An Uncharged Amine in the Transition State of the Ribosomal Peptidyl Transfer Reaction

The ribosome has an active site comprised of RNA that catalyzes peptide bond formation. To understand how RNA promotes this reaction requires a detailed understanding of the chemical transition state. Here, we report the Brønsted coefficient of the α-amino nucleophile with a series of puromycin derivatives. Both 50S subunit- and 70S ribosome-catalyzed reactions displayed linear free-energy relationships with slopes close to zero under conditions where chemistry is rate limiting. These results indicate that, at the transition state, the nucleophile is neutral in the ribosome-catalyzed reaction, in contrast to the substantial positive charge reported for typical uncatalyzed aminolysis reactions. This suggests that the ribosomal transition state involves deprotonation to a degree commensurate with nitrogen-carbon bond formation. Such a transition state is significantly different from that of uncatalyzed aminolysis reactions in solution

Bioactive Endophytes Warrant Intensified Exploration and Conservation

A key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value.We isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15–30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive.The novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance

Cognitive Behavior Therapy for Anxious Adolescents: Developmental Influences on Treatment Design and Delivery

Anxiety disorders in adolescence are common and disruptive, pointing to a need for effective treatments for this age group. Cognitive behavior therapy (CBT) is one of the most popular interventions for adolescent anxiety, and there is empirical support for its application. However, a significant proportion of adolescent clients continue to report anxiety symptoms post-treatment. This paper underscores the need to attend to the unique developmental characteristics of the adolescent period when designing and delivering treatment, in an effort to enhance treatment effectiveness. Informed by the literature from developmental psychology, developmental psychopathology, and clinical child and adolescent psychology, we review the ‘why’ and the ‘how’ of developmentally appropriate CBT for anxious adolescents. ‘Why’ it is important to consider developmental factors in designing and delivering CBT for anxious adolescents is addressed by examining the age-related findings of treatment outcome studies and exploring the influence of developmental factors, including cognitive capacities, on engagement in CBT. ‘How’ clinicians can developmentally tailor CBT for anxious adolescents in six key domains of treatment design and delivery is illustrated with suggestions drawn from both clinically and research-oriented literature. Finally, recommendations are made for research into developmentally appropriate CBT for anxious adolescents

Sex-Based Differences in Outcomes of Tibial Tubercle Anteromedialization.

UNLABELLED: Bulletin of the Hospital for Joint Diseases 2022;80(4):252-6252 Bloom DA, Gonzalez M, Hurley ET, Kingery MT, Carter CW, Jazrawi LM, Strauss EJ. Sex-based differences in outcomes of tibial tubercle anteromedi- alization. Bull Hosp Jt Dis. 2022;80(4):252-6. Abstract Background: Previous research has demonstrated sex- based differences in patient-reported outcomes of orthopedic surgical procedures. The hypothesis of the current study was that females would have inferior patient-reported outcomes to their male peers following a tibial tubercle anteromedial- ization (AMZ) procedure for both patellofemoral instability and cartilage defects. METHODS: Patients who had undergone AMZ for isolated osteochondral defect or patellofemoral instability with a minimum follow-up time of 1 year were identified. They were then asked to complete several patient-reported outcome questionnaires that were then statistically analyzed. RESULTS: Overall, 109 patients were included in this study. Seventy-nine patients (72.5%) were female with a mean follow-up duration of 3.4 ± 2.0 years. Forty-seven females had AMZ for patellar instability while 32 females had AMZ for osteochondral defects. There were no statistically signifi- cant differences between sexes with respect to concomitant procedures performed, visual analog scale (VAS) pain score, or patient reported outcome (PRO) scores at follow-up (p \u3e 0.05). There was no statistically significant difference with respect to outcomes between the sexes for AMZ overall and when isolating the sexes based on indication. CONCLUSION: This study demonstrates that female patients undergoing AMZ have short-term clinical and functional outcomes that are not significantly different to those reported in males