Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1

A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Evaluation eines projekt- und problemorientierten Lehransatzes im Fachgebiet Arbeitsmedizin

Die Pflichtlehrveranstaltungen im Fachgebiet Arbeitsmedizin in Münster werden auf der methodischen Grundlage des projekt- und problemorientierten Lernens durchgeführt mit unmittelbarem Praxisbezug in Betrieben unterschiedlicher Industrie- und Gewerbezweige. Im Erhebungs¬zeitraum (WS 1999/2000-SS 2003, insgesamt 1020 Studierende) wurde kontinuierlich institutsintern evaluiert. Die Validität des Evaluationsverfahrens wurde statistisch gesichert. 981 Fragebögen wurden ausgewertet. Die Bewertungen der Indikatoren für Struktur, Didaktik und Lehrkompetenz sowie Teilnahmemotivation und Lernerfolg verbesserten sich signifikant. Die positive Einschätzung der Gruppenarbeit korrelierte signifikant mit der Akzeptanz und dem Interesse für das Fach. Insgesamt kann kontinuierliche studentische Lehrevaluation zur Qualität der Lehre in der Arbeitsmedizin beitragen

An interlaboratory study of TEX86 and BIT analysis of sediments, extracts and standard mixtures.

Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility ±3-4°C when translated to temperature) but a large spread in BIT measurements (reproducibility ±0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0°C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the "true" (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values

Plasmodium falciparum metacaspase PfMCA-1 triggers a z-VAD-fmk inhibitable protease to promote cell death.

Activation of proteolytic cell death pathways may circumvent drug resistance in deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this end, it is important to define the cell death pathway(s) in parasites and thus characterize proteases such as metacaspases (MCA), which have been reported to induce cell death in plants and Leishmania parasites. We, therefore, investigated whether the cell death function of MCA is conserved in different protozoan parasite species such as Plasmodium falciparum and Leishmania major, focusing on the substrate specificity and functional role in cell survival as compared to Saccharomyces cerevisae. Our results show that, similarly to Leishmania, Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity and its expression in yeast induced growth inhibition as well as an 82% increase in cell death under oxidative stress, a situation encountered by parasites during the host or when exposed to drugs such as artemisins. Furthermore, we show that MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk inhibitable protease. Our data provide evidence that MCA from both Leishmania and Plasmodium falciparum is able to induce cell death in stress conditions, where it specifically activates a downstream enzyme as part of a cell death pathway. This enzymatic activity is also induced by the antimalarial drug chloroquine in erythrocytic stages of Plasmodium falciparum. Interestingly, we found that blocking parasite cell death influences their drug sensitivity, a result which could be used to create therapeutic strategies that by-pass drug resistance mechanisms by acting directly on the innate pathways of protozoan cell death

Secondary cities as catalysts for nutritious diets in low- and middle-income countries

The world is facing a malnutrition crisis in the midst of rising rates of urbanization; more than half of the world's population lives in urban areas, a number that is expected to reach two-thirds by 2050, consuming 80% of the world's food. Instead of the development of existing cities into 'mega-cities, ' urbanization is creating a patchwork of smaller urban areas. In 2018, close to half of the world's urban residents lived in settlements or towns with less than 500, 000 inhabitants. These settlements are classified as secondary cities and are, in terms of population, the fastest growing urban areas. Poor diets among city inhabitants are the consequence of a combination of forces. These include changes in types of occupation, particularly for women; food-environment factors; shifts in norms and attitudes regarding food; globalization of food supply chains; lack of infrastructure; post-harvest food loss and waste, etc. Secondary cities offer entry points for food system transformation. Secondary cities are characterized by strong urban-rural linkages and the opportunity for localized food production and consumption. These cities could also play a key role in enhancing resilience to food security shocks. This chapter discusses the challenge of the growing triple burden of malnutrition in urban contexts and argues for the important role of secondary cities in transforming urban food systems. Through three case studies of secondary cities in LMICs, these cities are shown as emerging players in nutrition-centered food system interventions. © The Author(s) 2023

Considerations of Efficiency and Distributive Justice in Multidimensional Poverty Measurement

