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Rationale, in silico docking, ADMET profile, design, synthesis and cytotoxicity evaluations of phthalazine derivatives as VEGFR-2 inhibitors and apoptosis inducers†
No full textNew phthalazine derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors were synthesized joined to different spacers including pyrazole, α,β-unsaturated ketonic fragment, pyrimidinone and/or pyrimidinthione. A docking study was carried out to explore the suggested binding orientations of the novel derivatives inside the active site of VEGFR-2. The obtained biological data were extremely interrelated to that of the docking study. In particular, compounds 4b and 3e showed the highest activities against Michigan Cancer Foundation-7 (MCF-7) and Hepatocellular carcinoma G2 (HepG2) with half maximal inhibitory concentration (IC50) = 0.06, 0.06 μM and 0.08, 0.19 μM respectively. Our derivatives 3a–e, 4a,b and 5a,b were evaluated for their cytotoxicity against normal VERO cells. Our compounds exhibited low toxicity concerning normal VERO cells with IC50 = 3.00–4.75 μM. In addition, our final derivatives 3a–e, 4a, 4b, 5a and 5b were investigated for their VEGFR-2 inhibitory activities. Derivative 4b exhibited the highest VEGFR-2 inhibitory activities at an IC50 value of 0.09 ± 0.02 μM. Derivatives 3e, 4a and 5b demonstrated good activities with IC50 values = 0.12 ± 0.02, 0.15 ± 0.03 and 0.13 ± 0.03 μM respectively. Furthermore, the activities of 4b were assessed against MCF-7 cancer cells for apoptosis induction, cell cycle distribution and growth inhibition. Compound 4b caused cell growth arrest in growth 2-mitosis (G2-M) phase; accumulation of cells at that phase became 6.92% after being 13.2 in control cells. Moreover, our derivatives 3e, 4b and 5b revealed a good in silico considered absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile in comparison to sorafenib
The City as an Evolutionary Hothouse—The Search for Rapid Evolution in Urban Settings
No full textCities are ubiquitous and, though a novel phenomenon by evolutionary standards, provide a home for many species and exert particularly strong and novel selection pressures on them. They thus offer a unique opportunity to study rapid evolutionary processes. We conducted a scoping review of published studies documenting evolutionary processes in urban environments, focusing primarily on more recent work. Unfortunately, cities have not been attractive environments for biological research and thus remain poorly studied, despite slowly growing interest in recent years. Nonetheless, we found studies documenting the effects of mutation, genetic drift, and selection in cities. However, studies show some geographic bias and were not always as conclusive as might be desired. There is even support for incipient urban speciation. Evidence across the board is less abundant and less conclusive than desirable, suggesting the need for more data collection. The urban setting, with its stronger selection, more common intermixing, and abundance of both human and widespread potential non-human zoonosis hosts and human-associated species offers great opportunities to further document evolution in action and explore its conservation implications
Bundesweite Umfrage zur Situation der Schutzgebietsbetreuung 2023
No full textDie Schutzgebietsbetreuung in Deutschland hat sich seit den 1970er Jahren und besonders in der letzten Dekade stark weiterentwickelt. Dies belegt die Studie zur Situation der Schutzgebietsbetreuung in Deutschland 2023 durch den Anstieg auf aktuell 114 Einsatzstellen mit insgesamt 852 hauptberuflich Beschäftigten. Der vorliegende Bericht bietet einen Gesamtüberblick hinsichtlich der quantitativen und organisatorischen Aufstellung der Schutzgebietsbetreuung in den unterschiedlichen Schutzgebietskategorien in Deutschland.
Während die 16 Nationalparke über vergleichsweise personalstarke Rangerdienste verfügen, ist die Ausstattung der Biosphärenreservate sehr heterogen und als eher stagnierend zu bewerten. Hinsichtlich der Naturparke trugen der Beschluss des Wartburger Programms und die „Qualitätsoffensive Naturparke“ zur Schaffung neuer Rangerstellen bei. Zudem förderten mehrere Bundesländer die Einstellung hauptberuflichen Personals für die Betreuung von Natura 2000-Flächen. In mehreren Ballungsräumen, in denen nicht zuletzt seit der Corona-Pandemie der Druck auf urbane Naturräume gestiegen ist, wurden erstmalig Ranger*innen für den Außendienst eingestellt.
