Structural Transition-Induced Raman Enhancement in Bioinspired Diphenylalanine Peptide Nanotubes

Semiconducting materials are increasingly proposed as alternatives to noble metal nanomaterials to enhance Raman scattering. We demonstrate that bioinspired semiconducting diphenylalanine peptide nanotubes annealed through a reported structural transition can support Raman detection of 10-7 M concentrations for a range of molecules including mononucleotides. The enhancement is attributed to the introduction of electronic states below the conduction band that facilitate charge transfer to the analyte molecule. These results show that organic semiconductor-based materials can serve as platforms for enhanced Raman scattering for chemical sensing. As the sensor is metal-free, the enhancement is achieved without the introduction of electromagnetic surface-enhanced Raman spectroscopy.Science Foundation IrelandUCD School of PhysicsSustainable Energy Authority of Ireland (SEAI

Thermally-controlled spherical peptide gel architectures prepared using the pH switch method

Self-assembling nanostructured peptide gels are promising materials for sensing, drug delivery, and energy harvesting. Of particular interest are short diphenylalanine (FF) peptides modified with 9-fluorenylmethyloxycarbonyl (Fmoc), which promotes the association of the peptide building blocks. Fmoc-FF gels generally form fibrous networks and while other structures have been demonstrated, further control of the gelation and resulting ordered three-dimensional structures potentially offers new possibilities in tissue engineering, sensing, and drug release applications. Herein, we report that the structure tunability of Fmoc-FF gels can be achieved by controlling the water content and the temperature. We further explore the incorporation of metal nanoparticles in the formation of the gel to enable optical sensing applications based on hybrid Fmoc-FF-nanoparticle microspheres. Finally, fluorescence lifetime imaging microscopy reveals a correlation between lifetime and reduced bandgap, in support of a semiconductor-induced charge transfer mechanism that might also increase the stability of an excited state of a probe molecule. The observations potentially further widen the use of these peptide materials in bioimaging and sensing applications.Science Foundation IrelandEuropean Commission Horizon 2020Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi ArabiaMinistry of Higher Education of Saudi Arabia under the King Abdullah Scholarship Progra

The Hot and Energetic Universe: End points of stellar evolution

White dwarfs, neutron stars and stellar mass black holes are key laboratories to study matter in most extreme conditions of gravity and magnetic field. The unprecedented effective area of Athena+ will allow us to advance our understanding of emission mechanisms and accretion physics over a wide range of mass accretion rates, starting from lower and sub-luminous quiescent X-ray binaries up to super-Eddington ultra-luminous sources. Athena+ will measure stellar black hole spins in a much higher number of binaries than achievable now, opening the possibility to study how spin varies with black hole history. The high throughput and energy resolution of the X-IFU will be instrumental in establishing how disc wind properties depend on accretion state, in determining wind launching mechanism and in quantifying the impact of the wind induced mass loss on binary evolution and environment. Triggers and high quality optical and radio data originating from large wide field contemporaneous instruments will provide essential complementary information on jet launching mechanisms and on the physics of rotation powered pulsars, for instance. In addition, Athena+ will furnish multiple, independent measurements of the neutron star mass/radius relation in a wide range of environments and conditions so as to constrain the debated equation of state.Comment: Supporting paper for the science theme "The Hot and Energetic Universe" to be implemented by the Athena+ X-ray observatory (http://www.the-athena-x-ray-observatory.eu). 9 pages, 4 figure

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance of exon 3 deletion in breast cancer predisposition

