Biosynthesis and Recycling of Nicotinamide Cofactors in<i>Mycobacterium tuberculosis</i> : <i>AN ESSENTIAL ROLE FOR NAD IN NONREPLICATING BACILLI</i>

Boshoff, Helena I. M.,Xu, Xia,Tahlan, Kapil,Dowd, Cynthia S.,Pethe, Kevin,Camacho, Luis R.,Park, Tae-Ho,Yun, Chang-Soo,Schnappinger, Dirk,Ehrt, Sabine,Williams, Kerstin J.,Barry III, Clifton E. American Society for Biochemistry and Molecular Bi 2008 The Journal of biological chemistry Vol.283 No.28

<P>Despite the presence of genes that apparently encode NAD salvage-specific enzymes in its genome, it has been previously thought that Mycobacterium tuberculosis can only synthesize NAD de novo. Transcriptional analysis of the de novo synthesis and putative salvage pathway genes revealed an up-regulation of the salvage pathway genes in vivo and in vitro under conditions of hypoxia. [14C]Nicotinamide incorporation assays in M. tuberculosis isolated directly from the lungs of infected mice or from infected macrophages revealed that incorporation of exogenous nicotinamide was very efficient in in vivo-adapted cells, in contrast to cells grown aerobically in vitro. Two putative nicotinic acid phosphoribosyltransferases, PncB1 (Rv1330c) and PncB2 (Rv0573c), were examined by a combination of in vitro enzymatic activity assays and allelic exchange studies. These studies revealed that both play a role in cofactor salvage. Mutants in the de novo pathway died upon removal of exogenous nicotinamide during active replication in vitro. Cell death is induced by both cofactor starvation and disruption of cellular redox homeostasis as electron transport is impaired by limiting NAD. Inhibitors of NAD synthetase, an essential enzyme common to both recycling and de novo synthesis pathways, displayed the same bactericidal effect as sudden NAD starvation of the de novo pathway mutant in both actively growing and nonreplicating M. tuberculosis. These studies demonstrate the plasticity of the organism in maintaining NAD levels and establish that the two enzymes of the universal pathway are attractive chemotherapeutic targets for active as well as latent tuberculosis.</P>

Sulphonamide and Sulphonyl-hydrazone Cyclic Imide Derivatives: Antinociceptive Activity, Molecular Modeling and In Silico ADMET Screening

Kely N. de Oliveira,Helena C. Castro,Márcia M. Souza,Plínio Cunha Sathler,Uiaran O. Magalhães,Carlos R. Rodrigues,Patrícia R. Palm,Maicon Sarda,Pablo E. Perotto,Sabrina Cezar,Monique A. de Brito,Arian 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.10

In this paper, we describe the antinociceptive activity, molecular modeling and in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and 11 showed the most potent analgesic activity (ID50 = 5.1 and 6.8 μmol/kg, respectively). Interestingly, all derivatives evaluated in this study have a better analgesic profile than the control drugs, acetyl salicylic acid and acetaminophen. Derivative 9 was the most promising compound; with a level of activity that was 24 times higher than the control drugs. Our SAR study showed a relationship among the distribution of the frontier orbital HOMO coefficients, HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski “rule-of-five”, which is theoretically important for good drug absorption and permeation.

High Levels of IL-8 and MCP-1 in Cerebrospinal Fluid of COVID-19 Patients with Cerebrovascular Disease

Guartazaca-Guerrero Sebastián,Rodríguez-Morales Jahir,Rizo-Téllez Salma A.,Solleiro-Villavicencio Helena,Hernández-Valencia Aldo F.,Carrillo-Ruiz José Damián,Escobedo Galileo,Méndez-García Lucía A. 한국뇌신경과학회 2021 Experimental Neurobiology Vol.30 No.3

The coronavirus family has tropism for the Central Nervous System (CNS), however, there is no solid evidence demonstrating that the neurological effects of COVID-19 result from direct viral infection or systemic inflammation. The goals of this study were to examine the cytokine profile and the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) in cerebrospinal fluids (CSF) from two patients with cerebrovascular disease and COVID-19. Although the SARS-CoV-2 mRNA was not detected in CSF of both patients, we found abnormally high levels of numerous proinflammatory cytokines and chemokines, especially IL-8 and MCP-1. Since these chemokines mediate activation and recruitment of neutrophils, monocytes, and macrophages, it is feasible that cerebrovascular disease related-neuroinflammation found in both patients results from an exacerbated inflammatory response instead of SARS-CoV-2 direct invasion to CNS. These results suggest that neuroinflammation plays a key role in cerebrovascular disease and COVID-19.

