Baculoviruses Mediate Efficient Gene Expression in a Wide Range of Vertebrate Cells

Author(s):  
Kari J. Airenne ◽  
Kaisa-Emilia Makkonen ◽  
Anssi J. Mähönen ◽  
Seppo Ylä-Herttuala
2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.


Ecotoxicology ◽  
2021 ◽  
Author(s):  
Daesik Park ◽  
Catherine R. Propper ◽  
Guangning Wang ◽  
Matthew C. Salanga

AbstractNaturally occurring arsenic is toxic at extremely low concentrations, yet some species persist even in high arsenic environments. We wanted to test if these species show evidence of evolution associated with arsenic exposure. To do this, we compared allelic variation across 872 coding nucleotides of arsenic (+3) methyltransferase (as3mt) and whole fish as3mt gene expression from three field populations of Gambusia affinis, from water sources containing low (1.9 ppb), medium-low (3.3 ppb), and high (15.7 ppb) levels of arsenic. The high arsenic site exceeds the US EPA’s Maximum Contamination Level for drinking water. Medium-low and high populations exhibited homozygosity, and no sequence variation across all animals sampled. Eleven of 24 fish examined (45.8%) in the low arsenic population harbored synonymous single nucleotide polymorphisms (SNPs) in exons 4 and/or 10. SNP presence in the low arsenic population was not associated with differences in as3mt transcript levels compared to fish from the medium-low site, where SNPs were noted; however, as3mt expression in fish from the high arsenic concentration site was significantly lower than the other two sites. Low sequence variation in fish populations from sites with medium-low and high arsenic concentrations suggests greater selective pressure on this allele, while higher variation in the low population suggests a relaxed selection. Our results suggest gene regulation associated with arsenic detoxification may play a more crucial role in influencing responses to arsenic than polymorphic gene sequence. Understanding microevolutionary processes to various contaminants require the evaluation of multiple populations across a wide range of pollution exposures.


2021 ◽  
Vol 11 (13) ◽  
pp. 5859
Author(s):  
Fernando N. Santos-Navarro ◽  
Yadira Boada ◽  
Alejandro Vignoni ◽  
Jesús Picó

Optimal gene expression is central for the development of both bacterial expression systems for heterologous protein production, and microbial cell factories for industrial metabolite production. Our goal is to fulfill industry-level overproduction demands optimally, as measured by the following key performance metrics: titer, productivity rate, and yield (TRY). Here we use a multiscale model incorporating the dynamics of (i) the cell population in the bioreactor, (ii) the substrate uptake and (iii) the interaction between the cell host and expression of the protein of interest. Our model predicts cell growth rate and cell mass distribution between enzymes of interest and host enzymes as a function of substrate uptake and the following main lab-accessible gene expression-related characteristics: promoter strength, gene copy number and ribosome binding site strength. We evaluated the differential roles of gene transcription and translation in shaping TRY trade-offs for a wide range of expression levels and the sensitivity of the TRY space to variations in substrate availability. Our results show that, at low expression levels, gene transcription mainly defined TRY, and gene translation had a limited effect; whereas, at high expression levels, TRY depended on the product of both, in agreement with experiments in the literature.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iman S. Naga ◽  
Amel Abdel Fattah Kamel ◽  
Said Ahmed Ooda ◽  
Hadeer Muhammad Fath Elbab ◽  
Rania Mohamed El-Sharkawy

Abstract Background Hepatitis C virus infection is a global health challenge with Egypt being one of the highly affected countries. IL-10 has been suggested as a suitable marker to assess necroinflammation and to monitor the progression of liver damage. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor playing a central role in many physiological as well as pathological processes. Several factors can be predictive of the response to treatment and achievement of SVR; some of which are host-related, and others are virus-related. The gene expression of IL-10 and VEGF have multiple effects for treatment response. The aim of the present work was to study the effect of treatment with directly acting agents (DAA) on the expression of VEGF and IL-10 genes in chronic hepatitis C virus-infected Egyptian genotype-4a patients. Twenty-five HCV subjects where evaluated for IL-10 and VEGF gene expression before and after treatment with DAA. Results IL-10 expression was downregulated in 92% of the cases. VEGF expression was heterogeneous showing spreading of values along a wide range with 64% of the cases being downregulated. Conclusion DAAs do not completely reverse the immunological imprints established upon chronic HCV infection.


Parasitology ◽  
1999 ◽  
Vol 117 (7) ◽  
pp. 191-203 ◽  
Author(s):  
M. S. TALARY ◽  
J. P. H. BURT ◽  
R. PETHIG

There has been an enormous growth in the development of biotechnological applications, where advances in the techniques of microelectronic fabrication and the technologies of miniaturization and integration in semiconductor industries are being applied to the production of Laboratory-on-a-Chip devices. The aim of this development is to create devices that will perform the same processes that are currently carried out in the laboratory in reduced timescales, at a lower cost, requiring less reagents, and with a greater resolution of detection and specificity. The expectations of this Laboratory-on-a-Chip revolution is that this technology will facilitate rapid advances in gene discovery, genetic mapping and gene expression with broader applications ranging from infectious diseases and cancer diagnostics to food quality and environmental testing. A review of the current state of development in this field reveals the scale of the ongoing revolution and serves to highlight the advances that can be perceived in the development of Laboratory-on-a-Chip technologies. Since miniaturization can be applied to such a wide range of laboratory processes, some of the sub-units that can be used as building blocks in these devices are described, with a brief description of some of the fabrication processes that can be used to create them.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jorge A. Ramírez-Tejero ◽  
Jaime Jiménez-Ruiz ◽  
Alicia Serrano ◽  
Angjelina Belaj ◽  
Lorenzo León ◽  
...  

