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A survey of isatin hybrids and their biological properties
Get PDFThe emergence of diverse infections worldwide, which is a serious global threat to human existence, necessitates the urgent development of novel therapeutic candidates that can combat these diseases with efficacy. Molecular hybridization has been established as an efficient technique in designing bioactive molecules capable of fighting infections. Isatin, a core nucleus of an array of compounds with diverse biological properties can be modified at different positions leading to the creation of novel drug targets, is an active area of medicinal chemistry. This review containing published articles from 2005 to 2022 highlights isatin hybrids which have been synthesized and reported in the literature alongside a discussion on their biological properties. The enriched structure–activity relationship studies discussed provides insights for the rational design of novel isatin hybrids with tailored biological properties as effective therapeutic candidates inspired by nature
Kontrolle der bakteriellen Peptidoglykanbiosynthese durch Proteinphosphorylierung und regulierte Proteolyse
Get PDFDie zentrale Komponente der Zellhülle von Gram-positiven Bakterien ist die
Zellwand, die durch eine dicke Peptidoglykanschicht gekennzeichnet ist. Der
Peptidoglykansacculus verleiht der Zelle Stabilität und Form und schützt sie vor
Umwelteinflüssen. Damit die Bakterienzelle in der Lage ist zu wachsen und sich
zu teilen, findet ein ständiger Umbau des Peptidoglykannetzwerks statt. Zu
diesem Zweck ist die Biosynthese neuer Peptidoglykanbausteine erforderlich.
Um zu verhindern, dass die Biosynthese zu viele Ressourcen verbraucht, wird
sie auf verschiedenen Ebenen streng reguliert. Eine Form der Regulation betrifft
den proteolytischen Abbau von MurA, dem ersten Enzym des
Biosyntheseweges. MurA wird durch die Protease ClpCP in Gegenwart von nicht-
phosphoryliertem ReoM abgebaut, was zur Verringerung der
Peptidoglykanbiosynthese führt. Wird ReoM jedoch durch die PASTA-eSTK
PrkA phosphoryliert, ist die Interaktion von ReoM mit MurA gehemmt, der Abbau
von MurA wird verhindert und die Peptidoglykanbiosynthese stabilisiert sich.
Durch die Phosphatase PrpC kann die Phosphorylierung von ReoM rückgängig
gemacht werden. Um herauszufinden, ob die Peptidoglykanbiosynthese
stattfindet oder nicht, wurde der Phosphorylierungszustand von ReoM in vivo
untersucht. Die Ergebnisse zeigen, dass die Peptidoglykanbiosynthese in der
späten stationären Wachstumsphase durch die PrpC-abhängige Abnahme der
ReoM-Phosphorylierung heruntergefahren wird. Die intrazelluläre Anreicherung
von MurA führte ebenfalls zur Abnahme der Phosphorylierung von ReoM. Dies
erforderte einen direkten Kontakt zwischen ReoM und MurA, sowie die
enzymatische Aktivität von MurA und die Bindung der Substrate. Weitere
Faktoren, die die ReoM-Phosphorylierung steuern, sind GpsB als Aktivator von
PrkA und die PASTA-Domänen von PrkA, die ebenfalls für die volle
Kinaseaktivität erforderlich sind. Proteomdaten legen außerdem nahe, dass
ReoM spezifisch die ClpCP-abhängige Proteolyse von MurA steuert.The central component of the cell envelope of Gram-positive bacteria is the cell
wall, which is characterised by a thick peptidoglycan layer. The peptidoglycan
sacculus ensures the stability and shape of the cell and protects it against harsh
environmental conditions. In order to be able to grow and divide, a constant
remodelling of the peptidoglycan network takes place. This requires the
biosynthesis of new peptidoglycan building blocks. However, in order to prevent
the excessive consumption of resources during peptidoglycan biosynthesis, it is
strictly regulated at various levels. One form of regulation concerns the proteolytic
degradation of MurA, the first enzyme in the biosynthetic pathway. In the
presence of non-phosphorylated ReoM, MurA is degraded by the protease
ClpCP, which leads to a reduction in peptidoglycan biosynthesis. However, ReoM
can be phosphorylated by the PASTA-eSTK PrkA. This phosphorylation inhibits
the interaction between ReoM and MurA and prevents the degradation of MurA.
As a result, the biosynthesis of peptidoglycan is maintained. The phosphatase
PrpC can reverse the phosphorylation of ReoM. To see under which conditions
peptidoglycan biosynthesis takes place or not, the phosphorylation state of ReoM
was analysed in vivo. The results show that peptidoglycan biosynthesis is down-
regulated in the late stationary phase of growth by the PrpC-dependent decrease
in ReoM phosphorylation. The intracellular accumulation of MurA also led to a
decrease in the phosphorylation of ReoM. For this direct contact between ReoM
and MurA. This required direct contact between ReoM and MurA. MurA also had
to be enzymatically active and able to bind its substrates. Other factors controlling
ReoM phosphorylation were GpsB, which acts as an activator of PrkA, and the
PASTA domains of PrkA, which are also required for full kinase activity.
