@phdthesis{Kortmann2022,
  author    = {Kortmann, Mareike},
  title     = {Biodiversity and recreation - Optimizing tourism and forest management in forests affected by bark beetles},
  doi       = {10.25972/OPUS-24031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240317},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Forests are multi-functional system, which have to fulfil different objectives at the same time. The main functions include the production of wood, storage of carbon, the promotion of biological diversity and the provision of recreational space. Yet, global forests are affected by large and intense natural disturbances, like bark beetle infestations. While natural disturbances threaten wood production and are perceived as 'catastrophe' diminishing recreational value, biodiversity can benefit from the disturbance-induced changes in forest structures. This trade-off poses a dilemma to managers of bark beetle affected stands, particularly in protected areas designated to both nature conservation and recreation. Forest landscapes need a sustainable management concept aligning these different objectives. In order to support this goal with scientific knowledge, the aim of this work is to analyse ecological and social effects along a gradient of different disturbance severities. In this context, I studied the effects of a disturbance severity gradient on the diversity of different taxonomic groups including vascular plants, mosses, lichens, fungi, arthropods and birds in five national parks in Central Europe. To analyse the recreational value of the landscape I conducted visitor surveys in the same study areas in which the biodiversity surveys were performed. To analyse possible psychological or demographic effects on preferences for certain disturbance intensities, an additional online survey was carried out.},
  subject      = {Borkenk{\"a}fer},
  language  = {en}
}
@phdthesis{Kuhlemann2022,
  author    = {Kuhlemann, Alexander},
  title     = {Bioorthogonal labeling of neuronal proteins using super-resolution fluorescence microscopy},
  doi       = {10.25972/OPUS-24373},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243731},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The synaptic cleft is of central importance for synaptic transmission, neuronal plasticity and memory and thus well studied in neurobiology. To target proteins of interest with high specificity and strong signal to noise conventional immunohistochemistry relies on the use of fluorescently labeled antibodies. However, investigations on synaptic receptors remain challenging due to the defined size of the synaptic cleft of ~20 nm between opposing pre- and postsynaptic membranes. At this limited space, antibodies bear unwanted side effects such as crosslinking, accessibility issues and a considerable linkage error between fluorophore and target of ~10 nm. With recent single molecule localization microscopy (SMLM) methods enabling localization precisions of a few nanometers, the demand for labeling approaches with minimal linkage error and reliable recognition of the target molecules rises. Within the scope of this work, different labeling techniques for super-resolution fluorescence microscopy were utilized allowing site-specific labeling of a single amino acid in synaptic proteins like kainate receptors (KARs), transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor regulatory proteins (TARPs), γ-aminobutyric acid type A receptors (GABA-ARs) and neuroligin 2 (NL2). The method exploits the incorporation of unnatural amino acids (uAAs) in the protein of interest using genetic code expansion (GCE) via amber suppression technology and subsequent labeling with tetrazine functionalized fluorophores. Implementing this technique, hard-to-target proteins such as KARs, TARPs and GABA-ARs could be labeled successfully, which could only be imaged insufficiently with conventional labeling approaches. Furthermore, functional studies involving electrophysiological characterization, as well as FRAP and FRET experiments validated that incorporation of uAAs maintains the native character of the targeted proteins. Next, the method was transferred into primary hippocampal neurons and in combination with super-resolution microscopy it was possible to resolve the nanoscale organization of γ2 and γ8 TARPs. Cluster analysis of dSTORM localization data verified synaptic accumulation of γ2, while γ8 was homogenously distributed along the neuron. Additionally, GCE and bioorthogonal labeling allowed visualization of clickable GABA-A receptors located at postsynaptic compartments in dissociated hippocampal neurons. Moreover, saturation experiments and FRET imaging of clickable multimeric receptors revealed successful binding of multiple tetrazine functionalized fluorophores to uAA-modified dimeric GABA-AR α2 subunits in close proximity (~5 nm). Further utilization of tetrazine-dyes via super-resolution microscopy methods such as dSTORM and click-ExM will provide insights to subunit arrangement in receptors in the future. This work investigated the nanoscale organization of synaptic proteins with minimal linkage error enabling new insights into receptor assembly, trafficking and recycling, as well as protein-protein interactions at synapses. Ultimately, bioorthogonal labeling can help to understand pathologies such as the limbic encephalitis associated with GABA-AR autoantibodies and is already in application for cancer therapies.},