Ursprünglich waren die Aufgaben der Schutzgebietsbetreuung auf Arten- und Biotopschutz-maßnahmen, technische Arbeiten und Gebietskontrolle konzentriert. Mit der zunehmenden Bedeutung des Naturschutzes (Biodiversitätsstrategie, Klimainitiative, Natura 2000 Richtlinie, etc.), der Bildung für Nachhaltige Entwicklung und der Digitalisierung hat sich das Berufsbild Ranger/Rangerin weiterentwickelt. Von einfachen Schutzmaßnahmen hin zu zunehmend komplexen Aufgabenstellungen haben Rangerdienste heute eine Schlüsselrolle zum Erreichen der Ziele des Gebietsschutzes und zur Erfüllung internationaler Verpflichtungen.
Der Wandel spiegelt sich auch in der wachsenden Zahl weiblicher und jüngerer Fachkräfte wider, ebenso wie in dem Trend zu höheren akademischen Qualifikationen. Angesichts der steigenden Anforderungen an die Rangerdienste ist es wichtig, diese Entwicklung fortzusetzen und den Generationswechsel als Chance für Verbesserungen zu nutzen.
Die EU-Biodiversitätsstrategie fordert bis 2030 ein effektives Management der bestehenden Schutzgebiete, ihre Ausweitung auf 30 % der Land- und Meeresfläche sowie einen strikten Schutz von 10 % dieser Gebiete. Um diese Ziele zu erreichen, ist nicht nur eine Professionalisierung des Schutzgebietsmanagements nötig, sondern auch ein Ausbau des Stellenkontingents erforderlich. Die zukünftige Gestaltung der Schutzgebietsbetreuung ist daher ein zentrales Thema im Kontext der Erreichung der Biodiversitätsziele
Food safety knowledge, attitudes, and practices of food vendors participating in Nigeria’s school feeding program
No full textAbstract
This study aimed to measure the food safety knowledge, attitude, and practices among food vendors engaged in Nigeria’s ongoing Home-grown School Feeding Program. A cross-sectional survey was conducted in face-to-face interviews with 240 food vendors from 3 states in northeast Nigeria involved in the school feeding program using a structured questionnaire. Multiple linear regression results revealed that increased education and access to information through radio, television, and food inspection institutions increased food safety knowledge. Food safety attitudes score increased with more years of vending experience and accessing food safety information via radio, food inspection institutions, and the Internet. An increase in household size and food safety information from friends and colleagues negatively affected food safety attitude scores. As a result, we emphasize the need for dissemination of improved food safety information via radio, television and food safety inspection institutes. Food vendors in the SFP should be selected after passing a food safety training and gaining food handling experience. Higher education should be a priority criterion in the hiring process
Legacy effect of 25 years reduced atmospheric sulphur deposition on spruce tree nutrition
No full textAbstract
Background
Since the mid‐1990s, sulphur (S) pollution was drastically reduced in Central Europe. Over time, this has led to a distinct reduction in S availability for Norway spruce ( Picea abies Karst.), which is still the most important timber species in Central European forestries.
Aims
Determination of the Norway spruce nutritional status of former strongly affected areas by S pollution (Saxony) with different degrees of liming by assessing their foliar element contents and comparing them to regions remote from historical high S deposition.
Methods
Sites were selected based on levels of S deposition in the 1970–1990s with historical high deposition in Saxony (NE Germany), low deposition at Schluchsee (SW Germany) and Davos (Switzerland) as a clean air reference. Needles were sampled in late autumn 2019/2020 and elemental contents determined. Additional historical data on foliar S contents were available.
Results
Historical data showed a clear decrease in foliar S contents in the Saxonian sites over the last 25 years, independent of liming. No difference between all study sites was found in the most recent sampling, whereas S together with other macronutrients strongly indicates deficiencies for forest growth and health.
Conclusions
After 25 years of reduced S deposition, S nutrition became low for Norway spruce trees in Saxony, whereas soil parent material determines the overall tree nutritional status with respect to other nutrients. As such, no difference between sites with historical high, low or no S deposition was found. Further studies should focus on the mineralization of organic S in the topsoil to understand if S is effectively recycled within the forest ecosystem and on the effect of other diminishing nutrients such as Mg and P
Seeing the Trees Without the Forest: What and How can Agroforestry and Urban Forestry Learn from Each Other?
No full textAbstract
Purpose of Review
Agroforestry and urban forestry have evolved mainly as separate disciplines, although they share a long history of tree cultivation in man-made environments. Here, we review their common threads, exploring how trees in both systems interact with and shape their environments. We examine common themes and methodologies – ranging from tree growth dynamics to environmental stressors, ecosystem services provision, and questions of governance – and identify opportunities for synergies between these fields.