Proteomic data also suggest that ReoM specifically controls ClpCP-dependent
proteolysis of MurA.Literaturverzeichnis: Seite 131-15
La Tunisie et le Ghana : histoires parallèles, démocraties divergentes
No full textMots-clés : Ghana, Tunisie, démocratisation, gouvernance, influence régionaleKeywords: Ghana, Tunisia, democratisation, governance, regional influenceSchlagworte: Ghana, Tunesien, Demokratisierung, Regierungsführung, regionaler Einflus
German youth and systemic racism : how conceptions of national identity relate to critical consciousness
No full textThis study focused on national identity conceptions and critical consciousness (CC) of systemic racism among adolescents with varying racialisation experiences, namely in terms of being perceived as ‘foreigner’, regardless of citizenship or self-identification (foreigner objectification). Specifically, we examined how heritage-based versus pluralistic national identity content relates to adolescents' critical interpersonal and structural anti-racist action through critical awareness of racialised inequities and critical anti-racist motivation. Our sample comprised 743 9th grade students (M = 15.04 years) in Thuringia, Germany. Path analyses revealed that across adolescents, pluralistic national identity content was not associated with critical awareness, but positively associated with motivation, which in turn was positively related to interpersonal and structural action. Heritage-based national identity content was negatively associated with interpersonal action for students experiencing low foreigner objectification and displaying high national attachment. In contrast, it was positively related to structural action for adolescents experiencing high foreigner objectification, and to interpersonal action when adolescents displayed low national attachment. Thus, adolescents' national identity and CC development are intertwined. While our results suggest that pluralistic conceptions of national identity are linked to adolescents' anti-racist action through critical anti-racist motivation, their potential to contribute to a holistic CC development may be limited given the lack of an observed association with critical awareness. More research is needed to disentangle various notions of pluralistic identities and examine whether and under which conditions these may relate to adolescents' critical awareness of racialised inequities. Furthermore, our results underscore the importance of continuously reflecting on heritage-based national identity conceptions and countering their exclusive nuances
Caveolin assemblies displace one bilayer leaflet to organize and bend membranes
No full textCaveolin is a monotopic integral membrane protein, widely expressed in metazoans and responsible for constructing enigmatic membrane invaginations known as caveolae. Recently, the high-resolution structure of a purified human caveolin assembly, the CAV1-8S complex, revealed a unique organization of 11 protomers arranged in a tightly packed, radially symmetric spiral disc. One face and the outer rim of this disc are hydrophobic, suggesting that the complex incorporates into membranes by displacing hundreds of lipids from one leaflet. The feasibility of this unique molecular architecture and its biophysical and functional consequences are currently unknown. Using Langmuir film balance measurements, we find that CAV1-8S is highly surface active, intercalating into lipid monolayers of various compositions. CAV1-8S can also incorporate into preformed bilayers, but only upon removal of phospholipids from the outer-facing leaflet. Atomistic and coarse-grained simulations of biomimetic bilayers support this “leaflet replacement” model and also reveal that CAV1-8S accumulates 40 to 70 cholesterol molecules into a disordered monolayer between the complex and its distal lipid leaflet. We find that CAV1-8S preferentially associates with positively curved membrane surfaces due to its influence on the conformations of distal leaflet lipids, and that these effects laterally sort lipids. Large-scale simulations of multiple caveolin assemblies confirmed their association with large, positively curved membrane morphologies consistent with the shape of caveolae. Further, association with curved membranes regulates the exposure of caveolin residues implicated in protein–protein interactions. Altogether, the unique structure of CAV1-8S imparts unusual modes of membrane interaction with implications for membrane organization, morphology, and physiology
Marital status and risk of cardiovascular disease : a multi-analyst study in epidemiology
No full textIn multi-analyst studies, several analysts use the same data to independently investigate identical research questions. Multi-analyst studies have been conducted mainly in psychology, social sciences, and neuroscience, but rarely in epidemiology. Sixteen analyst groups (24 researchers) with backgrounds mainly in statistics, mathematics, and epidemiology were asked to independently perform an analysis on the influence of marital status (never married versus cohabiting married) on cardiovascular outcomes. They were asked to use data from the Survey of Health, Ageing and Retirement in Europe (SHARE), a panel study of 140,000 persons aged 50 years and above from 28 European countries and Israel, and to provide an effect estimate, a comment on their results, and the full syntax of their analyses. In additional analyses beyond the multi-analyst approach, one group selected an exemplary regression model and varied definitions of exposure and outcome and the confounder adjustment set. Each analysis was unique. The size of the 16 datasets used for the analyses ranged from 15,592 to 336,914 observations. The effect estimates (odds ratios, hazard ratios, or relative risks) ranged from 0.72 to 1.02 (reference: cohabiting married) in strictly or partly cross-sectional analyses and from 0.95 to 1.31 in strictly longitudinal analyses. The choice of regression models, adjustment sets for confounding, and variations in the precise definition of exposure and outcome, all had only small effects on the effect estimates. The range of results was mainly due to differences from cross-sectional versus longitudinal analyses rather than to single analytical decisions each of which had less influence