Prevention of Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Mice by Yellow Passion Fruit Extract and Antiproliferative Effects of Its Bioactive Compound Piceatannol

Larissa Akemi Kido,Eun-Ryeong Hahm,Su-Hyeong Kim,Andressa Mara Baseggio,Valeria Helena Alves Cagnon,Shivendra V. Singh,Mário Roberto Maróstica Jr 대한암예방학회 2020 Journal of cancer prevention Vol.25 No.2

Piceatannol (PIC), a polyphenol presents in many vegetables and fruits including yellow passion fruit extract (PFE; Passiflora edulis), has anti-cancer activity, but its molecular targets are still poorly understood. The aims of this study were to investigate the molecular mechanistic actions of PIC in prostate cancer cell lines and to test if the extract from PFE rich in PIC can affect the growth of prostate cancer cells in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The PC-3, 22Rv1, LNCaP, and VCaP prostate cancer cells were exposed to PIC (10-40 μM), and cell viability, lactate measurement, Western blot, and flow cytometric analyses were performed. For an in vivo experiments, eight-week-old TRAMP mice (n = 10 per group each) received an aqueous extract of PFE containing 20 mg of PIC/kg or water (control group) by gavage for 4 or 10 weeks for further analyses. PIC treatment concentration- and time-dependently reduced viability of all cell lines tested. 22Rv1 and LNCaP cells treated with PIC did not exhibit any significant alteration in the intracellular accumulation of lactate. PIC treatment caused G0/G1 phase cell cycle arrest and induction of apoptosis in both LNCaP and 22Rv1 cells. PIC-treated cells exhibited altered protein levels of p53, p21, cyclin D1, and cyclin-dependent kinase 4 (cdk4). The short and long-term PFE treatments also affected p21, cyclin D1 and cdk4 and delayed disease progression in TRAMP, with a decreased incidence of preneoplastic lesions. In conclusion, PIC apparently does not alter glucose metabolism in prostate cancer cells, while cell cycle arrest and p53 modulation are likely important in anti-cancer effects of PIC alone or as a food matrix byproduct in prostate cancer cells, especially those with an androgen-dependent phenotype.

Risk Synchronization in International Stock Markets

Helena Chuliá,Andrés D. Pinchao,Jorge M. Uribe 연세대학교 동서문제연구원 2018 Global economic review Vol.47 No.2

We explore international risk synchronization in global stock markets over the last two decades. To this end, we construct global indices of risk synchronization based on individual estimations of market risk and their aggregation via spatial correlations. We then use these indices to analyze the effects of several financial crises on market risk synchronization. Our results reveal different risk-profile dynamics for mature and emerging markets. Contrary to general reports, we also find that not all financial crises induce a higher level of synchronization among markets, at least in relative terms. Indeed, some crises had the opposite effect, that is, a decoupling of market risk.

Nonlinear analysis of service stresses in reinforced concrete sections-closed form solutions

Helena F.M. Barros,Rogério A.F. Martins 사단법인 한국계산역학회 2012 Computers and Concrete, An International Journal Vol.10 No.5

This paper presents an algorithm for the evaluation of stresses in reinforced concrete sections under service loads. The algorithm is applicable to any section defined by polygonal contours and is based on an analytical integration of the stresses. The nonlinear behaviour of concrete is represented by the parabola-rectangle law used in the Eurocode-2 for the ultimate concrete design. An integrated definition of the strains in concrete and steel is possible by the use of Heaviside functions, similarly to what is done for ultimate section design in Barros et al. (2004). Other constitutive equations for the definition of the stresses in the concrete or steel can be easily incorporated into the code. The examples presented consist in the evaluation of resulting axial load and bending moment in an irregular section and in a section in L shape. The results, for service stresses, can also be plotted in terms of design abacus; a rectangular doubly reinforced section is presented as example.

딥 러닝 기반의 초해상도 이미지 복원 기법 성능 분석

이현재,신현광,최규상,진성일,Lee, Hyunjae,Shin, Hyunkwang,Choi, Gyu Sang,Jin, Seong-Il 대한임베디드공학회 2020 대한임베디드공학회논문지 Vol.15 No.2

Convolutional Neural Networks (CNN) have been used extensively in recent times to solve image classification and segmentation problems. However, the use of CNNs in image super-resolution problems remains largely unexploited. Filter interpolation and prediction model methods are the most commonly used algorithms in super-resolution algorithm implementations. The major limitation in the above named methods is that images become totally blurred and a lot of the edge information are lost. In this paper, we analyze super resolution based on CNN and the wavelet transform super resolution method. We compare and analyze the performance according to the number of layers and the training data of the CNN.

