Verbal Probability Terms for Communicating Clinical Risk - a Systematic Review.

Verbal probability expressions such as 'likely' and 'possible' are commonly used to communicate uncertainty in diagnosis, treatment effectiveness as well as the risk of adverse events. Probability terms that are interpreted consistently can be used to standardize risk communication. A systematic review was conducted. Research studies that evaluated numeric meanings of probability terms were reviewed. Terms with consistent numeric interpretation across studies were selected and were used to construct a Visual Risk Scale. Five probability terms showed reliable interpretation by laypersons and healthcare professionals in empirical studies. 'Very Likely' was interpreted as 90% chance (range 80 to 95%); 'Likely/Probable,' 70% (60 to 80%); 'Possible,' 40% (30 to 60%); 'Unlikely,' 20% (10 to 30%); and 'Very Unlikely' with 10% chance (5% to 15%). The corresponding frequency terms were: Very Frequently, Frequently, Often, Infrequently, and Rarely, respectively. Probability terms should be presented with their corresponding numeric ranges during discussions with patients. Numeric values should be presented as X-in-100 natural frequency statements, even for low values; and not as percentages, X-in-1000, X-in-Y, odds, fractions, 1-in-X, or as number needed to treat (NNT). A Visual Risk Scale was developed for use in clinical shared decision making.

Exploring the macrominerals and heavy metals profile of deep-sea fishes: A pioneering study on trawl bycatch and discards in the Arabian Sea.

This study assesses macrominerals (Na, K, Ca, Mg, P) and heavy metals (As, Cd, Cr, Cu, Ni, Pb, Se, Sn, Mn, Co, Fe, and Zn) content of deep-sea fish bycatch in the Arabian Sea, offering insights into their nutritional value, toxicant levels and health implications. Variations in Ca, K, P, Mg, and Na levels across species highlight mineral diversity. Setarches guentheri has the highest Ca (7716 mg/kg ww), K (2030.5 mg/kg ww), and P (13,180 mg/kg ww) concentrations. Dactyloptena orientalis exceeds the Cd limit (0.1284 mg/kg ww). Elevated Se levels in fishes were noted, with Dactyloptena orientalis (0.8607 mg/kg ww), Satyrichthys laticeps (0.7303 mg/kg ww), and Snyderina guentheri (0.6193 mg/kg ww). Fish like Pterygotrigla hemisticta contains high Zn (32 mg/kg ww), meeting Recommended Dietary Allowance limits. Deep-sea fish have safe heavy metal levels, but Cd, Se, and Zn exceed acceptable limits. It has been concluded that the consumption of fish species will not pose a potential health risk to humans.

Molecular detection of ruminal micro-flora and micro-fauna in Saudi Arabian camels: Effects of season and region.

This study investigated and explored the availability of micro-flora and micro-fauna in the ruminal contents of Arabian camel (Camelus dromedarius) from three different regions in Saudi Arabia along with two seasons. Samples were prepared and tested by conventional polymerase chain reaction (PCR). This study confirmed that the bacterial flora were dominating over other microbes. Different results of the availability of each microbe in each region and season were statistically analyzed and discussed. There was no significant effect of season on the micro-flora or micro-fauna however, the location revealed a positive effect with Ruminococcus flavefaciens (p < 0 0.03) in the eastern region. This study was the first to investigate the abundance of micro-flora and micro-fauna in the ruminal contents of camels of Saudi Arabia. This study underscores the significance of camel ruminal micro-flora and micro-fauna abundance, highlighting their correlation with both seasonality and geographic location. This exploration enhances our comprehension of camel rumination and digestion processes. The initial identification of these microbial communities serves as a foundational step, laying the groundwork for future in-depth investigations into camel digestibility and nutritional requirements.

Direct Measurement of 8OG Syn-Anti Flips in Mutagenic 8OG·A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics Using 1H CEST NMR.

