Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis

Spontaneous Embedding of DNA Mismatches Within the RNA:DNA Hybrid of CRISPR-Cas9.

CRISPR-Cas9 is the forefront technology for editing the genome. In this system, the Cas9 protein is programmed with guide RNAs to process DNA sequences that match the guide RNA forming an RNA:DNA hybrid structure. However, the binding of DNA sequences that do not fully match the guide RNA can limit the applicability of CRISPR-Cas9 for genome editing, resulting in the so-called off-target effects. Here, molecular dynamics is used to probe the effect of DNA base pair mismatches within the RNA:DNA hybrid in CRISPR-Cas9. Molecular simulations revealed that the presence of mismatched pairs in the DNA at distal sites with respect to the Protospacer Adjacent Motif (PAM) recognition sequence induces an extended opening of the RNA:DNA hybrid, leading to novel interactions established by the unwound nucleic acids and the protein counterpart. On the contrary, mismatched pairs upstream of the RNA:DNA hybrid are rapidly incorporated within the heteroduplex, with minor effect on the protein-nucleic acid interactions. As a result, mismatched pairs at PAM distal ends interfere with the activation of the catalytic HNH domain, while mismatches fully embedded in the RNA:DNA do not affect the HNH dynamics and enable its activation to cleave the DNA. These findings provide a mechanistic understanding to the intriguing experimental evidence that PAM distal mismatches hamper a proper function of HNH, explaining also why mismatches within the heteroduplex are much more tolerated. This constitutes a step forward in understanding off-target effects in CRISPR-Cas9, which encourages novel structure-based engineering efforts aimed at preventing the onset of off-target effects

Seismic-proof buildings in developing countries

The use of \u201cductile seismic frames,\u201d whose proper seismic behavior largely depends upon construction details and specific design rules, may do not always lead to effective seismic resistant structures, as dramatically denounced by the famous Chinese artist Ai Weiwei in his artwork Straight. The artwork (96 t of undulating metal bars that were salvaged from schools destroyed by the 2008 Sichuan, China earthquake, where over 5,000 students were killed) is a clear denounce against the corruption yielding to shoddy construction methods. The issue of safe constructions against natural hazards appears even more important in developing countries where, in most cases, building structures are realized by non-expert workers, or even by simple \u201cpeople from the street,\u201d who does not have any technical knowledge on construction techniques and seismic engineering. In this paper, a brief history from the first frame structures to the more efficient wall-based structures is provided within Earthquake Engineering perspectives. The superior structural properties of box-type wall structures with respect to conventional frame structures envisage a change of paradigm from actual \u201cductility-based\u201d Earthquake Engineering (centered on frame structures) toward 100% safe buildings through a \u201cstrength-based\u201d design exploiting the use of box-type wall-based structures

How to finance energy renovation of residential buildings: Review of current and emerging financing instruments in the EU

The Paris Agreement goals require net-zero CO2 emissions by mid-century. The European Commission in its recent proposal for climate and energy strategy for 2050 indicated the need for more intensified actions to substantially improve the energy performances of buildings. With the rate of new construction in Europe, the challenge is to increase both the pace and depth of building energy renovations. Several barriers inhibit the wide uptake of comprehensive energy renovations, including the inability or inertia to finance upfront costs of energy renovations. Despite various policies implemented to address some of these barriers, current investments in buildings remain at suboptimal levels. The paper reviews current financing practices for energy renovations and investigates some innovative instruments with a special focus on their applicability to residential buildings. In addition to “traditional” financial schemes such as subsidies, tax incentives, and loans, the paper assesses innovative financing schemes: On property tax and on-bill financing, energy efficiency mortgages, and energy efficiency feed-in tariffs. The paper also investigates the concept of one-stop shops for building renovations and crowdfunding. The paper offers an assessment of the characteristics, benefits, and challenges of each analyzed financing instrument and provides policy recommendations for their successful implementation. In general, as financing instruments involve different stakeholders and due to complex nature of the sector, there is no single solution to accelerate energy renovation investment in buildings. The emerging financial models offer the potential to address the long-standing barriers to investment in energy efficiency. This article is categorized under: Energy Efficiency > Economics and Policy Energy Efficiency > Climate and Environment Energy and Climate > Economics and Policy

