Parasite Mitochondria as Drug Target: Diversity and Dynamic Changes During the Life Cycle

2003 ◽  
Vol 10 (23) ◽  
pp. 2535-2548 ◽  
Author(s):  
Kiyoshi Kita ◽  
Coichi Nihei ◽  
Eriko Tomitsuka
Keyword(s):  
Life Cycle ◽  
Drug Target ◽  
Dynamic Changes ◽  
Target Diversity

scholarly journals Dynamic changes in the transcriptome and methylome of Chlamydomonas reinhardtii throughout its life cycle

2015 ◽  
pp. pp.00861.2015 ◽  
Author(s):  
David Adrian Lopez ◽  
Takashi Hamaji ◽  
Janette Kropat ◽  
Peter De Hoff ◽  
Marco Morselli ◽  
...  
Keyword(s):  
Life Cycle ◽  
Chlamydomonas Reinhardtii ◽  
Dynamic Changes

scholarly journals Predicted antiviral drugs Darunavir, Indinavir and Rimantadine can potentially bind to neutralize COVID-19 conserved proteins

2020 ◽  
Author(s):  
Umesh Chandra Halder
Keyword(s):  
Life Cycle ◽  
Drug Target ◽  
Antiviral Drugs ◽  
Drug Binding ◽  
Human Society ◽  
Binding Motifs ◽  
Replicase Proteins ◽  
Fast Spreading ◽  
Vertebrate Hosts ◽  
Novel Coronavirus

Abstract Background: Novel Coronavirus disease 2019 or COVID-19 has become a threat to human society due to fast spreading and increasing mortality. It uses vertebrate hosts and presently deploying humans. Life cycle and pathogenicity of COVID-19 have already been deciphered and possible drug target tests are on the way.Results: The present study was aimed to analyze conserved Endoribonuclease, protease and replicase proteins of the virus as targets to all known drugs. A bioinformatics based web server Drug ReposeER predicted several drug binding motifs in these analyzed proteins. Results revealed that anti-viral Darunavir, Indinavir and Rimantadine were the most potent to have 3D-drug binding motifs on COVID-19 proteins.Conclusions: Repurposing of the antiviral drugs Darunavir, Indinavir and Rimantadine to treat COVID-19 infected persons could be useful that can potentially prevent thousands of human mortality.

scholarly journals Dynamic changes of nutrient composition throughout the entire life cycle of black soldier fly

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0182601 ◽  
Author(s):  
Xiu Liu ◽  
Xuan Chen ◽  
Hui Wang ◽  
Qinqin Yang ◽  
Kashif ur Rehman ◽  
...  
Keyword(s):  
Life Cycle ◽  
Nutrient Composition ◽  
Dynamic Changes ◽  
Black Soldier Fly ◽  
Entire Life ◽  
Entire Life Cycle

Contemporary Family and the Diversity of Family Life Forms

2014 ◽  
Vol 4 (1) ◽  
pp. 74-92
Author(s):  
Eleonóra Mendelová
Keyword(s):  
Life Cycle ◽  
Family Life ◽  
Nuclear Family ◽  
Life Forms ◽  
Family Life Cycle ◽  
Current Development ◽  
Dynamic Changes ◽  
Dominant Type ◽  
Behaviour Changes ◽  
Family Behaviour

Contemporary Family and the Diversity of Family Life Formpp. Slovakia (as well as other post communistic countries) has been experiencing dynamic changes in family behaviour since 1989, which is reflected in the diversity of family life formpp. The dominant type, nuclear family, which is formed by two parents and a child or children, has been extended, in the process of family behaviour changes, by forms such as a family formed by one adult (a parent) or informal partnership couplepp. The study is aimed at the process of diversification of family behaviour, seeks to present a view of new forms of family and partnership life, and analyzes their difficulties and limitpp. This analysis focuses on five forms of family and partnership life which are typical of the current development and are organized with regard to family life cycle: single, cohabitation, marriage, one parent and reconstructed family. In the conclusion, the author indicates recommendations for family and school education aiming at improving the preparation of students and the young for family life.