Elucidating how damage impacts DNA dynamics is essential for understanding the mechanisms of damage recognition and repair. Many DNA lesions alter their propensities to form low-populated and short-lived conformational states. However, NMR methods to measure these dynamics require isotopic enrichment, which is difficult for damaged nucleotides. Here, we demonstrate the utility of the 1H chemical exchange saturation transfer (CEST) NMR experiment in measuring the dynamics of oxidatively damaged 8-oxoguanine (8OG) in the mutagenic 8OGsyn·Aanti mismatch. Using 8OG-H7 as an NMR probe of the damaged base, we directly measured 8OG syn-anti flips to form a lowly populated (pop. ∼ 5%) and short-lived (lifetime ∼50 ms) nonmutagenic 8OGanti·Aanti. These exchange parameters were in quantitative agreement with values from 13C off-resonance R1ρ and CEST on the labeled partner adenine. The Watson-Crick-like 8OGsyn·Aanti mismatch also rescued the kinetics of Hoogsteen motions at distant A-T base pairs, which the G·A mismatch had slowed down. The results lend further support for 8OGanti·Aanti as a minor conformational state of 8OG·A, reveal that 8OG damage can impact Hoogsteen dynamics at a distance, and demonstrate the utility of 1H CEST for measuring damage-dependent dynamics in unlabeled DNA.

Acute Chest Syndrome: A Bibliometric Analysis of the Top 100 Most Cited Articles.

Acute chest syndrome (ACS) is a major cause of morbidity and mortality in patients with SCD (SCD). The analysis of research productivity and trends in ACS may serve as a valuable guide for investigators, institutions, and funding agencies to plan the future directions of research. The current review aims to evaluate the productivity and trends of publications related to ACS in adults by analyzing the top 100 most cited articles. A bibliometric analysis of the top 100 most cited articles related to ACS in adults was conducted on May 20, 2021. The Scopus database was searched to identify the top-cited articles. The following term was applied: "acute chest syndrome" in the fields of title, abstract, and keyword. The most cited article received a total of 776 citations, while the least cited received a total of 10 citations. Over half of the identified articles received 35 citations or less. The articles originated in 12 different countries; the overwhelming majority of articles originated in the United States (n = 75), with small contributions from developing countries with a high prevalence of sickle cell disease. Blood and American Journal of Hematology published the largest number of articles, with nine articles each. The Author "Vichinsky, E.P." has the largest contribution with a total of 10 articles. The plethora of the highly cited articles were Observational studies, while randomized controlled trials were represented by seven articles. The present study demonstrates that research in ACS may be receiving less attention than it should. Therefore, research empowerment and adequate funding are of paramount importance to improve research productivity and quality. Additionally, more collaborative efforts should be encouraged to reduce the gap between developed and developing countries.

NMR measurements of transient low-populated tautomeric and anionic Watson-Crick-like G·T/U in RNA:DNA hybrids: implications for the fidelity of transcription and CRISPR/Cas9 gene editing.

Many biochemical processes use the Watson-Crick geometry to distinguish correct from incorrect base pairing. However, on rare occasions, mismatches such as G·T/U can transiently adopt Watson-Crick-like conformations through tautomerization or ionization of the bases, giving rise to replicative and translational errors. The propensities to form Watson-Crick-like mismatches in RNA:DNA hybrids remain unknown, making it unclear whether they can also contribute to errors during processes such as transcription and CRISPR/Cas editing. Here, using NMR R1ρ experiments, we show that dG·rU and dT·rG mismatches in two RNA:DNA hybrids transiently form tautomeric (Genol·T/U $ \mathbin{\lower.3ex\hbox{$\buildrel\textstyle\rightarrow\over {\smash{\leftarrow}\vphantom{_{\vbox to.5ex{\vss}}}}$}}$ G·Tenol/Uenol) and anionic (G·T-/U-) Watson-Crick-like conformations. The tautomerization dynamics were like those measured in A-RNA and B-DNA duplexes. However, anionic dG·rU- formed with a ten-fold higher propensity relative to dT-·rG and dG·dT- and this could be attributed to the lower pKa (ΔpKa ∼0.4-0.9) of U versus T. Our findings suggest plausible roles for Watson-Crick-like G·T/U mismatches in transcriptional errors and CRISPR/Cas9 off-target gene editing, uncover a crucial difference between the chemical dynamics of G·U versus G·T, and indicate that anionic Watson-Crick-like G·U- could play a significant role evading Watson-Crick fidelity checkpoints in RNA:DNA hybrids and RNA duplexes.

Direct Measurement of 8OG syn-anti Flips in Mutagenic 8OG•A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics Using 1H CEST NMR.