  subject      = {microscopy},
  language  = {en}
}
@phdthesis{Boetzl2022,
  author    = {B{\"o}tzl, Fabian Alexander},
  title     = {The influence of crop management and adjacent agri-environmental scheme type on natural pest control in differently structured landscapes},
  doi       = {10.25972/OPUS-24140},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241400},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Summary Chapters I \& II: General Introduction \& General Methods Agriculture is confronted with a rampant loss of biodiversity potentially eroding ecosystem service potentials and adding up to other stressors like climate change or the consequences of land-use change and intensive management. To counter this 'biodiversity crisis', agri-environment schemes (AES) have been introduced as part of ecological intensification efforts. These AES combine special management regimes with the establishment of tailored habitats to create refuges for biodiversity in agricultural landscapes and thus ensure biodiversity mediated ecosystem services such as pest control. However, little is known about how well different AES habitats fulfil this purpose and whether they benefit ecosystem services in adjacent crop fields. Here I investigated how effective different AES habitats are for restoring biodiversity in different agricultural landscapes (Chapter V) and whether they benefit natural pest control in adjacent oilseed rape (Chapter VI) and winter cereal fields (Chapter VII). I recorded biodiversity and pest control potentials using a variety of different methods (Chapters II, V, VI \& VII). Moreover, I validated the methodology I used to assess predator assemblages and predation rates (Chapters III \& IV). Chapter III: How to record ground dwelling predators? Testing methodology is critical as it ensures scientific standards and trustworthy results. Pitfall traps are widely used to record ground dwelling predators, but little is known about how different trap types affect catches. I compared different types of pitfall traps that had been used in previous studies in respect to resulting carabid beetle assemblages. While barrier traps collected more species and deliver more complete species inventories, conventional simple pitfall traps provide reliable results with comparatively little handling effort. Placing several simple pitfall traps in the field can compensate the difference while still saving handling effort.   Chapter IV: How to record predation rates? A plethora of methods has been proposed and used for recording predation rates, but these have rarely been validated before use. I assessed whether a novel approach to record predation, the use of sentinel prey cards with glued on aphids, delivers realistic results. I compared different sampling efforts and showed that obtained predation rates were similar and could be linked to predator (carabid beetle) densities and body-sizes (a proxy often used for food intake rates). Thus, the method delivers reliable and meaningful predation rates. Chapter V: Do AES habitats benefit multi-taxa biodiversity? The main goal of AES is the conservation of biodiversity in agricultural landscapes. I investigated how effectively AES habitats with different temporal continuity fulfil this goal in differently structured landscapes. The different AES habitats investigated had variable effects on local biodiversity. Temporal continuity of AES habitats was the most important predictor with older, more temporally continuous habitats harbouring higher overall biodiversity and different species assemblages in most taxonomic groups than younger AES habitats. Results however varied among taxonomic groups and natural enemies were equally supported by younger habitats. Semi-natural habitats in the surrounding landscape and AES habitat size were of minor importance for local biodiversity and had limited effects. This stresses that newly established AES habitats alone cannot restore farmland biodiversity. Both AES habitats as well as more continuous semi-natural habitats synergistically increase overall biodiversity in agricultural landscapes. Chapter VI: The effects of AES