Ab den 1980er Jahren entwickelte Amartya Sen eine neue Wohlfahrtstheorie: den Capability Approach (Sen, 1979; 1985; 1992; 1999; 2009). Dabei ersetzen Capabilities und Functionings, d.h. das, was Personen tatsächlich in der Lage sind zu tun und zu sein, den traditionellen Einkommensansatz. Armut ist im Capability Approach das Unvermögen, ein bestimmtes Minimum an zentralen Capabilities zu erreichen, die benötigt werden, um das Leben nach den eigenen Vorstellungen zu gestalten. Der Capability Approach hat so viele interessante Eigenschaften, besonders in Bezug auf die Armutsmessung, dass er zunehmend Einfluss in der Wohlfahrtsökonomie gewinnt. Diese Entwicklung wird durch empirische Untersuchungen gefördert, die zeigen, dass dieser multidimensionale Ansatz zur Armutsmessung deutlich andere Ergebnisse generiert als der traditionelle Einkommensansatz (vgl. Klasen, 2000, Alkire und Santos, 2010, Figari, 2012). Der derzeitige multidimensionale Ansatz hat jedoch eine methodische Schwäche: Ungleichheit zwischen Armutsdimensionen wird entweder als Korrelationssensitivität definiert – womit Effizienz aber nicht Verteilungsgerechtigkeit berücksichtigt wird – oder als die Verteilung multipler Mangelerscheinungen in einer Gesellschaft – womit Verteilungsgerechtigkeit aber nicht Effizienz berücksichtigt wird. Die ersten beiden Kapitel dieser Dissertation widmen sich der Behebung dieser methodischen Schwäche. Dazu wird Ungleichheit zwischen Dimensionen zunächst als „korrelationssensitive Verteilung multipler Mangelerscheinungen in einer Gesellschaft“ definiert. Die ersten beiden Kapitel operationalisieren diese erweiterte Definition für den Fall ordinaler und kardinaler Armutsindices. Im Einzelnen wird ein neues Axiom für den ordinalen sowie den kardinalen Fall eingeführt, das das Ausmaß, mit dem ein Ungleichheitsfördernder Tausch Armut sinken (oder steigen) lässt, von der Beziehung zwischen den Armutsdimensionen abhängig macht. Diese Neuerung wird benutzt um eine neue Klasse ordinaler bzw. kardinaler Armutsindices herzuleiten. Diese zwei Klassen sind die ersten additiven Armutsindices die in der Lage sind, sowohl Ungleichheit als auch Korrelationssensitivität zu erfassen. Das dritte Kapitel nutzt das deutsche sozio-ökonomische Panel um zwei ordinale Armutsindices für Deutschland vorzuschlagen, die auf der zuvor entwickelten Methode basieren: den „Deutschen Korrelationssensitiven Armutsindex“ und den „Subjektiven Korrelationssensitiven Armutsindex“. Die beiden Indices werden mit dem offiziellen deutschen Armutsmaß, der Armutsgefährdungsquote, über Dimensionen, Regionen und über die Zeit hinweg verglichen. Die Resultate zeigen vor allem eines: die signifikanten Unterschiede in der Beurteilung von Armut und Armutstrends die durch die verschiedenen Indices versursacht werden und den hohen Mehrwert den die Operationalisierung des Capability Approachs darstellt

Interaction of plant growth regulators and reactive oxygen species to regulate petal senescence in wallflowers (Erysimum linifolium)

Background In many species floral senescence is coordinated by ethylene. Endogenous levels rise, and exogenous application accelerates senescence. Furthermore, floral senescence is often associated with increased reactive oxygen species, and is delayed by exogenously applied cytokinin. However, how these processes are linked remains largely unresolved. Erysimum linifolium (wallflower) provides an excellent model for understanding these interactions due to its easily staged flowers and close taxonomic relationship to Arabidopsis. This has facilitated microarray analysis of gene expression during petal senescence and provided gene markers for following the effects of treatments on different regulatory pathways. Results In detached Erysimum linifolium (wallflower) flowers ethylene production peaks in open flowers. Furthermore senescence is delayed by treatments with the ethylene signalling inhibitor silver thiosulphate, and accelerated with ethylene released by 2-chloroethylphosphonic acid. Both treatments with exogenous cytokinin, or 6-methyl purine (which is an inhibitor of cytokinin oxidase), delay petal senescence. However, treatment with cytokinin also increases ethylene biosynthesis. Despite the similar effects on senescence, transcript abundance of gene markers is affected differentially by the treatments. A significant rise in transcript abundance of WLS73 (a putative aminocyclopropanecarboxylate oxidase) was abolished by cytokinin or 6-methyl purine treatments. In contrast, WFSAG12 transcript (a senescence marker) continued to accumulate significantly, albeit at a reduced rate. Silver thiosulphate suppressed the increase in transcript abundance both of WFSAG12 and WLS73. Activity of reactive oxygen species scavenging enzymes changed during senescence. Treatments that increased cytokinin levels, or inhibited ethylene action, reduced accumulation of hydrogen peroxide. Furthermore, although auxin levels rose with senescence, treatments that delayed early senescence did not affect transcript abundance of WPS46, an auxin-induced gene. Conclusions A model for the interaction between cytokinins, ethylene, reactive oxygen species and auxin in the regulation of floral senescence in wallflowers is proposed. The combined increase in ethylene and reduction in cytokinin triggers the initiation of senescence and these two plant growth regulators directly or indirectly result in increased reactive oxygen species levels. A fall in conjugated auxin and/or the total auxin pool eventually triggers abscission

Oxidative discolouration in whole-head and cut lettuce: biochemical and environmental influences on a complex phenotype and potential breeding strategies to improve shelf-life

Lettuce discolouration is a key post-harvest trait. The major enzyme controlling oxidative discolouration has long been considered to be polyphenol oxidase (PPO) however, levels of PPO and subsequent development of discolouration symptoms have not always correlated. The predominance of a latent state of the enzyme in plant tissues combined with substrate activation and contemporaneous suicide inactivation mechanisms are considered as potential explanations for this phenomenon. Leaf tissue physical properties have been associated with subsequent discolouration and these may be influenced by variation in nutrient availability, especially excess nitrogen and head maturity at harvest. Mild calcium and irrigation stress has also been associated with a reduction in subsequent discolouration, although excess irrigation has been linked to increased discolouration potentially through leaf physical properties. These environmental factors, including high temperature and UV light intensities, often have impacts on levels of phenolic compounds linking the environmental responses to the biochemistry of the PPO pathway. Breeding strategies targeting the PALand PPOpathway biochemistry and environmental response genes are discussed as a more cost-effective method of mitigating oxidative discolouration then either modified atmosphere packaging or post-harvest treatments, although current understanding of the biochemistry means that such programs are likely to be limited in nature and it is likely that they will need to be deployed alongside other methods for the foreseeable future