Explore the vast range of titles available.

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)—a complex chaperoning the selection of branch and 3′ splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept. Chemical modulation of intron selection has emerged as a route for cancer therapy. Here, structures of the U2 snRNP’s SF3B module and of prespliceosome- both in complexes with splicing modulators- provide insight into the mechanisms of intron recognition and branch site inactivation.

Music should be integrated into our daily activities due to its great effects on human holistic health, through its characteristics of melody, rhythm and harmony. Music orchestras use different instruments, with strings, bow, percussion, wind, keyboards, etc. Musical triangles, although not so well known by the general public, are appreciated for their crystalline and percussive sound. Even if it is a seemingly simple instrument being made of a bent metal bar, the problem of the dynamics of the musical triangle is complex. The novelty of the paper consists in the ways of investigating the elastic and dynamic properties of the two types of materials used for musical triangles. Thus, to determine the mechanical properties, samples of material from the two types of triangles were obtained and tested by the tensile test. The validation of the results was carried out by means of another method, based on the modal analysis of a ternary system; by applying the intrinsic transfer matrix, the difference between the obtained values was less than 5%. As the two materials behaved differently at rupture, one having a ductile character and the other brittle, the morphology of the fracture surface and the elementary chemical composition were investigated by scanning electron microscopy (SEM) and analysis by X-ray spectroscopy with dispersion energy (EDX). The results were further transferred to the finite element modal analysis in order to obtain the frequency spectrum and vibration modes of the musical triangles. The modal analysis indicated that the first eigenfrequency differs by about 5.17% from one material to another. The first mode of vibration takes place in the plane of the triangle (transverse mode), at a frequency of 156 Hz and the second mode at 162 Hz, which occurs due to vibrations of the free sides of the triangle outside the plane, called the torsion mode. The highest dominant frequency of 1876 Hz and the sound speed of 5089 m/s were recorded for the aluminum sample with the ductile fracture in comparison with the dominant frequency of 1637 Hz and the sound speed of 4889 m/s in the case of the stainless steel sample, characterized by brittle fracture.

Background and Objectives: the purpose of this study was to evaluate students’ level of knowledge and attitude towards oral hygiene. Materials and Methods: the evaluation was carried out by a questionnaire, with 30 Q (questions) as follows: demographic data (Q1–Q5), oral hygiene knowledge data (Q6–Q23) and oral hygiene attitude data (Q24–Q30). The study included students from Romanian schools and the selection of the study group was made following selection criteria in accordance with ethical issues. A descriptive statistical analysis was performed and a value of p ≤ 0.05 was considered statistically significant. Results: the study included a number of 718 subjects with a mean age of 14.54 (±2.22), male 250 (34.8%) and female 468 (65.2%), MS (middle school students) 354 (49.4%) and HH (high school students) 364 (50.6%). Most of the subjects 292 (MS = 160; HS = 132) know a toothbrushing technique, p = 0.009, r = 0.091 and 587 (MS = 278; HS = 309) know that brushing removes the bacterial plaque p = 0.027, r = −0.082 but only 147 (MS = 71; HS = 76) know that (by) brushing can re-mineralize hard dental structures. The duration of the toothbrushing is variable, for 2- or 3-min p = 0.058, r = 0.043. Criteria for choosing the toothbrush were based mainly on the indications of the dentist, respectively, for toothpaste on its properties. The frequency of toothbrushing is mainly twice a day 428 (MS = 234; HS = 248), p = 0.079, r = 0.037, 73 (MS = 33; HS = 40) after every meal. p = 0.099, r = 0.095. Mouthwash is used by 421 (MS = 199; HS = 222) p = 0.111, r = −0.048, and 228 (MS = 199; HS = 222) after each brushing. Dental floss is used by 240 (MS = 106; HS = 134), p = 0.031, r = −0.073 and only 74 (MS = 41; HS = 33) after each brushing. Conclusions: there are differences in the level of knowledge and attitudes regarding the determinants of oral hygiene depending on the level of education.

Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated B act  and the branching-competent B * spliceosomes. Catalytic activation occurs through an ATP-dependent remodelling mediated by the helicase PRP2 (also known as DHX16) 1 – 3 . However, because PRP2 is observed only at the periphery of spliceosomes 3 – 5 , its function has remained elusive. Here we show that catalytic activation occurs in two ATP-dependent stages driven by two helicases: PRP2 and Aquarius. The role of Aquarius in splicing has been enigmatic 6 , 7 . Here the inactivation of Aquarius leads to the stalling of a spliceosome intermediate—the B AQR complex—found halfway through the catalytic activation process. The cryogenic electron microscopy structure of B AQR reveals how PRP2 and Aquarius remodel B act and B AQR , respectively. Notably, PRP2 translocates along the intron while it strips away the RES complex, opens the SF3B1 clamp and unfastens the branch helix. Translocation terminates six nucleotides downstream of the branch site through an assembly of PPIL4, SKIP and the amino-terminal domain of PRP2. Finally, Aquarius enables the dissociation of PRP2, plus the SF3A and SF3B complexes, which promotes the relocation of the branch duplex for catalysis. This work elucidates catalytic activation in human splicing, reveals how a DEAH helicase operates and provides a paradigm for how helicases can coordinate their activities. Cryogenic electron microscopy images of a spliceosome complex undergoing catalytic activation provide mechanistic insight into how the two ATP-dependent RNA helicases involved in this process, PRP2 and Aquarius, work together.

