Commentary: Basic Research in HIV Vaccinology Is Hampered by Reductionist Thinking

King, Mike

doi:10.3389/fimmu.2016.00042

Cited by 5 publications

(4 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RT-qPCR was performed as previously described [19, 20]. For AML patient samples RT-qPCR experiments were carried out using SYBR Green PCR Master Mix (Applied Biosystems) with an ABI 7900 Real-Time PCR System (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia

et al. 2017

View full text Add to dashboard Cite

BackgroundLong non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia.Results CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis. Enforced expression of CASC15 led to a myeloid bias in development, and overall, decreased engraftment and colony formation. At the cellular level, CASC15 regulated cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown were enriched for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. Interestingly, we found that CASC15 enhances YY1-mediated regulation of the SOX4 promoter.ConclusionsOur findings represent the first characterization of this CASC15 in RUNX1-translocated leukemia, and point towards a mechanistic basis for its action.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0692-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, it is increasingly evident that this approach is insufficient for understanding a process like exosome transfer of miRNA epigenetic functions. Instead these processes may be analyzed more comprehensively by applying concepts of systems biology [ 134 , 135 , 136 , 137 , 138 , 139 ]. Thus, we hypothesize that such “big thinking” alternative convergent systems’ biologic concepts apply to the functional activities of miRNAs delivered into targeted cells by exosomes.…”

Section: Systems Biology Is More Appropriate For Delivered Exosome Fu...mentioning

confidence: 99%

Exosome Carrier Effects; Resistance to Digestion in Phagolysosomes May Assist Transfers to Targeted Cells; II Transfers of miRNAs Are Better Analyzed via Systems Approach as They Do Not Fit Conventional Reductionist Stoichiometric Concepts

Askenase

2022

IJMS

View full text Add to dashboard Cite

Carrier effects of extracellular vesicles (EV) like exosomes refer to properties of the vesicles that contribute to the transferred biologic effects of their contents to targeted cells. This can pertain to ingested small amounts of xenogeneic plant miRNAs and oral administration of immunosuppressive exosomes. The exosomes contribute carrier effects on transfers of miRNAs by contributing both to the delivery and the subsequent functional intracellular outcomes. This is in contrast to current quantitative canonical rules that dictate just the minimum copies of a miRNA for functional effects, and thus successful transfers, independent of the EV carrier effects. Thus, we argue here that transfers by non-canonical minute quantities of miRNAs must consider the EV carrier effects of functional low levels of exosome transferred miRNA that may not fit conventional reductionist stoichiometric concepts. Accordingly, we have examined traditional stoichiometry vs. systems biology that may be more appropriate for delivered exosome functional responses. Exosome carrier properties discussed include; their required surface activating interactions with targeted cells, potential alternate targets beyond mRNAs, like reaching a threshold, three dimensional aspects of the RNAs, added EV kinetic dynamic aspects making transfers four dimensional, and unique intracellular release from EV that resist intracellular digestion in phagolysosomes. Together these EV carrier considerations might allow systems analysis. This can then result in a more appropriate understanding of transferred exosome carrier-assisted functional transfers. A plea is made that the miRNA expert community, in collaboration with exosome experts, perform new experiments on molecular and quantitative miRNA functional effects in systems that include EVs, like variation in EV type and surface constituents, delivery, dose and time to hopefully create more appropriate and truly current canonical concepts of the consequent miRNA functional transfers by EVs like exosomes.

show abstract

“…Using the convergence argument ( 4 ), I suggested that all these independently obtained negative results justified the conclusion that RV was unlikely to lead to a successful vaccine because it is based on invalid reductionist thinking ( 5 ). King ( 6 ) disagreed with this conclusion because it was based on inductive reasoning (i.e., generalizing from a limited body of evidence), and there was therefore no “proof” that the conclusion was correct ( 7 ). Indeed, experimental science never leads to absolute certainty, since certainties are only achieved by logical, deductive reasoning and are not derived from empirical experimentation.…”

mentioning

confidence: 99%

“…King ( 6 ) also pointed out that HIV vaccine development and related efficacy trials in humans present numerous ethical constraints that are particularly challenging. He suggested that it may be unethical to pursue attempts to develop an HIV-1 vaccine by RV, if scarce resources could be used more effectively to combat the AIDS epidemic and its huge societal problems by other means.…”

mentioning

confidence: 99%