#23: Investigation of Phosphomannomutase as an Antimalarial Drug Target

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S10-S10
Author(s):  
Philip Frasse ◽  
Daniel Goldberg ◽  
Audrey Odom John
Keyword(s):  
Life Cycle ◽  
Metabolic Pathways ◽  
Drug Target ◽  
Large Family ◽  
Parasite Development ◽  
Parasite Life Cycle ◽  
Parasite Protein ◽  
Symptomatic Infection ◽  
Human Orthologs ◽  
Future Drug

Abstract Background Malaria continues to pose an enormous economic and global health threat, killing over 200,000 people annually, primarily children under the age of 5. With the constant barrier of antimalarial resistance and the rise of delayed clearance by artemisinin, it is especially important to identify drug/target pairs that rapidly kill parasites. We study targetable metabolic pathways in the malaria parasite, Plasmodium falciparum, to guide such future drug development against this disease. In recent years, we have discovered that a large family of hydrolases, the Haloacid Dehalogenase (HAD) Superfamily of proteins, are implicated in regulating a variety of P. falciparum metabolic pathways, which can lead to dramatic changes in central carbon metabolism and drug resistance. We now turn our attention to a related HAD protein, the putative phosphomannomutase in these parasites, HAD5, responsible for the interconversion of mannose-6-phosphate and mannose-1-phosphate. This is an essential process for all stages of the parasite, and thus has potential as a broad antimalarial target. We examined the role of HAD5 in these parasites, and its potential to be chemically inhibited. Methods Recombinant protein was generated and purified for enzymatic assays to determine HAD5 activity and test inhibitor potency against HAD5 compared to recombinant human orthologs, PMM1 and PMM2. In parallel, CRISPR/Cas9 was used to generate inducible knockdown parasite strains to demonstrate this gene’s essentiality and its role in parasite biology. Parasite growth was measured by flow cytometry and light microscopy. Immunofluorescence analysis (IFA) was used to track the parasite development on a molecular scale. Results Inhibition of HAD5 was achieved in biochemical assays, with an IC50 of 68µM in our most potent compound, representing roughly 10-fold increased potency against the parasite protein compared to human orthologs. In culture, knockdown of HAD5 leads to interrupted egress from and reinvasion into red blood cells, culminating in parasite death. In IFA-visualized parasites, reinvasion-facilitating proteins were no longer anchored to parasite surfaces, accounting for the inhibition of the parasite life cycle. Conclusion In the search for new antimalarial targets, identifying proteins that are essential across multiple parasite life-stages while being distinct from human orthologs is necessary to block parasite transmission, cure symptomatic infection, and minimize off-target effects. HAD5 is an essential protein in malaria parasites that is expressed throughout the parasite’s life cycle, and can be specifically targeted by inhibitors, giving it promise as a future drug target.

scholarly journals pulseTD: RNA life cycle dynamics analysis based on pulse model of 4sU-seq time course sequencing data

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9371
Author(s):  
Xin Wang ◽  
Siyu He ◽  
Jian Li ◽  
Jun Wang ◽  
Chengyi Wang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Time Course ◽  
Functional Form ◽  
R Package ◽  
Rna Seq ◽  
Sequencing Data ◽  
Future Time ◽  
Dynamic Changes ◽  
Robust Identification ◽  
Course Sequencing

The life cycle of intracellular RNA mainly involves transcriptional production, splicing maturation and degradation processes. Their dynamic changes are termed as RNA life cycle dynamics (RLCD). It is still challenging for the accurate and robust identification of RLCD under unknow the functional form of RLCD. By using the pulse model, we developed an R package named pulseTD to identify RLCD by integrating 4sU-seq and RNA-seq data, and it provides flexible functions to capture continuous changes in RCLD rates. More importantly, it also can predict the trend of RNA transcription and expression changes in future time points. The pulseTD shows better accuracy and robustness than some other methods, and it is available on the GitHub repository (https://github.com/bioWzz/pulseTD_0.2.0).

scholarly journals Strain-level analysis reveals the vertical microbial transmission during the life cycle of bumblebee

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Qinzhi Su ◽  
Qinglin Wang ◽  
Xiaohuan Mu ◽  
Hao Chen ◽  
Yujie Meng ◽  
...  
Keyword(s):  
Life Cycle ◽  
Gut Microbiota ◽  
Gut Bacteria ◽  
Strain Level ◽  
Colony Development ◽  
Annual Life Cycle ◽  
Dynamic Changes ◽  
Metagenome Analysis ◽  
Underlying Mechanisms ◽  
Genomic Regions