Abstract Background Olive orchards are threatened by a wide range of pathogens. Of these, Verticillium dahliae has been in the spotlight for its high incidence, the difficulty to control it and the few cultivars that has increased tolerance to the pathogen. Disease resistance not only depends on detection of pathogen invasion and induction of responses by the plant, but also on barriers to avoid the invasion and active resistance mechanisms constitutively expressed in the absence of the pathogen. In a previous work we found that two healthy non-infected plants from cultivars that differ in V. dahliae resistance such as ‘Frantoio’ (resistant) and ‘Picual’ (susceptible) had a different root morphology and gene expression pattern. In this work, we have addressed the issue of basal differences in the roots between Resistant and Susceptible cultivars. Results The gene expression pattern of roots from 29 olive cultivars with different degree of resistance/susceptibility to V. dahliae was analyzed by RNA-Seq. However, only the Highly Resistant and Extremely Susceptible cultivars showed significant differences in gene expression among various groups of cultivars. A set of 421 genes showing an inverse differential expression level between the Highly Resistant to Extremely Susceptible cultivars was found and analyzed. The main differences involved higher expression of a series of transcription factors and genes involved in processes of molecules importation to nucleus, plant defense genes and lower expression of root growth and development genes in Highly Resistant cultivars, while a reverse pattern in Moderately Susceptible and more pronounced in Extremely Susceptible cultivars were observed. Conclusion According to the different gene expression patterns, it seems that the roots of the Extremely Susceptible cultivars focus more on growth and development, while some other functions, such as defense against pathogens, have a higher expression level in roots of Highly Resistant cultivars. Therefore, it seems that there are constitutive differences in the roots between Resistant and Susceptible cultivars, and that susceptible roots seem to provide a more suitable environment for the pathogen than the resistant ones.


2003 ◽  
Vol 01 (03) ◽  
pp. 541-586 ◽  
Author(s):  
Tero Aittokallio ◽  
Markus Kurki ◽  
Olli Nevalainen ◽  
Tuomas Nikula ◽  
Anne West ◽  
...  

Microarray analysis has become a widely used method for generating gene expression data on a genomic scale. Microarrays have been enthusiastically applied in many fields of biological research, even though several open questions remain about the analysis of such data. A wide range of approaches are available for computational analysis, but no general consensus exists as to standard for microarray data analysis protocol. Consequently, the choice of data analysis technique is a crucial element depending both on the data and on the goals of the experiment. Therefore, basic understanding of bioinformatics is required for optimal experimental design and meaningful interpretation of the results. This review summarizes some of the common themes in DNA microarray data analysis, including data normalization and detection of differential expression. Algorithms are demonstrated by analyzing cDNA microarray data from an experiment monitoring gene expression in T helper cells. Several computational biology strategies, along with their relative merits, are overviewed and potential areas for additional research discussed. The goal of the review is to provide a computational framework for applying and evaluating such bioinformatics strategies. Solid knowledge of microarray informatics contributes to the implementation of more efficient computational protocols for the given data obtained through microarray experiments.


2021 ◽  
pp. bjophthalmol-2020-318330
Author(s):  
Rohan Verma ◽  
Dongseok Choi ◽  
Allison J Chen ◽  
Christina A Harrington ◽  
David J Wilson ◽  
...  

BackgroundOrbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy.AimsTo test the hypothesis that shared signalling pathways are activated in different forms of OID.MethodsIn this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls.ResultsAmong the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways.ConclusionsAlthough OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.


1996 ◽  
Vol 271 (2) ◽  
pp. E253-E260 ◽  
Author(s):  
C. E. Torgan ◽  
W. E. Kraus

Skeletal muscle exhibits a wide range in functional phenotype in response to changes in physiological demands. We have observed that, in response to changes in work patterns, alterations in gene expression of some proteins coincide with changes in adenylyl cyclase (AC) activity [Kraus, W.E., J.P. Longabaugh, and S. B. Liggett. Am. J. Physiol 263 (Endocrinol. Metab. 26): E266-E230, 1992]. We now examine AC isoform transcript prevalence in various rabbit skeletal muscles and in response to changing work demands. Using reverse transcriptase-polymerase chain reaction, we detected type II AC isoform transcripts in rabbit skeletal muscle. Ribonuclease protection analyses revealed that expression of the type II isoform significantly correlated with the percentage of fast-twitch type IIb/IId fibers (r2 = 0.765, P < 0.01). When a fast-twitch muscle was converted to a slow-twitch muscle via chronic electrical pacing, expression of type II AC mRNA significantly decreased. This response occurred 3 days after the onset of stimulation (78% decrease) and was still present after 21 days of stimulation (76% decrease). As type II AC is relatively insensitive to calcium regulation while sensitive to protein kinase C (PKC) signaling, these data provide further impetus for investigations of protein kinase A and PKC cross-talk signaling mechanisms in the regulation of gene expression.


Sign in / Sign up

Export Citation Format

Share Document