Elucidating how damage impacts DNA dynamics is essential for understanding the mechanisms of damage recognition and repair. Many DNA lesions alter the propensities to form lowly-populated and short-lived conformational states. However, NMR methods to measure these dynamics require isotopic enrichment, which is difficult for damaged nucleotides. Here, we demonstrate the utility of the 1H chemical exchange saturation transfer (CEST) NMR experiment in measuring the dynamics of oxidatively damaged 8-oxoguanine (8OG) in the mutagenic 8OGsyn•Aanti mismatch. Using 8OG-H7 as an NMR probe of the damaged base, we directly measured 8OG syn-anti flips to form a lowly-populated (pop. ~ 5%) and short-lived (lifetime ~ 50 ms) non-mutagenic 8OGanti•Aanti. These exchange parameters were in quantitative agreement with values from 13C off-resonance R1ρ and CEST on a labeled partner adenine. The Watson-Crick-like 8OGsyn•Aanti mismatch also rescued the kinetics of Hoogsteen motions at distance A-T base pairs, which the G•A mismatch had slowed down. The results lend further support for 8OGanti•Aanti as a minor conformational state of 8OG•A, reveal that 8OG damage can impact Hoogsteen dynamics at a distance, and demonstrate the utility of 1H CEST for measuring damage-dependent dynamics in unlabeled DNA.

hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS).

Neurodegeneration is the primary driver of disease progression in multiple sclerosis (MS) resulting in permanent disability, creating an urgent need to discover its underlying mechanisms. Herein, we establish that dysfunction of the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) results in differential of binding to RNA targets causing alternative RNA splicing, which contributes to neurodegeneration in MS and its models. Using RNAseq of MS brains, we discovered differential expression and aberrant splicing of hnRNP A1 target RNAs involved in neuronal function and RNA homeostasis. We confirmed this in vivo in experimental autoimmune encephalomyelitis employing CLIPseq specific for hnRNP A1, where hnRNP A1 differentially binds and regulates RNA, including aberrantly spliced targets identified in human samples. Additionally, dysfunctional hnRNP A1 expression in neurons caused neurite loss and identical changes in splicing, corroborating hnRNP A1 dysfunction as a cause of neurodegeneration. Collectively, these data indicate hnRNP A1 dysfunction causes altered neuronal RNA splicing, resulting in neurodegeneration in MS.

Hydrogen bonding in duplex DNA probed by DNP enhanced solid-state NMR N-H bond length measurements.

Numerous biological processes and mechanisms depend on details of base pairing and hydrogen bonding in DNA. Hydrogen bonds are challenging to quantify by X-ray crystallography and cryo-EM due to difficulty of visualizing hydrogen atom locations but can be probed with site specificity by NMR spectroscopy in solution and the solid state with the latter particularly suited to large, slowly tumbling DNA complexes. Recently, we showed that low-temperature dynamic nuclear polarization (DNP) enhanced solid-state NMR is a valuable tool for distinguishing Hoogsteen base pairs (bps) from canonical Watson-Crick bps in various DNA systems under native-like conditions. Here, using a model 12-mer DNA duplex containing two central adenine-thymine (A-T) bps in either Watson-Crick or Hoogsteen confirmation, we demonstrate DNP solid-state NMR measurements of thymine N3-H3 bond lengths, which are sensitive to details of N-H···N hydrogen bonding and permit hydrogen bonds for the two bp conformers to be systematically compared within the same DNA sequence context. For this DNA duplex, effectively identical TN3-H3 bond lengths of 1.055 ± 0.011 Å and 1.060 ± 0.011 Å were found for Watson-Crick A-T and Hoogsteen A (syn)-T base pairs, respectively, relative to a reference amide bond length of 1.015 ± 0.010 Å determined for N-acetyl-valine under comparable experimental conditions. Considering that prior quantum chemical calculations which account for zero-point motions predict a somewhat longer effective peptide N-H bond length of 1.041 Å, in agreement with solution and solid-state NMR studies of peptides and proteins at ambient temperature, to facilitate direct comparisons with these earlier studies TN3-H3 bond lengths for the DNA samples can be readily scaled appropriately to yield 1.083 Å and 1.087 Å for Watson-Crick A-T and Hoogsteen A (syn)-T bps, respectively, relative to the 1.041 Å reference peptide N-H bond length. Remarkably, in the context of the model DNA duplex, these results indicate that there are no significant differences in N-H···N A-T hydrogen bonds between Watson-Crick and Hoogsteen bp conformers. More generally, high precision measurements of N-H bond lengths by low-temperature DNP solid-state NMR based methods are expected to facilitate detailed comparative analysis of hydrogen bonding for a range of DNA complexes and base pairing environments.

