There is evidence on the microbiotas’ impact on the effectiveness of vaccines, suggesting a direct link between a high diversity of gut microbiota and a more reasonable response to vaccination. It is comprehended that HIV infection reduces the richness and diversity of the gut microbial population and depletes some of the genera associated with anti-inflammatory conditions. In addition, microbiota composition can predict immune status in HIV infection (Pastor-Ibáñez, 2021). However, the prospect of using transcriptomics and metagenomics as surrogate markers of vaccine response is not thoroughly researched. Therefore, the Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine objective is to correlate mRNA expression profiles. Moreover, it aims to evaluate the effect of gut microbiome profiles that may predict VL control after ATI in participants who received a DC-based HIV-1 vaccine trial.
Materials and Methods
All materials and tools used in the article have been certified and are reliable. All patients were with chronic HIV-1 infection, older than 18, with a baseline CD4+ T-cell count greater than 450 cells/mm3, a nadir CD4+ T-cell count more than 350 mm3 undetectable plasma VL levels (Pastor-Ibáñez, 2021). BMCs were gathered from study participants 1 week before each vaccine dose was administered. Monocytes were sequestered from them and incubated with granulocyte-macrophage colony-stimulating factor and interleukin to induce cells in MDDC that were manipulated for vaccine production. Patients were divided into responders and nonresponders based on the VL factor. Total RNA was isolated from 5 × 106 frozen monocytes removed from PBMC; they underwent quality control, then pooled into equimolar mixtures (Pastor-Ibáñez, 2021). Finally, the DNA sequence of each cluster on flow cells was determined using cycles of Sequencing-By-Synthesis technology.
The number of amplicon sequence variants was collapsed to the bacterial phylum and genus level using the GreenGenes database to assess the abundance of genera. As applicable, distinctions between groups were evaluated using multiple Mann-Whitney-Wilcoxon or Kruskal-Wallis tests with Bonferroni correction. Two separate approaches were also operated to examine the effects of the intervention between the vaccine and placebo groups, these being time point comparisons and estimates of mathematical changes between the groups. The microbiome samples were clustered by genus composition using nonmetric multivariate scaling based on environmental distance matrices calculated by Bray-Curtis dissimilarity and implemented in packages (Pastor-Ibáñez, 2021). To reach the articles aim, the normalized numbers of phylotypes were multiplied by the corresponding set of gene numbers estimated for each taxon to determine the gene content.
The results revealed that no differential gene expression was detected in patients before or after vaccination compared with the placebo group, regardless of the cutoff for change multiplicity applied. Therefore, it can be suggested that the DC vaccine did not affect blood transcriptomes (Pastor-Ibáñez, 2021). The gut microbiota composition between baseline and postvaccine data was examined by LEfSe analysis, which revealed no differences in bacterial composition between the vaccine and control groups. These outcomes indicated that the DC vaccine did not affect the gut microbiota’s richness, diversity, or design.
The TSUT microbiota was analyzed using the relative abundance rates obtained at the phylum and genus levels. Responders showed enriched Bacteroides, Prevotella, Oribacterium, Methanosphaera, Bulleidia, Akkermansia, and Butyrivibrio. In contrast, according to Pastor-Ibáñez (2021), nonresponders had elevated Phascolarctobacterium, Mogibacterium, and Collinsella. PICRUSt2 analysis to predict the metagenomic functional content of the gut microbiota revealed significant differences between the responding and nonresponding groups at the KEGG III level. In particular, the predicted amino acid metabolic pathway for short-chain fatty acid production was significantly increased in responders.
Although the transcriptomic regulation of the biological processes during HIV infection has been studied, much remains unclear. HIV-1 infection leads to a host immune response that is qualitatively and quantitatively distinct from other viral infections. The DC-based therapeutic vaccine induced a major transcriptomic shift in recipients by five weeks, unchanged after ATI and subsequent viral relapse. Vaccination-induced modifications in the gut bacteriome were also detected. This may reflect the remoteness of the lymph node from the gut and the short follow-up period after vaccination. Therefore, intranodal administration of the DC vaccine did not affect the composition of the core bacterial populations in the present study (Pastor-Ibáñez, 2021). Although the vaccine did not appear to affect BMC transcriptomes or the gut microbiome, both omics showed an appropriate association with the VL response after ATI.