habitats on predators in adjacent oilseed rape fields Apart from biodiversity conservation, ensuring ecosystem service delivery in agricultural landscapes is a crucial goal of AES. I therefore investigated the effects of adjacent AES habitats on ground dwelling predator assemblages in oilseed rape fields. I found clear distance decay effects from the field edges into the field centres on both richness and densities of ground dwelling predators. Direct effects of adjacent AES habitats on assemblages in oilseed rape fields however were limited and only visible in functional traits of carabid beetle assemblages. Adjacent AES habitats doubled the proportion of predatory carabid beetles indicating a beneficial role for pest control. My results show that pest control potentials are largest close to the field edges and beneficial effects are comparably short ranged. Chapter VII: The effects of AES habitats on pest control in adjacent cereal fields Whether distance functions and potential effects of AES habitats are universal across crops is unknown. Therefore, I assessed distance functions of predators, pests, predation rates and yields after crop rotation in winter cereals using the same study design as in the previous year. Resulting distance functions were not uniform and differed from those found in oilseed rape in the previous year, indicating that the interactions between certain adjacent habitats vary with habitat and crop types. Distance functions of cereal-leaf beetles (important cereal pests) and parasitoid wasps were moreover modulated by semi-natural habitat proportion in the surrounding landscapes. Field edges buffered assemblage changes in carabid beetle assemblages over crop rotation confirming their important function as refuges for natural enemies. My results emphasize the beneficial role of field edges for pest control potentials. These findings back the calls for smaller field sizes and more diverse, more heterogeneously structured agricultural landscapes. Chapter VIII: General Discussion Countering biodiversity loss and ensuring ecosystem service provision in agricultural landscapes is intricate and requires strategic planning and restructuring of these landscapes. I showed that agricultural landscapes could benefit maximally from (i) a mixture of AES habitats and semi-natural habitats to support high levels of overall biodiversity and from (ii) smaller continuously managed agricultural areas (i.e. smaller field sizes or the insertion of AES elements within large fields) to maximize natural pest control potentials in crop fields. I propose a mosaic of younger AES habitats and semi-natural habitats to support ecosystem service providers and increase edge density for ecosystem service spillover into adjacent crops. The optimal extent and density of this network as well as the location in which AES and semi-natural habitats interact most beneficially with adjacent crops need further investigation. My results provide a further step towards more sustainable agricultural landscapes that simultaneously allow biodiversity to persist and maintain agricultural production under the framework of ecological intensification.},
  subject      = {{\"O}kologie},
  language  = {en}
}
@phdthesis{Vellmer2022,
  author    = {Vellmer, Tim},
  title     = {New insights into the histone variant H2A.Z incorporation pathway in \(Trypanosoma\) \(brucei\)},
  doi       = {10.25972/OPUS-25796},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257960},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {The histone variant H2A.Z is a key player in transcription regulation in eukaryotes. Histone acetylations by the NuA4/TIP60 complex are required to enable proper incorporation of the histone variant and to promote the recruitment of other complexes and proteins required for transcription initiation. The second key player in H2A.Z-mediated transcription is the chromatin remodelling complex SWR1, which replaces the canonical histone H2A with its variant. By the time this project started little was known about H2A.Z in the unicellular parasite Trypanosoma brucei. Like in other eukaryotes H2A.Z was exclusively found in the transcription start sites of the polycistronic transcription units where it keeps the chromatin in an open conformation to enable RNA-polymerase II-mediated transcription. Previous studies showed the variant colocalizing with an acetylation of lysine on histone H4 and a methylation of lysine 4 on histone H3. Data indicated that HAT2 is linked to H2A.Z since it is required for acetylation of lyinse 10 on histone H4. A SWR1-like complex and a complex homologous to the NuA4/TIP60 could not be identified yet. This study aimed at identifying a SWR1-like remodelling complex in T. brucei and at identifying a protein complex orthologous to NuA4/TIP60 as well as at