The paper presents the interdisciplinary approach of two fields - the artistic (musical) and technical (forestry engineering, wood processing engineering, mechanical and physical engineering) apparently opposite but which can be happily exploited for both parties. Thus, we can speak of a new paradigm of education through which art can combine with the technical sciences for the benefit of all. The aim of the paper is to present experimental methods in mechanical and acoustic evaluation of violins from engineering and artistic perspectives. The presented results are part of a larger study carried out within an experimental demonstration research project.

The paper presents the interdisciplinary approach of two fields - the artistic (musical) and technical (forestry engineering, wood processing engineering, mechanical and physical engineering) apparently opposite but which can be happily exploited for both parties. Thus, we can speak of a new paradigm of education through which art can combine with the technical sciences for the benefit of all. The aim of the paper is to present experimental methods in mechanical and acoustic evaluation of violins from engineering and artistic perspectives. The presented results are part of a larger study carried out within an experimental demonstration research project.

Ferlins, ancient membrane proteins with a unique architecture, are central to multiple essential, Ca2+-dependent vesicle fusion processes. Despite numerous functional studies and their link to burdening human diseases, a mechanistic understanding of how these multi-C2 domain proteins interact with lipid membranes to promote their remodeling and fusion is currently lacking. Here, we elucidate the near-complete cryo-electron microscopy structures of human myoferlin and dysferlin in their Ca2+ and lipid-bound states. We show that ferlins adopt compact, ring-like tertiary structures achieved upon membrane binding. The top arch of the ferlin ring, comprising the C2C-C2D region, is rigid and varies little across the observed functional states. In contrast, the N-terminal C2B and the C-terminal C2F-C2G domains cycle between alternative conformations and, in response to Ca2+, close the ferlin ring, promoting tight interaction with the target membrane. Probing key domain interfaces validates the observed architecture and informs a model of how ferlins engage lipid bilayers in a Ca2+-dependent manner. This work reveals the general principles of human ferlin structures and provides a framework for future analyses of ferlin-dependent cellular functions and disease mechanisms.Competing Interest StatementThe authors have declared no competing interest.

Our sense of hearing relies upon speedy synaptic transmission of sound information from cochlear inner hair cells (IHCs) to spiral ganglion neurons (SGNs). To accomplish this, IHCs employ a sophisticated presynaptic machinery including the multi-C2-domain protein otoferlin which is affected by human deafness mutations. Otoferlin is essential for IHC-exocytosis but how it binds Ca2+ and the target membrane to serve synaptic vesicle (SV) tethering, docking and fusion remained unclear. Here, we obtained cryo-electron-microscopy structures of Ca2+-bound otoferlin and employed molecular dynamics simulations of membrane binding. We show that membrane binding involves C2B-C2G-domains and repositions C2F- and C2G-domains. Progressive disruption of Ca2+-binding by the C2D-domain in mice increasingly altered synaptic sound encoding and eliminated the Ca2+-cooperativity of SV-exocytosis, indicating that this Ca2+-cooperativity reflects binding of several Ca2+-ions to otoferlin. Together, our findings elucidate molecular mechanisms underlying otoferlin-mediated SV-docking and support a role of otoferlin as Ca2+-sensor of SV-fusion in IHCs.

COVID-19 and influenza are highly contagious respiratory viral diseases and priority global public health concerns. We conducted a retrospective observational study of COVID-19 and/or influenza hospitalized cases, during 2023. We identified 170 influenza cases, 150 COVID-19 cases and 3 co-infections. Overall, 29.10% of patients had at least one COVID-19 vaccine dose and 4.6% received the seasonal Flu vaccine. The demographic data found older patients in the COVID-19 group and a higher index of the comorbidities, mainly due to chronic heart diseases, hypertension, and diabetes. Fever, chills, and rhinorrhea were more frequently related to influenza, while cough was prevalent in COVID-19. Antibiotics were more used in influenza than COVID-19, either pre-hospital or in-hospital. The mortality rate within the first 30 days from the onset of the respiratory infection was higher in influenza compared to COVID-19. We concluded that the COVID-19 clinical picture in hospitalized patients is changing to influenza-like symptoms. The evolution is variable, related to chronic comorbidities, but influenza had more frequent severe forms. All through 2023, due to poor vaccination rates, COVID-19 and influenza have continued to cause numerous hospitalizations, and a new strategy for efficient vaccinations is required.

The paper is presenting the experimental analysis of the use of biodiesel from waste sunflower oil and a blend of sunflower oil with palm oil as fuel for aviation turbo-engines. A comparative analysis for fuel mixtures made of Jet A + 5% Aeroshell 500 Oil (Ke) with 10%, 30%, and 50% for each bio-fuel type has been performed and Ke has been used as reference. Firstly, the following physical and chemical properties were determined: density, viscosity, flash point, freezing point, calorific power. Then, elemental analysis and Fourier transform infrared spectroscopy (FTIR) analysis were conducted for Ke, biodiesel obtained from recycled sunflower oil (SF), biodiesel obtained from blending recycled sunflower oil, and recycled palm oil (SFP), and for each fuel blend. Secondly, experimental tests of the blends have been conducted on the Jet Cat P80® micro-turbo engine (Gunt Hamburg, Barsbüttel, Germany). The tests have been conducted at different engine working regimes as follows: idle, cruise, intermediate, and maximum. For each regime, a one-minute testing period was chosen, and the engine parameters have been monitored. The turbo engine instrumentation recorded the temperature after the compressor and before the turbine, the fuel consumption and air flow, pressure inside the combustion chamber, and generated thrust. The burning efficiency and the specific consumption have been calculated for all four above-mentioned regimes and for all fuel blends. Two accelerometers have been installed on the engine’s support to register radial and axial vibrations allowing the assessment of engine stability.