LE REGIONI D'EUROPA TRA IDENTITÀ LOCALI, NUOVE COMUNITÀ E DISPARITÀ TERRITORIALI

L’Europa è oggi attraversata da una forte domanda di autonomia da parte dei territori: da un lato, a tutela dell’identità delle comunità locali e, dall’altro, per la crescente rivendicazione di una più ampia rappresentanza delle cittadinanze. Queste istanze possono, però, mettere a rischio gli obiettivi di equilibrio e di coesione economica, sociale e territoriale, da sempre al centro della riflessione e delle proposte sviluppate dagli studiosi delle scienze regionali. La recente crisi ha acuito l’instabilità e allargato i complessivi divari tra le regioni, anche nella loro dinamica interna di evoluzione. Alla resilienza economica non sempre è corrisposto, nell’attuale transizione verso un nuovo paradigma, il mantenimento di solidi livelli di coesione sociale e di integrazione tra aree e comunità. Il volume raccoglie una selezione di contributi presentati alla XXXIX Conferenza Italiana di Scienze Regionali, svoltasi a Bolzano il 17, 18 e 19 settembre 2018. Nella sua articolazione, esso si sviluppa in tre parti. La prima analizza il tema della domanda di autonomia da parte dei territori all’interno dello sviluppo economico e sociale di regioni e paesi, e dell’attuale dibattito sul federalismo differenziato. Nella seconda le riflessioni si estendono alla crescente disparità tra aree centrali e aree periferiche, tra aree interne e aree esposte, tra Nord e Sud dei Paesi e dell’Europa, mentre nella terza parte, l’analisi guarda ai mutevoli equilibri tra territori e sistemi locali urbani e rurali, tra pianura e montagna e, all’interno delle aree montane, tra i fondivalle maggiormente urbanizzati e i territori di alta quota, zone spesso di confine tra province, regioni e stati. La novità editoriale di quest’anno è rappresentata da uno spazio dedicato a brevi contributi a cura di giovani autori vincitori dei premi AISRe.Europe is today crossed by a strong demand for autonomy from the territories: to protect the identity of local communities and, also analyze the growing demand for a broader representation of citizens. However, these issues can jeopardize the objectives of balance and economic, social and territorial cohesion, which have always been at the center of the reflection and proposals developed by scholars of regional sciences. The recent crisis has worsened instability and widened the overall gaps between the regions, including in their internal dynamics of evolution. Economic resilience is not always matched, in the current transition towards a new paradigm, by maintaining solid levels of social cohesion and integration between areas and communities. The volume collects a selection of contributions presented at the XXXIX Italian Conference of Regional Science, held in Bolzano on 17, 18 and 19 September 2018. The volume is divided into three parts. The first analyzes the issue of the demand for autonomy by the territories within the economic and social development of regions and countries, and the current debate on differentiated federalism. In the second, the reflections extend to the growing disparity between central and peripheral areas, between internal and exposed areas, between North and South of countries and Europe, while in the third part, the analysis looks at the changing balance between territories and systems. urban and rural areas, between plains and mountains and, within mountain areas, between the most urbanized valleys and high altitude territories, areas often bordering provinces, regions and states. This year ia space is dedicated to short contributions by young authors who have won the AISRe Awards

LE REGIONI D’EUROPA TRA IDENTITÀ LOCALI, NUOVE COMUNITÀ E DISPARITÀ TERRITORIAL

Europe today is crossed by a strong demand for autonomy from the territories: on the one hand, to protect the identities of local communities and, on the other, for the growing demand for a wider representation of resident citizens. However, these requests can jeopardize the objectives of balance and integration between parts of the territory and between those who live in them, objectives that have always been at the center of reflection and proposals developed in the context of regional sciences. The recent crisis has heightened instability and widened economic and social gaps not only between regions, but also within the regions themselves. The North-South gaps in Italy have further increased and, in a post-crisis phase, this unstoppable process requires ever greater scientific and policy insights in terms of commitment and intervention capacity. If the economic growth of the past decade had found impetus in expanding the spaces of relationships and exchanges, the responses to the threats brought about by the crisis materialized in the closure of borders and in the defense of local levels of well-being. A particular specification of this theme also concerns the relationships between urban and rural territories and local systems, between plains and mountains as well as mountain areas, . The preface is therefore an acute reflection on issues of urgent relevance for Italy and of great interest for the regional sciences, accepting important scientific and policy challenges

Coastal evolution on Earth and Titan

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 2022.The morphology of a shoreline can provide insight into the processes that have modified the coast. This thesis investigates how coastal processes can leave fingerprints on the morphology of a coast in sandy environments (barrier islands) and detachment-limited environments (rocky coasts of Earth and possibly Titan). Barrier islands are dynamic and ephemeral, facing an uncertain future from climate change and anthropogenic redistribution of sediment. To evaluate barrier resilience to sea-level rise, I propose a novel dimensionless metric called the Washover Ratio which compares cross-shore (overwash) and alongshore transport. Using this ratio, I find that decreases in overwash flux within the narrow middle section—possibly representing the effects of development—lead to a diminished response to sea-level rise across the entire barrier, and therefore a more vulnerable barrier overall. Further investigation of the balance between overwash and alongshore sediment transport allows for an evaluation of barrier island stability to overwash-induced breaching, which is applied to barriers in the Gulf of Mexico. Beyond Earth, Titan, Saturn’s largest moon, is home to the only other active coastlines in our solar system. However, data is sparse for this icy moon. I investigate the signatures of coastal processes found in the planform shape of its coasts using a combination of landscape evolution models and measurements of shoreline shape. Results show that the coastlines of Titan’s seas are consistent with those of both modelled and Earth lakes with flooded river valleys that have been subsequently eroded by waves, particularly when waves saturate (no longer grow in height) at scales up to 10s of km.Work toward this thesis was funded by the National Science Foundation (NSF) and National Aeronautics and Space Administration (NASA). NSF funding was awarded through the Graduate Research Fellowship Program (#1745302) and the Coupled Natural Hazards program (#CNH-1518503). NASA funding was awarded through the Cassini Data Analysis Program (#80NSSC18K1057) and (#80NSSC20K0484)