answering the question whether HAT2 is part of this complex or not. To this end, I performed multiple mass spectrometry-coupled co-Immunoprecipitation assays with potential subunits of a SWR1 complex, HAT2 and a putative homolog of a NuA4/TIP60 subunit. In the course of these experiments, I was able to identify the TbSWR1 complex. Subsequent cell fractionation and chromatin immunoprecipitation-coupled sequencing analysis experiments confirmed, that this complex is responsible for the incorporation of the histone variant H2A.Z in T. brucei. In addition to this chromatin remodelling complex, I was also able to identify two histone acetyltransferase complexes assembled around HAT1 and HAT2. In the course of my study data were published by the research group of Nicolai Siegel that identified the histone acetyltransferase HAT2 as being responsible for histone H4 acetylation, in preparation to promote H2A.Z incorporation. The data also indicated that HAT1 is responsible for acetylation of H2A.Z. According to the literature, this acetylation is required for proper transcription initiation. Experimental data generated in this study indicated, that H2A.Z and therefore TbSWR1 is involved in the DNA double strand break response of T. brucei. The identification of the specific complex composition of all three complexes provided some hints about how they could interact with each other in the course of transcription regulation and the DNA double strand break response. A proximity labelling approach performed with one of the subunits of the TbSWR1 complex identified multiple transcription factors, PTM writers and proteins potentially involved in chromatin maintenance. Overall, this work will provide some interesting insights about the composition of the complexes involved in H2A.Z incorporation in T. brucei. Furthermore, it is providing valuable information to set up experiments that could shed some light on RNA-polymerase II-mediated transcription and chromatin remodelling in T. brucei in particular and Kinetoplastids in general.},
  subject      = {Chromatinremodelling},
  language  = {en}
}
@phdthesis{Lasway2022,
  author    = {Lasway, Julius Vincent},
  title     = {Impact of human land use on bee diversity and plant-pollinator interactions in Tanzania savannah ecosystems},
  doi       = {10.25972/OPUS-25772},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257726},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {One of the pronounced global challenges facing ecologists is how to feed the current growing human population while sustaining biodiversity and ecosystem services. To shed light on this, I investigated the impact of human land use on bee diversity and plant-pollinator interactions in Tanzania Savannah ecosystems. The thesis comprises the following chapters: Chapter I: General Introduction This chapter provides the background information including the study objectives and hypotheses. It highlights the ecological importance of bees and the main threats facing bee pollinators with a focus on two land-use practices namely livestock grazing and agriculture. It also highlights the diversity and global distribution of bees. It further introduces the tropical savannah ecosystem, its climate, and vegetation characteristics and explains spectacular megafauna species of the system that form centers of wildlife tourism and inadequacy knowledge on pollinators diversity of the system. Finally, this chapter describes the study methodology including, the description of the study area, study design, and data collection. Chapter II: Positive effects of low livestock grazing intensity on East African bee assemblages mediated by increases in floral resources The impact of livestock grazing intensity on bee assemblage has been subjected to research over decades. Moreover, most of these studies have been conducted in temperate Europe and America leaving the huge tropical savannah of East Africa less studied. Using sweep netting and pan traps, a total of 183 species (from 2,691 individuals) representing 55 genera and five families were collected from 24 study sites representing three levels of livestock grazing intensity in savannah ecosystem of northern Tanzania. Results have shown that moderate livestock grazing slightly increased bee species richness. However, high livestock grazing intensity led to a strong decline. Besides, results revealed a unimodal distribution pattern of bee species richness and mean annual temperature. It was also found that the effect of livestock grazing and environmental temperature on bee species richness was mediated by a positive effect of moderate grazing on floral resource richness. The study, therefore, reveals that bee communities of the African savannah zone may benefit from low levels of livestock grazing as this favors the growth