mechanistically, the results showed that pyruvate dehydrogenase complex E1ɑ subunit (PDHA1) and the pyruvate dehydrogenase complex (PDC) activator pyruvate dehydrogenase phosphatase 1 (PDP1) did not noticeable change after intermittent hypoxia. Consistent with those results, the level of Acetyl-CoA in hippocampus did not significantly change after CIH exposure. Interestingly, we found that CIH produced large quantities of ROS, which activated the JNK/SREBP/ACC pathway in neurocytes. ACC catalyzed the carboxylation of Acetyl-CoA to malonyl-CoA and then more lipid acids were synthesized, which finally caused aberrant LDs accumulation. Additionally, LDs were peroxidized by the high level of ROS under CIH conditions. An active component of Salvia miltiorrhiza, SMND-309, dramatically alleviated these injuries and improved cognitive deficits of CIH mice. ConclusionTherefore, the JNK/SREBP/ACC pathway played a crucial role in the cognitive deficits caused by LDs accumulation after CIH exposure. Together, lipid metabolic disorders contributed to neurocytes damage, which ultimately caused behavioral dysfunction. An active component of Salvia miltiorrhiza, SMND-309, dramatically alleviated these injuries and improved cognitive deficits of CIH mice.