Furthermore, the results underscore the importance of IFN pathways in the control of HIV, supporting studies claiming that HIV infection triggers IFN responses in acute conditions and contributes to the power of HIV replication. Evaluation of predicted metabolic functions revealed that several functional amino acid metabolic pathways were increased in respondents. Among these were fermentation of L-lysine to acetate and butanoate, degradation of ethyl malonyl-CoA, and degradation of L-tyrosine (Pastor-Ibáñez, 2021). These three pathways can produce SCFA, directly or indirectly, as acetate, acetoacetate, and butyrate. The end products of microbial fermentation, SCFAs, have been described as critical metabolites in the regulation of intestinal permeability and intestinal inflammation. It has also been investigated that SCFAs can be degraded to acetoacetate via β-oxidation in mitochondria.
In conclusion, there were no results indicating any effect of the DC vaccine on BMP transcriptomes and the gut microbiota in the present study. An alternative analysis revealed that responders who had more time to viral relapse had enrichment of genes related to the IFN type I signaling pathway and were involved in the host defense response. In addition, the gut microbiota of responders was more diverse, and more associated with metabolic SCFA production than nonresponders.
Pastor-Ibáñez, R., Díez-Fuertes, F., Sánchez-Palomino, S., Alcamí, J., Plana, M., Torrents, D., Leal, L.,and García, F. (2021). Impact of transcriptome and gut microbiome on the response of HIV-1 infected individuals to a dendritic cell-based HIV therapeutic vaccine. Vaccines, 9(7), 694.
We Often Learn More From Failures Than Successes, But Not Always
Failures can teach people to think differently or break down completely, depending on the type of it. Successes may lead to over-relaxation when a person stops working actively in order to take pleasure in them. In contrast, causing pain and failures can stimulate work more actively and more productively, avoiding such mistakes. Still, it is necessary to extract lessons from short-term failures and avoid long-term ones; in other cases, success would become very hard to achieve.
Successful Learning from Failures
When people fail, for example, in doing business or in the study, which are probably, the most common examples of modern failures, there can be different reactions to that. There is a concept of negative knowledge, which means the knowledge contradictory to a previous experience (Darabi et al., 2018). It is beneficial, as it shows past mistakes and is usually very deeply grounded, as failures are primarily painful and, thus, very well remembered.
Still, sometimes failures not only teach us nothing but even lead to a complete breakdown. Only relatively short-term loss can be beneficial, as it will lead, eventually, to long-term success (Darabi et al., 2018). If a failure is constant and prolonged, there would scarcely be any success at all: such hardships can lead to total demoralization and exhaustion. While a strong-willed person can still succeed from such a series of problems, becoming even more robust and stiffer, long-term failures are better to be avoided when possible.
Learning from Successes
To be happy and successful can also teach a lot, despite not in all cases. The productive and unproductive successes can be distinguished based on the long-term results of that success (Darabi et al., 2018). Productive ones provide tools and experience for future problem solving, facilitating further work and enabling to prosper in the future if a person is able to use those tools again in the proper context.
As one can conclude, we can really learn more from failures than from successes, but risks are higher, too. If a person can extract a lesson from mistakes, they will be very beneficial, showing how not to do and remember for a long while, while only productive successes work similarly. Along with that, constant failures can break a person down, killing any motivation to continue; only a powerful personality would persist in such conditions.
Darabi, A., Arrington, T. L., & Sayilir, E. (2018). Learning from failure: a meta-analysis of the empirical studies. Educational Technology Research and Development, 66(5), 1101–1118. Web.
Reading Romans In Context: Paul’s Letter To The Romans
Paul’s Letter to the Romans is acknowledged as one of the most important letters from Paul that presents the apostle’s systematic explanation of relationships between the Jewish and Roman Christians. The letter was purposed to explain salvation through faith and bring peace to both house churches. While reading and understanding Romans requires a thorough study of the letter, one should also concern the historical and cultural background of the letter. The book Reading Romans in Context addresses the issue with the collection of essays that focus on comparing Paul’s Letter to the Romans with other Jewish writing from the period.
The book itself presents a collection of essays written by students of Durham University, collected and edited by Durham Ph.D. graduates Ben C. Blackwell, John K. Goodrich, and Jason Maston. Durham University is one of England’s oldest universities that originated as a church university, with a highly acknowledged Religious Studies department that holds high positions among world university rankings. Blackwell is an associate professor of Early Christianity who wrote many articles on Historical Theology and currently works at Houston Baptist University. Maston is a New Testament lecturer, and Goodrich is a Bible professor at Moody Bible Institute. Zondervan published the book with a collection of essays in July of 2015. Considering the editors’ similar backgrounds and approaches, one can identify that the collection essays can include potential biases or presuppositions commonly practiced at Durham University. However, in featuring twenty pieces from different authors, the editors minimized the opportunities for biases and predispositions.