of flowering plant species. A high level of livestock grazing intensity will cause significant species losses, an effect that may increase with climatic warming. Chapter III: Agricultural intensification with seasonal fallow land promotes high bee diversity in Afrotropical drylands This study investigated the impact of local agriculture intensification on bee diversity in the Afro tropical drylands of northern Tanzania. Using sweep netting and pan traps, a total of 219 species (from 3,428 individuals) representing 58 genera and six families were collected from 24 study sites (distributed from 702 to 1708 m. asl) representing three levels of agriculture intensity spanning an extensive gradient of mean annual temperature. Results showed that bee species richness increased with agricultural intensity and with increasing temperature. However, the effects of agriculture intensity and temperature on bee species richness were mediated by the positive effects of agriculture and temperature on floral resource richness used by bee pollinators. Moreover, results showed that variation of bee body sizes increases with agricultural intensification, "that effect", however, diminished in environments with higher temperatures. This study reveals that bee assemblages in Afrotropical drylands benefit from agriculture intensification in the way it is currently practiced. Further intensification, including year-round irrigated crop monocultures and extensive use of agrochemicals, is likely to exert a negative impact on bee diversity and pollination services, as reported in temperate regions. Moreover, several bee species were restricted to natural savannah habitats. Therefore, to conserve bee communities in Afro tropical drylands and guarantee pollination services, a mixture of savannah and agriculture, with long periods of fallow land should be maintained. Chapter IV: Impact of land use intensification and local features on plants and pollinators in Sub-Saharan smallholder farms For the first time in the region, this study explores the impact of land-use intensification on plants and pollinators in Sub-Saharan smallholder farms. The study complemented field surveys of bees with a modern DNA metabarcoding approach to characterize the foraged plants and thus built networks describing plant-pollinator interactions at the individual insect level. This information was coupled with quantitative traits of landscape composition and floral availability surrounding each farm. The study found that pollinator richness decreased with increasing impervious and agricultural cover in the landscape, whereas the flower density at each farm correlated with pollinator richness. The intensification of agricultural land use and urbanization correlated with a higher foraging niche overlap among pollinators due to the convergence of individuals' flower-visiting strategies. Furthermore, within farms, the higher availability of floral resources drove lower niche overlap among individuals, greater abundance of flower visitors shaped higher generalization at the networks level (H2I), possibly due to increased competition. These mechanistic understandings leading to individuals' foraging niche overlap and generalism at the network level, could imply stability of interactions and the pollination ecosystem service. The integrative survey proved that plant-pollinator systems are largely affected by land use intensification and by local factors in smallholder farms of Sub-Saharan Africa. Thus, policies promoting nature-based solutions, among which the introduction of more pollinator-friendly practices by smallholder farmers, could be effective in mitigating the intensification of both urban and rural landscapes in this region, as well as in similar Sub-Saharan contexts. Chapter V: A synopsis of the Bee occurrence data of northern Tanzania This study represents a synopsis of the bee occurrence data of northern Tanzania obtained from a survey in the Kilimanjaro, Arusha, and Manyara regions. Bees were sampled using two standardized methods, sweep netting and colored pan traps. The study summed up 953 species occurrences of 45 species belonging to 20 genera and four families (Halictidae, Apidae, Megachilidae, and andrenidae) A. This study serves as the baseline information in understanding the diversity and distribution of bees in the northern parts of the country. Understanding the richness and distribution of bees is a critical step in devising robust conservation and monitoring strategies for their populations since limited taxonomic information of the existing and unidentified bee species makes their conservation haphazard. Chapter VI: General discussion In general, findings obtained in these studies suggest that livestock grazing and agriculture intensification affects bee assemblages and floral resources