Abstract Background Microbial acquisition and development of the gut microbiota impact the establishment of a healthy host-microbes symbiosis. Compared with other animals, the eusocial bumblebees and honeybees possess a simple, recurring, and similar set of gut microbiota. However, all bee gut phylotypes have high strain-level diversity. Gut communities of different bee species are composed of host-specific groups of strains. The variable genomic regions among strains of the same species often confer critical functional differences, such as carbon source utilization, essential for the natural selection of specific strains. The annual bumblebee colony founded by solitary queens enables tracking the transmission routes of gut bacteria during development stages. Results Here, we first showed the changes in the microbiome of individual bumblebees across their holometabolous life cycle. Some core gut bacteria persist throughout different stages of development. Gut microbiota of newly emerged workers always resembles those of their queens, suggesting a vertical transmission of strains from queens to the newborn workers. We then follow the dynamic changes in the gut community by comparing strain-level metagenomic profiles of queen-worker pairs longitudinally collected across different stages of the nest development. Species composition of both queen and worker shifts with the colony’s growth, and the queen-to-worker vertical inheritance of specific strains was identified. Finally, comparative metagenome analysis showed clear host-specificity for microbes across different bee hosts. Species from honeybees often possess a higher level of strain variation, and they also exhibited more complex gene repertoires linked to polysaccharide digestion. Our results demonstrate bacterial transmission events in bumblebee, highlighting the role of social interactions in driving the microbiota composition. Conclusions By the community-wide metagenomic analysis based on the custom genomic database of bee gut bacteria, we reveal strain transmission events at high resolution and the dynamic changes in community structure along with the colony development. The social annual life cycle of bumblebees is key for the acquisition and development of the gut microbiota. Further studies using the bumblebee model will advance our understanding of the microbiome transmission and the underlying mechanisms, such as strain competition and niche selection.

Ultrastructural Cytopiasmic Changes of Adrenal Cortex During Pregnancy

1969 ◽  
Vol 27 ◽  
pp. 298-299
Author(s):  
T. M. Murad ◽  
Karen Israel ◽  
Jack C. Geer
Keyword(s):  
Adrenal Gland ◽  
Steroid Hormones ◽  
Adrenal Cortex ◽  
Lipid Droplets ◽  
Plasma Cholesterol ◽  
Adrenal Steroids ◽  
Dynamic Changes ◽  
Cortical Cells ◽  
Acetyl Coenzyme A ◽  
Adrenal Cortical Cells

Adrenal steroids are normally synthesized from acetyl coenzyme A via cholesterol. Cholesterol is also shown to enter the adrenal gland and to be localized in the lipid droplets of the adrenal cortical cells. Both pregnenolone and progesterone act as intermediates in the conversion of cholesterol into steroid hormones. During pregnancy an increased level of plasma cholesterol is known to be associated with an increase of the adrenal corticoid and progesterone. The present study is designed to demonstrate whether the adrenal cortical cells show any dynamic changes during pregnancy.

Ultrastructural analysis of “Sensory” surface nerve endings and “putative” neurotransmitter sites in Schistosoma mansoni Miracidia

1989 ◽  
Vol 47 ◽  
pp. 962-963
Author(s):  
Betty Ruth Jones ◽  
Steve Chi-Tang Pan
Keyword(s):  
Nervous System ◽  
Life Cycle ◽  
Schistosoma Mansoni ◽  
Snail Host ◽  
Complex Life Cycle ◽  
Rational Approach ◽  
Effective Control ◽  
The Social ◽  
Social And Economic Development ◽  
Basic Biology

INTRODUCTION: Schistosomiasis has been described as “one of the most devastating diseases of mankind, second only to malaria in its deleterious effects on the social and economic development of populations in many warm areas of the world.” The disease is worldwide and is probably spreading faster and becoming more intense than the overall research efforts designed to provide the basis for countering it. Moreover, there are indications that the development of water resources and the demands for increasing cultivation and food in developing countries may prevent adequate control of the disease and thus the number of infections are increasing.Our knowledge of the basic biology of the parasites causing the disease is far from adequate. Such knowledge is essential if we are to develop a rational approach to the effective control of human schistosomiasis. The miracidium is the first infective stage in the complex life cycle of schistosomes. The future of the entire life cycle depends on the capacity and ability of this organism to locate and enter a suitable snail host for further development, Little is known about the nervous system of the miracidium of Schistosoma mansoni and of other trematodes. Studies indicate that miracidia contain a well developed and complex nervous system that may aid the larvae in locating and entering a susceptible snail host (Wilson, 1970; Brooker, 1972; Chernin, 1974; Pan, 1980; Mehlhorn, 1988; and Jones, 1987-1988).

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