Recent Findings
We emphasize the potential of agroforestry and urban forestry for enhancing multifunctional landscapes. Geographical divides in research are evident, with agroforestry predominantly studied in the Global South and urban forestry receiving more attention in the Global North. However, significant research gaps provide avenues for collaboration, for instance, addressing challenges in capturing the monetary and socio-cultural value of ecosystem services and environmental justice considerations.
Summary
In light of the growing need for integrated approaches in addressing contemporary challenges, from climate change mitigation and adaptation to community well-being, our review explores what these research fields can learn from each other and provides recommendations for fostering greater interdisciplinary dialogue and new avenues for collaborations in a meaningful and synergistic manner, aiming to advance policy, research, and practice in agroforestry and urban forestry
Metabonomic analysis to identify exometabolome changes underlying antifungal and growth promotion mechanisms of endophytic Actinobacterium Streptomyces albidoflavus for sustainable agriculture practice
No full textIn recent years, there has been an increasing focus on microbial ecology and its possible impact on agricultural production, owing to its eco-friendly nature and sustainable use. The current study employs metabolomics technologies and bioinformatics approaches to identify changes in the exometabolome of Streptomyces albidoflavus B24. This research aims to shed light on the mechanisms and metabolites responsible for the antifungal and growth promotion strategies, with potential applications in sustainable agriculture. Metabolomic analysis was conducted using Q Exactive UPLC–MS/MS. Our findings indicate that a total of 3,840 metabolites were identified, with 137 metabolites exhibiting significant differences divided into 61 up and 75 downregulated metabolites based on VIP >1, |FC| >1, and p < 0.01. The interaction of S. albidoflavus B24 monoculture with the co-culture demonstrated a stronger correlation coefficient. The Principal Component Analysis (PCA) demonstrates that PCA1 accounted for 23.36%, while PCA2 accounted for 20.28% distinction. OPLS-DA score plots indicate significant separation among different groups representing (t1) 24% as the predicted component (to1) depicts 14% as the orthogonal component. According to the findings of this comprehensive study, crude extracts from S. albidoflavus demonstrated varying abilities to impede phytopathogen growth and enhance root and shoot length in tested plants. Through untargeted metabolomics, we discovered numerous potential molecules with antagonistic activity against fungal phytopathogens among the top 10 significant metabolites with the highest absolute log2FC values. These include Tetrangulol, 4-Hydroxybenzaldehyde, and Cyclohexane. Additionally, we identified plant growth-regulating metabolites such as N-Succinyl-L-glutamate, Nicotinic acid, L-Aspartate, and Indole-3-acetamide. The KEGG pathway analysis has highlighted these compounds as potential sources of antimicrobial properties. The inhibitory effect of S. albidoflavus crude extracts on pathogen growth is primarily attributed to the presence of specific gene clusters responsible for producing cyclic peptides such as ansamycins, porphyrin, alkaloid derivatives, and neomycin. Overall, it is apparent that crude extracts from S. albidoflavus exhibited varying abilities to inhibit the growth of three phytopathogens and enhancement in both root and shoot length of tested plants. This research enhances our understanding of how secondary metabolites contribute to growth promotion and biocontrol, supporting ecosystem sustainability and resilience while boosting productivity in sustainable agriculture
Exploration of the VEGFR-2 inhibition activity of phthalazine derivatives: design, synthesis, cytotoxicity, ADMET, molecular docking and dynamic simulation†
No full textNovel phthalazine derivatives were designed, synthesized and evaluated against Hep G2 and MCF-7 as VEGFR-2 inhibitors. In particular, compounds 2g and 4a were found to be the most potent derivatives among all the tested compounds against MCF-7 and Hep G2 cancer cell lines with IC50 values of 0.15 and 0.12 and 0.18 and 0.09 μM respectively. Moreover, compounds 3a, 3c, 5a and 5b displayed excellent anticancer activities against MCF-7 and Hep G2 cancer cell lines. The highly active derivatives 2g, 3a, 3c, 4a, 5a and 5b were evaluated for their inhibitory activities against VEGFR-2. The tested compounds displayed high to low inhibitory activities with IC50 values ranging from 0.148 to 0.892 μM. Among them, compounds 2g and 4a were found to be the most potent derivatives that inhibited VEGFR-2 with IC50 values of 0.148 and 0.196 μM respectively. Compounds 3a, 3c, 5a and 5b exhibited good activity with IC50 values of 0.375, 0.892, 0.548 and 0.331 μM respectively. Sorafenib was used as a reference drug in this study. Molecular modeling studies were carried out for all compounds against the VEGFR-2 active site. The data obtained from biological testing highly correlated with those obtained from molecular modeling studies. Moreover, MD simulation results indicated the stability of ligand–target interaction. Furthermore, our derivatives 2g and 4a showed a good in silico calculated ADMET profile
