Nature4Cities: A természetalapú megoldások (nature-based solutions) alkalmazási lehetőségei a várostervezésben

A növekvő létszámú városi lakosságot sújtó problémákat (kedvezőtlen városklíma, szennyezett környezet, nagymértékű stressz) tovább súlyosbítja a szárazföldi területek hőmérsékletének emelkedése és a szélsőséges időjárási események egyre gyakoribb előfordulása. Válaszolva a fokozott urbanizáció és az antropogén okokra visszavezethető klímaváltozás hatásaiból eredő problémákra, a közelmúltban új stratégiai prioritás jelent meg az Európai Unió kutatási és innovációs keretprogramjában: a városi környezet élhetőbbé tétele természetalapú tervezési megoldások (nature-based solutions) segítségével. A városi kihívásokra sok esetben adható természetalapú válasz, amely – a költséghatékonyságon túl – elősegíti, hogy a városi életforma újra közelebb kerüljön egy természetesebb állapothoz (re-naturing cities). A tanulmányban áttekintjük a természetalapú megoldások fogalmát, majd ismertetjük a 26 partnert magában foglaló nemzetközi Nature4Cities projektet, melynek alapvető célja, hogy segítse az efféle megoldások várostervezésbe történő integrálását. Ehhez a kapcsolódó kutatások és innovációk közös alapokra helyezése szükséges, valamint egy teljesen új szemléletmód kialakítása a gyakorlatban, továbbá újfajta döntéshozatali, üzleti és pénzügyi modellek adaptálása. Magyarországról három partnerintézmény, a Szegedi Tudományegyetem (mint a tudományos oldal képviselője), a Magyar Urbanisztikai Tudásközpont (várostervezési szakértőként), s Szeged Megyei Jogú Város Önkormányzata (mint döntéshozói oldal, illetve a projekt egyik mintavárosa) dolgozik együtt a projekt sikerén

Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts

Heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV) dysfunc- tion are frequent complications of diabetic cardiomyopathy. Here we aimed to characterize RV and left ventricular (LV) remodeling and its prevention by vardenafil (a long-acting phosphodiesterase- 5A (PDE-5A) inhibitor) administration in a diabetic HFpEF model. Zucker Diabetic Fatty (ZDF) and control, ZDF Lean (Lean) male rats received 10 mg/kg vardenafil (ZDF + Vard; Lean + Vard) per os, on a daily basis for a period of 25 weeks. In vitro force measurements, biochemical and histochemical assays were employed to assess cardiomyocyte function and signaling. Vardenafil treatment increased cyclic guanosine monophosphate (cGMP) levels and decreased 3-nitrotyrosine (3-NT) levels in the left and right ventricles of ZDF animals, but not in Lean animals. Cardiomyocyte passive tension (Fpassive) was higher in LV and RV cardiomyocytes of ZDF rats than in those receiving preventive vardenafil treatment. Levels of overall titin phosphorylation did not differ in the four experimental groups. Maximal Ca2+-activated force (Fmax) of LV and RV cardiomyocytes were preserved in ZDF animals. Ca2+-sensitivity of isometric force production (pCa50) was significantly higher in LV (but not in RV) cardiomyocytes of ZDF rats than in their counterparts in the Lean or Lean + Vard groups. In accordance, the phosphorylation levels of cardiac troponin I (cTnI) and myosin binding protein-C (cMyBP-C) were lower in LV (but not in RV) cardiomyocytes of ZDF animals than in their counterparts of the Lean or Lean + Vard groups. Vardenafil treatment normalized pCa50 values in LV cardiomyocytes, and it decreased pCa50 below control levels in RV cardiomyocytes in the ZDF + Vard group. Our data illustrate partially overlapping myofilament protein alterations for LV and RV cardiomyocytes in diabetic rat hearts upon long-term PDE-5A inhibition. While uniform patterns in cGMP, 3-NT and Fpassive levels predict identical effects of vardenafil therapy for the diastolic function in both ventricles, the uneven cTnI, cMyBP-C phosphorylation levels and pCa50 values implicate different responses for the systolic function

The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms

Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation. Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures and animal models. AUTEN-99 appears to effectively penetrate through the blood-brain barrier, and impedes the progression of neurodegenerative symptoms in Drosophila models of Parkinson's and Huntington's diseases. Furthermore, the molecule increases the survival of isolated neurons under normal and oxidative stress-induced conditions. Thus, AUTEN-99 serves as a potent neuroprotective drug candidate for preventing and treating diverse neurodegenerative pathologies, and may promote healthy aging

How to evaluate nature-based solutions performance for microclimate, water and soil management issues – Available tools and methods from Nature4Cities European project results