used by bee pollinators. Results have shown that moderate livestock grazing intensity may be important in preserving bee diversity. However, high level of livestock grazing intensity may result in a strong decline in bee species richness and abundance. Moreover, findings indicate that agriculture intensification with seasonal fallow lands supports high floral resource richness promoting high bee diversity in Afrotropical drylands. Nonetheless, natural savannahs were found to contain unique bee species. Therefore, agriculture intensification with seasonal fallow should go in hand with conserving remnant savannah in the landscapes to increase bee diversity and ensure pollination services. Likewise, findings suggest that increasing urbanization and agriculture cover at the landscape level reduce plant and pollinator biodiversity with negative impacts on their complex interactions with plants. Conversely, local scale availability of floral resources has shown the positive effects in buffering pollinators decline and mitigating all detrimental effects induced by land-use intensification. Moreover, findings suggest that the impact of human land use (livestock grazing and agriculture) do not act in isolation but synergistically interacts with climatic factors such as mean annual temperature, MAT. The impact of MAT on bee species richness in grazing gradient showed to be more detrimental than in agriculture habitats. This could probably be explained by the remaining vegetation cover following anthropogenic disturbance. Meaning that the remaining vegetation cover in the agricultural gradient probably absorbs the solar radiations hence reducing detrimental effect of mean annual temperature on bee species richness. This one is not the case in grazing gradient since the impact of livestock grazing is severe, leaving the bare land with no vegetation cover. Finally, our findings conclude that understanding the interplay of multiple anthropogenic activities and their interaction with MAT as a consequence of ongoing climate change is necessary for mitigating their potential consequences on bee assemblages and the provision of ecosystem services. Morever, future increases in livestock grazing and agriculture intensification (including year-round crop irrigated monocultures and excessive use of agrochemicals) may lead to undesirable consequences such as species loss and impair provision of pollination services.},
  subject      = {Human land use},
  language  = {en}
}
@article{BahenaDaftarianMaroofianetal.2022,
  author    = {Bahena, Paulina and Daftarian, Narsis and Maroofian, Reza and Linares, Paola and Villalobos, Daniel and Mirrahimi, Mehraban and Rad, Aboulfazl and Doll, Julia and Hofrichter, Michaela A. H. and Koparir, Asuman and R{\"o}der, Tabea and Han, Seungbin and Sabbaghi, Hamideh and Ahmadieh, Hamid and Behboudi, Hassan and Villanueva-Mendoza, Cristina and Cort{\´e}s-Gonzalez, Vianney and Zamora-Ortiz, Rocio and Kohl, Susanne and Kuehlewein, Laura and Darvish, Hossein and Alehabib, Elham and La Arenas-Sordo, Maria de Luz and Suri, Fatemeh and Vona, Barbara and Haaf, Thomas},
  title     = {Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment},
  series = {Human Genetics},
  volume    = {141},
  journal   = {Human Genetics},
  number    = {3-4},
  issn      = {1432-1203},
  doi       = {10.1007/s00439-021-02303-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267750},
  pages     = {785-803},
  year      = {2022},
  abstract  = {Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75\%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15\%) probands displayed other genetic entities with dual sensory impairment, including Alstr{\"o}m syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92\%. Two (3\%) probands were partially solved and only 3 (5\%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.},
  language  = {en}
}
@article{LichterPaulPaulietal.2022,
  author    = {Lichter, Katharina and Paul, Mila Marie and Pauli, Martin and Schoch, Susanne and Kollmannsberger, Philip and Stigloher, Christian and Heckmann, Manfred and Sir{\´e}n, Anna-Leena},
  title     = {Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse},
  series = {Cell Reports},
  volume    = {40},
  journal   = {Cell Reports},
  number    = {12},
  doi       = {10.1016/j.celrep.2022.111382},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300913},
  year      = {2022},
  abstract  = {Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{-/-}\) and wild-type mice. In RIM1α\(^{-/-}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0-2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{-/-}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.},
  language  = {en}
}
@article{JeanclosSchloetzerHadameketal.2022,