Nachhaltigkeit an Brandenburger Hochschulen - Bericht 2019-2023
No full textIn diesem Bericht wird die Arbeit der Arbeitsgemeinschaft Nachhaltigkeit an Brandenburger Hochschulen in den Jahren 2019 – 2023 dargestellt. Neben dem Auftrag und den Handlungsfeldern der AG-Arbeit, etwa der hochschulspezifischen Beratung oder der Weiterbildung für Lehrende, werden auch Gute Praxis – Beispiele der beteiligten Hochschulen vorgestellt
Kommunen als Partner für Systeminnovationen zur Nachhaltigkeitstransformation. Am Fallbeispiel einer Recyclinganlage zur Verwertung menschlicher Ausscheidungen in Brandenburg
No full textDie vorliegende Veröffentlichung geht der Frage nach, wie Systeminnovationen mit Kommunen als Partner als Beitrag zur Nachhaltigkeitstransformation gelingen können. Dabei basieren die Erkenntnisse auf einer qualitativ explorativen Studie, die zwischen November 2021 und November 2023 im Fallgebiet durchgeführt wurde. Insgesamt wurden drei Fragestellung verfolgt: Erstens, wie konnte sich die Systeminnovation in Eberswalde durch die vorhandenen Partnerschaften entwickeln? Zweitens, welche Alltagspraktiken von Kommunen beeinflussten den Innovationsentwicklungsprozess? Und drittens, welche Merkmale und Eigenschaften der beteiligten Organisationen und Individuen waren für die Entwicklung der Systeminnovation von Bedeutung? Die Entwicklung der hier vorgestellten Systeminnovation ist ein Gemeinschaftswerk. Alle Partner trugen relevante Anteile dazu bei. Da die Innovation die Daseinsvorsorge berührt, kam den Kommunen, die die Daseinsvorsorge in Deutschland verantworten, eine besondere Rolle zu: Sie nutzten ihren Einflussfaktor und setzten ihre Ermessensspielräume vor allem in entscheidenden regulativen Verfahren für die Innovationsentwicklung ein. Dies war unter anderem möglich, weil die Innovation an ein für die untersuchte Kommune zentrales Strategiepapier anknüpft. Die Ergebnisse machen sichtbar, dass neben der Entwicklung von Strategien die Ausrichtung der Ausführung der Pflichtaufgaben an diese Strategien, intrakommunale Kommunikation mittels verschiedener Austauschformate, die Leitung von Fachausschüssen, die Entscheidungsfindung sowie die Einbeziehung verschiedener Akteure und die Führung der Mitarbeitenden zentrale Alltagspraktiken von öffentlicher Verwaltung sind, an die die Entwicklung von Systeminnovation sinnvoll anschließen kann. Der hier untersuchte Innovationsentwicklungsprozess profitierte von unterschiedlichsten Merkmalen und Eigenschaften der Beteiligten. Dabei war nicht ausschlaggebend, dass eine Person oder Organisation möglichst viele innehat, sondern dass sie innerhalb der Kooperation möglichst breit verteilt vorhanden und zugänglich gemacht wurden.This publication explores how system innovations with municipalities as partners can contribute to sustainability transformation. The findings are based on a qualitative case study conducted from November 2021 to November 2023. Overall, three questions were pursued: Firstly, how could the system innovation in Eberswalde develop through existing partnerships? Secondly, which everyday practices of municipalities influenced the innovation development process? And thirdly, which characteristics and attributes of the organizations and individuals involved were important for the development of the system innovation? The here presented development of the system innovation is a joint effort. All partners made relevant contributions. As the innovation affects provision of public services, the municipalities, which are responsible for those in Germany, played a special role: they used their influence and applied their leeway, particularly in decisive regulatory procedures, to contribute to the development of the innovation. This was possible, among other things, because the innovation was linked to key strategy papers in the examined municipalities. The results show different everyday practices of municipalities are linked to the development of system innovation, such as (1) development of strategies, (2) alignment of mandatory tasks with strategies, (3) formal and informal communication, (4) management of expert committees, (5) decision-making, (6) involvement of various stakeholders and (7) leadership of employees. The innovation development process benefited from a wide variety of characteristics and attributes of the participants. The decisive factor was not that one individual or organization should hold as many as possible, but that they should be available and accessible as widely as possible within the cooperation network