An RNA excited conformational state at atomic resolution.

Sparse and short-lived excited RNA conformational states are essential players in cell physiology, disease, and therapeutic development, yet determining their 3D structures remains challenging. Combining mutagenesis, NMR spectroscopy, and computational modeling, we determined the 3D structural ensemble formed by a short-lived (lifetime ~2.1 ms) lowly-populated (~0.4%) conformational state in HIV-1 TAR RNA. Through a strand register shift, the excited conformational state completely remodels the 3D structure of the ground state (RMSD from the ground state = 7.2 ± 0.9 Å), forming a surprisingly more ordered conformational ensemble rich in non-canonical mismatches. The structure impedes the formation of the motifs recognized by Tat and the super elongation complex, explaining why this alternative TAR conformation cannot activate HIV-1 transcription. The ability to determine the 3D structures of fleeting RNA states using the presented methodology holds great promise for our understanding of RNA biology, disease mechanisms, and the development of RNA-targeting therapeutics.

Prevalence of stroke among patients with chronic kidney disease, Taif, Saudi Arabia.

OBJECTIVES: To evaluate the prevalence of stroke among chronic kidney disease (CKD) patients in Taif, Saudi Arabia. METHODS: A multicentric retrospective study was carried out from May 2021 to August 2022 on 4 dialysis centers in Taif, Saudi Arabia. With a total of 1857 CKD patients (aged ≥18 years old) participated in this study. Data were collected by reviewing patients' files. RESULTS: Approximately 98.3% of the participants had severely decreased glomerular filtration rate. Approximately 49.1% of them were on dialysis; the majority of them (87.2%) underwent hemodialysis. The prevalence of stroke in these CKD patients was 8.3%. Ischemic stroke was the most frequently reported issue (81.2%). Ischemic stroke was comparatively more frequently observed in peritoneal dialysis patients (12.1%); whereas hemorrhagic stroke was more on hemodialysis patients with statistically significant association (p=0.029). However, there was no significant association between the prevalence of stroke and stages of CKD. CONCLUSION: The prevalence of stroke in our cohort was 8.3%, and the majority of cases were ischemic strokes. Furthermore, ischemic strokes were more frequent in peritoneal dialysis patients, whereas hemorrhagic strokes occurred more frequently in hemodialysis patients with a statistically significant association.

Kinetic Resolution of the Atomic 3D Structures Formed by Ground and Excited Conformational States in an RNA Dynamic Ensemble.

Knowing the 3D structures formed by the various conformations populating the RNA free-energy landscape, their relative abundance, and kinetic interconversion rates is required to obtain a quantitative and predictive understanding of how RNAs fold and function at the atomic level. While methods integrating ensemble-averaged experimental data with computational modeling are helping define the most abundant conformations in RNA ensembles, elucidating their kinetic rates of interconversion and determining the 3D structures of sparsely populated short-lived RNA excited conformational states (ESs) remains challenging. Here, we developed an approach integrating Rosetta-FARFAR RNA structure prediction with NMR residual dipolar couplings and relaxation dispersion that simultaneously determines the 3D structures formed by the ground-state (GS) and ES subensembles, their relative abundance, and kinetic rates of interconversion. The approach is demonstrated on HIV-1 TAR, whose six-nucleotide apical loop was previously shown to form a sparsely populated (∼13%) short-lived (lifetime ∼ 45 µs) ES. In the GS, the apical loop forms a broad distribution of open conformations interconverting on the pico-to-nanosecond time scale. Most residues are unpaired and preorganized to bind the Tat-superelongation protein complex. The apical loop zips up in the ES, forming a narrow distribution of closed conformations, which sequester critical residues required for protein recognition. Our work introduces an approach for determining the 3D ensemble models formed by sparsely populated RNA conformational states, provides a rare atomic view of an RNA ES, and kinetically resolves the atomic 3D structures of RNA conformational substates, interchanging on time scales spanning 6 orders of magnitude, from picoseconds to microseconds.

NMR measurements of transient low-populated tautomeric and anionic Watson-Crick-like G·T/U in RNA:DNA hybrids: Implications for the fidelity of transcription and CRISPR/Cas9 gene editing.