A case series shows a relation between intracochlear electric field distribution and vestibular co-stimulation with cochlear implants
No full textThe objective of this study was to investigate the relation between the electric field distribution within the cochlea during cochlear implant stimulation and the electrical vestibular co-stimulation measured by vestibular evoked myogenic potentials (e-VEMPs). Measurements were done in adult Nucleus cochlear implant (CI) users with perimodiolar electrode arrays. The electric field distribution within the cochlea was determined by Transimpedance Matrices recorded for all participants with a pulse width of 25 µs and a current level of 110 CL. Study measurements were conducted in 25 ears of 24 participants. In 10 participants, e-VEMPs could be elicited (40%). The occurrence of e-VEMPs stimulated by the cochlear implant was correlated with the magnitude of a corrected transimpedance at the most basal electrode. Since the results also suggest that there are patients with vestibular co-stimulation already present at their everyday CI stimulation level, this needs to be taken into account by audiologists creating programming maps for CIs, e.g. by deactivation of basal electrode contacts, if dizziness occurs during CI stimulation
Lithium-phase identification in an industrial lithium-ion-battery recycling slag : implications for the recovery of lithium
No full textThe recycling of lithium-ion batteries (LIBs) through extractive pyrometallurgy is widely used, but a significant drawback is the loss of lithium to the slag. To address this, lithium-bearing slag from an industrial LIB recycling plant is analyzed using wavelength dispersive X-ray fluorescence, inductively coupled plasma optical emission spectroscopy, X-ray diffraction (XRD), and thermogravimetry coupled infrared. The slag's chemical composition is complex, best described by the ternary system CaO–SiO2–Al2O3, with additional major components being Na2O, Fe2O3, MgO, V2O5, Mn2O3, and Cr2O3. The slag cone shows little chemical zonation and a relatively constant lithium content of Ø 0.82 mass%. The recycling slag shows a mineralogical composition typical of nonferrous slags (e.g., melilite, clinopyroxene, nepheline). Lithium is either bound in β-eucryptite or, to a lesser extent, in lithium metasilicate. β-eucryptite contains up to 5.51 mass% lithium stoichiometrically, which is more than typical lithium ores contain. Moreover, β-eucryptite has potential for the engineering of artificial minerals strategy as an easily implementable lithium phase. β-eucryptite forms in slags with lower overall lithium content, allowing for the use of slag modifiers that reduce the process temperature. Hence, β-eucryptite could prove as efficient and feasible option for improving lithium recovery from smelting processes
Clinical ophthalmic outcomes and impact of single large-scale mitochondrial DNA deletions
No full textIntroduction/Objectives: Chronic progressive external ophthalmoplegia (CPEO) is commonly associated with mtDNA deletions. Multiple deletions result mostly due to nuclear DNA defects that lead to an autosomal mode of inheritance, whereas single mtDNA deletions are mostly sporadic events with low inheritance risk. The study focused on assessing the clinical ophthalmic outcomes and their effects on patients with mitochondrial DNA disorders. Methods: A retrospective analysis of clinical characteristics in a cohort of CPEO patients (n = 36; 11 males, 25 females; mean age of onset: 41.2 years (±SD)) was performed. The underlying genetic defects, as well as histological features and their correlation with the clinical features, were evaluated. Results: Ptosis (56% of patients) was a frequently identified clinical symptom. Single mtDNA deletions were reported in all patients, and the ‘common’ 4977 bp deletion (CD) was detected in 11 patients (30.6%). The incidence of the common deletion was higher (36.36%) in older patients (≥51 years) as compared to younger patients (18.18%). The mean age of onset in patients harboring CD was 27 years (±11.9). Furthermore, a tendency to increase the frequency of COX-deficient fibers with increasing age was observed in patients harboring the CD. Conclusions: The present study shows that CD is typically associated with elderly patients with CPEO. Moreover, ptosis and the presence of a single deletion in patients with mitochondrialopathy seem to be preliminary diagnostic criteria
Transition towards a bioeconomy : discourses, vantage points, and actors’ contextualized institutional work
No full textThis thesis explores the status and prospects of transition towards a bioeconomy. It asks how bioeconomy actors’ sociotechnical imaginaries, their perception of context conditions and their institutional work contribute to the current status of an emerging bioeconomy. Theoretical concepts from evolutionary economics (innovation systems; sociotechnical systems) and organisational sociology (neo-institutional theory) guided the empirical research. Main results show that transition is held back by insufficient societal deliberations and blurred objectives of bioeconomy promotion. The institutional conditions differ markedly in different industries: the impact on actors’ institutional work can be conducive, barricading or exhausting. Progress towards transition appears more likely where institutional logic change is combined with tightening regulation. Policy may strengthen field-level coordination mechanism and help SMEs advancing new quality management systems for a bioeconomy