<p>Abstract</p> <p>Background</p> <p>Germ-line mutations in the <it>BRCA1 </it>and <it>BRCA2 </it>genes are major contributors to hereditary breast/ovarian cancer. Large rearrangements are less frequent in the <it>BRCA2 </it>gene than in <it>BRCA1</it>. We report, here, the first total deletion of exon 3 in the <it>BRCA2 </it>gene that was detected during screening of 2058 index cases from breast/ovarian cancer families for <it>BRCA2 </it>large rearrangements. Deletion of exon 3, which is in phase, does not alter the reading frame. Low levels of alternative transcripts lacking exon 3 (Δ3 delta3 transcript) have been reported in normal tissues, which raises the question whether deletion of exon 3 is pathogenic.</p> <p>Methods</p> <p>Large <it>BRCA2 </it>rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex Ligation-Dependent Probe Amplification). The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the <it>BRCA2 </it>gene and sequencing. To determine the effect of exon 3 deletion and assess its pathogenic effect, three methods of transcript quantification were used: fragment analysis of FAM-labelled PCR products, specific allelic expression using an intron 2 polymorphism and competitive quantitative RT-PCR.</p> <p>Results</p> <p>Large rearrangements of <it>BRCA2 </it>were detected in six index cases out of 2058 tested (3% of all deleterious <it>BRCA2 </it>mutations). This study reports the first large rearrangement of the <it>BRCA2 </it>gene that includes all of exon 3 and leads to an <it>in frame </it>deletion of exon 3 at the transcriptional level. Thirty five variants in exon 3 and junction regions of <it>BRCA2 </it>are also reported, that contribute to the interpretation of the pathogenicity of the deletion. The quantitative approaches showed that there are three classes of delta3 <it>BRCA2 </it>transcripts (low, moderate and exclusive). Exclusive expression of the delta3 transcript by the mutant allele and segregation data provide evidence for a causal effect of the exon 3 deletion.</p> <p>Conclusion</p> <p>This paper highlights that large rearrangements and total deletion of exon 3 in the <it>BRCA2 </it>gene could contribute to hereditary breast and/or ovarian cancer. In addition, our findings suggest that, to interpret the pathogenic effect of any variants of exon 3, both accurate transcript quantification and co-segregation analysis are required.</p

Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients

Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients

LabTEm abre sus puertas en la Semana Nacional de la Ciencia y la Tecnología

El Laboratorio de Tecnologías Emergentes(LabTEm) abre sus puertas a la ciencia en laSemana Nacional de la Ciencia y Tecnología es unaactividad compuesta por un muestra y tres talleressobre distintas líneas de aplicación de ciencia ytecnología.En primer lugar, se desarrolló un taller de TeamBuilding que buscó mejorar el trabajo en equipo y laconciencia ambiental de los participantes, mediantetres dinámicas: Nombres Voladores, Rory StoryCubes y Cantando en tono de Cumpleaños. Ensegundo lugar se presentó un taller de InteligenciaArtificial Generativa que explicó qué es lainteligencia artificial generativa (IAG), que es unarama de la inteligencia artificial (IA) que creacontenido nuevo y original. Se presentaron dosherramientas con IAG: ChatGPT, que genera textoconversacional, y DALL-E, que genera imágenes apartir de texto. En tercer lugar, se dio un taller deProgramación sin Codificar donde enseñó a crearaplicaciones móviles sin necesidad de saberprogramar, usando una herramienta llamadaAppMaker. Esta herramienta es una plataforma deprogramación no-code, que permite diseñar ydesarrollar aplicaciones de forma visual e intuitiva,arrastrando y soltando componentes. Los asistentesconstruyeron una aplicación desde cero, eligiendo eltema, el diseño, la funcionalidad y el contenido. Alfinalizar, probaron y compartieron su aplicación.Finalmente, se realizó una muestra de LabTEm:Una muestra de un laboratorio de tecnologíasemergentes que se enfoca en la sostenibilidad y lainnovación. Se mostraron seis actividades que serealizaron en el laboratorio: Impresión 3D, MáquinaPET, Robots en LabTEm, Chatbot Ambiental, Comunidades Virtuales y e-Waste. En cadaactividad se mostró cómo se pueden usar lastecnologías emergentes para crear soluciones eco-amigables y creativas para el cuidado del ambiente yla sociedad. Se entregaron llaveros impresos,material informativo y baterías portátiles a losvisitantes. Se introdujeron conceptos de inteligenciaartificial y se fomentó la participación de losestudiantes del laboratorio

Ejecta Evolution Following a Planned Impact into an Asteroid: The First Five Weeks

The impact of the DART spacecraft into Dimorphos, moon of the asteroid Didymos, changed Dimorphos' orbit substantially, largely from the ejection of material. We present results from twelve Earth-based facilities involved in a world-wide campaign to monitor the brightness and morphology of the ejecta in the first 35 days after impact. After an initial brightening of ~1.4 magnitudes, we find consistent dimming rates of 0.11-0.12 magnitudes/day in the first week, and 0.08-0.09 magnitudes/day over the entire study period. The system returned to its pre-impact brightness 24.3-25.3 days after impact through the primary ejecta tail remained. The dimming paused briefly eight days after impact, near in time to the appearance of the second tail. This was likely due to a secondary release of material after re-impact of a boulder released in the initial impact, through movement of the primary ejecta through the aperture likely played a role.Comment: 16 pages, 5 Figures, accepted in the Astrophysical Journal Letters (ApJL) on October 16, 202