Many biochemical processes use the Watson-Crick geometry to distinguish correct from incorrect base pairing. However, on rare occasions, mismatches such as G•T/U can transiently adopt Watson-Crick-like conformations through tautomerization or ionization of the bases, giving rise to replicative and translational errors. The propensities to form Watson-Crick-like mismatches in RNA:DNA hybrids remain unknown, making it unclear whether they can also contribute to errors during processes such as transcription and CRISPR/Cas editing. Here, using NMR R 1ρ experiments, we show that dG•rU and dT•rG mismatches in two RNA:DNA hybrids transiently form tautomeric (G enol •T/U ⇄G•T enol /U enol ) and anionic (G•T - /U - ) Watson-Crick-like conformations. The tautomerization dynamics were like those measured in A-RNA and B-DNA duplexes. However, anionic dG•rU - formed with a ten-fold higher propensity relative to dT - •rG and dG•dT - and this could be attributed to the lower pK a (Δ pK a ∼0.4-0.9) of U versus T. Our findings suggest plausible roles for Watson-Crick-like G•T/U mismatches in transcriptional errors and CRISPR/Cas9 off-target gene editing, uncover a crucial difference between the chemical dynamics of G•U versus G•T, and indicate that anionic Watson-Crick-like G•U - could play a significant role evading Watson-Crick fidelity checkpoints in RNA:DNA hybrids and RNA duplexes.

Efficacy of varicocelectomy on semen parameters and conception rates.

Objective: Varicocele, the dilation of the pampiniform plexus of the spermatic cord. It is discovered incidentally in most patients. Symptoms vary, but its impact is especially experienced in the field of fertility and reflected in semen parameters. Varicocelectomy is a surgical approach to correct the varicocele, however, reports are conflicting regarding its success. Our aim was to evaluate the efficacy of varicocelectomy on semen parameters and conception rates in patients who underwent surgery and its association with comorbidities such as diabetes, hypertension, and obesity. Materials and Methods: This cross-sectional study included the complete medical records of 86 patients. Data collection form included the patient's age, body mass index (BMI), chronic diseases, smoking, surgical history, medication usage, and the reason for performing surgery. Presurgical and postsurgical semen parameters were evaluated 3 months before surgery and an average of 6 months postoperatively. Data were analyzed with SPSS, Chi-square test, and independent and paired t-test. Results: No significant difference was found between primary and secondary infertility regarding semen analysis, postoperative semen analysis indicated an improvement in semen motility at 180 min with no effect on other parameters. Using spontaneous intercourse or in vitro fertilization (IVF) after varicocelectomy was significantly associated with increasing conception rates irrespective of the type of infertility. Diabetes, hypertension, BMI, and smoking did not appear to affect semen parameters. Conclusion: Patients who underwent varicocelectomy had improved sperm motility at 180 min and subsequently had a higher chance of successful conception either through spontaneous intercourse or IVF. Further studies are needed to understand the relationship between conception and sperm motility. Semen parameters were not affected if the patient had comorbidities such as diabetes and hypertension. Furthermore, smoking and BMI did not appear to affect the conception rate.

Correlation of Physical Activity to Mental Health State and Grade Point Average Among Medical Students in Saudi Arabia: A Cross-Sectional Study.

INTRODUCTION: Physical activity (PA) significantly impacts mental health. However, studies addressing the influence of PA on the mental health and academic performance of medical students are scarce. MATERIALS AND METHODS: A cross-sectional study was carried out among 2,819 students pursuing their medical degrees in Saudi Arabia. PA was measured using the Global Physical Activity Questionnaire, and the state of their mental health was recorded using the Hospital Anxiety and Depression Scale. A multi-logistic regression was performed to predict the risk factor of poor academic performance. RESULTS: The prevalence of abnormal anxiety and depression levels were found to be 45.3% and 31.6%, respectively, which were comparatively more prevalent among students of younger age (p < 0.001). Students with abnormal anxiety levels had significantly lower grade point average (GPA) levels than others (p < 0.001). Those who were aged < 21 years, female gender, with chronic disease presence, low PA levels, and abnormal anxiety levels were independently associated with lower GPA levels (p < 0.05). CONCLUSION: Low PA and high anxiety and depression levels were found to affect the academic performance of medical students in Saudi Arabia. Hence, health education about the importance of PA should be directed to those students.

Aquatic toxicity of hydroquinone and catechol following metal oxide treatment to Ceriodaphnia dubia and Pimephales promelas.