Behaviour of cold-formed steel hollow and concrete-filled members

G. M. Samuel Knight,H. Jane Helena 국제구조공학회 2005 Steel and Composite Structures, An International J Vol.5 No.1

This paper presents the results of a series of tests carried out on hollow and concrete-filled coldformed steel sections subjected to axial and bending forces. The effects of eccentricity ratio and strength of in-fill on the behaviour of these sections were studied. A total of forty-eight medium sized columns and six beams were tested to failure. Extensive measurements of material properties, strains, axial shortening and lateral deflection were carried out. Interaction of local and overall buckling was observed in the tests. Failure mode observations were local buckling coupled with overall buckling. A description of the specially fabricated end fixtures for applying eccentric loading to the columns and to simulate pinned end condition is also presented. The experimental results of hollow columns are compared with the existing Indian, British and American codes of practice and the results of concrete-filled columns are compared with EC4 recommendations. It is seen that in the case of hollow columns predictions based on British and American codes of practice and in the case of concrete-filled columns predictions based on EC4 recommendations agree reasonably well with the experimental results. From the experiments it is seen that the provision of in-fill substantially increases the ultimate load carrying capacity of the order of one and a half to two times and the increase in strength of the in-filled concrete from a low grade concrete of compressive strength 24.94 MPa to a high grade concrete of compressive strength 33.26 MPa increases the ultimate load carrying capacity by one and a half times irrespective of the eccentricity of loading.

Neural Mechanisms in Eating Behaviors: A Pilot fMRI Study of Emotional Processing

Rosa M. Molina-Ruiz,T. García-Saiz,Jeffrey C.L. Looi,E. Via Virgili,M. Rincón Zamorano,Laura de Anta Tejado,Helena Trebbau López,Jose Luis Carrasco Perera,Marina Díaz-Marsá 대한신경정신의학회 2020 PSYCHIATRY INVESTIGATION Vol.17 No.3

Objective Emotional processing dysfunction evident in eating disorders (ED) such as anorexia nervosa (AN) and bulimia nervosa (BN), is considered relevant to the development and maintenance of these disorders. The purpose of the current functional magnetic resonance imaging (fMRI) study was to pilot a comparison of the activity of the fronto-limbic and fronto-striatal brain areas during an emotion processing task in persons with ED. Methods 24 women patients with ED were scanned, while showing emotionally stimulating (pleasant, unpleasant) and neutral images from the International Affective Picture System (IAPS). Results During the pleasant condition, significant differences in Dorsolateral Prefrontal Cortex (DLPFC) activations were found with AN participants presenting greater activation compared to BN and ED comorbid groups (EDc) and healthy controls also showing greater activation of this brain area compared to BN and EDc. Left putamen was less activated in EDc compared to both controls (C) and AN. During the unpleasant condition, AN participants showed hyperactivation of the Orbito-Frontal Cortex (OFC) when compared to EDc. Conclusion This study highlights the potential functional relevance of brain areas that have been associated with self-control. These findings should help advance understanding the neural substrate of ED, though they should be considered as preliminary and be cautiously interpreted.

DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities

Abuetabh Yasser,Wu H. Helena,Chai Chengsen,Al Yousef Habib,Persad Sujata,Sergi Consolato M.,Leng Roger 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Antitumor therapeutic strategies that fundamentally rely on the induction of DNA damage to eradicate and inhibit the growth of cancer cells are integral approaches to cancer therapy. Although DNA-damaging therapies advance the battle with cancer, resistance, and recurrence following treatment are common. Thus, searching for vulnerabilities that facilitate the action of DNA-damaging agents by sensitizing cancer cells is an active research area. Therefore, it is crucial to decipher the detailed molecular events involved in DNA damage responses (DDRs) to DNA-damaging agents in cancer. The tumor suppressor p53 is active at the hub of the DDR. Researchers have identified an increasing number of genes regulated by p53 transcriptional functions that have been shown to be critical direct or indirect mediators of cell fate, cell cycle regulation, and DNA repair. Posttranslational modifications (PTMs) primarily orchestrate and direct the activity of p53 in response to DNA damage. Many molecules mediating PTMs on p53 have been identified. The anticancer potential realized by targeting these molecules has been shown through experiments and clinical trials to sensitize cancer cells to DNA-damaging agents. This review briefly acknowledges the complexity of DDR pathways/networks. We specifically focus on p53 regulators, protein kinases, and E3/E4 ubiquitin ligases and their anticancer potential.