International audienceIn the context of climate change, Nature-Based Solutions (NBSs), a recently developed concept, are increasingly considered as part of the adaptation strategies of the cities. Studies using expert models and methods (EMM) receive a great deal of scientific attention. Considering EMM increasing use, this study aims to perform an analysis of the reported evaluation results, reflecting the capability of the EMM to accurately tackle urban challenges identified within the EU Nature4Cities project. Then, we propose a set of indicators and recommendations about sixteen EMM to be used by funders, researchers and practitioners when evaluating the performance of NBSs. The coupling of the different components (climate, water and soil) is not a simple matter. The analysis relies on the definition of the range of the reported metrics and on the investigation of the relationship between the various indices, applied for the EMM evaluation. Secondly, the study assesses the existing EMM, indicating the potential of NBSs: (i) to reduce urban heat island, (ii) to limit surface warming, (iii) to increase the thermal comfort of people, (iv) to limit the overheating and runoff of surfaces due to impervious areas, (v) to increase water retention during stormy episodes, (vi) to improve storm water quality at the outlet of the sustainable urban drainage systems, (vii) to promote the filtration and epuration of storm water runoff in soil and (viii) to be a support for vegetation. The analysis reveals that EMM can be considered as helpful tools for urban microclimate, urban soil and water management analysis, provided their limitations and characteristics are taken into account by the user when choosing tools and interpreting results (e.g. application scale). With regard to the performance of NBSs, the most commonly used indicators clearly depend on the scale of the project

Integrated Analysis of Residue Coevolution and Protein Structure in ABC Transporters

Intraprotein side chain contacts can couple the evolutionary process of amino acid substitution at one position to that at another. This coupling, known as residue coevolution, may vary in strength. Conserved contacts thus not only define 3-dimensional protein structure, but also indicate which residue-residue interactions are crucial to a protein’s function. Therefore, prediction of strongly coevolving residue-pairs helps clarify molecular mechanisms underlying function. Previously, various coevolution detectors have been employed separately to predict these pairs purely from multiple sequence alignments, while disregarding available structural information. This study introduces an integrative framework that improves the accuracy of such predictions, relative to previous approaches, by combining multiple coevolution detectors and incorporating structural contact information. This framework is applied to the ABC-B and ABC-C transporter families, which include the drug exporter P-glycoprotein involved in multidrug resistance of cancer cells, as well as the CFTR chloride channel linked to cystic fibrosis disease. The predicted coevolving pairs are further analyzed based on conformational changes inferred from outward- and inward-facing transporter structures. The analysis suggests that some pairs coevolved to directly regulate conformational changes of the alternating-access transport mechanism, while others to stabilize rigid-body-like components of the protein structure. Moreover, some identified pairs correspond to residues previously implicated in cystic fibrosis

Weighted combination of coevolution detector and .

<p>(<b>A</b>) Green and orange dots represent a set of pairs of amino acid positions in a protein family. , where is the set of structural contact pairs (orange) and is the set of structurally distant pairs (green). and are coevolution detectors with statistics and , respectively, which are evaluated separately for each pair. A combined detector uses a pair of thresholds to define the set of predicted pairs (eq. 15). The set of true positives is defined as ; the true positive rate is linearly related to the number of true positives. False positives and the false positive rate are defined analogously but with instead of (eq. 16–17). Even if is fixed, (and thus ) can still vary if and change in the opposite direction. Changing at fixed is called <i>detector weighting</i>. For example, for all 6 thresholds marked by the arrowheads. For the threshold labeled as “equal ” the two detectors are combined in equal weights. “ more ” refers to the weight of relative to . “Only ” means that has zero weight and therefore is the same as using only. “ more ” and “only ” have analogous meanings. Finally, the threshold denoted as characterizes the optimally weighted , which by definition has the highest for each . Black circles in (<b>B</b>) indicate for all 6 thresholds, at , and thus report on the corresponding performance. The optimal clearly outperforms the equally weighted one, which in this case happens to perform precisely as well as “only (their circles overlap). (<b>B</b>-<b>C</b>) Obtaining for all results in receiver operating characteristic curves, which describe the performance of coevolution detectors with respect to theoretical random, and perfect, detectors. Each curve is determined by the parameter set , which includes and therefore the weights on combined detectors. Integrating a curve on yields the area , which is used as a scalar measure of performance (eq. 18, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036546#pone-0036546-g004" target="_blank">Figure 4</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036546#pone-0036546-g005" target="_blank">5</a>). Conditions: ; ; ; protein family  =  ABC-C; optimal phylogenetic filtering.</p

Coevolving position pairs in ABC-C proteins.

<p>(<b>A</b>) Labeled residue side chains connected by lines form subset of predicted coevolving position pairs (eq. 24, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036546#pone-0036546-t002" target="_blank">Table 2</a>) in NBD1, including (E474, R1066) that connects NBD1 to ICL4. Large colored numbers identify helices of the TMDs. Helix H1 of NBD1 is also labeled as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036546#pone-0036546-g007" target="_blank">Figure 7</a>. (<b>B</b>) The subset of predicted pairs (eq. 25, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036546#pone-0036546-t003" target="_blank">Table 3</a>) are indicated in a topological map of the TMD dimer, in which 12 TM helices (large colored numbers), 2 wings and 4 intracellular loops (ICLs) are labeled. The map was obtained by cylindrical projection of the two polypeptide chains of the TMD dimer. Note that TM1-TM3 are shown twice. In both <b>A</b> and <b>B</b> the color of the lines connecting predicted pairs reports on the extent of distance change induced by the modeled outward inward conformational transition (eq. 23). Black: ; purple: ; red: .</p