The editors explain that their approach to Paul’s letters was influenced by John Barclay, historian of early Christianity, and Francis Watson, theology and New Testament scholar. Both Barclay and Watson hold the position of professor at Durham University. The editors’ thesis, stated in the book’s preface, suggests that reading Paul’s letter to the Romans alongside other nonscriptural texts from the same period can enhance and enrich the reader’s understanding (p.27). To illustrate the need to examine Paul’s letter to the Romans in connection with other nonscriptural texts, the authors draw an example of Christian radicalism that can only be defined in related literature (p.25). Moreover, according to Watson, perceiving Paul’s Letter to the Romans as an isolated piece diminishes its meaning (p.25). Therefore, the editors’ primary objective in this book was to illustrate the importance of viewing Paul’s letter to Romans in historical and cultural contexts through comparing the letters with other relevant texts. Even though the thesis cannot be developed through the book that features several different essays, the essays are structured in narrative progression depending on which part of Paul’s letter to the Romans they observe.
Furthermore, comparing the text of Paul’s Letter to the Romans with other pieces from the Second Temple literature works cannot define whether Paul was writing the letters concerning the existing literature. However, comparing the letters with other pieces helps to develop an understanding of issues addressed by Paul and how these issues were perceived by Jewish people. Furthermore, to illustrate the importance of relevant literature, the authors state that most Jewish literature from the Second Temple period survived because it was preserved in Christian communities (p.24). Moreover, Jewish literature was translated to other languages as Christian communities acknowledged it as a beneficial context to canonical literature reading (p.24).
The essays featured in Reading Romans in Context explore a wide range of themes that emphasizes similarities between Paul’s Letter to the Romans and relevant literature from the Second Temple era. For example, one of the essays written by J. R. Dodson pointed at the similarities in the personification of Grace, Death, and Sin in Paul’s Letter to the Romans and personification of Wisdom in Wisdom of Solomon (p.131-139). Dodson suggests that for believers choosing to serve Righteousness as their lord is similar to the challenge of embracing wisdom instead of death in the Wisdom of Solomon. The similarity emphasizes the aspect of holiness in faith and the significance of the ability to resist sins.
However, while the collection of essays provides a significant amount of context for Paul’s Letter to the Romans, sometimes comparing the texts has little to no relevance due to different approaches to the topic. For example, the same chapter that discusses the use of personification in Wisdom of Solomon and Paul’s Letter to the Romans makes two conclusions (p.131-139). One of the author’s conclusions focuses on how the pieces perceive the death of the Righteous one. The author determines contradiction between two pieces: in Romans, the crucifixion of Christ is perceived as freedom of those who were previously enslaved by Death and Sin. On the other hand, the Wisdom of Solomon defines the holy one’s execution as an act of sin made out of foolishness, and all participants of the execution will be doomed forever. Such striking differences between the two texts can potentially make the interpretation of the text as well as its purpose more complicated and obscure.
Next, another chapter of the book, which presents an essay by A. Linebaugh, also compared Paul’s Letter to the Romans with Wisdom of Solomon (p.57-68). The chapter examines how both pieces approach the apostolic announcement of God’s wrath. The chapter does sufficient work comparing the descriptions of divine justice in defining several stages of theological contact in both texts that have similarities. In particular, the author focuses a significant amount of his essay on determining the meaning of “God’s wrath against all people” and how it is related to the people of Israel (p.63). The author’s finds suggest that Romans applied the wrath of God to all people with no differences between Jews and Gentiles as they all have sinned. On the other hand, the Wisdom of Solomon utilizes an opposite approach and focuses on opposing Israel’s innocence and immorality of non-Jews (p.66). Therefore, the chapter provides sufficient context to Paul’s letter in emphasizing the immorality in all Adamic humanity, including Israel.
In conclusion, Reading Romans in Context presents a significant resource for additional context to Paul’s letter to the Romans. However, the essay collection content can be beneficial to understanding the initial letters and misleading, as some additional details can be confusing for an average reader. Therefore, while the essays intelligibly explain the differences and similarities of Paul’s letter and other literature pieces of the Second Temple era, its primary audience is scholars and overall people interested in the theme. The editors’ objective of conveying the idea that context can improve the understanding of Paul’s letter is fulfilled in the book; however, not all featured essays can be perceived as sufficient context. Compared to other works in the same field, Reading Romans in Context presents a valuable joint scientific work of people with similar views. The book can be beneficial for the purpose of expanding personal knowledge in the field of study.