  author    = {Jeanclos, Elisabeth and Schl{\"o}tzer, Jan and Hadamek, Kerstin and Yuan-Chen, Natalia and Alwahsh, Mohammad and Hollmann, Robert and Fratz, Stefanie and Yesilyurt-Gerhards, Dilan and Frankenbach, Tina and Engelmann, Daria and Keller, Angelika and Kaestner, Alexandra and Schmitz, Werner and Neuenschwander, Martin and Hergenr{\"o}der, Roland and Sotriffer, Christoph and von Kries, Jens Peter and Schindelin, Hermann and Gohla, Antje},
  title     = {Glycolytic flux control by drugging phosphoglycolate phosphatase},
  series = {Nature Communications},
  volume    = {13},
  journal   = {Nature Communications},
  number    = {1},
  doi       = {10.1038/s41467-022-34228-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300928},
  year      = {2022},
  abstract  = {Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates.},
  language  = {en}
}
@article{KayaZeebEngelmayerStrassburgeretal.2022,
  author    = {Kaya-Zeeb, Sinan and Engelmayer, Lorenz and Straßburger, Mara and Bayer, Jasmin and B{\"a}hre, Heike and Seifert, Roland and Scherf-Clavel, Oliver and Thamm, Markus},
  title     = {Octopamine drives honeybee thermogenesis},
  series = {eLife},
  volume    = {11},
  journal   = {eLife},
  doi       = {10.7554/eLife.74334},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301327},
  year      = {2022},
  abstract  = {In times of environmental change species have two options to survive: they either relocate to a new habitat or they adapt to the altered environment. Adaptation requires physiological plasticity and provides a selection benefit. In this regard, the Western honeybee (Apis mellifera) protrudes with its thermoregulatory capabilities, which enables a nearly worldwide distribution. Especially in the cold, shivering thermogenesis enables foraging as well as proper brood development and thus survival. In this study, we present octopamine signaling as a neurochemical prerequisite for honeybee thermogenesis: we were able to induce hypothermia by depleting octopamine in the flight muscles. Additionally, we could restore the ability to increase body temperature by administering octopamine. Thus, we conclude that octopamine signaling in the flight muscles is necessary for thermogenesis. Moreover, we show that these effects are mediated by β octopamine receptors. The significance of our results is highlighted by the fact the respective receptor genes underlie enormous selective pressure due to adaptation to cold climates. Finally, octopamine signaling in the service of thermogenesis might be a key strategy to survive in a changing environment.},
  language  = {en}
}
@article{ReinhardBertoliniSaitoetal.2022,
  author    = {Reinhard, Nils and Bertolini, Enrico and Saito, Aika and Sekiguchi, Manabu and Yoshii, Taishi and Rieger, Dirk and Helfrich-F{\"o}rster, Charlotte},
  title     = {The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond},
  series = {Journal of Comparative Neurology},
  volume    = {530},
  journal   = {Journal of Comparative Neurology},
  number    = {9},
  doi       = {10.1002/cne.25294},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276456},
  pages     = {1507 -- 1529},
  year      = {2022},
  abstract  = {Drosophila's lateral posterior neurons (LPNs) belong to a small group of circadian clock neurons that is so far not characterized in detail. Thanks to a new highly specific split-Gal4 line, here we describe LPNs' morphology in fine detail, their synaptic connections, daily bimodal expression of neuropeptides, and propose a putative role of this cluster in controlling daily activity and sleep patterns. We found that the three LPNs are heterogeneous. Two of the neurons with similar morphology arborize in the superior medial and lateral protocerebrum and most likely promote sleep. One unique, possibly wakefulness-promoting, neuron with wider arborizations extends from the superior lateral protocerebrum toward the anterior optic tubercle. Both LPN types exhibit manifold connections with the other circadian clock neurons, especially with those that control the flies' morning and evening activity (M- and E-neurons, respectively). In addition, they form synaptic connections with neurons of the mushroom bodies, the fan-shaped body, and with many additional still unidentified neurons. We found that both LPN types rhythmically express three neuropeptides, Allostatin A, Allostatin C, and Diuretic Hormone 31 with maxima in the morning and the evening. The three LPN neuropeptides may, furthermore, signal to the insect hormonal center in the pars intercerebralis and contribute to rhythmic modulation of metabolism, feeding, and reproduction. We discuss our findings in the light of anatomical details gained by the recently published hemibrain of a single female fly on the electron microscopic level and of previous functional studies concerning the LPN.},
  language  = {en}
}