On the purported "backbone fluorescence" in protein three-dimensional fluorescence spectra

In this study, several proteins (albumin, lysozyme, insulin) and model compounds (Trp, Tyr, homopolypeptides) were used to demonstrate the origin of the fluorescence observed upon their excitation at 220–230 nm. In the last 10 years we have observed a worrying increase in the number of articles claiming that this fluorescence originates from the protein backbone, contrary to the established knowledge that UV protein emission is due to aromatic amino acids only. Overall, our data clearly demonstrate that the observed emission upon excitation at 220–230 nm is due to the excitation of Tyr and/or Trp, with subsequent emission from the lowest excited state (i.e. the same as obtained with 280 nm excitation) in agreement with Kasha's rule. Therefore, this fluorescence peak does not provide any information on backbone conformation, but simply reports on the local environment around the aromatic side chains, just as any traditional protein emission spectrum. The many papers in reputable journals erroneously reporting this peak assignment, contradicting 5 decades of prior knowledge, have led to the creation of a new dogma, where many authors and reviewers now take the purported backbone fluorescence as an established fact. We hope the current paper helps counter this new situation and leads to a reassessment of those papers that make this erroneous claim

Antigene MYCN Silencing by BGA002 Inhibits SCLC Progression Blocking mTOR Pathway and Overcomes Multidrug Resistance

: Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in MYC family members are biomarkers of poor prognosis for a large number of SCLC. In particular, MYCN alterations define SCLC cases with immunotherapy failure. MYCN has a highly restricted pattern of expression in normal cells and is an ideal target for cancer therapy but is undruggable by traditional approaches. We propose an innovative approach to MYCN inhibition by an MYCN-specific antigene-PNA oligonucleotide (BGA002)-as a new precision medicine for MYCN-related SCLC. We found that BGA002 profoundly and specifically inhibited MYCN expression in SCLC cells, leading to cell-growth inhibition and apoptosis, while also overcoming multidrug resistance. These effects are driven by mTOR pathway block in concomitance with autophagy reactivation, thus avoiding the side effects of targeting mTOR in healthy cells. Moreover, we identified an MYCN-related SCLC gene signature comprehending CNTFR, DLX5 and TNFAIP3, that was reverted by BGA002. Finally, systemic treatment with BGA002 significantly increased survival in MYCN-amplified SCLC mouse models, including in a multidrug-resistant model in which tumor vascularization was also eliminated. These findings warrant the clinical testing of BGA002 in MYCN-related SCLC

The Impact of a Peer-to-Peer Mentoring Program on University Choices and Performance

We study the impact of a personalized mentoring program on university enrollment choices and academic outcomes. Conducting a randomized controlled trial among 337 high school students, we find that the program significantly influences students' decisions, increasing the likelihood of choosing a field aligned with their mentor's by 22 percentage points, representing a 45% increase from the baseline. Notably, the program also shifts preferences towards STEM/Economics fields, enhancing prospective wages by 3.1-3.7%, without negatively impacting university performance. These findings underscore the mentorship's potential to guide students towards more informed and beneficial educational choices

Late failure of double-inlet left ventricle septation: treatment by orthotopic heart transplantation.

We report a patient in whom orthotopic heart transplantation was performed after late failure of ventricular septation for double-inlet left ventricle. This case shows that orthotopic heart transplantation represents a valid therapeutic alternative in children with previous correction of complex congenital heart defects not amenable to further intracardiac repai

The feasibility of using passive injectable transponders in field operations for individual identification of sheep in Italy

This trial evaluates the feasibility of using passive injectable transponders (PITs) in field operations by testing identification procedures on 185 one-year-old Biellese ewes reared under nomadic farming conditions. Commercial PITs of 3.85 ± 0.05 mm × 31.2 mm were used at two application sites, the armpit and the retro-auricular region. The two application sites were compared taking into account the ease of injection, animal reaction, injection duration, inflammatory response, PIT readability at up to 12 months post-injection and PIT recovery at the slaughterhouse. The injection site influenced the reaction of the animal and the ease and duration of the injection, but it did not affect the palpation and the reading findings during the rearing period. The injection site also influenced the PIT retrieval at the slaughterhouse depending on the operator who recovered the PIT. The readability values observed at the end of the observation period for both injection sites (83% in the retro-auricular region and 79% in the armpit region) were too low to be suitable for long-term animal identification. In addition, the failed retrieval of PITs at slaughter, determined the destruction of 40 (22%) carcases to avoid any risks in the food chain. These findings suggest that the limited use of PITs is indicated when other methods of electronic identification cannot be employed, while a wider application of the device tested in the present study is not recommended in farming practices