Metal oxides comprise a large group of chemicals used in water treatment to adsorb organic pollutants. The ability of titanium dioxide (TiO2) and iron (III) oxide (Fe2O3) to reduce the chronic toxicity of (phenolic) C6H6(OH)2 isomers, namely hydroquinone (HQ) and catechol (CAT) to Ceriodaphnia dubia and Pimephales promelas (less than 24 h-old) were investigated. The toxic endpoints following metal oxide treatment were compared to endpoints of untreated CAT and HQ. In chronic toxicity testing, HQ resulted in greater toxicity than CAT for both test organisms; the median lethal concentrations (LC50) for CAT were 3.66 to 12.36 mg.L-1 for C. dubia and P. promelas, respectively, while LC50 for HQ were 0.07 to 0.05 mg.L-1, respectively. Although both treated solutions presented lower toxic endpoints than those in the untreated solutions, Fe2O3 had a better potential to reduce the toxic effects of CAT and HQ than TiO2.

Turing, von Neumann, and the computational architecture of biological machines.

In the mid-1930s, the English mathematician and logician Alan Turing invented an imaginary machine which could emulate the process of manipulating finite symbolic configurations by human computers. His machine launched the field of computer science and provided a foundation for the modern-day programmable computer. A decade later, building on Turing's machine, the American-Hungarian mathematician John von Neumann invented an imaginary self-reproducing machine capable of open-ended evolution. Through his machine, von Neumann answered one of the deepest questions in Biology: Why is it that all living organisms carry a self-description in the form of DNA? The story behind how two pioneers of computer science stumbled on the secret of life many years before the discovery of the DNA double helix is not well known, not even to biologists, and you will not find it in biology textbooks. Yet, the story is just as relevant today as it was eighty years ago: Turing and von Neumann left a blueprint for studying biological systems as if they were computing machines. This approach may hold the key to answering many remaining questions in Biology and could even lead to advances in computer science.

Seasonal variations of vitamin A, D and E levels in serum of female camels (Camelus dromedarius) and their calves raised in five geographic regions of Saudi Arabia.

The aim of this study was to investigate the serum level of fat-soluble vitamins A, D and E in clinically healthy lactating female camel (Camelus dromedarius) and suckling calf > one-year-old during winter and summer seasons in five main regions of Saudi Arabia. 60 sera samples were collected and tested for vitamins A, D and E levels and the results were statistically analyzed. The statistical mean value of vitamin A was within the reported range but for D and E, there were minor variations. The effect of season was insignificant (p > 0.05) for vitamins A and E in the combined results of the dam and newborn together. This seasonal effect was highly significant in dam serum (p < 0.05). Region effect was significant for vitamin A in the northern area (p < 0.05) and for vitamin E in the southern region (p < 0.05). Correlations analysis revealed significant results in the season vs vitamin A and E p < 0.05. Mean values of vitamins A, D and E in dam and newborn did not observe significant variations however, in the season and regions there were significant variations which can be attributed to the climate difference, availability of balanced rations and camel management in each location of the five main regions of Saudi Arabia. There is a great need for further studies and the consequent development of supplementation programs and camel feed manufacturers awareness of such results is highly recommended.

RNA conformational propensities determine cellular activity.

Cellular processes are the product of interactions between biomolecules, which associate to form biologically active complexes1. These interactions are mediated by intermolecular contacts, which if disrupted, lead to alterations in cell physiology. Nevertheless, the formation of intermolecular contacts nearly universally requires changes in the conformations of the interacting biomolecules. As a result, binding affinity and cellular activity crucially depend both on the strength of the contacts and on the inherent propensities to form binding-competent conformational states2,3. Thus, conformational penalties are ubiquitous in biology and must be known in order to quantitatively model binding energetics for protein and nucleic acid interactions4,5. However, conceptual and technological limitations have hindered our ability to dissect and quantitatively measure how conformational propensities affect cellular activity. Here we systematically altered and determined the propensities for forming the protein-bound conformation of HIV-1 TAR RNA. These propensities quantitatively predicted the binding affinities of TAR to the RNA-binding region of the Tat protein and predicted the extent of HIV-1 Tat-dependent transactivation in cells. Our results establish the role of ensemble-based conformational propensities in cellular activity and reveal an example of a cellular process driven by an exceptionally rare and short-lived RNA conformational state.